US20060194290A1 - Polypeptide variants with altered effector function - Google Patents

Polypeptide variants with altered effector function Download PDF

Info

Publication number
US20060194290A1
US20060194290A1 US11/429,792 US42979206A US2006194290A1 US 20060194290 A1 US20060194290 A1 US 20060194290A1 US 42979206 A US42979206 A US 42979206A US 2006194290 A1 US2006194290 A1 US 2006194290A1
Authority
US
United States
Prior art keywords
region
binding
polypeptide
amino acid
antibody
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/429,792
Other languages
English (en)
Inventor
Leonard Presta
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Genentech Inc
Original Assignee
Genentech Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/483,588 external-priority patent/US6737056B1/en
Application filed by Genentech Inc filed Critical Genentech Inc
Priority to US11/429,792 priority Critical patent/US20060194290A1/en
Publication of US20060194290A1 publication Critical patent/US20060194290A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/283—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4283—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
    • C07K16/4291—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/022—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from an adenovirus

Definitions

  • Antibodies are proteins which exhibit binding specificity to a specific antigen.
  • Native antibodies are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies between the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (V H ) followed by a number of constant domains.
  • V H variable domain
  • the constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions.
  • antibodies or immunoglobulins can be assigned to different classes.
  • the heavy chain constant regions that correspond to the different classes of immunoglobulins are called ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ , respectively.
  • human immunoglobulin classes only human IgG1, IgG2, IgG3 and IgM are known to activate complement; and human IgG1 and IgG3 mediate ADCC more effectively than IgG2 and IgG4.
  • an antibody While binding of an antibody to the requisite antigen has a neutralizing effect that might prevent the binding of a foreign antigen to its endogenous target (e.g. receptor or ligand), binding alone may not remove the foreign antigen.
  • an antibody To be efficient in removing and/or destructing foreign antigens, an antibody should be endowed with both high affinity binding to its antigen, and efficient effector functions.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • CDC complement dependent cytotoxicity
  • Fc ⁇ RIIIB is found only on neutrophils
  • Fc ⁇ RIIIA is found on macrophages, monocytes, natural killer (NK) cells, and a subpopulation of T-cells.
  • Fc ⁇ RIIIA is the only FcR present on NK cells, one of the cell types implicated in ADCC.
  • Fc ⁇ RI, Fc ⁇ RII and Fc ⁇ RIII are immunoglobulin superfamily (IgSF) receptors; Fc ⁇ RI has three IgSF domains in its extracellular domain, while Fc ⁇ RII and Fc ⁇ RIII have only two IgSF domains in their extracellular domains.
  • IgSF immunoglobulin superfamily
  • FcRn neonatal Fc receptor
  • MHC major histocompatibility complex
  • G316-K338 human IgG for human Fc ⁇ RI (by sequence comparison only; no substitution mutants were evaluated) (Woof et al. Molec. Immunol. 23:319-330 (1986)); K274-R301 (human IgG1) for human Fc ⁇ RIII (based on peptides) (Sarmay et al. Molec. Immunol. 21:43-51 (1984)); Y407-R416 (human IgG) for human Fc ⁇ RIII (based on peptides) (Gergely et al. Biochem. Soc. Trans.
  • Pro331 in IgG3 was changed to Ser, and the affinity of this variant to target cells analyzed.
  • the affinity was found to be six-fold lower than that of unmutated IgG3, indicating the involvement of Pro331 in Fc ⁇ RI binding.
  • the residue Pro331 has been implicated in C1q binding by analysis of the ability of human IgG subclasses to carry out complement mediated cell lysis. Mutation of Ser331 to Pro331 in IgG4 conferred the ability to activate complement. (Tao et al., J. Exp. Med., 178:661-667 (1993); Brekke et al., Eur. J. Immunol., 24:2542-47 (1994)).
  • the polypeptide variant may display reduced binding to an Fc ⁇ RI and comprise an amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 327 or 329 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
  • the polypeptide variant may display reduced binding to an Fc ⁇ RII and comprise an amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 292, 294, 295, 298, 303, 324, 327, 329, 333, 335, 338, 373, 376, 414, 416, 419, 435, 438 or 439 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
  • the polypeptide variant of interest may display reduced binding to an Fc ⁇ RIII and comprise an amino acid modification at one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 293, 294, 295, 296, 301, 303, 322, 327, 329, 338, 340, 373, 376, 382, 388, 389, 416, 434, 435 or 437 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
  • the invention further provides a polypeptide comprising a variant Fc region with altered neonatal Fc receptor (FcRn) binding affinity, which polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 252, 253, 254, 255, 256, 265, 272, 286, 288, 303, 305, 307, 309, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 386, 388, 400, 413, 415, 424, 433, 434, 435, 436, 439 or 447 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
  • FcRn neonatal Fc receptor
  • polypeptide variants may, alternatively, display increased binding to FcRn and comprise an amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
  • the invention also provides a composition comprising the polypeptide variant and a physiologically or pharmaceutically acceptable carrier or diluent.
  • This composition for potential therapeutic use is sterile and may be lyophilized.
  • the invention provides a method for determining the presence of an antigen of interest comprising exposing a sample suspected of containing the antigen to the polypeptide variant and determining binding of the polypeptide variant to the sample.
  • the invention provides a method of treating a mammal suffering from or predisposed to a disease or disorder, comprising administering to the mammal a therapeutically effective amount of a polypeptide variant as disclosed herein, or of a composition comprising the polypeptide variant and a pharmaceutically acceptable carrier.
  • Step (b) of the method may comprise determining binding of the variant Fc region to one or more FcRs in vitro. Moreover, the method may result in the identification of a variant Fc region with improved FcR binding affinity, or with improved ADCC activity, in step (b) thereof.
  • the FcR may, for example, be human Fc gamma receptor III (Fc ⁇ RIII).
  • step (b) comprises determining binding of the variant Fc region to at least two different FcRs
  • the FcRs tested preferably include human Fc gamma receptor II (Fc ⁇ RII) and human Fc gamma receptor III (Fc ⁇ RIII).
  • FIG. 2 shows C1q binding of wild type (wt) C2B8 antibody; C2B8 antibody with a human IgG2 constant region (IgG2); and variants K322A, K320A and E318A.
  • FIG. 5 is a schematic diagram of the “immune complex” prepared for use in the FcR assay described in Example 1.
  • the hexamer comprising three anti-IgE antibody molecules (the “Fc region-containing polypeptide”) and three IgE molecules (the “first target molecule”) is shown.
  • IgE has two “binding sites” for the anti-IgE antibody (E27) in the Fc region thereof.
  • Each IgE molecule in the complex is further able to bind two VEGF molecules (“the second target polypeptide”).
  • VEGF has two “binding sites” for IgE.
  • FIG. 7 depicts complement dependent cytotoxicity (CDC) of variants D270K and D270V, compared to wild type C2B8.
  • FIG. 10 depicts the three-dimensional structure of a human lgG Fc region, highlighting residues: Asp270, Lys326, Pro329, Pro331, Lys322 and Glu333.
  • FIGS. 15A and 15B show binding patterns for parent antibody (E27) to Fc ⁇ RIIB and Fc ⁇ RIIIA.
  • FIG. 15A shows the binding pattern for the humanized anti-IgE E27 IgG1 as a monomer (open circles), hexamer (closed squares), and immune complex consisting of multiple hexamers (closed triangles) to a recombinant GST fusion protein of the human Fc ⁇ RIIB (CD32) receptor a subunit.
  • the hexameric complex (closed squares) was formed by the mixture of equal molar concentrations of E27 (which binds to the Fc region of human IgE) and a human myeloma IgE.
  • the hexamer is a stable 1.1 kD complex consisting of 3 IgG molecules (150 kD each) and 3 IgE molecules (200 kD each).
  • the immune complex (closed triangles) was formed sequentially by first mixing equal molar concentrations of E27 and recombinant anti-VEGF IgE (human IgE with Fab variable domains that bind human VEGF) to form the hexamer. Hexamers were then linked to form an immune complex by the addition of 2 ⁇ molar concentration of human VEGF, a 44 kD homodimer which has two binding sites for the anti-VEGF IgE per mole of VEGF.
  • FIG. 15B shows the binding pattern to a recombinant GST fusion protein of the human Fc ⁇ RIIIA (CD16) receptor a subunit.
  • FIG. 16A shows the binding of immune complexes using different antigen-antibody pairs to recombinant GST fusion protein of the Fc ⁇ RIIA receptor a subunit.
  • FIG. 16B shows the binding of the same antigen-antibody pairs to the GST fusion protein of the Fc ⁇ RIIIA receptor a subunit. Closed circles represent binding of human IgE:anti-IgE E27 IgG1; open circles represent binding of human VEGF:humanized anti-VEGF IgG1.
  • FIG. 17 summarizes differences in binding selectivity of some alanine variants between the different Fc ⁇ Rs. Binding of alanine variants at residues in the CH2 domain of anti-IgE E27 IgG1 are shown to Fc ⁇ RIIA, Fc ⁇ RIIB, and Fc ⁇ RIIIA. Type 1 abrogates binding to all three receptors: D278A (265 in EU numbering). Type 2 improves binding to Fc ⁇ RIIA and Fc ⁇ RIIB, while binding to Fc ⁇ RIIIA is unaffected: S280A (267 in EU numbering). Type 3 improves binding to Fc ⁇ RIIA and Fc ⁇ RIIB, but reduces binding to Fc ⁇ RIIIA: H281A (268 in EU numbering).
  • Type 4 reduces binding to Fc ⁇ RIIA and Fc ⁇ RIIB, while improving binding to Fc ⁇ RIIIA: S317A (298 in EU numbering).
  • Type 5 improves binding to Fc ⁇ RIIIA, but does not affect binding to Fc ⁇ RIIA and Fc ⁇ RIIB: E352A, K353A (333 and 334 in EU numbering).
  • FIGS. 18A and 18B compare the Fc ⁇ RIIIA protein/protein assay and CHO GPI-Fc ⁇ RIIIA cell based assay, respectively.
  • FIG. 18A illustrates binding of selected alanine variants to Fc ⁇ RIIIA-GST fusion protein. S317A (298 in EU numbering) and S317A/K353A (298 and 334 in EU numbering) bind better than E27 wildtype, while D278A (265 in EU numbering) almost completely abrogates binding.
  • FIG. 18B illustrates that a similar pattern of binding is found on CHO cells expressing a recombinant GPI-linked form of Fc ⁇ RIIIA.
  • FIGS. 19A and 19B compare the Fc ⁇ RIIB protein/protein assay and CHO GPI-Fc ⁇ RIIB cell based assay, respectively.
  • FIG. 19A illustrates binding of selected alanine variants to Fc ⁇ RIIB-GST fusion protein. H281A (268 in EU numbering) binds better than E27 wildtype while S317A (298 in EU numbering) shows reduced binding.
  • FIG. 19B illustrates that a similar pattern of binding is found on CHO cells expressing a recombinant membrane bound form of Fc ⁇ RIIB.
  • FIG. 20 shows single alanine substitutions in the CH2 domain of anti-HER2 IgG1 (HERCEPTIN®) that influence Fc ⁇ RIIIA binding in both the protein-protein and cell-based assays alter the ability to bind to Fc ⁇ RIIIA on peripheral blood mononuclear cell (PBMC) effector cells.
  • PBMC peripheral blood mononuclear cell
  • a single alanine mutation that only slightly increased binding to Fc ⁇ RIIIA, variant G30 K307A (290 in EU numbering), also showed slightly improved ADCC (i.e., a 1.1 fold improvement in ADCC activity, calculated as area under the curve) at 1.25 ng/ml at all E:T ratios (filled diamonds) compared to wildtype antibody at 1.25 ng/ml (filled square).
  • a single alanine mutation that decreased binding to Fc ⁇ RIIIA, variant G34 Q312A (295 in EU numbering), also showed decreased ADCC activity (filled inverted triangles).
  • G36 displayed a 1.7 fold improvement in ADCC activity, calculated as area under the curve.
  • the effector cells were PBMCs.
  • FIG. 22A depicts alignments of native sequence IgG Fc regions.
  • Native sequence human IgG Fc region sequences humIgG1 (non-A and A allotypes) (SEQ ID NOs: 3 and 4, respectively), humIgG2 (SEQ ID NO:5), humIgG3 (SEQ ID NO:6) and humIgG4 (SEQ ID NO:7), are shown.
  • the human IgG1 sequence is the non-A allotype, and differences between this sequence and the A allotype (at positions 356 and 358; EU numbering system) are shown below the human IgG1 sequence.
  • FIG. 22B shows percent identity among the Fc region sequences of FIG. 22A .
  • FIG. 23 depicts alignments of native sequence human IgG Fc region sequences, humIgG1 (non-A and A allotypes; SEQ ID NOs:3 and 4, respectively), humIgG2 (SEQ ID NO:5), humIgG3 (SEQ ID NO:6) and humIgG4 (SEQ ID NO:7) with differences between the sequences marked with asterisks.
  • FIG. 24 shows area under curve (AUC) for selected variants compared to anti-HER2 IgG1 (HERCEPTIN®) in a 4 hour ADCC assay.
  • Variant G36 (S317A; 298 in Eu numbering) with improved binding to Fc ⁇ RIIIA showed improved ADCC activity; variant G31 (R309A; 292 in Eu numbering) which did not display altered Fc ⁇ RIIIA binding, also had unaltered ADCC activity; and G14 (D265A; 278 in Eu numbering) which had reduced Fc ⁇ RIIIA binding, also had reduced ADCC activity.
  • the numbering of the residues in an immunoglobulin heavy chain is that of the EU index as in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991), expressly incorporated herein by reference.
  • the “EU index as in Kabar” refers to the residue numbering of the human IgG1 EU antibody.
  • a “parent polypeptide” is a polypeptide comprising an amino acid sequence which lacks one or more of the Fc region modifications disclosed herein and which differs in effector function compared to a polypeptide variant as herein disclosed.
  • the parent polypeptide may comprise a native sequence Fc region or an Fc region with pre-existing amino acid sequence modifications (such as additions, deletions and/or substitutions).
  • the term “Fc region” is used to define a C-terminal region of an immunoglobulin heavy chain, e.g., as shown in FIG. 1 .
  • the “Fc region” may be a native sequence Fc region or a variant Fc region.
  • the human IgG heavy chain Fc region is usually defined to stretch from an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof.
  • the Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3, as shown, for example, in FIG. 1 .
  • the “CH2 domain” of a human IgG Fc region usually extends from about amino acid 231 to about amino acid 340.
  • the CH2 domain is unique in that it is not closely paired with another domain. Rather, two N-linked branched carbohydrate chains are interposed between the two CH2 domains of an intact native IgG molecule. It has been speculated that the carbohydrate may provide a substitute for the domain-domain pairing and help stabilize the CH2 domain.
  • the “CH3 domain” comprises the stretch of residues C-terminal to a CH2 domain in an Fc region (i.e. from about amino acid residue 341 to about amino acid residue 447 of an IgG)
  • a “functional Fc region” possesses an “effector function” of a native sequence Fc region.
  • exemplary “effector functions” include C1q binding; complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g. B cell receptor; BCR), etc.
  • Such effector functions generally require the Fc region to be combined with a binding domain (e.g. an antibody variable domain) and can be assessed using various assays as herein disclosed, for example.
  • a “native sequence Fc region” comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature.
  • Native sequence human Fc regions are shown in FIG. 23 and include a native sequence human IgG1 Fc region (non-A and A allotypes); native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 Fc region as well as naturally occurring variants thereof.
  • Native sequence murine Fc regions are shown in FIG. 22A .
  • a “variant Fc region” comprises an amino acid sequence which differs from that of a native sequence Fc region by virtue of at least one “amino acid modification” as herein defined.
  • the variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, e.g. from about one to about ten amino acid substitutions, and preferably from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide.
  • the variant Fc region herein will preferably possess at least about 80% homology with a native sequence Fc region and/or with an Fc region of a parent polypeptide, and most preferably at least about 90% homology therewith, more preferably at least about 95% homology therewith.
  • “Homology” is defined as the percentage of residues in the amino acid sequence variant that are identical after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent homology. Methods and computer programs for the alignment are well known in the art. One such computer program is “Align 2”, authored by Genentech, Inc., which was filed with user documentation in the United States Copyright Office, Washington, D.C. 20559, on Dec. 10, 1991.
  • Fc region-containing polypeptide refers to a polypeptide, such as an antibody or immunoadhesin (see definitions below), which comprises an Fc region.
  • Fc receptor or “FcR” are used to describe a receptor that binds to the Fc region of an antibody.
  • the preferred FcR is a native sequence human FcR.
  • a preferred FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
  • Fc ⁇ RII receptors include Fc ⁇ RIIA (an “activating receptor”) and Fc ⁇ RIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
  • Activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain.
  • Inhibiting receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain.
  • ITAM immunoreceptor tyrosine-based activation motif
  • ITIM immunoreceptor tyrosine-based inhibition motif
  • FcR FcR
  • FcRn neonatal receptor
  • Antibody-dependent cell-mediated cytotoxicity and “ADCC” refer to a cell-mediated reaction in which nonspecific cytotoxic cells that express FcRs (e.g. Natural Killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on a target cell and subsequently cause lysis of the target cell.
  • FcRs e.g. Natural Killer (NK) cells, neutrophils, and macrophages
  • the primary cells for mediating ADCC NK cells, express Fc ⁇ RIII only, whereas monocytes express Fc ⁇ RI, Fc ⁇ RII and Fc ⁇ RIII.
  • FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991).
  • Human effector cells are leukocytes which express one or more FcRs and perform effector functions. Preferably, the cells express at least Fc ⁇ RIII and perform ADCC effector function. Examples of human leukocytes which mediate ADCC include peripheral blood mononuclear cells (PBMC), natural killer (NK) cells, monocytes, cytotoxic T cells and neutrophils; with PBMCs and NK cells being preferred.
  • PBMC peripheral blood mononuclear cells
  • NK natural killer cells
  • monocytes cytotoxic T cells and neutrophils
  • the effector cells may be isolated from a native source thereof, e.g. from blood or PBMCs as described herein.
  • a polypeptide variant with “altered” FcR binding affinity or ADCC activity is one which has either enhanced or diminished FcR binding activity and/or ADCC activity compared to a parent polypeptide or to a polypeptide comprising a native sequence Fc region.
  • the polypeptide variant which “displays increased binding” to an FcR binds at least one FcR with better affinity than the parent polypeptide.
  • the polypeptide variant which “displays decreased binding” to an FcR binds at least one FcR with worse affinity than a parent polypeptide.
  • Such variants which display decreased binding to an FcR may possess little or no appreciable binding to an FcR, e.g., 0-20% binding to the FcR compared to a native sequence IgG Fc region, e.g. as determined in the Examples herein.
  • the polypeptide variant which binds an FcR with “better affinity” than a parent polypeptide is one which binds any one or more of the above identified FcRs with substantially better binding affinity than the parent antibody, when the amounts of polypeptide variant and parent polypeptide in the binding assay are essentially the same.
  • the polypeptide variant with improved FcR binding affinity may display from about 1.15 fold to about 100 fold, e.g. from about 1.2 fold to about 50 fold improvement in FcR binding affinity compared to the parent polypeptide, where FcR binding affinity is determined, for example, as disclosed in the Examples herein.
  • the polypeptide variant which “mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human effector cells more effectively” than a parent antibody is one which in vitro or in vivo is substantially more effective at mediating ADCC, when the amounts of polypeptide variant and parent antibody used in the assay are essentially the same.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • Such variants will be identified using the in vitro ADCC assay as herein disclosed, but other assays or methods for determining ADCC activity, e.g. in an animal model etc, are contemplated.
  • the preferred variant is from about 1.5 fold to about 100 fold, e.g. from about two fold to about fifty fold, more effective at mediating ADCC than the parent, e.g. in the in vitro assay disclosed herein.
  • amino acid modification refers to a change in the amino acid sequence of a predetermined amino acid sequence.
  • exemplary modifications include an amino acid substitution, insertion and/or deletion.
  • the preferred amino acid modification herein is a substitution.
  • amino acid modification at a specified position, e.g. of the Fc region, refers to the substitution or deletion of the specified residue, or the insertion of at least one amino acid residue adjacent the specified residue.
  • insertion “adjacent” a specified residue is meant insertion within one to two residues thereof. The insertion may be N-terminal or C-terminal to the specified residue.
  • amino acid substitution refers to the replacement of at least one existing amino acid residue in a predetermined amino acid sequence with another different “replacement” amino acid residue.
  • the replacement residue or residues may be “naturally occurring amino acid residues” (i.e. encoded by the genetic code) and selected from the group consisting of: alanine (Ala); arginine (Arg); asparagine (Asn); aspartic acid (Asp); cysteine (Cys); glutamine (Gln); glutamic acid (Glu); glycine (Gly); histidine (His); isoleucine (lie): leucine (Leu); lysine (Lys); methionine (Met); phenylalanine (Phe); proline (Pro); serine (Ser); threonine (Thr); tryptophan (Trp); tyrosine (Tyr); and valine (Val).
  • the replacement residue is not cysteine.
  • substitution with one or more non-naturally occurring amino acid residues is also encompassed by the definition of an amino acid substitution herein.
  • a “non-naturally occurring amino acid residue” refers to a residue, other than those naturally occurring amino acid residues listed above, which is able to covalently bind adjacent amino acid residues(s) in a polypeptide chain. Examples of non-naturally occurring amino acid residues include norleucine, ornithine, norvaline, homoserine and other amino acid residue analogues such as those described in Ellman et al. Meth. Enzym. 202:301-336 (1991). To generate such non-naturally occurring amino acid residues, the procedures of Noren et al.
  • amino acid insertion refers to the incorporation of at least one amino acid into a predetermined amino acid sequence. While the insertion will usually consist of the insertion of one or two amino acid residues, the present application contemplates larger “peptide insertions”, e.g. insertion of about three to about five or even up to about ten amino acid residues.
  • the inserted residue(s) may be naturally occurring or non-naturally occurring as disclosed above.
  • amino acid deletion refers to the removal of at least one amino acid residue from a predetermined amino acid sequence.
  • Hinge region is generally defined as stretching from Glu216 to Pro230 of human IgG1 (Burton, Molec. Immunol. 22:161-206 (1985)). Hinge regions of other IgG isotypes may be aligned with the IgG1 sequence by placing the first and last cysteine residues forming inter-heavy chain S—S bonds in the same positions.
  • the “lower hinge region” of an Fc region is normally defined as the stretch of residues immediately C-terminal to the hinge region, i.e. residues 233 to 239 of the Fc region. Prior to the present invention, Fc ⁇ R binding was generally attributed to amino acid residues in the lower hinge region of an IgG Fc region.
  • C1q is a polypeptide that includes a binding site for the Fc region of an immunoglobulin. C1q together with two serine proteases, C1r and C1s, forms the complex C1, the first component of the complement dependent cytotoxicity (CDC) pathway. Human C1q can be purchased commercially from, e.g. Quidel, San Diego, Calif.
  • binding domain refers to the region of a polypeptide that binds to another molecule.
  • the binding domain can comprise a portion of a polypeptide chain thereof (e.g. the a chain thereof) which is responsible for binding an Fc region.
  • One useful binding domain is the extracellular domain of an FcR a chain.
  • antibody is used in the broadest sense and specifically covers monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired biological activity.
  • Antibody fragments comprise a portion of an intact antibody, generally including the antigen binding or variable region of the intact antibody or the Fc region of an antibody which retains FcR binding capability.
  • antibody fragments include linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.
  • the antibody fragments preferably retain at least part of the hinge and optionally the CH1 region of an IgG heavy chain. More preferably, the antibody fragments retain the entire constant region of an IgG heavy chain, and include an IgG light chain.
  • the term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen.
  • the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
  • the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567).
  • the “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature 352:624-628 (1991) and Marks et al., J. Mol. Biol. 222:581-597 (1991), for example.
  • the monoclonal antibodies herein specifically include “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984)).
  • chimeric antibodies immunoglobulins in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences
  • “Humanized” forms of non-human (e.g., murine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin.
  • humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity.
  • donor antibody such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity.
  • Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues.
  • humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance.
  • the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence.
  • the humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
  • Fc immunoglobulin constant region
  • hypervariable region when used herein refers to the amino acid residues of an antibody which are responsible for antigen-binding.
  • the hypervariable region comprises amino acid residues from a “complementarity determining region” or “CDR” (i.e. residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the light chain variable domain and 31-35 (H1), 50-65 (H2) and 95-102 (H3) in the heavy chain variable domain; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)) and/or those residues from a “hypervariable loop” (i.e.
  • “Framework” or “FR” residues are those variable domain residues other than the hypervariable region residues as herein defined.
  • immunoadhesin designates antibody-like molecules which combine the “binding domain” of a heterologous “adhesin” protein (e.g. a receptor, ligand or enzyme) with an immunoglobulin constant domain.
  • adhesin protein e.g. a receptor, ligand or enzyme
  • the immunoadhesins comprise a fusion of the adhesin amino acid sequence with the desired binding specificity which is other than the antigen recognition and binding site (antigen combining site) of an antibody (i.e. is “heterologous”) and an immunoglobulin constant domain sequence.
  • ligand binding domain refers to any native cell-surface receptor or any region or derivative thereof retaining at least a qualitative ligand binding ability of a corresponding native receptor.
  • the receptor is from a cell-surface polypeptide having an extracellular domain that is homologous to a member of the immunoglobulin supergenefamily.
  • Other receptors which are not members of the immunoglobulin supergenefamily but are nonetheless specifically covered by this definition, are receptors for cytokines, and in particular receptors with tyrosine kinase activity (receptor tyrosine kinases), members of the hematopoietin and nerve growth factor receptor superfamilies, and cell adhesion molecules, e.g. (E-, L- and P-) selectins.
  • receptor binding domain is used to designate any native ligand for a receptor, including cell adhesion molecules, or any region or derivative of such native ligand retaining at least a qualitative receptor binding ability of a corresponding native ligand. This definition, among others, specifically includes binding sequences from ligands for the above-mentioned receptors.
  • an “antibody-immunoadhesin chimera” comprises a molecule that combines at least one binding domain of an antibody (as herein defined) with at least one immunoadhesin (as defined in this application).
  • Exemplary antibody-immunoadhesin chimeras are the bispecific CD4-lgG chimeras described in Berg et al., PNAS ( USA ) 88:4723-4727 (1991) and Chamow et al., J. Immunol. 153:4268 (1994).
  • an “isolated” polypeptide is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes.
  • the polypeptide will be purified (1) to greater than 95% by weight of polypeptide as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain.
  • Isolated polypeptide includes the polypeptide in situ within recombinant cells since at least one component of the polypeptide's natural environment will not be present. Ordinarily, however, isolated polypeptide will be prepared by at least one purification step.
  • Treatment refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disorder as well as those in which the disorder is to be prevented.
  • a “disorder” is any condition that would benefit from treatment with the polypeptide variant. This includes chronic and acute disorders or diseases including those pathological conditions which predispose the mammal to the disorder in question.
  • the disorder is cancer.
  • cancer and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth.
  • Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia.
  • cancers include squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.
  • a “HER2-expressing cancer” is one comprising cells which have HER2 receptor protein (Semba et al., PNAS ( USA ) 82:6497-6501 (1985) and Yamamoto et al. Nature 319:230-234 (1986) (Genebank accession number X03363)) present at their cell surface, such that an anti-HER2 antibody is able to bind to the cancer.
  • label when used herein refers to a detectable compound or composition which is conjugated directly or indirectly to the polypeptide.
  • the label may be itself be detectable (e.g., radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition which is detectable.
  • an “isolated” nucleic acid molecule is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the natural source of the polypeptide nucleic acid.
  • An isolated nucleic acid molecule is other than in the form or setting in which it is found in nature. Isolated nucleic acid molecules therefore are distinguished from the nucleic acid molecule as it exists in natural cells.
  • an isolated nucleic acid molecule includes a nucleic acid molecule contained in cells that ordinarily express the polypeptide where, for example, the nucleic acid molecule is in a chromosomal location different from that of natural cells.
  • control sequences refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism.
  • the control sequences that are suitable for prokaryotes include a promoter, optionally an operator sequence, and a ribosome binding site.
  • Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
  • Nucleic acid is “operably linked” when it is placed into a functional relationship with another nucleic acid sequence.
  • DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide;
  • a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or
  • a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation.
  • “operably linked” means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.
  • the expressions “cell,” “cell line,” and “cell culture” are used interchangeably and all such designations include progeny.
  • the words “transformants” and “transformed cells” include.the primary subject cell and cultures derived therefrom without regard for the number of transfers. It is also understood that all progeny may not be precisely identical in DNA content, due to deliberate or inadvertent mutations. Mutant progeny that have the same function or biological activity as screened for in the originally transformed cell are included. Where distinct designations are intended, it will be clear from the context.
  • molecular complex when used herein refers to the relatively stable structure which forms when two or more heterologous molecules (e.g. polypeptides) bind (preferably noncovalently) to one another.
  • heterologous molecules e.g. polypeptides
  • the preferred molecular complex herein is an immune complex.
  • Immuno complex refers to the relatively stable structure which forms when at least one target molecule and at least one heterologous Fc region-containing polypeptide bind to one another forming a larger molecular weight complex.
  • immune complexes are antigen-antibody aggregates and target molecule-immunoadhesin aggregates.
  • target molecule refers to a molecule, usually a polypeptide, which is capable of being bound by a heterologous molecule and has one or more binding sites for the heterologous molecule.
  • binding site refers to a region of a molecule to which another molecule can bind.
  • the “first target molecule” herein comprises at least two distinct binding sites (for example, two to five separate binding sites) for an analyte (e.g. an Fc region-containing polypeptide) such that at least two analyte molecules can bind to the first target molecule.
  • the two or more binding sites are identical (e.g. having the same amino acid sequence, where the target molecule is a polypeptide).
  • the first target molecule was IgE and had two separate binding sites in the Fc region thereof to which the Fc region-containing polypeptide (an anti-IgE antibody, E27) could bind.
  • Other first target molecules include dimers of substantially identical monomors (e.g. neurotrophins, IL8 and VEGF) or are polypeptides comprising two or more substantially identical polypeptide chains (e.g. antibodies or immunoadhesins).
  • the “second target molecule” comprises at least two distinct binding sites (for example, two to five separate binding sites) for the first target molecule such that at least two first target molecules can bind to the second target molecule.
  • the two or more binding sites are identical (e.g.
  • the second target molecule was VEGF, which has a pair of distinct binding sites to which the variable domain of the IgE antibody could bind.
  • Other second target molecules are contemplated, e.g. other dimers of substantially identical monomers (e.g. neurotrophins or IL8) or poiypeptides comprising two or more substantially identical domains (e.g. antibodies or immunoadhesins).
  • an “analyte” is a substance that is to be analyzed.
  • the preferred analyte is an Fc region-containing polypeptide that is to be analyzed for its ability to bind to an Fc receptor.
  • a “receptor” is a polypeptide capable of binding at least one ligand.
  • the preferred receptor is a cell-surface receptor having an extracellular ligand-binding domain and, optionally, other domains (e.g. transmembrane domain, intracellular domain and/or membrane anchor).
  • the receptor to be evaluated in the assay described herein may be an intact receptor or a fragment or derivative thereof (e.g. a fusion protein comprising the binding domain of the receptor fused to one or more heterologous polypeptides).
  • the receptor to be evaluated for its binding properties may be present in a cell or isolated and optionally coated on an assay plate or some other solid phase.
  • low affinity receptor denotes a receptor that has a weak binding affinity for a ligand of interest, e.g. having a binding constant of about 50 nM or worse affinity.
  • exemplary low affinity receptors include Fc ⁇ RII and Fc ⁇ RIII.
  • the invention herein relates to a method for making a polypeptide variant.
  • the “parent”, “starting” or “nonvariant” polypeptide is prepared using techniques available in the art for generating polypeptides comprising an Fc region.
  • the parent polypeptide is an antibody and exemplary methods for generating antibodies are described in more detail in the following sections.
  • the parent polypeptide may, however, be any other polypeptide comprising an Fc region, e.g. an immunoadhesin. Methods for making immunoadhesins are elaborated in more detail hereinbelow.
  • a variant Fc region may be generated according to the methods herein disclosed and this “variant Fc region” can be fused to a heterologous polypeptide of choice, such as an antibody variable domain or binding domain of a receptor or ligand.
  • the parent polypeptide comprises an Fc region.
  • the Fc region of the parent polypeptide will comprise a native sequence Fc region, and preferably a human native sequence Fc region.
  • the Fc region of the parent polypeptide may have one or more pre-existing amino acid sequence alterations or modifications from a native sequence Fc region.
  • the C1q binding activity of the Fc region may have been previously altered (other types of Fc region modifications are described in more detail below).
  • the parent polypeptide Fc region is “conceptual” and, while it does not physically exist, the antibody engineer may decide upon a desired variant Fc region amino acid sequence and generate a polypeptide comprising that sequence or a DNA encoding the desired variant Fc region amino acid sequence.
  • nucleic acid encoding an Fc region of a parent polypeptide is available and this nucleic acid sequence is altered to generate a variant nucleic acid sequence encoding the Fc region variant.
  • DNA encoding an amino acid sequence variant of the starting polypeptide is prepared by a variety of methods known in the art. These methods include, but are not limited to, preparation by site-directed (or oligonucleotide-mediated) mutagenesis, PCR mutagenesis, and cassette mutagenesis of an earlier prepared DNA encoding the polypeptide
  • Site-directed mutagenesis is a preferred method for preparing substitution variants. This technique is well known in the art (see, e.g., Carter et al. Nucleic Acids Res. 13:4431-4443 (1985) and Kunkel et al., Proc. Natl. Acad.Sci. USA 82:488 (1985)). Briefly, in carrying out site-directed mutagenesis of DNA, the starting DNA is altered by first hybridizing an oligonucleotide encoding the desired mutation to a single strand of such starting DNA.
  • a DNA polymerase is used to synthesize an entire second strand, using the hybridized oligonucleotide as a primer, and using the single strand of the starting DNA as a template.
  • the oligonucleotide encoding the desired mutation is incorporated in the resulting double-stranded DNA.
  • PCR mutagenesis is also suitable for making amino acid sequence variants of the starting polypeptide. See Higuchi, in PCR Protocols, pp.177-183 (Academic Press, 1990); and Vallette et al., Nuc. Acids Res. 17:723-733 (1989). Briefly, when small amounts of template DNA are used as starting material in a PCR, primers that differ slightly in sequence from the corresponding region in a template DNA can be used to generate relatively large quantities of a specific DNA fragment that differs from the template sequence only at the positions where the primers differ from the template.
  • the starting material is the plasmid (or other vector) comprising the starting polypeptide DNA to be mutated.
  • the codon(s) in the starting DNA to be mutated are identified. There must be a unique restriction endonuclease site on each side of the identified mutation site(s). If no such restriction sites exist, they may be generated using the above-described oligonucleotide-mediated mutagenesis method to introduce them at appropriate locations in the starting polypeptide DNA.
  • the plasmid DNA is cut at these sites to linearize it.
  • a double-stranded oligonucleotide encoding the sequence of the DNA between the restriction sites but containing the desired mutation(s) is synthesized using standard procedures, wherein the two strands of the oligonucleotide are synthesized separately and then hybridized together using standard techniques.
  • This double-stranded oligonucleotide is referred to as the cassette.
  • This cassette is designed to have 5′ and 3′ ends that are compatible with the ends of the linearized plasmid, such that it can be directly ligated to the plasmid.
  • This plasmid now contains the mutated DNA sequence.
  • the desired amino acid sequence encoding a polypeptide variant can be determined, and a nucleic acid sequence encoding such amino acid sequence variant can be generated synthetically.
  • the amino acid sequence of the parent polypeptide is modified in order to generate a variant Fc region with altered Fc receptor binding affinity or activity in vitro and/or in vivo and/or altered antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro and/or in vivo.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • the modification entails one or more amino acid substitutions.
  • the replacement residue does not correspond to a residue present in the same position in any of the native sequence Fc regions in FIG. 22A .
  • Pro331 of a human IgG3 or IgG1 Fc region is replaced with a residue other than Ser (the corresponding aligned residue found in native sequence human IgG4).
  • the residue in the parent polypeptide which is substituted with a replacement residue is not an alanine and/or is not residue Ala339 of an Fc region.
  • an amino acid substitution preferably the residue in the parent polypeptide is replaced with an alanine residue.
  • the present invention contemplates replacement of the residue of the parent polypeptide with any other amino acid residue.
  • the substitution may, for example, be a “conservative substitution”. Such conservative substitutions are shown in Table 1 under the heading of “preferred substitution”. More substantial changes may be achieved by making one or more “exemplary substitutions” which are not the preferred substitution in Table 1.
  • Substantial modifications in the biological properties of the Fc region may be accomplished by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain.
  • Naturally occurring residues are divided into groups based on common side-chain properties:
  • hydrophobic norleucine, met, ala, val, leu, ile
  • Non-conservative substitutions will entail exchanging a member of one of these classes for a member of another class.
  • Conservative and non-conservative amino acid substitutions are exemplified in Table 8 hereinbelow.
  • Example 4 one can engineer an Fc region variant with altered binding affinity for one or more FcRs.
  • different classes of Fc region variants can be made e.g,. as summarized in the following table. Where the variant Fc region has more than one amino acid substitution, generally, but not necessarily, amino acid substitutions in the same class are combined to achieve the desired result.
  • the present invention contemplates other modifications of the parent Fc region amino acid sequence in order to generate an Fc region variant with altered effector function.
  • one will delete one or more of the Fc region residues identified herein as effecting FcR binding (see Example 4 below) in order to generate such an Fc region variant.
  • no more than one to about ten Fc region residues will be deleted according to this embodiment of the invention.
  • the Fc region herein comprising one or more amino acid deletions will preferably retain at least about 80%, and preferably at least about 90%, and most preferably at least about 95%, of the parent Fc region or of a native sequence human Fc region.
  • variant Fc region which (a) mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human effector cells more effectively and/or (b) binds an Fc gamma receptor (Fc ⁇ R) with better affinity than the parent polypeptide.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • Fc ⁇ R Fc gamma receptor
  • Such Fc region variants will generally comprise at least one amino acid modification in the Fc region. Combining amino acid modifications is thought to be particularly desirable.
  • the variant Fc region may include two, three, four, five, etc substitutions therein, e.g. of the specific Fc region positions identified herein.
  • the parent polypeptide Fc region is a human Fc region, e.g. a native sequence human Fc region human IgG1 (A and non-A allotypes), IgG2, IgG3 or IgG4 Fc region. Such sequences are shown in FIG. 23 .
  • the parent polypeptide preferably has pre-existing ADCC activity, e.g., it comprises a human IgG1 or human IgG3 Fc region.
  • the variant with improved ADCC mediates ADCC substantially more effectively than an antibody with a native sequence IgG1 or IgG3 Fc region and the antigen-binding region of the variant.
  • the variant comprises, or consists essentially of, substitutions of two or three of the residues at positions 298, 333 and 334 of the Fc region. Most preferably, residues at positions 298, 333 and 334 are substituted, (e.g. with alanine residues).
  • an Fc region variant with improved binding affinity for Fc ⁇ RIII which is thought to be an important FcR for mediating ADCC.
  • Fc ⁇ RIII an amino acid modification (e.g. a substitution) into the parent Fc region at any one or more of amino acid positions 256, 290, 298, 312, 326, 330, 333, 334, 360, 378 or 430 to generate such a variant.
  • the variant with improved binding affinity for Fc ⁇ RIII may further have reduced binding affinity for Fc ⁇ RII, especially reduced affinity for the inhibiting Fc ⁇ RIIB receptor.
  • the amino acid modification(s) are preferably introduced into the CH2 domain of a Fc region, since the experiments herein indicate that the CH2 domain is important for FcR binding activity. Moreover, unlike the teachings of the above-cited art, the instant application contemplates the introduction of a modification into a part of the Fc region other than in the lower hinge region thereof.
  • Useful amino acid positions for modification in order to generate a variant IgG Fc region with altered Fc gamma receptor (Fc ⁇ R) binding affinity or activity include any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301, 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, 388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439 of the Fc region.
  • Fc ⁇ R Fc gamma receptor
  • the parent Fc region used as the-template to generate such variants comprises a human IgG Fc region.
  • the parent Fc region is preferably not human native sequence IgG3, or the variant Fc region comprising a substitution at position 331 preferably displays increased FcR binding, e.g. to Fc ⁇ RII.
  • Variants which display reduced binding to Fc ⁇ RI include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 327 or 329.
  • Variants which display reduced binding to Fc ⁇ RII include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 292, 294, 295, 298, 303, 324, 327, 329, 333, 335, 338, 373, 376, 414, 416, 419, 435, 438 or 439.
  • Fc region variants which display reduced binding to Fc ⁇ RIII include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 293, 294, 295, 296, 301, 303, 322, 327, 329, 338, 340, 373, 376, 382, 388, 389, 416, 434, 435 or 437.
  • Fc region variants may comprise an amino acid modification at any one or more of amino acid positions 255, 256, 258, 267, 268, 272, 276, 280, 283, 285, 286, 290, 298, 301, 305, 307, 309, 312, 315, 320, 322, 326, 330, 331, 333, 334, 337, 340, 360, 378, 398 or 430 of the Fc region.
  • the variant with improved Fc ⁇ R binding activity may display increased binding to Fc ⁇ RIII, and optionally may further display decreased binding to Fc ⁇ RII; e.g. the variant may comprise an amino acid modification at position 298 and/or 333 of an Fc region.
  • Variants with increased binding to Fc ⁇ RII include those comprising an amino acid modification at any one or more of amino acid positions 255, 256, 258, 267, 268, 272, 276, 280, 283, 285, 286, 290, 301, 305, 307, 309, 312, 315, 320, 322, 326, 330, 331, 337, 340, 378, 398 or 430 of an Fc region.
  • Such variants may further display decreased binding to Fc ⁇ RIII.
  • they may include an Fc region amino acid modification at any one or more of amino acid positions 268, 272, 298, 301, 322 or 340.
  • Fc region variants with altered binding affinity for the neonatal receptor are also contemplated herein.
  • Fc region variants with improved affinity for FcRn are anticipated to have longer serum half-lives, and such molecules will have useful applications in methods of treating mammals where long half-life of the administered polypeptide is desired, e.g., to treat a chronic disease or disorder.
  • Fc region variants with decreased FcRn binding affinity are expected to have shorter half-lives, and such molecules may, for example, be administered to a mammal where a shortened circulation time may be advantageous, e.g.
  • Fc region variants with decreased FcRn binding affinity are anticipated to be less likely to cross the placenta, and thus may be utilized in the treatment of diseases or disorders in pregnant women.
  • Fc region variants with altered binding affinity for FcRn include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 252, 253, 254, 255, 256, 265, 272, 286, 288, 303, 305, 307, 309, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 386, 388, 400, 413, 415, 424, 433, 434, 435, 436, 439 or 447.
  • Those which display reduced binding to FcRn will generally comprise an Fc region amino acid modification at any one or more of amino acid positions 252, 253, 254, 255, 288, 309, 386, 388, 400, 415, 433, 435, 436, 439 or 447; and those with increased binding to FcRn will usually comprise an Fc region amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434.
  • polypeptide variant(s) prepared as described above may be subjected to further modifications, oftentimes depending on the intended use of the polypeptide. Such modifications may involve further alteration of the amino acid sequence (substitution, insertion and/or deletion of amino acid residues), fusion to heterologous polypeptide(s) and/or covalent modifications. Such “further modifications” may be made prior to, simultaneously with, or following, the amino acid modification(s) disclosed above which result in an alteration of Fc receptor binding and/or ADCC activity. In one embodiment, one may combine the Fc region modification herein with Fc region substitutions disclosed in the references cited in the “Related Art” section of this application.
  • the starting polypeptide of particular interest herein is usually one that binds to C1q and displays complement dependent cytotoxicity (CDC).
  • CDC complement dependent cytotoxicity
  • the further amino acid substitutions described herein will generally serve to alter the ability of the starting polypeptide to bind to C1q and/or modify its complement dependent cytotoxicity function, e.g. to reduce and preferably abolish these effector functions.
  • polypeptides comprising substitutions at one or more of the described positions with improved C1q binding and/or complement dependent cytotoxicity (CDC) function are contemplated herein.
  • the starting polypeptide may be unable to bind C1q and/or mediate CDC and may be modified according to the teachings herein such that it acquires these further effector functions.
  • polypeptides with pre-existing C1q binding activity, optionally further having the ability to mediate CDC may be modified such that one or both of these activities are enhanced.
  • the amino acid positions to be modified are generally selected from heavy chain positions 270, 322, 326, 327, 329, 331, 333, and 334, where the numbering of the residues in an IgG heavy chain is that of the EU index as in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991). In one embodiment, only one of the eight above-identified positions is altered in order to generate the polypeptide variant region with altered C1q binding and/or complement dependent cytotoxicity (CDC) function.
  • residue 270, 329 or 322 is altered if this is the case.
  • two or more of the above-identified positions are modified. If substitutions are to be combined, generally substitutions which enhance human C1q binding (e.g. at residue positions 326, 327, 333 and 334) or those which diminish human C1q binding (e.g., at residue positions 270, 322, 329 and 331) are combined. In the latter embodiment, all four positions (i.e., 270, 322, 329 and 331) may be substituted.
  • Proline is conserved at position 329 in human IgG's. This residue is preferably replaced with alanine, however substitution with any other amino acid is contemplated, e.g., serine, threonine, asparagine, glycine or valine.
  • Proline is conserved at position 331 in human IgG1, IgG2 and IgG3, but not IgG4 (which has a serine residue at position 331).
  • Residue 331 is preferably replaced by alanine or another amino acid, e.g. serine (for IgG regions other than IgG4), glycine or valine.
  • Lysine 322 is conserved in human IgGs, and this residue is preferably replaced by an alanine residue, but substitution with any other amino acid residue is contemplated, e.g. serine, threonine, glycine or valine.
  • D270 is conserved in human IgGs, and this residue may be replaced by another amino acid residue, e.g. alanine, serine, threonine, glycine, valine, or lysine.
  • K326 is also conserved in human IgGs. This residue may be substituted with another residue including, but not limited to, valine, glutamic acid, alanine, glycine, aspartic acid, methionine or tryptophan, with tryptophan being preferred.
  • E333 is also conserved in human IgGs.
  • E333 is preferably replaced by an amino acid residue with a smaller side chain volume, such as valine, glycine, alanine or serine, with serine being preferred.
  • K334 is conserved in human IgGs and may be substituted with another residue such as alanine or other residue.
  • residue 327 is an alanine. In order to generate a variant with improved C1q binding, this alanine may be substituted with another residue such as glycine. In IgG2 and IgG4, residue 327 is a glycine and this may be replaced by alanine (or another residue) to diminish C1q binding.
  • one can design an Fc region with altered effector function e.g., by modifying C1q binding and/or FcR binding and thereby changing CDC activity and/or ADCC activity.
  • one may increase only one of these activities, and optionally also reduce the other activity, e.g. to generate an Fc region variant with improved ADCC activity, but reduced CDC activity and vice versa.
  • any cysteine residue not involved in maintaining the proper conformation of the polypeptide variant also may be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant cross linking.
  • Another type of amino acid substitution serves to alter the glycosylation pattern of the polypeptide. This may be achieved by deleting one or more carbohydrate moieties found in the polypeptide, and/or adding one or more glycosylation sites that are not present in the polypeptide.
  • Glycosylation of polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue.
  • the tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain.
  • O-linked glycosylation refers to the attachment of one of the sugars N-aceylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.
  • Addition of glycosylation sites to the polypeptide is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites).
  • the alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the sequence of the original polypeptide (for O-linked glycosylation sites).
  • An exemplary glycosylation variant has an amino acid substitution of residue Asn 297 of the heavy chain.
  • the class, subclass or allotype of the Fc region may be altered by one or more further amino acid substitutions to generate an Fc region with an amino acid sequence more homologous to a different class, subclass or allotype as desired.
  • a murine Fc region may be altered to generate an amino acid sequence more homologous to a human Fc region; a human non-A allotype IgG1 Fc region may be modified to achieve a human A allotype IgG1 Fc region etc.
  • the amino modification(s) herein which alter FcR binding and/or ADCC activity are made in the CH2 domain of the Fc region and the CH3 domain is deleted or replaced with another dimerization domain. Preferably, however, the CH3 domain is retained (aside from amino acid modifications therein which alter effector function as herein disclosed).
  • the polypeptide variant may be subjected to one or more assays to evaluate any change in biological activity compared to the starting polypeptide.
  • the polypeptide variant essentially retains the ability to bind antigen compared to the nonvariant polypeptide, i.e. the binding capability is no worse than about 20 fold, e.g. no worse than about 5 fold of that of the nonvariant polypeptide.
  • the binding capability of the polypeptide variant may be determined using techniques such as fluorescence activated cell sorting (FACS) analysis or radioimmunoprecipitation (RIA), for example.
  • the ability of the polypeptide variant to bind an FcR may be evaluated.
  • the FcR is a high affinity Fc receptor, such as Fc ⁇ RI, FcRn or Fc ⁇ RIIIA-V158
  • binding can be measured by titrating monomeric polypeptide variant and measuring bound polypeptide variant using an antibody which specifically binds to the polypeptide variant in a standard ELISA format (see Example 2 below).
  • Another FcR binding assay for low affinity FcRs is described in Examples 1 and 4.
  • ADCC activity of the polypeptide variant may be assessed in vivo, e.g., in a animal model such as that disclosed in Clynes et al. PNAS ( USA ) 95:652-656 (1998).
  • the ability of the variant to bind C1q and mediate complement dependent cytotoxicity (CDC) may be assessed.
  • a C1q binding ELISA may be performed. Briefly, assay plates may be coated overnight at 4° C. with polypeptide variant or starting polypeptide (control) in coating buffer. The plates may then be washed and blocked. Following washing, an aliquot of human C1q may be added to each well and incubated for 2 hrs at room temperature. Following a further wash, 100 ⁇ l of a sheep anti-complement C1q peroxidase conjugated antibody may be added to each well and incubated for 1 hour at room temperature. The plate may again be washed with wash buffer and 100 ⁇ l of substrate buffer containing OPD (0-phenylenediamine dihydrochloride (Sigma)) may be added to each well. The oxidation reaction, observed by the appearance of a yellow color, may be allowed to proceed for 30 minutes and stopped by the addition of 100 ⁇ l of 4.5 N H 2 SO 4 . The absorbance may then read at (492-405) nm.
  • An exemplary polypeptide variant is one that displays a “significant reduction in C1q binding” in this assay. This means that about 100 ⁇ g/ml of the polypeptide variant displays about 50 fold or more reduction in C1q binding compared to 100 ⁇ g/ml of a control antibody having a nonmutated IgG1 Fc region. In the most preferred embodiment, the polypeptide variant “does not bind C1q”, i.e. 100 ⁇ g/ml of the polypeptide variant displays about 100 fold or more reduction in C1q binding compared to 1001 ⁇ g/ml of the control antibody.
  • Another exemplary variant is one which “has a better binding affinity for human C1q than the parent polypeptide”.
  • a molecule may display, for example, about two-fold or more, and preferably about five-fold or more, improvement in human C1q binding compared to the parent polypeptide (e.g. at the IC 50 values for these two molecules).
  • human C1q binding may be about two-fold to about 500-fold, and preferably from about two-fold or from about five-fold to about 1000-fold improved compared to the parent polypeptide.
  • a complement dependent cytotoxicity (CDC) assay may be performed, e.g. as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1997). Briefly, various concentrations of the polypeptide variant and human complement may be diluted with buffer. Cells which express the antigen to which the polypeptide variant binds may be diluted to a density of ⁇ 1 ⁇ 10 6 cells/ml. Mixtures of polypeptide variant, diluted human complement and cells expressing the antigen may be added to a flat bottom tissue culture 96 well plate and allowed to incubate for 2 hrs at 37° C. and 5% CO 2 to facilitate complement mediated cell lysis.
  • CDC complement dependent cytotoxicity
  • alamar blue (Accumed International) may then be added to each well and incubated overnight at 37° C.
  • the absorbance is measured using a 96-well fluorometer with excitation at 530 nm and emission at 590 nm.
  • the results may be expressed in relative fluorescence units (RFU).
  • the sample concentrations may be computed from a standard curve and the percent activity as compared to nonvariant polypeptide is reported for the polypeptide variant of interest.
  • Yet another exemplary variant “does not activate complement”.
  • 0.6 ⁇ g/ml of the polypeptide variant displays about 0-10% CDC activity in this assay compared to a 0.6 ⁇ g/ml of a control antibody having a nonmutated IgG1 Fc region.
  • the variant does not appear to have any CDC activity in the above CDC assay.
  • the invention also pertains to a polypeptide variant with enhanced CDC compared to a parent polypeptide, e.g., displaying about two-fold to about 100-fold improvement in CDC activity in vitro or in vivo (e.g. at the IC50 values for each molecule being compared).
  • a receptor binding assay has been developed herein which is particularly useful for determining binding of an analyte of interest to a receptor where the affinity of the analyte for the receptor is relatively weak, e.g. in the micromolar range as is the case for Fc ⁇ RIIA, Fc ⁇ RIIB, Fc ⁇ RIIIA and Fc ⁇ RIIIB.
  • the method involves the formation of a molecular complex that has an improved avidity for the receptor of interest compared to the noncomplexed analyte.
  • the preferred molecular complex is an immune complex comprising: (a) an Fc region-containing polypeptide (such as an antibody or an immunoadhesin); (b) a first target molecule which comprises at least two binding sites for the Fc region-containing polypeptide; and (c) a second target molecule which comprises at least two binding sites for the first target molecule.
  • an Fc region-containing polypeptide such as an antibody or an immunoadhesin
  • a first target molecule which comprises at least two binding sites for the Fc region-containing polypeptide
  • a second target molecule which comprises at least two binding sites for the first target molecule.
  • the Fc region-containing polypeptide is an anti-IgE antibody, such as the E27 antibody ( FIGS. 4A-4B ).
  • E27 when mixed with human IgE at an 1:1 molar ratio, forms a stable hexamer consisting of three E27 molecules and three IgE molecules.
  • the “first target molecule” is a chimeric form of IgE in which the Fab portion of an anti-VEGF antibody is fused to the human IgE Fc portion and the “second target molecule” is the antigen to which the Fab binds (i.e. VEGF).
  • VEGF antigen to which the Fab binds
  • VEGF also binds two molecules of IgE per molecule of VEGF.
  • recombinant human VEGF was added at a 2:1 molar ratio to IgE:E27 hexamers, the hexamers were linked into larger molecular weight complexes via the IgE:VEGF interaction ( FIG. 5 ).
  • the Fc region of the anti-IgE antibody of the resultant immune complex binds to FcR with higher avidity than either uncomplexed anti-IgE or anti-IgE:IgE hexamers.
  • Examples comprising only an Fc region-containing polypeptide:first target molecule combination include an immunoadhesin:ligand combination such as VEGF receptor (KDR)-immunoadhesin:VEGF and a full-length bispecific antibody (bsAb):first target molecule.
  • an Fc region-containing polypeptide:first target molecule:second target molecule combination include a nonblocking antibody:soluble receptor:ligand combination such as anti-Trk antibody:soluble Trk receptor:neurotrophin (Urfer et al. J. Biol. Chem. 273(10):5829-5840 (1998)).
  • the immune complexes described above have further uses including evaluation of Fc region-containing polypeptide function and immune complex clearance in vivo.
  • the immune complex may be administered to a mammal (e.g. in a pre-clinical animal study) and evaluated for its half-life etc.
  • a polypeptide comprising at least the binding domain of the receptor of interest may be coated on solid phase, such as an assay plate.
  • the binding domain of the receptor alone or a receptor-fusion protein may be coated on the plate using standard procedures.
  • receptor-fusion proteins include receptor-glutathione S-transferase (GST) fusion protein, receptor-chitin binding domain fusion protein, receptor-hexaHis tag fusion protein (coated on glutathione, chitin, and nickel coated plates, respectively).
  • GST receptor-glutathione S-transferase
  • a capture molecule may be coated on the assay plate and used to bind the receptor-fusion protein via the non-receptor portion of the fusion protein.
  • Examples include anti-hexaHis F(ab′) 2 coated on the assay plate used to capture receptor-hexaHis tail fusion or anti-GST antibody coated on the assay plate used to capture a receptor-GST fusion.
  • binding to cells expressing at least the binding domain of the receptor may be evaluated.
  • the cells may be naturally occurring hematopoietic cells that express the FcR of interest or may be transformed with nucleic acid encoding the FcR or a binding domain thereof such that the binding domain is expressed at the surface of the cell to be tested.
  • the immune complex described hereinabove is added to the receptor-coated plates and incubated for a sufficient period of time such that the analyte binds to the receptor. Plates may then be washed to remove unbound complexes, and binding of the analyte may be detected according to known methods. For example, binding may be detected using a reagent (e.g. an antibody or fragment thereof) which binds specifically to the analyte, and which is optionally conjugated with a detectable label (detectable labels and methods for conjugating them to polypeptides are described below in the section entitled “Non-Therapeutic Uses for the Polypeptide Variant”).
  • a reagent e.g. an antibody or fragment thereof
  • the reagents can be provided in an assay kit, i.e., a packaged combination of reagents, for combination with the analyte in assaying the ability of the analyte to bind to a receptor of interest.
  • the components of the kit will generally be provided in predetermined ratios.
  • the kit may provide the first target molecule and/or the second target molecule, optionally complexed together.
  • the kit may further include assay plates coated with the receptor or a binding domain thereof (e.g. the extracellular domain of the a subunit of an FcR).
  • kits such as an antibody that binds specifically to the analyte to be assayed, labeled directly or indirectly with an enzymatic label
  • the detectable label is an enzyme
  • the kit will include substrates and cofactors required by the enzyme (e.g. a substrate precursor which provides the detectable chromophore or fluorophore).
  • other additives may be included such as stabilizers, buffers (e.g. assay and/or wash lysis buffer) and the like.
  • the relative amounts of the various reagents may be varied widely to provide for concentrations in solution of the reagents that substantially optimize the sensitivity of the assay.
