RU2808563C2 - MONOCLONAL ANTIBODY OR ITS ANTIGEN-BINDING FRAGMENT WHICH SPECIFICALLY BINDS TO 4Rα (GD2 GANGLIOSIDE) AND ITS USE - Google Patents

Abstract

FIELD: biotechnology; medicine.

SUBSTANCE: monoclonal antibody or its antigen-binding fragment, which specifically binds to IL-4Rα (subunit of IL-4Rα interleukin receptor 4). The invention also relates to nucleic acids encoding the said antibody, expression vectors, host cells and methods of their production, methods of producing antibodies of the invention, pharmaceutical compositions containing an antibody of the invention, pharmaceutical compositions containing an antibody of the invention and other therapeutically active compounds, methods of treatment of IL-4Rα mediated diseases or disorders, uses of the antibodies or pharmaceutical compositions thereof for the treatment of IL-4Rα mediated diseases or disorders, and uses of the antibodies of the invention and other therapeutically active compounds for the treatment of IL-4Rα mediated diseases or disorders.

EFFECT: obtaining monoclonal antibody or its antigen-binding fragment which specifically binds to 4Rα (GD2 ganglioside).

41 cl, 8 dwg, 6 tbl, 12 ex

Description

Field of technology to which the invention relates

The present invention relates to the field of biotechnology and medicine, namely to a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to IL-4Rα (a subunit of the IL-4Rα interleukin 4 receptor). The invention also relates to nucleic acids encoding the specified antibody, expression vectors, host cells and methods for their production, methods for producing antibodies according to the invention, pharmaceutical compositions containing the antibody according to the invention, pharmaceutical compositions containing the antibody according to the invention and other therapeutically active compounds, methods treating diseases or disorders mediated by IL-4Rα, uses of antibodies or pharmaceutical compositions thereof for treating diseases or disorders mediated by IL-4Rα, and uses of antibodies of the invention and other therapeutically active compounds for treating diseases or disorders mediated by IL-4Rα.

State of the art

Interleukin 4 (IL-4) is a pro-inflammatory cytokine produced predominantly by T lymphocytes belonging to the Th2 subset. In addition to Th2 cell differentiation, IL-4 induces the synthesis of cytokines and chemokines, including both IL-4 itself and IL-5, IL-9, IL-13, eotaxin and CCL17. Also (together with IL-13), IL-4 regulates the switch of B cells to the production of immunoglobulin E. The wide range of effects exerted by IL-4 on various cells is mediated by two variants of the IL-4 receptor (IL-4R), consisting of three types subunits: IL-4Rα, IL-2Rγ and IL-13Rα.

The IL-2Rγ subunit, or γc protein, is a common component of the receptors IL-2, IL-4, IL-7 and several others. By combining, IL-4Rα and γс form IL-4R, a high-affinity receptor of the first type, which is expressed on the surface of a wide range of immunocompetent and hematopoietic cells: T- and B-lymphocytes, monocytes, granulocytes. The second type of IL-4 receptor, IL-4R II, is formed by the IL-13Rα and IL-4Rα subunits. IL-4R II is low-affinity and can bind both IL-4 and IL-13. It is assumed that this phenomenon provides a known overlap in the effects of these cytokines: IL-4 and IL-13, interacting with the same receptor, are involved in the development of Th2-dependent inflammation.

The binding of IL-4 to its receptor occurs in two stages: first, IL-4 is captured by the highly related IL-4Rα, then one of the two less affinity subunits (IL-13Rα1 or γC) is included in the resulting complex. For IL-13, the order of interaction is reverse: first the ligand binds to IL-13Rα1 with relatively low affinity, and then IL-4Rα, which has a slightly higher affinity, joins this complex.

Thus, when IL-4Rα is blocked, IL-4 cannot bind to the receptor, and IL-13, having bound to IL-13Rα1 with low affinity, cannot complete the formation of the complex.

To date, an important pathogenetic role of IL-4 has been established in the formation of bronchial asthma (BA), namely in the formation of allergic inflammation due to the proliferation of T-lymphocytes, increased production of immunoglobulin E and eosinophil chemotaxis.

All patients with bronchial asthma experience significant fluctuations in the levels of IL-4 in the peripheral blood: thus, a significant increase in the levels of this cytokine is detected in patients with any severity of asthma during exacerbation of the disease, with a tendency to decrease in the remission phase. However, the concentration of IL-4 in the blood in patients with asthma (including those with mild disease) always exceeded that in healthy individuals.

For atopic dermatitis, an important role for IL-4 and IL-13 in pathogenesis has been shown through their participation in Th2 inflammation. When the IL-4R receptor binds, the level of these interleukins in the blood is expected to increase.

Two approaches have been developed to inhibit IL-13 and/or IL-4:

1) inhalation of a dissolved IL-4R selective IL-4 antagonist;

2) blocking IL-4Rα, a key signaling component of the receptor complex for IL-4 and IL-13.

Thus, blockade of IL-4Rα will disrupt the formation of Th2 inflammation, which should affect the clinical manifestations of the above diseases and significantly improve the quality of life of patients with severe chronic pathologies.

International application WO 2008054606 describes the antibody dupilumab, which specifically binds to IL-4Rα.

Currently, only one anti-IL-4Rα antibody has been approved for therapeutic use in the world (dupilumab). In connection with the above, it is relevant to create new antibodies that specifically bind to IL-4Rα.

Brief description of drawings

Figure 1 is a map of an expression vector carrying the genetic sequence of the variable domains.

Figure 2 is a map of a vector carrying the genetic sequence of an antibody heavy chain.

Figure 3 is a map of a vector carrying the genetic sequence of an antibody light chain.

For figures 2-3

Figure 4 is an electropherogram of antibodies 01-08 in a 7.5% polyacrylamide gel under denaturing non-reducing conditions after the first stage of purification on a Protein A sorbent.

M - molecular weight marker.

1-antibody 01.

2-antibody 02.

3-antibody 03.

4-antibody 04.

5-antibody 05.

6-antibody 06.

7-antibody 07.

8-antibody 08.

Figure 5 is an electropherogram of antibodies 09-16 in a 7.5% polyacrylamide gel under denaturing non-reducing conditions after the first stage of purification on a Protein A sorbent.

M - molecular weight marker.

1-antibody 09.

2- antibody 10.

3-antibody 11.

4-antibody 12.

5-antibody 13.

6-antibody 14.

7-antibody 15.

8-antibody 16.

Figure 6 is an electropherogram of antibody 17-22 in a 7.5% polyacrylamide gel under denaturing non-reducing conditions after the first stage of purification on a Protein A sorbent.

M - molecular weight marker.

1-antibody 17.

2- antibody 18.

3-antibody 19.

4- antibody 20.

5-antibody 21.

6-antibody 22.

Figure 7 is an electropherogram of antibodies 23-29 in a 7.5% polyacrylamide gel under denaturing non-reducing conditions after the first stage of purification on a Protein A sorbent.

M - molecular weight marker.

1- antibody 23.

2- antibody 24.

3- antibody 25.

4-antibody 26.

5-antibody 27.

6-antibody 28.

7-antibody 29.

Figure 8 is an electropherogram of antibodies 30-037 in a 7.5% polyacrylamide gel under denaturing non-reducing conditions after the first stage of purification on a Protein A sorbent.

M - molecular weight marker.

1- antibody 30.

2- antibody 31.

3- antibody 32.

4-antibody 33.

5-antibody 34.

6-antibody 35.

7-antibody 36.

8-antibody 37.

Definitions and general methods

Unless otherwise defined herein, scientific and technical terms used in connection with the present invention will have meanings that are commonly understood by those skilled in the art.

In addition, unless the context otherwise requires, terms in the singular include plural terms, and plural terms include singular terms. In general, the classification and methods of cell culture, molecular biology, immunology, microbiology, genetics, analytical chemistry, organic synthesis chemistry, medicinal and pharmaceutical chemistry, and hybridization and protein and nucleic acid chemistry described herein are well known to those skilled in the art. widely used in this field. Enzymatic reactions and purification methods are carried out in accordance with the manufacturer's instructions, as is typically carried out in the art, or as described herein.

The term "KD" as used herein refers to the affinity constant (or equilibrium constant) which is derived from the ratio of Kd to Ka (ie Kd/Ka) and is expressed as molar concentration (M).

“Binding affinity” generally refers to the strength of the aggregate non-covalent interactions between a single binding site of a molecule (eg, an antibody) and its binding partner (eg, an antigen). Unless otherwise specified, “binding affinity” refers to the intrinsic binding affinity that reflects the 1:1 interaction between members of a binding pair (eg, antibody and antigen). The affinity of a molecule X for its partner Y can usually be represented by an affinity constant (KD). It is desirable that the KD value is about 200 nM, 150 nM, 100 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 8 nM, 6 nM, 4 nM, 2 nM, 1 nM or less. Affinity can be measured by conventional methods known in the art, including methods described herein. Low-affinity antibodies typically bind antigen slowly and tend to dissociate easily, whereas high-affinity antibodies typically bind antigen more quickly and tend to remain bound longer. Various methods for measuring binding affinity are known in the art, any of these methods can be used for the purposes of the present invention.

The term "Kd", "koff" or "kdis" refers to the dissociation rate constant of a particular binding molecule-antigen interaction. The dissociation rate constant koff can be measured by biolayer interferometry, such as the Octet™ system.

The term "Ka", "kon" or "on-rate" refers to the rate constant of the association.

The term " ^R2 " refers to the coefficient of determination.

The term "Response" refers to the signal that an antibody binds to an antigen.

The term "in vitro" refers to a biological entity, biological process, or biological reaction outside the body, simulated under artificial conditions. For example, in vitro cell growth should be understood as the growth of cells in an environment outside the body, such as a test tube, culture flask, or microplate.

The term ED ₅₀ (EC ₅₀ ) (50% effective dose/concentration) refers to the drug concentrations at which 50% of the measured biological effect (may include cytotoxicity) is achieved.

In the present specification and in the following claims, unless the context otherwise requires, the words “include” and “comprise” or variations thereof such as “includes”, “comprising”, “contains” or “comprising” are to be understood as including the specified whole or group of wholes, but not to the exclusion of any other whole or group of wholes.

Detailed Description of the Invention

The authors of this group of inventions have developed antibodies that specifically bind to IL-4Rα and have high binding affinity parameters for the IL-4Rα antigen.

Antibody

The present invention provides a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to IL-4Rα (a subunit of the interleukin 4 receptor IL-4Rα).

The term "monoclonal antibody" or "mAb" refers to an antibody that is synthesized and secreted by a distinct clonal population of cells.

The antibody of the invention is a recombinant antibody.

The term “recombinant antibody” means an antibody that is expressed in a cell or cell line containing the nucleotide sequence(s) that encodes the antibody, wherein the nucleotide sequence(s) are not naturally associated with the cell.

In one aspect, the present invention provides an isolated monoclonal antibody or antigen binding fragment thereof that specifically binds IL-4Rα and includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 with the amino acid sequence X ₁ YWX ₂ H, where

X ₁ = T, Y, S, A or H;

X ₂ = M, F, L, I or V;

(ii) CDR2 with the amino acid sequence X3IRPAGSTYYTDSVKG, where

X ₃ = T or S;

And

(iii) CDR3 with the amino acid sequence GGX ₄ SX ₅ X ₆ WX ₇ X ₈ X ₉ X ₁₀ X ₁₁ ,

Where

X ₄ = Y, R or N;

X ₅ = S, A or R;

X ₆ = T, Q, E, R or S;

X ₇ = Y, H, G, T or V;

X ₈ = R, V, K or S;

X ₉ = Y, M, A, G, L or Q;

X ₁₀ = D, S, E, G, Q, H or N;

X ₁₁ = P, Y or S; And

(b) a light chain variable domain comprising:

(i) CDR1 with the amino acid sequence X ₁₂ GSX ₁₃ SNIGX ₁₄ X ₁₅ X ₁₆ VG, where

X ₁₂ = S or T;

X ₁₃ = T, R or S;

X ₁₄ = S, G or D;

X ₁₅ = N or Y;

X ₁₆ = V, T or Y;

(ii) CDR2 with the amino acid sequence X ₁₇ X ₁₈ X ₁₉ X ₂₀ X ₂₁ X ₂₂ S, where

X ₁₇ = R, I or S;

X ₁₈ = D or N;

X ₁₉ =N, S or T;

X ₂₀ = Q, E, N or R;

X ₂₁ = R or H;

X ₂₂ = P or A; And

(iii) CDR3 with amino acid sequence X ₂₃ X ₂₄ WDDX ₂₅ LX ₂₆ X ₂₇ VV

X ₂₃ = S, A or T;

X ₂₄ = T, A or S;

X ₂₅ = S or G;

X ₂₆ = N or S;

X ₂₇ = G or 0.

The term "isolated" as used to describe the various antibodies herein means an antibody that has been identified and isolated and/or recovered from the cell or cell culture in which it is expressed. Impurities (contaminants) from the natural environment are materials that typically interfere with the diagnostic or therapeutic use of the polypeptide, and may include enzymes, hormones, and other protein or non-protein solutes. Typically, the isolated polypeptide is obtained through at least one purification step.

The term "antibody" or "immunoglobulin" (Ig) as used herein includes whole antibodies. The term "antibody" refers to a glycoprotein containing at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, or an antigen-binding portion thereof. Each heavy chain contains a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. There are five known types of mammalian antibody heavy chains, which are designated by Greek letters: α, δ, ε, γ and μ. (Janeway S.A., Jr. et al., Munobiology, 5th ed., Garland Publishing, 2001). The type of heavy chain present determines the class of the antibody; these chains are found in antibodies of the IgA, IgD, IgE, IgG and IgM types, respectively (Rhoades R.A., Pflanzer R.G., Human Physiology, 4th ed., Thomson Learning, 2002). Different heavy chains differ in size and composition; α and γ contain approximately 450 amino acids, α μ and ε consist of approximately 550 amino acids. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. The heavy chains γ, α and δ contain a constant region, which consists of three constant domains CH1, CH2 and CH3 (arranged in a row) and a hinge region, which provides flexibility (Woof J., Burton D., Nat Rev Immunol 4, 2004, cc.89-99); The u and s heavy chains contain a constant region, which consists of four constant domains CH1, CH2, CH3 and CH4 (Janeway C.A., Jr. et al., Immunobiology, 5th ed., Garland Publishing, 2001 ). In mammals, only two types of light chains are known, designated lambda (λ) and kappa (κ). Each light chain consists of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The approximate length of the light chain is 211-217 amino acids. Preferably, the light chain is a kappa (κ) light chain and the CL constant domain is preferably a C-kappa (κ) chain.

"Antibodies" according to the invention can be antibodies of any class (eg, IgA, IgD, IgE, IgG and IgM, preferably IgG) or subclass (eg, IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2, preferably IgG4).

The VH and VL regions can be further subdivided into regions of hypervariability called complementarity determining regions (CDRs), interspersed between regions that are more conserved called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs, arranged from the amino terminus to the carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The heavy and light chain variable regions contain a binding domain that interacts with the antigen. Antibody constant regions can mediate the binding of immunoglobulin to host tissues or factors, including various cells of the immune system (eg, effector cells), and the first component (C1q) of the classical complement system.

The term "antigen binding portion" of an antibody or "antigen binding fragment" as used herein refers to one or more antibody fragments that retain the ability to specifically bind an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments included in the term “antigen-binding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of VL, VH, CL and CHI domains; (ii) P(ab')2 fragment, a divalent fragment containing two Fab fragments linked by a disulfide bridge in the hinge region; (iii) Fd fragment consisting of VH and CH1 domains; (iv) Fv fragment, consisting of VL and VH domains in a single antibody arm, (v) dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of VH/VHH domain. In addition, the two regions of the Fv fragment, VL and VH, are encoded by different genes; they can be joined by recombinant methods using a synthetic linker, which makes it possible to obtain them in the form of a single protein chain in which the VL and VH regions are paired to form monovalent molecules (known as single chain Fv (scFv); see, for example, Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879 -5883). It is intended that such single chain molecules are also included in the term "antigen binding portion" of an antibody. Such antibody fragments are prepared using conventional methods known to those skilled in the art, and these fragments are screened in the same manner as intact antibodies.

The term "variable" refers to the fact that certain segments of variable domains vary widely in sequence among antibodies. Domain V mediates antigen binding and determines the specificity of a particular antibody for its particular antigen. However, variability is not evenly distributed across the 110 amino acid stretch of variable domains. In contrast, V regions are composed of invariant fragments called framework regions (FRs) of 15–30 amino acids, separated by shorter regions of extreme variability called “hypervariable regions” or CDRs. Each variable domain of the native heavy and light chains contains four FRs, generally adopting a beta-sheet configuration, linked by three hypervariable regions that form binding loops and, in some cases, are part of a beta-sheet structure. The hypervariable regions on each chain are held together in close proximity by FR and, with the hypervariable regions on the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., Sequences of Proteins of Immunological Interest. 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991). Constant domains are not directly involved in the binding of the antibody to the antigen, but exhibit various effector functions, such as the participation of the antibody in antibody-dependent cellular cytotoxicity (ADCC).

The term "hypervariable region" as used herein refers to the amino acid residues of an antibody that are responsible for antigen binding. Typically, the hypervariable region contains amino acid residues from the “complementarity determining region” or “CDR” and/or such residues from the “hypervariable loop”.

“Kabat nomenclature” or “Kabat nomenclature” is used herein to refer to a numbering system for amino acid residues that are more variable (i.e., hypervariable) than other amino acid residues in the variable regions of the heavy and light chain of an antibody (Kabat et al. Ann. N.Y. Acad. Sci., 190:382-93 (1971); Kabat et al. Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242 (1991)).

An antibody of the present invention “that binds” a target antigen is an antibody that binds an antigen with sufficient affinity such that the antibody can be used as a diagnostic and/or therapeutic agent when targeting a protein or cell or tissue expressing the antigen, and in cross-reacts slightly with other proteins. According to analytical methods: fluorescence-activated cell sorting (FACS), radioimmunoprecipitation assay (RIA) or ELISA, in such embodiments of the invention the degree of binding of the antibody to a protein that is not a “target” (with a “non-target protein”) is less than 10 % of antibody binding to a specific target protein. With respect to the binding of an antibody to a target molecule, the term "specific binding" or the expressions "specifically binds to" or "specific to" a particular polypeptide or epitope on a particular target polypeptide means binding that is markedly (measurably) different from a nonspecific interaction.