  • the reagents may be provided as dry powders, usually lyophilized, including excipients that on dissolution will provide a reagent solution having the appropriate concentration.
  • the kit also suitably includes instructions for carrying out the assay.
  • the Fc region-containing polypeptide which is modified according to the teachings herein is an antibody. Techniques for producing antibodies follow:
  • the polypeptide is an antibody
  • it is directed against an antigen of interest.
  • the antigen is a biologically important polypeptide and administration of the antibody to a mammal suffering from a disease or disorder can result in a therapeutic benefit in that mammal.
  • antibodies directed against nonpolypeptide antigens are also contemplated.
  • the antigen is a polypeptide, it may be a transmembrane molecule (e.g. receptor) or ligand such as a growth factor.
  • exemplary antigens include molecules such as renin; a growth hormone, including human growth hormone and bovine growth hormone; growth hormone releasing factor; parathyroid hormone; thyroid stimulating hormone; lipoproteins; alpha-1-antitrypsin; insulin A-chain; insulin B-chain; proinsulin; follicle stimulating hormone; calcitonin; luteinizing hormone; glucagon; clotting factors such as factor VIIIC, factor IX, tissue factor (TF), and von Willebrands factor; anti-clotting factors such as Protein C; atrial natriuretic factor; lung surfactant; a plasminogen activator, such as urokinase or human urine or tissue-type plasminogen activator (t-PA); bombesin; thrombin; hemopoietic growth factor; tumor necrosis factor-alpha and
  • CD proteins such as CD3, CD4, CD8, CD19, CD20 and CD34
  • members of the ErbB receptor family such as the EGF receptor, HER2, HER3 or HER4 receptor
  • cell adhesion molecules such as LFA-1, Mac1, p150.95, VLA-4, ICAM-1, VCAM, ⁇ 4/ ⁇ 7 integrin, and ⁇ v/ ⁇ 3 integrin including either ⁇ or ⁇ subunits thereof (e.g.
  • anti-CD11a, anti-CD18 or anti-CD11b antibodies growth factors such as VEGF; tissue factor (TF); alpha interferon ( ⁇ -IFN); an interleukin, such as IL-8; IgE; blood group antigens; flk2/flt3 receptor; obesity (OB) receptor; mpl receptor; CTLA-4; protein C etc.
  • growth factors such as VEGF; tissue factor (TF); alpha interferon ( ⁇ -IFN); an interleukin, such as IL-8; IgE; blood group antigens; flk2/flt3 receptor; obesity (OB) receptor; mpl receptor; CTLA-4; protein C etc.
  • Soluble antigens or fragments thereof, optionally conjugated to other molecules, can be used as immunogens for generating antibodies.
  • immunogens for transmembrane molecules, such as receptors, fragments of these (e.g. the extracellular domain of a receptor) can be used as the immunogen.
  • transmembrane molecules such as receptors
  • fragments of these e.g. the extracellular domain of a receptor
  • cells expressing the transmembrane molecule can be used as the immunogen.
  • Such cells can be derived from a natural source (e.g. cancer cell lines) or may be cells which have been transformed by recombinant techniques to express the transmembrane molecule.
  • Other antigens and forms thereof useful for preparing antibodies will be apparent to those in the art.
  • Polyclonal antibodies are preferably raised in animals by multiple subcutaneous (sc) or intraperitoneal (ip) injections of the relevant antigen and an adjuvant. It may be useful to conjugate the relevant antigen to a protein that is immunogenic in the species to be immunized, e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, or soybean trypsin inhibitor using a bifunctional or derivatizing agent, for example, maleimidobenzoyl sulfosuccinimide ester (conjugation through cysteine residues), N-hydroxysuccinimide (through lysine residues), glutaraldehyde, succinic anhydride, SOCl 2 , or R 1 N ⁇ C ⁇ NR, where R and R 1 are different alkyl groups.
  • a protein that is immunogenic in the species to be immunized e.g., keyhole limpet hemocyanin, serum albumin, bovine thy
  • Animals are immunized against the antigen, immunogenic conjugates, or derivatives by combining, e.g., 100 ⁇ g or 5 ⁇ g of the protein or conjugate (for rabbits or mice, respectively) with 3 volumes of Freund's complete adjuvant and injecting the solution intradermally at multiple sites.
  • the animals are boosted with 1 ⁇ 5 to 1/10 the original amount of peptide or conjugate in Freund's complete adjuvant by subcutaneous injection at multiple sites.
  • Seven to 14 days later the animals are bled and the serum is assayed for antibody titer. Animals are boosted until the titer plateaus.
  • the animal is boosted with the conjugate of the same antigen, but conjugated to a different protein and/or through a different cross-linking reagent.
  • Conjugates also can be made in recombinant cell culture as protein fusions.
  • aggregating agents such as alum are suitably used to enhance the immune response.
  • Monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., Nature, 256:495 (1975), or may be made by recombinant DNA methods (U.S. Pat. No. 4,816,567).
  • a mouse or other appropriate host animal such as a hamster or macaque monkey
  • lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization.
  • lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp.59-103 (Academic Press, 1986)).
  • the hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
  • a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
  • the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.
  • Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium.
  • preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, Calif. USA, and SP-2 or X63-Ag8-653 cells available from the American Type Culture Collection, Rockville, Md. USA.
  • Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al, Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)).
  • Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen.
  • the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).
  • RIA radioimmunoassay
  • ELISA enzyme-linked immunoabsorbent assay
  • the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, Monoclonal Antibodies: Principles and Practice, pp.59-103 (Academic Press, 1986)). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium.
  • the hybridoma cells may be grown in vivoas ascites tumors in an animal.
  • the monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
  • DNA encoding the monoclonal antibodies is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies).
  • the hybridoma cells serve as a preferred source of such DNA.
  • the DNA may be placed into expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. Recombinant production of antibodies will be described in more detail below.
  • antibodies or antibody fragments can be isolated from antibody phage libraries generated using the techniques described in McCafferty et al., Nature, 348:552-554 (1990). Clackson et al, Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991) describe the isolation of murine and human antibodies, respectively, using phage libraries.
  • the DNA also may be modified, for example, by substituting the coding sequence for human heavy- and light-chain constant domains in place of the homologous murine sequences (U.S. Pat. No.4,816,567; Morrison, et al., Proc. Natl Acad. Sci. USA, 81:6851 (1984)), or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide.
  • non-immunoglobulin polypeptides are substituted for the constant domains of an antibody, or they are substituted for the variable domains of one antigen-combining site of an antibody to create a chimeric bivalent antibody comprising one antigen-combining site having specificity for an antigen and another antigen-combining site having specificity for a different antigen.
  • a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as “import” residues, which are typically taken from an “import” variable domain. Humanization can be essentially performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such “humanized” antibodies are chimeric antibodies (U.S. Pat. No.
  • humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
  • variable domains both light and heavy
  • the choice of human variable domains, both light and heavy, to be used in making the humanized antibodies is very important to reduce antigenicity.
  • the sequence of the variable domain of a rodent antibody is screened against the entire library of known human variable-domain sequences.
  • the human sequence which is closest to that of the rodent is then accepted as the human framework (FR) for the humanized antibody (Sims et al., J. Immunol., 151:2296 (1993); Chothia et al., J. Mol. Biol., 196:901 (1987)).
  • Another method uses a particular framework derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains.
  • the same framework may be used for several different humanized antibodies (Carter et al., Proc. Natl. Acad. Sci. USA, 89:4285 (1992); Presta et al., J. Immnol., 151:2623 (1993)).
  • humanized antibodies are prepared by a process of analysis of the parental sequences and various conceptual humanized products using three-dimensional models of the parental and humanized sequences.
  • Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art.
  • Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen.
  • FR residues can be selected and combined from the recipient and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved.
  • the CDR residues are directly and most substantially involved in influencing antigen binding.
  • transgenic animals e.g., mice
  • transgenic animals e.g., mice
  • J H antibody heavy-chain joining region
  • Human antibodies can also be derived from phage-display libraries (Hoogenboom et al., J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581-597 (1991); Vaughan et al. Nature Biotech 14:309 (1996)).
  • Multispecific antibodies have binding specificities for at least two different antigens. While such molecules normally will only bind two antigens (i.e. bispecific antibodies, BsAbs), antibodies with additional specificities such as trispecific antibodies are encompassed by this expression when used herein.
  • BsAbs include those with one arm directed against a tumor cell antigen and the other arm directed against a cytotoxic trigger molecule such as anti-Fc ⁇ RI/anti-CD15, anti-p185 HER2 /Fc ⁇ RIII (CD16), anti-CD3/anti-malignant B-cell (1D10), anti-CD3/anti-p185 HER2 , anti-CD3/anti-p97, anti-CD3/anti-renal cell carcinoma, anti-CD3/anti-OVCAR-3, anti-CD3/L-D1 (anti-colon carcinoma), anti-CD3/anti-melanocyte stimulating hormone analog, anti-EGF receptor/anti-CD3, anti-CD3/anti-CAMA1, anti-CD3/anti-CD19, anti-CD3/MoV18, anti-neural cell ahesion molecule (NCAM)/anti-CD3, anti-folate binding protein (FBP)/anti-CD3, anti-pan carcinoma associated antigen (AMOC-31)/anti-CD3; BsAbs with one arm which binds
  • BsAbs for use in therapy of infectious diseases such as anti-CD3/anti-herpes simplex virus (HSV), anti-T-cell receptor:CD3 complex/anti-influenza, anti-Fc ⁇ R/anti-HIV; BsAbs for tumor detection in vitro or in vivo such as anti-CEA/anti-EOTUBE, anti-CEA/anti-DPTA, anti-p185 HER2 /anti-hapten; BsAbs as vaccine adjuvants; and BsAbs as diagnostic tools such as anti-rabbit IgG/anti-ferritin, anti-horse radish peroxidase (HRP)/anti-hormone, anti-somatostatin/anti-substance P, anti-HRP/anti-FITC, anti-CEA/anti- ⁇ -galactosidase.
  • HRP anti-horse radish peroxidase
  • HRP anti-somatostatin/anti-substance P
  • trispecific antibodies examples include anti-CD3/anti-CD4/anti-CD37, anti-CD3/anti-CD5/anti-CD37 and anti-CD3/anti-CD8/anti-CD37.
  • Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab′) 2 bispecific antibodies).
  • bispecific antibodies are known in the art. Traditional production of full length bispecific antibodies is based on the coexpression of two immunoglobulin heavy chain-light chain pairs, where the two chains have different specificities (Millstein et al., Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of 10 different antibody molecules, of which only one has the correct bispecific structure. Purification of the correct molecule, which is usually done by affinity chromatography steps, is rather cumbersome, and the product yields are low. Similar procedures are disclosed in WO 93/08829, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).
  • antibody variable domains with the desired binding specificities are fused to immunoglobulin constant domain sequences.
  • the fusion preferably is with an immunoglobulin heavy chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light chain binding, present in at least one of the fusions.
  • DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain are inserted into separate expression vectors, and are co-transfected into a suitable host organism.
  • the bispecific antibodies are composed of a hybrid immunoglobulin heavy chain with a first binding specificity in one arm, and a hybrid immunoglobulin heavy chain-light chain pair (providing a second binding specificity) in the other arm. It was found that this asymmetric structure facilitates the separation of the desired bispecific compound from unwanted immunoglobulin chain combinations, as the presence of an immunoglobulin light chain in only one half of the bispecific molecule provides for a facile way of separation. This approach is disclosed in WO 94/04690. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).
  • the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture.
  • the preferred interface comprises at least a part of the CH3 domain of an antibody constant domain.
  • one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan).
  • Compensatory “cavities” of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.
  • Bispecific antibodies include cross-linked or “heteroconjugate” antibodies.
  • one of the antibodies in the heteroconjugate can be coupled to avidin, the other to biotin.
  • Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980), and for treatment of HIV infection (WO 91/00360, WO 92/200373, and EP 03089).
  • Heteroconjugate antibodies may be made using any convenient cross-linking methods. Suitable cross-linking agents are well known in the art, and are disclosed in U.S. Pat. No. 4,676,980, along with a number of cross-linking techniques.
  • Antibodies with more than two valencies are contemplated.
  • trispecific antibodies can be prepared. Tutt et al. J. Immunol. 147: 60 (1991).
  • polypeptide of interest herein is preferably an antibody
  • Fc region-containing polypeptides which can be modified according to the methods described herein are contemplated.
  • An example of such a molecule is an immunoadhesin.
  • the simplest and most straightforward immunoadhesin design combines the binding domain(s) of the adhesin (e.g. the extracellular domain (ECD) of a receptor) with the Fc region of an immunoglobulin heavy chain.
  • ECD extracellular domain
  • nucleic acid encoding the binding domain of the adhesin will be fused C-terminally to nucleic acid encoding the N-terminus of an immunoglobulin constant domain sequence, however N-terminal fusions are also possible.
  • the encoded chimeric polypeptide will retain at least functionally active hinge, C H 2 and C H 3 domains of the constant region of an immunoglobulin heavy chain. Fusions are also made to the C-terminus of the Fc portion of a constant domain, or immediately N-terminal to the C H 1 of the heavy chain or the corresponding region of the light chain.
  • the precise site at which the fusion is made is not critical; particular sites are well known and may be selected in order to optimize the biological activity, secretion, or binding characteristics of the immunoadhesin.
  • the adhesin sequence is fused to the N-terminus of the Fc region of immunoglobulin G 1 (IgG 1 ). It is possible to fuse the entire heavy chain constant region to the adhesin sequence. However, more preferably, a sequence beginning in the hinge region just upstream of the papain-cleavage site which defines IgG Fc chemically (i.e. residue 216, taking the first residue of heavy chain constant region to be 114), or analogous sites of other immunoglobulins is used in the fusion.
  • the adhesin amino acid sequence is fused to (a) the hinge region and C H 2 and C H 3 or (b) the C H 1, hinge, C H 2 and C H 3 domains, of an IgG heavy chain.
  • the immunoadhesins are assembled as multimers, and particularly as heterodimers or heterotetramers.
  • these assembled immunoglobulins will have known unit structures.
  • a basic four chain structural unit is the form in which IgG, IgD, and IgE exist.
  • a four chain unit is repeated in the higher molecular weight immunoglobulins; IgM generally exists as a pentamer of four basic units held together by disulfide bonds.
  • IgA globulin, and occasionally IgG globulin may also exist in multimeric form in serum. In the case of multimer, each of the four units may be the same or different.
  • each A represents identical or different adhesin amino acid sequences
  • V L is an immunoglobulin light chain variable domain
  • V H is an immunoglobulin heavy chain variable domain
  • C L is an immunoglobulin light chain constant domain
  • C H is an immunoglobulin heavy chain constant domain
  • n is an integer greater than 1;
  • Y designates the residue of a covalent cross-linking agent.
  • the adhesin sequences can be inserted between immunoglobulin heavy chain and light chain sequences, such that an immunoglobulin comprising a chimeric heavy chain is obtained.
  • the adhesin sequences are fused to the 3′ end of an immunoglobulin heavy chain in each arm of an immunoglobulin, either between the hinge and the C H 2 domain, or between the C H 2 and C H 3 domains. Similar constructs have been reported by Hoogenboom, et al., Mol. Immunol. 28:1027-1037 (1991).
  • an immunoglobulin light chain might be present either covalently associated to an adhesin-immunoglobulin heavy chain fusion polypeptide, or directly fused to the adhesin.
  • DNA encoding an immunoglobulin light chain is typically coexpressed with the DNA encoding the adhesin-immunoglobulin heavy chain fusion protein.
  • the hybrid heavy chain and the light chain will be covalently associated to provide an immunoglobulin-like structure comprising two disulfide-linked immunoglobulin heavy chain-light chain pairs.
  • Immunoadhesins are most conveniently constructed by fusing the cDNA sequence encoding the adhesin portion in-frame to an immunoglobulin cDNA sequence.
  • fusion to genomic immunoglobulin fragments can also be used (see, e.g. Aruffo et al., Cell 61:1303-1313 (1990); and Stamenkovic et al., Cell 66:1133-1144 (1991)).
  • the latter type of fusion requires the presence of Ig regulatory sequences for expression.
  • cDNAs encoding IgG heavy-chain constant regions can be isolated based on published sequences from cDNA libraries derived from spleen or peripheral blood lymphocytes, by hybridization or by polymerase chain reaction (PCR) techniques.
  • the cDNAs encoding the “adhesin” and the immunoglobulin parts of the immunoadhesin are inserted in tandem into a plasmid vector that directs efficient expression in the chosen host cells.
  • the invention also provides isolated nucleic acid encoding a polypeptide variant as disclosed herein, vectors and host cells comprising the nucleic acid, and recombinant techniques for the production of the polypeptide variant.
  • the nucleic acid encoding it is isolated and inserted into a replicable vector for further cloning (amplification of the DNA) or for expression.
  • DNA encoding the polypeptide variant is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the polypeptide variant).
  • Many vectors are available.
  • the vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence.
  • polypeptide variant of this invention may be produced recombinantly not only directly, but also as a fusion polypeptide with a heterologous polypeptide, which is preferably a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypeptide.
  • a heterologous polypeptide which is preferably a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypeptide.
  • the heterologous signal sequence selected preferably is one that is recognized and processed (i.e., cleaved by a signal peptidase) by the host cell.
  • the signal sequence is substituted by a prokaryotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, lpp, or heat-stable enterotoxin II leaders.
  • a prokaryotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, lpp, or heat-stable enterotoxin II leaders.
  • yeast secretion the native signal sequence may be substituted by, e.g., the yeast invertase leader, a factor leader (including Saccharomyces and Kluyveromyces ⁇ -factor leaders), or acid phosphatase leader, the C. albicans glucoamylase leader, or the signal described in WO 90/13646.
  • mammalian signal sequences as well as viral secretory leaders for example, the herpes simplex gD signal, are available.
  • the DNA for such precursor region is ligated in reading frame to DNA encoding the polypeptide variant.
  • Both expression and cloning vectors contain a nucleic acid sequence that enables the vector to replicate in one or more selected host cells.
  • this sequence is one that enables the vector to replicate independently of the host chromosomal DNA, and includes origins of replication or autonomously replicating sequences.
  • origins of replication or autonomously replicating sequences are well known for a variety of bacteria, yeast, and viruses.
  • the origin of replication from the plasmid pBR322 is suitable for most Gram-negative bacteria, the 2 ⁇ plasmid origin is suitable for yeast, and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) are useful for cloning vectors in mammalian cells.
  • the origin of replication component is not needed for mammalian expression vectors (the SV40 origin may typically be used only because it contains the early promoter).
  • Selection genes may contain a selection gene, also termed a selectable marker.
  • Typical selection genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, neomycin, methotrexate, or tetracycline, (b) complement auxotrophic deficiencies, or (c) supply critical nutrients not available from complex media, e.g., the gene encoding D-alanine racemase for Bacilli.
  • One example of a selection scheme utilizes a drug to arrest growth of a host cell. Those cells that are successfully transformed with a heterologous gene produce a protein conferring drug resistance and thus survive the selection regimen. Examples of such dominant selection use the drugs neomycin, mycophenolic acid and hygromycin.
  • suitable selectable markers for mammalian cells are those that enable the identification of cells competent to take up the polypeptide variant nucleic acid, such as DHFR, thymidine kinase, met allothionein-I and -II, preferably primate met allothionein genes, adenosine deaminase, ornithine decarboxylase, etc.
  • cells transformed with the DHFR selection gene are first identified by culturing all of the transformants in a culture medium that contains methotrexate (Mtx), a competitive antagonist of DHFR.
  • Mtx methotrexate
  • An appropriate host cell when wild-type DHFR is employed is the Chinese hamster ovary (CHO) cell line deficient in DHFR activity.
  • host cells transformed or co-transformed with DNA sequences encoding polypeptide variant, wild-type DHFR protein, and another selectable marker such as aminoglycoside 3′-phosphotransferase (APH) can be selected by cell growth in medium containing a selection agent for the selectable marker such as an aminoglycosidic antibiotic, e.g., kanamycin, neomycin, or G418. See U.S. Pat. No. 4,965,199.
  • APH aminoglycoside 3′-phosphotransferase
  • a suitable selection gene for use in yeast is the trp1 gene present in the yeast plasmid YRp7 (Stinchcomb et al., Nature, 282:39 (1979)).
  • the trp1 gene provides a selection marker for a mutant strain of yeast lacking the ability to grow in tryptophan, for example, ATCC No.44076 or PEP4-1. Jones, Genetics, 85:12 (1977).
  • the presence of the trp1 lesion in the yeast host cell genome then provides an effective environment for detecting transformation by growth in the absence of tryptophan.
  • Leu2-deficient yeast strains (ATCC 20,622 or 38,626) are complemented by known plasmids bearing the Leu2 gene.
  • vectors derived from the 1.6 ⁇ m circular plasmid pKD1 can be used for transformation of Kluyveromyces yeasts.
  • an expression system for large-scale production of recombinant calf chymosin was reported for K. lactis. Van den Berg, Bio/Technology, 8:135 (1990).
  • Stable multi-copy expression vectors for secretion of mature recombinant human serum albumin by industrial strains of Kluyveromyces have also been disclosed. Fleer et al., Bio/Technology, 9:968-975 (1991).
  • Expression and cloning vectors usually contain a promoter that is recognized by the host organism and is operably linked to the polypeptide variant nucleic acid.
  • Promoters suitable for use with prokaryotic hosts include the phoA promoter, ⁇ -lactamase and lactose promoter systems, alkaline phosphatase, a tryptophan (trp) promoter system, and hybrid promoters such as the tac promoter.
  • trp tryptophan
  • Other known bacterial promoters are suitable. Promoters for use in bacterial systems also will contain a Shine-Dalgarno (S.D.) sequence operably linked to the DNA encoding the polypeptide variant.
  • S.D. Shine-Dalgarno
  • Promoter sequences are known for eukaryotes. Virtually all eukaryotic genes have an AT-rich region located approximately 25 to 30 bases upstream from the site where transcription is initiated. Another sequence found 70 to 80 bases upstream from the start of transcription of many genes is a CNCAAT region where N may be any nucleotide. At the 3′ end of most eukaryotic genes is an AATAAA sequence that may be the signal for addition of the poly A tail to the 3′ end of the coding sequence. All of these sequences are suitably inserted into eukaryotic expression vectors.
  • suitable promoting sequences for use with yeast hosts include the promoters for 3-phosphoglycerate kinase or other glycolytic enzymes, such as enolase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate isomerase, phosphoglucose isomerase, and glucokinase.
  • 3-phosphoglycerate kinase or other glycolytic enzymes such as enolase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate
  • yeast promoters which are inducible promoters having the additional advantage of transcription controlled by growth conditions, are the promoter regions for alcohol dehydrogenase 2, isocytochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, met allothionein, glyceraldehyde-3-phosphate dehydrogenase, and enzymes responsible for maltose and galactose utilization.
  • Suitable vectors and promoters for use in yeast expression are further described in EP 73,657.
  • Yeast enhancers also are advantageously used with yeast promoters.
  • Polypeptide variant transcription from vectors in mammalian host cells is controlled, for example, by promoters obtained from the genomes of viruses such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and most preferably Simian Virus 40 (SV40), from heterologous mammalian promoters, e.g., the actin promoter or an immunoglobulin promoter, from heat-shock promoters, provided such promoters are compatible with the host cell systems.
  • viruses such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and most preferably Simian Virus 40 (
  • the early and late promoters of the SV40 virus are conveniently obtained as an SV40 restriction fragment that also contains the SV40 viral origin of replication.
  • the immediate early promoter of the human cytomegalovirus is conveniently obtained as a HindIII E restriction fragment.
  • a system for expressing DNA in mammalian hosts using the bovine papilloma virus as a vector is disclosed in U.S. Pat. No. 4,419,446. A modification of this system is described in U.S. Pat. No. 4,601,978. See also Reyes et al, Nature 297:598-601 (1982) on expression of human ⁇ -interferon cDNA in mouse cells under the control of a thymidine kinase promoter from herpes simplex virus. Alternatively, the rous sarcoma virus long terminal repeat can be used as the promoter.
  • Enhancer sequences are now known from mammalian genes (globin, elastase, albumin, ⁇ -fetoprotein, and insulin). Typically, however, one will use an enhancer from a eukaryotic cell virus. Examples include the SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers.
  • the enhancer may be spliced into the vector at a position 5′ or 3′ to the polypeptide variant-encoding sequence, but is preferably located at a site 5′ from the promoter.
  • Expression vectors used in eukaryotic host cells will also contain sequences necessary for the termination of transcription and for stabilizing the mRNA. Such sequences are commonly available from the 5′ and, occasionally 3′, untranslated regions of eukaryotic or viral DNAs or cDNAs. These regions contain nucleotide segments transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding the polypeptide variant.
  • One useful transcription termination component is the bovine growth hormone polyadenylation region. See WO94/11026 and the expression vector disclosed therein.
  • Suitable host cells for cloning or expressing the DNA in the vectors herein are the prokaryote, yeast, or higher eukaryote cells described above.
  • Suitable prokaryotes for this purpose include eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B. subtilis and B. licheniformis (e.g., B.
  • E. coli 294 ATCC 31,446
  • E. coli B E. coli X1776
  • E. coli W3110 ATCC 27,325
  • eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for polypeptide variant-encoding vectors.
  • Saccharomyces cerevisiae or common baker's yeast, is the most commonly used among lower eukaryotic host microorganisms.
  • a number of other genera, species, and strains are commonly available and useful herein, such as Schizosaccharomyces pombe; Kluyveromyces hosts such as, e.g., K. lactis, K. fragilis (ATCC 12,424), K. bulgaricus (ATCC 16,045), K. wickeramii (ATCC 24,178), K.
  • waltii ATCC 56,500
  • K. drosophilarum ATCC 36,906
  • K. thermotolerans K. marxianus
  • yarrowia EP 402,226
  • Pichia pastoris EP 183,070
  • Candida Trichoderma reesia
  • Neurospora crassa Schwanniomyces such as Schwanniomyces occidentalis
  • filamentous fungi such as, e.g., Neurospora, Penicillium, Tolypocladium, and Aspergillus hosts such as A. nidulans and A. niger.
  • Suitable host cells for the expression of glycosylated polypeptide variant are derived from multicellular organisms.
  • invertebrate cells include plant and insect cells.
  • Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruitfly), and Bombyx mori have been identified.
  • a variety of viral strains for transfection are publicly available, e.g., the L-1 variant of Autographa californica NPV and the Bm-5 strain of Bombyx mori NPV, and such viruses may be used as the virus herein according to the present invention, particularly for transfection of Spodoptera frugiperda cells.
  • Plant cell cultures of cotton, corn, potato, soybean, petunia, tomato, and tobacco can also be utilized as hosts.
  • vertebrate cells have been greatest in vertebrate cells, and propagation of vertebrate cells in culture (tissue culture) has become a routine procedure.
  • useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK, ATCC CCL 10); Chinese hamster ovary cells/-DHFR (CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); mouse sertoli cells (TM4, Mather, Biol. Reprod.
  • monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL-1 587); human cervical carcinoma cells (HELA, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); mouse mammary tumor (MMT 060562, ATCC CCL51); TRI cells (Mather et al, Annals N.Y. Acad. Sci. 383:44-68 (1982)); MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2).
  • Host cells are transformed with the above-described expression or cloning vectors for polypeptide variant production and cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences.
  • the host cells used to produce the polypeptide variant of this invention may be cultured in a variety of media.
  • Commercially available media such as Ham's F10 (Sigma), Minimal Essential Medium ((MEM), (Sigma), RPMI-1640 (Sigma), and Dulbecco's Modified Eagle's Medium ((DMEM), Sigma) are suitable for culturing the host cells.
  • any of these media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics (such as GENTAMYCINTM drug), trace elements (defined as inorganic compounds usually present at final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art.
  • the culture conditions such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.
  • the polypeptide variant can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the polypeptide variant is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. Carter et al., Bio/Technology 10:163-167 (1992) describe a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli. Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 min.
  • sodium acetate pH 3.5
  • EDTA EDTA
  • PMSF phenylmethylsulfonylfluoride
  • Cell debris can be removed bycentrifugation.
  • supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit.
  • a protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants.
  • the polypeptide variant composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being the preferred purification technique.
  • affinity chromatography is the preferred purification technique.
  • the suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc region that is present in the polypeptide variant.
  • Protein A can be used to purify polypeptide variants that are based on human ⁇ 1, ⁇ 2, or ⁇ 4 heavy chains (Lindmark et al., J. Immunol. Meth. 62:1-13 (1983)). Protein G is recommended for all mouse isotypes and for human Y (Guss et al., EMBO J.
  • the matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the polypeptide variant comprises a C H 3 domain, the Bakerbond ABXTM resin (J. T. Baker, Phillipsburg, N.J.) is useful for purification.
  • the mixture comprising the polypeptide variant of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5-4.5, preferably performed at low salt concentrations (e.g.,from about 0-0.25M salt).
  • Therapeutic formulations of the polypeptide variant are prepared for storage by mixing the polypeptide variant having the desired degree of purity with optional physiologically acceptable carriers, excipients or stabilizers ( Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions.
  • Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arg
  • the formulation herein may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.
  • Such molecules are suitably present in combination in amounts that are effective for the purpose intended.
  • the active ingredients may also be entrapped in microcapsule prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsule and poly-(methylmethacylate) microcapsule, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions.
  • colloidal drug delivery systems for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules
  • the formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.
  • Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the polypeptide variant, which matrices are in the form of shaped articles, e.g., films, or microcapsule. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No.
  • copolymers of L-glutamic acid and y ethyl-L-glutamate non-degradable ethylene-vinyl acetate
  • degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOTTM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate)
  • poly-D-( ⁇ )-3-hydroxybutyric acid While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.
  • encapsulated antibodies When encapsulated antibodies remain in the body for a long time, they may denature or aggregate as a result of exposure to moisture at 37° C., resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S—S bond formation through thio-disulfide interchange, stabilization may be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.
  • the polypeptide variant of the invention may be used as an affinity purification agent.
  • the polypeptide variant is immobilized on a solid phase such a Sephadex resin or filter paper, using methods well known in the art.
  • the immobilized polypeptide variant is contacted with a sample containing the antigen to be purified, and thereafter the support is washed with a suitable solvent that will remove substantially all the material in the sample except the antigen to be purified, which is bound to the immobilized polypeptide variant. Finally, the support is washed with another suitable solvent, such as glycine buffer, pH 5.0, that will release the antigen from the polypeptide variant.
  • the polypeptide variant may also be useful in diagnostic assays, e.g., for detecting expression of an antigen of interest in specific cells, tissues, or serum.
  • polypeptide variant typically will be labeled with a detectable moiety.
  • labels are available which can be generally grouped into the following categories:
  • Radioisotopes such as 35 S, 14 C, 125 I, 3 H, and 131 I.
  • the polypeptide variant can be labeled with the radioisotope using the techniques described in Current Protocols in Immunology, Volumes 1 and 2, Coligen et al., Ed. Wiley-lnterscience, New York, New York, Pubs. (1991) for example and radioactivity can be measured using scintillation counting.
  • Fluorescent labels such as rare earth chelates (europium chelates) or fluorescein and its derivatives, rhodamine and its derivatives, dansyl, Lissamine, phycoerythrin and Texas Red are available.
  • the fluorescent labels can be conjugated to the polypeptide variant using the techniques disclosed in Current Protocols in Immunology, supra, for example. Fluorescence can be quantified using a fluorimeter.
  • the enzyme generally catalyzes a chemical alteration of the chromogenic substrate that can be measured using various techniques. For example, the enzyme may catalyze a color change in a substrate, which can be measured spectrophotometrically. Alternatively, the enzyme may alter the fluorescence or chemiluminescence of the substrate. Techniques for quantifying a change in fluorescence are described above.
  • the chemiluminescent substrate becomes electronically excited by a chemical reaction and may then emit light which can be measured (using a chemiluminometer, for example) or donates energy to a fluorescent acceptor.
  • enzymatic labels include luciferases (e.g., firefly luciferase and bacterial luciferase; U.S. Pat. No. 4,737,456), luciferin, 2,3-dihydrophthalazinediones, malate dehydrogenase, urease, peroxidase such as horseradish peroxidase (HRPO), alkaline phosphatase, ⁇ -galactosidase, glucoamylase, lysozyme, saccharide oxidases (e.g., glucose oxidase, galactose oxidase, and glucose-6-phosphate dehydrogenase), heterocyclic oxidases (such as uricase and xanthine oxidase), lactoperoxidase, microperoxidase, and the like.
  • luciferases e.g., firefly luciferase and bacterial lucifera
  • enzyme-substrate combinations include, for example:
  • HRPO Horseradish peroxidase
  • OPD orthophenylene diamine
  • TMB 3,3′,5,5′-tetramethyl benzidine hydrochloride
  • ⁇ -D-galactosidase ( ⁇ -D-Gal) with a chromogenic substrate (e.g., p-nitrophenyl- ⁇ -D-galactosidase) or fluorogenic substrate 4-methylumbelliferyl- ⁇ -D-galactosidase.
  • a chromogenic substrate e.g., p-nitrophenyl- ⁇ -D-galactosidase
  • fluorogenic substrate 4-methylumbelliferyl- ⁇ -D-galactosidase
  • the label is indirectly conjugated with the polypeptide variant.
  • the polypeptide variant can be conjugated with biotin and any of the three broad categories of labels mentioned above can be conjugated with avidin, or vice versa. Biotin binds selectively to avidin and thus, the label can be conjugated with the polypeptide variant in this indirect manner.
  • the polypeptide variant is conjugated with a small hapten (e.g., digoxin) and one of the different types of labels mentioned above is conjugated with an anti-hapten polypeptide variant (e.g., anti-digoxin antibody).
  • a small hapten e.g., digoxin
  • an anti-hapten polypeptide variant e.g., anti-digoxin antibody
  • the polypeptide variant need not be labeled, and the presence thereof can be detected using a labeled antibody which binds to the polypeptide variant.
  • polypeptide variant of the present invention may be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays. Zola, Monoclonal Antibodies: A Manual of Techniques, pp.147-158 (CRC Press, Inc. 1987).
  • the polypeptide variant may also be used for in vivo diagnostic assays.
  • the polypeptide variant is labeled with a radionuclide (such as 111 In, 99 Tc, 14 C, 131 I, 125 I, 3 H, 32 P or 35 S) so that the antigen or cells expressing it can be localized using immunoscintiography.
  • a radionuclide such as 111 In, 99 Tc, 14 C, 131 I, 125 I, 3 H, 32 P or 35 S
  • the polypeptide variant of the present invention may be used to treat a mammal e.g. a patient suffering from, or predisposed to, a disease or disorder who could benefit from administration of the polypeptide variant.
  • the conditions which can be treated with the polypeptide variant are many and include cancer (e.g. where the polypeptide variant binds the HER2 receptor, CD20 or vascular endothelial growth factor (VEGF)); allergic conditions such as asthma (with an anti-IgE antibody); and LFA-1-mediated disorders (e.g. where the polypeptide variant is an anti-LFA-1 or anti-ICAM-1 antibody) etc.
  • cancer e.g. where the polypeptide variant binds the HER2 receptor, CD20 or vascular endothelial growth factor (VEGF)
  • allergic conditions such as asthma (with an anti-IgE antibody)
  • LFA-1-mediated disorders e.g. where the polypeptide variant is an anti-LFA-1 or anti-ICAM-1 antibody
  • the disorder preferably is HER2-expressing cancer, e.g. a benign or malignant tumor characterized by overexpression of the HER2 receptor.
  • cancers include, but are not limited to, breast cancer, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.
  • the polypeptide variant with improved ADCC activity may be employed in the treatment of diseases or disorders where destruction or elimination of tissue or foreign micro-organisms is desired.
  • the polypeptide may be used to treat cancer; inflammatory disorders; infections (e.g. bacterial, viral, fungal or yeast infections); and other conditions (such as goiter) where removal of tissue is desired, etc.
  • the polypeptide variant may be used to treat diseases or disorders where a Fc region-containing polypeptide with long half-life is desired, but the polypeptide preferably does not have undesirable effector function(s).
  • the Fc region-containing polypeptide may be an anti-tissue factor (TF) antibody; anti-IgE antibody; and anti-integrin antibody (e.g. an anti- ⁇ 4 ⁇ 7 antibody).
  • TF tissue factor
  • anti-IgE antibody anti-integrin antibody
  • the desired mechanism of action of such Fc region-containing polypeptides may be to block ligand-receptor binding pairs.
  • the Fc-region containing polypeptide with diminished ADCC activity may be an agonist antibody.
  • the polypeptide variant is administered by any suitable means, including parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal, and, if desired for local immunosuppressive treatment, intralesional administration.
  • Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration.
  • the polypeptide variant is suitably administered by pulse infusion, particularly with declining doses of the polypeptide variant.
  • the dosing is given by injections, most preferably intravenous or subcutaneous injections, depending in part on whether the administration is brief or chronic.
  • polypeptide variant For the prevention or treatment of disease, the appropriate dosage of polypeptide variant will depend on the type of disease to be treated, the severity and course of the disease, whether the polypeptide variant is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the polypeptide variant, and the discretion of the attending physician.
  • the polypeptide variant is suitably administered to the patient at one time or over a series of treatments.
  • polypeptide variant is an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations, or by continuous infusion.
  • a typical daily dosage might range from about 1 ⁇ g/kg to 100 mg/kg or more, depending on the factors mentioned above.
  • the treatment is sustained until a desired suppression of disease symptoms occurs.
  • other dosage regimens may be useful. The progress of this therapy is easily monitored by conventional techniques and assays.
  • the polypeptide variant composition will be formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners.
  • the “therapeutically effective amount” of the polypeptide variant to be administered will be governed by such considerations, and is the minimum amount necessary to prevent, ameliorate, or treat a disease or disorder.
  • the polypeptide variant need not be, but is optionally formulated with one or more agents currently used to prevent or treat the disorder in question.
  • the effective amount of such other agents depends on the amount of polypeptide variant present in the formulation, the type of disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as used hereinbefore or about from 1 to 99% of the heretofore employed dosages.
  • This assay determines binding of an IgG Fc region to recombinant Fc ⁇ RIIA, Fc ⁇ RIlB and Fc ⁇ RIIIA a subunits expressed as His6-glutathione S transferase (GST)-tagged fusion proteins. Since the affinity of the Fc region of IgG1 for the Fc ⁇ RI is in the nanomolar range, the binding of IgG1 Fc variants can be measured by titrating monomeric IgG and measuring bound IgG with a polyclonal anti-IgG in a standard ELISA format (Example 2 below). The affinity of the other members of the Fc ⁇ R family, i.e. Fc ⁇ RIIA, Fc ⁇ RIlB and Fc ⁇ RIIIA for IgG is however in the micromolar range and binding of monomeric IgG1 for these receptors can not be reliably measured in an ELISA format.
  • the following assay utilizes Fc variants of recombinant anti-IgE E27 ( FIGS. 4A and 4B ) which, when mixed with human IgE at a 1:1 molar ratio, forms a stable hexamer consisting of three anti-IgE molecules and three IgE molecules.
  • a recombinant chimeric form of IgE (chimeric IgE) was engineered and consists of a human IgE Fc region and the Fab of an anti-VEGF antibody (Presta et al. Cancer Research 57:4593-4599 (1997)) which binds two VEGF molecules per mole of anti-VEGF.
  • Receptor Coat Fc ⁇ receptor a subunits were expressed as GST fusions of His6 tagged extracellular domains (ECDs) in 293 cells resulting in an ECD-6His-GST fusion protein (Graham et al. J. Gen. Virol. 36:59-74 (1977) and Gorman et al. DNA Prot. Eng. Tech. 2:3-10 (1990)) and purified by Ni-NTA column chromatography (Qiagen, Australia) and buffer exchanged into phosphate buffered saline (PBS). Concentrations were determined by absorption at 280 nm using extinction coefficients derived by amino acid composition analysis. Receptors were coated onto Nunc F96 maxisorb plates (cat no.
  • E27:chimeric IgE:VEGF: (1:1:2 molar ratio) complexes are added to Fc ⁇ R a subunit coated plates at E27 concentrations of 5 ⁇ g and 1 ⁇ g total IgG in quadruplicate in assay buffer and incubated for 120 minutes at 25° C. on an orbital shaker.
  • HRP horse radish peroxidase conjugated goat anti-human IgG
  • y horse radish peroxidase
  • Plates are washed 5 ⁇ with wash buffer to remove unbound HRP goat anti-human IgG and bound anti-IgG is detected by adding 100 ⁇ l of substrate solution (0.4 mg/ml o-phenylenedaimine dihydrochloride, Sigma P6912, 6 mM H 2 O 2 in PBS) and incubating for 8 min at 25° C. Enzymatic reaction is stopped by the addition of 100 ⁇ l 4.5N H 2 SO 4 and colorimetric product is measured at 490 nm on a 96 well plate densitometer (Molecular Devices). Binding of E27 variant complexes is expressed as a percent of the wild type E27 containing complex.
  • C2B8 Variants The chimeric light and heavy chains of anti-CD20 antibody C2B8 (Reff et al., Blood 83:435 (1994)) subcloned separately into previously described PRK vectors (Gorman et al., DNA Protein Eng. Tech. 2:3 (1990)) were used. By site directed mutagenesis (Kunkel et al., Proc. Natl. Acad.Sci.USA 82:488 (1985)), alanine scan variants of the Fc region in the heavy chain were constructed. The heavy and light chain plasmids were co-transfected into an adenovirus transformed human embryonic kidney cell line as previously described (Werther et al., J.
  • the media was changed to serum-free 24 hours after transfection and the secreted antibody was harvested after five days.
  • the antibodies were purified using Protein A-SEPHAROSE CL-4BTM (Pharmacia), buffer exchanged and concentrated to 0.5 ml with PBS using a Centricon-30 (Amicon), and stored at 4° C. The concentration of the antibody was determined using total Ig-binding ELISA.
  • C1q Binding ELISA Costar 96 well plates were coated overnight at 4° C. with the indicated concentrations of C2B8 in coating buffer (0.05 M sodium carbonate buffer), pH 9. The plates were then washed 3 ⁇ with PBS/0.05% TWEEN 20TM, pH 7.4 and blocked with 200 ⁇ l of ELISA diluent without thimerosal (0.1 M NaPO4/0.1 M NaCl/0.1% gelatin /0.05% TWEEN 20TM/0.05% ProClin300) for 1 hr at room temperature.
  • the plate was washed 3x with wash buffer, an aliquot of 100 ⁇ l of 2 ⁇ g/ml C1q (Quidel, San Diego, Calif.) was added to each well and incubated for 2 hrs at room temperature. The plate was then washed 6 ⁇ with wash buffer. 100 ⁇ l of a 1:1000 dilution of sheep anti-complement C1q peroxidase conjugated antibody (Biodesign) was added to each well and incubated for 1 hour at room temperature. The plate was again washed 6 ⁇ with wash buffer and 100 ⁇ l of substrate buffer (PBS/0.012% H 2 O 2 ) containing OPD (O-phenylenediamine dihydrochloride (Sigma)) was added to each well.
  • substrate buffer PBS/0.012% H 2 O 2
  • OPD O-phenylenediamine dihydrochloride
  • the oxidation reaction observed by the appearance of a yellow color, was allowed to proceed for 30 minutes and stopped by the addition of 100 ⁇ l of 4.5 N H 2 SO 4 .
  • the absorbance was then read at (492-405) nm using a microplate reader (SPECTRA MAX 250TM, Molecular Devices Corp.).
  • the appropriate controls were run in parallel (i.e. the ELISA was performed without C1q for each concentration of C2B8 used and also the ELISA was performed without C2B8).
  • C1q binding was measured by plotting the absorbance (492-405) nm versus concentration of C2B8 in ⁇ g/ml using a 4-parameter curve filting program (KALEIDAGRAPHTM) and comparing EC 50 values.
  • CDC Complement Dependent Cytotoxicity
  • Human complement (Quidel) was diluted 1:3 in RHB buffer and WIL2-S cells (available from the ATCC, Manassas, Va.) which express the CD20 antigen were diluted to a density of 1 ⁇ 10 6 cells/ml with RHB buffer.
  • Mixtures of 150 ⁇ l containing equal volumes of C2B8, diluted human complement and WIL2-S cells were added to a flat bottom tissue culture 96 well plate and allowed to incubate for 2 hrs at 37° C. and 5% CO 2 to facilitate complement mediated cell lysis. 50 ⁇ l of alamar blue (Accumed International) was then added to each well and incubated overnight at 37° C.
  • the absorbance was measured using a 96-well fluorometer with excitation at 530 nm and emission at 590 nm. As described by Gazzano-Santoro et al., the results are expressed in relative fluorescence units (RFU). The sample concentrations were computed from a C2B8 standard curve and the percent activity as compared to wild type C2B8 is reported for each variant.
  • CD20 Binding Potency of the C2B8 Variants The binding of C2B8 and variants to the CD20 antigen were assessed by a method previously described (Reff et al., (1994), supra; reviewed in Gazzano-Santoro et al., (1997), supra). WIL2-S cells were grown for 3-4 days to a cell density of 1 ⁇ 10 6 cells/ml. The cells were washed and spun twice in FACS buffer (PBS/0.1% BSA/0.02% NaN 3 ) and resuspended to a cell density of 5 ⁇ 10 6 cells/ml.
  • FACS buffer PBS/0.1% BSA/0.02% NaN 3
  • Fc ⁇ R Binding ELISAs Fc ⁇ RI ⁇ subunit-GST fusion was coated onto Nunc F96 maxisorb plates (cat no.439454) by adding 100 ⁇ l of receptor-GST fusion at 1 ⁇ g/ml in PBS and incubated for 48 hours at 4° C. Prior to assay, plates are washed 3 ⁇ with 250 [l of wash buffer (PBS pH 7.4 containing 0.5% TWEEN 20TM) and blocked with 250 ⁇ l of assay buffer (50 mM Tris buffered saline, 0.05% TWEEN 20TM, 0.5% RIA grade bovine albumin (Sigma A7888), and 2 mM EDTA pH 7.4).
  • wash buffer PBS pH 7.4 containing 0.5% TWEEN 20TM
  • assay buffer 50 mM Tris buffered saline, 0.05% TWEEN 20TM, 0.5% RIA grade bovine albumin (Sigma A7888), and 2 mM EDTA pH 7.4
  • Plates are washed 5 ⁇ with wash buffer to remove unbound HRP goat anti-human IgG and bound anti-IgG is detected by adding 100 ⁇ l of substrate solution (0.4 mg/ml o-phenylenedaimine dihydrochloride, Sigma P6912, 6 mM H 2 O 2 in PBS) and incubating for 8 min at 25° C. Enzymatic reaction is stopped by the addition of 100 ⁇ l 4.5N H 2 SO 4 and colorimetric product is measured at 490 nm on a 96 well plate densitometer (Molecular Devices). Binding of variant is expressed as a percent of the wild type molecule.
  • Fc ⁇ RII and III binding ELISAs were performed as described in Example 1 above.
  • ELISA plates were coated with 2 ⁇ g/ml streptavidin (Zymed, South San Francisco) in 50 mM carbonate buffer, pH 9.6, at 4° C. overnight and blocked with PBS-0.5% BSA, pH 7.2 at room temperature for one hour.
  • Biotinylated FcRn prepared using biotin-X-NHS from Research Organics, Cleveland, Ohio and used at 1-2 ⁇ g/ml
  • PBS-0.5% BSA 0.05% polysorbate 20, pH 7.2
  • the IgG2 variant appears to have a much lower affinity for C1q than the E318A and K320A variants ( FIG. 2 ).
  • the results demonstrate that E318 and K320 do not constitute the core C1q binding sites for human IgG1.
  • the K322A substitution had a significant effect on both complement activity and C1q binding.
  • the K322A variant did not have CDC activity when tested in the above CDC assay and was more than a 100 fold lower than wild type C2B8 in binding to C1q ( FIG. 2 ).
  • K322 is the only residue of the proposed core C1q binding sites that appeared to have a significant effect on complement activation and C1q binding.
  • Variants constructed, K274A, N276A, Y278A, S324A, P329A, P331A, K334A, and T335A were assessed for their ability to bind C1q and also to activate complement. Many of these substitutions had little or no effect on C1q binding or complement activation.
  • the P329A and the P331A variants did not activate complement and had decreased binding to C1q.
  • the mutation P329A results in an antibody that does not activate complement and is more than a 100 fold lower in binding to C1q ( FIG. 3 ) when compared to wild type C2B8 ( FIG. 2 ).
  • Variants that did not bind to C1q and hence did not activate complement were examined for their ability to bind to the Fc receptors: Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIB, Fc ⁇ RIIIA and FcRn.
  • This particular study was performed using a humanized anti-IgE antibody, an IgG1 antibody with these mutations (see Example 1 above).
  • a further residue involved in binding human C1q was identified using the methods described in the present example.
  • the residue D270 was replaced with lysine and valine to generate variants D270K and D270V, respectively. These variants both showed decreased binding to human C1q ( FIG. 6 ) and were non-lytic ( FIG. 7 ).
  • the two variants bound the CD20 antigen normally and recruited ADCC.
  • K326, A327, E333 and K334 are potential sites for improving the efficacy of antibodies by way of the CDC pathway.
  • the aim of this study was to improve CDC activity of an antibody by increasing binding to C1q.
  • K326M, K326D, K326E and E333S were constructed with at least a two-fold increase in binding to C1q when compared to wild type.
  • Variant K326W displayed about a five-fold increase in binding to C1q.
  • Variants of the wild type C2B8 antibody were prepared as described above in Example 2.
  • the C1q binding ELISA, CDC assay, and CD20 binding potency assay in this example were performed as described in Example 2 above.
  • K326A, K326D, K326E, K326G, K326V, K326M and K326W were all bound to C1q with a better affinity than the wild type antibody.
  • K326W, K326M, K326D and K326E showed at least a two-fold increase in binding to C1q (Table 5).
  • K326W had the best affinity for C1q.
  • E333 was also substituted with other amino acid residues.
  • E333S, E333G, E333V, E333D, and E333Q all had increased binding to C1q when compared to the wild type ( FIG. 11 ).
  • the order of binding affinity for C1q was as follows: E333S>E333A>E333G>E333V>E333D>E333Q.
  • Substitutions with amino acid residues with small side chain volumes, i.e. serine, alanine and glycine resulted in variants with higher affinity for C1q in comparison to the other variants, E333V, E333D and E333Q, with larger side chain volumes.
  • the variant E333S had the highest affinity for C1q, showing a two-fold increase in binding when compared to the wild type. Without being bound to anyone theory, this indicates the effect on C1q binding at 333 may also be due in part to the polarity of the residue.
  • Double variants were also generated. As shown in FIGS. 12 and 13 , double variants K326M-E333S and K326A-E333A were at least three-fold better at binding human C1q than wild type C2B8 ( FIG. 12 ) and at least two-fold better at mediating CDC compared to wild type C2B8 ( FIG. 13 ). Additivity indicates these are independently acting variants.
  • IgG1 Variants Recombinant anti-IgE E27 having the light chain and heavy chain sequences in FIGS. 4A and 4B , respectively, was used as the parent antibody in the following experiments. This antibody binds the antigen IgE and has a non-A allotype IgG1 Fc region. By site directed mutagenesis (Kunkel et al., Proc. Natl. Acad.Sci.USA 82:488 (1985)), variants of the Fc region in the heavy chain of the above parent antibody were constructed. The heavy and light chain plasmids were co-transfected into an adenovirus transformed human embryonic kidney cell line as previously described (Werther et al, J. Immunol.
  • the media was changed to serum-free 24 hours after transfection and the secreted antibody was harvested after five days.
  • the antibodies were purified by Protein G SEPHAROSE® (Pharmacia), buffer exchanged and concentrated to 0.5 ml with PBS using a Centricon-30 (Amicon), and stored at 4° C. Concentration was determined by adsorption at 280 nm using extinction coefficients derived by amino acid composition analysis.
  • Fc ⁇ RIA was expressed as a GST fusion of His6 tagged extracellular domain in 293 cells and purified by Ni-NTA column chromatography.
  • Purified receptors were coated onto Nunc F96 maxisorb plates (cat no. 439545) at approximately 150 ng per well by adding 100 ⁇ L of receptor at 1.5 ⁇ g/mL in PBS and incubated for 24 hours at 4° C. Prior to assay, plates were washed 3 ⁇ with 250 ⁇ L of wash buffer (phosphate buffered saline pH 7.4 containing 0.5% TWEEN 20®) and blocked with 250 ⁇ L of assay buffer (50 mM tris buffered saline, 0.05% TWEEN 20®, 0.5% RIA grade bovine albumin (Sigma A7888), and 2 mM EDTA pH 7.4).
  • wash buffer phosphate buffered saline pH 7.4 containing 0.5% TWEEN 20®
  • assay buffer 50 mM tris buffered saline, 0.05% TWEEN 20®, 0.5% RIA grade bovine albumin (Sigma A7888), and 2 mM EDTA pH 7.4
  • E27 100 ⁇ L of E27 was added to the first four wells of the Fc ⁇ RIA subunit coated plated at a concentration of 10 ⁇ g/mL. 80 ⁇ L of assay buffer was added to the next four well followed by 20 ⁇ L of the 10 ⁇ g/mL E27 ⁇ gG to give a final concentration of 2 ⁇ g/mL. Plates were incubated at 25° C. for 2 hours on an orbital shaker.
  • HRP horse radish peroxidase conjugated protein G
  • BIORAD horse radish peroxidase conjugated protein G
  • HRP conjugates were incubated for 1.5 hours at 25° C. on an orbital shaker. Plates were washed ⁇ 5 with wash buffer to remove unbound HRP conjugate. Binding was detected by adding 100-L of substrate solution (0.4 mg/mL o-phenylenedaimine dihydrochloride, Sigma P6912, 6 mM H 2 O 2 in PBS) and incubating for 10 minutes at 25° C. Enzymatic reaction was stopped by the addition of 100 ⁇ L of 4.5 N H 2 SO 4 and colorimetric product was measured at 490 nm on a 96 well plate densitometer (Molecular Devices).
  • Binding of E27 variants at IgG concentration of 2 ⁇ g/mL was expressed as a ratio of wild type E27.
  • IgG binding Fc ⁇ RIA was detected by adding 100 ⁇ L FITC conjugated F(ab′) 2 fragment of goat anti-human IgG heavy chain specific. (Jackson lmmunoresearch) at 1:200. FITC conjugates were incubated with cells for 30 minutes on ice. Cells were washed ⁇ 3 with assay buffer to remove unbound FITC conjugate. Cells were stained with P.I. (SIGMA) at 2.5 ⁇ g/mL and analyzed by flow cytometry.
  • SIGMA P.I.
  • Binding of E27 variants at IgG concentration of 1.5 pg/mL was expressed as a ratio of wild type E27.
  • Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA binding ELISAs were performed as described in Example 1 above, with detection of the stable hexamer (consisting of three anti-IgE molecules and three IgE molecules).
  • FcRn Binding ELISA For measuring FcRn binding activity of IgG variants, ELISA plates were coated with 2 ⁇ g/ml streptavidin (Zymed, South San Francisco) in 50 mM carbonate buffer, pH 9.6, at 4° C. overnight and blocked with PBS-0.5% BSA, pH 7.2 at room temperature for one hour. Biotinylated FcRn (prepared using biotin-X-NHS from Research Organics, Cleveland, Ohio and used at 1-2 ⁇ g/ml) in PBS-0.5% BSA, 0.05% polysorbate 20, pH 7.2, was added to the plate and incubated for one hour.
  • IgG standard 1.6-100 ng/ml
  • PBS-0.5% BSA, 0.05% polysorbate 20, pH 6.0 Two fold serial dilutions of IgG standard (1.6-100 ng/ml) or variants in PBS-0.5% BSA, 0.05% polysorbate 20, pH 6.0, were added to the plate and incubated for two hours. Bound IgG was detected using peroxidase labeled goat F(ab′) 2 anti-human IgG F(ab′) 2 in the above pH 6.0 buffer (Jackson lmmunoResearch, West Grove, Pa.) followed by 3,3′,5,5′-tetramethyl benzidine (Kirgaard & Perry Laboratories) as the substrate. Plates were washed between steps with PBS-0.05% TWEEN 20® at either pH 7.2 or 6.0.
  • chromium 51-labeled target cells tumor cell lines were grown in tissue culture plates and harvested using sterile 10 mM EDTA in PBS. SK-BR-3 cells, a 3+HER2-overexpressing human breast cancer cell line, were used as targets in all assays. The detached cells were washed twice with cell culture medium. Cells (5 ⁇ 10 6 ) were labeled with 200 ⁇ Ci of chromium51 (New England Nuclear/DuPont) at 37° C. for one hour with occasional mixing. Labeled cells were washed three times with cell culture medium, then were resuspended to a concentration of 1 ⁇ 10 5 cells/mL.
  • Cells were used either without opsonization, or were opsonized prior to the assay by incubation with rhuMAb HER2 wildtype (HERCEPTIN®) or seven Fc mutants (G14, G18, G17, G36, G30, G31 and G34) at 100 ng/mL and 1.25 ng/mL in PBMC assay or 20 ng/mL and 1 ng/mL in NK assay.
  • rhuMAb HER2 wildtype HERCEPTIN®
  • Fc mutants G14, G18, G17, G36, G30, G31 and G34
  • Peripheral blood mononuclear cells were prepared by collecting blood on heparin from normal healthy donors and dilution with an equal volume of phosphate buffered saline (PBS). The blood was then layered over LYMPHOCYTE SEPARATION MEDIUM® (LSM: Organon Teknika) and centrifuged according to the manufacturer's instructions. Mononuclear cells were collected from the LSM-plasma interface and were washed three times with PBS. Effector cells were suspended in cell culture medium to a final concentration of 1 ⁇ 10 7 cells/mL.
  • PBS phosphate buffered saline
  • NK cells natural killer cells were isolated from PBMCs by negative selection using an NK cell isolation kit and a magnetic column (Miltenyi Biotech) according to the manufacturer's instructions. Isolated NK cells were collected, washed and resuspended in cell culture medium to a concentration of 2 ⁇ 10 6 cells/mL. The identity of the NK cells was confirmed by flow cytometric analysis.
  • Varying effector:target ratios were prepared by serially diluting the effector (either PBMC or NK) cells two-fold along the rows of a microtiter plate (100 ⁇ L final volume) in cell culture medium.
  • the concentration of effector cells ranged from 1.0 ⁇ 10 7 /mL to 2.0 ⁇ 10 4 /mL for PBMC and from 2.0 ⁇ 10 6 /mL to 3.9 ⁇ 10 3 /mL for NK.
  • 100 ⁇ L of chromium 51-labeled target cells (opsonized or nonoponsonized) at 1 ⁇ 10 5 cells/mL were added to each well of the plate.
  • a variety of antibody variants were generated which had FcR binding activity that differed from the parent antibody.
  • the FcR binding data for the variants generated is shown in Tables 6 and 7 below.
  • Variants with increased binding to FcRn generally had binding values ⁇ 1.30 as determined in this Example and those with reduced binding to FcRn generally had binding values ⁇ 0.70 as determined in this Example.
  • various non-alanine substitution variants were made, and the FcR binding activity of those variants is summarized in the following table.
  • This study includes a complete mapping of human IgG1 for human Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIlB, Fc ⁇ RIIIA, and FcRn.
  • Fc ⁇ RI and FcRn are high affinity receptors and monomeric IgG could be evaluated in the assays for these two receptors.
  • Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA are low affinity receptors and required use of an immune complex.
  • an ELISA-type assay was used for Fc ⁇ RIIA, Fc ⁇ RIIB, and Fc ⁇ RIIIA, in which pre-formed hexamers, consisting of three anti-IgE E27 and three IgE molecules were bound to the Fc ⁇ R and either anti-human IgG Fc-HRP or protein G-HRP used as detection reagent.
  • these hexamers could be linked into multimers by addition of human VEGF (using anti-VEGF IgE).
  • the hexameric complexes were used since these provided sufficient binding and required less IgG. Complexes formed using other antibody:antigen combinations are also possible reagents, as long as the antigen contains at least two identical binding sites per molecule for the antibody.
  • VEGF contains two binding sites per VEGF dimer for anti-VEGF A.4.6.1 (Kim et al., Growth Factors 7:53 (1992) and Kim et al. Nature 362:841 (1993)). VEGF:anti-VEGF multimers also bound to the low affinity Fc ⁇ RIIA and Fc ⁇ RIIIA ( FIGS. 16A and 16B ).
  • alanine variants were found. Some variants exhibited reduced binding to all Fc ⁇ R (G14, FIG. 17 ), while other variants showed reduced binding only to one Fc ⁇ R (G36, FIG. 17 ), improved binding only to one Fc ⁇ R (G15, G54, G55, FIG. 17 ), or simultaneous reduction to one Fc ⁇ R with improvement to another (G16, FIG. 17 ).
  • the IgG Fc variants used in this assay were generated by substituting the VHNL domains of anti-IgE E27 with those from anti-HER2 antibody; HERCEPTIN® (humAb4D5-8 in Table 1 of Carter et al PNAS ( USA ) 89:4285-4289 (1992)).
  • the pattern of ADCC exhibited by the variants correlated well with the pattern of binding to Fc ⁇ RIIIA ( FIGS. 20 and 21 ).
  • variant 36 S298(317)A also showed improvement in ADCC compared to wildtype HERCEPTIN® at 1.25 ng/ml ( FIG. 21 ).
  • allelic variants of several of the human Fc ⁇ R have been found in the human population. These allelic variant forms have been shown to exhibit differences in binding of human and murine IgG and a number of association studies have correlated clinical outcomes with the presence of specific allelic forms (reviewed in Lehrnbecher et al. Blood 94(12):4220-4232 (1999)). Several studies have investigated two forms of Fc ⁇ RIIA, R131 and H131, and their association with clinical outcomes (Hatta et al. Genes and Immunity 1:53-60 (1999); Yap et al. Lupus 8:305-310 (1999); and Lorenz et al. European J. Immunogenetics 22:397-401 (1995)).
  • the pattern of binding of the selected IgG1 variants to the relatively higher affinity Fc ⁇ RIIIA-V158 was the same as for the relatively lower affinity Fc ⁇ RIIIA-F158 (the F158 form was used in assaying all variants).
  • IgG1 variants which showed improved binding to the Fc ⁇ RIIIA-F158 form also showed improved binding to the Fc ⁇ RIIIA-V158 form though the improvement was not as pronounced.
  • Fc ⁇ RIIA-R131 used in assaying all variants
  • Fc ⁇ RIIA-H131 the binding pattern of the selected IgG1 variants did show some distinct differences.
  • S267(280)A, H268(281)A, and S267(280)A/H268(281)A exhibited improved binding to Fc ⁇ RIIA-R131, compared to native IgG1, but not to Fc ⁇ RIIA-H131.
  • S267(280)G showed improved binding to Fc ⁇ RIIA-R131 but reduced binding to Fc ⁇ RIIA-H131 (Table 10).

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US11/429,792 1999-01-15 2006-05-08 Polypeptide variants with altered effector function Abandoned US20060194290A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/429,792 US20060194290A1 (en) 1999-01-15 2006-05-08 Polypeptide variants with altered effector function

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US11602399P 1999-01-15 1999-01-15
US09/483,588 US6737056B1 (en) 1999-01-15 2000-01-14 Polypeptide variants with altered effector function
US10/757,863 US7416727B2 (en) 1999-01-15 2004-01-15 Polypeptide variants with altered effector function
US11/158,839 US7332581B2 (en) 1999-01-15 2005-06-22 Polypeptide variants with altered effector function
US11/429,792 US20060194290A1 (en) 1999-01-15 2006-05-08 Polypeptide variants with altered effector function

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US11/158,839 Division US7332581B2 (en) 1999-01-15 2005-06-22 Polypeptide variants with altered effector function

Publications (1)

Publication Number Publication Date
US20060194290A1 true US20060194290A1 (en) 2006-08-31

Family

ID=22364785

Family Applications (4)

Application Number Title Priority Date Filing Date
US11/429,792 Abandoned US20060194290A1 (en) 1999-01-15 2006-05-08 Polypeptide variants with altered effector function
US11/429,793 Expired - Lifetime US7371826B2 (en) 1999-01-15 2006-05-08 Polypeptide variants with altered effector function
US11/941,750 Expired - Fee Related US7790858B2 (en) 1999-01-15 2007-11-16 Polypeptide variants with altered effector function
US12/033,642 Expired - Fee Related US7785791B2 (en) 1999-01-15 2008-02-19 Polypeptide variants with altered effector function

Family Applications After (3)

Application Number Title Priority Date Filing Date
US11/429,793 Expired - Lifetime US7371826B2 (en) 1999-01-15 2006-05-08 Polypeptide variants with altered effector function
US11/941,750 Expired - Fee Related US7790858B2 (en) 1999-01-15 2007-11-16 Polypeptide variants with altered effector function
US12/033,642 Expired - Fee Related US7785791B2 (en) 1999-01-15 2008-02-19 Polypeptide variants with altered effector function

Country Status (16)

Country Link
US (4) US20060194290A1 (2)
EP (4) EP2364997A3 (2)
JP (4) JP2003512019A (2)
KR (5) KR20060067983A (2)
CN (2) CN1763097B (2)
AU (2) AU778683B2 (2)
BR (1) BR0008758A (2)
CA (1) CA2359067C (2)
ES (1) ES2694002T3 (2)
HU (2) HU230769B1 (2)
IL (5) IL144056A0 (2)
MX (2) MXPA01007170A (2)
NZ (1) NZ539776A (2)
PL (3) PL209392B1 (2)
WO (1) WO2000042072A2 (2)
ZA (1) ZA200105484B (2)

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040228856A1 (en) * 1999-01-15 2004-11-18 Genentech, Inc. Polypeptide variants with altered effector function
US20060067930A1 (en) * 2004-08-19 2006-03-30 Genentech, Inc. Polypeptide variants with altered effector function
US20060194291A1 (en) * 1999-01-15 2006-08-31 Genentech, Inc. Polypeptide variants with altered effector function
US20060275283A1 (en) * 2003-11-12 2006-12-07 Biogen Idec Ma Inc. Fcgamma receptor-binding polypeptide variants and methods related thereto
US20090136936A1 (en) * 2007-05-01 2009-05-28 George Georgiou Immunoglobulin fc libraries
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
US7820161B1 (en) 1999-05-07 2010-10-26 Biogen Idec, Inc. Treatment of autoimmune diseases
US20100330076A1 (en) * 2009-06-30 2010-12-30 George Georgiou Immunoglobulin fc polypeptides
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
US8163882B2 (en) 1999-01-15 2012-04-24 Genentech, Inc. Polypeptide variants with altered effector function
WO2014093396A1 (en) 2012-12-10 2014-06-19 Biogen Idec Ma Inc. Anti-blood dendritic cell antigen 2 antibodies and uses thereof
WO2014143739A2 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anti-alpha v beta 6 antibodies and uses thereof
WO2014144466A1 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anti-alpha v beta 6 antibodies and uses thereof
WO2014151680A1 (en) 2013-03-15 2014-09-25 Biogen Idec Ma Inc. Treatment and prevention of acute kidney injury using anti-alpha v beta 5 antibodies
US8969526B2 (en) 2011-03-29 2015-03-03 Roche Glycart Ag Antibody Fc variants
US9238878B2 (en) 2009-02-17 2016-01-19 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
WO2016075099A1 (en) 2014-11-10 2016-05-19 Medimmune Limited Binding molecules specific for cd73 and uses thereof
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
US9540438B2 (en) 2011-01-14 2017-01-10 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof
US9695233B2 (en) 2012-07-13 2017-07-04 Roche Glycart Ag Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases
WO2018022479A1 (en) 2016-07-25 2018-02-01 Biogen Ma Inc. Anti-hspa5 (grp78) antibodies and uses thereof
US10184001B2 (en) * 2014-11-26 2019-01-22 Adventist Health System/Sunbelt Inc. Effector-deficient anti-CD32a antibodies
EP3524626A1 (en) 2007-03-22 2019-08-14 Biogen MA Inc. Binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind cd154 and uses thereof
US10457737B2 (en) 2015-02-09 2019-10-29 Research Development Foundation Engineered immunoglobulin Fc polypeptides displaying improved complement activation
US10654916B2 (en) 2011-04-21 2020-05-19 The Regents Of The University Of California, A California Corporation Compositions and methods for the treatment of neuromyelitis optica
WO2020210358A1 (en) 2019-04-08 2020-10-15 Biogen Ma Inc. Anti-integrin antibodies and uses thereof
US11208632B2 (en) 2016-04-26 2021-12-28 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
US11447551B2 (en) 2018-12-28 2022-09-20 Sparx Bioscience Limited Binding molecules specific for claudin 18.2, compositions and methods thereof, for the treatment of cancer and other diseases
US12503503B2 (en) 2018-10-29 2025-12-23 Hoffmann-La Roche Inc. Bispecific anti-VEGF/ANG2 antibody formulation