Specific binding can be quantified, for example, by measuring the binding of a molecule compared to the binding of a control molecule. For example, specific binding can be determined by a competitive reaction with another molecule similar to the target, for example, with an excess of unlabeled target. In this case, specific binding is indicated if the binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target. As used herein, the term “specific binding” or the expressions “specifically binds to” or “specific to” a particular polypeptide or epitope on a particular target polypeptide can be characterized by a molecule having a KD to the target of at least about 200 nM, or at least at least about 150 nM, or at least about 100 nM, or at least about 60 nM, or at least about 50 nM, or at least about 40 nM, or at least about 30 nM, or at least about 20 nM, or at least about 10 nM, or at least about 8 nM, or at least about 6 nM, or at least about 4 nM, or at least about 2 nM, or at least about 1 nM or higher. In one embodiment, the term “specific binding” refers to binding in which a molecule binds to a specific polypeptide or epitope on a specific polypeptide without substantially binding to any other polypeptide or epitope on the polypeptide.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a heavy chain variable domain that contains a CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 362.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a heavy chain variable domain that contains a CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 11 or SEQ ID NO: 12.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a heavy chain variable domain that contains a CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30 or SEQ ID NO: 363.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a light chain variable domain that contains a CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 31, SEQ ID NO: 32, or SEQ ID NO: 33.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a light chain variable domain that contains a CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38 or SEQ ID NO: 39.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a light chain variable domain that contains a CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, or SEQ ID NO: 43.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes:

(a) a heavy chain variable domain comprising:

(i) a CDRT with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 362;

(ii) a CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 11 or SEQ ID NO: 12;

And

(iii) a CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO : 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30 or SEQ ID NO: 363; And

(b) a light chain variable domain comprising:

(i) a CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 31, SEQ ID NO: 32 or SEQ ID NO: 33;

(ii) a CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, or SEQ ID NO: 39;

And

(iii) a CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42 or SEQ ID NO: 43.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes:

(i) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 13; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 34 and

CDR3 with amino acid sequence SEQ ID NO: 40;

(ii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 14; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(iii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 15; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(iv) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 16; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 34 and

CDR3 with amino acid sequence SEQ ID NO: 40;

(v) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 17; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 34 and

CDR3 with amino acid sequence SEQ ID NO: 40;

(vi) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 2,

CDR2 with amino acid sequence SEQ ID NO: 12 and

CDR3 with amino acid sequence SEQ ID NO: 18; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 33,

CDR2 with amino acid sequence SEQ ID NO: 36 and

CDR3 with amino acid sequence SEQ ID NO: 42;

(vii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 3,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 19; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 33,

CDR2 with amino acid sequence SEQ ID NO: 37 and

CDR3 with amino acid sequence SEQ ID NO: 42;

(viii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 4,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 20, and

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 33,

CDR2 with amino acid sequence SEQ ID NO: 36 and

CDR3 with amino acid sequence SEQ ID NO: 42;

(ix) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 5,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 21; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 33,

CDR2 with amino acid sequence SEQ ID NO: 36 and

CDR3 with amino acid sequence SEQ ID NO: 42;

(x) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 22; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 33,

CDR2 with amino acid sequence SEQ ID NO: 36 and

CDR3 with amino acid sequence SEQ ID NO: 42;

(xi) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 6,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 23; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 33,

CDR2 with amino acid sequence SEQ ID NO: 36 and

CDR3 with amino acid sequence SEQ ID NO: 42;

(xii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 17; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 38 and

CDR3 with amino acid sequence SEQ ID NO: 40;

(xiii)(a) a heavy chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 362,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 363; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xiv) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 7,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 24; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xv) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 8,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 25, and

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xvi) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 9,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 21; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xvii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 8,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 26; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xviii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 8,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 27; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32,

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xix) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 29; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 34 and

CDR3 with amino acid sequence SEQ ID NO: 40;

(xx) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 8,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 30; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 32;

CDR2 with amino acid sequence SEQ ID NO: 35 and

CDR3 with amino acid sequence SEQ ID NO: 41;

(xxi) CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 17; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 34 and

CDR3 with amino acid sequence SEQ ID NO: 43; or

(xxii) (a) a heavy chain variable domain containing:

CDR1 with amino acid sequence SEQ ID NO: 1,

CDR2 with amino acid sequence SEQ ID NO: 11 and

CDR3 with amino acid sequence SEQ ID NO: 17; And

(b) a light chain variable domain comprising:

CDR1 with amino acid sequence SEQ ID NO: 31,

CDR2 with amino acid sequence SEQ ID NO: 39 and

CDR3 with amino acid sequence SEQ ID NO: 40.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a heavy chain variable domain that contains an amino acid sequence selected from the group: SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 366, SEQ ID NO: 368, SEQ ID NO: 370 or SEQ ID NO: 372.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes a light chain variable domain that contains an amino acid sequence selected from the group: SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86 or SEQ ID NO: 87.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes:

(a) a heavy chain variable domain that contains an amino acid sequence selected from the group: SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 366, SEQ ID NO: 368, SEQ ID NO: 370 or SEQ ID NO: 372.

And

(b) the light chain variable domain contains an amino acid sequence selected from the group: SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86 or SEQ ID NO: 87.

In some embodiments, the isolated monoclonal antibody or antigen binding fragment thereof includes:

(i) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 44 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(ii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 45 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(iii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 46 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(iv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 47 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(v) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 48 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(vi) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 49 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(vii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 50 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(viii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 51 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(ix) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 52 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(x)(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(xi) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 54 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76;

(xii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 55 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 77;

(xiii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 56 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76;

(xiv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 57 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76;

(xv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 58 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76;

(xvi) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 59 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76;

(xvii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 78;

(xviii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 60 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xix) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 61 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xx) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 62 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xxi) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 63;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xxii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 64 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xxiii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 65 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(xxiv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 66 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xxv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 67 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(xxvi) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 79;

(xxvii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 68 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xxviii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 69 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 80;

(xxix) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 70 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 81;

(xxx) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 71 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75;

(xxxi) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 72 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 82;

(xxxii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 73 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74;

(xxxiii) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 83;

(xxxiv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53 and

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 84;

(xxxv) (a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53 and

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 85;

(xxxvi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 86;

(xxxvii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 87;

(xxxviii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 366;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74;

(xxxix) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 368;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74;

(xxxx) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 370;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; or

(xxxxi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 372;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74.

In some embodiments, the isolated monoclonal antibody that specifically binds IL-4Rα is a full-length IgG antibody.

In some embodiments, the isolated monoclonal antibody is a full-length IgG antibody that is of the human IgG1, IgG2, IgG3, or IgG4 isotype.

In some embodiments, the isolated monoclonal antibody is a full-length IgG antibody that is of the human IgG4 isotype.

In some embodiments, the isolated monoclonal antibody contains the S228P mutation in the hinge region. The above mutation in the hinge region is numbered according to the amino acid numbering of the EU antibody chains (Edelman G.M. et al., Proc. Natl. Acad. Sci. USA 63, 1969, ee. 78-85; Kabat E.A. et al., Sequences of Proteins of Immunological Interest , 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991). The same mutation can be designated S241P according to the amino acid numbering of the Kabat antibody chains or S229P according to continuous numbering from the beginning of the chain.

In some embodiments, the isolated monoclonal antibody includes a heavy chain that contains an amino acid sequence selected from the group: SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 367, SEQ ID NO: 369, SEQ ID NO: 371 or, SEQ ID NO: 373.

In some embodiments, the isolated monoclonal antibody includes a light chain that contains an amino acid sequence selected from the group: SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130 or SEQ ID NO: 131.

In some embodiments, the isolated monoclonal antibody includes:

(i) (a) a heavy chain containing an amino acid sequence selected from the group: SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 367, SEQ ID NO: 369, SEQ ID NO: 371 or, SEQ ID NO: 373, and

(b) a light chain containing an amino acid sequence selected from the group: SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123 , SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130 or SEQ ID NO: 131;

(ii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 88, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(iii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 89, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(iv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 90, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(v) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 91, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(vi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 92, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(vii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 93, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(viii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 94, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(ix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 95, and

(b) a light chain containing the amino acid sequence SEQ ID NO: 118,

(x) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 96, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 98, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120;

(xiii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 99, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 121;

(xiv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 100, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120;

(xv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 101, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120;

(xvi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 102, and

(b) a light chain containing the amino acid sequence SEQ ID NO: 120,

(xvii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 103, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120;

(xviii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 122;

(xix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 104, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xx) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 105, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 106, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 107, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxiii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 108, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxiv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 109, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xxv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 110, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxvi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 111, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xxvii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 123;

(xxviii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 112, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 113, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 124;

(xxx) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 114, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 125;

(xxxi)(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 115, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119;

(xxxii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 116, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 126;

(xxxiii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 117, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xxxiv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 127;

(xxxv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 128;

(xxxvi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 129;

(xxxvii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 130;

(xxxviii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 131;

(xxxix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 367, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xxxx) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 369, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

(xxxxi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 371, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118;

or

(xxxxii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 373, and

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 01.

Antibody 01 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 88; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 01 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 44;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74.

Antibody 01 includes:

(a) a heavy chain variable domain containing:

(i) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 01 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 132,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 143, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 01 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 174,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 185, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 02.

Antibody 02 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 89; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 02 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 45;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 02 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 02 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 133,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 143, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 02 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 175,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 185, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 03.

Antibody 03 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 90; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 03 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 46;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 03 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 14, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 03 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 134,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 144, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 03 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 176,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 186, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 04.

Antibody 04 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 91; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 04 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 47;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 04 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 04 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 135,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 143, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 04 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 177,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 185, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 05.

Antibody 05 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 92; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 05 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 48;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 05 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 15, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 05 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 145, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 05 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 187, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 06.

Antibody 06 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 93; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 06 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 49;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 06 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 06 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 143, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 06 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 185, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 07.

Antibody 07 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 94; And

(b) a light chain containing the amino acid sequence SEQ ID NO: 118

Antibody 07 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 50;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 07 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 16, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 07 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 146, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 07 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 188, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 08.

Antibody 08 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 95; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 08 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 51;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 08 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 08 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 137,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 143, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 08 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 179,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 185, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 09.

Antibody 09 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 96; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 09 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 52;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 09 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 09 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 137,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 143, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 09 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 179,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 185, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 10.

Antibody 10 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 10 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 10 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 10 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 10 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 11.

Antibody 11 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 98; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120.

Antibody 11 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 54;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76.

Antibody 11 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 2,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 12,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 18, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 33,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 36,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 42.

Antibody 11 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 148, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 163,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 166,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 172.

Antibody 11 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 190, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 205,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 208,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 212.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 12.

Antibody 12 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 99; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 121.

Antibody 12 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 55;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 77.

Antibody 12 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 3,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 19, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 33,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 37,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 42.

Antibody 12 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 149, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 163,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 167,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 172.

Antibody 12 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 191, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 205,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 209,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 212.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 13.

Antibody 13 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 100; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120.

Antibody 13 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 56;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76.

Antibody 13 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 4,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 20, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 33,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 36,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 42.

Antibody 13 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 150, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 163,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 166,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 172.

Antibody 13 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 192, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 205,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 208,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 212.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 14.

Antibody 14 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 101; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120.

Antibody 14 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 57;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76.

Antibody 14 includes:

(a) heavy chain variable domain; containing:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 5,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 11, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 33,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 36,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 42.

Antibody 14 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 139,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 151, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 163,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 166,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 172.

Antibody 14 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 181,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 193, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 205,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 208,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 212.

In some embodiments, the isolated monoclonal antibody that specifically binds IL-4Rα is antibody 15.

Antibody 15 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 102; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120.

Antibody 15 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 58;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76.

Antibody 15 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 22, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 33,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 36,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 42.

Antibody 15 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 152, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 163,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 166,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 172.

Antibody 15 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 194, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 205,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 208,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 212.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 16.

Antibody 16 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 103; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 120.

Antibody 16 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 59;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 76.

Antibody 16 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 6,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 23, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 33,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 36,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 42.

Antibody 16 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 140,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 153, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 163,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 166,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 172.

Antibody 16 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 182,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 195, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 205,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 208,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 212.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 17.

Antibody 17 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 122.

Antibody 17 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 78.

Antibody 17 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 38,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 17 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 168,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 17 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 18.

Antibody 18 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 104; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 18 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 60;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 18 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 362,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 363, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 18 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 364, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 18 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 365, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 19.

Antibody 19 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 105; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 19 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 61;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 19 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 7,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 24, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 19 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 141,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 154, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 19 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 183,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 196, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 20.

Antibody 20 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 106; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 20 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 62;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 20 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 8,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 25, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 20 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 155, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 20 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 197, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 21.

Antibody 21 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 107; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 21 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 63;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 21 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 9,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 21, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 21 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 141,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 151, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 21 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 183,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 193, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 22.

Antibody 22 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 108; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 22 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 64;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 22 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 8,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 26, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 22 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 156, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 22 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 198, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 23.

Antibody 23 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 109; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 23 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 65;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 23 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 23 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 23 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 24.

Antibody 24 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 110; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 24 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 66;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 24 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 8,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 27, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 24 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 157, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 24 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 199, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 25.

Antibody 25 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 111; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 25 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 67;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 25 includes:

(a) heavy chain variable domain; containing:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 25 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 25 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 26.

Antibody 26 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 123.

Antibody 26 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 79.

Antibody 26 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 26 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 26 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 27.

Antibody 27 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 112; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 27 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 68;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 27 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 10,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 28, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 27 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 141,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 158, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 27 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 183,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 200, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 28.

Antibody 28 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 113; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 124.

Antibody 28 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 69;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 80.

Antibody 28 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 29, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 28 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 159, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 28 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with the amino acid sequence of SEQ ID NO: 201, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 29.

Antibody 29 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 114; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 125.

Antibody 29 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 70;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 81.

Antibody 29 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 29 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 29 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 30.

Antibody 30 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 115; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 119.

Antibody 30 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 71;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 75.

Antibody 30 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 8,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 30, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 32,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 35,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 41.

Antibody 30 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 138,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 160, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 162,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 165,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 171.

Antibody 30 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 180,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 202, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 204,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 207,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 211.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 31.

Antibody 31 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 116; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 126.

Antibody 31 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 72;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 82.

Antibody 31 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 31 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 31 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 32.

Antibody 32 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 117; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 32 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 73;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 74.

Antibody 32 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 32 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 32 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 33.

Antibody 33 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 127.

Antibody 33 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 83.

Antibody 33 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 43.

Antibody 33 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 173.

Antibody 33 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 213.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 34.

Antibody 34 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 128.

Antibody 34 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 84.

Antibody 34 includes:

(a) a heavy chain variable domain containing:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 39,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 34 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 169,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 34 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 35.

Antibody 35 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 129.

Antibody 35 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 85.

Antibody 35 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 35 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 35 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 36.

Antibody 36 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 130.

Antibody 36 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 86.

Antibody 36 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 36 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 36 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

In some embodiments, the isolated monoclonal antibody that specifically binds to IL-4Rα is antibody 37.

Antibody 37 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 131.

Antibody 37 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 53;

(b) a light chain variable domain which contains the amino acid sequence of SEQ ID NO: 87.

Antibody 37 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 37 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 136,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 142,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 147, and

(b) a light chain variable domain comprising:

(i) CDR1 (Chothia) with amino acid sequence SEQ ID NO: 161,

(ii) CDR2 (Chothia) with amino acid sequence SEQ ID NO: 164,

(iii) CDR3 (Chothia) with amino acid sequence SEQ ID NO: 170.

Antibody 37 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 178,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 184,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 189, and

(b) a light chain variable domain comprising:

(i) CDR1 (IMGT) with amino acid sequence SEQ ID NO: 203,

(ii) CDR2 (IMGT) with amino acid sequence SEQ ID NO: 206,

(iii) CDR3 (IMGT) with amino acid sequence SEQ ID NO: 210.

Antibody 38 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 367; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 38 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 366;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74.

Antibody 38 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 39 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 369; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 39 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 368;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74.

Antibody 39 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 40 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 371; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 40 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 370;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74.

Antibody 40 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 13, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody 41 includes:

(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 373; And

(b) a light chain containing the amino acid sequence of SEQ ID NO: 118.

Antibody 41 includes:

(a) a heavy chain variable domain which contains the amino acid sequence of SEQ ID NO: 372;

(b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74.

Antibody 41 includes:

(a) a heavy chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 1,

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 11,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 17, and

(b) a light chain variable domain comprising:

(i) CDR1 (Kabat) with amino acid sequence SEQ ID NO: 31

(ii) CDR2 (Kabat) with amino acid sequence SEQ ID NO: 34,

(iii) CDR3 (Kabat) with amino acid sequence SEQ ID NO: 40.

Antibody fragments

In certain circumstances, it may be appropriate to use antibody fragments rather than full antibodies. The smaller size of the fragments facilitates their rapid clearance and may allow for better penetration into solid tumors.

Various methods have been developed to obtain antibody fragments. Traditionally, these fragments have been prepared by proteolytic cleavage of intact antibodies (see, for example, Morimoto et al., Journal of Biochemical and Biophysical Methods, 24, 1992, pp. 107-117 and Brennan et al., Science, 229, 1985, p. 81). However, these fragments can now be produced directly from recombinant host cells. Fab, Fv, and scFv antibody fragments can be expressed and secreted from E. coli, allowing the production of large quantities of these fragments to be facilitated. Antibody fragments can be isolated from phage antibody libraries. In another embodiment, Fab'-SH fragments can be directly isolated from E. coli and chemically cross-linked to produce P(ab')2 fragments (Carter et al., Bio/Technology, 10, 1992, pp. 163-167). According to another approach, F(ab')2 fragments can be isolated directly from a culture of recombinant host cells. Fab and P(ab')2 fragments with increased in vivo half-lives that retain epitope-binding receptor residues are described in US Pat. No. 5,869,046. Other techniques for producing antibody fragments will be apparent to those skilled in the art. In other embodiments, the antibody selected is a single chain Fv fragment (scFv) (see WO 93/16185; US 5,571,894 and US US 5,587,458). Fv and scFv are the only species with intact binding sites lacking constant regions; as a result, they can be used for reduced nonspecific binding when used in vivo. ScFv-carrying fusion proteins can be engineered to produce an effector protein fusion at either the N- or C-terminus of the scFv (see Antibody Engineering, ed. Borrebaeck, supra). The antibody fragment may also be a "linear antibody" such as that described in US Pat. No. 5,641,870.

Nucleic acid molecule

In one aspect, the present invention provides a nucleic acid that encodes any of the above antibodies or antigen binding fragments thereof that specifically binds IL-4Rα.

In any of these embodiments, the nucleic acid molecules may be isolated.

The terms "nucleic acid", "nucleic sequence" or "nucleic acid sequence", "polynucleotide", "oligonucleotide", "polynucleotide sequence" and "nucleotide sequence", as used interchangeably herein, refer to a distinct sequence of nucleotides, modified or unmodified , defining a fragment or region of nucleic acid, containing or not containing unnatural nucleotides and being either double-stranded DNA or RNA, or single-stranded DNA or RNA, or transcription products of these DNAs.

It should also be mentioned here that this invention does not relate to nucleotide sequences in their natural chromosomal environment, i.e. in its natural state. The sequences of the present invention have been isolated and/or purified, i.e. were taken directly or indirectly, for example by copying, and their environment was at least partially modified. Thus, it should also be understood here as isolated nucleic acids obtained by genetic recombination, for example by host cells, or obtained by chemical synthesis.

Nucleotide sequence reference covers its complement unless otherwise noted. Thus, reference to a nucleic acid having a specific sequence should be understood to include its complementary strand with its complementary sequence.

An “isolated” nucleic acid molecule is a nucleic acid molecule that has been identified and separated from at least one contaminant nucleic acid molecule with which it is typically associated in a natural source of antibody nucleic acid. The isolated nucleic acid molecule differs from the form or set in which it occurs naturally. Thus, the isolated nucleic acid molecule is different from the nucleic acid molecule that naturally exists in cells.

In one aspect, the present invention provides a nucleic acid molecule comprising a nucleotide sequence that encodes an amino acid sequence selected from SEQ ID NO: 1-213, 362-373. The nucleic acid molecule may also contain any combination of these nucleotide sequences.

It will be apparent to one skilled in the art that the amino acid sequence of the light or heavy chain of an antibody of the invention or fragments thereof (VH, VL, CDR, etc.) can be encoded by a wide variety of different DNA sequences, taking into account the degeneracy of the genetic code. It is well known to those skilled in the art to obtain such alternative DNA sequences encoding the same amino acid sequences. Such variant DNA sequences are within the scope of the present invention.

In some embodiments, the isolated nucleic acid is DNA.