Families Citing this family (1814)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
US6855493B2 (en) 2000-11-28 2005-02-15 Medimmune, Inc. Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment
US7083784B2 (en) 2000-12-12 2006-08-01 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
US7658921B2 (en) 2000-12-12 2010-02-09 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
US20030133939A1 (en) 2001-01-17 2003-07-17 Genecraft, Inc. Binding domain-immunoglobulin fusion proteins
US7754208B2 (en) 2001-01-17 2010-07-13 Trubion Pharmaceuticals, Inc. Binding domain-immunoglobulin fusion proteins
AU2002250293B2 (en) * 2001-03-09 2007-10-11 Arnason, Barry G. Mr Polymeric immunoglobulin fusion proteins that target low-affinity FCGammaReceptors
US20110045005A1 (en) 2001-10-19 2011-02-24 Craig Crowley Compositions and methods for the treatment of tumor of hematopoietic origin
CA2463879C (en) * 2001-10-25 2012-12-04 Genentech, Inc. Glycoprotein compositions
US20040002587A1 (en) * 2002-02-20 2004-01-01 Watkins Jeffry D. Fc region variants
US8188231B2 (en) 2002-09-27 2012-05-29 Xencor, Inc. Optimized FC variants
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US7662925B2 (en) 2002-03-01 2010-02-16 Xencor, Inc. Optimized Fc variants and methods for their generation
ATE483472T1 (de) 2002-05-30 2010-10-15 Macrogenics Inc Cd16a bindungsproteine und verwendung zur behandlung von immunkrankheiten
US7132100B2 (en) 2002-06-14 2006-11-07 Medimmune, Inc. Stabilized liquid anti-RSV antibody formulations
US8968730B2 (en) 2002-08-14 2015-03-03 Macrogenics Inc. FcγRIIB specific antibodies and methods of use thereof
DK1534335T4 (en) * 2002-08-14 2015-10-05 Macrogenics Inc FCGAMMARIIB-SPECIFIC ANTIBODIES AND PROCEDURES FOR USE THEREOF
US8946387B2 (en) 2002-08-14 2015-02-03 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
EP1553975B8 (en) 2002-09-27 2023-04-12 Xencor, Inc. Optimized fc variants and methods for their generation
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
US7365168B2 (en) 2002-10-15 2008-04-29 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
DK1562972T3 (da) 2002-10-15 2010-12-06 Facet Biotech Corp Modifikation af FcRn-bindingsaffiniteter eller serumhalveringstider for antistoffer ved mutagenese
US7361740B2 (en) 2002-10-15 2008-04-22 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
TWI335821B (en) 2002-12-16 2011-01-11 Genentech Inc Immunoglobulin variants and uses thereof
AU2011265460B2 (en) * 2003-01-09 2014-07-17 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
CA2512729C (en) * 2003-01-09 2014-09-16 Macrogenics, Inc. Identification and engineering of antibodies with variant fc regions and methods of using same
US7960512B2 (en) 2003-01-09 2011-06-14 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
CA2512974A1 (en) 2003-01-13 2004-07-29 Macrogenics, Inc. Soluble fc.gamma.r fusion proteins and methods of use thereof
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US20090010920A1 (en) 2003-03-03 2009-01-08 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRIIb
EP1613350B1 (en) 2003-04-09 2009-03-18 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor
JP4685764B2 (ja) * 2003-04-10 2011-05-18 アボット バイオセラピューティクス コーポレイション 変異誘発による抗体のＦｃＲｎ結合親和力又は血清半減期の改変
RU2337107C2 (ru) * 2003-05-02 2008-10-27 Ксенкор, Инк. ОПТИМИЗИРОВАННЫЕ Fc-ВАРИАНТЫ, ИМЕЮЩИЕ ИЗМЕНЕННОЕ СВЯЗЫВАНИЕ С FcγR, И СПОСОБЫ ИХ ПОЛУЧЕНИЯ
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
TWI353991B (en) 2003-05-06 2011-12-11 Syntonix Pharmaceuticals Inc Immunoglobulin chimeric monomer-dimer hybrids
AR044388A1 (es) 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
JP2007526220A (ja) 2003-06-05 2007-09-13 ジェネンテック・インコーポレーテッド Ｂ細胞疾患の併用療法
HRP20170342T1 (hr) 2003-07-24 2017-05-19 Innate Pharma S.A. Metode i sastavi za povećanje učinkovitosti terapijskih protutijela koristeći tvari koje potenciraju nk stanice
US20050106667A1 (en) 2003-08-01 2005-05-19 Genentech, Inc Binding polypeptides with restricted diversity sequences
AU2004266159A1 (en) 2003-08-22 2005-03-03 Biogen Idec Ma Inc. Improved antibodies having altered effector function and methods for making the same
US8101720B2 (en) * 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
WO2005037867A1 (en) 2003-10-15 2005-04-28 Pdl Biopharma, Inc. ALTERATION OF Fc-FUSION PROTEIN SERUM HALF-LIVES BY MUTAGENESIS OF POSITIONS 250, 314 AND/OR 428 OF THE HEAVY CHAIN CONSTANT REGION OF IG
GB0324368D0 (en) * 2003-10-17 2003-11-19 Univ Cambridge Tech Polypeptides including modified constant regions
US9296820B2 (en) 2003-11-05 2016-03-29 Roche Glycart Ag Polynucleotides encoding anti-CD20 antigen binding molecules with increased Fc receptor binding affinity and effector function
WO2005047327A2 (en) 2003-11-12 2005-05-26 Biogen Idec Ma Inc. NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO
JP2007511604A (ja) * 2003-11-18 2007-05-10 アイコニック セラピューティクス インコーポレイティッド キメラタンパク質の均質製剤
AU2004297616B2 (en) 2003-12-04 2008-12-18 Xencor, Inc. Methods of generating variant proteins with increased host string content and compositions thereof
KR101225299B1 (ko) 2003-12-10 2013-01-24 메다렉스, 인코포레이티드 인터페론 알파 항체 및 그의 용도
PL1691837T3 (pl) 2003-12-10 2012-11-30 Squibb & Sons Llc IP-10 przeciwciała i ich zastosowanie
SI1706424T1 (sl) 2004-01-12 2010-01-29 Applied Molecular Evolution Variante fc regij
AU2005214382B2 (en) 2004-02-19 2011-08-04 Genentech, Inc. CDR-repaired antibodies
EP1737890A2 (en) 2004-03-24 2007-01-03 Xencor, Inc. Immunoglobulin variants outside the fc region
PT1737891E (pt) * 2004-04-13 2013-04-16 Hoffmann La Roche Anticorpos anti p-selectina
CA2565874C (en) 2004-05-10 2017-10-03 Macrogenics, Inc. Humanized fc.gamma.riib-specific antibodies and methods of use thereof
KR100545720B1 (ko) * 2004-05-31 2006-01-24 메덱스젠 주식회사 당화된 면역글로불린 및 이를 포함하는 면역접합체
AU2005249566B2 (en) 2004-06-04 2010-11-11 Genentech, Inc. Method for treating multiple sclerosis
US7662381B2 (en) 2004-06-21 2010-02-16 Medarex, Inc. Interferon alpha receptor 1 antibodies and their uses
CN101189028B (zh) * 2004-07-12 2013-05-29 马克罗基因公司 具有变异Fc区的抗体的鉴定和工程化以及使用方法
EP2471813B1 (en) 2004-07-15 2014-12-31 Xencor, Inc. Optimized Fc variants
US20150010550A1 (en) 2004-07-15 2015-01-08 Xencor, Inc. OPTIMIZED Fc VARIANTS
AU2005287406B2 (en) 2004-07-26 2011-08-18 Biogen Ma Inc. Anti-CD154 antibodies
AU2005274905B2 (en) 2004-08-04 2010-12-23 Mentrik Biotech, Llc Variant Fc regions
EP1778726A4 (en) * 2004-08-16 2009-03-18 Medimmune Inc INTEGRIN ANTAGONISTS WITH IMPROVED ANTIBODY-DEPENDENT CELL-ASSAYED CYTOTOXICITY ACTIVITY
BRPI0516297A (pt) 2004-10-05 2008-09-02 Genentech Inc métodos de tratamento de vasculite e artigos de fabricação
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
AU2005335714B2 (en) * 2004-11-10 2012-07-26 Macrogenics, Inc. Engineering Fc antibody regions to confer effector function
AU2005304624B2 (en) 2004-11-12 2010-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US20070135620A1 (en) * 2004-11-12 2007-06-14 Xencor, Inc. Fc variants with altered binding to FcRn
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
CN101120021A (zh) * 2004-12-31 2008-02-06 基因技术公司 结合br3的多肽及其用途
CN102580084B (zh) 2005-01-21 2016-11-23 健泰科生物技术公司 Her抗体的固定剂量给药
US8029783B2 (en) * 2005-02-02 2011-10-04 Genentech, Inc. DR5 antibodies and articles of manufacture containing same
US8444973B2 (en) 2005-02-15 2013-05-21 Duke University Anti-CD19 antibodies and uses in B cell disorders
HUE025945T2 (en) 2005-02-15 2016-07-28 Univ Duke Anti-CD19 antibodies and their applications in oncology
EP1850874B1 (en) 2005-02-23 2013-10-16 Genentech, Inc. Extending time to disease progression or survival in ovarian cancer patients using pertuzumab
JP5225069B2 (ja) 2005-03-23 2013-07-03 ゲンマブ エー／エス 多発性骨髄腫の治療のためのｃｄ３８に対する抗体
US20110123440A1 (en) * 2005-03-29 2011-05-26 Genevieve Hansen Altered Antibody FC Regions and Uses Thereof
WO2006105338A2 (en) * 2005-03-31 2006-10-05 Xencor, Inc. Fc VARIANTS WITH OPTIMIZED PROPERTIES
US11254748B2 (en) 2005-04-15 2022-02-22 Macrogenics, Inc. Covalent diabodies and uses thereof
US9284375B2 (en) 2005-04-15 2016-03-15 Macrogenics, Inc. Covalent diabodies and uses thereof
US9963510B2 (en) 2005-04-15 2018-05-08 Macrogenics, Inc. Covalent diabodies and uses thereof
ES2971647T3 (es) 2005-04-15 2024-06-06 Macrogenics Inc Diacuerpos covalentes y usos de los mismos
JO3058B1 (ar) 2005-04-29 2017-03-15 Applied Molecular Evolution Inc الاجسام المضادة لمضادات -اي ال-6,تركيباتها طرقها واستعمالاتها
EP1885755A4 (en) 2005-05-05 2009-07-29 Univ Duke CD19 ANTIBODY THERAPY FOR AUTOIMMUNE DISEASES
DK2439273T3 (da) 2005-05-09 2019-06-03 Ono Pharmaceutical Co Humane monoklonale antistoffer til programmeret død-1(pd-1) og fremgangsmåder til behandling af cancer ved anvendelse af anti-pd-1- antistoffer alene eller i kombination med andre immunterapeutika
ZA200709956B (en) 2005-05-20 2009-02-25 Genentech Inc Pretreatment of a biological sample from an autoimmune disease subject
KR20080025174A (ko) 2005-06-23 2008-03-19 메디뮨 인코포레이티드 응집 및 단편화 프로파일이 최적화된 항체 제제
SI2452694T1 (sl) 2005-06-30 2019-05-31 Janssen Biotech, Inc. Protitelesa proti-IL-23, sestavki in postopki uporabe
PT1907424E (pt) 2005-07-01 2015-10-09 Squibb & Sons Llc Anticorpos monoclonais humanos para o ligando 1 de morte programada (pd-l1)
WO2007008943A2 (en) 2005-07-08 2007-01-18 Xencor, Inc. Optimized anti-ep-cam antibodies
WO2007009469A2 (en) * 2005-07-21 2007-01-25 Genmab A/S Potency assays for antibody drug substance binding to an fc receptor
RU2423381C2 (ru) 2005-07-25 2011-07-10 Трабьон Фармасьютикалз, Инк. Снижение количества в-клеток с использованием cd37-специфических и cd20-специфических связывающих молекул
RU2421242C2 (ru) 2005-07-25 2011-06-20 Трабьон Фармасьютикалз, Инк. Применение однократной дозы cd20-специфических связывающих молекул
PL2573114T3 (pl) 2005-08-10 2016-10-31 Identyfikacja i inżynieria przeciwciał z wariantami regionów FC oraz sposoby ich stosowania
AU2006290433B2 (en) 2005-08-26 2012-06-07 Roche Glycart Ag Modified antigen binding molecules with altered cell signaling activity
WO2007041635A2 (en) * 2005-10-03 2007-04-12 Xencor, Inc. Fc variants with optimized fc receptor binding properties
WO2007044616A2 (en) 2005-10-06 2007-04-19 Xencor, Inc. Optimized anti-cd30 antibodies
WO2007045477A2 (en) 2005-10-21 2007-04-26 Novartis Ag Human antibodies against il-13 and therapeutic uses
SG10201804008UA (en) 2005-11-04 2018-06-28 Genentech Inc Use of complement pathway inhibitors to treat ocular diseases
ES2577292T3 (es) 2005-11-07 2016-07-14 Genentech, Inc. Polipéptidos de unión con secuencias hipervariables de VH/VL diversificadas y consenso
US20080286819A1 (en) 2005-11-07 2008-11-20 Ravetch Jeffrey V Reagents, Methods and Systems for Selecting a Cytotoxic Antibody or Variant Thereof
MY149159A (en) 2005-11-15 2013-07-31 Hoffmann La Roche Method for treating joint damage
ES2618543T3 (es) 2005-11-23 2017-06-21 Genentech, Inc. Métodos y composiciones relacionados con ensayos de linfocitos B
CA2631327C (en) 2005-12-02 2015-10-13 Genentech, Inc. Her2 binding polypeptides and uses thereof
BRPI0619118A2 (pt) 2005-12-02 2011-09-13 Genentech Inc composições e métodos para o tratamento de doenças e desordens associadas com a sinalização de citocina
US8383118B2 (en) 2005-12-08 2013-02-26 Medarex, Inc. Human monoclonal antibodies to fucosyl-GM1 and methods for using anti-fucosyl-GM1
AU2006326867A1 (en) 2005-12-20 2007-06-28 Cephalon Australia Pty Ltd Chimeric antibodies with part New World primate binding regions
HUE034269T2 (en) 2005-12-29 2018-02-28 Janssen Biotech Inc Human anti-IL-23 antibodies, preparations, methods and applications
BRPI0706840A2 (pt) 2006-01-05 2011-04-05 Genentech Inc anticorpos anti- ephb4 isolado polinucleotìdeo, vetor, célula hospedeira, método para produção de um anticorpo anti ephb4, método para produção de um imunoconjugado anti ephb4, método para a detecção de ephb4, método para diagnosticar um distúrbio composição, método para inibir a angiogênese, método para tratar um cáncer, tumor e/ou distúrbio da proliferação celular e uso de um anticorpo
SI1976884T1 (sl) 2006-01-20 2013-04-30 Genetech, Inc. Anti-efrinB2 protitelesa in postopki uporabe le teh
US7846439B2 (en) 2006-02-01 2010-12-07 Cephalon Australia Pty Ltd Domain antibody construct
EP1999148B8 (en) 2006-03-06 2014-03-05 Medlmmune, LLC Humanized anti-cd22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease
AR059851A1 (es) 2006-03-16 2008-04-30 Genentech Inc Anticuerpos de la egfl7 y metodos de uso
NZ615012A (en) 2006-03-21 2015-11-27 Genentech Inc Combinatorial therapy involving alpha5beta1 antagonists
CN104761637B (zh) 2006-03-31 2021-10-15 中外制药株式会社 调控抗体血液动力学的方法
EP2009101B1 (en) 2006-03-31 2017-10-25 Chugai Seiyaku Kabushiki Kaisha Antibody modification method for purifying bispecific antibody
EP2011870A4 (en) * 2006-04-14 2010-09-15 Medical & Biol Lab Co Ltd MUTANT POLYPEPTIDE WITH EFFECTOR FUNCTION
EP2032606B1 (en) 2006-05-30 2013-11-27 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
NZ572177A (en) 2006-06-06 2012-02-24 Genentech Inc Anti-dll4 antibodies and methods using same
NZ573646A (en) 2006-06-12 2012-04-27 Wyeth Llc Single-chain multivalent binding proteins with effector function
ES2599319T3 (es) 2006-06-26 2017-02-01 Macrogenics, Inc. Anticuerpos específicos de Fc RIIB y métodos de uso de éstos
WO2008002933A2 (en) 2006-06-26 2008-01-03 Macrogenics, Inc. Combination of fcgammariib antibodies and cd20-specific antibodies and methods of use thereof
EP2046833B9 (en) 2006-07-14 2014-02-19 AC Immune S.A. Humanized antibody against amyloid beta
JP2009543579A (ja) 2006-07-19 2009-12-10 ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア 抗炎症反応のための標的としてのＷＳＸ−１／ｐ２８
PL2383297T3 (pl) 2006-08-14 2013-06-28 Xencor Inc Zoptymalizowane przeciwciała ukierunkowane na CD19
CA2662350A1 (en) 2006-09-05 2008-03-13 Medarex, Inc. Antibodies to bone morphogenic proteins and receptors therefor and methods for their use
RU2495882C2 (ru) 2006-09-08 2013-10-20 Медиммун, Ллк. Гуманизированные антитела к cd19 и их применение для лечения онкологического, связанного с трансплантацией и аутоиммунного заболевания
ES2372217T3 (es) 2006-09-12 2012-01-17 Genentech, Inc. Procedimientos y composiciones para el diagnóstico y tratamiento del cáncer de pulmón utilizando el gen de pdgfra, kit o kdr como marcador genético.
WO2008032833A1 (en) 2006-09-14 2008-03-20 Medical & Biological Laboratories Co., Ltd. Antibody having enhanced adcc activity and method for production thereof
WO2008036688A2 (en) 2006-09-18 2008-03-27 Xencor, Inc. Optimized antibodies that target hm1.24
MX2009003306A (es) 2006-10-02 2009-04-23 Medarex Inc Anticuerpos humanos que se unen a cxcr4 y sus usos.
UA94484C2 (uk) * 2006-10-12 2011-05-10 Дженентек, Інк. Антитіла до лімфотоксину-альфа
AU2007313300A1 (en) * 2006-10-16 2008-04-24 Medimmune, Llc. Molecules with reduced half-lives, compositions and uses thereof
AU2007319605B2 (en) 2006-10-19 2011-02-17 Csl Limited Anti-IL-13R alpha 1 antibodies and their uses thereof
PL2829551T3 (pl) 2006-10-19 2018-04-30 Csl Limited Antagonisty przeciwciała o wysokim powinowactwie wobec receptora alfa 1 interleukiny-13
BRPI0717638A2 (pt) 2006-10-27 2013-11-12 Genentech Inc Anticorpors e imunoconjugados e usos para os mesmos
US8618248B2 (en) 2006-10-31 2013-12-31 President And Fellows Of Harvard College Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides
TW201716437A (zh) 2006-11-02 2017-05-16 建南德克公司 人類化之抗-因子ｄ抗體及其用途
EP2097447A4 (en) 2006-11-15 2010-12-29 Medarex Inc HUMAN MONOCLONAL ANTIBODIES AGAINST BTLA AND METHODS OF USE
DK2102239T3 (da) 2006-11-30 2012-05-29 Res Dev Foundation Forbedrede immunoglobulin-biblioteker
US8481683B2 (en) 2006-12-01 2013-07-09 Medarex, Inc. Human antibodies that bind CD22 and uses thereof
US20080127996A1 (en) * 2006-12-04 2008-06-05 Weinhold Dennis G Method and apparatus to remediate an acid and/or liquid spill
US8652466B2 (en) 2006-12-08 2014-02-18 Macrogenics, Inc. Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for FcγRactivating and FcγRinhibiting
CL2007003622A1 (es) 2006-12-13 2009-08-07 Medarex Inc Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales.
MX2009006277A (es) 2006-12-14 2009-07-24 Medarex Inc Anticuerpos humanos que se enlazan a cd70 y usos de los mismos.
HUE029445T2 (en) 2006-12-19 2017-02-28 Genentech Inc VEGF-specific antagonists for adjuvant and neoadjuvant therapy and treatment of early-stage tumors
AU2008208288B2 (en) 2007-01-24 2014-04-03 Kyowa Kirin Co., Ltd. Genetically recombinant antibody composition having enhanced effector activity
US20110236374A1 (en) 2007-01-24 2011-09-29 Kyowa Hakko Kirin Co., Ltd. Genetically recombinant antibody composition capable of binding specifically to ganglioside gm2
MX2009008430A (es) 2007-02-09 2009-10-28 Genentech Inc Anticuerpos anti-robo4 y sus usos.
SI2132573T1 (sl) 2007-03-02 2014-07-31 Genentech, Inc. Napovedovanje odziva na inhibitor dimerizacije HER na osnovi nizke ekspresije HER3
PL3199180T3 (pl) 2007-03-08 2022-08-08 Humanigen, Inc. Przeciwciała przeciwko epha3 do leczenia guzów litych
WO2008118324A2 (en) 2007-03-26 2008-10-02 Macrogenics, Inc. Composition and method of treating cancer with an anti-uroplakin ib antibody
EP2599791A1 (en) 2007-04-27 2013-06-05 Genentech, Inc. Potent, stable and non-immunosuppressive anti-CD4 antibodies
AU2008247382B2 (en) 2007-05-07 2014-06-05 Medimmune, Llc Anti-ICOS antibodies and their use in treatment of oncology, transplantation and autoimmune disease
WO2008141197A1 (en) * 2007-05-10 2008-11-20 Sea Lane Biotechnologies, Llc Chain reaction creating oligomers from repeat units of binding molecules
JP2010526868A (ja) 2007-05-14 2010-08-05 ノビミューン エスアー 改変されたエフェクター機能を有するＦｃ受容体結合ポリペプチド
EP2176298B1 (en) 2007-05-30 2017-11-15 Xencor, Inc. Methods and compositions for inhibiting cd32b expressing cells
JP6071165B2 (ja) * 2007-05-31 2017-02-01 ゲンマブ エー／エス 安定なＩｇＧ４抗体
EP1997830A1 (en) 2007-06-01 2008-12-03 AIMM Therapeutics B.V. RSV specific binding molecules and means for producing them
PE20090321A1 (es) 2007-06-04 2009-04-20 Genentech Inc Anticuerpos anti-notch1 nrr, metodo de preparacion y composicion farmaceutica
PL2171090T3 (pl) 2007-06-08 2013-09-30 Genentech Inc Markery ekspresji genów odporności guza na leczenie hamujące HER2
US8613923B2 (en) 2007-06-12 2013-12-24 Ac Immune S.A. Monoclonal antibody
US8048420B2 (en) 2007-06-12 2011-11-01 Ac Immune S.A. Monoclonal antibody
ES2529174T3 (es) * 2007-06-12 2015-02-17 Ac Immune S.A. Anticuerpos humanizados para amiloide beta
EP2158221B1 (en) 2007-06-21 2018-08-29 MacroGenics, Inc. Covalent diabodies and uses thereof
CN101827610A (zh) * 2007-06-29 2010-09-08 森托科尔奥索生物科技公司 抗mcp-1抗体、组合物、方法和用途
KR102055873B1 (ko) 2007-07-09 2019-12-13 제넨테크, 인크. 폴리펩티드의 재조합 생산 동안의 디술피드 결합 환원의 방지
EP2078091A4 (en) * 2007-07-10 2010-09-01 Medimmune Llc CRYSTALS AND STRUCTURE OF THE VARIANT OF IGG FC HUMAN
EP2176295B1 (en) 2007-07-16 2014-11-19 Genentech, Inc. Humanized anti-cd79b antibodies and immunoconjugates and methods of use
PE20090943A1 (es) 2007-07-16 2009-08-05 Genentech Inc Anticuerpos anti-cd79b e inmunoconjugados
KR20100058509A (ko) 2007-07-31 2010-06-03 메디뮨 엘엘씨 다중특이적 에피토프 결합 단백질 및 이의 용도
JP5607530B2 (ja) 2007-09-04 2014-10-15 コンピュゲン エルティーディー． ポリペプチド並びにポリヌクレオチド、並びに薬剤および生物製剤生産のための薬剤標的としてのその利用
KR101680906B1 (ko) 2007-09-26 2016-11-30 추가이 세이야쿠 가부시키가이샤 항체 정상영역 개변체
ES2595638T3 (es) 2007-09-26 2017-01-02 Chugai Seiyaku Kabushiki Kaisha Método para modificar el punto isoeléctrico de un anticuerpo mediante la sustitución de aminoácidos en una CDR
AU2008311367B2 (en) 2007-10-05 2014-11-13 Ac Immune S.A. Use of anti-amyloid beta antibody in ocular diseases
BRPI0818623A2 (pt) * 2007-10-05 2017-05-23 Ac Immune Sa composição farmacêutica, e, métodos para reduzir a carga da placa na camada de célula de gânglio retinal de um animal, para reduzir a quantidade de placas na camada de célula de gânglio retinal de um animal, para diminuir a quantidade total de amilóide-beta solúvel na camada de célula de gânglio retinal de um animal, para prevenir, tratar e/ou aliviar os efeitos de uma doença ocular associada com anormalidades patológicas/mudanças no tecido do sistema visual, para monitorar doença ocular residual mínima associada com anormalidades patológicas/mudanças nos tecidos do sistema visual, para predizer responsividade de um paciente, e para reter ou diminuir a pressão ocular nos olhos de um animal
TWI489993B (zh) 2007-10-12 2015-07-01 Novartis Ag 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法
HUE030134T2 (en) 2007-10-16 2017-04-28 Zymogenetics Inc Combination of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and anti-CD20 agents for the treatment of autoimmune diseases
JP5620106B2 (ja) 2007-10-24 2014-11-05 株式会社糖鎖工学研究所 増強されたエフェクター機能を有するポリペプチド
BRPI0820327A2 (pt) 2007-11-02 2020-10-06 Novartis Ag moléculas e métodos para modulação de proteína relacionada ao receptor de lipoproteína de baixa densidade 6 (lrp6)
KR101867606B1 (ko) 2007-11-07 2018-06-18 제넨테크, 인크. 미생물 질환의 치료를 위한 조성물 및 방법
TWI468417B (zh) 2007-11-30 2015-01-11 Genentech Inc 抗－ｖｅｇｆ抗體
AU2008337517B2 (en) 2007-12-14 2014-06-26 Novo Nordisk A/S Antibodies against human NKG2D and uses thereof
US8795667B2 (en) 2007-12-19 2014-08-05 Macrogenics, Inc. Compositions for the prevention and treatment of smallpox
KR101759457B1 (ko) 2007-12-21 2017-07-31 메디뮨 리미티드 인터루킨-4 수용체 알파(ＩＬ-4Ｒα)에 대한 결합 구성원-173
HRP20150279T1 (hr) 2007-12-26 2015-05-08 Xencor, Inc. Fc inaäśice s promijenjenim vezanjem na fcrn
EP2077281A1 (en) 2008-01-02 2009-07-08 Bergen Teknologioverforing AS Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
US7914785B2 (en) 2008-01-02 2011-03-29 Bergen Teknologieverforing As B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
BRPI0907046A2 (pt) 2008-01-18 2015-07-28 Medimmune Llc Anticorpo de cisteína engenheirada, ácido nucleico isolado, vetor, célula hospedeira, conjugado de anticorpo, composição farmacêutica, métodos de detecção de câncer, doenças ou distúrbios autoimunes, inflamatórios ou infecciosos em um indivíduo e de inibição de proliferação de uma célula alvo
TWI472339B (zh) 2008-01-30 2015-02-11 Genentech Inc 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物
KR101607346B1 (ko) 2008-01-31 2016-03-29 제넨테크, 인크. 항-ｃｄ７９ｂ 항체 및 면역접합체 및 사용 방법
EP2650017A3 (en) 2008-02-05 2014-01-22 Bristol-Myers Squibb Company Alpha 5 - beta 1 antibodies and their uses
KR20160070165A (ko) 2008-02-08 2016-06-17 메디뮨 엘엘씨 Ｆｃ 리간드 친화성이 감소된 항-ＩＦＮＡＲ１ 항체
US12492253B1 (en) 2008-02-25 2025-12-09 Xencor, Inc. Anti-human C5 antibodies
BRPI0906261A2 (pt) * 2008-03-31 2015-07-07 Genentech Inc "métodos de diagnóstico de um subtipo de asma em uma amostra de paciente, usos de um agente terapêutico e kits de diagnóstico de um subtipo de asma em uma amostra de paciente"
WO2009123894A2 (en) 2008-04-02 2009-10-08 Macrogenics, Inc. Her2/neu-specific antibodies and methods of using same
ES2589912T3 (es) 2008-04-02 2016-11-17 Macrogenics, Inc. Anticuerpos específicos para el complejo BCR y procedimientos de uso de los mismos
KR102057826B1 (ko) 2008-04-11 2019-12-20 추가이 세이야쿠 가부시키가이샤 복수 분자의 항원에 반복 결합하는 항원 결합 분자
CR20170001A (es) 2008-04-28 2017-08-10 Genentech Inc Anticuerpos anti factor d humanizados
SG190572A1 (en) * 2008-04-29 2013-06-28 Abbott Lab Dual variable domain immunoglobulins and uses thereof
CA2726087A1 (en) 2008-06-03 2009-12-10 Tariq Ghayur Dual variable domain immunoglobulins and uses thereof
TW201006485A (en) 2008-06-03 2010-02-16 Abbott Lab Dual variable domain immunoglobulins and uses thereof
US20110081347A1 (en) 2008-06-04 2011-04-07 Macrogenics, Inc. Antibodies with Altered Binding to FcRn and Methods of Using Same
CN102149825B (zh) 2008-07-08 2015-07-22 Abbvie公司 前列腺素e2双重可变结构域免疫球蛋白及其用途
WO2010009129A2 (en) * 2008-07-15 2010-01-21 Genentech, Inc. Methods of treating autoimmune diseases using cd4 antibodies
PY09026846A (es) 2008-08-05 2015-09-01 Novartis Ag Composiciones y métodos para anticuerpos que se dirigen a la proteína de complemento c5
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
AU2009294415B2 (en) 2008-09-19 2015-09-24 Medimmune Llc Antibodies directed to DLL4 and uses thereof
JP5913980B2 (ja) * 2008-10-14 2016-05-11 ジェネンテック， インコーポレイテッド 免疫グロブリン変異体及びその用途
US8298533B2 (en) 2008-11-07 2012-10-30 Medimmune Limited Antibodies to IL-1R1
JP5933975B2 (ja) 2008-11-12 2016-06-15 メディミューン，エルエルシー 抗体製剤
DK2361085T4 (en) 2008-11-22 2018-10-08 Hoffmann La Roche USE OF ANTI-VEGF ANTIBODY IN COMBINATION WITH CHEMOTHERY TO TREAT CANCER CANCER
US20110311450A1 (en) 2008-12-08 2011-12-22 Zurit Levine Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics
WO2010068722A1 (en) 2008-12-12 2010-06-17 Medimmune, Llc Crystals and structure of a human igg fc variant with enhanced fcrn binding
DK2786762T3 (da) 2008-12-19 2019-05-06 Macrogenics Inc Kovalente diabodies og anvendelser deraf
CA2748158A1 (en) 2008-12-23 2010-07-01 Astrazeneca Ab Targeted binding agents directed to .alpha.5.beta.1 and uses thereof
JP2012514458A (ja) 2008-12-31 2012-06-28 バイオジェン・アイデック・エムエイ・インコーポレイテッド 抗リンホトキシン抗体
CN102421800A (zh) 2009-02-23 2012-04-18 格兰马克药品股份有限公司 结合cd19的人源化抗体及其用途
CN102341412B (zh) 2009-03-05 2018-01-05 梅达雷克斯有限责任公司 特异于cadm1 的全人抗体
AU2010221159B2 (en) 2009-03-06 2015-11-26 Humanigen, Inc. Treatment of leukemias and chronic myeloproliferative diseases with antibodies to EphA3
EP2433967A3 (en) 2009-03-16 2013-05-01 Cephalon Australia Pty Ltd Humanised antibodies with anti-tumour activity
MY152068A (en) 2009-03-20 2014-08-15 Genentech Inc Bispecific anti-her antibodies
EP2233500A1 (en) 2009-03-20 2010-09-29 LFB Biotechnologies Optimized Fc variants
JP5739865B2 (ja) * 2009-03-24 2015-06-24 バイエル・ヘルスケア・エルエルシー 第ｖｉｉｉ因子変異体および使用の方法
NZ594343A (en) 2009-03-25 2013-10-25 Genentech Inc Novel anti-alpha5beta1 antibodies and uses thereof
MA33208B1 (fr) 2009-03-25 2012-04-02 Genentech Inc Anticorps anti-fgfr3 et procédés d'utilisation de ceux-ci
ES2363358B1 (es) 2009-04-03 2012-06-21 FUNDACIÓ INSTITUT DE RECERCA HOSPITAL UNIVERSITARI VALL D'HEBRON (Titular al Agentes terapéuticos para el tratamiento de enfermedades asociadas con una proliferación celular indeseable.
SG175077A1 (en) 2009-04-07 2011-11-28 Roche Glycart Ag Trivalent, bispecific antibodies
DK2421898T3 (en) 2009-04-20 2016-05-30 Oxford Biotherapeutics Ltd Cadherin-17 SPECIFIC ANTIBODIES
US9062116B2 (en) 2009-04-23 2015-06-23 Infinity Pharmaceuticals, Inc. Anti-fatty acid amide hydrolase-2 antibodies and uses thereof
JP2012524524A (ja) 2009-04-27 2012-10-18 ノバルティス アーゲー ＩＬ−１２レセプターβ１サブユニットに特異的な治療用抗体の組成物および使用方法
PE20120532A1 (es) 2009-04-27 2012-05-18 Novartis Ag ANTICUERPOS ANTI-ActRIIB
US20110008766A1 (en) * 2009-05-01 2011-01-13 Abbott Laboratories Dual Variable Domain Immunoglobulins and Uses Thereof
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
EP3431501A1 (en) 2009-06-18 2019-01-23 Pfizer Inc Anti notch-1 antibodies
EP2711018A1 (en) 2009-06-22 2014-03-26 MedImmune, LLC Engineered Fc regions for site-specific conjugation
AU2010273585B2 (en) 2009-07-13 2015-04-23 Genentech, Inc. Diagnostic methods and compositions for treatment of cancer
TW201106972A (en) 2009-07-27 2011-03-01 Genentech Inc Combination treatments
NZ597531A (en) 2009-07-31 2014-05-30 Genentech Inc Inhibition of tumor metastasis using bv8- or g-csf-antagonists
BR112012007875A2 (pt) 2009-07-31 2016-11-22 Medarex Inc anticorpos totalmente humanos para btla
HRP20200768T4 (hr) 2009-08-11 2025-03-28 F. Hoffmann - La Roche Ag Proizvodnja proteina u mediju za uzgoj stanica bez glutamina
EP2464744A1 (en) 2009-08-14 2012-06-20 F. Hoffmann-La Roche AG Biological markers for monitoring patient response to vegf antagonists
NZ598131A (en) 2009-08-15 2014-08-29 Genentech Inc Anti-angiogenesis therapy for the treatment of previously treated breast cancer
WO2011021146A1 (en) 2009-08-20 2011-02-24 Pfizer Inc. Osteopontin antibodies
GB0914691D0 (en) * 2009-08-21 2009-09-30 Lonza Biologics Plc Immunoglobulin variants
CA2771999A1 (en) 2009-08-24 2011-03-10 Amunix Operating Inc. Coagulation factor vii compositions and methods of making and using same
WO2011028952A1 (en) 2009-09-02 2011-03-10 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
CA2772715C (en) 2009-09-02 2019-03-26 Genentech, Inc. Mutant smoothened and methods of using the same
JP5996429B2 (ja) 2009-09-03 2016-09-21 ジェネンテック， インコーポレイテッド 関節リウマチの治療、診断及びモニターするための方法
WO2011029823A1 (en) 2009-09-09 2011-03-17 Novartis Ag Monoclonal antibody reactive with cd63 when expressed at the surface of degranulated mast cells
RU2012114094A (ru) 2009-09-11 2013-10-20 Дженентек, Инк. Способ идентификации пациента с увеличенной вероятностью ответа на противораковый агент
AU2010297344A1 (en) 2009-09-17 2012-02-23 F. Hoffmann-La Roche Ag Methods and compositions for diagnostics use in cancer patients
US8568726B2 (en) 2009-10-06 2013-10-29 Medimmune Limited RSV specific binding molecule
JP5898082B2 (ja) 2009-10-07 2016-04-06 マクロジェニクス，インコーポレーテッド フコシル化程度の変更により改良されたエフェクター機能を示すＦｃ領域含有ポリペプチドおよびその使用法
EP2470569A1 (en) 2009-10-13 2012-07-04 Oxford Biotherapeutics Ltd. Antibodies against epha10
CA2777068C (en) 2009-10-14 2020-05-26 Humanigen, Inc. Antibodies to epha3
BR112012008833A2 (pt) * 2009-10-15 2015-09-08 Abbott Lab imunoglobulinas de dominio variavel duplo e usos das mesmas
RU2559533C2 (ru) 2009-10-22 2015-08-10 Дженентек, Инк. Антитела против гепсина и способы их применения
SG10201407757XA (en) 2009-10-23 2015-01-29 Millennium Pharm Inc Anti-gcc antibody molecules and related compositions and methods
WO2011056502A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Bone morphogenetic protein receptor type ii compositions and methods of use
WO2011056494A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations
WO2011056497A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Activin receptor type iib compositions and methods of use
UY32979A (es) 2009-10-28 2011-02-28 Abbott Lab Inmunoglobulinas con dominio variable dual y usos de las mismas
MX341084B (es) 2009-11-02 2016-08-05 Univ Washington Composiciones de nucleasas terapéuticas y métodos.
ES2784123T3 (es) 2009-11-04 2020-09-22 Merck Sharp & Dohme Anticuerpo anti TSLP genomodificado
CA2778552A1 (en) 2009-11-05 2011-05-12 Cephalon Australia Pty Ltd Treatment of cancer involving mutated kras or braf genes
EP2496601B1 (en) 2009-11-05 2017-06-07 F. Hoffmann-La Roche AG Methods and composition for secretion of heterologous polypeptides
WO2011060015A1 (en) 2009-11-11 2011-05-19 Genentech, Inc. Methods and compositions for detecting target proteins
PL2504364T3 (pl) 2009-11-24 2017-12-29 Medimmune Limited Ukierunkowane środki wiążące przeciwko B7-H1
US8961967B2 (en) * 2009-11-30 2015-02-24 Janssen Biotech, Inc. Antibody Fc mutants with ablated effector functions
EP2507265B1 (en) 2009-12-01 2016-05-11 Compugen Ltd. Antibody specific for heparanase splice variant T5 and its use.
JP2013512674A (ja) 2009-12-02 2013-04-18 アクセルロン ファーマ， インコーポレイテッド Ｆｃ融合タンパク質の血清半減期を増加させるための組成物および方法
WO2011071577A1 (en) 2009-12-11 2011-06-16 Genentech, Inc. Anti-vegf-c antibodies and methods using same
BR112012017164A2 (pt) 2009-12-22 2019-09-24 Novartis Ag proteína de fusão de região constante de anticorpo-cd47 tetravalente
EP2516465B1 (en) 2009-12-23 2016-05-18 F.Hoffmann-La Roche Ag Anti-bv8 antibodies and uses thereof
WO2011091078A2 (en) 2010-01-19 2011-07-28 Xencor, Inc. Antibody fc variants with enhanced complement activity
US20120296403A1 (en) 2010-02-10 2012-11-22 Novartis Ag Methods and compounds for muscle growth
US9556249B2 (en) 2010-02-18 2017-01-31 Genentech, Inc. Neuregulin antagonists and use thereof in treating cancer
TWI619509B (zh) 2010-02-23 2018-04-01 建南德克公司 治療先前未經治療之ⅲ期或ⅳ期卵巢癌、輸卵管癌或原發性腹膜癌之卡鉑、太平洋紫杉醇與抗-vegf抗體之組合
CA2790866C (en) 2010-02-23 2019-02-12 Sanofi Anti-alpha2 integrin antibodies and their uses
US9260529B2 (en) 2010-02-24 2016-02-16 The University Of Washington Through Its Center For Commercialization Molecules that bind CD180, compositions and methods of use
ES2602971T3 (es) 2010-03-02 2017-02-23 Kyowa Hakko Kirin Co., Ltd. Composición de anticuerpo modificado
EP2542256B1 (en) 2010-03-04 2019-05-22 MacroGenics, Inc. Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof
PH12012501751A1 (en) 2010-03-04 2012-11-12 Macrogenics Inc Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof
AR080795A1 (es) 2010-03-24 2012-05-09 Genentech Inc Anticuerpos anti-lrp6 (proteina relacionada con el receptor ldl tipo 6)
US20150231215A1 (en) 2012-06-22 2015-08-20 Randolph J. Noelle VISTA Antagonist and Methods of Use
MX374075B (es) 2010-03-26 2025-03-05 Dartmouth College Proteina mediadora de celula t regulatoria vista, agentes de enlace de vista y uso de los mismos.
US10745467B2 (en) 2010-03-26 2020-08-18 The Trustees Of Dartmouth College VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders
JP2013528357A (ja) 2010-03-29 2013-07-11 ザイムワークス，インコーポレイテッド 強化又は抑制されたエフェクター機能を有する抗体
TWI667257B (zh) 2010-03-30 2019-08-01 中外製藥股份有限公司 促進抗原消失之具有經修飾的ＦｃＲｎ親和力之抗體
EP2371860A1 (en) 2010-04-05 2011-10-05 Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron Antibody recognising human leukemia inhibitory factor (LIF) and use of anti-LIF antibodies in the treatment of diseases associated with unwanted cell proliferation
PH12012502193A1 (en) 2010-05-06 2021-08-09 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies
EP2566892B1 (en) 2010-05-06 2017-12-20 Novartis AG Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies
WO2011146568A1 (en) 2010-05-19 2011-11-24 Genentech, Inc. Predicting response to a her inhibitor
WO2011147834A1 (en) 2010-05-26 2011-12-01 Roche Glycart Ag Antibodies against cd19 and uses thereof
JP5956982B2 (ja) 2010-05-27 2016-07-27 メルク・シャープ・エンド・ドーム・コーポレイション 改善された特性を有する抗体の製造方法
WO2011153243A2 (en) 2010-06-02 2011-12-08 Genentech, Inc. Anti-angiogenesis therapy for treating gastric cancer
WO2011153224A2 (en) 2010-06-02 2011-12-08 Genentech, Inc. Diagnostic methods and compositions for treatment of cancer
NZ701208A (en) 2010-06-03 2016-05-27 Genentech Inc Immuno-pet imaging of antibodies and immunoconjugates and uses thereof
RU2577986C2 (ru) 2010-06-18 2016-03-20 Дженентек, Инк. Антитела против axl и способы их применения
US20130189268A1 (en) 2010-06-22 2013-07-25 Precision Biologics, Inc. Colon and pancreas cancer specific antigens and antibodies
WO2011161119A1 (en) 2010-06-22 2011-12-29 F. Hoffmann-La Roche Ag Antibodies against insulin-like growth factor i receptor and uses thereof
WO2011161189A1 (en) 2010-06-24 2011-12-29 F. Hoffmann-La Roche Ag Anti-hepsin antibodies and methods of use
TW201217527A (en) 2010-07-09 2012-05-01 Biogen Idec Hemophilia Inc Processable single chain molecules and polypeptides made using same
WO2012006503A1 (en) 2010-07-09 2012-01-12 Genentech, Inc. Anti-neuropilin antibodies and methods of use
CA2805618A1 (en) 2010-07-19 2012-01-26 F. Hoffmann-La Roche Ag Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy
KR20130126576A (ko) 2010-07-19 2013-11-20 에프. 호프만-라 로슈 아게 항암요법에 반응할 가능성이 증가된 환자를 확인하는 방법
WO2012010582A1 (en) 2010-07-21 2012-01-26 Roche Glycart Ag Anti-cxcr5 antibodies and methods of use
EP2595657A4 (en) 2010-07-22 2015-09-23 Univ California ANTI-TUMOR ANTIGEN ANTIBODIES AND USE PROCESSES
EP2596026B1 (en) 2010-07-23 2020-04-08 Trustees of Boston University Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery
ES2952394T3 (es) 2010-07-29 2023-10-31 Buzzard Pharmaceuticals AB Antagonistas quiméricos del receptor IL-1 de tipo I
EP2598882B1 (en) 2010-07-30 2017-07-26 AC Immune S.A. Safe and functional humanized antibodies for use in treating an amyloidosis
AU2011286024B2 (en) 2010-08-02 2014-08-07 Macrogenics, Inc. Covalent diabodies and uses thereof
EP3252072A3 (en) 2010-08-03 2018-03-14 AbbVie Inc. Dual variable domain immunoglobulins and uses thereof
KR20130045914A (ko) 2010-08-03 2013-05-06 에프. 호프만-라 로슈 아게 만성 림프구성 백혈병(cll) 생체지표
WO2012019061A2 (en) 2010-08-05 2012-02-09 Stem Centrx, Inc. Novel effectors and methods of use
JP2013541937A (ja) 2010-08-05 2013-11-21 エフ．ホフマン−ラ ロシュ アーゲー 抗ｍｈｃ抗体−抗ウイルス性サイトカイン融合タンパク質
JP2013537416A (ja) 2010-08-13 2013-10-03 メディミューン リミテッド 変異型Ｆｃ領域を含むモノマーポリペプチド及び使用方法
CA2806021C (en) 2010-08-13 2019-05-21 Roche Glycart Ag Anti-fap antibodies and methods of use
EP2603529A1 (en) 2010-08-13 2013-06-19 Roche Glycart AG Anti-tenascin-c a2 antibodies and methods of use
WO2012022734A2 (en) 2010-08-16 2012-02-23 Medimmune Limited Anti-icam-1 antibodies and methods of use
AU2011290672B2 (en) 2010-08-20 2015-07-09 Novartis Ag Antibodies for epidermal growth factor receptor 3 (HER3)
KR101603001B1 (ko) 2010-08-25 2016-03-11 에프. 호프만-라 로슈 아게 Il-18r1에 대한 항체 및 그의 용도
JP2013539364A (ja) 2010-08-26 2013-10-24 アッヴィ・インコーポレイテッド 二重可変ドメイン免疫グロブリンおよびその使用
SG10201506782XA (en) 2010-08-27 2015-10-29 Stem Centrx Inc Notum protein modulators and methods of use
MX2013002084A (es) 2010-08-31 2013-05-09 Genentech Inc Biomarcadores y metodos de tratamiento.
TWI560199B (en) 2010-08-31 2016-12-01 Sanofi Sa Peptide or peptide complex binding to α2 integrin and methods and uses involving the same
AU2011295715B9 (en) 2010-09-03 2017-02-23 Abbvie Stemcentrx Llc Novel modulators and methods of use
KR20140019284A (ko) 2010-09-03 2014-02-14 아카데미아 시니카 항-C-Met 항체 및 이의 이용 방법들
WO2012032080A1 (en) 2010-09-07 2012-03-15 F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H Stabilised human fc
WO2012035518A1 (en) 2010-09-17 2012-03-22 Compugen Ltd. Compositions and methods for treatment of drug resistant multiple myeloma
ES2719624T3 (es) 2010-09-23 2019-07-11 Prec Biologics Inc Peptidomiméticos de cáncer de colon y de páncreas
DK2621531T3 (en) 2010-09-27 2017-02-27 Morphosys Ag ANTI-CD38 ANTIBODY AND LENALIDOMIDE OR BORTEZOMIB FOR TREATMENT OF MULTIPLE MYELOM AND NHL
DK2625197T3 (en) 2010-10-05 2016-10-03 Genentech Inc Smoothened MUTANT AND METHODS OF USING THE SAME