The nucleic acid molecule of the present invention can be isolated from any source that produces a monoclonal antibody or antigen binding fragment thereof that specifically binds IL-4Rα. In certain embodiments of the invention, the nucleic acid molecule of this invention may be synthesized rather than isolated.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of Antibody 01, and includes the nucleotide sequence of SEQ ID NO: 214.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of Antibody 01, and includes the nucleotide sequence of SEQ ID NO: 215.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of Antibody 01 and includes the nucleotide sequence of SEQ ID NO: 216.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of Antibody 01 and includes the nucleotide sequence of SEQ ID NO: 217.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 02 heavy chain variable domain and includes the nucleotide sequence of SEQ ID NO: 218.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 02 light chain variable domain and includes the nucleotide sequence of SEQ ID NO: 219.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 02, and includes the nucleotide sequence of SEQ ID NO: 220.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 02, and includes the nucleotide sequence of SEQ ID NO: 221.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 03 heavy chain variable domain and includes the nucleotide sequence of SEQ ID NO: 222.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 03 light chain variable domain and includes the nucleotide sequence of SEQ ID NO: 223.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 03, and includes the nucleotide sequence of SEQ ID NO: 224.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 03, and includes the nucleotide sequence of SEQ ID NO: 225.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 04 heavy chain variable domain and includes the nucleotide sequence of SEQ ID NO: 226.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 04, and includes the nucleotide sequence of SEQ ID NO: 227.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of Antibody 04 and includes the nucleotide sequence of SEQ ID NO: 228.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 04, and includes the nucleotide sequence of SEQ ID NO: 229.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 05, and includes the nucleotide sequence of SEQ ID NO: 230.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 05, and includes the nucleotide sequence of SEQ ID NO: 231.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of Antibody 05 and includes the nucleotide sequence of SEQ ID NO: 232.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 05, and includes the nucleotide sequence of SEQ ID NO: 233.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 06 heavy chain variable domain and includes the nucleotide sequence of SEQ ID NO: 234.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 06, and includes the nucleotide sequence of SEQ ID NO: 235.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 06, and includes the nucleotide sequence of SEQ ID NO: 236.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 06, and includes the nucleotide sequence of SEQ ID NO: 237.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the antibody 07 heavy chain variable domain and includes the nucleotide sequence of SEQ ID NO: 238.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 07, and includes the nucleotide sequence of SEQ ID NO: 239.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 07, and includes the nucleotide sequence of SEQ ID NO: 240.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 07, and includes the nucleotide sequence of SEQ ID NO: 241.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of Antibody 08, and includes the nucleotide sequence of SEQ ID NO: 242.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 08, and includes the nucleotide sequence of SEQ ID NO: 243.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 08, and includes the nucleotide sequence of SEQ ID NO: 244.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 08, and includes the nucleotide sequence of SEQ ID NO: 245.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 09, and includes the nucleotide sequence of SEQ ID NO: 246.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 09, and includes the nucleotide sequence of SEQ ID NO: 247.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 09, and includes the nucleotide sequence of SEQ ID NO: 248.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 09, and includes the nucleotide sequence of SEQ ID NO: 249.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 10, and includes the nucleotide sequence of SEQ ID NO: 250.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 10, and includes the nucleotide sequence of SEQ ID NO: 251.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 10, and includes the nucleotide sequence of SEQ ID NO: 252.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 10 and includes the nucleotide sequence of SEQ ID NO: 253.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 11, and includes the nucleotide sequence of SEQ ID NO: 254.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 11, and includes the nucleotide sequence of SEQ ID NO: 255.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 11 and includes the nucleotide sequence of SEQ ID NO: 256.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 11 and includes the nucleotide sequence of SEQ ID NO: 257.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 12, and includes the nucleotide sequence of SEQ ID NO: 258.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 12, and includes the nucleotide sequence of SEQ ID NO: 259.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 12 and includes the nucleotide sequence of SEQ ID NO: 260.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 12 and includes the nucleotide sequence of SEQ ID NO: 261.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 13, and includes the nucleotide sequence of SEQ ID NO: 262.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 13, and includes the nucleotide sequence of SEQ ID NO: 263.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 13 and includes the nucleotide sequence of SEQ ID NO: 264.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 13 and includes the nucleotide sequence of SEQ ID NO: 265.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 14, and includes the nucleotide sequence of SEQ ID NO: 266.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 14, and includes the nucleotide sequence of SEQ ID NO: 267.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 14 and includes the nucleotide sequence of SEQ ID NO: 268.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 14 and includes the nucleotide sequence of SEQ ID NO: 269.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 15, and includes the nucleotide sequence of SEQ ID NO: 270.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 15, and includes the nucleotide sequence of SEQ ID NO: 271.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 15 and includes the nucleotide sequence of SEQ ID NO: 272.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 15 and includes the nucleotide sequence of SEQ ID NO: 273.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 16, and includes the nucleotide sequence of SEQ ID NO: 274.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 16, and includes the nucleotide sequence of SEQ ID NO: 275.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 16 and includes the nucleotide sequence of SEQ ID NO: 276.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 16 and includes the nucleotide sequence of SEQ ID NO: 277.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 17, and includes the nucleotide sequence of SEQ ID NO: 278.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 17, and includes the nucleotide sequence of SEQ ID NO: 279.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 17 and includes the nucleotide sequence of SEQ ID NO: 280.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 17 and includes the nucleotide sequence of SEQ ID NO: 281.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 18, and includes the nucleotide sequence of SEQ ID NO: 282.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 18, and includes the nucleotide sequence of SEQ ID NO: 283.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 18 and includes the nucleotide sequence of SEQ ID NO: 284.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 18 and includes the nucleotide sequence of SEQ ID NO: 285.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 19, and includes the nucleotide sequence of SEQ ID NO:286.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 19, and includes the nucleotide sequence of SEQ ID NO: 287.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 19 and includes the nucleotide sequence of SEQ ID NO: 288.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 19 and includes the nucleotide sequence of SEQ ID NO: 289.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 20, and includes the nucleotide sequence of SEQ ID NO: 290.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 20, and includes the nucleotide sequence of SEQ ID NO: 291.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 20 and includes the nucleotide sequence of SEQ ID NO: 292.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 20 and includes the nucleotide sequence of SEQ ID NO: 293.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 21, and includes the nucleotide sequence of SEQ ID NO: 294.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 21, and includes the nucleotide sequence of SEQ ID NO: 295.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 21, and includes the nucleotide sequence of SEQ ID NO: 296.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 21 and includes the nucleotide sequence of SEQ ID NO: 297.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 22, and includes the nucleotide sequence of SEQ ID NO: 298.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 22, and includes the nucleotide sequence of SEQ ID NO: 299.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 22 and includes the nucleotide sequence of SEQ ID NO: 300.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 22 and includes the nucleotide sequence of SEQ ID NO: 301.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 23, and includes the nucleotide sequence of SEQ ID NO: 302.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 23, and includes the nucleotide sequence of SEQ ID NO: 303.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 23 and includes the nucleotide sequence of SEQ ID NO: 304.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 23 and includes the nucleotide sequence of SEQ ID NO: 305.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 24, and includes the nucleotide sequence of SEQ ID NO: 306.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 24, and includes the nucleotide sequence of SEQ ID NO: 307.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 24 and includes the nucleotide sequence of SEQ ID NO: 308.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 24 and includes the nucleotide sequence of SEQ ID NO: 309.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 25, and includes the nucleotide sequence of SEQ ID NO: 310.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 25, and includes the nucleotide sequence of SEQ ID NO: 311.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 25 and includes the nucleotide sequence of SEQ ID NO: 312.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 25, and includes the nucleotide sequence of SEQ ID NO: 313.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 26, and includes the nucleotide sequence of SEQ ID NO: 314.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 26, and includes the nucleotide sequence of SEQ ID NO: 315.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 26 and includes the nucleotide sequence of SEQ ID NO: 316.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 26 and includes the nucleotide sequence of SEQ ID NO: 317.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 27, and includes the nucleotide sequence of SEQ ID NO: 318.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 27, and includes the nucleotide sequence of SEQ ID NO: 319.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 27, and includes the nucleotide sequence of SEQ ID NO: 320.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 27, and includes the nucleotide sequence of SEQ ID NO: 321.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 28, and includes the nucleotide sequence of SEQ ID NO: 322.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 28, and includes the nucleotide sequence of SEQ ID NO: 323.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 28 and includes the nucleotide sequence of SEQ ID NO: 324.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 28 and includes the nucleotide sequence of SEQ ID NO: 325.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 29, and includes the nucleotide sequence of SEQ ID NO: 326.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 29, and includes the nucleotide sequence of SEQ ID NO: 327.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 29 and includes the nucleotide sequence of SEQ ID NO: 328.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 29, and includes the nucleotide sequence of SEQ ID NO: 329.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 30, and includes the nucleotide sequence of SEQ ID NO: 330.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 30, and includes the nucleotide sequence of SEQ ID NO: 331.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 30 and includes the nucleotide sequence of SEQ ID NO: 332.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 30 and includes the nucleotide sequence of SEQ ID NO: 333.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 31, and includes the nucleotide sequence of SEQ ID NO: 334.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 31, and includes the nucleotide sequence of SEQ ID NO: 335.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 31 and includes the nucleotide sequence of SEQ ID NO: 336.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 31 and includes the nucleotide sequence of SEQ ID NO: 337.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 32, and includes the nucleotide sequence of SEQ ID NO: 338.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 32, and includes the nucleotide sequence of SEQ ID NO: 339.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 32 and includes the nucleotide sequence of SEQ ID NO: 340.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 32 and includes the nucleotide sequence of SEQ ID NO: 341.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 33, and includes the nucleotide sequence of SEQ ID NO: 342.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 33, and includes the nucleotide sequence of SEQ ID NO: 343.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 33 and includes the nucleotide sequence of SEQ ID NO: 344.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 33 and includes the nucleotide sequence of SEQ ID NO: 345.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 34, and includes the nucleotide sequence of SEQ ID NO: 346.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 34, and includes the nucleotide sequence of SEQ ID NO: 347.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 34 and includes the nucleotide sequence of SEQ ID NO: 348.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 34 and includes the nucleotide sequence of SEQ ID NO: 349.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 35, and includes the nucleotide sequence of SEQ ID NO: 350.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 35, and includes the nucleotide sequence of SEQ ID NO: 351.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 35 and includes the nucleotide sequence of SEQ ID NO: 352.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 35 and includes the nucleotide sequence of SEQ ID NO: 353.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 36, and includes the nucleotide sequence of SEQ ID NO: 354.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 36, and includes the nucleotide sequence of SEQ ID NO: 355.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 36 and includes the nucleotide sequence of SEQ ID NO: 356.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 36 and includes the nucleotide sequence of SEQ ID NO: 357.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 37, and includes the nucleotide sequence of SEQ ID NO: 358.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 37, and includes the nucleotide sequence of SEQ ID NO: 359.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 37 and includes the nucleotide sequence of SEQ ID NO: 360.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 37, and includes the nucleotide sequence of SEQ ID NO: 361.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 38, and includes the nucleotide sequence of SEQ ID NO: 374.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 38, and includes the nucleotide sequence of SEQ ID NO: 215.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 38 and includes the nucleotide sequence of SEQ ID NO: 375.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 38 and includes the nucleotide sequence of SEQ ID NO: 217.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 39, and includes the nucleotide sequence of SEQ ID NO: 376.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 39, and includes the nucleotide sequence of SEQ ID NO: 215.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 39 and includes the nucleotide sequence of SEQ ID NO: 377.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 39, and includes the nucleotide sequence of SEQ ID NO: 217.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 40, and includes the nucleotide sequence of SEQ ID NO: 378.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 40, and includes the nucleotide sequence of SEQ ID NO: 215.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 40 and includes the nucleotide sequence of SEQ ID NO: 379.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 40 and includes the nucleotide sequence of SEQ ID NO: 217.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 41, and includes the nucleotide sequence of SEQ ID NO: 380.

In some embodiments, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 41, and includes the nucleotide sequence of SEQ ID NO: 215.

In some embodiments, the nucleic acid is a nucleic acid that encodes the heavy chain amino acid sequence of antibody 41 and includes the nucleotide sequence of SEQ ID NO: 381.

In some embodiments, the nucleic acid is a nucleic acid that encodes the light chain amino acid sequence of antibody 41 and includes the nucleotide sequence of SEQ ID NO: 217.

Nucleic acid molecules can be used to express a recombinant monoclonal antibody or antigen binding fragment thereof that specifically binds IL-4Rα.

Vector

In one aspect, the present invention relates to an expression vector containing the above isolated nucleic acid. The present invention provides a vector suitable for expressing any of the nucleotide sequences described herein.

The term “vector” as used herein means a nucleic acid molecule capable of transporting another nucleic acid to which it is linked. In some embodiments, the vector is a plasmid, i.e. a circular double-stranded portion of DNA into which additional DNA segments can be ligated. In some embodiments, the vector is a viral vector in which additional DNA segments can be ligated into the viral genome. In some embodiments, the vectors are capable of autonomous replication in the host cell into which they are introduced (eg, bacterial vectors having a bacterial origin of replication and mammalian episomal vectors). In other embodiments, vectors (eg, non-episomal mammalian vectors) can be integrated into the host cell genome upon introduction into the host cell, and thus replicate along with the host gene. Moreover, some vectors are capable of directing the expression of genes to which they are operably linked. Such vectors are referred to herein as “recombinant expression vectors” (or simply “expression vectors” (“expression vector” or “expression vector”)).

The present invention relates to vectors containing nucleic acid molecules that encode any of the amino acid sequences of a monoclonal antibody that specifically binds to IL-4Rα, or portions thereof (e.g., heavy chain and/or light chain binding domain sequences) as described herein . The present invention further relates to vectors containing nucleic acid molecules encoding antibodies or fragments of these antibodies.

Expression vectors include plasmids, retroviruses, adenoviruses, adeno-associated viruses (AAV), plant viruses such as cauliflower mosaic virus, tobacco mosaic virus, cosmid, YAC, EBV-derived episomes and the like. DNA molecules can be ligated into a vector such that the transcription and translation control sequences in the vector perform the intended function of regulating DNA transcription and translation. The expression vector and expression control sequences can be selected to be compatible with the expression host cell used. DNA molecules encoding partial or entire sequences of the first and second binding domains (eg, heavy and light chain sequences, where the binding domain contains a heavy and light chain sequence) can be introduced into separate vectors. In one embodiment of the invention, any combination of the above DNA molecules is introduced into the same expression vector. DNA molecules can be introduced into the expression vector by standard methods (eg, by ligating complementary restriction sites on the antibody gene fragment and the vector, or blunt-end ligation if restriction sites are not present).

In some embodiments, a suitable vector is one that includes restriction sites such that any VH or VL sequence can be readily included and expressed as described above. Termination of polyadenylation and transcription can occur downstream of the native chromosome site of the encoded regions. The recombinant expression vector may also encode a signal peptide that facilitates production of an antibody chain by the host cell. The antibody chain gene can be cloned into a vector such that the signal peptide is linked to the amino terminus of the immunoglobulin chain. The signal peptide may be an immunoglobulin signal peptide or a heterologous signal peptide (ie, a non-immunoglobulin protein signal peptide).

In some embodiments, in addition to the antibody gene chain, the recombinant expression vectors of the present invention may carry regulatory sequences that control expression of the antibody chain genes in the host cell. Those skilled in the art will appreciate that the design of an expression vector, including the choice of regulatory sequences, may depend on factors such as the selection of the host cell for transformation, the level of expression of the desired protein, etc. Preferred regulatory sequences for a mammalian host expression cell include viral elements that provide high level expression of proteins in mammalian cells, such as promoters and/or enhancers derived from a retroviral LTR, cytomegalovirus (CMV) (eg, CMV promoter/enhancer), simian virus 40 (SV40) (eg, SV40 promoter/enhancer), adenovirus (eg, adenovirus large late promoter (AdMLP)), polyoma virus, as well as strong mammalian promoters such as the native immunoglobulin promoter or the actin promoter. Methods for expressing polypeptides in bacterial or fungal cells, such as yeast cells, are also well known in the art.

In some embodiments, in addition to antibody chain genes and regulatory sequences, recombinant expression vectors of the invention may carry additional sequences, such as sequences that regulate replication of the vector in host cells (eg, origins of replication) and selectable marker genes. The selectable marker gene facilitates selection of host cells into which the vector has been introduced.

In some embodiments, the vector may include an expression control sequence. The term "expression control sequence" as used herein refers to polynucleotide sequences that are necessary to influence the expression and processing of the coding sequences to which they are ligated. Expression control sequences include the corresponding transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that increase translation efficiency (ie, the Kozak consensus sequence); sequences that increase protein stability; and, if desired, sequences that enhance protein secretion. The nature of such control sequences varies depending on the host organism; in prokaryotes, such control sequences typically include a promoter, a ribosome binding site, and transcription termination sequences; in eukaryotes, such control sequences typically include promoters and transcription termination sequences. The term “control sequences” includes, at a minimum, all components whose presence is essential for expression and processing, and may also include additional components whose presence is beneficial, such as leader sequences and fusion sequences. Host cell

In one aspect, the present invention relates to a method of obtaining a host cell for producing any of the above antibodies or antigen binding fragments thereof that specifically binds IL-4Rα, and includes transforming the cell with the above vector.

In one aspect, the present invention relates to a host cell for producing any of the above antibodies or an antigen binding fragment thereof that specifically binds to IL-4Rα that contains any of the above nucleic acids.

The term "recombinant host cell" (or simply "host cell") as used herein means a cell into which a recombinant expression vector has been introduced. The present invention relates to host cells, which may include, for example, a vector in accordance with the present invention described above. The present invention also relates to host cells that include, for example, a nucleotide sequence encoding a heavy chain or antigen binding portions thereof, a nucleotide sequence encoding a light chain or antigen binding portions thereof, or both, of the binding domain of a binding molecule of the invention. It should be understood that “recombinant host cell” and “host cell” mean not only the specific cell claimed, but also the progeny of such cell. Since modifications may occur in subsequent generations due to mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but such cells are still included within the scope of the term “host cell” as used herein.

Nucleic acid molecules encoding a monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα of the invention, and vectors containing these nucleic acid molecules, can be used to transfect a suitable mammal or cell thereof, plant or cell thereof, bacterial or yeast host cells. The transformation can occur by any known method for introducing polynucleotides into the host cell. Methods for introducing heterologous polynucleotides into mammalian cells are well known in the art and include dextran-mediated transfection, nucleic acid-positively charged polymer complex transfection, nucleic acid-calcium phosphate precipitate transfection, polybrene-mediated transfection, protoplast fusion, transfection with liposome-encapsulated polynucleotides, and direct microinjection. DNA into nuclei. In addition, nucleic acid molecules can be introduced into mammalian cells by viral vectors.

Mammalian cell lines used as hosts for transformation are well known in the art and include many immortalized cell lines available. These include, for example, Chinese hamster ovary (CHO) cells, NS0 cells, SP2 cells, HEK-293T cells, 293 Freestyle cells (Invitrogen), NIH-3T3 cells, HeLa cells, hamster kidney (HK) cells, African kidney cells vervet monkeys (COS), human hepatocellular carcinoma cells (eg Hep G2), A549 cells and a number of other cell lines. Cell lines are selected by determining which cell lines have high levels of expression and provide the desired characteristics of the protein produced. Other cell lines that can be used are insect cell lines such as Sf9 or Sf21 cells. When recombinant expression vectors encoding a monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα are introduced into mammalian host cells, the antibodies or fragments thereof are produced by culturing the host cells for a time sufficient to express the antibodies or fragments thereof in host cells or, preferably, releasing antibodies or fragments thereof into the culture medium in which the host cells are grown. A monoclonal antibody or antigen binding fragment thereof that specifically binds to IL-4Rα can be isolated from the culture medium using standard protein purification techniques. Plant host cells, for example, include Nicotiana, Arabidopsis, duckweed, corn, wheat, potato, etc. Host bacterial cells include Escherichia and Streptomyces species. Yeast host cells include Schizosaccharomyces pombe, Saccharomyces cerevisiae and Pichiapastoris.

In addition, the level of production of a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to IL-4Rα from a producing cell line can be enhanced by a number of known methods. For example, the glutamine synthetase gene expression system (GS system) is common enough to enhance expression under certain conditions.

It is likely that a monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα from different cell lines will differ in its glycosylation profile. However, a monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα encoded by the nucleic acid molecules described herein or containing the amino acid sequences described herein is part of the present invention, regardless of the glycosylation state of the binding molecules and in general , regardless of the presence or absence of post-translational modifications.

The above host cell does not refer to a host cell obtained using human embryos.

The above host cell does not refer to a host cell obtained by modifying the genetic integrity of human germline cells.

Antibody production method

In one aspect, the present invention relates to a method for producing an antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα, comprising culturing the above-described host cell in a culture medium under conditions sufficient to obtain said antibody or fragment thereof, if necessary, followed by isolation and purification of the resulting antibody or its fragment.

The present invention relates to methods for producing a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to IL-4Rα according to the present invention. One embodiment of the invention relates to a method of producing a monoclonal antibody or antigen binding fragment thereof that specifically binds IL-4Rα, as defined herein, comprising producing a recombinant host cell capable of expressing a monoclonal antibody or antigen binding fragment thereof that specifically binds IL -4Rα, culturing said host cell under conditions suitable for expressing the production of a monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα, and isolating the resulting monoclonal antibody or fragment thereof that specifically binds IL-4Rα. A monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα produced by such expression in such recombinant host cells is referred to herein as a “recombinant monoclonal antibody that specifically binds IL-4Rα” or “an antigen-binding fragment of a recombinant monoclonal antibody that which specifically binds to IL-4Rα."

Pharmaceutical compositions

Another aspect of the invention is a pharmaceutical composition containing as an active ingredient (or as the only active ingredient) a monoclonal antibody of the present invention or an antigen binding fragment thereof that specifically binds to IL-4Rα.

In one aspect, the present invention provides a pharmaceutical composition for treating a disease or disorder mediated by IL-4Rα, which contains any of the above antibody or antigen binding fragment thereof in a therapeutically effective amount in combination with one or more pharmaceutically acceptable excipients.

"Pharmaceutical composition" means a composition comprising an antibody according to the invention and at least one of the components selected from the group consisting of pharmaceutically acceptable and pharmacologically compatible excipients, solvents, diluents, carriers, auxiliary, distributing and receptive agents, agents delivery agents, such as preservatives, stabilizers, fillers, disintegrants, humectants, emulsifiers, suspending agents, thickeners, sweeteners, flavorings, flavorings, antibacterial agents, fungicides, lubricants, sustained delivery regulators, the choice and ratio of which depends on the nature and method of administration and dosage . Examples of suspending agents are ethoxylated isostearyl alcohol, polyoxyethylene, sorbitol and sorbitol ether, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures of these substances. Protection against the action of microorganisms can be provided by a variety of antibacterial and antifungal agents, such as parabens, chlorobutanol, sorbic acid and the like. The composition may also include isotonic agents, for example, sugars, polyols, sodium chloride and the like. Prolonged action of the composition can be achieved using agents that slow down the absorption of the active principle, for example, aluminum monostearate and gelatin. Examples of suitable carriers, solvents, diluents and delivery vehicles include water, ethanol, polyalcohols, as well as mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters (such as ethyl oleate). Examples of fillers are lactose, milk sugar, sodium citrate, calcium carbonate, calcium phosphate and the like. Examples of grinders and distributing agents are starch, alginic acid and its salts, and silicates. Examples of lubricants are magnesium stearate, sodium lauryl sulfate, talc, and high molecular weight polyethylene glycol. A pharmaceutical composition for oral, sublingual, transdermal, intraocular, intramuscular, intravenous, subcutaneous, topical or rectal administration of an active principle, alone or in combination with another active principle, can be administered to animals and humans in a standard form of administration as a mixture with traditional pharmaceutical carriers . Suitable unit dosage forms include oral forms such as tablets, gelatin capsules, pills, powders, granules, chewing gums and oral solutions or suspensions, sublingual and buccal administration forms, aerosols, implants, topical, transdermal, subcutaneous, intramuscular, intravenous, intranasal or intraocular administration forms and rectal administration forms.

The term "excipient" or "excipient" is used herein to describe any component other than the antibody of this invention. These are substances of inorganic or organic origin, used in the production process of medicines to give them the necessary physical and chemical properties.

In some embodiments, the compositions are for the improvement, prevention, or treatment of diseases or disorders that may be mediated by IL-4Rα.

The term “IL-4Rα-mediated disease or disorder” means all diseases or disorders that are either directly or indirectly associated with IL-4Rα, including the etiology, development, progression, persistence or pathology of the disease or disorder.

“Treat,” “cure,” and “therapy” refer to a method of alleviating or eliminating a biological disorder and/or at least one of its associated symptoms. In addition, references to “treatment” contained herein include references to curative, palliative, and preventative therapies.

In one aspect, the subject of treatment or patient is a mammal, preferably a human subject. The above subject may be male or female of any age.

The term "disorder" means any condition that can be improved by treatment according to the present invention. The definition of this term includes chronic and acute disorders or diseases, including pathological conditions that predispose a mammal to the occurrence of a given disorder.

A “therapeutically effective amount” is defined as the amount of a therapeutic agent administered during treatment that will relieve, to a certain extent, one or more symptoms of the disease being treated.

The pharmaceutical compositions of the present invention and methods for their manufacture will be readily apparent to those skilled in the art. The production of pharmaceutical compositions should preferably comply with GMP (Good Manufacturing Practices) requirements. The composition may include a buffer composition, tonic agents, stabilizers and solubilizers. Prolonged action of the composition can be achieved by using agents that slow down the absorption of the active pharmaceutical ingredient, for example, aluminum monostearate and gelatin. Examples of suitable carriers, solvents, diluents and delivery vehicles are water, ethanol, polyalcohols, as well as mixtures thereof, oils and injectable organic esters.

Any method of administering peptides, proteins or antibodies accepted in the art can suitably be used for a monoclonal antibody or antigen binding fragment thereof that specifically binds IL-4Rα of the present invention.

The term "pharmaceutically acceptable" means one or more compatible liquid or solid components that are suitable for administration to a mammal, preferably a human.

The term “buffer”, “buffer composition”, “buffering agent” refers to a solution capable of maintaining a pH value, due to the interaction of the acidic and alkaline components included in its composition, which allows the antibody preparation that specifically binds to IL-4Rα to exhibit resistance to pH changes. In general, pH values of the pharmaceutical composition from 4.0 to 8.0 are preferred. As buffering agents, for example, acetate, phosphate, citrate, histidine, succinate, etc. can be used. buffer solutions, but not limited to them.

The terms “tonic agent,” “osmolytic,” or “osmotic agent,” as used herein, refer to an excipient that can adjust the osmotic pressure of a liquid antibody preparation. An "isotonic" drug is a drug that has an osmotic pressure equivalent to that of human blood. Isotonic drugs typically have an osmotic pressure of approximately 250 to 350 mOsm/kg. Polyols, mono- and disaccharides, amino acids, metal salts such as sodium chloride, etc. can be used as isotonic agents, but are not limited to them.

By "stabilizer" is meant an excipient or a mixture of two or more excipients that provides physical and/or chemical stability to the active agent. Amino acids can be used as stabilizers, for example, but not limited to, arginine, histidine, glycine, lysine, glutamine, proline; surfactants, e.g. polysorbate 20 (trade name Tween 20), polysorbate 80 (trade name Tween 80), polyethylene-polypropylene glycol and its copolymers (trade names Poloxaner, Pluronic), sodium dodecyl sulfate (SDS) ), but not limited to them; antioxidants, for example, but not limited to, methionine, acetylcysteine, ascorbic acid, monothioglycerol, sulfuric acid salts, etc.; chelating agents such as ethylenediaminetetraacetic acid (EDTA),

diethylenetriaminepentaacetic acid (DTPA), sodium citrate, etc., but not limited to.

The pharmaceutical composition according to the invention is stable. A pharmaceutical composition is “stable” if the active agent retains its physical stability and/or chemical stability and/or biological activity through its stated shelf life at storage temperature, for example, 2-8°C. It is preferred that the active agent retains both physical and chemical stability as well as biological activity. The storage period is selected based on the results of stability studies during accelerated and natural storage.

The pharmaceutical composition of this invention may be manufactured, packaged or widely sold as a single unit dose or a plurality of unit dose units in a finished dosage form. As used herein, the term "unit unit dose" means a discrete amount of a pharmaceutical composition containing a predetermined amount of the active ingredient. The amount of active ingredient is typically equal to the dosage of the active ingredient to be administered to the subject, or a convenient portion of such dosage, such as one-half or one-third of such dosage.

The pharmaceutical compositions of the present invention are generally suitable for parenteral administration in the form of sterile medicinal products intended for introduction into the human body through disruption of the skin or mucous membranes, bypassing the gastrointestinal tract by injection, infusion or implantation. In particular, parenteral administration is intended to include, but is not limited to, subcutaneous, intraperitoneal, intramuscular, intravenous, intra-arterial, intrathecal, intraventricular, intraurethral, intracranial, intra-articular, transdermal injection or infusion; and renal dialysis infusion techniques. Intratumoral delivery, such as intratumoral injection, may also be applicable. Regional perfusion is also provided. Preferred embodiments of the invention include intravenous and subcutaneous routes. The most preferred route of administration of the pharmaceutical composition of the present invention is subcutaneous administration. Any method of administering peptides or proteins accepted in the art can suitably be used for an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα of the present invention.

Injectable drugs may be manufactured, packaged or sold in unit dosage form, such as, but not limited to, ampoules, vials, polymer containers, pre-filled syringes, auto-injection devices. Drugs for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous bases, pastes and the like.

Another embodiment of the invention is a medicament for parenteral administration, wherein the pharmaceutical composition is provided in dry form, that is, powder or granules for dissolution in a suitable solvent (eg, sterile pyrogen-free water) before administration. Such a medicinal product can be obtained, for example, by lyophilization, i.e. a process known in the art as freeze drying, which involves freezing the preparation and then removing the solvent from the frozen contents.

An antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα of the present invention may also be administered intranasally or by inhalation, alone, mixed with a suitable pharmaceutically acceptable excipient from an inhaler, such as a pressurized aerosol container, pump, spray, nebulizer or a nebulizer, with or without the use of a suitable propellant, or in the form of nasal drops or spray.

The drug for parenteral administration may be immediate or modified release. Modified release drugs include delayed, sustained, pulsatile, controlled, targeted and programmable release.

In one aspect, the present invention provides a pharmaceutical composition for treating a disease or disorder mediated by IL-4Rα, which contains any of the above antibody or antigen binding fragment thereof and at least one other therapeutically active compound.

In one aspect, the present invention provides a pharmaceutical composition for treating a disease or disorder mediated by IL-4Rα, which contains any of the above antibody or antigen binding fragment and at least one other therapeutically active compound, which is an antibody, a small molecule, an agent for hormonal therapy or a combination thereof.

In some embodiments of the pharmaceutical composition, the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis , fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton's syndrome, ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, stomach cancer, colorectal cancer, malignant neoplasm colon, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome.

Therapeutic use of a monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα

In one aspect, an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα is used in the treatment of disorders mediated by IL-4Rα activity.

In one aspect, the subject of treatment or patient is a mammal, preferably a human subject. The above subject may be male or female and of any age.

In one aspect, the present invention provides a method of treating a disease or disorder mediated by IL-4Rα, comprising administering to a subject in need of such treatment any of the above antibody or antigen binding fragment thereof or the above pharmaceutical composition in a therapeutically effective amount.

In one aspect, the present invention provides a method of treating a disease or disorder mediated by IL-4Rα, comprising administering to a subject in need of such treatment any of the above antibodies or antigen binding fragment thereof and at least one other therapeutically active compound in a therapeutically effective amount.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis , fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton's syndrome, ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, stomach cancer, colorectal cancer, malignant neoplasm colon, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome.

In some embodiments of the method of treatment, the other therapeutically active compound is an antibody, a small molecule, a hormone therapy, or a combination thereof.

In one aspect, the present invention relates to the use of the above antibody or antigen binding fragment thereof or the above pharmaceutical composition for treating a disease or disorder mediated by IL-4Rα in a subject in need of such treatment.

In one aspect, the present invention relates to the use of the above antibody or an antigen binding fragment thereof and at least one other therapeutically active compound for the treatment of a disease or disorder mediated by IL-4Rα.

In some embodiments, the IL-4Rα-mediated disease or disorder is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton syndrome, ichthyosis, eosinophilic gastritis , eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, stomach cancer, colorectal cancer, colon malignancy intestines, malignant neoplasms of the breast, pancreatic cancer, malignant neoplasms of the extrahepatic bile duct, cancer of the intrahepatic bile duct, malignant neoplasms of the gallbladder, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome.

In some embodiments, the other therapeutically active compound is an antibody, a small molecule, a hormone therapy, or a combination thereof.

For the treatment of the above diseases, a monoclonal antibody or an antigen binding fragment thereof that specifically binds to IL-4Rα as provided in the present invention can be administered in combination with another therapeutic agent such as an immunosuppressive agent, an anti-inflammatory drug, a systemic hormonal drug, an antineoplastic agent, and an immunomodulatory agent. drug or others using a multi-drug regimen.

As used herein, uses or methods relating to an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα, one or more other therapeutic agents are intended to mean, refer to, or include:

1) simultaneous administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα and a therapeutic agent to a patient in need of treatment, when such components are formulated together in a single dosage form from which said components are released substantially simultaneously to said patient,

2) simultaneous administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα and a therapeutic agent to a patient in need of treatment, when such components are formulated separately in different dosage forms, the administration of which occurs at substantially the same time to the specified patient, after which the specified components are released almost simultaneously to the specified patient,

3) sequential administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα and a therapeutic agent to a patient in need of treatment, when such components are formulated separately from each other in separate dosage forms that are administered at sequentially specified times patient with a significant time interval between each administration, after which said components are released at substantially different times to said patient; and

4) sequential administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα and a therapeutic agent to a patient in need of treatment, where such components are formulated together in a single dosage form from which the release of said components occurs in a controlled manner, after whereby they are simultaneously, sequentially or jointly released at the same time and/or different times to a specified patient, wherein each portion may be administered by the same or different routes.

An antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα can be administered without additional therapeutic treatment, i.e. as an independent therapy.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is atopic dermatitis (eczema, coin-shaped eczema).

In some embodiments of a method of treating atopic dermatitis (eczema, coin-shaped eczema), any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, either as monotherapy or in combination with topical agents (moisturizing agents). and emollients, topical glucocorticoids (GCs), topical calcineurin inhibitors, topical antibiotics and antiseptics), systemic GCs, immunosuppressants (cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, interferon gamma), oral calcineurin inhibitors, oral antihistamines, monoclonal antibodies against TSLP or any combination of them.

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is asthma (aspirin-induced asthma, aspirin triad).

In some embodiments of a method of treating bronchial asthma (aspirin asthma, aspirin triad), any of the above antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα is administered to a subject in need of such treatment, as monotherapy or in combination with inhaled and/or oral GCs, beta2-agonists, muscarinic receptor antagonists, leukotriene receptor antagonists, methylxanthines, anti-immunoglobulin E monoclonal antibodies, anti-interleukin 5 monoclonal antibodies, anti-interleukin 5 receptor monoclonal antibodies, anti-TSLP monoclonal antibodies, or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is chronic obstructive pulmonary disease.

In some embodiments of a method of treating chronic obstructive pulmonary disease, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, as monotherapy or in combination with beta2 agonists, methylxanthines, GCs, phosphodiesterase inhibitors 4, muscarinic receptor antagonists or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is allergic bronchopulmonary aspergillosis.

In some embodiments of a method of treating allergic bronchopulmonary aspergillosis, any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, in combination with antifungals, systemic GCs, or any combination thereof.

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis (nasal polyp), or allergic rhinitis.

In some embodiments of a method of treating chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis (nasal polyp), or allergic rhinitis, any of the above antibody or antigen binding fragment thereof that specifically binds to IL-4Rα is administered to a subject in need of such treatment. , as monotherapy or in combination with antifungals (for fungal rhinosinusitis), intranasal GCs, anti-interleukin 5 monoclonal antibodies, anti-interleukin 5 receptor monoclonal antibodies, anti-TSLP monoclonal antibodies, or any combination thereof.

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is Churg-Strauss Syndrome.

In some embodiments of a method of treating Churg-Strauss Syndrome: administering to a subject in need of such treatment any of the above antibody or antigen binding fragment thereof that specifically binds to IL-4Rα, as monotherapy or in combination with GCs, immunosuppressants (cyclophosphamide, azathiorine, methotrexate, mycophenolate mofetil), immunoglobulins, intranasal GCs, anti-interleukin 5 monoclonal antibodies, anti-interleukin 5 receptor monoclonal antibodies, anti-CD20 monoclonal antibodies (eg, rituximab), or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is pruritus associated with chronic liver disease.

In some embodiments of a method for treating pruritus associated with chronic liver disease, any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, either as monotherapy or in combination with therapy for the underlying liver disease. .

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is a hypertrophic scar.

In some embodiments of a method of treating a hypertrophic scar, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, either as monotherapy or in combination with GC.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is alopecia areata or scleroderma areata.

In some embodiments of a method of treating alopecia areata or scleroderma areata, any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, as monotherapy or in combination with GC, minoxidil, anthralin, immunosuppressants ( cyclophosphamide, azathiorine, methotrexate, mycophenolate mofetil), TNF-alpha inhibitors or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is urticaria.

In some embodiments of a method of treating urticaria, any of the above antibodies or antigen-binding fragments thereof that specifically binds IL-4Rα is administered to a subject in need of such treatment, as monotherapy or in combination with antihistamines, leukotriene receptor antagonists, immunosuppressants (cyclosporine), monoclonal antibodies against immunoglobulin E or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is pemphigus.

In some embodiments of a method of treating pemphigus, any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, in combination with GCs, immunosuppressants (cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, chlorambucil), intravenous immunoglobulins, anti-immunoglobulin E monoclonal antibodies, anti-CD20 monoclonal antibodies, or any combination thereof.

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is Netherton syndrome.

In some embodiments of a method of treating Netherton syndrome, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, either as monotherapy or in combination with symptomatic therapy (different groups of drugs may be used depending on clinical manifestations).

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is ichthyosis.

In some embodiments of a method of treating ichthyosis, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, either as monotherapy or in combination with retinoids.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is atopic keratoconjunctivitis.

In some embodiments of a method of treating atopic keratoconjunctivitis, any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, as monotherapy or in combination with GCs, calcineurin inhibitors, or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is prurigo nodularis.

In some embodiments, a method of treating prurigo nodosum is administered to a subject in need of such treatment, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα, as monotherapy or in combination with GCs, calcineurin inhibitors, immunosuppressants (cyclosporine, methotrexate) , thalidomide, calcipotriol, capsaicin, antiepileptic drugs and antidepressants or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is colitis.

In some embodiments of a method of treating colitis, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, as monotherapy or in combination with GCs, TNF-alpha inhibitors, vedolizumab, tofacitinib, ustekinumab , methotrexate, sulfasalazine or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is filariasis, leishmaniasis, or schistosomiasis.

In some embodiments of a method of treating filariasis, leishmaniasis, schistosomiasis, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα, in combination with antiparasitic drugs, are administered to a subject in need of such treatment.

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is hypertension.

In some embodiments of a method of treating hypertension, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, in combination with antihypertensive drugs, diuretics, or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is interstitial lung disease

In some embodiments of a method of treating interstitial lung diseases, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα, in combination with GCs, antifibrotic drugs, or any combination thereof, are administered to a subject in need of such treatment.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is metastatic non-small cell lung cancer or other cancers.

In some embodiments, a method of treating metastatic non-small cell lung cancer or other cancers, administering to a subject in need of such treatment any of the above antibody or antigen binding fragment thereof that specifically binds IL-4Rα, in combination with immunotherapy, targeted therapy, chemotherapy, or any combination thereof .

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is a hypereosinophilic syndrome.

In some embodiments of a method of treating hypereosinophilic syndrome, any of the above antibodies or antigen binding fragments thereof that specifically bind to IL-4Rα, in combination with GC, anti-interleukin 5 monoclonal antibodies, anti-interleukin 5 receptor monoclonal antibodies, are administered to a subject in need of such treatment. monoclonal antibodies against the CD52 receptor or any combination thereof.

In some embodiments of the method of treatment, the disease or disorder mediated by IL-4Rα is an allergic reaction.