EP2625203A1 (en) 2010-10-05 2013-08-14 Novartis AG Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders
KR101920250B1 (ko) 2010-10-13 2018-11-20 얀센 바이오테크 인코포레이티드 인간 온코스타틴 m 항체 및 이용 방법
US20130259878A1 (en) * 2010-10-20 2013-10-03 Oxford Biotherapeutics Ltd Antibodies
ES2758994T3 (es) 2010-11-05 2020-05-07 Zymeworks Inc Diseño anticuerpo heterodimérico estable con mutaciones en el dominio Fc
KR20190120439A (ko) 2010-11-08 2019-10-23 제넨테크, 인크. 피하 투여용 항―ｉｌ―6 수용체 항체
WO2012064836A1 (en) 2010-11-10 2012-05-18 Genentech, Inc. Methods and compositions for neural disease immunotherapy
CA2818813C (en) 2010-11-23 2020-10-06 Alder Biopharmaceuticals, Inc. Anti-il-6 antibodies for the treatment of oral mucositis
TWI504609B (zh) 2010-11-23 2015-10-21 Glaxo Group Ltd 抗原結合蛋白質
AU2011333738A1 (en) 2010-11-24 2013-07-11 Glaxo Group Limited Multispecific antigen binding proteins targeting HGF
CA2818173C (en) 2010-11-30 2022-05-03 Genentech, Inc. Low affinity blood brain barrier receptor antibodies and uses therefor
PT3434767T (pt) * 2010-11-30 2026-01-23 Chugai Pharmaceutical Co Ltd Agente terapêutico indutor de citotoxicidade
EP2647706B1 (en) 2010-11-30 2023-05-17 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly
NZ611428A (en) 2010-12-08 2015-07-31 Stemcentrx Inc Novel modulators and methods of use
AU2011342799B2 (en) 2010-12-15 2016-06-09 Wyeth Llc Anti-Notch1 antibodies
RU2578468C2 (ru) 2010-12-16 2016-03-27 Дженентек, Инк. Способы диагностики и лечения, связанные с ингибированием th2
BR112013014527A2 (pt) 2010-12-20 2017-03-07 Genentech Inc anticorpo isolado, ácido nucleico isolado, célula hospedeira, método para produzir um anticorpo, imunoconjugado, formulação farmacêutica, uso do imunoconjugado, método para tratamento de um indivíduo que tem um câncer positivo para mesotelina, para inibição de proliferação de uma célula positiva para mesotelina, para detecção de mesotelina humana em uma amostra biológica e para detectar um câncer positivo para mesotelina
CN103261230A (zh) 2010-12-22 2013-08-21 霍夫曼-拉罗奇有限公司 抗pcsk9抗体及使用方法
ES2623912T3 (es) 2010-12-23 2017-07-12 Janssen Biotech, Inc. Mutantes FC de anticuerpo activo resistente a proteasa
WO2012092539A2 (en) 2010-12-31 2012-07-05 Takeda Pharmaceutical Company Limited Antibodies to dll4 and uses thereof
CN102128937B (zh) * 2010-12-31 2014-05-28 江苏华冠生物技术股份有限公司 用于脱敏治疗效果评价的过敏原特异性IgG4抗体检测试剂盒的制备方法
US10689447B2 (en) 2011-02-04 2020-06-23 Genentech, Inc. Fc variants and methods for their production
US8952132B2 (en) 2011-02-07 2015-02-10 Research Development Foundation Engineered immunoglobulin FC polypeptides
SA112330278B1 (ar) 2011-02-18 2015-10-09 ستيم سينتركس، انك. مواد ضابطة جديدة وطرق للاستخدام
MX352889B (es) 2011-02-25 2017-12-13 Chugai Pharmaceutical Co Ltd Anticuerpo de fc especifico para fcyriib.
MX353143B (es) 2011-02-28 2017-12-20 Genentech Inc Marcadores biologicos y metodos para pronosticar respuesta a antagonistas de celulas b.
AR085404A1 (es) 2011-02-28 2013-09-25 Hoffmann La Roche Proteinas de union a antigeno
MX342034B (es) 2011-02-28 2016-09-12 Hoffmann La Roche Proteinas monovalentes que se unen a antigenos.
AU2012233313C1 (en) 2011-03-30 2017-08-03 Chugai Seiyaku Kabushiki Kaisha Method for altering plasma retention and immunogenicity of antigen-binding molecule
MX2018012383A (es) 2011-03-30 2023-03-07 Chugai Pharmaceutical Co Ltd Método para alterar la retención en plasma e inmunogenicidad de la molécula de union al antígeno.
RU2016127812A (ru) 2011-03-31 2018-12-06 Дженентек, Инк. Способы введения антагонистов интегрина бета7
CA2828890A1 (en) 2011-04-07 2012-10-11 Genentech, Inc. Anti-fgfr4 antibodies and methods of use
EP3415528B1 (en) 2011-04-13 2021-05-26 Bristol-Myers Squibb Company Fc fusion proteins comprising novel linkers or arrangements
NZ713461A (en) 2011-04-15 2017-02-24 Compugen Ltd Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer
JP6072771B2 (ja) 2011-04-20 2017-02-01 メディミューン，エルエルシー Ｂ７−ｈ１およびｐｄ−１に結合する抗体およびその他の分子
GB201107170D0 (en) 2011-04-28 2011-06-15 Clark Michael Binding molecules with biased recognition
WO2012146630A1 (en) 2011-04-29 2012-11-01 F. Hoffmann-La Roche Ag N-terminal acylated polypeptides, methods for their production and uses thereof
ES2666303T3 (es) 2011-04-29 2018-05-03 University Of Washington Composiciones terapéuticas de nucleasa y métodos
US8679767B2 (en) 2011-05-12 2014-03-25 Genentech, Inc. Multiple reaction monitoring LC-MS/MS method to detect therapeutic antibodies in animal samples using framework signature peptides
NO2707391T3 (2) 2011-05-13 2018-04-07
EA030462B1 (ru) 2011-05-16 2018-08-31 Дженентек, Инк. Агонисты fgfr1 и способы их применения
KR102060389B1 (ko) 2011-05-21 2019-12-31 마크로제닉스, 인크. 사람 및 비-사람 cd3에 결합할 수 있는 cd3-결합 분자
BR112013029892A2 (pt) 2011-05-21 2016-12-20 Macrogenics Inc polipeptídeo, molécula de ligação a antígeno, diacorpo e uso de uma porção polipeptídica de uma proteína de ligação a soro desimunizada
EP2714738B1 (en) 2011-05-24 2018-10-10 Zyngenia, Inc. Multivalent and monovalent multispecific complexes and their uses
AU2012258907A1 (en) 2011-05-25 2013-11-07 Merck Sharp & Dohme Corp. Method for preparing Fc-containing polypeptides having improved properties
WO2012170742A2 (en) 2011-06-07 2012-12-13 University Of Hawaii Treatment and prevention of cancer with hmgb1 antagonists
US9244074B2 (en) 2011-06-07 2016-01-26 University Of Hawaii Biomarker of asbestos exposure and mesothelioma
US9486507B2 (en) 2011-06-10 2016-11-08 Biogen Ma Inc. Pro-coagulant compounds and methods of use thereof
WO2012172495A1 (en) 2011-06-14 2012-12-20 Novartis Ag Compositions and methods for antibodies targeting tem8
US8623666B2 (en) 2011-06-15 2014-01-07 Hoffmann-La Roche Inc. Method for detecting erythropoietin (EPO) receptor using anti-human EPO receptor antibodies
BR112013031762A2 (pt) 2011-06-16 2016-09-13 Novartis Ag proteínas solúveis para utilização como terapêuticos
CN103649125A (zh) 2011-06-22 2014-03-19 霍夫曼-拉罗奇有限公司 利用包含mhc i类的复合物通过循环中的病毒特异性细胞毒性t细胞清除靶细胞
CA2839508A1 (en) 2011-06-22 2012-12-27 Inserm (Institut National De La Sante Et De La Recherche Medicale) Anti-axl antibodies and uses thereof
ES2677367T3 (es) 2011-06-22 2018-08-01 INSERM (Institut National de la Santé et de la Recherche Médicale) Anticuerpos anti-Axl y usos de los mismos
EP2537864B1 (en) * 2011-06-24 2019-08-07 Laboratoire Français du Fractionnement et des Biotechnologies Fc variants with reduced effector functions
PL2726508T3 (pl) 2011-06-28 2017-12-29 Oxford Biotherapeutics Ltd Przeciwciała przeciwko cyklazie ADP-rybozylowej 2
AR086823A1 (es) 2011-06-30 2014-01-22 Genentech Inc Formulaciones de anticuerpo anti-c-met, metodos
US9428574B2 (en) 2011-06-30 2016-08-30 Compugen Ltd. Polypeptides and uses thereof for treatment of autoimmune disorders and infection
TWI687439B (zh) 2011-06-30 2020-03-11 中外製藥股份有限公司 異源二聚化多胜肽
JP6472999B2 (ja) 2011-07-01 2019-02-20 ノバルティス アーゲー 代謝障害を治療するための方法
UA117901C2 (uk) 2011-07-06 2018-10-25 Ґенмаб Б.В. Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування
WO2013008171A1 (en) 2011-07-11 2013-01-17 Glenmark Pharmaceuticals S.A. Antibodies that bind to ox40 and their uses
WO2013012733A1 (en) 2011-07-15 2013-01-24 Biogen Idec Ma Inc. Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto
WO2013010955A1 (en) 2011-07-15 2013-01-24 Morphosys Ag Antibodies that are cross-reactive for macrophage migration inhibitory factor (mif) and d-dopachrome tautomerase (d-dt)
GB201112429D0 (en) 2011-07-19 2011-08-31 Glaxo Group Ltd Antigen-binding proteins with increased FcRn binding
US20130022551A1 (en) 2011-07-22 2013-01-24 Trustees Of Boston University DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS
JP5987057B2 (ja) 2011-07-27 2016-09-06 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Ｆｃドメインと融合した抗ｖｅｇｆ単一可変ドメイン
US9676854B2 (en) 2011-08-15 2017-06-13 Medimmune, Llc Anti-B7-H4 antibodies and their uses
KR20140068877A (ko) 2011-08-17 2014-06-09 제넨테크, 인크. 불응성 종양에서의 혈관신생의 억제
MX2014001766A (es) 2011-08-17 2014-05-01 Genentech Inc Anticuerpos de neuregulina y sus usos.
RU2014109038A (ru) 2011-08-23 2015-09-27 Рош Гликарт Аг Антитела к хондроитинсульфат протеогликану меланомы
US20130058947A1 (en) 2011-09-02 2013-03-07 Stem Centrx, Inc Novel Modulators and Methods of Use
UY34317A (es) 2011-09-12 2013-02-28 Genzyme Corp Anticuerpo antireceptor de célula T (alfa)/ß
WO2013039954A1 (en) 2011-09-14 2013-03-21 Sanofi Anti-gitr antibodies
WO2013040433A1 (en) 2011-09-15 2013-03-21 Genentech, Inc. Methods of promoting differentiation
SG11201400724SA (en) 2011-09-19 2014-04-28 Genentech Inc Combination treatments comprising c-met antagonists and b-raf antagonists
TW201817744A (zh) * 2011-09-30 2018-05-16 日商中外製藥股份有限公司 具有促進抗原清除之ＦｃＲｎ結合域的治療性抗原結合分子
RU2014117505A (ru) 2011-09-30 2015-11-10 Чугаи Сейяку Кабусики Кайся Антигенсвязывающая молекула для ускорения удаления антигенов
HUE034044T2 (en) 2011-09-30 2018-01-29 Dana Farber Cancer Inst Inc Therapeutic peptides
JP6322411B2 (ja) 2011-09-30 2018-05-09 中外製薬株式会社 複数の生理活性を有する抗原の消失を促進する抗原結合分子
EP2752200B1 (en) 2011-09-30 2023-11-01 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule inducing immune response to target antigen
US9663573B2 (en) 2011-10-05 2017-05-30 Genentech, Inc. Methods of treating liver conditions using Notch2 antagonists
JP6271251B2 (ja) 2011-10-05 2018-01-31 中外製薬株式会社 糖鎖受容体結合ドメインを含む抗原の血漿中からの消失を促進する抗原結合分子
BR112014008862A2 (pt) 2011-10-14 2018-08-07 Genentech Inc anticorpo isolado que se liga à htra1, ácido nucleico isolado, célula hospedeira, imunoconjugado, formulação farmacêutica, métodos e usos
WO2013054307A2 (en) 2011-10-14 2013-04-18 Novartis Ag Antibodies and methods for wnt pathway-related diseases
US9358250B2 (en) 2011-10-15 2016-06-07 Genentech, Inc. Methods of using SCD1 antagonists
WO2013059531A1 (en) 2011-10-20 2013-04-25 Genentech, Inc. Anti-gcgr antibodies and uses thereof
WO2013059740A1 (en) 2011-10-21 2013-04-25 Foundation Medicine, Inc. Novel alk and ntrk1 fusion molecules and uses thereof
MX2014004991A (es) 2011-10-28 2014-05-22 Genentech Inc Combinaciones terapeuticas y metodos para tratar el melanoma.
EP3559049B1 (en) 2011-10-28 2025-06-11 Teva Pharmaceuticals Australia Pty Ltd Polypeptide constructs and uses thereof
CN109134658B (zh) 2011-10-31 2022-10-14 中外制药株式会社 控制了重链与轻链的缔合的抗原结合分子
CN104053671A (zh) 2011-11-01 2014-09-17 生态学有限公司 治疗癌症的抗体和方法
US9221907B2 (en) 2011-11-01 2015-12-29 Bionomics Inc. Anti-GPR49 monoclonal antibodies
US10598653B2 (en) 2011-11-01 2020-03-24 Bionomics Inc. Methods of blocking cancer stem cell growth
WO2013067057A1 (en) 2011-11-01 2013-05-10 Bionomics, Inc. Anti-gpr49 antibodies
BR112014010580B1 (pt) 2011-11-04 2021-01-12 Zymeworks, Inc. constructo de fc heteromultimérico isolado, composição, uso de um constructo de fc heteromultimérico isolado, composição de ácido nucléico e método para expressar o constructo de fc heteromultimérico isolado
US9580509B2 (en) 2011-11-07 2017-02-28 Medimmune, Llc Multispecific and multivalent binding proteins and uses thereof
SG11201402485UA (en) 2011-11-21 2014-06-27 Genentech Inc Purification of anti-c-met antibodies
BR112014012590A8 (pt) 2011-11-23 2017-12-19 Igenica Inc Anticorpos anti-cd98 e métodos de uso dos mesmos
KR20230143201A (ko) 2011-11-30 2023-10-11 추가이 세이야쿠 가부시키가이샤 면역 복합체를 형성하는 세포내로의 운반체（캐리어）를 포함하는 의약
CN104105709A (zh) 2011-12-05 2014-10-15 诺华股份有限公司 抗her3的结构域ii的表皮生长因子受体3(her3)抗体
EP3590538A1 (en) 2011-12-05 2020-01-08 Novartis AG Antibodies for epidermal growth factor receptor 3 (her3)
AU2012347972B2 (en) 2011-12-05 2018-05-10 X-Body, Inc. PDGF receptor beta binding polypeptides
WO2013083497A1 (en) 2011-12-06 2013-06-13 F. Hoffmann-La Roche Ag Antibody formulation
RU2685867C2 (ru) 2011-12-15 2019-04-23 Алтернатив Инновейтив Текнолоджиз Ллц Гибридные белки и белковые конъюгаты на основе белка теплового шока-70 (БТШ70) и способы их применения (варианты)
RS60499B1 (sr) 2011-12-20 2020-08-31 Medimmune Llc Modifikovani polipeptidi za bispecifične skelete antitela
ES2728278T3 (es) 2011-12-21 2019-10-23 Novartis Ag Composiciones que comprenden anticuerpos dirigidos al factor P y C5
AR089434A1 (es) 2011-12-23 2014-08-20 Genentech Inc Procedimiento para preparar formulaciones con alta concentracion de proteinas
JP2015502397A (ja) 2011-12-23 2015-01-22 ファイザー・インク 部位特異的コンジュゲーションのための操作された抗体定常領域、ならびにそのための方法および使用
TWI593705B (zh) 2011-12-28 2017-08-01 Chugai Pharmaceutical Co Ltd Humanized anti-epiregulin antibody and cancer therapeutic agent containing the antibody as an active ingredient
TW201333035A (zh) 2011-12-30 2013-08-16 Abbvie Inc 針對ｉｌ－１３及／或ｉｌ－１７之雙特異性結合蛋白
WO2013101771A2 (en) 2011-12-30 2013-07-04 Genentech, Inc. Compositions and method for treating autoimmune diseases
JP2015509091A (ja) 2012-01-09 2015-03-26 ザ スクリプス リサーチ インスティテュート ヒト化抗体
CA2863224A1 (en) 2012-01-09 2013-07-18 The Scripps Research Institute Ultralong complementarity determining regions and uses thereof
CN104271150A (zh) 2012-01-12 2015-01-07 比奥根艾迪克Ma公司 嵌合因子viii多肽及其用途
WO2013106765A1 (en) 2012-01-13 2013-07-18 Genentech, Inc. Biological markers for identifying patients for treatment with vegf antagonists
JP2015506944A (ja) 2012-01-18 2015-03-05 ジェネンテック， インコーポレイテッド Ｆｇｆ１９修飾薬を使用する方法
US9200072B2 (en) 2012-01-18 2015-12-01 Genentech Inc. Anti-LRP5 antibodies and methods of use
CA2848985A1 (en) 2012-02-01 2013-08-08 Compugen Ltd. C10rf32 antibodies, and uses thereof for treatment of cancer
AU2013218017B2 (en) 2012-02-07 2017-12-07 Innate Pharma MICA binding agents
SG11201404751UA (en) 2012-02-09 2014-09-26 Chugai Pharmaceutical Co Ltd Modified fc region of antibody
KR102148303B1 (ko) 2012-02-11 2020-08-26 제넨테크, 인크. R-스폰딘 전위 및 그의 사용 방법
MX360352B (es) 2012-02-15 2018-10-30 Hoffmann La Roche Cromatografia de afinidad basada en receptores fc.
EP2822577B1 (en) 2012-02-15 2019-02-06 Bioverativ Therapeutics Inc. Recombinant factor viii proteins
JP6256882B2 (ja) 2012-02-15 2018-01-10 アムニクス オペレーティング インコーポレイテッド 第ｖｉｉｉ因子組成物、ならびに組成物の作製方法および用途
EP3738980A1 (en) 2012-02-24 2020-11-18 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule for promoting disappearance of antigen via fc gamma riib
BR112014020826A8 (pt) 2012-02-24 2017-09-19 Stem Centrx Inc Anticorpo que se liga especificamente a um epítopo, ácido nucleico, vetor ou célula hospedeira, conjugado de fármaco – anticorpo, composição farmacêutica compreendendo o referido anticorpo, uso do mesmo, kit e método de preparação do conjugado
US20130259867A1 (en) 2012-03-27 2013-10-03 Genentech, Inc. Diagnosis and treatments relating to her3 inhibitors
HUE037720T2 (hu) 2012-03-28 2018-09-28 Sanofi Sa Bradikinin B1 receptor ligandumok elleni antitestek
EP2832856A4 (en) 2012-03-29 2016-01-27 Chugai Pharmaceutical Co Ltd ANTI-LAMP5 ANTIBODIES AND USE THEREOF
AR090549A1 (es) 2012-03-30 2014-11-19 Genentech Inc Anticuerpos anti-lgr5 e inmunoconjugados
KR20140142719A (ko) 2012-03-30 2014-12-12 제넨테크, 인크. 암의 치료를 위한 진단 방법 및 조성물
RU2644242C2 (ru) 2012-04-05 2018-02-08 Ац Иммуне С.А. Гуманизированное тау-антитело
US9156915B2 (en) 2012-04-26 2015-10-13 Thomas Jefferson University Anti-GCC antibody molecules
US9056910B2 (en) 2012-05-01 2015-06-16 Genentech, Inc. Anti-PMEL17 antibodies and immunoconjugates
WO2013166290A1 (en) 2012-05-04 2013-11-07 Abbvie Biotherapeutics Inc. P21 biomarker assay
MX2014013637A (es) 2012-05-07 2015-02-05 Sanofi Sa Metodos para prevencion de la formacion de biopelicula.
WO2013170191A1 (en) 2012-05-11 2013-11-14 Genentech, Inc. Methods of using antagonists of nad biosynthesis from nicotinamide
EP2849723B1 (en) 2012-05-18 2018-05-02 Genentech, Inc. High-concentration monoclonal antibody formulations
WO2013177062A2 (en) * 2012-05-21 2013-11-28 Genentech, Inc. Methods for improving safety of blood-brain barrier transport
RU2625771C2 (ru) 2012-05-23 2017-07-18 Дженентек, Инк. Способ отбора терапевтических средств
EP2852610B1 (en) 2012-05-23 2018-07-11 Glykos Finland Oy Production of fucosylated glycoproteins
WO2013175276A1 (en) 2012-05-23 2013-11-28 Argen-X B.V Il-6 binding molecules
WO2013177386A1 (en) 2012-05-24 2013-11-28 Abbvie Biotherapeutics Inc. Biomarkers for predicting response to tweak receptor (tweakr) agonist therapy
EP2857419B1 (en) 2012-05-30 2021-01-13 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule for eliminating aggregated antigens
WO2013180200A1 (ja) 2012-05-30 2013-12-05 中外製薬株式会社 標的組織特異的抗原結合分子
EP2855520B1 (en) 2012-06-04 2018-09-26 Novartis AG Site-specific labeling methods and molecules produced thereby
WO2013185113A1 (en) 2012-06-08 2013-12-12 Biogen Idec Ma Inc. Procoagulant compounds
ES2666126T3 (es) 2012-06-08 2018-05-03 Glenmark Pharmaceuticals S.A. Anticuerpos anti-TrkA humanizados con sustituciones de aminoácidos
CA2875247A1 (en) 2012-06-08 2013-12-12 Biogen Idec Ma Inc. Chimeric clotting factors
JP6628966B2 (ja) * 2012-06-14 2020-01-15 中外製薬株式会社 改変されたＦｃ領域を含む抗原結合分子
EP2861624A1 (en) 2012-06-15 2015-04-22 F. Hoffmann-La Roche AG Anti-pcsk9 antibodies, formulations, dosing, and methods of use
HK1209034A1 (en) * 2012-06-21 2016-03-24 Indiana University Research And Technology Corporation Incretin receptor ligand polypeptide fc-region fusion polypeptides and conjugates with altered fc-effector function
JP6285923B2 (ja) 2012-06-22 2018-02-28 トラスティーズ・オブ・ダートマス・カレッジ 新規ＶＩＳＴＡ−Ｉｇコンストラクト及び自己免疫、アレルギー性及び炎症性障害の処置のためのＶＩＳＴＡ−Ｉｇの使用
US9890215B2 (en) 2012-06-22 2018-02-13 King's College London Vista modulators for diagnosis and treatment of cancer
US9499634B2 (en) 2012-06-25 2016-11-22 Zymeworks Inc. Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells
UY34887A (es) 2012-07-02 2013-12-31 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos
DK2869837T3 (en) 2012-07-04 2016-09-26 Hoffmann La Roche Anti-theophylline antibodies and methods of use
EP2870180B1 (en) 2012-07-04 2024-08-28 F. Hoffmann-La Roche AG Anti-biotin antibodies and methods of use
RU2684595C2 (ru) 2012-07-04 2019-04-09 Ф.Хоффманн-Ля Рош Аг Ковалентно связанные конъюгаты антиген-антитело
US9803191B2 (en) 2012-07-05 2017-10-31 Genentech, Inc. Expression and secretion system
EP3632462A1 (en) 2012-07-06 2020-04-08 Genmab B.V. Dimeric protein with triple mutations
CN104736174B (zh) 2012-07-06 2019-06-14 根马布私人有限公司 具有三重突变的二聚体蛋白质
US10023628B2 (en) 2012-07-06 2018-07-17 Bioverativ Therapeutics Inc. Cell line expressing single chain factor VIII polypeptides and uses thereof
IN2014DN10652A (2) 2012-07-09 2015-09-11 Genentech Inc
AR091703A1 (es) 2012-07-09 2015-02-25 Genentech Inc Anticuerpos e inmunoconjugados que comprenden anticuerpos anti-cd22
CN104428007B (zh) 2012-07-09 2018-03-16 基因泰克公司 包含抗cd22抗体的免疫缀合物
CN104411337A (zh) 2012-07-09 2015-03-11 基因泰克公司 包含抗cd79b抗体的免疫偶联物
CN104661674A (zh) 2012-07-11 2015-05-27 阿穆尼克斯运营公司 具有xten和血管性血友病因子蛋白的因子viii复合物、及其用途
BR112014032169A2 (pt) 2012-07-18 2017-08-01 Glycotope Gmbh tratamentos terapêuticos com anticorpos anti-her2 tendo uma fucosilação baixa
NZ630363A (en) 2012-07-25 2018-09-28 Celldex Therapeutics Inc Anti-kit antibodies and uses thereof
EP2888279A1 (en) 2012-08-22 2015-07-01 Glaxo Group Limited Anti lrp6 antibodies
WO2014030750A1 (ja) 2012-08-24 2014-02-27 中外製薬株式会社 マウスFcγRII特異的Fc抗体
SG10201709559PA (en) 2012-08-24 2017-12-28 Chugai Pharmaceutical Co Ltd Fcγriib-specific fc region variant
HUE045144T2 (hu) 2012-08-29 2019-12-30 Hoffmann La Roche Véragygát-shuttle
US9381244B2 (en) 2012-09-07 2016-07-05 King's College London VISTA modulators for diagnosis and treatment of cancer
US9376489B2 (en) 2012-09-07 2016-06-28 Novartis Ag IL-18 binding molecules
PL3366705T3 (pl) 2012-09-12 2023-09-18 Genzyme Corporation FC zawierające polipeptydy o zmienionej glikozylacji i zmniejszonej funkcji efektorowej
US9790268B2 (en) 2012-09-12 2017-10-17 Genzyme Corporation Fc containing polypeptides with altered glycosylation and reduced effector function
CA2887129A1 (en) 2012-10-09 2014-04-17 Igenica, Inc. Anti-c16orf54 antibodies and methods of use thereof
TW202037609A (zh) 2012-11-01 2020-10-16 美商艾伯維有限公司 抗-vegf/dll4雙重可變區域免疫球蛋白及其用途
EP2914621B1 (en) 2012-11-05 2023-06-07 Foundation Medicine, Inc. Novel ntrk1 fusion molecules and uses thereof
US11230589B2 (en) 2012-11-05 2022-01-25 Foundation Medicine, Inc. Fusion molecules and uses thereof
MA38165A1 (fr) 2012-11-08 2018-07-31 Hoffmann La Roche Protéines de liaison à l'antigène her3 se liant à l'épingle à cheveux beta de her3
CA2890483A1 (en) 2012-11-09 2014-05-15 Robert ARCH Platelet-derived growth factor b specific antibodies and compositions and uses thereof
CN104968367B (zh) 2012-11-13 2018-04-13 弗·哈夫曼-拉罗切有限公司 抗血凝素抗体和使用方法
EP2733153A1 (en) 2012-11-15 2014-05-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the preparation of immunoconjugates and uses thereof
US9914785B2 (en) 2012-11-28 2018-03-13 Zymeworks Inc. Engineered immunoglobulin heavy chain-light chain pairs and uses thereof
WO2014083379A1 (en) 2012-11-30 2014-06-05 Institut Pasteur Use of anti-fcyri and/or anti-fcyriia antibodies for treating arthritis, inflammation, thrombocytopenia and allergic shock
WO2014084859A1 (en) 2012-11-30 2014-06-05 Novartis Ag Molecules and methods for modulating tmem16a activities
DK2928921T3 (da) 2012-12-05 2021-04-19 Novartis Ag Sammensætninger og fremgangsmåder til antistoffer målrettet epo
CA2894879A1 (en) 2012-12-19 2014-06-26 Amplimmune, Inc. B7-h4 specific antibodies, and compositions and methods of use thereof
TWI693073B (zh) 2012-12-21 2020-05-11 日商中外製藥股份有限公司 對ｇｐｃ３標的治療劑療法為有效之患者投與的ｇｐｃ３標的治療劑
WO2014096015A1 (en) 2012-12-21 2014-06-26 F. Hoffmann-La Roche Ag Disulfide-linked multivalent mhc class i comprising multi-function proteins
EP3557260B1 (en) 2012-12-21 2022-05-18 Chugai Seiyaku Kabushiki Kaisha Gpc3-targeting drug which is administered to patient responsive to gpc3-targeting drug therapy
BR112015014621A2 (pt) 2012-12-21 2017-10-03 Amplimmune Inc Anticorpos anti-h7cr
ES2876009T3 (es) 2012-12-27 2021-11-11 Chugai Pharmaceutical Co Ltd Polipéptido heterodimerizado
CA2896723C (en) 2012-12-28 2024-02-13 Precision Biologics, Inc. Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer
WO2014106602A1 (en) 2013-01-02 2014-07-10 Glenmark Pharmaceuticals S.A. Antibodies that bind to tl1a and their uses
WO2014107739A1 (en) 2013-01-07 2014-07-10 Eleven Biotherapeutics, Inc. Antibodies against pcsk9
KR20200024345A (ko) 2013-01-10 2020-03-06 젠맵 비. 브이 인간 IgG1 Fc 영역 변이체 및 그의 용도
CA3150658A1 (en) 2013-01-18 2014-07-24 Foundation Medicine, Inc. Methods of treating cholangiocarcinoma
WO2014116749A1 (en) 2013-01-23 2014-07-31 Genentech, Inc. Anti-hcv antibodies and methods of using thereof
BR112015017619A2 (pt) 2013-01-24 2017-11-21 Glaxosmithkline Ip Dev Ltd formulação líquida, uso de uma formulação, e, kit
TWI635098B (zh) 2013-02-01 2018-09-11 再生元醫藥公司 含嵌合恆定區之抗體
WO2014122143A1 (en) 2013-02-05 2014-08-14 Engmab Ag Method for the selection of antibodies against bcma
EP2762496A1 (en) 2013-02-05 2014-08-06 EngMab AG Method for the selection of antibodies against BCMA
EP2953976B1 (en) 2013-02-08 2021-03-24 Novartis Ag Specific sites for modifying antibodies to make immunoconjugates
LT2953969T (lt) 2013-02-08 2019-12-10 Novartis Ag Anti-il-17a antikūnai ir jų panaudojimas autoimuninių ir uždegiminių ligų gydymui
WO2014124258A2 (en) 2013-02-08 2014-08-14 Irm Llc Specific sites for modifying antibodies to make immunoconjugates
WO2014126871A1 (en) 2013-02-12 2014-08-21 Bristol-Myers Squibb Company Tangential flow filtration based protein refolding methods
US10065987B2 (en) 2013-02-12 2018-09-04 Bristol-Myers Squibb Company High pH protein refolding methods
ES2747920T3 (es) 2013-02-14 2020-03-12 Innate Pharma Anticuerpo anti-NKP46 para diagnóstico de un linfoma de células T periféricas no cutáneo (PTCL)
WO2014127215A1 (en) 2013-02-15 2014-08-21 Biogen Idec Ma Inc. Optimized factor viii gene
ES2878749T3 (es) 2013-02-20 2021-11-19 Innate Pharma Un compuesto que se une específicamente a KIR3DL2 para el uso en el tratamiento de linfoma de células T periférico
ES2731681T3 (es) 2013-02-22 2019-11-18 Abbvie Stemcentrx Llc Conjugados de anticuerpo anti-DLL3 y PBD y usos de los mismos
JP2016509045A (ja) 2013-02-22 2016-03-24 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト がんを治療し、薬剤耐性を防止する方法
EP2959014B1 (en) 2013-02-25 2019-11-13 Genentech, Inc. Methods and compositions for detecting and treating drug resistant akt mutant
US20140242083A1 (en) 2013-02-26 2014-08-28 Roche Glycart Ag Anti-mcsp antibodies
US9487587B2 (en) 2013-03-05 2016-11-08 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells of a companion animal that express an activating receptor and cells that express B7-H3 and uses thereof
MX2015011428A (es) 2013-03-06 2016-02-03 Genentech Inc Metodos para tratar y prevenir la resistencia a los farmacos para el cancer.
US9701753B2 (en) 2013-03-11 2017-07-11 Genzyme Corporation Hyperglycosylated binding polypeptides
US9498532B2 (en) 2013-03-13 2016-11-22 Novartis Ag Antibody drug conjugates
EP2968468B1 (en) 2013-03-13 2021-07-14 Buzzard Pharmaceuticals AB Chimeric cytokine formulations for ocular delivery
JP6436965B2 (ja) 2013-03-14 2018-12-12 ジェネンテック， インコーポレイテッド 抗ｂ７−ｈ４抗体及びイムノコンジュゲート
MX2015010854A (es) 2013-03-14 2016-07-20 Genentech Inc Combinaciones de un compuesto inhibidor de mek con un compuesto inhibidor de her3/egfr y metodos de uso.
JP2016516046A (ja) 2013-03-14 2016-06-02 ジェネンテック， インコーポレイテッド がんの治療方法及びがん薬物耐性を阻止する方法
EP3611189A1 (en) 2013-03-14 2020-02-19 Novartis AG Antibodies against notch 3
SMT202100464T1 (it) 2013-03-14 2021-11-12 Macrogenics Inc Molecole bispecifiche che sono immunoreattive con cellule effettrici immunitarie che esprimono un recettore di attivazione
US9562099B2 (en) 2013-03-14 2017-02-07 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
WO2014150877A2 (en) 2013-03-15 2014-09-25 Ac Immune S.A. Anti-tau antibodies and methods of use
FR3003171B1 (fr) * 2013-03-15 2015-04-10 Lab Francais Du Fractionnement Nouveaux medicaments comprenant une composition d'anticorps enrichie en isoforme de charge majoritaire
KR20150131177A (ko) 2013-03-15 2015-11-24 제넨테크, 인크. 항-CRTh2 항체 및 그의 용도
US10344088B2 (en) 2013-03-15 2019-07-09 Glaxosmithkline Intellectual Property Development Limited Antigen binding proteins
WO2014145016A2 (en) 2013-03-15 2014-09-18 Genentech, Inc. Il-22 polypeptides and il-22 fc fusion proteins and methods of use
WO2014144549A1 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Factor ix polypeptide formulations
SG11201506766PA (en) 2013-03-15 2015-09-29 Dana Farber Cancer Inst Inc Therapeutic peptides
ES2708565T3 (es) 2013-03-15 2019-04-10 Atyr Pharma Inc Conjugados de Fc-histidil-ARNt sintetasa
PT3611180T (pt) 2013-03-15 2022-03-15 Biomolecular Holdings Llc Imunoglobulina híbrida que contém uma ligação não peptídica
SG11201507427QA (en) 2013-03-15 2015-10-29 Genentech Inc Compositions and methods for diagnosis and treatment of hepatic cancers
WO2014144280A2 (en) 2013-03-15 2014-09-18 Abbvie Inc. DUAL SPECIFIC BINDING PROTEINS DIRECTED AGAINST IL-1β AND / OR IL-17
US10150800B2 (en) 2013-03-15 2018-12-11 Zyngenia, Inc. EGFR-binding modular recognition domains
BR112015023120A2 (pt) 2013-03-15 2017-11-21 Genentech Inc método para identificar um indivíduo com uma doença ou disfunção, método para prever a responsividade de um indivíduo com uma doença ou disfunção, método para determinar a probabilidade de que um indivíduo com uma doença ou disfunção exibirá benefício do tratamento, método para selecionar uma terapia, usos de um antagonista de ligação do eixo pd-l1, ensaio para identificar um indivíduo com uma doença, kit de diagnóstico, método para avaliar uma resposta ao tratamento e método para monitorar a resposta de um indivíduo tratado
JP2016514676A (ja) 2013-03-15 2016-05-23 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ 四価二重特異性抗体
ES2701051T3 (es) 2013-03-15 2019-02-20 Novartis Ag Conjugados de anticuerpo-fármaco
CA2905123A1 (en) 2013-03-15 2014-09-18 Genentech, Inc. Methods of treating cancer and preventing cancer drug resistance
CN105143876B (zh) 2013-03-27 2018-04-20 豪夫迈·罗氏有限公司 生物标志物用于评估用β7整联蛋白拮抗剂治疗胃肠炎性病症的用途
CN105246914B (zh) 2013-04-02 2021-08-27 中外制药株式会社 Fc区变体
CA2908819A1 (en) 2013-04-22 2014-10-30 Glycotope Gmbh Anti-cancer treatments with anti-egfr antibodies having a low fucosylation
UA118029C2 (uk) 2013-04-29 2018-11-12 Ф. Хоффманн-Ля Рош Аг Модифіковане антитіло, що зв'язується з людським fcrn, й способи його застосування
US11117975B2 (en) 2013-04-29 2021-09-14 Teva Pharmaceuticals Australia Pty Ltd Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B
WO2014177459A2 (en) 2013-04-29 2014-11-06 F. Hoffmann-La Roche Ag Fc-receptor binding modified asymmetric antibodies and methods of use
BR112015027313A2 (pt) 2013-04-29 2017-09-26 Teva Pharmaceuticals Australia Pty Ltd anticorpos anti-cd38 e fusões ao interferon alfa-2b atenuado
EP3594240B1 (en) 2013-05-20 2023-12-06 F. Hoffmann-La Roche AG Anti-transferrin receptor antibodies and methods of use
WO2014186877A1 (en) 2013-05-24 2014-11-27 Uger Marni Diane FasR ANTIBODIES FOR DIAGNOSTIC AND THERAPEUTIC USE
BR112015029395A2 (pt) 2013-05-24 2017-09-19 Medimmune Llc Anticorpos anti-b7-h5 e seus usos
KR102332303B1 (ko) 2013-05-31 2021-11-26 자임워크스 인코포레이티드 감소되거나 침묵화된 효과기 기능을 갖는 이종다량체
AR096601A1 (es) 2013-06-21 2016-01-20 Novartis Ag Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso
UY35620A (es) 2013-06-21 2015-01-30 Novartis Ag Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso
MX2015017852A (es) 2013-06-24 2016-08-11 Chugai Pharmaceutical Co Ltd Agente terapeutico que comprende el anticuerpo anti-epirregulina humanizado con ingrediente activo contra el carcinoma de pulmon de celulas no pequeñas excluyendo el adenocarcinoma.
WO2015017146A2 (en) 2013-07-18 2015-02-05 Fabrus, Inc. Antibodies with ultralong complementarity determining regions
CA2918370A1 (en) 2013-07-18 2015-01-22 Fabrus, Inc. Humanized antibodies with ultralong complementarity determining regions
WO2015021423A2 (en) 2013-08-08 2015-02-12 Biogen Idec Ma Inc. Purification of chimeric fviii molecules
US11384149B2 (en) 2013-08-09 2022-07-12 Macrogenics, Inc. Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof
UA116479C2 (uk) 2013-08-09 2018-03-26 Макродженікс, Інк. БІСПЕЦИФІЧНЕ МОНОВАЛЕНТНЕ Fc-ДІАТІЛО, ЯКЕ ОДНОЧАСНО ЗВ'ЯЗУЄ CD32B I CD79b, ТА ЙОГО ЗАСТОСУВАННЯ
SG11201601044XA (en) 2013-08-12 2016-03-30 Genentech Inc Compositions and method for treating complement-associated conditions
HK1221725A1 (zh) 2013-08-13 2017-06-09 Sanofi 纤溶酶原激活剂抑制剂-1(pai-1)的抗体及其用途
TW201722994A (zh) 2013-08-13 2017-07-01 賽諾菲公司 胞漿素原活化素抑制劑-１（ｐａｉ-１）之抗體及其用途
HK1219280A1 (zh) 2013-08-14 2017-03-31 Novartis Ag 治疗偶发性包涵体肌炎之方法
TW202003554A (zh) 2013-08-14 2020-01-16 美商百歐維拉提夫治療公司 因子ｖｉｉｉ－ｘｔｅｎ融合物及其用途
EP2840091A1 (en) 2013-08-23 2015-02-25 MacroGenics, Inc. Bi-specific diabodies that are capable of binding gpA33 and CD3 and uses thereof
EP2839842A1 (en) 2013-08-23 2015-02-25 MacroGenics, Inc. Bi-specific monovalent diabodies that are capable of binding CD123 and CD3 and uses thereof
CN105792836A (zh) 2013-08-28 2016-07-20 施特姆森特克斯股份有限公司 新型sez6调节剂以及应用方法
US20150093399A1 (en) 2013-08-28 2015-04-02 Bioasis Technologies, Inc. Cns-targeted conjugates having modified fc regions and methods of use thereof
SG11201601424PA (en) 2013-08-28 2016-03-30 Stemcentrx Inc Site-specific antibody conjugation methods and compositions
CN112552401B (zh) 2013-09-13 2023-08-25 广州百济神州生物制药有限公司 抗pd1抗体及其作为治疗剂与诊断剂的用途
JP2016537399A (ja) 2013-09-17 2016-12-01 ジェネンテック， インコーポレイテッド 抗ｌｇｒ５抗体を使用する方法
HUE057005T2 (hu) 2013-09-25 2022-04-28 Bioverativ Therapeutics Inc Oszlopon történõ vírusinaktiváló eljárások
ES2881306T3 (es) 2013-09-27 2021-11-29 Chugai Pharmaceutical Co Ltd Método para la producción de heteromultímeros de polipéptidos
WO2015050959A1 (en) 2013-10-01 2015-04-09 Yale University Anti-kit antibodies and methods of use thereof
SI3052192T1 (sl) 2013-10-02 2020-11-30 Medimmune, Llc Nevtralizarijoča protitelesa proti-influenci A in njihove uporabe
BR112016006929A2 (pt) 2013-10-11 2017-09-19 Hoffmann La Roche Anticorpo, ácido nucleico, vetor de expressão, célula hospedeira, métodos de preparação de anticorpo, de tratamento de pacientes e de geração de um anticorpo, composição farmacêutica e uso do anticorpo
JP2016537965A (ja) 2013-10-11 2016-12-08 ジェネンテック， インコーポレイテッド Ｎｓｐ４阻害剤及び使用方法
BR112016008477A2 (pt) 2013-10-18 2017-10-03 Genentech Inc Corpos, ácido nucleico, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica e usos do anticorpo
AR098155A1 (es) 2013-10-23 2016-05-04 Genentech Inc Métodos para diagnosticar y tratar trastornos eosinofílicos
HRP20192080T1 (hr) 2013-10-31 2020-02-07 Resolve Therapeutics, Llc Terapeutske fuzije nukleaza-albumine i postupci
RU2016122041A (ru) 2013-11-06 2017-12-11 ЭББВИ СТЕМСЕНТРКС ЭлЭлСи Новые анти-клаудин антитела и способы их применения
CN104623637A (zh) 2013-11-07 2015-05-20 健能隆医药技术（上海）有限公司 Il-22二聚体在制备静脉注射药物中的应用
CN105849125B (zh) 2013-11-07 2020-05-15 国家医疗保健研究所 神经调节蛋白变构抗her3抗体
EP3065769A4 (en) 2013-11-08 2017-05-31 Biogen MA Inc. Procoagulant fusion compound
KR102813659B1 (ko) 2013-11-11 2025-05-28 추가이 세이야쿠 가부시키가이샤 개변된 항체 가변영역을 포함하는 항원 결합 분자
US9683998B2 (en) 2013-11-13 2017-06-20 Pfizer Inc. Tumor necrosis factor-like ligand 1A specific antibodies and compositions and uses thereof
LT3071597T (lt) 2013-11-21 2020-10-12 F. Hoffmann-La Roche Ag Antikūnai prieš alfa-sunukleiną ir jų naudojimo būdai
DK3078744T3 (da) 2013-12-04 2020-09-28 Chugai Pharmaceutical Co Ltd Antigen-bindende molekyler, antigen-bindingsaktiviteten af hvilke varierer i henhold til koncentrationen af forbindelser, og biblioteker af molekylerne
EP3077504B1 (en) 2013-12-06 2019-08-14 Dana-Farber Cancer Institute, Inc. Therapeutic peptides
NZ720769A (en) 2013-12-09 2022-10-28 Allakos Inc Anti-siglec-8 antibodies and methods of use thereof
WO2015089375A1 (en) 2013-12-13 2015-06-18 The General Hospital Corporation Soluble high molecular weight (hmw) tau species and applications thereof
SG11201604784XA (en) 2013-12-13 2016-07-28 Genentech Inc Anti-cd33 antibodies and immunoconjugates
AU2014364593A1 (en) 2013-12-17 2016-07-07 Genentech, Inc. Methods of treating cancer using PD-1 axis binding antagonists and an anti-CD20 antibody
JP2017507900A (ja) 2013-12-17 2017-03-23 ジェネンテック， インコーポレイテッド Ｐｄ−１軸結合アンタゴニスト及び抗ｈｅｒ２抗体を使用してｈｅｒ２陽性がんを治療する方法
US8980273B1 (en) 2014-07-15 2015-03-17 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
IL263466B2 (en) 2013-12-17 2023-10-01 Genentech Inc Anti-CD3 antibodies and methods of using them
US8986691B1 (en) 2014-07-15 2015-03-24 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
WO2015095423A2 (en) 2013-12-17 2015-06-25 Genentech, Inc. Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists
AU2014368696A1 (en) * 2013-12-20 2016-06-02 F. Hoffmann-La Roche Ag Humanized anti-Tau(pS422) antibodies and methods of use
TWI670283B (zh) 2013-12-23 2019-09-01 美商建南德克公司 抗體及使用方法
WO2015097536A2 (en) 2013-12-24 2015-07-02 Janssen Pharmaceutical Nv Anti-vista antibodies and fragments
US11014987B2 (en) 2013-12-24 2021-05-25 Janssen Pharmaceutics Nv Anti-vista antibodies and fragments, uses thereof, and methods of identifying same
SG11201605203UA (en) 2013-12-24 2016-07-28 Argen X N V Fcrn antagonists and methods of use
EP3089758B1 (en) 2014-01-03 2021-01-27 F.Hoffmann-La Roche Ag Covalently linked helicar-anti-helicar antibody conjugates and uses thereof
CN105899540B (zh) 2014-01-03 2020-02-07 豪夫迈·罗氏有限公司 双特异性抗-半抗原/抗-血脑屏障受体的抗体、其复合物及它们作为血脑屏障穿梭物的应用
BR112016014945A2 (pt) 2014-01-03 2018-01-23 F. Hoffmann-La Roche Ag conjugado, formulação farmacêutica e uso
CA2932547C (en) 2014-01-06 2023-05-23 F. Hoffmann-La Roche Ag Monovalent blood brain barrier shuttle modules
AU2015204646B2 (en) 2014-01-10 2020-08-27 Bioverativ Therapeutics Inc. Factor VIII chimeric proteins and uses thereof
RU2727639C2 (ru) 2014-01-15 2020-07-22 Ф.Хоффманн-Ля Рош Аг Варианты fc-области с модифицированной способностью связываться с fcrn и с сохраненной способностью связываться с белком а
WO2015109212A1 (en) 2014-01-17 2015-07-23 Pfizer Inc. Anti-il-2 antibodies and compositions and uses thereof
PE20170256A1 (es) 2014-01-24 2017-04-22 Ngm Biopharmaceuticals Inc Proteinas de union y sus metodos de uso
EP3096797A1 (en) 2014-01-24 2016-11-30 F. Hoffmann-La Roche AG Methods of using anti-steap1 antibodies and immunoconjugates
ES2694857T3 (es) 2014-02-04 2018-12-27 Genentech, Inc. Smoothened mutante y métodos de uso de la misma
EP3102230B1 (en) 2014-02-08 2021-04-28 F. Hoffmann-La Roche AG Methods of treating alzheimer's disease
CA2938466C (en) 2014-02-08 2021-11-02 Genentech, Inc. Methods of treating alzheimer's disease
EA201691610A8 (ru) 2014-02-12 2018-05-31 Дженентек, Инк. Анти-jagged1 антитела и способы применения
KR20160135190A (ko) 2014-02-14 2016-11-25 앤드류 에스. 카이 혈관형성 암의 치료를 위한 개선된 방법
UA117608C2 (uk) 2014-02-21 2018-08-27 Дженентек, Інк. Спосіб лікування еозинофільного захворювання у пацієнта шляхом застосування біспецифічного анти-il-13/il-17 антитіла
US9732154B2 (en) * 2014-02-28 2017-08-15 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia
DK3110446T3 (da) 2014-02-28 2022-02-28 Allakos Inc Fremgangsmåder og sammensætninger til behandling af Siglec-8-associerede sygdomme
NZ631007A (en) 2014-03-07 2015-10-30 Alexion Pharma Inc Anti-c5 antibodies having improved pharmacokinetics
JP2017509337A (ja) 2014-03-12 2017-04-06 ノバルティス アーゲー イムノコンジュゲートを作製する抗体を修飾するための特定部位
KR102587838B1 (ko) 2014-03-14 2023-10-12 바이오몰레큘러 홀딩스 엘엘씨 비-펩티드 결합을 함유하는 하이브리드 면역글로불린
KR102345173B1 (ko) 2014-03-14 2021-12-29 이나뜨 파르마 에스.에이. 증가된 안정성을 가진 인간화 항체
CA2939006A1 (en) 2014-03-14 2015-09-17 Dana-Farber Cancer Institute, Inc. Vaccine compositions and methods for restoring nkg2d pathway function against cancers
AU2015229035B2 (en) 2014-03-14 2021-08-05 Genentech, Inc. Methods and compositions for secretion of heterologous polypeptides
TWI701042B (zh) 2014-03-19 2020-08-11 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