In some embodiments of a method of treating allergic reactions, any of the above antibodies or antigen-binding fragments thereof that specifically bind to IL-4Rα are administered to a subject in need of such treatment, as monotherapy or in combination with GCs, antihistamines, or any combination thereof.

In some embodiments of the treatment method, the disease or disorder mediated by IL-4Rα is acute respiratory distress syndrome (eg, acute respiratory distress syndrome that is caused by SARS-cov2).

In some embodiments of a method of treating acute respiratory distress syndrome (e.g., acute respiratory distress syndrome that is caused by SARS-cov2), any of the above antibody or antigen binding fragment thereof that specifically binds IL-4Rα is administered to a subject in need of such treatment, in combination with etiotropic therapy, anti-Covid plasma, human immunoglobulin against COVID-19, with anti-inflammatory therapy (GC, monoclonal antibodies), with antithrombotic therapy or any combination thereof.

Doses and routes of administration

A monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα of the present invention will be administered in an amount effective to treat the condition in question, i.e. in doses and for periods of time necessary to achieve the desired result. The therapeutically effective amount may vary depending on factors such as the specific condition being treated, the age, sex and weight of the patient, and whether administration of a monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα is a stand-alone treatment or it is given in combination with one or more additional drugs or treatments.

Drug regimens can be adjusted to provide the optimal desired response. For example, a single bolus may be administered, multiple divided doses may be administered over time, or the dose may be proportionally decreased or increased depending on the acuity of the therapeutic situation. It is particularly advantageous to formulate parenteral compositions in unit dosage form for ease of administration and uniformity of dosage. Unit dosage form as used herein refers to physically discrete units suitable as unitary dosages for patients/subjects to be treated; each unit contains a predetermined amount of active compound calculated to produce the desired therapeutic effect in combination with the required pharmaceutical carrier.

The specification for unit dosage forms of the present invention is generally dictated by and directly depends on (a) the unique characteristics of the therapeutic agent and the particular therapeutic or prophylactic effect to be achieved, and (b) the limitations inherent in the technique of compounding such active compound for treating sensitivity in subjects.

Thus, those skilled in the art will appreciate from the disclosure provided herein that dosages and dosage regimens will be adjusted in accordance with methods well known in the therapeutic field. This means that the maximum tolerated dose can be easily determined and the effective amount to provide a detectable therapeutic effect for the patient can also be determined, as well as the timing requirements for each agent to achieve a detectable therapeutic effect for the patient. Thus, although certain dosages and dosage regimens are given as examples herein, these examples are not intended to limit in any way the dosages and dosage regimens that may be needed for a patient to practice the present invention.

It should be noted that dosage values may vary depending on the type and severity of the condition to be alleviated, and may include one or more doses. In addition, it should be understood that for any particular patient, specific dosage regimens must be adjusted over time according to individual need and at the discretion of the healthcare professional administering or supervising the administration of the compositions, and that the concentration ranges given herein are provided only by way of example and are not intended to limit the scope or practice of the claimed compositions. In addition, the dosage regimen of the compositions of this invention may be based on various factors, including the type of disease, age, weight, gender, medical conditions of the patient, severity of the condition, route of administration, and the particular monoclonal antibody used or antigen binding fragment thereof that specifically binds to IL-4Rα. Thus, the dosage regimen may vary widely, but can be determined regularly using standard methods. For example, dosages may be adjusted based on pharmacokinetic and pharmacodynamic parameters, which may include clinical effects such as toxic effects or laboratory values. Thus, the present invention covers individual dose escalation, which is determined by a qualified specialist. Determination of the required dosage and regimens are well known in the relevant art and will be apparent to one skilled in the art upon familiarization with the concepts disclosed herein.

Examples of suitable routes of administration are provided above.

It is expected that a suitable dose of a monoclonal antibody or antigen binding fragment thereof that specifically binds to IL-4Rα according to the present invention will be in the range of 0.1-200 mg/kg, preferably 0.1-100 mg/kg, including about 0.5-50 mg/kg, for example about 1-20 mg/kg. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα may be administered, for example, at a dose of at least 0.25 mg/kg, such as at least 0.5 mg/kg, including at least 1 mg/kg, for example at least 1.5 mg/kg, for example, as well as at least 2 mg/kg, for example at least 3 mg/kg, including at least 4 mg/kg, for example , at least 5 mg/kg; and for example up to a maximum of 50 mg/kg, including up to a maximum of 30 mg/kg, for example, up to a maximum of 20 mg/kg, including up to a maximum of 15 mg/kg. Administration will be repeated usually at suitable intervals, for example once a week, once every two weeks, once every three weeks or once every four weeks, and for as long as is considered appropriate by the responsible physician, which may in some cases increase or reduce dose if necessary.

Diagnostic use of an antibody that specifically binds to IL-4Rα

The monoclonal antibody or antigen-binding fragment thereof that specifically binds IL-4Rα of the present invention is also used for diagnostic purposes (eg, in vitro, ex vivo). For example, a given monoclonal antibody or an antigen-binding fragment thereof that specifically binds to IL-4Rα of the present invention can be used to detect or measure the level of IL-4Rα in samples obtained from a patient, for example, a tissue sample or a body fluid sample, such as an inflammatory exudate, blood, serum, bowel fluid, saliva or urine. Suitable detection and measurement methods include immunological methods such as flow cytometry, enzyme-linked immunosorbent assay (ELISA), chemiluminescence assay, radioimmunoassay and immunohistology.

Examples

For a better understanding of the invention, the following examples are provided. These examples are provided for illustrative purposes only and should not be construed as limiting the scope of the invention in any form.

All publications, patents and patent applications referenced in this specification are incorporated herein by reference. Although the foregoing invention has been described in some detail by way of illustration and example in order to avoid ambiguity, those skilled in the art will appreciate from the teachings disclosed herein that certain changes and modifications may be made without departing from the spirit and scope of the appended embodiments. implementation of the invention.

Materials and general methods

General information regarding the nucleotide sequences of the light and heavy chains of human immunoglobulin is presented in: Kabat E.A. et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service Publishing, National Institutes of Health, Bethesda, MD, 1991. Amino acid chains of antibodies are numbered according to EU numbering (Edelman G.M. et al., Proc Natl. Acad. Sci. USA 63, 1969, ee. 78-85; Kabat E. A. et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991).

Recombinant DNA methods

For DNA manipulation, standard methods were used as described in Sambrook J. et al., Molecular cloning: A laboratory manual; Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1989. Molecular biology reagents were used according to the manufacturers' instructions.

Gene synthesis

The required gene segments were obtained from oligonucleotides created by chemical synthesis. Gene segments ranging from 300 to 1400 bp in length, which are flanked by unique restriction sites, were assembled by annealing and ligation of oligonucleotides, including PCR amplification and subsequent cloning through restriction sites. The DNA sequences of the subcloned gene fragments were confirmed by DNA sequencing.

Determination of DNA sequences

DNA sequences were determined by Sanger sequencing.

DNA and protein sequence analysis and sequence data processing

Unipro software package UGENE version 1.29 and SnapGene Viewer were used to create, map, analyze, annotate and illustrate sequences.

Expression vectors

To express the antibodies described in the application materials, variants of expression plasmids intended for the expression of antibodies in prokaryotic cells (E. coli) and short-term expression in eukaryotic cells (for example, in CHO cells) were used. In addition to the antibody expression cassette, the vectors contained: an initiation site of replication that ensures replication of the specified plasmid in E. coli, genes that confer resistance in E. coli to various antibiotics (for example, ampicillin, kanamycin).

Fusion of genes containing the antibody chains described, as described below, was accomplished by PCR and/or gene synthesis and assembly using known recombination methods and procedures by joining appropriate nucleic acid segments, for example, using unique restriction sites in appropriate vectors. Subcloned nucleotide sequences were confirmed by DNA sequencing. For short-term transfections, large quantities of plasmids were created by obtaining plasmids from transformed cultures, E. coli.

Example 1. Production of recombinant antigens in a suspension culture of mammalian cells.

The sequences of the extracellular domains of the human IL-4Rα receptor (subunit of the IL-4Rα interleukin 4 receptor) (SEQ https://www.uniprot.org/uniprot/P24394 (27-227 aa)) were cloned into pEE plasmids to produce the protein in cells mammals with Fclama, His-Flag tags at SalIl/NotI restriction sites. Plasmids were produced in the required quantities in E. Coli cells and purified using a Qiagen kit.

The sequence of the extracellular domain of macaque (Cynomolgus monkey) IL-4Rα (SEQ https://www.uniprot.org/uniprot/A0A2K5V580 (24-232 aa)) was cloned into the pEE plasmid to produce the protein in mammalian cells with Fc tag sites SalIl/NotI restriction. Plasmids were produced in the required quantities in E. coli cells and purified using a Qiagen kit.

Example 2. Production of recombinant antigens in a suspension culture of mammalian cells

Antigens were produced in cells of a permanent cell line derived from Chinese hamster ovary cells (CHO-T line). Suspension cultivation was carried out in flasks on an orbital shaker-incubator, using serum-free media supplemented with 8 mM L-glutamine and 1 g/l Pluronic 68. For transient expression, cells were transfected at a concentration of 1.9-2.2×10 ⁶ cells/ml using linear polyethyleneimine. The DNA/PEI ratio was 1:6/1:7. 9 days after transfection, the culture liquid was separated from the cells by filtration through a depth filter with a pore size of 0.5/0.22 μm.

The IL-4Rα-Fclama antigen, cIL-4Rα-Fclama (cynomolgus) was isolated and purified from the culture liquid using a sorbent column for affinity chromatography with Protein A. The clarified culture liquid was passed through a 20 ml column equilibrated with phosphate-buffered saline (PBS , pH 7.4). The column was then washed with 5 column volumes of PBS to wash away nonspecific binding components. Bound antigen was eluted using 0.1 Μ glycine buffer pH 2.5. The main protein elution peak was collected and adjusted to pH neutrality with 1 Μ Tris buffer (pH 7.5). Next, the protein was transferred to PBS (pH 7.4) by dialysis and 1 mM DTT was added, filtered through Millex GP 0.22 μm, transferred to tubes and stored at -70°C.

0.5 Μ Imidazole and 0.1 Μ NiCl ₂ were added to the clarified culture liquid with IL-4Rα-6HisFlag antigens to the content of 0.02 Μ Imidazole and 0.001 Μ NiCl ₂ . The culture liquid was then passed through a 10 ml column equilibrated with phosphate-buffered saline supplemented with 10 mM imidazole (PBS, pH 7.4). The column was then washed with 5 column volumes of PBS supplemented with 10 mM imidazole to wash away nonspecific binding components. Bound antigen was eluted using PBS supplemented with 500 mM imidazole (pH 7.4). Next, the protein was transferred into PBS using dialysis. After this, the protein was applied to a gel filtration column pre-equilibrated with PBS. Protein was eluted with PBS, filtered through Millex GP 0.22 μm, transferred to tubes and stored at -70°C.

Electrophoresis of antigens was carried out in a denaturing 10% polyacrylamide gel under non-reducing conditions without the addition of mercaptoethanol and under reducing conditions with the addition of mercaptoethanol.

Example 3. Cloning of antibody variable domain genes into an expression plasmid

Cloning of the developed gene sequences for the variable domains of antibodies according to the invention into the expression plasmid pLL (Fig. 1) was carried out according to a standard protocol using the restriction enzyme ligase method.

Subsequently, expression vectors containing antibody fragments were transformed into E. coli strain BL21-Gold.

Example 4. Production and primary analysis of Fab fragments of antibodies 1-37 that specifically bind human IL-4Rα

Fab production was carried out according to the standard method: E. coli BL21-Gold bacterial cells were transformed with expression vectors containing Fab genes, and the subsequent addition of an inducer triggered transcription of the lac operon, which, when cultivating the resulting transformants, caused the expression of Fabs, which were exported into the periplasmic space of the cells. Next, ELISA was performed to check the binding of Fab to the IL-4Rα-Fclama antigen immobilized on the substrate at a concentration of 0.2 μg/ml on plates (high binding) in 0.1 Μ NaHCO ₃ (pΗ 9.0) (the antigen was immobilized overnight at 4°C). All subsequent steps were carried out at room temperature according to the standard ELISA protocol. After each step, washing was carried out with 300 μl per well of 1× PBST in triplicate. Nonspecific binding sites were blocked on the plate with 1% skim milk in 1× PBST; after washing, an analyte was added, which was the supernatant of E. coli cells in a volume of 60 μl per well. Detection of immune complexes was carried out using goat anti-Fab antibodies conjugated with peroxidase at a dilution of 1:7500. Staining of the substrate-chromogenic mixture was carried out by adding a substrate solution (H ₂ O ₂ - 0.02% and TMB in CH ₃ COONa (pH5.5)) in a volume of 50 μl for 15 minutes. The reaction was stopped with 25 μl of H ₂ SO ₄ 1%. The color signal was measured at 450 nm using a suitable Tecan-Sunrise plate reader. The degree of antibody binding was proportional to the production of a color signal.

Thus, all analyzed Fab fragments of antibodies 1-37 show specific binding to IL-4Rα-Fclama.

Example 5. Analysis of Fab fragments to human IL-4Rα antigen on Forte Bio

Experiments to study the affinity of purified Fab fragments were carried out on a Forte Bio device using FAB2G biosensors (ForteBio) allowing immobilization of Fab antibodies for the CH1 domain region. The analysis was carried out at 30°C using a kinetic buffer solution (4.3 mM Na ₂ HPO ₄ ; 136.9 mM NaCl, 1.5 mM KH2PO4; 2.7 mM KCl; volume fraction of added Tween 20 was 0.1%; the mass fraction of added BSA was 0.1%; pH 7.4), this buffer was used at all stages of the analysis. Fab samples were immobilized on the sensors for 600 seconds, the concentration was 20 μg/ml. The baseline after loading was recorded for 300 s. After baseline recording, sensors with immobilized Fabs were immersed in wells with an analyte solution (IL-4Rα-His), where the association of the antigen-Fab complex occurred for 300 seconds. The IL-4Rα-His antigen concentration was 400 nM, and the reference signal of the kinetic buffer solution without IL-4Rα-His was recorded for each Fab. Then the dissociation of the complex in the buffer solution was detected for 600 seconds.

To test the nonspecific interaction of the analyte with the sensors (negative control), sensors not loaded with Fab antibody fragments were used. At the loading stage, negative control sensors were immersed in a kinetic buffer solution containing no Fab; all other steps were similar to sensors loaded with Fab samples.

Binding curves were analyzed using Octet Data Analysis software (version 9.0) using a 1:1 interaction model (Table 2).

Thus, all analyzed Fab fragments of anti-IL-4Rα antibodies 1-37 interact with the target antigen IL-4Rα-His (Table 2).

Example 6. Analysis of nonspecific binding of produced Fabs to other antigens

To analyze the nonspecific binding of the studied Fab fragments to other antigens, ELISA was used. IL5R-Fclama, INFβ2a, CD3-FLAG-EPEA in 0.1 Μ NaHCO3 (pH 9.0) were used as antigens for immobilization (the antigen was immobilized overnight at 4°C). IL-4Rα-Fclama, IL-4Rα-His were used as a control for specific binding (the antigen was immobilized overnight at 4°C). All subsequent steps were carried out at room temperature according to the standard ELISA protocol. After each step, washing was carried out with 300 μl per well of 1× PBST in triplicate. Nonspecific binding sites were blocked on the plate with 1% skim milk in 1× PBST; after washing, an analyte was added, which was supernatants of E. coli cells in a volume of 60 μl per well. Detection of immune complexes was carried out using goat anti-Fab antibodies conjugated with peroxidase at a dilution of 1:7500. Staining of the substrate-chromogenic mixture was carried out by adding a substrate solution (H ₂ O ₂ - 0.02% and TMB in CH ₃ COONa (pH5.5)) in a volume of 50 μl for 15 minutes. The reaction was stopped with 25 μl of H ₂ SO ₄ 1%. The color signal was measured at 450 nm using a suitable Tecan-Sunrise plate reader. The degree of antibody binding was proportional to the production of a color signal.

Thus, all analyzed Fab fragments of antibodies 1-37 show specific binding to IL-4Rα-Fclama, IL-4Rα-His and do not show nonspecific interaction with IL5R-Fclama, INFβ2a, CD3-FLAG-EPEA.

Example 7. Obtaining genetic constructs for the synthesis of full-length antibodies

Cloning was carried out according to standard methods. PCR products were generated containing genes for the variable domains of the heavy and light chains of antibodies with primers containing restriction sites. The heavy chain variable domain (VH) was cloned into the pEE-HC IgG4 vector (Fig. 2) at the Sal1/Nhe1 restriction sites. The light chain variable domain (VL) was cloned into the pEE-CK vector (Fig. 3) at the Sal1/BsiW1 restriction sites. The resulting genetic constructs were transferred to the transient production of proteins in the CHO-T cell line.

Example 8. Preparation of full-length antibodies

Full-length antibodies were produced in cells of a permanent cell line obtained from Chinese hamster ovary cells (line CHO-T) using transient transfection in duplicate. Suspension cultivation was carried out in bioreactors on an orbital shaker, using serum-free media supplemented with 8 mM L-Glutamine and 1 g/l Pluronic 68. For transient expression, cells at a concentration of 2-2.2×10 ⁶ cells/ml were transfected using linear polyethylenimine . The DNA/PEI ratio was 1:7. On the 10th day of cultivation, the cell suspension was centrifuged at 2000 g for 15 minutes and filtered through a filter with a pore size of 0.22 μm.

Antibodies were purified by affinity chromatography on columns using a robotic station. The column was equilibrated with a buffer of 50 tM NaPB, 150 tM NaCl (pH 7.5), filtered culture liquid with antibodies was applied, then the column was washed with 8 volumes of buffer 50 mM NaPB, 150 mM NaCl and 4 volumes of 50 mM NaPB (pH 7.5). Protein elution was carried out with a solution of 50 mM NaPB, 100 mM NaCl (pH 3) for 6 column volumes. The resulting samples were neutralized with 25 μl of 1 M phosphate buffer (pH 8).

To control the purity of antibodies, polyacrylamide gel electrophoresis and size exclusion HPLC were used. Electrophoresis was carried out in a 7.5% polyacrylamide gel under denaturing non-reducing conditions. Protein purity was determined by the intensity of bend staining at a protein load of 10 μg per lane. Electropherograms are presented in Fig. 4, fig. 5, fig. 6, fig. 7, fig. 8. Size exclusion HPLC was carried out on a column in a mobile phase of 0.05 M NaH2PO4, 0.3 Μ NaCl pH = 7.0.

Example 9. Determination of the affinity of full-length antibodies to human IL-4Rα on Forte Bio

Experiments to study the binding affinity of antibodies to the human IL-4Rα-His antigen were performed on a Forte Bio instrument. Antibodies at a concentration of 20 μg/ml were immobilized on the surface of Protein A biosensors (ForteBio). The analysis was carried out at 30°C using a kinetic buffer solution (4.3 mM Na2HPO4; 136.9 mM NaCl, 1.5 mM KH2PO4; 2.7 mM KCl; volume fraction of added Tween 20 was 0.1%; mass fraction of added BSA was 0.1%; pH 7.4). After a baseline was prescribed in the kinetic buffer solution, sensors with immobilized antibody were immersed in wells with an analyte solution (IL-4Rα-His), where association of the complex occurred for 300 seconds. For each test antibody, three sensorgrams were recorded for IL-4Rα-His solutions with concentrations of 96.2 nM, 48.1 nM, 24.0 nM and a reference signal (reference sensorgram) of a kinetic buffer solution without IL-4Rα-His. Then the dissociation of the complex in the buffer solution was detected for 600 seconds. To test for nonspecific interaction of the analyte with the sensors (negative control), sensors not loaded with antibodies were used. At the loading stage, negative control sensors were immersed in a kinetic buffer solution containing no antibodies; all other stages were similar to sensors loaded with antibodies.

Reference signal-subtracted binding curves were analyzed using Octet Data Analysis (version 9.0) using a 1:1 Global interaction model.

Thus, all anti-IL-4Rα antibodies analyzed specifically bind to the human IL-4Rα antigen (Table 3).

Example 10: Testing interactions of full-length antibodies with macaque cIL-4Rα using a Forte Bio instrument.

The purpose of this experiment was to confirm the interaction of antibodies with the macaque antigen cIL-4Rα-Fclama (macaca fascicularis, IL-4Rα with an Fc fragment and a 6His tag at the C-terminus). The interaction of antibodies with the macaque antigen cIL-4Rα-Fclama was tested on a Forte Bio device using AR2G biosensors (ForteBio). The experiment consisted of the following stages: sensor activation, protein loading on the sensors, quenching of unreacted activated groups, baseline recording, analyte association recording, dissociation recordings. The sensors were activated in an aqueous solution containing 20 mM EDC and 10 mM sNHS for 300 s. Antibodies were loaded onto the surface of the biosensors in a sodium acetate buffer solution with pH 5.0 for 300 s. The loading protein concentration was 20 μg/ml. Quenching of unreacted active centers on the surface of the sensors was carried out in a 1 M aqueous solution of ethanolamine with pH 8.5 for 300 s. To check the nonspecific interaction of the analyte with the sensors (negative control), a sensor not loaded with antibodies was used (at the loading stage, the sensor was immersed in a sodium acetate buffer solution with pH 5.0; all other stages are similar to the sensors loaded with antibodies). The baseline and all subsequent steps of the experiment were carried out in a kinetic buffer solution (4.3 mM Na2HPO4; 136.9 mM NaCl, 1.5 mM KH2PO4; 2.7 mM KCl; volume fraction of added Tween 20 was 0.1%; mass fraction added BSA was 0.1%; pH 7.4). At the association stage (stage duration 300 s), sensors with loaded protein were immersed in wells with an analyte solution (cIL-4Rα-Fclama) prepared in a kinetic buffer. The analyte concentration was 197.2 nM. At the dissociation stage, the sensors were immersed in wells with a kinetic buffer, in which the baseline was recorded. The measurements were carried out at a temperature of 30°C.

Binding curves were processed using Octet Data Analysis software (version 9.0) using a 1:1 interaction model. The processing results are presented in Table 4 (the value kdis<1.0E-07 (1/s) and the corresponding value KD<1.0E-12 (M) means that, within the framework of the applied measurement and processing technique for this sample, the sensitivity limit for the constant is exceeded dissociation rate for the model curve describing the sensorogram). The obtained values of kinetic constants are of an estimated nature due to the use of a bivalent analyte (the antigen is present in the solution in the form of a dimer due to the presence of the Fc fragment) and can only be used for comparison of samples. For all anti-IL-4Rα antibodies, a binding signal with the macaque antigen cIL-4Rα-Fclama is observed at the association stage and a slow decline in the signal at the dissociation stage, which confirms interaction with this antigen.

Thus, all anti-IL-4Rα antibodies analyzed specifically bind to the macaque antigen cIL-4Rα-Fclama (Table 4).

Example 11 Inhibition of the biological effect of hIL-4 and hIL-13 in vitro

The assay is designed to evaluate the ability of antibodies to inhibit the hIL-4Rα-dependent cellular cascade in vitro using the HEK-Blue IL4/IL13 transgenic cell line carrying STAT6 and a reporter construct (SEAP) driven by a STAT6-inducible promoter.

Cells were passaged into 96-well plates (5*10 ⁴ cells/well), incubated for 4 hours, a pre-prepared antibody titer was added (serial dilution method, from 0 to 25 μg/ml) and hIL-4 solution (1 ng/ml ) or hIL-13 (5 ng/ml). Cells were incubated for 24 hours under standard conditions. Cellular response was assessed by determining alkaline phosphatase activity. The results are shown in Table 5.

Thus, all anti-IL-4Rα antibodies tested inhibit hIL-4 and hIL-13 dependent signaling in vitro.

Example 12. Inhibition of hIL-4 dependent proliferation in the TF-1 cell line.

The assay was designed to evaluate the ability of antibodies to inhibit the proliferation of the TF-1 cell line, mediated by the interaction of IL-4Rα Type 2, expressed on the surface of the membrane of the TF-1 cell line, with hIL-4.

Cells were passaged into 96-well plates (3*10 ⁴ cells/well), pre-prepared antibody titer (serial dilution method, from 0 to 100 μg/ml) and hIL-4 solution (100 ng/ml) were added. The cells were incubated for 3 days under standard conditions. Cellular response was assessed using the vital dye Alamar blue according to the manufacturer's instructions. The results are shown in Table 6.

Thus, all anti-IL-4Rα antibodies tested inhibit the proliferation of the TF-1 cell line, mediated by the interaction of IL-4Rα Type 2, expressed on the surface of the cell line membrane.

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LIST OF SEQUENCES

<110> JSC "BIOCAD"

<120> MONOCLONAL ANTIBODY OR ANTIGEN-BINDING FRAGMENT WHICH

SPECIFICALLY BINDS TO IL-4Rα AND ITS USES

<160> 381

<170> BiSSAP 1.3.6

<210> 1

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 01, 02, 03, 04, 05, 06, 07, 08, 09,

10, 15, 17, 23, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 or

41

<400> 1

Thr Tyr Trp Met His

15

<210> 2

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 11

<400> 2

Thr Tyr Trp Phe His

15

<210> 3

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 12

<400> 3

Tyr Tyr Trp Leu His

15

<210> 4

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 13

<400> 4

Tyr Tyr Trp Met His

15

<210> 5

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 14

<400> 5

Ser Tyr Trp Phe His

15

<210> 6

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 16

<400> 6

Ala Tyr Trp Leu His

15

<210> 7

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 19

<400> 7

His Tyr Trp Ile His

15

<210> 8

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domains 20, 22, 24 and 30

<400> 8

Tyr Tyr Trp Val His

15

<210> 9

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 21

<400> 9

His Tyr Trp Leu His

15

<210> 10

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 27

<400> 10

His Tyr Trp Val His

15

<210> 11

<211> 17

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody heavy chain domain 01, 02, 03, 04, 05, 06, 07, 08, 09,

10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,

27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 or 41

<400> 11

Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val Lys

1 5 10 15

Gly

<210> 12

<211> 17

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody heavy chain domain 11

<400> 12

Ser Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val Lys

1 5 10 15

Gly

<210> 13

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 01, 02, 04, 06, 08, 09, 38, 39 or 40

<400> 13

Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro

1 5 10

<210> 14

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 03

<400> 14

Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Tyr

1 5 10

<210> 15

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 05

<400> 15

Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Ser

1 5 10

<210> 16

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 07

<400> 16

Gly Gly Tyr Ser Ala Thr Trp Tyr Lys Tyr Asp Pro

1 5 10

<210> 17

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 10, 17, 23, 25, 26, 29, 31, 32, 33,

34, 35, 36, 37 or 41

<400> 17

Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro

1 5 10

<210> 18

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 11

<400> 18

Gly Gly Asn Ser Ser Gln Trp His Arg Met Ser Pro

1 5 10

<210> 19

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 12

<400> 19

Gly Gly Arg Ser Ser Gln Trp His Val Ala Glu Tyr

1 5 10

<210> 20

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 13

<400> 20

Gly Gly Arg Ser Ser Glu Trp His Val Gly Gly Tyr

1 5 10

<210> 21

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 14, 21

<400> 21

Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr

1 5 10

<210> 22

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 15

<400> 22

Gly Gly Arg Ser Ser Glu Trp Gly Ser Leu Gly Ser

1 5 10

<210> 23

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 16

<400> 23

Gly Gly Arg Ser Ser Glu Trp His Val Gly His Tyr

1 5 10

<210> 24

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 19

<400> 24

Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Gly Tyr

1 5 10

<210> 25

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 20

<400> 25

Gly Gly Arg Ser Ser Thr Trp Thr Val Leu Asp Tyr

1 5 10

<210> 26

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 22

<400> 26

Gly Gly Arg Ser Ser Arg Trp Thr Val Leu Asp Tyr

1 5 10

<210> 27

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 24

<400> 27

Gly Gly Arg Ser Ser Ser Trp Thr Val Leu Asp Tyr

1 5 10

<210> 28

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 27

<400> 28

Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Ser Tyr

1 5 10

<210> 29

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 28

<400> 29

Gly Gly Tyr Ser Ser Thr Trp His Arg Tyr Asp Pro

1 5 10

<210> 30

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 30

<400> 30

Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Asn Tyr

1 5 10

<210> 31

<211> 13

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37

<400> 31

Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn Val Val Asn

1 5 10

<210> 32

<211> 13

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 32

Ser Gly Ser Arg Ser Asn Ile Gly Gly Tyr Thr Val Asn

1 5 10

<210> 33

<211> 13

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody light chain domain 11, 12, 13, 14, 15, 16

<400> 33

Thr Gly Ser Ser Ser Asn Ile Gly Asp Asn Tyr Val Asn

1 5 10

<210> 34

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 23,

25, 26, 28, 29, 31, 32, 33, 35, 36, 37

<400> 34

Arg Asp Asn Gln Arg Pro Ser

15

<210> 35

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 35

Ile Asn Asn Glu Arg Pro Ser

15

<210> 36

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody light chain domain 11, 13, 14, 15, 16

<400> 36

Arg Asp Ser Asn Arg Ala Ser

15

<210> 37

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody light chain domain 12

<400> 37

Ser Asn Thr Asn Arg Ala Ser

15

<210> 38

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody light chain domain 17

<400> 38

Arg Asp Asn Arg Arg Pro Ser

15

<210> 39

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Kabat) variable

antibody light chain domain 34

<400> 39

Arg Asp Asn Gln His Pro Ser

15

<210> 40

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 34, 35, 36, 37

<400> 40

Ser Thr Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 41

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 41

Ala Ala Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 42

<211> 10

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody light chain domain 11, 12, 13, 14, 15, 16

<400> 42

Ser Ser Trp Asp Asp Gly Leu Ser Val Val

1 5 10

<210> 43

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody light chain domain 33

<400> 43

Thr Thr Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 44

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 01

<400> 44

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gln Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 45

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 02

<400> 45

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 46

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 03

<400> 46

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Lys Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 47

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 04

<400> 47

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 48

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 05

<400> 48

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 49

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 06

<400> 49

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 50

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 07

<400> 50

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Lys Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 51

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 08

<400> 51

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 52

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 09

<400> 52

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 53

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 10, 17, 26, 33, 34, 35, 36, 37

<400> 53

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 54

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 11

<400> 54

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Phe His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Asn Ser Ser Gln Trp His Arg Met Ser Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 55

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 12

<400> 55

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp His Val Ala Glu Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 56

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 13

<400> 56

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Gly Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 57

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 14

<400> 57

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Trp Phe His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 58

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 15

<400> 58

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp Gly Ser Leu Gly Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 59

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 16

<400> 59

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ala Tyr

20 25 30

Trp Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Gly His Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 60

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 18

<400> 60

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Phe His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Arg Trp Val Val Gln Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 61

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 19

<400> 61

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr

20 25 30

Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Asn Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 62

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 20

<400> 62

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Thr Trp Thr Val Leu Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 63

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 21

<400> 63

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr

20 25 30

Trp Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 64

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 22

<400> 64

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Arg Trp Thr Val Leu Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 65

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 23

<400> 65

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Asn Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 66

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 24

<400> 66

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ile Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Ser Trp Thr Val Leu Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 67

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 25

<400> 67

Gln Asp Thr Leu Arg Glu Ser Gly Gly Gly Phe Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 68

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 27

<400> 68

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Ser Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 69

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 28

<400> 69

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp His Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 70

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 29

<400> 70

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Phe Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 71

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 30

<400> 71

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Asn Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 72

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 31

<400> 72

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Ile Leu Val Thr Val Ser Ser

115 120

<210> 73

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 32

<400> 73

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 74

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 01, 02, 04, 06, 07, 08, 09, 10, 23, 25, 32, 38, 39, 40 or 41

<400> 74

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 75

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 75

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly Gly Tyr

20 25 30

Thr Val Asn Trp Tyr Gln Gln Phe Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Ile Asn Asn Glu Arg Pro Ser Gly Val Pro Glu Arg Phe Ser

50 55 60

Ala Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 76

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 11, 13, 14, 15, 16

<400> 76

Gln Ala Gly Leu Thr Gln Pro Pro Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Lys Phe Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Asp Asn

20 25 30

Tyr Val Asn Trp Tyr Arg His Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ser Ser Ala Ser Leu Thr Ile Thr Gly Leu Gln

65 70 75 80

Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Asp Gly Leu

85 90 95

Ser Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gln

100 105 110

<210> 77

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chain 12

<400> 77

Gln Ala Gly Leu Thr Gln Pro Pro Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Lys Phe Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Asp Asn

20 25 30

Tyr Val Asn Trp Tyr Gln His Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Ser Asn Thr Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ser Ser Ala Ser Leu Thr Ile Thr Gly Leu Gln

65 70 75 80

Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Asp Gly Leu

85 90 95

Ser Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gln

100 105 110

<210> 78

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chain 17

<400> 78

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ala Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 79

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 26

<400> 79

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Ser Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Val Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 80

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 28

<400> 80

Leu Pro Val Leu Thr Gln Pro Pro Leu Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 81

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 29

<400> 81

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Leu Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 82

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 31

<400> 82

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Arg

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 83

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chain 33

<400> 83

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Thr Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 84

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 34

<400> 84

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln His Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 85

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chains 35

<400> 85

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Val Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 86

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chain 36

<400> 86

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Ser Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 87

<211> 110

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the lung variable domain

antibody chain 37

<400> 87

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Ser Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu

100 105 110

<210> 88

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 01

<400> 88

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gln Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 89

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 02

<400> 89

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 90

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 03

<400> 90

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Lys Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 91

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 04

<400> 91

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 92

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 05

<400> 92

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 93

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 06

<400> 93

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 94

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 07

<400> 94

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Lys Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 95

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 08

<400> 95

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 96

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 09

<400> 96

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 97

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibodies 10, 17,

26, 33, 34, 35, 36, 37

<400> 97

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 98

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 11

<400> 98

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Phe His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Asn Ser Ser Gln Trp His Arg Met Ser Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 99

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 12

<400> 99

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp His Val Ala Glu Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 100

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 13

<400> 100

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Gly Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 101

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 14

<400> 101

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Trp Phe His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 102

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 15

<400> 102

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp Gly Ser Leu Gly Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 103

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 16

<400> 103

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ala Tyr

20 25 30

Trp Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Gly His Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 104

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 18

<400> 104

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Phe His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Arg Trp Val Val Gln Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 105

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 19

<400> 105

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr

20 25 30

Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Asn Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 106

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 20

<400> 106

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Thr Trp Thr Val Leu Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 107

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody 21 heavy chain

<400> 107

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr

20 25 30

Trp Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 108

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody 22 heavy chain

<400> 108

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Arg Trp Thr Val Leu Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 109

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 23

<400> 109

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Asn Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 110

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody 24 heavy chain

<400> 110

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ile Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Ser Trp Thr Val Leu Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 111

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 25

<400> 111

Gln Asp Thr Leu Arg Glu Ser Gly Gly Gly Phe Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 112

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 27

<400> 112

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Ser Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 113

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 28

<400> 113

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp His Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 114

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 29

<400> 114

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Phe Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 115

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 30

<400> 115

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Tyr

20 25 30

Trp Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Asn Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 116

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 31

<400> 116

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Ile Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 117

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the heavy chain of antibody 32

<400> 117

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 118

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the light chain of antibodies 01, 02, 04,

06, 07, 08, 09, 10, 23, 25, 32, 38, 39, 40 or 41

<400> 118

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 119

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the light chain of antibodies 03, 05, 18,

19, 20, 21, 22, 24, 27, 30

<400> 119

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly Gly Tyr

20 25 30

Thr Val Asn Trp Tyr Gln Gln Phe Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Ile Asn Asn Glu Arg Pro Ser Gly Val Pro Glu Arg Phe Ser

50 55 60

Ala Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 120

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the light chain of antibodies 11, 13, 14,

15, 16

<400> 120

Gln Ala Gly Leu Thr Gln Pro Pro Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Lys Phe Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Asp Asn

20 25 30

Tyr Val Asn Trp Tyr Arg His Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ser Ser Ala Ser Leu Thr Ile Thr Gly Leu Gln

65 70 75 80

Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Asp Gly Leu

85 90 95

Ser Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gln Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 121

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 12

<400> 121

Gln Ala Gly Leu Thr Gln Pro Pro Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Lys Phe Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Asp Asn

20 25 30

Tyr Val Asn Trp Tyr Gln His Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Ser Asn Thr Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ser Ser Ala Ser Leu Thr Ile Thr Gly Leu Gln

65 70 75 80

Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Asp Gly Leu

85 90 95

Ser Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gln Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 122

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 17

<400> 122

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ala Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 123

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 26

<400> 123

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Ser Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Val Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 124

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 28

<400> 124

Leu Pro Val Leu Thr Gln Pro Pro Leu Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 125

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 29

<400> 125

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Leu Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 126

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 31

<400> 126

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Arg

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 127

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 33

<400> 127

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Thr Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 128

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 34

<400> 128

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln His Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 129

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 35

<400> 129

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Val Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 130

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 36

<400> 130

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Ser Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 131

<211> 217

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody light chain 37

<400> 131

Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Ile Thr Ile Ser Cys Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn

20 25 30

Val Val Asn Trp Tyr Arg Gln Val Ser Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Gln

65 70 75 80

Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Trp Asp Asp Ser Leu

85 90 95

Asn Gly Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Arg Thr

100 105 110

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

115 120 125

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

130 135 140

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

145 150 155 160

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

165 170 175

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185 190

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 132

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 01

<400> 132

Gly Phe Thr Phe Gln Thr Tyr

15

<210> 133

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 02

<400> 133

Gly Phe Thr Phe Thr Thr Tyr

15

<210> 134

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 03

<400> 134

Gly Phe Thr Phe Lys Thr Tyr

15

<210> 135

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 04

<400> 135

Gly Phe Thr Phe Asn Thr Tyr

15

<210> 136

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 05, 06, 07, 10, 11, 15, 17, 23, 25,

26, 28, 29, 31, 32, 33, 34, 35, 36, 37

<400> 136

Gly Phe Thr Phe Ser Thr Tyr

15

<210> 137

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 08, 09

<400> 137

Gly Phe Thr Phe Gly Thr Tyr

15

<210> 138

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 12, 13, 18, 20, 22, 24, 30

<400> 138

Gly Phe Thr Phe Ser Tyr Tyr

15

<210> 139

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 14

<400> 139

Gly Phe Thr Phe Ser Ser Tyr

15

<210> 140

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 16

<400> 140

Gly Phe Thr Phe Ser Ala Tyr

15

<210> 141

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody heavy chain domain 19, 21, 27

<400> 141

Gly Phe Thr Phe Ser His Tyr

15

<210> 142

<211> 6

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody heavy chain domain 01, 02, 03, 04, 05, 06, 07, 08, 09,

10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37

<400> 142

Arg Pro Ala Gly Ser

15

<210> 143

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 01, 02, 04, 06, 08, 09

<400> 143

Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro

1 5 10

<210> 144

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 03

<400> 144

Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Tyr

1 5 10

<210> 145

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 05

<400> 145

Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Ser

1 5 10

<210> 146

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 07

<400> 146

Gly Gly Tyr Ser Ala Thr Trp Tyr Lys Tyr Asp Pro

1 5 10

<210> 147

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 10, 17, 23, 25, 26, 29, 31, 32, 33,