WO2015143091A1 (en) 2014-03-19 2015-09-24 Genzyme Corporation Site-specific glycoengineering of targeting moieties
WO2015140591A1 (en) 2014-03-21 2015-09-24 Nordlandssykehuset Hf Anti-cd14 antibodies and uses thereof
KR102399028B1 (ko) 2014-03-21 2022-05-17 엑스-바디 인코포레이티드 이중-특이적 항원-결합 폴리펩티드
RU2016141385A (ru) 2014-03-24 2018-04-28 Дженентек, Инк. Лечение рака антагонистами с-мет и их корреляция с экспрессией hgf
WO2015148809A1 (en) 2014-03-27 2015-10-01 Genentech, Inc. Methods for diagnosing and treating inflammatory bowel disease
KR20160146747A (ko) 2014-03-31 2016-12-21 제넨테크, 인크. 항혈관신생제 및 ox40 결합 효능제를 포함하는 조합 요법
SG11201607969XA (en) 2014-03-31 2016-10-28 Genentech Inc Anti-ox40 antibodies and methods of use
CA2944649C (en) 2014-04-04 2022-06-21 Bionomics, Inc. Humanized antibodies that bind lgr5
AU2015244814B2 (en) 2014-04-07 2020-12-24 Chugai Seiyaku Kabushiki Kaisha Immunoactivating antigen-binding molecule
SG11201608192SA (en) 2014-04-11 2016-10-28 Medimmune Llc Bispecific her2 antibodies
JP2017518737A (ja) 2014-04-21 2017-07-13 ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． ＳＹＫ標的治療薬のための抗ｐＳＹＫ抗体分子及びその使用
TW201622746A (zh) 2014-04-24 2016-07-01 諾華公司 改善或加速髖部骨折術後身體復原之方法
WO2015164615A1 (en) 2014-04-24 2015-10-29 University Of Oslo Anti-gluten antibodies and uses thereof
UA119352C2 (uk) 2014-05-01 2019-06-10 Тева Фармасьютикалз Острейліа Пті Лтд Комбінація леналідоміду або помалідоміду і конструкції анти-cd38 антитіло-атенуйований інтерферон альфа-2b та спосіб лікування суб'єкта, який має cd38-експресуючу пухлину
AU2015253042A1 (en) 2014-05-01 2016-10-20 Genentech, Inc. Anti-factor D antibody variants and uses thereof
JP6827319B2 (ja) 2014-05-08 2021-02-10 中外製薬株式会社 Ｇｐｃ３標的治療剤療法が有効である患者に投与されるｇｐｃ３標的治療剤
MX2016014434A (es) 2014-05-13 2017-02-23 Chugai Pharmaceutical Co Ltd Molecula de union a antigeno redirigida a celulas t para celulas que tienen funcion de inmunosupresion.
EP4707303A2 (en) 2014-05-16 2026-03-11 Ablynx NV Improved immunoglobulin variable domains
IL318433A (en) 2014-05-16 2025-03-01 Ablynx Nv Improved immunoglobulin variable complexes
WO2015179658A2 (en) 2014-05-22 2015-11-26 Genentech, Inc. Anti-gpc3 antibodies and immunoconjugates
RU2016144405A (ru) 2014-05-23 2018-06-26 Дженентек, Инк. MiT БИОМАРКЕРЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
SI3148579T1 (sl) 2014-05-28 2021-07-30 Agenus Inc. Proti GITR antitelesa in postopki z njihovo uporabo
EA035419B9 (ru) 2014-05-29 2020-08-07 Мэкроудженикс, Инк. Триспецифичные связывающие молекулы и способы их применения
EP3613433B1 (en) 2014-05-30 2022-01-05 Shanghai Henlius Biotech, Inc. Anti-epidermal growth factor receptor (egfr) antibodies
PE20170441A1 (es) 2014-06-06 2017-04-26 Bristol Myers Squibb Co Anticuerpos contra el receptor del factor de necrosis tumoral inducido por glucocorticoides (gitr) y sus usos
CN106459202A (zh) 2014-06-11 2017-02-22 豪夫迈·罗氏有限公司 抗LgR5抗体及其用途
US11123426B2 (en) 2014-06-11 2021-09-21 The Trustees Of Dartmouth College Use of vista agonists and antagonists to suppress or enhance humoral immunity
CN107073121A (zh) 2014-06-13 2017-08-18 基因泰克公司 治疗及预防癌症药物抗性的方法
EP3161001A2 (en) 2014-06-25 2017-05-03 Novartis AG Antibodies specific for il-17a fused to hyaluronan binding peptide tags
BR112016029935A2 (pt) 2014-06-26 2017-10-31 Hoffmann La Roche ?anticorpos anti-brdu, complexo, formulação farmacêutica e uso de anticorpo?
AR100978A1 (es) 2014-06-26 2016-11-16 Hoffmann La Roche LANZADERAS CEREBRALES DE ANTICUERPO HUMANIZADO ANTI-Tau(pS422) Y USOS DE LAS MISMAS
JP6822849B2 (ja) 2014-06-27 2021-01-27 イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅ Ｐｈａｒｍａ Ｐｈａｒｍａ Ｓ．Ａ． 多重特異的ＮＫｐ４６結合タンパク質
WO2015197598A2 (en) 2014-06-27 2015-12-30 Innate Pharma Multispecific antigen binding proteins
US11008561B2 (en) 2014-06-30 2021-05-18 Bioverativ Therapeutics Inc. Optimized factor IX gene
CN106604742B (zh) 2014-07-03 2019-01-11 百济神州有限公司 抗pd-l1抗体及其作为治疗剂及诊断剂的用途
CN106488775A (zh) 2014-07-11 2017-03-08 基因泰克公司 Notch途径抑制
RU2715038C2 (ru) 2014-07-11 2020-02-21 Дженентек, Инк. Антитела анти-pd-l1 и способы их диагностического применения
MX392761B (es) 2014-07-15 2025-03-21 Medimmune Llc Anticuerpos anti-influenza b neutralizantes y usos de los mismos.
BR112017001385B1 (pt) 2014-07-22 2023-12-05 Cb Therapeutics, Inc. Anticorpo isolado ou fragmento do mesmo que liga a pd-1, uso deste, composição, polinucleotídeo isolado e vetor de expressão
KR102476226B1 (ko) 2014-08-05 2022-12-12 아폴로믹스 인코포레이티드 항-pd-l1 항체
WO2016020791A1 (en) 2014-08-05 2016-02-11 Novartis Ag Ckit antibody drug conjugates
WO2016020880A2 (en) 2014-08-07 2016-02-11 Novartis Ag Angiopoietin-like 4 antibodies and methods of use
WO2016020882A2 (en) 2014-08-07 2016-02-11 Novartis Ag Angiopoetin-like 4 (angptl4) antibodies and methods of use
MA40513A (fr) 2014-08-12 2017-06-21 Novartis Ag Conjugués médicament-anticorps anti-cdh6
JO3663B1 (ar) 2014-08-19 2020-08-27 Merck Sharp & Dohme الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين
MD4733C1 (ro) 2014-08-19 2021-07-31 Merck Sharp & Dohme Corp Anticorpi anti-TIGIT
WO2016030488A1 (en) 2014-08-27 2016-03-03 Innate Pharma Treatment of celiac disease
DK4074735T3 (da) 2014-08-28 2025-07-14 Bioatla Inc Betinget aktive kimæriske antigenreceptorer til modificerede t-celler
TW201617368A (zh) 2014-09-05 2016-05-16 史坦森特瑞斯公司 新穎抗ｍｆｉ２抗體及使用方法
FR3025515B1 (fr) 2014-09-05 2016-09-09 Lab Francais Du Fractionnement Procede de purification d'un anticorps monoclonal
MA40579A (fr) 2014-09-12 2016-03-17 Genentech Inc Anticorps anti-cll-1 et immunoconjugués
LT3191135T (lt) 2014-09-12 2020-11-25 Genentech, Inc. Anti-her2 antikūnai ir imunokonjugatai
WO2016040724A1 (en) 2014-09-12 2016-03-17 Genentech, Inc. Anti-b7-h4 antibodies and immunoconjugates
SG11201701128YA (en) 2014-09-12 2017-03-30 Genentech Inc Cysteine engineered antibodies and conjugates
MX2017003472A (es) 2014-09-17 2017-10-31 Genentech Inc Inmunoconjugados que comprenden anticuerpos anti-her2.
HUE049175T2 (hu) 2014-09-23 2020-09-28 Hoffmann La Roche Eljárás anti-CD79b immunkonjugátumok alkalmazására
MA40764A (fr) 2014-09-26 2017-08-01 Chugai Pharmaceutical Co Ltd Agent thérapeutique induisant une cytotoxicité
CU20170038A7 (es) 2014-09-26 2017-10-05 Bayer Pharma AG Derivados de adrenomedulina estabililzados especialmente útiles en el tratamiento y/o prevención de trastornos cardiovasculares, edematosos y/o inflamatorios
MX386297B (es) 2014-09-29 2025-03-18 Univ Duke Moleculas biespecificas que comprenden un brazo orientado a la envoltura vih-1.
US20160108105A1 (en) * 2014-10-06 2016-04-21 Genexine, Inc. Human igg4 fc polypeptide variant
MA41044A (fr) 2014-10-08 2017-08-15 Novartis Ag Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer
CA3205824A1 (en) 2014-10-09 2016-04-14 Genzyme Corporation Glycoengineered antibody drug conjugates
BR112017007765B1 (pt) 2014-10-14 2023-10-03 Halozyme, Inc Composições de adenosina deaminase-2 (ada2), variantes do mesmo e métodos de usar o mesmo
JP2017536102A (ja) 2014-10-16 2017-12-07 ジェネンテック， インコーポレイテッド 抗アルファ−シヌクレイン抗体及び使用方法
MA41480A (fr) 2014-10-17 2017-12-19 Glenmark Pharmaceuticals Sa Anticorps qui se lient au ccr6 et leurs utilisations
US10329348B2 (en) 2014-10-23 2019-06-25 Innate Pharma Treatment of cancers using anti-NKG2A agents
US10544199B2 (en) 2014-10-29 2020-01-28 Teva Pharmaceuticals Australia Pty Ltd Interferon alpha 2B variants
WO2016073380A1 (en) 2014-11-03 2016-05-12 Genentech, Inc. Method and biomarkers for predicting efficacy and evaluation of an ox40 agonist treatment
CA2966523A1 (en) 2014-11-03 2016-05-12 Genentech, Inc. Assays for detecting t cell immune subsets and methods of use thereof
CA2961439A1 (en) 2014-11-05 2016-05-12 Genentech, Inc. Anti-fgfr2/3 antibodies and methods using same
US10066002B2 (en) 2014-11-05 2018-09-04 Genentech, Inc. Methods of producing two chain proteins in bacteria
WO2016073791A1 (en) 2014-11-05 2016-05-12 Genentech, Inc. Methods of producing two chain proteins in bacteria
CA2960569A1 (en) 2014-11-06 2016-05-12 F. Hoffmann-Laroche Ag Fc-region variants with modified fcrn- and protein a-binding properties
DK3215528T3 (da) 2014-11-06 2019-10-07 Hoffmann La Roche Fc-regionvarianter med modificeret FcRn-binding og anvendelsesfremgangsmåder
US20160152720A1 (en) 2014-11-06 2016-06-02 Genentech, Inc. Combination therapy comprising ox40 binding agonists and tigit inhibitors
WO2016073157A1 (en) 2014-11-06 2016-05-12 Genentech, Inc. Anti-ang2 antibodies and methods of use thereof
CN107105632A (zh) 2014-11-10 2017-08-29 豪夫迈·罗氏有限公司 肾病动物模型及其治疗剂
CR20170240A (es) 2014-11-10 2018-04-03 Genentech Inc Anticuerpos anti-interleucina-33 y sus usos
GB2538120A (en) 2014-11-11 2016-11-09 Medimmune Ltd Therapeutic combinations comprising anti-CD73 antibodies and uses thereof
TWI831044B (zh) 2014-11-11 2024-02-01 日商中外製藥股份有限公司 抗原結合分子、包含抗原結合分子的醫藥組合物以及製造及選擇抗原結合分子之方法
TW201625692A (zh) 2014-11-14 2016-07-16 諾華公司 抗體藥物結合物
SG10201807625PA (en) 2014-11-17 2018-10-30 Genentech Inc Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists
KR102614189B1 (ko) 2014-11-17 2023-12-18 리제너론 파아마슈티컬스, 인크. Cd3xcd20 이특이적 항체를 이용한 종양의 치료 방법
JP6859259B2 (ja) 2014-11-19 2021-04-14 ジェネンテック， インコーポレイテッド ＢＡＣＥｌに対する抗体及び神経疾患免疫療法のためのその使用
CN107428820B (zh) 2014-11-19 2022-03-22 阿克松神经系统科学公司 在阿尔茨海默氏病中的人源化tau抗体
US10508151B2 (en) 2014-11-19 2019-12-17 Genentech, Inc. Anti-transferrin receptor antibodies and methods of use
WO2016081640A1 (en) 2014-11-19 2016-05-26 Genentech, Inc. Anti-transferrin receptor / anti-bace1 multispecific antibodies and methods of use
AU2015349878A1 (en) 2014-11-21 2017-05-25 Bristol-Myers Squibb Company Antibodies against CD73 and uses thereof
JP6668345B2 (ja) 2014-11-21 2020-03-18 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 修飾された重鎖定常領域を含む抗体
EP3227332B1 (en) 2014-12-03 2019-11-06 F.Hoffmann-La Roche Ag Multispecific antibodies
CA2969730A1 (en) 2014-12-05 2016-06-09 Immunext, Inc. Identification of vsig8 as the putative vista receptor and its use thereof to produce vista/vsig8 modulators
ES2744540T3 (es) 2014-12-05 2020-02-25 Hoffmann La Roche Anticuerpos anti-CD79b y procedimientos de uso
JP6864953B2 (ja) 2014-12-09 2021-04-28 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル Ａｘｌに対するヒトモノクローナル抗体
KR20170085595A (ko) 2014-12-10 2017-07-24 제넨테크, 인크. 혈뇌 장벽 수용체 항체 및 사용 방법
US10093733B2 (en) 2014-12-11 2018-10-09 Abbvie Inc. LRP-8 binding dual variable domain immunoglobulin proteins
EP3633371A1 (en) 2014-12-18 2020-04-08 F. Hoffmann-La Roche AG Assay and method for determining cdc eliciting antibodies
BR112017011235A2 (pt) 2014-12-19 2018-02-06 Chugai Pharmaceutical Co Ltd anticorpos anti-c5 e métodos de uso
UY36449A (es) 2014-12-19 2016-07-29 Novartis Ag Composiciones y métodos para anticuerpos dirigidos a bmp6
KR101860280B1 (ko) 2014-12-19 2018-05-21 추가이 세이야쿠 가부시키가이샤 항-마이오스타틴 항체, 변이체 Fc 영역을 함유하는 폴리펩타이드, 및 사용 방법
WO2016097865A1 (en) 2014-12-19 2016-06-23 Regenesance B.V. Antibodies that bind human c6 and uses thereof
JP6180663B2 (ja) 2014-12-23 2017-08-16 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｔｉｇｉｔに対する抗体
WO2016115345A1 (en) 2015-01-14 2016-07-21 The Brigham And Women's Hospital, Treatment of cancer with anti-lap monoclonal antibodies
CN113956354A (zh) 2015-01-22 2022-01-21 中外制药株式会社 两种以上抗-c5抗体的组合与使用方法
RU2017129236A (ru) 2015-01-26 2019-03-07 Макродженикс, Инк. Мультивалентные молекулы, содержащие dr5-связывающие домены
JP2018506275A (ja) 2015-01-28 2018-03-08 ジェネンテック， インコーポレイテッド 多発性硬化症の遺伝子発現マーカー及び治療
EP3253784B1 (en) 2015-02-04 2020-05-06 Genentech, Inc. Mutant smoothened and methods of using the same
KR102605798B1 (ko) 2015-02-05 2023-11-23 추가이 세이야쿠 가부시키가이샤 이온 농도 의존적 항원 결합 도메인을 포함하는 항체, Fc 영역 개변체, IL-8에 결합하는 항체, 및 그들의 사용
US10550173B2 (en) 2015-02-19 2020-02-04 Compugen, Ltd. PVRIG polypeptides and methods of treatment
DK3653221T5 (da) 2015-02-19 2024-08-26 Compugen Ltd Anti-pvrig-antistoffer og anvendelsesfremgangsmåder
WO2016135041A1 (en) 2015-02-26 2016-09-01 INSERM (Institut National de la Santé et de la Recherche Médicale) Fusion proteins and antibodies comprising thereof for promoting apoptosis
HK1244229A1 (zh) 2015-02-26 2018-08-03 F. Hoffmann-La Roche Ag 治疗CROHN病的整联蛋白β7拮抗剂和方法
CA2978253A1 (en) 2015-03-09 2016-09-15 Argenx Bvba Methods of reducing serum levels of fc-containing agents using fcrn antagonists
MX2017011486A (es) 2015-03-16 2018-06-15 Genentech Inc Métodos de detección y cuantificación de il-13 y sus usos en el diagnóstico y tratamiento de enfermedades asociadas a th2.
WO2016146833A1 (en) 2015-03-19 2016-09-22 F. Hoffmann-La Roche Ag Biomarkers for nad(+)-diphthamide adp ribosyltransferase resistance
WO2016161010A2 (en) 2015-03-30 2016-10-06 Regeneron Pharmaceuticals, Inc. Heavy chain constant regions with reduced binding to fc gamma receptors
FR3034420A1 (fr) 2015-03-31 2016-10-07 Lab Francais Du Fractionnement Anticorps monoclonaux anti-cd303
AR104368A1 (es) 2015-04-03 2017-07-19 Lilly Co Eli Anticuerpos biespecíficos anti-cd20- / anti-baff
WO2016161390A1 (en) 2015-04-03 2016-10-06 Eureka Therapeutics, Inc. Constructs targeting afp peptide/mhc complexes and uses thereof
KR20180002653A (ko) 2015-04-07 2018-01-08 제넨테크, 인크. 효능작용 활성을 갖는 항원 결합 복합체 및 사용 방법
CN121159719A (zh) 2015-04-17 2025-12-19 高山免疫科学股份有限公司 具有可调的亲和力的免疫调节蛋白
CN107810197B (zh) 2015-04-24 2022-10-25 豪夫迈·罗氏有限公司 鉴定包含结合多肽的细菌的方法
EP3288981A1 (en) 2015-05-01 2018-03-07 Genentech, Inc. Masked anti-cd3 antibodies and methods of use
SG11201708804WA (en) 2015-05-07 2017-11-29 Agenus Inc Anti-ox40 antibodies and methods of use thereof
HK1248577A1 (zh) 2015-05-11 2018-10-19 F. Hoffmann-La Roche Ag 治疗狼疮性肾炎的组合物和方法
ES2835866T5 (es) 2015-05-12 2024-12-02 Hoffmann La Roche Procedimientos terapéuticos y de diagnóstico para el cáncer
TW201702272A (zh) 2015-05-22 2017-01-16 美國紀念斯隆 凱特琳癌症中心 Ｐｒａｍｅ肽專一性類ｔ細胞受體抗體
WO2016188911A1 (en) 2015-05-22 2016-12-01 INSERM (Institut National de la Santé et de la Recherche Médicale) Human monoclonal antibodies fragments inhibiting both the cath-d catalytic activity and its binding to the lrp1 receptor
AR105618A1 (es) 2015-05-29 2017-10-25 Genentech Inc Metilación del promotor del ligando al receptor de muerte programada (pd-l1) en cáncer
DK3303396T5 (da) 2015-05-29 2024-10-07 Bristol Myers Squibb Co Antistoffer mod ox40 og anvendelser deraf
ES2789500T5 (es) 2015-05-29 2023-09-20 Hoffmann La Roche Procedimientos terapéuticos y de diagnóstico para el cáncer
HK1250723A1 (zh) 2015-05-29 2019-01-11 F. Hoffmann-La Roche Ag 人源化抗埃博拉病毒糖蛋白抗体和使用方法
EP3303373B1 (en) 2015-05-30 2020-04-08 Molecular Templates, Inc. De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
HK1249016A1 (zh) 2015-06-02 2018-10-26 豪夫迈‧罗氏有限公司 使用抗il-34抗体治疗神经疾病的组合物和方法
NZ775762A (en) 2015-06-05 2025-02-28 Genentech Inc Anti-tau antibodies and methods of use
EP3303387A2 (en) 2015-06-05 2018-04-11 Novartis AG Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor
TWI773646B (zh) 2015-06-08 2022-08-11 美商宏觀基因股份有限公司 結合lag-3的分子和其使用方法
MX2017015937A (es) 2015-06-08 2018-12-11 Genentech Inc Métodos de tratamiento del cáncer con anticuerpos anti-ox40 y antagonistas de unión al eje de pd-1.
JP2018521019A (ja) 2015-06-08 2018-08-02 ジェネンテック， インコーポレイテッド 抗ｏｘ４０抗体を使用して癌を治療する方法
CN108064246A (zh) 2015-06-15 2018-05-22 基因泰克公司 抗体和免疫结合物
TW201710286A (zh) 2015-06-15 2017-03-16 艾伯維有限公司 抗ｖｅｇｆ、ｐｄｇｆ及／或其受體之結合蛋白
DK3310814T5 (da) 2015-06-16 2024-10-07 Hoffmann La Roche Humaniserede og affinitetsmodnede antistoffer mod FcRH5 og fremgangsmåder til anvendelse
EP3916018A1 (en) 2015-06-16 2021-12-01 Genentech, Inc. Anti-cd3 antibodies and methods of use
US10501545B2 (en) 2015-06-16 2019-12-10 Genentech, Inc. Anti-CLL-1 antibodies and methods of use
KR102689256B1 (ko) 2015-06-17 2024-07-30 제넨테크, 인크. Pd-1 축 결합 길항제 및 탁산을 사용하여 국소적 진행성 또는 전이성 유방암을 치료하는 방법
US20190194315A1 (en) 2015-06-17 2019-06-27 Novartis Ag Antibody drug conjugates
CN107787331B (zh) 2015-06-17 2022-01-11 豪夫迈·罗氏有限公司 抗her2抗体和使用方法
US10774145B2 (en) 2015-06-17 2020-09-15 Allakos Inc. Methods and compositions for treating fibrotic diseases
DK3313876T3 (da) 2015-06-23 2025-04-22 Innate Pharma Multispecifikke antigenbindende proteiner
AU2016284871B2 (en) 2015-06-23 2022-09-29 Innate Pharma Multispecific NK engager proteins
HUE057952T2 (hu) 2015-06-24 2022-06-28 Hoffmann La Roche Anti-transzferrin receptor antitestek testreszabott affinitással
CA2990360C (en) 2015-06-24 2024-02-13 Janssen Pharmaceutica Nv Anti-vista antibodies and fragments
WO2016207245A1 (en) 2015-06-24 2016-12-29 F. Hoffmann-La Roche Ag Humanized anti-tau(ps422) antibodies and methods of use
JP7114460B2 (ja) 2015-06-26 2022-08-08 サノフィ・バイオテクノロジー モノクローナル抗ＩＬ－１ＲＡｃＰ抗体
UY36751A (es) 2015-06-26 2017-01-31 Novartis Ag Anticuerpos de factor xi y métodos de uso
EP3978525A1 (en) 2015-06-29 2022-04-06 Ventana Medical Systems, Inc. Materials and methods for performing histochemical assays for human pro-epiregulin and amphiregulin
EP3313885A1 (en) 2015-06-29 2018-05-02 H. Hoffnabb-La Roche Ag Type ii anti-cd20 antibody for use in organ transplantation
US20180305451A1 (en) 2015-07-13 2018-10-25 Compugen Ltd. Hide1 compositions and methods
RU2737637C2 (ru) * 2015-07-22 2020-12-01 Инатерис Антитела против tfr и их применение при лечении пролиферативных и воспалительных расстройств
US11066481B2 (en) 2015-07-23 2021-07-20 The Regents Of The University Of California Antibodies to coagulation factor XIa and uses thereof
WO2017019729A1 (en) 2015-07-27 2017-02-02 The General Hospital Corporation Antibody derivatives with conditionally enabled effector function
HUE068868T2 (hu) 2015-07-30 2025-02-28 Macrogenics Inc PD-1-hez kötõdõ molekulák és alkalmazásukra szolgáló eljárások
EP3328994A4 (en) 2015-07-31 2019-04-17 Memorial Sloan-Kettering Cancer Center CD56-Faced Antigen-Binding Proteins and Uses Thereof
US11236159B2 (en) 2015-08-03 2022-02-01 Novartis Ag Methods of treating FGF21-associated disorders
EA201890423A1 (ru) 2015-08-03 2018-07-31 Биовератив Терапьютикс Инк. Слитые белки фактора ix, способы их получения и применения
SI3331910T1 (sl) 2015-08-03 2020-07-31 Engmab Sarl Monoklonska protitelesa proti humani antigen dozorevanja limfocitov B (BCMA)
CN105384825B (zh) 2015-08-11 2018-06-01 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
WO2018028647A1 (en) 2016-08-10 2018-02-15 Legend Biotech Usa Inc. Chimeric antigen receptors targeting bcma and methods of use thereof
CN108026180B (zh) 2015-08-28 2022-06-07 豪夫迈·罗氏有限公司 抗羟腐胺赖氨酸抗体及其用途
AU2016317915B2 (en) 2015-09-01 2021-02-18 Agenus Inc. Anti-PD-1 antibodies and methods of use thereof
CN117510633A (zh) 2015-09-02 2024-02-06 伊缪泰普有限公司 抗lag-3抗体
HRP20210650T1 (hr) 2015-09-09 2021-05-28 Novartis Ag Protutijela koja vežu timusni stromalni limfopoetin (tslp) i postupci uporabe protutijela
EA038332B1 (ru) 2015-09-09 2021-08-10 Новартис Аг Молекулы, связывающиеся с тимусным стромальным лимфопоэтином (tslp), и способы применения таких молекул
WO2017046746A1 (en) 2015-09-15 2017-03-23 Acerta Pharma B.V. Therapeutic combinations of a btk inhibitor and a gitr binding molecule, a 4-1bb agonist, or an ox40 agonist
US9862760B2 (en) 2015-09-16 2018-01-09 Novartis Ag Polyomavirus neutralizing antibodies
UA120981C2 (uk) 2015-09-18 2020-03-10 Чугаі Сейяку Кабусікі Кайся Антитіло, що зв'язується з il-8, та його застосування
TWI703158B (zh) 2015-09-18 2020-09-01 美商希佛隆公司 特異性結合tl1a之抗體
WO2017053469A2 (en) 2015-09-21 2017-03-30 Aptevo Research And Development Llc Cd3 binding polypeptides
CA2999369C (en) 2015-09-22 2023-11-07 Spring Bioscience Corporation Anti-ox40 antibodies and diagnostic uses thereof
PE20181363A1 (es) 2015-09-23 2018-08-27 Genentech Inc Variantes optimizadas de anticuerpos anti-vegf
AU2016325630B2 (en) 2015-09-23 2022-11-17 Regeneron Pharmaceuticals, Inc. Optimized anti-CD3 bispecific antibodies and uses thereof
JP6955487B2 (ja) 2015-09-24 2021-10-27 アブビトロ， エルエルシー Ｈｉｖ抗体組成物および使用方法
PE20181046A1 (es) 2015-09-25 2018-07-03 Genentech Inc Anticuerpos anti-tigit y metodos de uso
BR112018006237A2 (pt) 2015-09-29 2018-10-09 Celgene Corp proteínas de ligação a pd-1 e métodos de uso das mesmas
AR106188A1 (es) 2015-10-01 2017-12-20 Hoffmann La Roche Anticuerpos anti-cd19 humano humanizados y métodos de utilización
CR20180243A (es) 2015-10-02 2018-07-31 Genentech Inc Conjugados de anticuerpo-fármaco de pirrolobenzodiazepina y métodos de uso
ES2895034T3 (es) 2015-10-02 2022-02-17 Hoffmann La Roche Anticuerpos anti-PD1 y procedimientos de uso
US10526413B2 (en) 2015-10-02 2020-01-07 Hoffmann-La Roche Inc. Bispecific antibodies specific for OX40
EP3150636A1 (en) 2015-10-02 2017-04-05 F. Hoffmann-La Roche AG Tetravalent multispecific antibodies
AR106189A1 (es) 2015-10-02 2017-12-20 Hoffmann La Roche ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO
TWI873952B (zh) 2015-10-02 2025-02-21 瑞士商赫孚孟拉羅股份公司 雙特異性抗‐人類cd20/人類轉鐵蛋白受體抗體及使用方法
WO2017055404A1 (en) 2015-10-02 2017-04-06 F. Hoffmann-La Roche Ag Bispecific antibodies specific for pd1 and tim3
IL293708B2 (en) 2015-10-06 2026-04-01 Genentech Inc A method for treating multiple sclerosis
AU2016334623A1 (en) 2015-10-07 2018-02-15 F. Hoffmann-La Roche Ag Bispecific antibodies with tetravalency for a costimulatory TNF receptor
WO2017066714A1 (en) 2015-10-16 2017-04-20 Compugen Ltd. Anti-vsig1 antibodies and drug conjugates
MA43354A (fr) 2015-10-16 2018-08-22 Genentech Inc Conjugués médicamenteux à pont disulfure encombré
EP3365025B1 (en) 2015-10-20 2020-07-15 Genentech, Inc. Calicheamicin-antibody-drug conjugates and methods of use
US10604577B2 (en) 2015-10-22 2020-03-31 Allakos Inc. Methods and compositions for treating systemic mastocytosis
CN115636880A (zh) 2015-10-23 2023-01-24 辉瑞有限公司 抗il-2抗体及其组合物和用途
JO3555B1 (ar) 2015-10-29 2020-07-05 Merck Sharp & Dohme جسم مضاد يبطل فعالية فيروس الالتهاب الرئوي البشري
WO2017072210A1 (en) 2015-10-29 2017-05-04 F. Hoffmann-La Roche Ag Anti-variant fc-region antibodies and methods of use
EP3184547A1 (en) 2015-10-29 2017-06-28 F. Hoffmann-La Roche AG Anti-tpbg antibodies and methods of use
EP3368092B9 (en) 2015-10-29 2020-07-29 Novartis AG Antibody conjugates comprising toll-like receptor agonist
MY196448A (en) 2015-10-30 2023-04-12 Genentech Inc Anti-Htra1 Antibodies and Methods of use Thereof
HRP20220064T1 (hr) 2015-10-30 2022-04-15 F. Hoffmann - La Roche Ag Zglobno modificirani fragmenti protutijela i postupci za pripravu
EP3368090A1 (en) 2015-10-30 2018-09-05 H. Hoffnabb-La Roche Ag Anti-factor d antibody variant conjugates and uses thereof
US10407510B2 (en) 2015-10-30 2019-09-10 Genentech, Inc. Anti-factor D antibodies and conjugates
CN118725134A (zh) 2015-11-08 2024-10-01 豪夫迈·罗氏有限公司 筛选多特异性抗体的方法
WO2017086419A1 (ja) 2015-11-18 2017-05-26 中外製薬株式会社 液性免疫応答の増強方法
WO2017086367A1 (ja) 2015-11-18 2017-05-26 中外製薬株式会社 免疫抑制機能を有する細胞に対するｔ細胞リダイレクト抗原結合分子を用いた併用療法
AU2016356780A1 (en) 2015-11-19 2018-06-28 Bristol-Myers Squibb Company Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR) and uses thereof
WO2017095875A1 (en) 2015-11-30 2017-06-08 Bristol-Myers Squibb Company Anti human ip-10 antibodies and their uses
CN108883173B (zh) 2015-12-02 2022-09-06 阿吉纳斯公司 抗体和其使用方法
EP3383911B1 (en) 2015-12-02 2021-01-20 STCube & Co. Inc. Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof
EP3383908A1 (en) 2015-12-02 2018-10-10 Stsciences, Inc. Antibodies specific to glycosylated btla (b- and t- lymphocyte attenuator)
RU2018124307A (ru) 2015-12-04 2020-01-14 Новартис Аг Антительно-цитокиновые привитые композиции и способы применения для иммунорегуляции
IL260021B (en) 2015-12-14 2022-09-01 Macrogenics Inc Bispecific molecules that are immunoreactive for pd1 and ctla4 and methods for using them
US11045547B2 (en) 2015-12-16 2021-06-29 Merck Sharp & Dohme Corp. Anti-LAG3 antibodies and antigen-binding fragments
AR107078A1 (es) 2015-12-18 2018-03-21 Chugai Pharmaceutical Co Ltd Anticuerpo antimiostatina, polipéptidos que contienen regiones fc variantes así como métodos de uso
HUE065073T2 (hu) 2015-12-18 2024-04-28 Chugai Pharmaceutical Co Ltd Anti-C5 antitestek és alkalmazási eljárások
RU2018126297A (ru) 2015-12-18 2020-01-22 Новартис Аг Антитела, нацеленные на cd32b, и способы их применения
WO2017110981A1 (en) 2015-12-25 2017-06-29 Chugai Seiyaku Kabushiki Kaisha Anti-myostatin antibodies and methods of use
AU2016381992B2 (en) 2015-12-28 2024-01-04 Chugai Seiyaku Kabushiki Kaisha Method for promoting efficiency of purification of Fc region-containing polypeptide
KR20180097615A (ko) 2016-01-08 2018-08-31 에프. 호프만-라 로슈 아게 Pd-1 축 결합 길항물질 및 항-cea/항-cd3 이중특이성 항체를 사용하는 cea-양성 암의 치료 방법
CN109069627A (zh) 2016-01-14 2018-12-21 纪念斯隆-凯特琳癌症中心 对foxp3衍生肽特异性的t细胞受体样抗体
US20190016791A1 (en) 2016-01-20 2019-01-17 Genentech, Inc. High dose treatments for alzheimer's disease
CA3012695A1 (en) 2016-02-01 2017-08-10 Bioverativ Therapeutics Inc. Optimized factor viii genes
EP3411396A1 (en) 2016-02-04 2018-12-12 Curis, Inc. Mutant smoothened and methods of using the same
WO2017137830A1 (en) 2016-02-12 2017-08-17 Janssen Pharmaceutica Nv Anti-vista (b7h5) antibodies
AU2017219254B2 (en) 2016-02-17 2019-12-12 Novartis Ag TGFbeta 2 antibodies
JP6821693B2 (ja) 2016-02-29 2021-01-27 ジェネンテック， インコーポレイテッド がんのための治療方法及び診断方法
EP3423494A1 (en) 2016-03-04 2019-01-09 Bristol-Myers Squibb Company Combination therapy with anti-cd73 antibodies
CA3011887C (en) * 2016-03-14 2024-10-29 Universitetet I Oslo Genetically transformed immunoglobulins with altered FCRN binding
US11072666B2 (en) 2016-03-14 2021-07-27 Chugai Seiyaku Kabushiki Kaisha Cell injury inducing therapeutic drug for use in cancer therapy
EP3430047A1 (en) 2016-03-15 2019-01-23 Innate Pharma Anti-mica antibodies
US11767362B1 (en) 2016-03-15 2023-09-26 Chugai Seiyaku Kabushiki Kaisha Methods of treating cancers using PD-1 axis binding antagonists and anti-GPC3 antibodies
AU2017234679A1 (en) 2016-03-16 2018-08-30 Merrimack Pharmaceuticals, Inc. Engineered trail for cancer therapy
CN109641955B (zh) 2016-03-22 2022-07-08 国家医疗保健研究所 人源化抗claudin-1抗体及其用途
WO2017161414A1 (en) 2016-03-22 2017-09-28 Bionomics Limited Administration of an anti-lgr5 monoclonal antibody
CN108700598A (zh) 2016-03-25 2018-10-23 豪夫迈·罗氏有限公司 多路总抗体和抗体缀合的药物量化测定法
CN109071653A (zh) 2016-03-29 2018-12-21 詹森生物科技公司 用增加的抗-il12和/或-23抗体给药间隔治疗牛皮癣
EP3865511A1 (en) 2016-04-14 2021-08-18 F. Hoffmann-La Roche AG Anti-rspo3 antibodies and methods of use
KR20190003958A (ko) 2016-04-15 2019-01-10 제넨테크, 인크. 암의 치료 및 모니터링 방법
MX2018012472A (es) 2016-04-15 2019-08-12 Alpine Immune Sciences Inc Proteinas inmunomoduladoras variantes de ligando icos y sus usos.
KR20230119259A (ko) 2016-04-15 2023-08-16 이뮤넥스트, 인크. 항-인간 vista 항체 및 이의 용도
GEP20227398B (en) 2016-04-15 2022-07-25 Macrogenics Inc Novel b7-h3 binding molecules, antibody drug conjugates thereof and usage thereof
WO2017181152A2 (en) 2016-04-15 2017-10-19 Alpine Immune Sciences, Inc. Cd80 variant immunomodulatory proteins and uses thereof
US11510966B2 (en) 2016-04-15 2022-11-29 Evive Biotechnology (Shanghai) Ltd Use of IL-22 in treating necrotizing enterocolitis
SMT202600033T1 (it) 2016-04-15 2026-03-09 Bioatla Inc Anticorpi anti-axl, frammenti di anticorpo e loro immunoconiugati e loro utilizzi
MX2018012493A (es) 2016-04-15 2019-06-06 Genentech Inc Métodos para controlar y tratar el cáncer.
CA3019588A1 (en) 2016-04-20 2017-10-26 Merck Sharp & Dohme Corp. Cmv neutralizing antigen binding proteins
JP2019522960A (ja) 2016-04-21 2019-08-22 アッヴィ・ステムセントルクス・エル・エル・シー 新規の抗ｂｍｐｒ１ｂ抗体及び使用方法
WO2017189724A1 (en) 2016-04-27 2017-11-02 Novartis Ag Antibodies against growth differentiation factor 15 and uses thereof
WO2017191101A1 (en) 2016-05-02 2017-11-09 F. Hoffmann-La Roche Ag The contorsbody - a single chain target binder
AR108377A1 (es) 2016-05-06 2018-08-15 Medimmune Llc Proteínas de unión biespecíficas y sus usos
MX392069B (es) 2016-05-09 2025-03-21 Bristol Myers Squibb Co Anticuerpos del ligando similar al factor de necrosis tumoral 1a (tl1a) y usos de los mismos.
JP7089483B2 (ja) 2016-05-11 2022-06-22 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 修飾された抗テネイシン抗体及び使用方法
PL3455261T3 (pl) 2016-05-13 2022-12-12 Bioatla, Inc. Przeciwciała anty-ror2, fragmenty przeciwciał, ich immunokoniugaty oraz ich zastosowania
CN118436801A (zh) 2016-05-20 2024-08-06 豪夫迈·罗氏有限公司 Protac抗体缀合物及其使用方法
TW201802121A (zh) 2016-05-25 2018-01-16 諾華公司 抗因子XI/XIa抗體之逆轉結合劑及其用途
EP3465221B1 (en) 2016-05-27 2020-07-22 H. Hoffnabb-La Roche Ag Bioanalytical method for the characterization of site-specific antibody-drug conjugates
EP3464360B1 (en) 2016-05-27 2025-11-12 Agenus Inc. Anti-tim-3 antibodies and methods of use thereof
CA3024618A1 (en) 2016-05-27 2017-11-30 Alexion Pharmaceuticals, Inc. Methods for treatment of refractory generalized myasthenia gravis
WO2017214024A1 (en) 2016-06-06 2017-12-14 Genentech, Inc. Silvestrol antibody-drug conjugates and methods of use
WO2017214452A1 (en) 2016-06-08 2017-12-14 Xencor, Inc. Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b
AU2017283787B2 (en) 2016-06-15 2020-09-17 Novartis Ag Methods for treating disease using inhibitors of bone morphogenetic protein 6 (BMP6)
KR102376582B1 (ko) 2016-06-17 2022-03-18 추가이 세이야쿠 가부시키가이샤 항-마이오스타틴 항체 및 사용 방법
JP7133477B2 (ja) 2016-06-24 2022-09-08 ジェネンテック， インコーポレイテッド 抗ポリユビキチン多重特異性抗体
CA3029627A1 (en) 2016-07-01 2018-01-04 Resolve Therapeutics, Llc Optimized binuclease fusions and methods
WO2018007314A1 (en) 2016-07-04 2018-01-11 F. Hoffmann-La Roche Ag Novel antibody format
US10864203B2 (en) 2016-07-05 2020-12-15 Beigene, Ltd. Combination of a PD-1 antagonist and a RAF inhibitor for treating cancer
CN109757103B (zh) 2016-07-14 2024-01-02 百时美施贵宝公司 针对tim3的抗体及其用途
CN117717604A (zh) 2016-07-19 2024-03-19 梯瓦制药澳大利亚股份有限公司 抗cd47联合治疗
WO2018014260A1 (en) 2016-07-20 2018-01-25 Nanjing Legend Biotech Co., Ltd. Multispecific antigen binding proteins and methods of use thereof
US20200148750A1 (en) 2016-07-21 2020-05-14 Emory University Ebola Virus Antibodies and Binding Agents Derived Therefrom
US11471488B2 (en) 2016-07-28 2022-10-18 Alpine Immune Sciences, Inc. CD155 variant immunomodulatory proteins and uses thereof
WO2018022946A1 (en) 2016-07-28 2018-02-01 Alpine Immune Sciences, Inc. Cd155 variant immunomodulatory proteins and uses thereof
WO2018022945A1 (en) 2016-07-28 2018-02-01 Alpine Immune Sciences, Inc. Cd112 variant immunomodulatory proteins and uses thereof
ES3041722T3 (en) 2016-07-29 2025-11-14 Inst Nat Sante Rech Med Antibodies targeting tumor associated macrophages and uses thereof
NL2017267B1 (en) 2016-07-29 2018-02-01 Aduro Biotech Holdings Europe B V Anti-pd-1 antibodies
US20190185578A1 (en) 2016-07-29 2019-06-20 Chugai Seiyaku Kabushiki Kaisha Bispecific antibody exhibiting increased alternative fviii-cofactor-function activity
HRP20260151T1 (hr) 2016-08-02 2026-03-27 Visterra, Inc. Modificirani polipeptidi i njihova uporaba
NL2017270B1 (en) 2016-08-02 2018-02-09 Aduro Biotech Holdings Europe B V New anti-hCTLA-4 antibodies
WO2018027042A1 (en) 2016-08-03 2018-02-08 Bio-Techne Corporation Identification of vsig3/vista as a novel immune checkpoint and use thereof for immunotherapy
KR20190077306A (ko) 2016-08-05 2019-07-03 메디뮨 엘엘씨 항-o2 항체 및 이의 용도
BR112019002331A2 (pt) 2016-08-05 2019-06-18 Allakos Inc anticorpos anti-siglec-7 para o tratamento do câncer e métodos para obtenção dos mesmos
EP3494991A4 (en) 2016-08-05 2020-07-29 Chugai Seiyaku Kabushiki Kaisha COMPOSITION FOR THE PROPHYLAXIS OR TREATMENT OF IL-8 RELATED DISEASES
WO2018029124A1 (en) 2016-08-08 2018-02-15 F. Hoffmann-La Roche Ag Therapeutic and diagnostic methods for cancer
CN109689111B (zh) 2016-08-11 2024-04-05 基因泰克公司 吡咯并苯并二氮杂䓬前药及其抗体缀合物
WO2018031258A1 (en) * 2016-08-12 2018-02-15 Janssen Biotech, Inc. Engineered antibodies and other fc-domain containing molecules with enhanced agonism and effector functions
IL317989A (en) 2016-08-17 2025-02-01 Compugen Ltd Anti-TIGIT antibodies, anti-PVRIG antibodies and combinations thereof
WO2018033135A1 (en) 2016-08-19 2018-02-22 Beigene, Ltd. Use of a combination comprising a btk inhibitor for treating cancers
US10981976B2 (en) 2016-08-31 2021-04-20 University Of Rochester Human monoclonal antibodies to human endogenous retrovirus K envelope (HERV-K) and use thereof
CA3035081A1 (en) 2016-09-02 2018-03-08 Dana-Farber Cancer Institute, Inc. Composition and methods of treating b cell disorders
US20190270821A1 (en) 2016-09-13 2019-09-05 Humanigen, Inc. Epha3 antibodies for the treatment of pulmonary fibrosis
CA3037144A1 (en) 2016-09-16 2018-03-22 Shanghai Henlius Biotech, Inc. Anti-pd-1 antibodies
SG10201607778XA (en) 2016-09-16 2018-04-27 Chugai Pharmaceutical Co Ltd Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use
JP2019534859A (ja) 2016-09-19 2019-12-05 セルジーン コーポレイション Ｐｄ−１結合タンパク質を使用して白斑を治療する方法
MX2019002867A (es) 2016-09-19 2019-11-12 Celgene Corp Metodos de tratamiento de trastornos inmunologicos usando proteinas de union a pd-1.
CN109689682B (zh) 2016-09-19 2022-11-29 豪夫迈·罗氏有限公司 基于补体因子的亲和层析
EP4360714A3 (en) 2016-09-21 2024-07-24 Nextcure, Inc. Antibodies for siglec-15 and methods of use thereof
DK3515478T3 (da) 2016-09-21 2024-05-21 Nextcure Inc Antistoffer til SIGLEC-15 og fremgangsmåder til anvendelse deraf
PT3528838T (pt) 2016-09-23 2023-09-04 Hoffmann La Roche Utilizações de antagonistas de il-13 para tratamento de dermatite atópica
JOP20190055A1 (ar) 2016-09-26 2019-03-24 Merck Sharp & Dohme أجسام مضادة ضد cd27
CA3037961A1 (en) 2016-09-30 2018-04-05 Janssen Biotech, Inc. Safe and effective method of treating psoriasis with anti-il23 specific antibody
JP7050770B2 (ja) 2016-10-05 2022-04-08 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 抗体薬物コンジュゲートの調製方法
CA3038712A1 (en) 2016-10-06 2018-04-12 Genentech, Inc. Therapeutic and diagnostic methods for cancer
WO2018068201A1 (en) 2016-10-11 2018-04-19 Nanjing Legend Biotech Co., Ltd. Single-domain antibodies and variants thereof against ctla-4
JP7066696B2 (ja) 2016-10-11 2022-05-13 アジェナス インコーポレイテッド 抗ｌａｇ－３抗体及びその使用方法
SG11201903063UA (en) 2016-10-19 2019-05-30 Medimmune Llc Anti-o1 antibodies and uses thereof
AU2017332960B2 (en) 2016-10-20 2019-09-12 I-Mab Biopharma Us Limited Novel CD47 monoclonal antibodies and uses thereof
TW202300515A (zh) 2016-10-20 2023-01-01 法商賽諾菲公司 抗ｃｈｉｋｖ抗體及其用途
EP3529277A1 (en) 2016-10-21 2019-08-28 Innate Pharma Treatment with anti-kir3dl2 agents
WO2018081648A2 (en) 2016-10-29 2018-05-03 Genentech, Inc. Anti-mic antibidies and methods of use
TWI788307B (zh) 2016-10-31 2023-01-01 美商艾歐凡斯生物治療公司 用於擴增腫瘤浸潤性淋巴細胞之工程化人造抗原呈現細胞
JP7267914B2 (ja) 2016-11-02 2023-05-02 エンクマフ エスアーエールエル Ｂｃｍａ及びｃｄ３に対する二重特異性抗体、及び多発性骨髄腫を治療するために併用して使用される免疫療法薬
MA46770A (fr) 2016-11-09 2019-09-18 Agenus Inc Anticorps anti-ox40, anticorps anti-gitr, et leurs procédés d'utilisation
US11370794B2 (en) 2016-11-11 2022-06-28 Dynavax Technologies Corporation Toll-like receptor antagonist compounds and methods of use
JP2020500020A (ja) 2016-11-14 2020-01-09 ノバルティス アーゲー 融合誘導性タンパク質ｍｉｎｉｏｎに関連する組成物、方法、および治療上の使用
JP7784795B2 (ja) 2016-11-15 2025-12-12 ジェネンテック， インコーポレイテッド 抗ｃｄ２０／抗ｃｄ３二重特異性抗体による処置のための投与
US11208474B2 (en) 2016-11-16 2021-12-28 Janssen Biotech, Inc. Method of treating psoriasis with anti-IL23 specific antibody
TW201829463A (zh) 2016-11-18 2018-08-16 瑞士商赫孚孟拉羅股份公司 抗hla-g抗體及其用途
JOP20190100A1 (ar) 2016-11-19 2019-05-01 Potenza Therapeutics Inc بروتينات ربط مولد ضد مضاد لـ gitr وطرق استخدامها
EP4015532A1 (en) 2016-11-21 2022-06-22 cureab GmbH Anti-gp73 antibodies and immunoconjugates
TN2019000164A1 (en) 2016-11-23 2020-10-05 Bioverativ Therapeutics Inc Mono- and bispecific antibodies binding to coagulation factor ix and coagulation factor x
JP2019536794A (ja) 2016-12-02 2019-12-19 バイオベラティブ セラピューティクス インコーポレイテッド 凝固因子に対する免疫寛容を誘導する方法
MX2019006444A (es) 2016-12-02 2019-10-30 Bioverativ Therapeutics Inc Métodos de tratamiento de artropatía hemofílica utilizando factores de coagulación quiméricos.
WO2018104893A1 (en) 2016-12-06 2018-06-14 Glaxosmithkline Intellectual Property Development Limited Alpha4-beta7 antibodies with incrased fcrn binding and/or half-life
MX2019006330A (es) 2016-12-07 2019-09-26 Genentech Inc Anticuerpos anti-tau y metodos de uso.
UA128383C2 (uk) 2016-12-07 2024-07-03 Дженентек, Інк. Антитіло до тау-білка та спосіб його застосування
CN110300599B (zh) 2016-12-07 2024-07-02 艾吉纳斯公司 抗体和其使用方法
DK3551660T5 (da) 2016-12-07 2024-09-02 Agenus Inc Anti-ctla-4-antistoffer og fremgangsmåder til anvendelse deraf
EP3551663A1 (en) 2016-12-12 2019-10-16 H. Hoffnabb-La Roche Ag Methods of treating cancer using anti-pd-l1 antibodies and antiandrogens
US10583191B2 (en) 2016-12-19 2020-03-10 Mosaic Biomedicals Slu Antibodies against LIF and uses thereof
AU2017381585B2 (en) 2016-12-19 2025-02-13 Fundacio Privada Institucio Catalana de Recerca i Estudis Avancats Antibodies against LIF and uses thereof
KR102692708B1 (ko) 2016-12-20 2024-08-07 에프. 호프만-라 로슈 아게 항-cd20/항-cd3 이중특이성 항체 및 4-1bb(cd137) 작용물질의 병용 요법
DK3558369T3 (da) 2016-12-21 2025-05-19 Cephalon Llc Antistoffer, der specifikt binder til humant il-15, og anvendelse heraf
AU2017383232B2 (en) 2016-12-23 2024-09-12 Novartis Ag Factor XI antibodies and methods of use
US20190322767A1 (en) 2016-12-23 2019-10-24 Innate Pharma Heterodimeric antigen binding proteins
JOP20190134A1 (ar) 2016-12-23 2019-06-02 Potenza Therapeutics Inc بروتينات رابطة لمولد ضد مضادة لنيوروبيلين وطرق استخدامها
WO2018127473A1 (en) 2017-01-03 2018-07-12 F. Hoffmann-La Roche Ag Bispecific antigen binding molecules comprising anti-4-1bb clone 20h4.9
US20180230218A1 (en) 2017-01-04 2018-08-16 Immunogen, Inc. Met antibodies and immunoconjugates and uses thereof
CA3049165A1 (en) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof
MX2019007963A (es) 2017-01-06 2019-10-21 Iovance Biotherapeutics Inc Expansion de linfocitos infiltrantes de tumor (til) con agonistas de la superfamilia de recptor de factor de necrosis tumoral (tnfrsf) y combinaciones terapeuticas de til- y agonistas de tnfrsf.