34, 35, 36, 37

<400> 147

Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro

1 5 10

<210> 148

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 11

<400> 148

Gly Gly Asn Ser Ser Gln Trp His Arg Met Ser Pro

1 5 10

<210> 149

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 12

<400> 149

Gly Gly Arg Ser Ser Gln Trp His Val Ala Glu Tyr

1 5 10

<210> 150

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 13

<400> 150

Gly Gly Arg Ser Ser Glu Trp His Val Gly Gly Tyr

1 5 10

<210> 151

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 14, 21

<400> 151

Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr

1 5 10

<210> 152

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 15

<400> 152

Gly Gly Arg Ser Ser Glu Trp Gly Ser Leu Gly Ser

1 5 10

<210> 153

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 16

<400> 153

Gly Gly Arg Ser Ser Glu Trp His Val Gly His Tyr

1 5 10

<210> 154

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 19

<400> 154

Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Gly Tyr

1 5 10

<210> 155

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 20

<400> 155

Gly Gly Arg Ser Ser Thr Trp Thr Val Leu Asp Tyr

1 5 10

<210> 156

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 22

<400> 156

Gly Gly Arg Ser Ser Arg Trp Thr Val Leu Asp Tyr

1 5 10

<210> 157

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 24

<400> 157

Gly Gly Arg Ser Ser Ser Trp Thr Val Leu Asp Tyr

1 5 10

<210> 158

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 27

<400> 158

Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Ser Tyr

1 5 10

<210> 159

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 28

<400> 159

Gly Gly Tyr Ser Ser Thr Trp His Arg Tyr Asp Pro

1 5 10

<210> 160

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 30

<400> 160

Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Asn Tyr

1 5 10

<210> 161

<211> 13

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37

<400> 161

Ser Gly Ser Thr Ser Asn Ile Gly Ser Asn Val Val Asn

1 5 10

<210> 162

<211> 13

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 162

Ser Gly Ser Arg Ser Asn Ile Gly Gly Tyr Thr Val Asn

1 5 10

<210> 163

<211> 13

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Chothia) variable

antibody light chain domain 11, 12, 13, 14, 15, 16

<400> 163

Thr Gly Ser Ser Ser Asn Ile Gly Asp Asn Tyr Val Asn

1 5 10

<210> 164

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 23,

25, 26, 28, 29, 31, 32, 33, 35, 36, 37

<400> 164

Arg Asp Asn Gln Arg Pro Ser

15

<210> 165

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 165

Ile Asn Asn Glu Arg Pro Ser

15

<210> 166

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody light chain domain 11, 13, 14, 15, 16

<400> 166

Arg Asp Ser Asn Arg Ala Ser

15

<210> 167

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody light chain domain 12

<400> 167

Ser Asn Thr Asn Arg Ala Ser

15

<210> 168

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody light chain domain 17

<400> 168

Arg Asp Asn Arg Arg Pro Ser

15

<210> 169

<211> 7

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Chothia) variable

antibody light chain domain 34

<400> 169

Arg Asp Asn Gln His Pro Ser

15

<210> 170

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 34, 35, 36, 37

<400> 170

Ser Thr Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 171

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 171

Ala Ala Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 172

<211> 10

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody light chain domain 11, 12, 13, 14, 15, 16

<400> 172

Ser Ser Trp Asp Asp Gly Leu Ser Val Val

1 5 10

<210> 173

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody light chain domain 33

<400> 173

Thr Thr Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 174

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 01

<400> 174

Gly Phe Thr Phe Gln Thr Tyr Trp

15

<210> 175

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 02

<400> 175

Gly Phe Thr Phe Thr Thr Tyr Trp

15

<210> 176

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 03

<400> 176

Gly Phe Thr Phe Lys Thr Tyr Trp

15

<210> 177

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 04

<400> 177

Gly Phe Thr Phe Asn Thr Tyr Trp

15

<210> 178

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 05, 06, 07, 10, 11, 15, 17, 23, 25,

26, 28, 29, 31, 32, 33, 34, 35, 36, 37

<400> 178

Gly Phe Thr Phe Ser Thr Tyr Trp

15

<210> 179

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 08, 09

<400> 179

Gly Phe Thr Phe Gly Thr Tyr Trp

15

<210> 180

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 12, 13, 18, 20, 22, 24, 30

<400> 180

Gly Phe Thr Phe Ser Tyr Tyr Trp

15

<210> 181

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 14

<400> 181

Gly Phe Thr Phe Ser Ser Tyr Trp

15

<210> 182

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 16

<400> 182

Gly Phe Thr Phe Ser Ala Tyr Trp

15

<210> 183

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody heavy chain domain 19, 21, 27

<400> 183

Gly Phe Thr Phe Ser His Tyr Trp

15

<210> 184

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Imgt) variable

antibody heavy chain domain 01, 02, 03, 04, 05, 06, 07, 08, 09,

10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37

<400> 184

Ile Arg Pro Ala Gly Ser Ser Thr

15

<210> 185

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 01, 02, 04, 06, 08, 09

<400> 185

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro

1 5 10

<210> 186

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 03

<400> 186

Ser Lys Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Tyr

1 5 10

<210> 187

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 05

<400> 187

Ser Lys Gly Gly Tyr Ser Arg Thr Trp Tyr Val Tyr Asp Ser

1 5 10

<210> 188

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 07

<400> 188

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Lys Tyr Asp Pro

1 5 10

<210> 189

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 10, 17, 23, 25, 26, 29, 31, 32, 33,

34, 35, 36, 37

<400> 189

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro

1 5 10

<210> 190

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 11

<400> 190

Ser Lys Gly Gly Asn Ser Ser Gln Trp His Arg Met Ser Pro

1 5 10

<210> 191

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 12

<400> 191

Ser Lys Gly Gly Arg Ser Ser Gln Trp His Val Ala Glu Tyr

1 5 10

<210> 192

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 13

<400> 192

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Gly Gly Tyr

1 5 10

<210> 193

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 14, 21

<400> 193

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Ala Gln Tyr

1 5 10

<210> 194

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 15

<400> 194

Ser Lys Gly Gly Arg Ser Ser Glu Trp Gly Ser Leu Gly Ser

1 5 10

<210> 195

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 16

<400> 195

Ser Lys Gly Gly Arg Ser Ser Glu Trp His Val Gly His Tyr

1 5 10

<210> 196

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 19

<400> 196

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Gly Tyr

1 5 10

<210> 197

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 20

<400> 197

Ser Lys Gly Gly Arg Ser Ser Thr Trp Thr Val Leu Asp Tyr

1 5 10

<210> 198

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 22

<400> 198

Ser Lys Gly Gly Arg Ser Ser Arg Trp Thr Val Leu Asp Tyr

1 5 10

<210> 199

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 24

<400> 199

Ser Lys Gly Gly Arg Ser Ser Ser Trp Thr Val Leu Asp Tyr

1 5 10

<210> 200

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 27

<400> 200

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Ser Tyr

1 5 10

<210> 201

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 28

<400> 201

Ser Lys Gly Gly Tyr Ser Ser Thr Trp His Arg Tyr Asp Pro

1 5 10

<210> 202

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 30

<400> 202

Ser Lys Gly Gly Arg Ser Ser Gln Trp Thr Val Leu Asn Tyr

1 5 10

<210> 203

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37

<400> 203

Thr Ser Asn Ile Gly Ser Asn Val

15

<210> 204

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 204

Arg Ser Asn Ile Gly Gly Tyr Thr

15

<210> 205

<211> 8

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Imgt) variable

antibody light chain domain 11, 12, 13, 14, 15, 16

<400> 205

Ser Ser Asn Ile Gly Asp Asn Tyr

15

<210> 206

<211> 3

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Imgt) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37

<400> 206

Arg Asp Asn

1

<210> 207

<211> 3

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Imgt) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 207

Ile Asn Asn

1

<210> 208

<211> 3

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Imgt) variable

antibody light chain domain 11, 13, 14, 15, 16

<400> 208

Arg Asp Ser

1

<210> 209

<211> 3

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR2 (Imgt) variable

antibody light chain domain 12

<400> 209

Ser Asn Thr

1

<210> 210

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody light chain domain 01, 02, 04, 06, 07, 08, 09, 10, 17,

23, 25, 26, 28, 29, 31, 32, 34, 35, 36, 37

<400> 210

Ser Thr Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 211

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody light chain domain 03, 05, 18, 19, 20, 21, 22, 24, 27, 30

<400> 211

Ala Ala Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 212

<211> 10

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody light chain domain 11, 12, 13, 14, 15, 16

<400> 212

Ser Ser Trp Asp Asp Gly Leu Ser Val Val

1 5 10

<210> 213

<211> 11

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody light chain domain 33

<400> 213

Thr Thr Trp Asp Asp Ser Leu Asn Gly Val Val

1 5 10

<210> 214

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 01

<400> 214

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttcaa acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcca cttggtatcg atacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 215

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibodies 01,

38, 39, 40 or 41

<400> 215

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 216

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 01

<400> 216

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttcaa acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcca cttggtatcg atacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 217

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 01, 38, 39, 40 or 41

<400> 217

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 218

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 02

<400> 218

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttact acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatcg atacgacccc tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 219

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 02

<400> 219

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 220

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 02

<400> 220

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttact acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatcg atacgacccc tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 221

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 02

<400> 221

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 222

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 03

<400> 222

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttaaa acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctcgca cttggtatgt ctacgactac tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 223

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 03

<400> 223

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 224

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 03

<400> 224

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttaaa acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctcgca cttggtatgt ctacgactac tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 225

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 03

<400> 225

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 226

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 04

<400> 226

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttaac acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatcg atacgacccc tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 227

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 04

<400> 227

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 228

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 04

<400> 228

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttaac acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatcg atacgacccc tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 229

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 04

<400> 229

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 230

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 05

<400> 230

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctcgta cttggtatgt ctacgactct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 231

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 05

<400> 231

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 232

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 05

<400> 232

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctcgta cttggtatgt ctacgactct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 233

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 05

<400> 233

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 234

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 06

<400> 234

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttagc acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggtggg 300

tattctgcca cttggtatcg gtacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 235

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 06

<400> 235

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 236

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 06

<400> 236

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttagc acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggtggg 300

tattctgcca cttggtatcg gtacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 237

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 06

<400> 237

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 238

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 07

<400> 238

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttcc acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaagggggg 300

tattctgcga cttggtataa gtacgacccc tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 239

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 07

<400> 239

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 240

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 07

<400> 240

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttcc acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaagggggg 300

tattctgcga cttggtataa gtacgacccc tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 241

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 07

<400> 241

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 242

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 08

<400> 242

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttggt acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatag atacgaccca tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 243

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 08

<400> 243

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 244

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 08

<400> 244

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttggt acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatag atacgaccca tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 245

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 08

<400> 245

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 246

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 09

<400> 246

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttcgc acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcta cttggtatcg ttacgacccc tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 247

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 09

<400> 247

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 248

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 09

<400> 248

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttcgc acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcta cttggtatcg ttacgacccc tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 249

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 09

<400> 249

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 250

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 10

<400> 250

caggtcacgc ttagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttagt acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ttacgaccca tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 251

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 10

<400> 251

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 252

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 10

<400> 252

caggtcacgc ttagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tacttttagt acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ttacgaccca tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 253

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 10

<400> 253

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 254

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 11

<400> 254

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc acttactggt tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagttct attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

aatagcagcc aatggcatag aatgagtccc tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 255

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 11

<400> 255

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag 330

<210> 256

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 11

<400> 256

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc acttactggt tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagttct attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

aatagcagcc aatggcatag aatgagtccc tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 257

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 11

<400> 257

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 258

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 12

<400> 258

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tactactggt tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcc agtggcatgt agctgaatac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 259

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 12

<400> 259

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgcactg gaagtagcag caacatcggg gataattatg taaactggta ccaacatctg 120

cccaggaacgg cccccaaact cctgatctac agtaacacca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag 330

<210> 260

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 12

<400> 260

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tactactggt tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcc agtggcatgt agctgaatac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 261

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 12

<400> 261

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgcactg gaagtagcag caacatcggg gataattatg taaactggta ccaacatctg 120

cccaggaacgg cccccaaact cctgatctac agtaacacca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 262

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 13

<400> 262

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactgga tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcg agtggcatgt aggcgggtac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 263

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 13

<400> 263

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag 330

<210> 264

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 13

<400> 264

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactgga tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcg agtggcatgt aggcgggtac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 265

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 13

<400> 265

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 266

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 14

<400> 266

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tcgtactggt tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgcagcagcg agtggcatgt agcgcagtac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 267

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 14

<400> 267

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag 330

<210> 268

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 14

<400> 268

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tcgtactggt tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgcagcagcg agtggcatgt agcgcagtac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 269

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 14

<400> 269

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 270

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 15

<400> 270

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc acttactgga tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcg aatgggggag tctcggcagt tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 271

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 15

<400> 271

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag 330

<210> 272

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 15

<400> 272

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc acttactgga tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcg aatgggggag tctcggcagt tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 273

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 15

<400> 273

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 274

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 16

<400> 274

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc gcatactggc tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgaagcagcg aatggcacgt agggcattac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 275

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 16

<400> 275

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag 330

<210> 276

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 16

<400> 276

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc gcatactggc tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgaagcagcg aatggcacgt agggcattac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 277

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 16

<400> 277

caggcagggc tgactcagcc gccctccgtg tctggatccc cgggccagaa gttcaccatc 60

tcctgtactg gaagtagcag caacattggg gataattatg taaactggta ccgacatctg 120

cccaggaacgg cccccaaact cctgatctac agagatagca atagggcctc gggggtcccg 180

gaccgcttct ctggctccaa gtctggcagc tcggcctccc tgaccatcac tgggctccag 240

gctgaggacg aggctgacta ttactgctca tcctgggatg acggcctcag tgttgtgttc 300

ggcggaggga ccaagctgac cgtcctacag cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 278

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 17

<400> 278

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 279

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 17

<400> 279

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaagtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc ggcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcgcc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 280

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 17

<400> 280

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 281

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 17

<400> 281

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaagtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc ggcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcgcc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 282

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 18

<400> 282

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggt tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcc gttgggtcgt acaggactac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 283

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 18

<400> 283

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 284

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 18

<400> 284

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggt tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcc gttgggtcgt acaggactac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 285

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 18

<400> 285

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 286

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 19

<400> 286

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc cactactgga tacactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acaacctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcc agtggacggt actcggctac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 287

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 19

<400> 287

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 288

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 19

<400> 288

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc cactactgga tacactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acaacctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cggagcagcc agtggacggt actcggctac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 289

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 19

<400> 289

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 290

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain variable domain sequence 20

<400> 290

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggg ttcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taaaggcgga 300

aggagcagca cttggaccgt acttgactac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 291

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 20

<400> 291

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 292

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 20

<400> 292

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggg ttcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taaaggcgga 300

aggagcagca cttggaccgt acttgactac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 293

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 20

<400> 293

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 294

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 21

<400> 294

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc cattactggt tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

aggagcagcg aatggcacgt agcgcagtac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 295

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 21

<400> 295

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 296

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 21

<400> 296

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc cattactggt tgcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

aggagcagcg aatggcacgt agcgcagtac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 297

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 21

<400> 297

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 298

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain variable domain sequence 22

<400> 298

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tactactggg ttcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

agaagcagcc gttggactgt actggattac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 299

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 22

<400> 299

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 300

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 22

<400> 300

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tactactggg ttcactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

agaagcagcc gttggactgt actggattac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 301

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 22

<400> 301

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 302

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 23

<400> 302

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaataa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 303

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 23

<400> 303

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 304

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 23

<400> 304

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaataa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 305

<211> 651

<212>RNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 23

<400> 305

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 306

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 24

<400> 306

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggg tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa catcctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgaagcagca gttggacggt actcgattac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 307

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 24

<400> 307

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 308

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 24

<400> 308

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggg tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa catcctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgaagcagca gttggacggt actcgattac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 309

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 24

<400> 309

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 310

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 25

<400> 310

caggacacgc tcagagaatc aggaggaggt tttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 311

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 25

<400> 311

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 312

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 25

<400> 312

caggacacgc tcagagaatc aggaggaggt tttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 313

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 25

<400> 313

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 314

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 26

<400> 314

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccgg cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 315

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 26

<400> 315

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctagcacc tcagcctccc tagtcatcag tggactccag 240

ccagaagacg aggctgttta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 316

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 26

<400> 316

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccgg cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 317

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 26

<400> 317

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctagcacc tcagcctccc tagtcatcag tggactccag 240

ccagaagacg aggctgttta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 318

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 27

<400> 318

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc cactactggg tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgtagcagcc agtggaccgt actgagttac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 319

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 27

<400> 319

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 320

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 27

<400> 320

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc cactactggg tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgtagcagcc agtggaccgt actgagttac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 321

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 27

<400> 321

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 322

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 28

<400> 322

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggcatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 323

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 28

<400> 323

ctgcctgtgc tgactcagcc gcccttagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 324

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 28

<400> 324

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggcatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 325

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 28

<400> 325

ctgcctgtgc tgactcagcc gcccttagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 326

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 29

<400> 326

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcgagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt acttttgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 327

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 29

<400> 327

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc tcgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact cctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 328

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 29

<400> 328

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcgagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt acttttgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 329

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 29

<400> 329

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc tcgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact cctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 330

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 30

<400> 330

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggg tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgtagcagcc agtggaccgt actaaattac tggggacaag gaaccttagt cactgtctcg 360

agt 363

<210> 331

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 30

<400> 331

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta 330

<210> 332

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 30

<400> 332

caggtaactc tgagggaaag tggaggaggc ctagtacagc caggaggaag tttaagatta 60

agttgcgcgg cgagcggatt cacctttagc tattactggg tccactgggt aaggcaagcg 120

ccaggcaaag gattagagtg ggtaagtact attaggcctg cgggcagctc cacctattac 180

actgattcag tcaaaggacg cttcaccatc agcagagaca acgcgaagaa caccctgtat 240

ctccagatga acagcctgaa aagcgaggac accgcagtat attattgcag taagggcgga 300

cgtagcagcc agtggaccgt actaaattac tggggacaag gaaccttagt cactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 333

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 30

<400> 333

ctgcctgtgc tgactcagcc accctcagcc tctgggaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcaggtc caatatcgga ggttatactg taaactggta ccagcagttc 120

ccaggcacgg cccccaaact cctcatctat attaataatg aacggccctc aggggtccct 180

gagcgattct ctgcctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttattgtgca gcgtgggatg acagcctgaa tggtgtggtg 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 334

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 31

<400> 334

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaattcttgt tactgtctcg 360

agt 363

<210> 335

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 31

<400> 335

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcggag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggtacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 336

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 31

<400> 336

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaattcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 337

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 31

<400> 337

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcggag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggtacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 338

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 32

<400> 338

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgtgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 339

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain variable domain sequence 32

<400> 339

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tctgcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 340

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 32

<400> 340

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgtgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 341

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 32

<400> 341

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tctgcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 342

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 33

<400> 342

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 343

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 33

<400> 343

ctgcctgtgc tgactcagcc gccttcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaactg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgtaca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 344

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 33

<400> 344

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 345

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 33

<400> 345

ctgcctgtgc tgactcagcc gccttcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaactg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgtaca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 346

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 34

<400> 346

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 347

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 34

<400> 347

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcatccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 348

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 34

<400> 348

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 349

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 34

<400> 349

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcatccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 350

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 35

<400> 350

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 351

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 35

<400> 351

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

ccaggaacgg tccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggagtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 352

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 35

<400> 352

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 353

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 35

<400> 353

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

ccaggaacgg tccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggagtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 354

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 36

<400> 354

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 355

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 36

<400> 355

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctagcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag gaacccagct caccgtttta 330

<210> 356

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 36

<400> 356

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 357

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 36

<400> 357

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

cccaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctagcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag gaacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 358

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 37

<400> 358

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 359

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the light chain of antibody 37

<400> 359

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

tcaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta 330

<210> 360

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 37

<400> 360

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 361

<211> 651

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody light chain sequence 37

<400> 361

ctgcctgtgc tgactcagcc gccctcagcg tctgggaccc ccgggcagag gatcaccatc 60

tcttgttctg gaagcacctc caacatcgga agtaatgttg taaactggta ccgccaggtc 120

tcaggaacgg cccccaaact tctcatctat agagataatc agcgtccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tagtcatcag tggactccag 240

cctgaagacg aggctgatta ttactgttca acatgggatg acagcctgaa tggtgtggtt 300

ttcggcggag ggacccagct caccgtttta cgtacggtgg ctgcaccatc tgtcttcatc 360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651

<210> 362

<211> 5

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR1 (Kabat) variable

antibody heavy chain domain 18

<400> 362

Tyr Tyr Trp Phe His

15

<210> 363

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Kabat) variable

antibody heavy chain domain 18

<400> 363

Gly Gly Arg Ser Ser Arg Trp Val Val Gln Asp Tyr

1 5 10

<210> 364

<211> 12

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Chothia) variable

antibody heavy chain domain 18

<400> 364

Gly Gly Arg Ser Ser Arg Trp Val Val Gln Asp Tyr

1 5 10

<210> 365

<211> 14

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of CDR3 (Imgt) variable

antibody heavy chain domain 18

<400> 365

Ser Lys Gly Gly Arg Ser Ser Arg Trp Val Val Gln Asp Tyr

1 5 10

<210> 366

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 38

<400> 366

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Lys Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asp Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 367

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 38

<400> 367

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Lys Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asp Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 368

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chains 39

<400> 368

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 369

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody heavy chain 39

<400> 369

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 370

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 40

<400> 370

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Tyr Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 371

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody 40 heavy chain

<400> 371

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Tyr Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ala Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 372

<211> 121

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of the variable domain of severe

antibody chain 41

<400> 372

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 373

<211> 447

<212>PRT

<213> Artificial sequence

<220>

<223> amino acid sequence of antibody 41 heavy chain

<400> 373

Gln Val Thr Leu Arg Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Arg Pro Ala Gly Ser Ser Thr Tyr Tyr Thr Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ser Lys Gly Gly Tyr Ser Ser Thr Trp Tyr Arg Tyr Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

<210> 374

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 38

<400> 374

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgtgg cgtcggggtt tacttttaag acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatgg actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatag gtacgaccca tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 375

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 38

<400> 375

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgtgg cgtcggggtt tacttttaag acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatgg actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcga cttggtatag gtacgaccca tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 376

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 39

<400> 376

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttcg acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggtggg 300

tattctgcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 377

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 39

<400> 377

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttcg acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggtggg 300

tattctgcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 378

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 40

<400> 378

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttat acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcca cttggtatcg ttacgacccc tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 379

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 40

<400> 379

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttat acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattctgcca cttggtatcg ttacgacccc tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<210> 380

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

sequence of the variable domain of the heavy chain of antibody 41

<400> 380

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agt 363

<210> 381

<211> 1341

<212> DNA

<213> Artificial sequence

<220>

<223> Nucleic acid that codes for amino acid

antibody heavy chain sequence 41

<400> 381

caggtcacgc tcagagaatc aggaggaggt cttgttcaac ccggaggatc gcttcgactt 60

tcttgcgcgg cgtcggggtt tactttttca acgtattgga tgcattgggt tcggcaagct 120

ccagggaaag gacttgaatg ggtttctaca atccggccag cgggatcttc tacttactac 180

actgactctg ttaaggggcg gttcactatc tcgcgggata acgccaagaa cacgctctac 240

cttcaaatga actccctgaa atcggaggac accgctgttt actattgctc taaaggcggg 300

tattcttcga cttggtatcg ctacgaccct tggggacagg gaactcttgt tactgtctcg 360

agtgctagca caaagggccc ctccgtgttc cctctggcac cttgctcccg tagcacttct 420

gaaagcactg ctgctctggg ctgtttggtg aaggactatt ttcccgaacc cgtgacagtg 480

tcatggaact ctggggcctt aacatctggt gttcacacat tccccgctgt gttgcagtct 540

tcaggtctgt actccctcag ctcagtagtg acagtcccaa gttcgtcctt gggtacgaag 600

acttatacct gcaatgtaga ccacaaaccc agtaatacca aggtggataa gcgtgtggag 660

tcgaaatacg gaccgccctg cccaccatgc cctgctcccg aattccttgg aggaccatcc 720

gtcttccttt ttcctcctaa accaaaggat accctgatga tctctaggac cccggaagtg 780

acttgcgtgg ttgtggacgt ttcccaggaa gatccagagg tgcagtttaa ttggtacgtg 840

gacggtgtgg aggtccataa tgcaaagaca aaacctaggg aagaacagtt taactctacc 900

tatagggtag taagtgtgct gactgtgctt caccaggact ggctgaacgg gaaggaatac 960

aagtgcaaag tgagtaataa ggggctcccg tctagcattg agaaaaccat ctccaaggca 1020

aaaggtcagc caagggaacc ccaagtgtac accctaccgc ctagtcagga ggaaatgacc 1080

aaaaaccaag tgtctctgac ctgcctcgtc aagggcttct atccttctga cattgctgtg 1140

gaatgggaga gcaatggtca gccagaaaat aactataaaa cccacacctcc tgtgctggac 1200

tccgatggca gcttcttcct ttacagccgc ctcacagtgg acaagagtcg gtggcaggaa 1260

ggtaatgtct tctcatgtag tgtaatgcat gaggctcttc acaaccacta cacccagaag 1320

tctctcagcc tgtctcttgg a 1341

<---

Claims (426)

1. An isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-4Rα (a subunit of the interleukin 4 receptor IL-4Rα), comprising (a) a heavy chain variable domain containing (i) CDR1 with the amino acid sequence X ₁ YWX ₂ H, where X ₁ = T, Y, S, A or H; X ₂ = M, F, L, I or V; (ii) CDR2 with amino acid sequence X ₃ IRPAGSSTYYTDSVKG, where X ₃ = T or S; (iii) CDR3 with the amino acid sequence GGX ₄ SX ₅ X ₆ WX ₇ X ₈ X ₉ X ₁₀ X ₁₁ , where X ₄ =Y, R or N; X ₅ = S, A or R; X ₆ = T, Q, E, R or S; X ₇ = Y, H, G, T or V; X ₈ =R, V, K or S; X ₉ =Y, M, A, G, L or Q; X ₁₀ =D, S, E, G, Q, H or N; X ₁₁ =P, Y or S; And (b) a light chain variable domain containing (i) CDR1 with the amino acid sequence X ₁₂ GSX ₁₃ SNIGX ₁₄ X ₁₅ X ₁₆ VG, where X ₁₂ =S or T; X ₁₃ =T, R or S; X ₁₄ =S, G or D; X ₁₅ =N or Y; X ₁₆ =V, T or Y; (ii) CDR2 with the amino acid sequence X ₁₇ X ₁₈ X ₁₉ X ₂₀ X ₂₁ X ₂₂ S, where X ₁₇ =R, I or S; X ₁₈ =D or N; X ₁₉ =N, S or T; X ₂₀ =Q, E, N or R; X ₂₁ =R or H; X ₂₂ =P or A; (iii) CDR3 with amino acid sequence X ₂₃ X ₂₄ WDDX ₂₅ LX ₂₆ X ₂₇ VV X ₂₃ =S, A or T; X ₂₄ =T, A or S; X ₂₅ =S or G; X ₂₆ =N or S; X ₂₇ =G or 0. 2. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 1, where the heavy chain variable domain contains CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 362. 3. The isolated monoclonal antibody or its antigen-binding fragment according to claim 1, where the heavy chain variable domain contains CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 11 or SEQ ID NO: 12. 4. The isolated monoclonal antibody or its antigen-binding fragment according to claim 1, where the heavy chain variable domain contains CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO : 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30 or SEQ ID NO: 363. 5. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 1, wherein the light chain variable domain contains a CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 31, SEQ ID NO: 32 or SEQ ID NO: 33. 6. The isolated monoclonal antibody or its antigen-binding fragment according to claim 1, where the light chain variable domain contains CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38 or SEQ ID NO: 39. 7. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 1, wherein the light chain variable domain contains a CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42 or SEQ ID NO: 43. 8. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 1, including (a) a heavy chain variable domain containing CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 362; CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 11 or SEQ ID NO: 12; CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30 or SEQ ID NO: 363; And (b) a light chain variable domain containing CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 31, SEQ ID NO: 32 or SEQ ID NO: 33; CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38 or SEQ ID NO: 39; CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42 or SEQ ID NO: 43. 9. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 8, including (i) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11, CDR3 with amino acid sequence SEQ ID NO: 13; (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 34, CDR3 with amino acid sequence SEQ ID NO: 40; (ii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11, CDR3 with amino acid sequence SEQ ID NO: 14; (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35, CDR3 with amino acid sequence SEQ ID NO: 41; (iii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11, CDR3 with amino acid sequence SEQ ID NO: 15; (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (iv) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 16; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 34 and CDR3 with amino acid sequence SEQ ID NO: 40; (v) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 17; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 34 and CDR3 with amino acid sequence SEQ ID NO: 40; (vi) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 2, CDR2 with amino acid sequence SEQ ID NO: 12 and CDR3 with amino acid sequence SEQ ID NO: 18; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 33, CDR2 with amino acid sequence SEQ ID NO: 36 and CDR3 with amino acid sequence SEQ ID NO: 42; (vii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 3, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 19; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 33, CDR2 with amino acid sequence SEQ ID NO: 37 and CDR3 with amino acid sequence SEQ ID NO: 42; (viii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 4, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 20, and (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 33, CDR2 with amino acid sequence SEQ ID NO: 36 and CDR3 with amino acid sequence SEQ ID NO: 42; (ix) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 5, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 21; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 33, CDR2 with amino acid sequence SEQ ID NO: 36 and CDR3 with amino acid sequence SEQ ID NO: 42; (x) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 22; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 33, CDR2 with amino acid sequence SEQ ID NO: 36 and CDR3 with amino acid sequence SEQ ID NO: 42; (xi) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 6, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 23; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 33, CDR2 with amino acid sequence SEQ ID NO: 36 and CDR3 with amino acid sequence SEQ ID NO: 42; (xii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 17; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 38 and CDR3 with amino acid sequence SEQ ID NO: 40; (xiii)(a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 362, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 363; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xiv) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 7, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 24; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xv) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 8, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 25, and (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xvi) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 9, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 21; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xvii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 8, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 26; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xviii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 8, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 27; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32, CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xix) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 29; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 34 and CDR3 with amino acid sequence SEQ ID NO: 40; (xx) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 8, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 30; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 32; CDR2 with amino acid sequence SEQ ID NO: 35 and CDR3 with amino acid sequence SEQ ID NO: 41; (xxi) CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 17; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 34 and CDR3 with amino acid sequence SEQ ID NO: 43; or (xxii) (a) a heavy chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 1, CDR2 with amino acid sequence SEQ ID NO: 11 and CDR3 with amino acid sequence SEQ ID NO: 17; And (b) a light chain variable domain containing CDR1 with amino acid sequence SEQ ID NO: 31, CDR2 with amino acid sequence SEQ ID NO: 39 and CDR3 with amino acid sequence SEQ ID NO: 40. 10. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable domain contains an amino acid sequence selected from the group: SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 366, SEQ ID NO: 368, SEQ ID NO: 370 or SEQ ID NO: 372. 11. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 1, wherein the light chain variable domain contains an amino acid sequence selected from the group: SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86 or SEQ ID NO: 87. 12. An isolated monoclonal antibody or its antigen-binding fragment according to claim 1, where (a) the heavy chain variable domain contains an amino acid sequence selected from the group: SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 366, SEQ ID NO: 368, SEQ ID NO: 370 or SEQ ID NO: 372; (b) the light chain variable domain contains an amino acid sequence selected from the group: SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86 or SEQ ID NO: 87. 13. An isolated monoclonal antibody or an antigen-binding fragment thereof according to claim 12, where (i) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 44 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (ii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 45 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (iii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 46 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (iv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 47 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (v) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 48 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (vi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 49 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (vii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 50 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (viii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 51 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (ix) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 52 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (x) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (xi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 54 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 76; (xii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 55 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 77; (xiii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 56 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 76; (xiv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 57 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 76; (xv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 58 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 76; (xvi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 59 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 76; (xvii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 78; (xviii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 60 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xix) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 61 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xx) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 62 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xxi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 63; (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xxii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 64 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xxiii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 65 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (xxiv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 66 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xxv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 67 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (xxvi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 79; (xxvii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 68 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xxviii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 69 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 80; (xxix) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 70 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 81; (xxx) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 71 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 75; (xxxi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 72 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 82; (xxxii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 73 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (xxxiii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 83; (xxxiv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 84; (xxxv) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 85; (xxxvi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53 and (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 86; (xxxvii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 53; (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 87; (xxxviii) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 366; (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (xxxix) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 368; (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; (xxxx) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 370; (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74; or (xxxxi) (a) the heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 372; (b) the light chain variable domain contains the amino acid sequence of SEQ ID NO: 74. 14. An isolated monoclonal antibody according to any one of paragraphs. 1-13, wherein the antibody that specifically binds to IL-4Rα is a full-length IgG antibody. 15. The isolated monoclonal antibody of claim 14, wherein the full-length IgG antibody is of the human IgG1, IgG2, IgG3 or IgG4 isotype. 16. The isolated monoclonal antibody according to claim 15, where the full-length IgG antibody is of the human IgG4 isotype. 17. The isolated monoclonal antibody of claim 16, wherein the antibody contains the S228P mutation in the hinge region. 18. An isolated monoclonal antibody according to claim 1, comprising a heavy chain containing an amino acid sequence selected from the group: SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO : 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100 , SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO : 117, SEQ ID NO: 367, SEQ ID NO: 369, SEQ ID NO: 371 or , SEQ ID NO: 373. 19. An isolated monoclonal antibody according to claim 1, comprising a light chain containing an amino acid sequence selected from the group: SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO : 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130 or SEQ ID NO: 131. 20. An isolated monoclonal antibody according to claim 1, including: (i) (a) a heavy chain containing an amino acid sequence selected from the group: SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 367, SEQ ID NO: 369, SEQ ID NO: 371, or SEQ ID NO: 373, and (b) a light chain containing an amino acid sequence selected from the group: SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123 , SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130 or SEQ ID NO: 131; (ii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 88, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (iii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 89, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (iv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 90, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (v) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 91, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (vi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 92, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (vii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 93, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (viii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 94, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (ix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 95, and (b) a light chain containing the amino acid sequence SEQ ID NO: 118, (x) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 96, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 98, and (b) a light chain containing the amino acid sequence SEQ ID NO: 120, (xiii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 99, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 121; (xiv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 100, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 120; (xv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 101, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 120; (xvi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 102, and (b) a light chain containing the amino acid sequence SEQ ID NO: 120, (xvii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 103, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 120; (xviii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 122; (xix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 104, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xx) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 105, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 106, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 107, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxiii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 108, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxiv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 109, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xxv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 110, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxvi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 111, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xxvii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 123; (xxviii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 112, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 113, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 124; (xxx) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 114, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 125; (xxxi)(a) a heavy chain containing the amino acid sequence of SEQ ID NO: 115, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 119; (xxxii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 116, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 126; (xxxiii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 117, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xxxiv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 127; (xxxv) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 128; (xxxvi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 129; (xxxvii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 130; (xxxviii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 97, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 131; (xxxix) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 367, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xxxx) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 369, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; (xxxxi) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 371, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118; or (xxxxii) (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 373, and (b) a light chain containing the amino acid sequence of SEQ ID NO: 118. 21. An isolated nucleic acid that encodes an antibody or an antigen-binding fragment thereof according to any one of claims. 1-20. 22. The isolated nucleic acid according to claim 21, where the nucleic acid is DNA. 23. An expression vector containing a nucleic acid according to any one of paragraphs. 21-22. 24. A method for obtaining a host cell for producing an antibody or an antigen-binding fragment thereof according to any one of claims. 1-20, including transforming the cell with the vector according to claim 23. 25. A host cell for producing an antibody or an antigen-binding fragment thereof according to any one of paragraphs. 1-20, containing a nucleic acid according to any one of paragraphs. 21-22. 26. A method for producing an antibody or an antigen-binding fragment thereof according to any one of claims. 1-20, which consists in cultivating the host cell according to claim 25 in a culture medium under conditions sufficient to obtain the specified antibody, if necessary, followed by isolation and purification of the resulting antibody. 27. A pharmaceutical composition for the treatment of a disease or disorder mediated by IL-4Rα, containing an antibody or an antigen-binding fragment according to any one of paragraphs. 1-20 in a therapeutically effective amount in combination with one or more pharmaceutically acceptable excipients. 28. The pharmaceutical composition according to claim 27, where the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton's syndrome , ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, stomach cancer, colorectal cancer, colon malignancy, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome. 29. A pharmaceutical composition for the treatment of a disease or disorder mediated by IL-4Rα, containing an antibody or an antigen-binding fragment according to any one of paragraphs. 1-20 and at least one other therapeutically active compound. 30. The pharmaceutical composition according to claim 29, where the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton's syndrome , ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, stomach cancer, colorectal cancer, colon malignancy, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome. 31. Pharmaceutical composition according to any one of paragraphs. 29, 30, wherein the other therapeutically active compound is an antibody, a small molecule, a hormone therapy, or a combination thereof. 32. A method of treating a disease or disorder mediated by IL-4Rα, comprising administering to a subject in need of such treatment an antibody or an antigen-binding fragment thereof according to any one of claims. 1-20 or a pharmaceutical composition according to any one of paragraphs. 27-31 in a therapeutically effective amount. 33. A method for treating a disease or disorder according to claim 32, where the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus , Netherton's syndrome, ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, cancer stomach, colorectal cancer, colon malignancy, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome. 34. A method of treating a disease or disorder mediated by IL-4Rα, comprising administering to a subject in need of such treatment an antibody or an antigen-binding fragment thereof according to any one of claims. 1-20 and at least one other therapeutically active compound in a therapeutically effective amount. 35. A method for treating a disease or disorder according to claim 34, where the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis, chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus , Netherton's syndrome, ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, cancer stomach, colorectal cancer, colon malignancy, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome. 36. A method of treating a disease or disorder according to any one of paragraphs. 34, 35, wherein the other therapeutically active compound is an antibody, a small molecule, a hormone therapy, or a combination thereof. 37. The use of an antibody or an antigen-binding fragment according to any one of paragraphs. 1-20 or a pharmaceutical composition according to any one of paragraphs. 27-31 for treating, in a subject in need of such treatment, a disease or disorder mediated by IL-4Rα. 38. Use according to claim 37, where the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis , chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton syndrome, ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, gastric cancer, colorectal cancer , colon malignancy, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome. 39. The use of an antibody or an antigen-binding fragment according to any one of paragraphs. 1-20 and at least one other therapeutically active compound for treating a disease or disorder mediated by IL-4Rα. 40. Use according to claim 39, where the disease or disorder mediated by IL-4Rα is selected from the group: atopic dermatitis, eczema, allergic dermatitis, atopic keratoconjunctivitis, bronchial asthma, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyposis , chronic rhinosinusitis, fungal rhinosinusitis, nasal polyposis, sleep apnea, allergic rhinitis, Churg-Strauss syndrome, pruritus associated with chronic liver disease, hypertrophic scar, alopecia areata, urticaria, allergic dermatitis, focal scleroderma, pemphigus, Netherton syndrome, ichthyosis, eosinophilic gastritis, eosinophilic esophagitis, prurigo nodosa, colitis, filariasis, leishmaniasis, schistosomiasis, arterial hypertension, interstitial pulmonary diseases, metastatic non-small cell lung cancer, metastases of epithelial tumors, prostate malignancy, brain malignancy, gastric cancer, colorectal cancer , colon malignancy, breast malignancy, pancreatic cancer, extrahepatic bile duct malignancy, intrahepatic bile duct cancer, gallbladder malignancy, Hodgkin's lymphoma, medulloblastoma, hypereosinophilic syndrome, allergic reactions, acute respiratory distress syndrome. 41. Use according to claim 39, wherein the other therapeutically active compound is an antibody, a small molecule, a hormone therapy, or a combination thereof.