EP3568468A4 (en) 2017-01-12 2020-12-30 Eureka Therapeutics, Inc. RECOMBINATION PRODUCTS TARGETING PEPTIDE HISTONE H3 / MHC COMPLEXES AND THEIR USES
US11555038B2 (en) 2017-01-25 2023-01-17 Beigene, Ltd. Crystalline forms of (S)-7-(1-(but-2-ynoyl)piperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide, preparation, and uses thereof
KR102365871B1 (ko) 2017-01-31 2022-02-21 추가이 세이야쿠 가부시키가이샤 C5-관련 질환의 치료 또는 예방용 의약 조성물 및 c5-관련 질환을 치료 또는 예방하기 위한 방법
KR102572663B1 (ko) 2017-02-08 2023-09-01 노파르티스 아게 Fgf21 모방 항체 및 이의 용도
EP3580233A1 (en) * 2017-02-10 2019-12-18 Genmab B.V. Polypeptide variants and uses thereof
JP6995127B2 (ja) 2017-02-10 2022-02-04 ジェネンテック， インコーポレイテッド 抗トリプターゼ抗体、その組成物、及びその使用
CN110506055A (zh) 2017-02-17 2019-11-26 戴纳立制药公司 工程改造的转铁蛋白受体结合多肽
CA3051839A1 (en) 2017-02-17 2018-08-23 Bristol-Myers Squibb Company Antibodies to alpha-synuclein and uses thereof
IL268959B2 (en) 2017-02-28 2025-01-01 Seagen Inc Cystine-mutated antibodies, compositions containing them and uses thereof
AU2018227428A1 (en) 2017-02-28 2019-10-17 Bristol-Myers Squibb Company Use of anti-CTLA-4 antibodies with enhanced ADCC to enhance immune response to a vaccine
TW201837467A (zh) 2017-03-01 2018-10-16 美商建南德克公司 用於癌症之診斷及治療方法
CN110392697A (zh) 2017-03-02 2019-10-29 国家医疗保健研究所 对nectin-4具有特异性的抗体及其用途
EP3596116B1 (en) 2017-03-16 2023-09-06 Alpine Immune Sciences, Inc. Pd-l1 variant immunomodulatory proteins and uses thereof
KR20190141146A (ko) 2017-03-16 2019-12-23 알파인 이뮨 사이언시즈, 인코포레이티드 Pd-l2 변이체 면역조절 단백질 및 그의 용도
SG11201907769XA (en) 2017-03-16 2019-09-27 Alpine Immune Sciences Inc Cd80 variant immunomodulatory proteins and uses thereof
MA49279A (fr) 2017-03-22 2020-02-05 Hoffmann La Roche Compositions d'anticorps optimisées pour le traitement de troubles oculaires
LT3600415T (lt) 2017-03-24 2025-12-29 Novartis Ag Antikūnas prieš ii tipo aktivino receptorių, skirtas naudoti širdies nepakankamumo gydymui
EP3601337A1 (en) 2017-03-28 2020-02-05 Genentech, Inc. Methods of treating neurodegenerative diseases
EP3601346A1 (en) 2017-03-29 2020-02-05 H. Hoffnabb-La Roche Ag Bispecific antigen binding molecule for a costimulatory tnf receptor
CN110573528B (zh) 2017-03-29 2023-06-09 豪夫迈·罗氏有限公司 针对共刺激性tnf受体的双特异性抗原结合分子
JOP20190203A1 (ar) 2017-03-30 2019-09-03 Potenza Therapeutics Inc بروتينات رابطة لمولد ضد مضادة لـ tigit وطرق استخدامها
WO2018185618A1 (en) 2017-04-03 2018-10-11 Novartis Ag Anti-cdh6 antibody drug conjugates and anti-gitr antibody combinations and methods of treatment
JP6997209B2 (ja) 2017-04-04 2022-02-04 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｃｄ４０およびｆａｐに特異的に結合することができる新規な二重特異性抗原結合分子
KR102294136B1 (ko) 2017-04-05 2021-08-26 에프. 호프만-라 로슈 아게 항-lag3 항체
EP4516809A3 (en) 2017-04-05 2025-09-03 F. Hoffmann-La Roche AG Bispecific antibodies specifically binding to pd1 and lag3
TWI796329B (zh) 2017-04-07 2023-03-21 美商默沙東有限責任公司 抗－ilt4抗體及抗原結合片段
KR20240017409A (ko) 2017-04-13 2024-02-07 아게누스 인코포레이티드 항-cd137 항체 및 이의 사용 방법
US20230227566A1 (en) 2017-04-14 2023-07-20 Gamamabs Pharma Amhrii-binding compounds for preventing or treating lung cancers
KR20200014276A (ko) 2017-04-14 2020-02-10 가마맵스 파마 암을 예방 또는 치료하기 위한 amhrii-결합 화합물
KR20200005540A (ko) 2017-04-14 2020-01-15 제넨테크, 인크. 암의 진단 및 치료 방법
CA3060514A1 (en) 2017-04-20 2018-10-25 Atyr Pharma, Inc. Compositions and methods for treating lung inflammation
EP3624820A1 (en) 2017-04-21 2020-03-25 H. Hoffnabb-La Roche Ag Use of klk5 antagonists for treatment of a disease
EP3615574A4 (en) 2017-04-26 2021-02-24 Eureka Therapeutics, Inc. SPECIFIC GLYPICAN 3 RECOGNIZING CONSTRUCTS AND THEIR USE
SG11201909395TA (en) 2017-04-27 2019-11-28 Tesaro Inc Antibody agents directed against lymphocyte activation gene-3 (lag-3) and uses thereof
AR111651A1 (es) 2017-04-28 2019-08-07 Novartis Ag Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación
LT3618863T (lt) 2017-05-01 2023-10-10 Agenus Inc. Anti-tigit antikūnai ir jų panaudojimo būdai
EP3618868A4 (en) 2017-05-05 2021-02-24 Allakos Inc. METHODS AND COMPOSITIONS FOR TREATING ALLERGIC EYE DISEASES
KR20200003913A (ko) 2017-05-10 2020-01-10 이오반스 바이오테라퓨틱스, 인크. 액상 종양으로부터의 종양 침윤 림프구의 확장 및 그의 치료 용도
EP3625251A1 (en) 2017-05-15 2020-03-25 University Of Rochester Broadly neutralizing anti-influenza monoclonal antibody and uses thereof
WO2018215938A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use
WO2018215937A1 (en) 2017-05-24 2018-11-29 Novartis Ag Interleukin-7 antibody cytokine engrafted proteins and methods of use in the treatment of cancer
JOP20190271A1 (ar) 2017-05-24 2019-11-21 Novartis Ag بروتينات مطعّمة بسيتوكين- الجسم المضاد وطرق الاستخدام للاضطرابات المتعلقة بالمناعة
MY206158A (en) 2017-05-24 2024-12-02 Novartis Ag Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer
US20200299400A1 (en) 2017-05-25 2020-09-24 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
KR20200015602A (ko) 2017-05-31 2020-02-12 주식회사 에스티큐브앤컴퍼니 Btn1a1에 면역특이적으로 결합하는 항체 및 분자 및 이의 치료적 용도
CN111051346A (zh) 2017-05-31 2020-04-21 斯特库伯株式会社 使用免疫特异性结合btn1a1的抗体和分子治疗癌症的方法
JP7348072B2 (ja) 2017-06-01 2023-09-20 コンピュジェン リミテッド 三重併用抗体療法
KR20200026209A (ko) 2017-06-06 2020-03-10 주식회사 에스티큐브앤컴퍼니 Btn1a1 또는 btn1a1-리간드에 결합하는 항체 및 분자를 사용하여 암을 치료하는 방법
UY37758A (es) 2017-06-12 2019-01-31 Novartis Ag Método de fabricación de anticuerpos biespecíficos, anticuerpos biespecíficos y uso terapéutico de dichos anticuerpos
WO2018229706A1 (en) 2017-06-16 2018-12-20 Novartis Ag Combination therapy for the treatment of cancer
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
EA201992502A1 (ru) 2017-06-20 2020-04-22 Эмджен Инк. Способ лечения или уменьшения интенсивности метаболических нарушений с применением белков, связывающих рецептор гастроингибиторного пептида (gipr), в комбинации с агонистами glp-1
AU2018289581C1 (en) 2017-06-23 2025-01-30 VelosBio Inc. ROR1 antibody immunoconjugates
EP3645569A4 (en) 2017-06-26 2021-03-24 BeiGene, Ltd. IMMUNOTHERAPY FOR LIVER CELL CARCINOMA
CA3063659A1 (en) 2017-06-28 2019-01-03 Novartis Ag Methods for preventing and treating urinary incontinence
JP7760242B2 (ja) 2017-07-21 2025-10-27 ジェネンテック， インコーポレイテッド がんの治療法及び診断法
CN107748259A (zh) * 2017-07-26 2018-03-02 东曜药业有限公司 一种FcRn受体的ELISA检测方法
CN107748262A (zh) * 2017-07-26 2018-03-02 东曜药业有限公司 一种FcγRIIIA受体的ELISA检测方法
CN107748253A (zh) * 2017-07-26 2018-03-02 东曜药业有限公司 一种FcγRI受体的ELISA检测方法
BR112020001653A2 (pt) 2017-07-26 2020-07-21 Forty Seven, Inc. anticorpos anti-sirp-alfa e métodos relacionados
CN107748258A (zh) * 2017-07-26 2018-03-02 东曜药业有限公司 一种FcγRII受体的ELISA检测方法
DK3658184T5 (da) 2017-07-27 2024-08-26 Alexion Pharma Inc Højkoncentrerede anti-c5-antistofformuleringer
NZ762100A (en) 2017-08-09 2025-12-19 Bioverativ Therapeutics Inc Nucleic acid molecules and uses thereof
MX2020000903A (es) 2017-08-11 2020-07-22 Genentech Inc Anticuerpos anti-cd8 y usos de los mismos.
CA3073537A1 (en) 2017-08-22 2019-02-28 Sanabio, Llc Soluble interferon receptors and uses thereof
US11306144B2 (en) 2017-08-25 2022-04-19 Five Prime Therapeutics, Inc. B7-H4 antibodies and methods of use thereof
ES2978167T3 (es) 2017-09-19 2024-09-06 Tillotts Pharma Ag Variantes de anticuerpos
HUE054261T2 (hu) 2017-09-19 2021-08-30 Tillotts Pharma Ag Antitest variánsok
WO2019059411A1 (en) 2017-09-20 2019-03-28 Chugai Seiyaku Kabushiki Kaisha DOSAGE FOR POLYTHERAPY USING PD-1 AXIS BINDING ANTAGONISTS AND GPC3 TARGETING AGENT
TW201922780A (zh) 2017-09-25 2019-06-16 美商健生生物科技公司 以抗ｉｌ１２／ｉｌ２３抗體治療狼瘡之安全且有效之方法
PE20210005A1 (es) 2017-09-29 2021-01-05 Chugai Pharmaceutical Co Ltd Molecula de union al antigeno multiespecifica que tiene actividad de sustitucion de la funcion de cofactor del factor viii de coagulacion de sangre (fviii) y formulacion farmaceutica que contiene tal molecula como ingrediente activo
EP3694552A1 (en) 2017-10-10 2020-08-19 Tilos Therapeutics, Inc. Anti-lap antibodies and uses thereof
JP7749319B2 (ja) 2017-10-10 2025-10-06 アルパイン イミューン サイエンシズ インコーポレイテッド Ｃｔｌａ－４変異型免疫調節タンパク質およびそれらの使用
AU2018347521A1 (en) 2017-10-12 2020-05-07 Immunowake Inc. VEGFR-antibody light chain fusion protein
EP3694885A1 (en) 2017-10-14 2020-08-19 CytomX Therapeutics, Inc. Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof
BR112020007542A2 (pt) 2017-10-18 2020-12-01 Alpine Immune Sciences, Inc. proteínas imunomoduladoras ligantes de icos variantes e composições e métodos relacionados
CN111246885B (zh) 2017-10-20 2024-06-11 豪夫迈·罗氏有限公司 从单特异性抗体生成多特异性抗体的方法
WO2019081983A1 (en) 2017-10-25 2019-05-02 Novartis Ag CD32B TARGETING ANTIBODIES AND METHODS OF USE
CN118512588A (zh) 2017-10-26 2024-08-20 亚力兄制药公司 用于治疗阵发性夜间性血红蛋白尿(pnh)和非典型溶血性尿毒症综合征(ahus)的抗c5抗体的剂量和施用
JP7438942B2 (ja) 2017-10-30 2024-02-27 エフ． ホフマン－ラ ロシュ アーゲー 単一特異性抗体から多重特異性抗体をインビボ生成させるための方法
TW201923089A (zh) 2017-11-06 2019-06-16 美商建南德克公司 癌症之診斷及治療方法
JP2021502349A (ja) 2017-11-06 2021-01-28 ヤンセン バイオテツク，インコーポレーテツド 抗ｉｌ２３特異的抗体で乾癬性関節炎を治療する安全かつ有効な方法
CA3081854A1 (en) 2017-11-08 2019-05-16 Kyowa Kirin Co., Ltd. Bispecific antibody which binds to cd40 and epcam
EP4640703A3 (en) 2017-11-14 2026-04-08 Chugai Seiyaku Kabushiki Kaisha Anti-c1s antibodies and methods of use
EP3713959A1 (en) 2017-11-21 2020-09-30 Innate Pharma Multispecific antigen binding proteins
EP3714041A1 (en) 2017-11-22 2020-09-30 Iovance Biotherapeutics, Inc. Expansion of peripheral blood lymphocytes (pbls) from peripheral blood
EP3713965A1 (en) 2017-11-22 2020-09-30 Novartis AG Reversal binding agents for anti-factor xi/xia antibodies and uses thereof
WO2019108795A1 (en) 2017-11-29 2019-06-06 Beigene Switzerland Gmbh Treatment of indolent or aggressive b-cell lymphomas using a combination comprising btk inhibitors
CA3083363A1 (en) 2017-12-01 2019-06-06 Novartis Ag Polyomavirus neutralizing antibodies
TW201938194A (zh) 2017-12-05 2019-10-01 日商中外製藥股份有限公司 包含結合cd3及cd137的改變的抗體可變區之抗原結合分子
CA3081144A1 (en) 2017-12-08 2019-06-13 Argenx Bvba Use of fcrn antagonists for treatment of generalized myasthenia gravis
US20210369775A1 (en) 2017-12-15 2021-12-02 Iovance Biotherapeutics, Inc. Systems and methods for determining the beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof and beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof
EP3498293A1 (en) 2017-12-15 2019-06-19 Institut National De La Sante Et De La Recherche Medicale (Inserm) Treatment of monogenic diseases with an anti-cd45rc antibody
WO2019126536A1 (en) 2017-12-20 2019-06-27 Alexion Pharmaceuticals Inc. Humanized anti-cd200 antibodies and uses thereof
WO2019126133A1 (en) 2017-12-20 2019-06-27 Alexion Pharmaceuticals, Inc. Liquid formulations of anti-cd200 antibodies
EP3502140A1 (en) 2017-12-21 2019-06-26 F. Hoffmann-La Roche AG Combination therapy of tumor targeted icos agonists with t-cell bispecific molecules
US20190211098A1 (en) 2017-12-22 2019-07-11 Genentech, Inc. Use of pilra binding agents for treatment of a disease
EP3732203A4 (en) 2017-12-28 2021-12-15 Nanjing Legend Biotech Co., Ltd. ANTIBODIES AND THEIR VARIANTS DIRECTED AGAINST PD-L1
CN117050184A (zh) 2017-12-28 2023-11-14 南京传奇生物科技有限公司 针对tigit的单域抗体和其变体
JP7314146B2 (ja) 2017-12-28 2023-07-25 中外製薬株式会社 細胞傷害誘導治療剤
EP3731864A1 (en) 2017-12-29 2020-11-04 F. Hoffmann-La Roche SA Anti-vegf antibodies and methods of use
FR3076294B1 (fr) 2017-12-29 2022-01-28 Lab Francais Du Fractionnement Procede de purification d'anticorps a partir de lait brut
AU2019205273B2 (en) 2018-01-03 2024-04-04 Alpine Immune Sciences, Inc. Multi-domain immunomodulatory proteins and methods of use thereof
MX2020007077A (es) 2018-01-04 2020-10-28 Iconic Therapeutics Inc Anticuerpos anti-factor tisular, conjugados anticuerpo-farmaco y metodos relacionados.
AU2019205090A1 (en) 2018-01-05 2020-08-06 Ac Immune Sa Misfolded TDP-43 binding molecules
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
EP3737700A1 (en) 2018-01-12 2020-11-18 Bristol-Myers Squibb Company Antibodies against tim3 and uses thereof
CN111699200B (zh) 2018-01-15 2023-05-26 南京传奇生物科技有限公司 针对pd-1的单域抗体和其变体
EP3740505A1 (en) 2018-01-16 2020-11-25 Lakepharma Inc. Bispecific antibody that binds cd3 and another target
CR20200327A (es) 2018-01-26 2020-11-05 Genentech Inc Proteínas de fusión fc il-22 y métodos de uso
IL276286B2 (en) * 2018-01-26 2025-07-01 Genzyme Corp FC variants with improved binding to FCRN and extended half-life
CN112020365A (zh) 2018-01-26 2020-12-01 豪夫迈·罗氏有限公司 组合物和使用方法
AU2019215063B2 (en) 2018-02-01 2025-10-16 Bioverativ Therapeutics, Inc. Use of lentiviral vectors expressing Factor VIII
WO2019148412A1 (en) 2018-02-01 2019-08-08 Merck Sharp & Dohme Corp. Anti-pd-1/lag3 bispecific antibodies
WO2019148410A1 (en) 2018-02-01 2019-08-08 Merck Sharp & Dohme Corp. Anti-pd-1 antibodies
US11787857B2 (en) 2018-02-02 2023-10-17 Bio-Techne Corporation Compounds that modulate the interaction of VISTA and VSIG3 and methods of making and using
IL325995A (en) 2018-02-08 2026-03-01 Genentech Inc Bispecific antigen binding molecules and methods of use
KR20220098056A (ko) 2018-02-09 2022-07-08 제넨테크, 인크. 비만 세포 매개 염증성 질환에 대한 치료 및 진단 방법
CA3090795A1 (en) 2018-02-13 2019-08-22 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes (tils) with adenosine a2a receptor antagonists and therapeutic combinations of tils and adenosine a2a receptor antagonists
JP7350756B2 (ja) 2018-02-14 2023-09-26 アバ セラピューティクス アーゲー 抗ヒトｐｄ－ｌ２抗体
KR20200123118A (ko) 2018-02-21 2020-10-28 제넨테크, 인크. IL-22 Fc 융합 단백질로 치료를 위한 투약
BR112020016986A2 (pt) 2018-02-21 2021-03-02 Five Prime Therapeutics, Inc. formulações de anticorpo contra b7-h4
CN111836831A (zh) 2018-02-26 2020-10-27 豪夫迈·罗氏有限公司 用于抗tigit拮抗剂抗体和抗pd-l1拮抗剂抗体治疗的给药
WO2019169229A1 (en) 2018-03-01 2019-09-06 Nextcure, Inc. Klrg1 binding compositions and methods of use thereof
KR20200144094A (ko) 2018-03-02 2020-12-28 파이브 프라임 테라퓨틱스, 인크. B7-h4 항체 및 이의 사용 방법
NL2020520B1 (en) 2018-03-02 2019-09-12 Labo Bio Medical Invest B V Multispecific binding molecules for the prevention, treatment and diagnosis of neurodegenerative disorders
MX2020009265A (es) 2018-03-05 2020-10-01 Janssen Biotech Inc Metodos para tratar la enfermedad de crohn con un anticuerpo especifico anti-il23.
EP3765489B1 (en) 2018-03-13 2024-10-16 F. Hoffmann-La Roche AG Therapeutic combination of 4-1bb agonists with anti-cd20 antibodies
EP3765517A1 (en) 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
US20200040103A1 (en) 2018-03-14 2020-02-06 Genentech, Inc. Anti-klk5 antibodies and methods of use
EP3765522A4 (en) 2018-03-14 2022-05-18 Beijing Xuanyi Pharmasciences Co., Ltd. ANTI-CLAUDIN 18.2 ANTIBODIES
CN112119090B (zh) 2018-03-15 2023-01-13 中外制药株式会社 对寨卡病毒具有交叉反应性的抗登革热病毒抗体及使用方法
US20210070860A1 (en) * 2018-03-21 2021-03-11 Dana-Farber Cancer Institute, Inc. Fc variant compositions and methods of use thereof
BR112020019083A2 (pt) 2018-03-21 2020-12-29 Five Prime Therapeutics, Inc. Anticorpos, ácido nucleico, composições, célula e métodos para preparar um anticorpo, para tratar câncer, para tratar uma doença infecciosa, para tratar uma inflamação, para a identificação de um anticorpo, para melhorar a eficácia antitumoral de um anticorpo, para melhorar a farmacocinética de um anticorpo, para selecionar um anticorpo, para melhorar a eficácia de anticorpos, para isolar anticorpos, para detectar vista em uma amostra e para tratar câncer
EP3768715A1 (en) 2018-03-23 2021-01-27 Bristol-Myers Squibb Company Antibodies against mica and/or micb and uses thereof
PE20210313A1 (es) 2018-03-28 2021-02-12 Bristol Myers Squibb Co Proteinas de fusion interleucina-2/receptor alfa de interleucina-2 y metodos de uso
JP2021519073A (ja) 2018-03-29 2021-08-10 ジェネンテック， インコーポレイテッド 哺乳動物細胞におけるラクトジェニック活性の制御
TW202003567A (zh) 2018-03-30 2020-01-16 大陸商南京傳奇生物科技有限公司 針對lag-3之單一結構域抗體及其用途
WO2019195126A1 (en) 2018-04-02 2019-10-10 Bristol-Myers Squibb Company Anti-trem-1 antibodies and uses thereof
TW202011029A (zh) 2018-04-04 2020-03-16 美商建南德克公司 偵測及定量fgf21之方法
AU2019247511B2 (en) 2018-04-06 2025-10-16 Atyr Pharma, Inc. Compositions and methods comprising anti-NRP2 antibodies
EP3552631A1 (en) 2018-04-10 2019-10-16 Inatherys Antibody-drug conjugates and their uses for the treatment of cancer
WO2019197903A1 (en) 2018-04-12 2019-10-17 Mosaic Biomedicals Slu Combination of lif inhibitors and pd-1 axis inhibitors for use in treating cancer
CR20250325A (es) 2018-04-13 2025-08-29 Genentech Inc Formulaciones inmunoconjugadas anti-cd79b estables (divisional expediente 2020-0550)
AR115052A1 (es) 2018-04-18 2020-11-25 Hoffmann La Roche Anticuerpos multiespecíficos y utilización de los mismos
AR114789A1 (es) 2018-04-18 2020-10-14 Hoffmann La Roche Anticuerpos anti-hla-g y uso de los mismos
CA3096703A1 (en) 2018-05-03 2019-11-07 University Of Rochester Anti-influenza neuraminidase monoclonal antibodies and uses thereof
US20190345245A1 (en) 2018-05-11 2019-11-14 Janssen Biotech, Inc. Methods of Treating Crohn's Disease with Anti-IL23 Specific Antibody
CN110464842B (zh) 2018-05-11 2022-10-14 信达生物制药(苏州)有限公司 包含抗pcsk9抗体的制剂及其用途
KR20210008514A (ko) 2018-05-14 2021-01-22 메디뮨 리미티드 Lif에 대한 항체 및 이의 투여 형태
CA3100071A1 (en) 2018-05-16 2019-11-21 Csl Limited Soluble complement receptor type 1 variants and uses thereof
PL3793588T3 (pl) 2018-05-18 2025-09-01 Bioverativ Therapeutics Inc. Sposoby leczenia hemofilii a
WO2019226658A1 (en) 2018-05-21 2019-11-28 Compass Therapeutics Llc Multispecific antigen-binding compositions and methods of use
BR112020023746A2 (pt) 2018-05-23 2021-02-17 Beigene, Ltd. anticorpo, composição farmacêutica, método para tratar câncer, ácido nucleico isolado, vetor, célula hospedeira, processo para a produção de um anticorpo e reagente de diagnóstico
TWI869346B (zh) 2018-05-30 2025-01-11 瑞士商諾華公司 Ｅｎｔｐｄ２抗體、組合療法、及使用該等抗體和組合療法之方法
EP3802593B1 (en) 2018-05-31 2024-09-11 Alexion Pharmaceuticals, Inc. Dosage and administration of anti-c5 antibodies for treatment of paroxysmal nocturnal hemoglobinuria (pnh) in pediatric patients
EP3801766A1 (en) 2018-05-31 2021-04-14 Novartis AG Hepatitis b antibodies
KR20210016448A (ko) 2018-06-01 2021-02-15 컴퓨젠 엘티디. 항-pvrig/항-tigit 이중특이적 항체 및 사용 방법
KR102870868B1 (ko) 2018-06-01 2025-10-15 노파르티스 아게 Bcma에 대한 결합 분자 및 이의 용도
EP3802603A1 (en) 2018-06-04 2021-04-14 Alexion Pharmaceuticals, Inc. Dosage and administration of anti-c5 antibodies for treatment of atypical hemolytic uremic syndrome (ahus) in pediatric patients
CN119080931A (zh) 2018-06-04 2024-12-06 马萨诸塞州渤健公司 具有降低的效应功能的抗vla-4抗体
WO2019235426A1 (ja) 2018-06-04 2019-12-12 中外製薬株式会社 細胞質内での半減期が変化した抗原結合分子
EP3802610A1 (en) 2018-06-05 2021-04-14 Amgen Inc. Modulating antibody dependent cellular phagocytosis
TWI851577B (zh) 2018-06-07 2024-08-11 美商思進公司 喜樹鹼結合物
US12202900B2 (en) 2018-06-08 2025-01-21 argenx BV Compositions and methods for treating immune thrombocytopenia
TWI848953B (zh) 2018-06-09 2024-07-21 德商百靈佳殷格翰國際股份有限公司 針對癌症治療之多特異性結合蛋白
WO2019241758A1 (en) 2018-06-15 2019-12-19 Alpine Immune Sciences, Inc. Pd-1 variant immunomodulatory proteins and uses thereof
US11993661B2 (en) 2018-06-18 2024-05-28 Eureka Therapeutics, Inc. Constructs targeting prostate-specific membrane antigen (PSMA) and uses thereof
AU2019291307B2 (en) 2018-06-18 2024-04-04 Fundacio Privada Institucio Catalana de Recerca i Estudis Avancats Combination of LIF inhibitors and platinum-based antineoplastic agents for use in treating cancer
KR20250156190A (ko) 2018-06-22 2025-10-31 큐진 인크. 인터루킨-2 변이체 및 이의 사용 방법
MY205645A (en) 2018-06-23 2024-11-02 Genentech Inc Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor
US12312394B2 (en) 2018-06-28 2025-05-27 Alexion Pharmaceuticals, Inc. Methods of producing anti-C5 antibodies
CA3105448A1 (en) 2018-07-03 2020-01-09 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
KR20210027426A (ko) 2018-07-03 2021-03-10 브리스톨-마이어스 스큅 컴퍼니 Fgf21 제제
WO2020007817A1 (en) 2018-07-04 2020-01-09 F. Hoffmann-La Roche Ag Novel bispecific agonistic 4-1bb antigen binding molecules
CN113056483B (zh) 2018-07-09 2025-08-01 戊瑞治疗有限公司 结合到ilt4的抗体
WO2020014306A1 (en) 2018-07-10 2020-01-16 Immunogen, Inc. Met antibodies and immunoconjugates and uses thereof
PE20210687A1 (es) 2018-07-11 2021-04-08 Bristol Myers Squibb Co Anticuerpos de union a vista a ph acido
US20200025776A1 (en) 2018-07-18 2020-01-23 Janssen Biotech, Inc. Sustained Response Predictors After Treatment With Anti-IL23 Specific Antibody
WO2020018789A1 (en) 2018-07-18 2020-01-23 Genentech, Inc. Methods of treating lung cancer with a pd-1 axis binding antagonist, an antimetabolite, and a platinum agent
JP7490925B2 (ja) 2018-07-26 2024-05-28 エータイアー ファーマ， インコーポレイテッド Ｎｒｐ２関連疾患を治療するための組成物および方法
MY210523A (en) 2018-08-01 2025-09-29 Univ Osaka A pharmaceutical composition for use in the treatment or prevention of a c5-related disease and a method for treating or preventing a c5-related disease
SG11202100928QA (en) 2018-08-02 2021-02-25 Dyne Therapeutics Inc Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy
MX2021000827A (es) 2018-08-03 2021-03-25 Chugai Pharmaceutical Co Ltd Molecula de union a antigeno que contiene dos dominios de union a antigeno que estan enlazados entre si.
MA50586A (fr) 2018-08-09 2020-09-16 Regeneron Pharma Procédés d'évaluation de l'affinité de liaison d'une variante d'anticorps au récepteur fc néonatal
EP3833766A1 (en) 2018-08-09 2021-06-16 Bioverativ Therapeutics Inc. Nucleic acid molecules and uses thereof for non-viral gene therapy
KR102259473B1 (ko) 2018-08-10 2021-06-02 추가이 세이야쿠 가부시키가이샤 항cd137 항원 결합 분자 및 그의 사용
CN121248772A (zh) 2018-08-17 2026-01-02 Ab工作室有限公司 催化抗体和其使用方法
TW202031273A (zh) 2018-08-31 2020-09-01 美商艾歐凡斯生物治療公司 抗ｐｄ－１抗體難治療性之非小細胞肺癌（ｎｓｃｌｃ）病患的治療
CA3110513A1 (en) 2018-08-31 2020-03-05 Regeneron Pharmaceuticals, Inc. Dosing strategy that mitigates cytokine release syndrome for cd3/c20 bispecific antibodies
GB201814281D0 (en) 2018-09-03 2018-10-17 Femtogenix Ltd Cytotoxic agents
WO2020053742A2 (en) 2018-09-10 2020-03-19 Novartis Ag Anti-hla-hbv peptide antibodies
EP3850013A4 (en) 2018-09-10 2022-10-05 Nanjing Legend Biotech Co., Ltd. SINGLE DOMAIN ANTIBODIES AGAINST CLL1 AND USES THEREOF
CA3110530A1 (en) 2018-09-11 2020-03-19 Amgen Inc. Methods of modulating antibody-dependent cell-mediated cytotoxicity
CA3109366A1 (en) 2018-09-13 2020-03-19 The Board Of Regents Of The University Of Texas System Novel lilrb4 antibodies and uses thereof
EP3853252A1 (en) 2018-09-18 2021-07-28 Merrimack Pharmaceuticals, Inc. Anti-tnfr2 antibodies and uses thereof
AU2019342099A1 (en) 2018-09-19 2021-04-08 Genentech, Inc. Therapeutic and diagnostic methods for bladder cancer
EP3853247A2 (en) 2018-09-19 2021-07-28 Alpine Immune Sciences, Inc. Methods and uses of variant cd80 fusion proteins and related constructs
KR102739487B1 (ko) 2018-09-21 2024-12-10 제넨테크, 인크. 3중-음성 유방암에 대한 진단 방법
IL326284A (en) 2018-09-24 2026-04-01 Janssen Biotech Inc A safe and effective method for treating ulcerative colitis with an anti-IL12/IL23 antibody
US20220002370A1 (en) 2018-09-27 2022-01-06 Xilio Development, Inc. Masked cytokine polypeptides
BR112021005585A2 (pt) 2018-09-27 2021-06-29 Celgene Corporation proteínas de ligação a sirpa e métodos de uso das mesmas
US11591390B2 (en) 2018-09-27 2023-02-28 Celgene Corporation SIRP-α binding proteins and methods of use thereof
BR112021005722A2 (pt) 2018-09-28 2021-07-06 Chugai Pharmaceutical Co Ltd moléculas de ligação ao antígeno capazes de ligar cd3 e cd137, porém não simultaneamente
US12509524B2 (en) 2018-09-28 2025-12-30 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule comprising altered antibody variable region
CN112654641A (zh) 2018-10-01 2021-04-13 豪夫迈·罗氏有限公司 具有与cd40的三价结合的双特异性抗原结合分子
WO2020070041A1 (en) 2018-10-01 2020-04-09 F. Hoffmann-La Roche Ag Bispecific antigen binding molecules comprising anti-fap clone 212
CN113164780A (zh) 2018-10-10 2021-07-23 泰洛斯治疗公司 抗lap抗体变体及其用途
UY38407A (es) 2018-10-15 2020-05-29 Novartis Ag Anticuerpos estabilizadores de trem2
WO2020081493A1 (en) 2018-10-16 2020-04-23 Molecular Templates, Inc. Pd-l1 binding proteins
EP3867646A1 (en) 2018-10-18 2021-08-25 F. Hoffmann-La Roche AG Diagnostic and therapeutic methods for sarcomatoid kidney cancer
EP3873602B1 (en) 2018-10-30 2023-12-06 Alexion Pharmaceuticals, Inc. Subcutaneous dosage and administration of anti-c5 antibodies for treatment of paroxysmal nocturnal hemoglobinuria (pnh)
WO2020089437A1 (en) 2018-10-31 2020-05-07 Engmab Sàrl Combination therapy
US20230053449A1 (en) 2018-10-31 2023-02-23 Novartis Ag Dc-sign antibody drug conjugates
KR20210108363A (ko) 2018-11-02 2021-09-02 오클라호마 메디컬 리써치 화운데이션 Eltd1에 대한 단일클론성 항체 및 이의 용도
EP3877407B1 (en) 2018-11-05 2026-03-11 F. Hoffmann-La Roche AG Methods of producing two chain proteins in prokaryotic host cells
US12611427B2 (en) 2018-11-05 2026-04-28 Iovance Biotherapeutics, Inc. Treatment of NSCLC patients refractory for anti-PD-1 antibody
CN113366022B (zh) 2018-11-16 2025-11-21 纪念斯隆凯特琳癌症中心 针对粘蛋白-16的抗体及其使用方法
AR117091A1 (es) 2018-11-19 2021-07-07 Bristol Myers Squibb Co Anticuerpos monoclonales antagonistas contra cd40 y sus usos
IL283192B2 (en) 2018-11-20 2025-10-01 Janssen Biotech Inc A safe and effective method for treating psoriasis with a specific anti-IL-23 antibody
US20220364171A1 (en) 2018-11-23 2022-11-17 Katholieke Universiteit Leuven Predicting a treatment response in inflammatory bowel disease
KR20210096559A (ko) 2018-11-27 2021-08-05 이노벤트 바이오로직스 (쑤저우) 컴퍼니, 리미티드 항IL-23p19 항체 및 이의 용도
CN116003597A (zh) 2018-11-27 2023-04-25 舒泰神（北京）生物制药股份有限公司 特异性识别粒细胞-巨噬细胞集落刺激因子受体α的抗体及其用途
EP3887397A1 (en) 2018-11-28 2021-10-06 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
CA3120868A1 (en) 2018-11-30 2020-06-04 Alpine Immune Sciences, Inc. Cd86 variant immunomodulatory proteins and uses thereof
WO2020115115A1 (en) 2018-12-05 2020-06-11 Morphosys Ag Multispecific antigen-binding molecules
JP7536294B2 (ja) 2018-12-05 2024-08-20 株式会社バイカ・セラピュティクス 抗体のＦｃ領域改変体
EP4198057A1 (en) 2018-12-05 2023-06-21 F. Hoffmann-La Roche AG Diagnostic methods and compositions for cancer immunotherapy
WO2020118011A1 (en) 2018-12-06 2020-06-11 Alexion Pharmaceuticals, Inc. Anti-alk2 antibodies and uses thereof
BR112021010908A2 (pt) 2018-12-06 2021-08-31 Genentech, Inc. Método para tratamento de linfoma difuso de grandes células b, kit e imunoconjugado
JP2022513198A (ja) 2018-12-10 2022-02-07 ジェネンテック， インコーポレイテッド Ｆｃ含有タンパク質への部位特異的コンジュゲーションのための光架橋性ペプチド
BR112021010634A2 (pt) 2018-12-14 2021-11-16 Boehringer Ingelheim Io Canada Inc Anticorpos antiperiostina e usos dos mesmos
CN113557244A (zh) 2018-12-18 2021-10-26 弹射器治疗有限公司 预防或治疗移植物抗宿主病(GvHD)的抗CCR7 mAb的用途
SG11202104352XA (en) 2018-12-18 2021-05-28 Boehringer Ingelheim Io Canada Inc Flt3 agonist antibodies and uses thereof
MA54562A (fr) 2018-12-18 2021-10-27 Janssen Biotech Inc Méthode sûre et efficace de traitement du lupus avec un anticorps anti-il12/il23
TW202039554A (zh) 2018-12-19 2020-11-01 瑞士商諾華公司 抗ＴＮＦ－α抗體
AR117453A1 (es) 2018-12-20 2021-08-04 Genentech Inc Fc de anticuerpos modificados y métodos para utilizarlas
KR102910209B1 (ko) 2018-12-21 2026-01-09 제넨테크, 인크. 세포사멸에 내성인 세포주를 사용한 폴리펩티드 생산 방법
EP3898671A1 (en) 2018-12-21 2021-10-27 F. Hoffmann-La Roche AG Antibody that binds to vegf and il-1beta and methods of use
CA3122773A1 (en) 2018-12-26 2020-07-02 Xilio Development, Inc. Anti-ctla4 antibodies and methods of use thereof
WO2020138487A1 (ja) 2018-12-28 2020-07-02 協和キリン株式会社 ＴｆＲに結合するバイスペシフィック抗体
EP3902830A1 (en) 2018-12-30 2021-11-03 F. Hoffmann-La Roche AG Anti-rabbit cd19 antibodies and methods of use
WO2020142740A1 (en) 2019-01-04 2020-07-09 Resolve Therapeutics, Llc Treatment of sjogren's disease with nuclease fusion proteins
WO2020148207A1 (en) 2019-01-14 2020-07-23 INSERM (Institut National de la Santé et de la Recherche Médicale) Human monoclonal antibodies binding to hla-a2
AU2020208193A1 (en) 2019-01-14 2021-07-29 BioNTech SE Methods of treating cancer with a PD-1 axis binding antagonist and an RNA vaccine
BR112021014276A2 (pt) 2019-01-22 2021-09-28 Genentech, Inc. Anticorpos iga isolados, moléculas de fusão igg-iga isoladas, ácido nucleico isolado, célula hospedeira, método para produzir um anticorpo, para tratar um indivíduo, para aumentar a expressão de dímeros, trímeros ou tetrâmeros, para aumentar a produção de polímeros, para aumentar a produção de dímeros, para aumentar a produção de um polímero, para diminuir a produção de polímeros, para aumentar a expressão transitória de um anticorpo, para expressar dímeros de moléculas de fusão, para expressar dímeros, trímeros ou tetrâmeros, para purificar um anticorpo, para purificar um estado oligomérico de um anticorpo, composição farmacêutica e uso do anticorpo
JP7611834B2 (ja) 2019-01-22 2025-01-10 イナート・ファルマ・ソシエテ・アノニム Ｔ細胞リンパ腫の処置
CN113396162B (zh) 2019-01-22 2024-08-16 百时美施贵宝公司 抗IL-7Rα亚基的抗体及其用途
SG11202107941TA (en) 2019-01-23 2021-08-30 Encefa Cd31 competitors and uses thereof
KR102794884B1 (ko) 2019-01-23 2025-04-15 제넨테크, 인크. 진핵 숙주 세포에서 다합체 단백질을 생산하는 방법
US11414496B2 (en) 2019-01-23 2022-08-16 Takeda Pharmaceutical Company Limited Anti-CD38 binding domains
WO2020153467A1 (ja) 2019-01-24 2020-07-30 中外製薬株式会社 新規がん抗原及びそれらの抗原に対する抗体
GB201901197D0 (en) 2019-01-29 2019-03-20 Femtogenix Ltd G-A Crosslinking cytotoxic agents
GB2599228B (en) 2019-02-21 2024-02-07 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
CN119039441A (zh) 2019-02-21 2024-11-29 马伦戈治疗公司 与nkp30结合的抗体分子及其用途
MX2021010254A (es) 2019-02-27 2021-09-21 Angiex Inc Conjugados de anticuerpo-farmaco que comprenden anticuerpos anti-tm4sf1 y metodos de uso de los mismos.
WO2020176748A1 (en) 2019-02-27 2020-09-03 Genentech, Inc. Dosing for treatment with anti-tigit and anti-cd20 or anti-cd38 antibodies
CA3131953A1 (en) 2019-03-01 2020-09-10 Merrimack Pharmaceuticals, Inc. Anti-tnfr2 antibodies and uses thereof
WO2020180733A1 (en) 2019-03-01 2020-09-10 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
WO2020185535A1 (en) 2019-03-08 2020-09-17 Genentech, Inc. Methods for detecting and quantifying membrane-associated proteins on extracellular vesicles
EP3938403A1 (en) 2019-03-14 2022-01-19 F. Hoffmann-La Roche AG Treatment of cancer with her2xcd3 bispecific antibodies in combination with anti-her2 mab
EP3938384A4 (en) 2019-03-14 2022-12-28 Janssen Biotech, Inc. PREPARATION PROCEDURES FOR THE PREPARATION OF ANTI-IL12/IL23 ANTIBODY COMPOSITIONS
JP2022526493A (ja) 2019-03-18 2022-05-25 ヤンセン バイオテツク，インコーポレーテツド 抗ｉｌ１２／ｉｌ２３抗体を用いた小児被験者の乾癬の治療方法
EP3943108A4 (en) 2019-03-19 2023-01-04 Chugai Seiyaku Kabushiki Kaisha ANTIGEN-BINDING MOLECULE WITH ANTIGEN-BINDING DOMAIN WITH VARIABLE BINDING ACTIVITY TO ANTIGEN DEPENDING ON MTA AND LIBRARY TO OBTAIN THE ANTIGEN-BINDING DOMAIN
JP2022526334A (ja) 2019-03-25 2022-05-24 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 新たなタウ種を標的化することによるタウオパチー障害の処置の方法
CN120192414A (zh) 2019-04-03 2025-06-24 建新公司 具有降低的断裂的抗αβTCR结合多肽
GB2589049C (en) 2019-04-11 2024-02-21 argenx BV Anti-IgE antibodies
US12006511B2 (en) 2019-04-15 2024-06-11 The Medical College Of Wisconsin, Inc. Recombinant PD-L1 peptides and methods of use
MX2021012607A (es) 2019-04-17 2022-03-11 Alpine Immune Sciences Inc Metodos y usos de proteinas de fusion de ligando icos (icosl) variante.
CN113924118A (zh) 2019-04-18 2022-01-11 百时美施贵宝公司 在低ph下具有增强的结合特异性的伊匹单抗变体
JP7689373B2 (ja) 2019-04-18 2025-06-06 エイシー イミューン ソシエテ アノニム 治療及び診断のための新規分子
CN114007643A (zh) 2019-04-19 2022-02-01 中外制药株式会社 识别抗体改变部位的嵌合受体
BR112021020867A2 (pt) 2019-04-19 2022-01-04 Genentech Inc Anticorpos, ácido nucleico, vetor, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica, usos do anticorpo, método de tratamento de um indivíduo com câncer e método para reduzir a depuração
CN114269376A (zh) 2019-05-03 2022-04-01 豪夫迈·罗氏有限公司 用抗pd-l1抗体治疗癌症的方法
AU2020275415B2 (en) 2019-05-14 2026-01-15 Genentech, Inc. Methods of using anti-CD79B immunoconjugates to treat follicular lymphoma
WO2020230899A1 (ja) 2019-05-15 2020-11-19 協和キリン株式会社 Ｃｄ４０とｆａｐに結合するバイスペシフィック抗体
EP4696320A2 (en) 2019-05-15 2026-02-18 Chugai Seiyaku Kabushiki Kaisha Anti-c1s antibody
WO2020230901A1 (ja) 2019-05-15 2020-11-19 協和キリン株式会社 Ｃｄ４０とｇｐｃ３に結合するバイスペシフィック抗体
CN113853219B (zh) 2019-05-20 2025-01-07 诺华股份有限公司 具有包含亲水性基团的接头的抗体药物缀合物
JP7489407B2 (ja) 2019-05-21 2024-05-23 ノバルティス アーゲー Ｃｄ１９結合分子及びその使用
CN118994397A (zh) 2019-05-21 2024-11-22 诺华股份有限公司 针对bcma的三特异性结合分子及其用途
US12037378B2 (en) 2019-05-21 2024-07-16 Novartis Ag Variant CD58 domains and uses thereof
AU2020278907A1 (en) 2019-05-23 2022-01-20 Ac Immune Sa Anti-TDP-43 binding molecules and uses thereof
MA56124A (fr) 2019-06-04 2022-04-13 Janssen Biotech Inc Méthode sûre et efficace de traitement de l'arthrite psoriasique au moyen d'un anticorps spécifique anti-il23
WO2020246563A1 (ja) 2019-06-05 2020-12-10 中外製薬株式会社 抗体切断部位結合分子
JP7565951B2 (ja) 2019-06-07 2024-10-11 アルジェニクス ビーブイ 皮下投与に好適なＦｃＲｎインヒビターの医薬製剤
WO2020250915A1 (ja) 2019-06-10 2020-12-17 中外製薬株式会社 サイトカイン阻害剤と組み合わせて使用するための抗ｔ細胞抗原結合分子
US20220298230A1 (en) * 2019-06-11 2022-09-22 The Rockefeller University Antibodies and methods for treatment of viral infections
WO2020260326A1 (en) 2019-06-27 2020-12-30 F. Hoffmann-La Roche Ag Novel icos antibodies and tumor-targeted antigen binding molecules comprising them
MY208387A (en) 2019-07-09 2025-05-05 Beijing Solobio Genetechnology Co Ltd Antibodies specifically recognizing pseudomonas pcrv and uses thereof
MX2022000111A (es) 2019-07-10 2022-02-10 Chugai Pharmaceutical Co Ltd Moleculas de union a claudina-6 y usos de las mismas.
WO2021005232A1 (en) 2019-07-11 2021-01-14 Umc Utrecht Holding B.V. Intranasal administration of neutralising antiviral antibodies
WO2021010326A1 (ja) 2019-07-12 2021-01-21 中外製薬株式会社 抗変異型ｆｇｆｒ３抗体およびその使用
WO2021011681A1 (en) 2019-07-15 2021-01-21 Bristol-Myers Squibb Company Antibodies against human trem-1 and uses thereof
CN114174536B (zh) 2019-07-15 2026-03-27 百时美施贵宝公司 抗trem-1抗体及其用途
EP3999540A1 (en) 2019-07-16 2022-05-25 Institut National de la Santé et de la Recherche Médicale (INSERM) Antibodies having specificity for cd38 and uses thereof
WO2021014389A1 (en) 2019-07-24 2021-01-28 H. Lundbeck A/S Anti-mglur5 antibodies and uses thereof
CN112300279A (zh) 2019-07-26 2021-02-02 上海复宏汉霖生物技术股份有限公司 针对抗cd73抗体和变体的方法和组合物
US12410241B2 (en) 2019-07-26 2025-09-09 Vanderbilt University Human monoclonal antibodies to enterovirus D68
EP4003417A2 (en) 2019-07-29 2022-06-01 Compugen Ltd. Anti-pvrig antibodies formulations and uses thereof
KR20240033090A (ko) 2019-07-31 2024-03-12 에프. 호프만-라 로슈 아게 항-c5 항체 크로발리맙의 사용에 의한 c5-관련 질병의 치료 또는 예방을 위한 투여량 및 투여 섭생
CR20220040A (es) 2019-07-31 2022-03-02 Hoffmann La Roche Régimen de dosificación y administración para el tratamiento o prevención de enfermedades relacionadas con c5 mediante el uso del anticuerpo anti-c5 crovalimab
JP7181438B2 (ja) 2019-08-06 2022-11-30 アプリノイア セラピューティクス リミテッド 病理学的タウ種に結合する抗体及びその使用
CN120204384A (zh) 2019-08-06 2025-06-27 葛兰素史密斯克莱知识产权发展有限公司 生物药物组合物和相关方法
US20220242962A1 (en) 2019-08-12 2022-08-04 Aptevo Research And Development Llc 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40
KR20220044534A (ko) 2019-08-13 2022-04-08 엘피스 바이오파마슈티컬즈 조작된 인터류킨-2 수용체 베타 효능제
TW202122420A (zh) 2019-08-30 2021-06-16 美商艾吉納斯公司 抗ｃｄ９６抗體及其使用方法
CN114340675A (zh) 2019-09-12 2022-04-12 豪夫迈·罗氏有限公司 治疗狼疮性肾炎的组合物和方法
PH12022550646A1 (en) 2019-09-18 2023-04-03 Genentech Inc Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use
TW202124446A (zh) 2019-09-18 2021-07-01 瑞士商諾華公司 與ｅｎｔｐｄ２抗體之組合療法
CN114502590A (zh) 2019-09-18 2022-05-13 诺华股份有限公司 Entpd2抗体、组合疗法、以及使用这些抗体和组合疗法的方法
CA3149719A1 (en) 2019-09-19 2021-03-25 Bristol-Myers Squibb Company Antibodies binding to vista at acidic ph
CN114423454A (zh) 2019-09-20 2022-04-29 豪夫迈·罗氏有限公司 抗类胰蛋白酶抗体的给药
US20220411511A1 (en) 2019-09-26 2022-12-29 Stcube & Co. Antibodies specific to glycosylated ctla-4 and methods of use thereof
EP4034560A1 (en) 2019-09-27 2022-08-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Anti-müllerian inhibiting substance antibodies and uses thereof
JP2022548978A (ja) 2019-09-27 2022-11-22 ジェネンテック， インコーポレイテッド 薬抗ｔｉｇｉｔ及び抗ｐｄ－ｌ１アンタゴニスト抗体を用いた処置のための投薬
EP4034160A1 (en) 2019-09-27 2022-08-03 Janssen Biotech, Inc. Anti-ceacam antibodies and uses thereof
WO2021058729A1 (en) 2019-09-27 2021-04-01 INSERM (Institut National de la Santé et de la Recherche Médicale) Anti-müllerian inhibiting substance type i receptor antibodies and uses thereof
KR20220097891A (ko) 2019-09-30 2022-07-08 바이오버라티브 테라퓨틱스 인크. 렌티바이러스 벡터 제형
EP4041392A1 (en) 2019-10-08 2022-08-17 Nectin Therapeutics Ltd. Antibodies against the poliovirus receptor (pvr) and uses thereof
EP4041768A1 (en) 2019-10-09 2022-08-17 StCube & Co. Antibodies specific to glycosylated lag3 and methods of use thereof
WO2021076196A1 (en) 2019-10-18 2021-04-22 Genentech, Inc. Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma
JP2023500651A (ja) 2019-11-04 2023-01-10 コンピュジェン リミテッド 抗ｐｖｒｉｇ抗体製剤および抗ｐｄ－１抗体による併用療法
KR20220092580A (ko) 2019-11-06 2022-07-01 제넨테크, 인크. 혈액암의 치료를 위한 진단과 치료 방법
US20220396839A1 (en) 2019-11-12 2022-12-15 Foundation Medicine, Inc. Methods of detecting a fusion gene encoding a neoantigen
CA3159964A1 (en) 2019-12-04 2021-06-10 Ac Immune Sa Novel molecules for therapy and diagnosis
EP4069736A1 (en) 2019-12-04 2022-10-12 MedImmune Limited Antibodies against lif and uses thereof
US20230057899A1 (en) 2019-12-05 2023-02-23 Compugen Ltd. Anti-pvrig and anti-tigit antibodies for enhanced nk-cell based tumor killing
EP4072682A1 (en) 2019-12-09 2022-10-19 Institut National de la Santé et de la Recherche Médicale (INSERM) Antibodies having specificity to her4 and uses thereof
WO2021119505A1 (en) 2019-12-13 2021-06-17 Genentech, Inc. Anti-ly6g6d antibodies and methods of use
JP7807076B2 (ja) 2019-12-13 2026-01-27 キュージーン インコーポレイテッド 新規インターロイキン－１５（ｉｌ－１５）融合タンパク質およびその使用
UA128549C2 (uk) 2019-12-27 2024-08-07 Чугаі Сейяку Кабусікі Кайся Антитіло до ctla-4 та його застосування
CN113045655A (zh) 2019-12-27 2021-06-29 高诚生物医药(香港)有限公司 抗ox40抗体及其用途
AU2020416273A1 (en) 2020-01-03 2022-07-28 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
CA3160204A1 (en) 2020-01-06 2021-07-15 Vaccinex, Inc. Anti-ccr8 antibodies and uses thereof
JP2023509195A (ja) 2020-01-08 2023-03-07 アルジェニクス ビーブイ 天疱瘡症を治療する方法
CN110818795B (zh) 2020-01-10 2020-04-24 上海复宏汉霖生物技术股份有限公司 抗tigit抗体和使用方法
WO2021194481A1 (en) 2020-03-24 2021-09-30 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
WO2022050954A1 (en) 2020-09-04 2022-03-10 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
MX2022009391A (es) 2020-01-31 2022-09-26 Genentech Inc Metodos para inducir linfocitos t especificos para neoepitopo con un antagonista de union al eje de pd-1 y una vacuna de arn.
JP2023514152A (ja) 2020-02-06 2023-04-05 ブリストル－マイヤーズ スクイブ カンパニー Ｉｌ－１０およびその使用
JP2023519105A (ja) 2020-02-11 2023-05-10 ヴァンダービルト ユニバーシティ 重症急性呼吸器症候群コロナウイルス２（ｓａｒｓ－ｃｏｖ－２）に対するヒトモノクローナル抗体
TWI895351B (zh) 2020-02-12 2025-09-01 日商中外製藥股份有限公司 用於癌症之治療的抗cd137抗原結合分子
TWI888487B (zh) 2020-02-14 2025-07-01 日商協和麒麟股份有限公司 與ｃｄ３結合之雙特異性抗體
EP4106794A4 (en) 2020-02-19 2024-03-20 Evive Biotechnology (Shanghai) Ltd METHOD FOR TREATING TRANSPLANT AND HOST DISEASE
WO2021173844A1 (en) 2020-02-26 2021-09-02 Biograph 55, Inc. C19 c38 bispecific antibodies
KR20220148209A (ko) 2020-02-28 2022-11-04 상하이 헨리우스 바이오테크, 인크. 항cd137 작제물 및 그 용도
KR20220145859A (ko) 2020-02-28 2022-10-31 상하이 헨리우스 바이오테크, 인크. 항cd137 작제물, 다중 특이적 항체 및 그 용도
KR20220148235A (ko) 2020-02-28 2022-11-04 젠자임 코포레이션 최적화된 약물 접합을 위한 변형된 결합 폴리펩티드
AU2021232158A1 (en) 2020-03-06 2022-09-29 Ona Therapeutics, S.L. Anti-CD36 antibodies and their use to treat cancer
AU2021236302A1 (en) 2020-03-12 2022-10-20 Immune-Onc Therapeutics, Inc. Novel anti-LILRB4 antibodies and derivative products
CA3170025A1 (en) 2020-03-13 2021-09-16 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Pvrig binding protein and its medical uses
PE20230252A1 (es) 2020-03-13 2023-02-07 Genentech Inc Anticuerpos anti-interleucina-33 y sus usos de estos
CN117551194A (zh) 2020-03-19 2024-02-13 基因泰克公司 同种型选择性抗TGF-β抗体及使用方法
US11365239B2 (en) 2020-03-20 2022-06-21 Tsb Therapeutics (Beijing) Co., Ltd. Anti-SARS-COV-2 antibodies and uses thereof
JP2023518815A (ja) 2020-03-23 2023-05-08 ジェネンテック， インコーポレイテッド Ｉｌ６アンタゴニストによるｃｏｖｉｄ－１９肺炎を含む肺炎の治療方法
CN115867577A (zh) 2020-03-23 2023-03-28 基因泰克公司 用于预测covid-19肺炎中对il-6拮抗剂反应的生物标志物
EP4107186A1 (en) 2020-03-23 2022-12-28 Genentech, Inc. Tocilizumab and remdesivir combination therapy for covid-19 pneumonia
AU2021242249A1 (en) 2020-03-24 2022-08-18 Genentech, Inc. Tie2-binding agents and methods of use
JP2023518841A (ja) 2020-03-26 2023-05-08 ジェネンテック， インコーポレイテッド 宿主細胞タンパク質が減少した修飾哺乳動物細胞
WO2021195385A1 (en) 2020-03-26 2021-09-30 Vanderbilt University HUMAN MONOCLONAL ANTIBODIES TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-GoV-2)
HRP20240182T1 (hr) 2020-03-26 2024-04-26 Vanderbilt University Ljudska monoklonska protutijela za teški akutni respiratorni sindrom koronavirusa 2 (sars-cov-2)
US20230128499A1 (en) 2020-03-27 2023-04-27 Novartis Ag Bispecific combination therapy for treating proliferative diseases and autoimmune diseases
CN115397850A (zh) 2020-03-30 2022-11-25 豪夫迈·罗氏有限公司 与vegf和pdgf-b结合的抗体及其使用方法
CR20220541A (es) 2020-03-31 2022-11-28 Chugai Pharmaceutical Co Ltd Moléculas de unión al antígeno multiespecíficas dirigidas a ligando de tipo delta 3 (dll3) y sus usos
MX2022011387A (es) 2020-03-31 2022-10-10 Chugai Pharmaceutical Co Ltd Metodo para producir moleculas de union a antigeno multiespecificas.
WO2021202235A1 (en) 2020-04-01 2021-10-07 University Of Rochester Monoclonal antibodies against the hemagglutinin (ha) and neuraminidase (na) of influenza h3n2 viruses
AR121706A1 (es) 2020-04-01 2022-06-29 Hoffmann La Roche Moléculas de unión a antígeno biespecíficas dirigidas a ox40 y fap
WO2021202959A1 (en) 2020-04-03 2021-10-07 Genentech, Inc. Therapeutic and diagnostic methods for cancer
EP4132576A1 (en) 2020-04-09 2023-02-15 Suzhou Abogen Biosciences Co., Ltd. Nucleic acid vaccines for coronavirus
US20230272056A1 (en) 2020-04-09 2023-08-31 Merck Sharp & Dohme Llc Affinity matured anti-lap antibodies and uses thereof
WO2021207662A1 (en) 2020-04-10 2021-10-14 Genentech, Inc. Use of il-22fc for the treatment or prevention of pneumonia, acute respiratory distress syndrome, or cytokine release syndrome
PE20230255A1 (es) 2020-04-17 2023-02-07 Hutchison Medipharma Ltd Anticuerpo anti-ox40 y usos del mismo
CN115916822A (zh) 2020-04-24 2023-04-04 基因泰克公司 使用抗CD79b免疫缀合物的方法
US20230265204A1 (en) 2020-04-24 2023-08-24 Hoffmann-La Roche Inc. Enzyme and pathway modulation with sulfhydryl compounds and their derivatives
JP2023523145A (ja) 2020-04-27 2023-06-02 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア リポ蛋白（ａ）に対するイソ型非依存性抗体
MX2021015024A (es) 2020-04-28 2022-01-18 Univ Rockefeller Anticuerpos anti-sars-cov-2 ampliamente neutralizantes y métodos de uso de los mismos.
EP4143345A1 (en) 2020-04-28 2023-03-08 Genentech, Inc. Methods and compositions for non-small cell lung cancer immunotherapy
TW202200212A (zh) 2020-05-03 2022-01-01 中國大陸商聯寧（蘇州）生物製藥有限公司 包含抗-trop-2抗體之抗體藥物結合物
US20210347880A1 (en) 2020-05-05 2021-11-11 Janssen Biotech, Inc. Methods of Treating Crohn's Disease with Anti-IL23 Specific Antibody
EP4146684A2 (en) 2020-05-08 2023-03-15 Alpine Immune Sciences, Inc. April and baff inhibitory immunomodulatory proteins with and without a t cell inhibitory protein and methods of use thereof
CA3180683A1 (en) 2020-05-12 2021-11-18 Inserm (Institut National De La Sante Et De La Recherche Medicale) New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas
KR20230012539A (ko) 2020-05-13 2023-01-26 디스크 메디슨, 인크. 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체
US20230192867A1 (en) 2020-05-15 2023-06-22 Bristol-Myers Squibb Company Antibodies to garp
TW202208423A (zh) 2020-05-17 2022-03-01 英商阿斯特捷利康英國股份有限公司 Ｓａｒｓ－ｃｏｖ－２抗體及其選擇和使用方法
GB2595299B (en) 2020-05-21 2022-08-03 Mabsolve Ltd Modified immunoglobulin FC regions
KR20230015365A (ko) 2020-05-22 2023-01-31 포르미콘 아게 Ace2 융합 단백질 및 이의 용도
EP4157881A4 (en) 2020-05-27 2024-10-09 Staidson (Beijing) Biopharmaceuticals Co., Ltd. ANTIBODIES THAT SPECIFICALLY RECOGNIZE NERVE GROWTH FACTOR AND THEIR USES
EP4157462A1 (en) 2020-06-02 2023-04-05 Dynamicure Biotechnology LLC Anti-cd93 constructs and uses thereof
CN116529260A (zh) 2020-06-02 2023-08-01 当康生物技术有限责任公司 抗cd93构建体及其用途
PE20240080A1 (es) 2020-06-08 2024-01-16 Hoffmann La Roche Anticuerpos anti-hbv y metodos de uso
JP7796415B2 (ja) 2020-06-10 2026-01-09 株式会社バイカ・セラピュティクス エリスロポエチンポリペプチドを含む融合タンパク質
JP2023529206A (ja) 2020-06-12 2023-07-07 ジェネンテック， インコーポレイテッド がん免疫療法のための方法及び組成物
AU2021293038A1 (en) 2020-06-16 2023-02-02 F. Hoffmann-La Roche Ag Methods and compositions for treating triple-negative breast cancer
KR20230024368A (ko) 2020-06-18 2023-02-20 제넨테크, 인크. 항-tigit 항체 및 pd-1 축 결합 길항제를 사용한 치료
MX2022015764A (es) 2020-06-19 2023-01-19 Chugai Pharmaceutical Co Ltd Molecula de union al antigeno anti-celulas t para usarse en combinacion con un inhibidor de angiogenesis.
JP2023532234A (ja) 2020-06-22 2023-07-27 イノベント バイオロジクス（スーチョウ）カンパニー，リミティド 抗ｃｄ７３抗体とその用途
MX2023000156A (es) 2020-06-24 2023-02-16 Bioverativ Therapeutics Inc Metodos para la eliminacion de factor viii libre de preparaciones de vectores lentivirales modificados para expresar dicha proteina.
CA3184747A1 (en) 2020-06-24 2021-12-30 Genentech, Inc. Apoptosis resistant cell lines
CA3183835A1 (en) 2020-06-25 2021-12-30 Jeanne E. Baker High affinity antibodies targeting tau phosphorylated at serine 413
CA3165342A1 (en) 2020-06-29 2022-01-06 James Arthur Posada Treatment of sjogren's syndrome with nuclease fusion proteins
KR20230030644A (ko) 2020-06-29 2023-03-06 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) 항-단백질 단일-도메인 항체 및 이를 포함하는 폴리펩타이드
WO2022013745A1 (en) 2020-07-13 2022-01-20 Janssen Biotech, Inc. Safe and effective method of treating psoriatic arthritis with anti-il23 specific antibody
JP7846667B2 (ja) 2020-07-16 2026-04-15 レジェンド バイオテック アイルランド リミテッド Ｃｄ２０結合分子及びその使用
PH12023550112A1 (en) 2020-07-17 2024-06-24 Genentech Inc Anti-notch2 antibodies and methods of use
GB2597532A (en) 2020-07-28 2022-02-02 Femtogenix Ltd Cytotoxic compounds
US20230322935A1 (en) 2020-07-29 2023-10-12 Dynamicure Biotechnology Llc Anti-cd93 constructs and uses thereof
US20220073603A1 (en) 2020-07-30 2022-03-10 Janssen Biotech, Inc. Method of Treating Psoriasis in Pediatric Subjects with Anti-IL12/IL23 Antibody
CN116194124A (zh) 2020-07-31 2023-05-30 中外制药株式会社 包含表达嵌合受体的细胞的药物组合物
JP2023536602A (ja) 2020-08-03 2023-08-28 ジェネンテック， インコーポレイテッド リンパ腫のための診断及び治療方法
IL300376A (en) 2020-08-06 2023-04-01 Bioverativ Usa Inc Inflammatory cytokines and fatigue in subjects with complement-mediated disease
US20220041694A1 (en) 2020-08-10 2022-02-10 Astrazeneca Uk Limited Sars-cov-2 antibodies for treatment and prevention of covid-19
TW202221026A (zh) 2020-08-14 2022-06-01 瑞士商Ａｃ 免疫有限公司 人源化抗ｔｄｐ－４３結合分子及其用途
SMT202500106T1 (it) 2020-08-18 2025-05-12 Cephalon Llc Anticorpi anti-par-2 e loro metodi d'uso
BR112023003036A2 (pt) * 2020-08-19 2023-04-25 Astellas Pharma Inc Região fc modificada de ocorrência não natural humana de igg especificamente ligando-se a receptor de fc modificado de ocorrência não natural
CA3188867A1 (en) 2020-08-20 2022-02-24 Xueyin Wang Compositions and methods for treating ceacam positive cancers
IL300500A (en) 2020-08-20 2023-04-01 A2 Biotherapeutics Inc Preparations and methods for the treatment of mesothelin positive cancer
WO2022040470A1 (en) * 2020-08-20 2022-02-24 A2 Biotherapeutics, Inc. Compositions and methods for treating ceacam positive cancers
WO2022043517A2 (en) 2020-08-27 2022-03-03 Cureab Gmbh Anti-golph2 antibodies for macrophage and dendritic cell differentiation
WO2022044248A1 (ja) * 2020-08-28 2022-03-03 中外製薬株式会社 ヘテロ二量体Ｆｃポリペプチド
WO2022047316A1 (en) 2020-08-28 2022-03-03 Sana Biotechnology, Inc. Modified anti-viral binding agents
CA3192344A1 (en) 2020-08-28 2022-03-03 Genentech, Inc. Crispr/cas9 multiplex knockout of host cell proteins
EP4208201A1 (en) 2020-09-04 2023-07-12 F. Hoffmann-La Roche AG Antibody that binds to vegf-a and ang2 and methods of use
EP4213877A1 (en) 2020-09-17 2023-07-26 Genentech, Inc. Results of empacta: a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of tocilizumab in hospitalized patients with covid-19 pneumonia
CN118146384A (zh) 2020-09-28 2024-06-07 安济盛生物医药有限公司 抗硬骨抑素构建体及其用途
WO2022069940A1 (en) 2020-09-30 2022-04-07 Compugen Ltd. Combination therapy with anti-pvrig antibodies formulations, anti-tigit antibodies, and anti-pd-1 antibodies
CN116406291A (zh) 2020-10-05 2023-07-07 基因泰克公司 用抗fcrh5/抗cd3双特异性抗体进行治疗的给药
WO2022076606A1 (en) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
JP2023546359A (ja) 2020-10-06 2023-11-02 アイオバンス バイオセラピューティクス，インコーポレイテッド 腫瘍浸潤リンパ球療法によるｎｓｃｌｃ患者の治療
EP4229082A1 (en) 2020-10-16 2023-08-23 AC Immune SA Antibodies binding to alpha-synuclein for therapy and diagnosis
WO2022084400A1 (en) 2020-10-20 2022-04-28 Kantonsspital St. Gallen Antibodies or antigen-binding fragments specifically binding to gremlin-1 and uses thereof
CA3199319A1 (en) 2020-10-22 2022-04-28 Janssen Biotech, Inc. Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses
EP4232822A2 (en) 2020-10-26 2023-08-30 Compugen Ltd. Pvrl2 and/or pvrig as biomarkers for treatment
WO2022093981A1 (en) 2020-10-28 2022-05-05 Genentech, Inc. Combination therapy comprising ptpn22 inhibitors and pd-l1 binding antagonists
KR20230093483A (ko) 2020-10-29 2023-06-27 포르미콘 아게 Ace2 융합 단백질 및 이의 용도
TW202227481A (zh) 2020-11-04 2022-07-16 美國洛克菲勒大學 中和抗sars-cov-2抗體
TWI874719B (zh) 2020-11-04 2025-03-01 美商建南德克公司 用抗cd20/抗cd3雙特異性抗體進行治療之給藥
AU2021374594B2 (en) 2020-11-04 2026-03-05 Genentech, Inc. Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates
JP7716473B2 (ja) 2020-11-04 2025-07-31 ジェネンテック， インコーポレイテッド 抗ｃｄ２０／抗ｃｄ３二重特異性抗体の皮下投薬
IL302412A (en) 2020-11-06 2023-06-01 Novartis Ag Anti-CD19 and B-cell targeting agent combination therapy for the treatment of B-cell malignancies
CA3199095A1 (en) 2020-11-06 2022-05-12 Novartis Ag Cd19 binding molecules and uses thereof
WO2022115865A2 (en) 2020-11-25 2022-06-02 Xilio Development, Inc. Tumor-specific cleavable linkers
IL303328A (en) 2020-12-01 2023-07-01 Aptevo Res & Development Llc Heterodimeric psma and cd3-binding bispecific antibodies
WO2022116877A1 (en) 2020-12-02 2022-06-09 Shanghai Henlius Biotech, Inc. ANTI-GARP/TGFβ ANTIBODIES AND METHODS OF USE
EP4255451A4 (en) 2020-12-03 2025-01-01 The Board Of Regents Of The University Of Texas System Methods for identifying lilrb-blocking antibodies
TW202237639A (zh) 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 鳥苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法
TW202237638A (zh) 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 烏苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法
EP4259164A1 (en) 2020-12-11 2023-10-18 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors
EP4259661A1 (en) 2020-12-14 2023-10-18 Novartis AG Reversal binding agents for anti-natriuretic peptide receptor 1 (npr1) antibodies and uses thereof
EP4262827A1 (en) 2020-12-17 2023-10-25 Iovance Biotherapeutics, Inc. Treatment of cancers with tumor infiltrating lymphocytes
AU2021401302A1 (en) 2020-12-17 2023-07-06 Iovance Biotherapeutics, Inc. Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors
MX2023007133A (es) 2020-12-17 2023-06-27 Hoffmann La Roche Anticuerpos anti-hla-g y uso de estos.
KR20230124959A (ko) 2020-12-23 2023-08-28 이노벤트 바이오로직스 (쑤저우) 컴퍼니, 리미티드 항-b7-h3 항체 및 이의 용도
WO2022140797A1 (en) 2020-12-23 2022-06-30 Immunowake Inc. Immunocytokines and uses thereof
CA3202832A1 (en) 2020-12-31 2022-07-07 Romesh R. Subramanian Muscle targeting complexes and uses thereof for treating myotonic dystrophy
JP2024501845A (ja) 2020-12-31 2024-01-16 アイオバンス バイオセラピューティクス，インコーポレイテッド 腫瘍浸潤リンパ球の自動化された産生のためのデバイス及びプロセス
JP2024503826A (ja) 2021-01-06 2024-01-29 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｐｄ１－ｌａｇ３二重特異性抗体及びｃｄ２０ ｔ細胞二重特異性抗体を用いる併用療法
WO2022155324A1 (en) 2021-01-15 2022-07-21 The Rockefeller University Neutralizing anti-sars-cov-2 antibodies
JP2024504372A (ja) 2021-01-22 2024-01-31 エルピス・バイオファーマシューティカルズ 抗ｐｄ－ｌ１モノクローナル抗体及びインターロイキン１５（ｉｌ－１５）、インターロイキン１５受容体１５アルファまたはインターロイキン２との融合タンパク質
CN117120084A (zh) 2021-01-28 2023-11-24 维肯芬特有限责任公司 用于调节b细胞介导的免疫应答的方法和手段
WO2022165266A1 (en) 2021-01-28 2022-08-04 Compugen Ltd. Anti-pvrig antibodies formulations and uses thereof
WO2022162203A1 (en) 2021-01-28 2022-08-04 Vaccinvent Gmbh Method and means for modulating b-cell mediated immune responses
WO2022165275A2 (en) 2021-01-28 2022-08-04 Compugen Ltd. Combination therapy with anti-pvrig antibodies formulations and anti-pd-1-antibodies
JP2024504493A (ja) 2021-01-28 2024-01-31 ヴァクスィーンヴェント ゲーエムベーハー Ｂ細胞媒介性免疫応答を調節するための方法及び手段
WO2022165260A1 (en) 2021-01-29 2022-08-04 Iovance Biotherapeutics, Inc. Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy
WO2022169872A1 (en) 2021-02-03 2022-08-11 Genentech, Inc. Multispecific binding protein degrader platform and methods of use
KR20230146032A (ko) 2021-02-15 2023-10-18 다케다 야쿠힌 고교 가부시키가이샤 Tgf-b 신호전달을 조절하기 위한 세포 치료 조성물 및 방법
GEAP202416351A (en) 2021-02-17 2024-02-12 Dr Falk Pharma Gmbh Anti-cd30l antibodies and uses thereof
EP4301467A1 (en) 2021-03-01 2024-01-10 Xilio Development, Inc. Combination of ctla4 and pd1/pdl1 antibodies for treating cancer
CA3209364A1 (en) 2021-03-01 2022-09-09 Jennifer O'neil Combination of masked ctla4 and pd1/pdl1 antibodies for treating cancer
AU2022230745A1 (en) 2021-03-03 2023-08-17 Formycon Ag Formulations of ace2 fc fusion proteins
US20240181073A1 (en) 2021-03-03 2024-06-06 Sorrento Therapeutics, Inc. Antibody-Drug Conjugates Comprising an Anti-BCMA Antibody
TW202302646A (zh) 2021-03-05 2023-01-16 美商當康生物科技有限公司 抗vista構築體及其用途
EP4301138A2 (en) 2021-03-05 2024-01-10 Iovance Biotherapeutics, Inc. Tumor storage and cell culture compositions
IL305758A (en) 2021-03-10 2023-11-01 Immunowake Inc Immunomodulatory compounds and their uses
WO2022192647A1 (en) 2021-03-12 2022-09-15 Genentech, Inc. Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use
IL305802A (en) 2021-03-12 2023-11-01 Janssen Biotech Inc A safe and effective method for the treatment of rheumatoid arthritis with a specific anti-IL23 antibody
EP4305062A1 (en) 2021-03-12 2024-01-17 Janssen Biotech, Inc. Method of treating psoriatic arthritis patients with inadequate response to tnf therapy with anti-il23 specific antibody
AU2022238526A1 (en) 2021-03-15 2023-09-07 F. Hoffmann-La Roche Ag Compositions and methods of treating lupus nephritis
WO2022197877A1 (en) 2021-03-19 2022-09-22 Genentech, Inc. Methods and compositions for time delayed bio-orthogonal release of cytotoxic agents
US20240191191A1 (en) 2021-03-19 2024-06-13 Iovance Biotherapeutics, Inc. Methods for infiltrating lymphocyte (til) expansion related to cd39/cd69 selection and gene knockout in tils
CA3213080A1 (en) 2021-03-23 2022-09-29 Krit RITTHIPICHAI Cish gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy
EP4314049A1 (en) 2021-03-25 2024-02-07 Dynamicure Biotechnology LLC Anti-igfbp7 constructs and uses thereof
JP2024512029A (ja) 2021-03-25 2024-03-18 アイオバンス バイオセラピューティクス，インコーポレイテッド Ｔ細胞共培養効力アッセイのための方法及び組成物、ならびに細胞療法製品との使用
WO2022200525A1 (en) 2021-03-26 2022-09-29 Innate Pharma Multispecific proteins comprising an nkp46-binding site, a cancer antgienge binding site fused to a cytokine for nk cell engaging
JP2024513172A (ja) 2021-03-26 2024-03-22 ヤンセン バイオテツク，インコーポレーテツド 対らせん状細線維タウに対するヒト化抗体及びその使用
WO2022212645A1 (en) 2021-03-31 2022-10-06 Bioverativ Usa Inc. Reducing surgery-associated hemolysis in cold agglutinin disease patients
EP4314068A1 (en) 2021-04-02 2024-02-07 The Regents Of The University Of California Antibodies against cleaved cdcp1 and uses thereof
CA3215830A1 (en) 2021-04-19 2022-10-27 Rafael CUBAS Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
EP4326855A1 (en) 2021-04-19 2024-02-28 Genentech, Inc. Modified mammalian cells
EP4334343A2 (en) 2021-05-06 2024-03-13 The Rockefeller University Neutralizing anti-sars- cov-2 antibodies and methods of use thereof
US20240279310A1 (en) 2021-05-07 2024-08-22 Alpine Immune Sciences, Inc. Methods of dosing and treatment with a taci-fc fusion immunomodulatory protein
IL308351A (en) 2021-05-12 2024-01-01 Genentech Inc Methods for using anti-CD79B immunoconjugates to treat diffuse large B-cell lymphoma
AU2022273303A1 (en) 2021-05-14 2023-11-02 Genentech, Inc. Agonists of trem2
EP4337330A1 (en) 2021-05-14 2024-03-20 Genentech, Inc. Methods for treatment of cd20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin
WO2022245877A1 (en) 2021-05-17 2022-11-24 Curia Ip Holdings, Llc Sars-cov-2 spike protein antibodies
US20220372114A1 (en) 2021-05-17 2022-11-24 Curia Ip Holdings, Llc Sars-cov-2 spike protein antibodies
JP2024519029A (ja) 2021-05-17 2024-05-08 アイオバンス バイオセラピューティクス，インコーポレイテッド Ｐｄ－１遺伝子編集された腫瘍浸潤リンパ球及び免疫療法におけるその使用
WO2022243261A1 (en) 2021-05-19 2022-11-24 F. Hoffmann-La Roche Ag Agonistic cd40 antigen binding molecules targeting cea
CN117396599A (zh) 2021-05-21 2024-01-12 基因泰克公司 用于生产目的重组产物的经修饰的细胞
CN117396513A (zh) 2021-05-28 2024-01-12 葛兰素史密斯克莱知识产权发展有限公司 治疗癌症的联合疗法
US20240270862A1 (en) 2021-06-01 2024-08-15 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of b cell depleting agents for the treatment of rheumatic heart disease
TW202306994A (zh) 2021-06-04 2023-02-16 日商中外製藥股份有限公司 抗ddr2抗體及其用途
KR20240019786A (ko) 2021-06-09 2024-02-14 이나뜨 파르마 에스.에이. Cd20, nkp46, cd16에 결합하고 il-2에 접합된 다중특이적 항체
BR112023025331A2 (pt) 2021-06-09 2024-02-27 Innate Pharma Proteína multiespecífica, composição farmacêutica, célula recombinante, ácido nucleico ou conjunto de ácidos nucleicos, uso de uma proteína ou composição, métodos ou uso
WO2022258691A1 (en) 2021-06-09 2022-12-15 Innate Pharma Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a
WO2022258678A1 (en) 2021-06-09 2022-12-15 Innate Pharma Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a
CN117980333A (zh) 2021-06-11 2024-05-03 基因泰克公司 用st2拮抗剂治疗慢性阻塞性肺疾病的方法
WO2022263357A1 (en) 2021-06-14 2022-12-22 Argenx Iip Bv Anti-il-9 antibodies and methods of use thereof
US12227574B2 (en) 2021-06-17 2025-02-18 Amberstone Biosciences, Inc. Anti-CD3 constructs and uses thereof
WO2022269451A1 (en) 2021-06-22 2022-12-29 Novartis Ag Bispecific antibodies for use in treatment of hidradenitis suppurativa
TWI879694B (zh) 2021-06-25 2025-04-01 日商中外製藥股份有限公司 抗ctla-4抗體的用途
US12448451B2 (en) 2021-06-25 2025-10-21 Chugai Seiyaku Kabushiki Kaisha Anti-CTLA-4 antibody and use thereof
AR126220A1 (es) 2021-06-25 2023-09-27 Chugai Pharmaceutical Co Ltd Anticuerpo anti-ctla-4
EP4363450A1 (en) 2021-07-01 2024-05-08 Compugen Ltd. Anti-tigit and anti-pvrig in monotherapy and combination treatments
WO2023279092A2 (en) 2021-07-02 2023-01-05 Genentech, Inc. Methods and compositions for treating cancer
CN118103397A (zh) 2021-07-08 2024-05-28 舒泰神(加州)生物科技有限公司 特异性识别tnfr2的抗体及其用途
JP2024527581A (ja) 2021-07-09 2024-07-25 ヤンセン バイオテツク，インコーポレーテツド 抗ｉｌ１２／ｉｌ２３抗体組成物を生産するための製造方法
EP4370545A1 (en) 2021-07-12 2024-05-22 Genentech, Inc. Structures for reducing antibody-lipase binding
US12240910B2 (en) 2021-07-14 2025-03-04 Genentech, Inc. Anti-C-C motif chemokine receptor 8 (CCR8) antibodies and methods of use
US20240343817A1 (en) 2021-07-14 2024-10-17 Staidson (Beijing) Biopharmaceuticals Co., Ltd. Antibody that specifically recognizes cd40 and application thereof
WO2023004386A1 (en) 2021-07-22 2023-01-26 Genentech, Inc. Brain targeting compositions and methods of use thereof
EP4373270A2 (en) 2021-07-22 2024-05-29 Iovance Biotherapeutics, Inc. Method for cryopreservation of solid tumor fragments
EP4373859A1 (en) 2021-07-22 2024-05-29 F. Hoffmann-La Roche AG Heterodimeric fc domain antibodies
JP2024527977A (ja) 2021-07-27 2024-07-26 ノヴァブ， インコーポレイテッド 免疫エフェクター機能を有する操作されたｖｌｒｂ抗体
AU2022317820A1 (en) 2021-07-28 2023-12-14 F. Hoffmann-La Roche Ag Methods and compositions for treating cancer
JP2024527961A (ja) 2021-07-28 2024-07-26 アイオバンス バイオセラピューティクス，インコーポレイテッド Ｋｒａｓ阻害剤と併用した腫瘍浸潤リンパ球療法によるがん患者の治療
KR20240042476A (ko) 2021-07-30 2024-04-02 오엔에이 테라퓨틱스 에스.엘. 항-cd36 항체 및 암을 치료하기 위한 이의 용도
CN117897404A (zh) 2021-08-02 2024-04-16 信达生物制药(苏州)有限公司 抗CD79b×CD3双特异性抗体及其用途
CN117794953A (zh) 2021-08-03 2024-03-29 豪夫迈·罗氏有限公司 双特异性抗体及使用方法
TW202323822A (zh) 2021-08-03 2023-06-16 英商葛蘭素史密斯克藍智慧財產發展有限公司 生藥組合物及穩定同位素標記肽之圖譜定位方法
US20240336697A1 (en) 2021-08-07 2024-10-10 Genentech, Inc. Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma
CN117897409A (zh) 2021-08-13 2024-04-16 基因泰克公司 抗类胰蛋白酶抗体的给药
WO2023021055A1 (en) 2021-08-19 2023-02-23 F. Hoffmann-La Roche Ag Multivalent anti-variant fc-region antibodies and methods of use
CA3229748A1 (en) 2021-08-26 2023-03-02 Akifumi Kato Bispecific antibody that binds to cd116 and cd131
JP2024534151A (ja) 2021-08-27 2024-09-18 ジェネンテック， インコーポレイテッド タウ病態の治療方法
WO2023034750A1 (en) 2021-08-30 2023-03-09 Genentech, Inc. Anti-polyubiquitin multispecific antibodies
MX2024002611A (es) 2021-08-30 2024-05-29 Lassen Therapeutics 1 Inc Anticuerpos anti-il-11ra.
WO2023039488A1 (en) 2021-09-09 2023-03-16 Iovance Biotherapeutics, Inc. Processes for generating til products using pd-1 talen knockdown
WO2023043124A1 (ko) * 2021-09-17 2023-03-23 고려대학교 산학협력단 Fcγrⅲa 결합력이 향상된 당화 fc 변이체들
US20250188185A1 (en) * 2021-09-17 2025-06-12 Korea University Research And Business Foundation GLYCOSYLATED FC VARIANTS WITH IMPROVED SELECTIVE BINDING AFFINITY TO FCyRIIIA
US20250000903A1 (en) 2021-09-24 2025-01-02 Iovance Biotherapeutics, Inc. Expansion processes and agents for tumor infiltrating lymphocytes
WO2023056240A2 (en) 2021-09-28 2023-04-06 Frontaim Biomedicines, Inc. Multiple formats of molecular complexes
WO2023053282A1 (ja) 2021-09-29 2023-04-06 中外製薬株式会社 がんの治療に用いるための細胞傷害誘導治療剤
WO2023056403A1 (en) 2021-09-30 2023-04-06 Genentech, Inc. Methods for treatment of hematologic cancers using anti-tigit antibodies, anti-cd38 antibodies, and pd-1 axis binding antagonists
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
AU2022358522A1 (en) 2021-09-30 2024-03-28 Seagen Inc. B7-h4 antibody-drug conjugates for the treatment of cancer
CA3233953A1 (en) 2021-10-05 2023-04-13 Matthew Bruce Combination therapies for treating cancer
CN116064598B (zh) 2021-10-08 2024-03-12 苏州艾博生物科技有限公司 冠状病毒的核酸疫苗
EP4413998A4 (en) 2021-10-08 2026-02-25 Chugai Pharmaceutical Co Ltd METHOD FOR PREPARING A PRE-FILLED SYRINGE FORMULATION
WO2023064958A1 (en) 2021-10-15 2023-04-20 Compugen Ltd. Combination therapy with anti-pvrig antibodies formulations, anti-tigit antibodies, and anti-pd-1 antibodies
WO2023077015A2 (en) 2021-10-27 2023-05-04 Iovance Biotherapeutics, Inc. Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy
EP4423126B1 (en) 2021-10-29 2026-05-06 Janssen Biotech, Inc. Methods of treating crohn's disease with anti-il23 specific antibody
US20250251400A1 (en) 2021-11-05 2025-08-07 American Diagnostics & Therapy, Llc (Adxrx) Monoclonal Antibodies Against Carcinoembryonic Antigens, and Their Uses
TW202342095A (zh) 2021-11-05 2023-11-01 英商阿斯特捷利康英國股份有限公司 用於治療和預防ｃｏｖｉｄ—１９之組成物
CA3237410A1 (en) 2021-11-10 2023-05-19 Friedrich Graf Finck VON FINCKENSTEIN Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes
EP4430072A1 (en) 2021-11-10 2024-09-18 Genentech, Inc. Anti-interleukin-33 antibodies and uses thereof
EP4433501A1 (en) 2021-11-15 2024-09-25 Janssen Biotech, Inc. Methods of treating crohn's disease with anti-il23 specific antibody
TW202337494A (zh) 2021-11-16 2023-10-01 美商建南德克公司 用莫蘇妥珠單抗治療全身性紅斑狼瘡（ｓｌｅ）之方法及組成物
AU2022390134A1 (en) 2021-11-16 2024-05-16 Ac Immune Sa Novel molecules for therapy and diagnosis
JP2024540480A (ja) 2021-11-17 2024-10-31 ディスク・メディシン・インコーポレイテッド 腎臓疾患の貧血を処置する方法
US20230159633A1 (en) 2021-11-23 2023-05-25 Janssen Biotech, Inc. Method of Treating Ulcerative Colitis with Anti-IL23 Specific Antibody
EP4437112A1 (en) 2021-11-24 2024-10-02 Formycon AG Improved ace2 fusion proteins
WO2023094571A1 (en) 2021-11-25 2023-06-01 Formycon Ag Stabilization of ace2 fusion proteins
EP4445911A4 (en) 2021-12-06 2025-10-22 Beijing Solobio Genetechnology Co Ltd BISPECIFIC ANTIBODY THAT BINDS SPECIFICALLY TO KLEBSIELLA PNEUMONIAE O1 AND O2 ANTIGENS AND COMPOSITION
WO2023114829A1 (en) 2021-12-15 2023-06-22 Genentech, Inc. Stabilized il-18 polypeptides and uses thereof
KR20240122784A (ko) 2021-12-17 2024-08-13 상하이 헨리우스 바이오테크, 인크. 항-ox40 항체 및 사용 방법
KR20240122840A (ko) 2021-12-17 2024-08-13 비이브 헬쓰케어 컴퍼니 Hiv 감염에 대한 조합 요법 및 그의 용도
KR20240116755A (ko) 2021-12-17 2024-07-30 상하이 헨리우스 바이오테크, 인크. 항-ox40 항체, 다중 특이적 항체 및 이의 사용 방법
CR20240246A (es) 2021-12-20 2024-07-19 Hoffmann La Roche Anticuerpos agonistas anti-ltbr y anticuerpos biespecificos que los comprenden
UY40097A (es) 2022-01-07 2023-07-14 Johnson & Johnson Entpr Innovation Inc Materiales y métodos de proteínas de unión a il-1b
IL314367A (en) 2022-01-18 2024-09-01 argenx BV Antibodies to galectin 10
US20230322958A1 (en) 2022-01-19 2023-10-12 Genentech, Inc. Anti-Notch2 Antibodies and Conjugates and Methods of Use
US20250333485A1 (en) 2022-01-27 2025-10-30 The Rockefeller University Broadly neutralizing anti-sars-cov-2 antibodies targeting the n-terminal domain of the spike protein and methods of use thereof
EP4469065A1 (en) 2022-01-28 2024-12-04 Iovance Biotherapeutics, Inc. Cytokine associated tumor infiltrating lymphocytes compositions and methods
CA3243416A1 (en) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. TUMOR INFILTRATION LYMPHOCYTES MODIFIED TO EXPRESS PAYLOADS
CA3243689A1 (en) 2022-02-16 2023-08-24 Ac Immune Sa Humanized Anti-TDP-43 Bonding Molecules and Their Uses
TW202342510A (zh) 2022-02-18 2023-11-01 英商Ｒｑ生物科技有限公司 抗體
US20230303719A1 (en) 2022-03-03 2023-09-28 Yale University Humanized 3e10 antibodies, variants, and antigen binding fragments thereof
WO2023172883A1 (en) 2022-03-07 2023-09-14 Alpine Immune Sciences, Inc. Immunomodulatory proteins of variant cd80 polypeptides, cell therapies thereof and related methods and uses
EP4489790A1 (en) 2022-03-10 2025-01-15 Vivasor, Inc. Antibody-drug conjugates and uses thereof
CN119173531A (zh) 2022-03-11 2024-12-20 詹森药业有限公司 多特异性抗体及其用途
CA3254442A1 (en) 2022-03-11 2023-09-14 Janssen Pharmaceutica Nv MULTISPECIFIC ANTIBODIES AND THEIR USES
AU2023232448A1 (en) 2022-03-11 2024-10-24 Janssen Pharmaceutica Nv Multispecific antibodies and uses thereof
WO2023178192A1 (en) 2022-03-15 2023-09-21 Compugen Ltd. Il-18bp antagonist antibodies and their use in monotherapy and combination therapy in the treatment of cancer
WO2023178357A1 (en) 2022-03-18 2023-09-21 Evolveimmune Therapeutics, Inc. Bispecific antibody fusion molecules and methods of use thereof
US20240103010A1 (en) 2022-03-18 2024-03-28 Compugen Ltd. Pvrl2 and/or pvrig as biomarkers for treatment
CA3245762A1 (en) 2022-03-25 2023-09-28 Shanghai Henlius Biologics Co., Ltd. ANTI-MSLN ANTIBODIES AND METHODS OF USE
JP2025511000A (ja) 2022-03-28 2025-04-15 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト インターフェロンガンマバリアントおよびこれを含む抗原結合分子
WO2023187657A1 (en) 2022-03-30 2023-10-05 Novartis Ag Methods of treating disorders using anti-natriuretic peptide receptor 1 (npr1) antibodies
JP2025512860A (ja) 2022-03-30 2025-04-22 ヤンセン バイオテツク，インコーポレーテツド Ｉｌ－２３に特異的な抗体によって軽度から中等度の乾癬を治療する方法
IL315770A (en) 2022-04-01 2024-11-01 Genentech Inc Dosage for treatment with bispecific anti-FCRH5/anti-CD3 antibodies
GB202204813D0 (en) 2022-04-01 2022-05-18 Bradcode Ltd Human monoclonal antibodies and methods of use thereof
WO2023196877A1 (en) 2022-04-06 2023-10-12 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
US20260043816A1 (en) 2022-04-08 2026-02-12 Ac Immune Sa Anti-TDP-43 Binding Molecules
WO2023201299A1 (en) 2022-04-13 2023-10-19 Genentech, Inc. Pharmaceutical compositions of therapeutic proteins and methods of use
JP2025512401A (ja) 2022-04-15 2025-04-17 アイオバンス バイオセラピューティクス，インコーポレイテッド 特定のサイトカインの組み合わせ及び／またはＡＫＴｉ処理を使用したＴＩＬ拡張プロセス
US20250257123A1 (en) 2022-04-20 2025-08-14 Kantonsspital St. Gallen Antibodies or antigen-binding fragments pan-specifically binding to gremlin-1 and gremlin-2 and uses thereof
US20250289871A1 (en) 2022-04-29 2025-09-18 Astrazeneca Uk Limited Sars-cov-2 antibodies and methods of using the same
WO2023212304A1 (en) 2022-04-29 2023-11-02 23Andme, Inc. Antigen binding proteins
AU2023264069A1 (en) 2022-05-03 2024-10-24 Genentech, Inc. Anti-ly6e antibodies, immunoconjugates, and uses thereof
CN119487065A (zh) 2022-05-09 2025-02-18 舒泰神（北京）生物制药股份有限公司 特异性识别gdf15的抗体及其应用
CN119731199A (zh) 2022-05-10 2025-03-28 艾佩斯瑞生物制药公司 工程化的白细胞介素-2受体β降低结合的激动剂
CA3251533A1 (en) 2022-05-10 2023-11-16 Iovance Biotherapeutics, Inc. TREATMENT OF CANCER PATIENTS WITH TUMOR-INFILTRATING LYMPHOCYTE THERAPIES IN COMBINATION WITH AN IL-15R AGONIST
AR129268A1 (es) 2022-05-11 2024-08-07 Hoffmann La Roche Anticuerpo que se une a vegf-a e il6 y métodos de uso
JP2025517650A (ja) 2022-05-11 2025-06-10 ジェネンテック， インコーポレイテッド 抗ＦｃＲＨ５／抗ＣＤ３二重特異性抗体による処置のための投与
EP4526342A1 (en) 2022-05-18 2025-03-26 Janssen Biotech, Inc. Method for evaluating and treating psoriatic arthritis with il23 antibody
KR20250019077A (ko) 2022-05-31 2025-02-07 퓨쳐진 바이오파머쓰티컬 (베이징) 코., 엘티디. 항-cd40 항체 및 항-pd-l1×cd40 이중특이성 항체 및 이의 용도
KR20250022049A (ko) 2022-06-07 2025-02-14 제넨테크, 인크. 항-pd-l1 길항제 및 항-tigit 길항제 항체를 포함하는, 폐암 치료의 효율을 결정하는 방법
EP4536290A1 (en) 2022-06-08 2025-04-16 Angiex, Inc. Anti-tm4sf1 antibody-drug conjugates comprising cleavable linkers and methods of using same
US20250382354A1 (en) 2022-06-08 2025-12-18 Institute For Research In Biomedicine (Irb) Cross-specific antibodies, uses and methods for discovery thereof
US20230406942A1 (en) 2022-06-10 2023-12-21 Horizon Therapeutics Ireland Dac Igf1r antibodies
CN119698429A (zh) 2022-06-15 2025-03-25 阿根思有限公司 Fcrn结合分子及使用方法
US20240117021A1 (en) 2022-06-15 2024-04-11 Bioverativ Usa Inc. Anti-complement c1s antibody formulation
CA3260415A1 (en) 2022-06-24 2023-12-28 Bioverativ Usa Inc. METHODS OF TREATMENT FOR COMPLEMENT-MEDICATED DISEASES
WO2024011114A1 (en) 2022-07-06 2024-01-11 Iovance Biotherapeutics, Inc. Devices and processes for automated production of tumor infiltrating lymphocytes
AU2023305619A1 (en) 2022-07-13 2025-01-23 F. Hoffmann-La Roche Ag Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
CN120322455A (zh) 2022-07-19 2025-07-15 舒泰神(加州)生物科技有限公司 特异性识别b和t淋巴细胞衰减器(btla)的抗体及其应用
KR20250040020A (ko) 2022-07-19 2025-03-21 제넨테크, 인크. 항-fcrh5/항-cd3 이중특이성 항체로 치료하기 위한 투약법
TW202417504A (zh) 2022-07-22 2024-05-01 美商建南德克公司 抗ｓｔｅａｐ１抗原結合分子及其用途
PE20251075A1 (es) 2022-07-22 2025-04-10 Bristol Myers Squibb Co Anticuerpos que se unen a la pad4 humana y usos de los mismos
KR20250044336A (ko) 2022-07-27 2025-03-31 세파론 엘엘씨 궤양성 결장염 및 크론병의 치료를 위한 항-tl1a 항체
IL318297A (en) 2022-07-27 2025-03-01 Cephalon Llc Anti-TL1A antibody formulations
US20260035460A1 (en) 2022-07-28 2026-02-05 Adeboye Henry ADEWOYE, MD Combination therapy with anti-pvrig antibodies formulations and anti-pd-1 antibodies
US20260021181A1 (en) 2022-08-01 2026-01-22 Iovance Biotherapeutics, Inc. Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
MA71684A (fr) 2022-08-05 2025-05-30 Janssen Biotech, Inc. Protéines de liaison de récepteur de transferrine pour traitement de tumeurs cérébrales
CA3263779A1 (en) 2022-08-05 2024-02-08 Janssen Biotech, Inc. CD98 LINKAGE CONSTRUCTIONS FOR THE TREATMENT OF BRAIN TUMORS
US20260053742A1 (en) 2022-08-19 2026-02-26 Evive Biotechnology (Shanghai) Ltd Formulations comprising g-csf and uses thereof
EP4577578A1 (en) 2022-08-22 2025-07-02 Abdera Therapeutics Inc. Dll3 binding molecules and uses thereof
US20250296995A1 (en) 2022-08-25 2025-09-25 Glaxosmithkline Intellectual Property Development Limited Antigen binding protein and uses thereof
WO2024044675A1 (en) 2022-08-25 2024-02-29 Beigene, Ltd. Methods of cancer treatment using anti-pd1 antibodies in combination with anti-tim3 antibodies
KR20250054799A (ko) 2022-08-29 2025-04-23 다이이찌 산쿄 가부시키가이샤 변이 Fc 영역을 포함하는 항체 약물 콘쥬게이트
EP4581366A1 (en) 2022-09-01 2025-07-09 Genentech, Inc. Therapeutic and diagnostic methods for bladder cancer
JP2025529210A (ja) 2022-09-01 2025-09-04 ユニバーシティ・オブ・ジョージア・リサーチ・ファウンデイション・インコーポレイテッド アポリポタンパク質ｌ１を導いて哺乳動物の細胞死を誘導するための組成物及び方法
EP4584296A1 (en) 2022-09-07 2025-07-16 Dynamicure Biotechnology LLC Anti-vista constructs and uses thereof
WO2024052503A1 (en) 2022-09-08 2024-03-14 Institut National de la Santé et de la Recherche Médicale Antibodies having specificity to ltbp2 and uses thereof
EP4587473A1 (en) 2022-09-12 2025-07-23 Institut National de la Santé et de la Recherche Médicale New anti-itgb8 antibodies and its uses thereof
AR130550A1 (es) 2022-09-21 2024-12-18 Sanofi Biotechnology Anticuerpo anti-il-1r3 humanizado y métodos de uso
WO2024061930A1 (en) 2022-09-22 2024-03-28 Institut National de la Santé et de la Recherche Médicale New method to treat and diagnose peripheral t-cell lymphoma (ptcl)
EP4596580A4 (en) 2022-09-27 2026-01-21 Staidson Beijing Biopharmaceuticals Co Ltd ANTIBODIES TO SPECIFICALLY RECOGNIZE LIGHT LIGANDS AND THEIR USE
KR20250099778A (ko) 2022-10-04 2025-07-02 알파인 이뮨 사이언시즈, 인코포레이티드 자가항체-매개 질환의 치료에 사용하기 위한 돌연변이된 taci-fc 융합 단백질
WO2024077239A1 (en) 2022-10-07 2024-04-11 Genentech, Inc. Methods of treating cancer with anti-c-c motif chemokine receptor 8 (ccr8) antibodies
CN120693395A (zh) 2022-10-20 2025-09-23 北京三诺佳邑生物技术有限责任公司 特异性结合TRAIL或FasL的抗体组合以及双特异性抗体
KR20250093336A (ko) 2022-10-25 2025-06-24 제넨테크, 인크. 다발성 골수종에 대한 치료 및 진단 방법
WO2024089609A1 (en) 2022-10-25 2024-05-02 Ablynx N.V. Glycoengineered fc variant polypeptides with enhanced effector function
JP2026502768A (ja) 2022-10-25 2026-01-27 アブレクシス， エルエルシー 抗ｃｄ３抗体
EP4612178A1 (en) 2022-11-03 2025-09-10 F. Hoffmann-La Roche AG Combination therapy with anti-cd19/anti-cd28 bispecific antibody
EP4612277A1 (en) 2022-11-04 2025-09-10 Iovance Biotherapeutics, Inc. Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd103 selection
WO2024098024A1 (en) 2022-11-04 2024-05-10 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
EP4615872A1 (en) 2022-11-08 2025-09-17 Genentech, Inc. Compositions and methods of treating childhood onset idiopathic nephrotic syndrome
WO2024107731A2 (en) 2022-11-14 2024-05-23 Ablexis, Llc Anti-pd-l1 antibodies
US20240190978A1 (en) 2022-11-15 2024-06-13 CSBioAsset LLC Compositions and methods for immunomodulatory bifunctional fusion molecules
EP4619045A1 (en) 2022-11-17 2025-09-24 Sanofi Ceacam5 antibody-drug conjugates and methods of use thereof
JP2025539816A (ja) 2022-11-21 2025-12-09 アイオバンス バイオセラピューティクス，インコーポレイテッド 腫瘍浸潤リンパ球の増幅のための２次元プロセス及びそれからの治療法
JP2025539712A (ja) 2022-11-21 2025-12-09 アイオバンス バイオセラピューティクス，インコーポレイテッド 遺伝子編集されたｔ細胞の増殖能を評価するための方法
AU2023383916A1 (en) 2022-11-22 2025-07-10 Janssen Biotech, Inc. Method of treating ulcerative colitis with anti-il23 specific antibody
TW202434306A (zh) 2022-11-24 2024-09-01 瑞士商百濟神州瑞士有限責任公司 抗ｃｅａ抗體藥物軛合物及使用方法
JPWO2024111657A1 (2) 2022-11-25 2024-05-30
EP4382120A1 (en) 2022-12-05 2024-06-12 Institut Regional du Cancer de Montpellier Anti-slc1a4 monoclonal antibodies and uses thereof
EP4588936A1 (en) 2022-12-08 2025-07-23 Changchun Bcht Biotechnology Co. Antibodies specifically binding to rsv
EP4386084A1 (en) 2022-12-14 2024-06-19 Formycon AG Improved ace2 fusion proteins
WO2024131956A1 (zh) 2022-12-23 2024-06-27 成都恩沐生物科技有限公司 靶向gprc5d的多特异性多肽复合物
WO2024131962A1 (zh) 2022-12-23 2024-06-27 成都恩沐生物科技有限公司 新型抗gprc5d抗体
EP4642488A1 (en) 2022-12-27 2025-11-05 Yale University Antibody drug conjugates
KR20250133728A (ko) 2023-01-06 2025-09-08 라센 테라퓨틱스, 인코포레이티드 항-il-18bp 항체
CN120787238A (zh) 2023-01-06 2025-10-14 拉森医疗公司 用于治疗甲状腺眼病的抗IL-11Rα抗体
TW202430560A (zh) 2023-01-06 2024-08-01 美商拉森醫療公司 抗ｉｌ－１８ｂｐ抗體
WO2024150074A2 (en) 2023-01-13 2024-07-18 Takeda Pharmaceutical Company Limited Coronavirus antibodies and therapeutic uses thereof
WO2024151885A1 (en) 2023-01-13 2024-07-18 Iovance Biotherapeutics, Inc. Use of til as maintenance therapy for nsclc patients who achieved pr/cr after prior therapy
JP2026510546A (ja) 2023-01-18 2026-04-08 ジェネンテック， インコーポレイテッド 多重特異性抗体およびその使用
CN121293352A (zh) 2023-01-19 2026-01-09 广州百济神州生物制药有限公司 抗cmet抗体及使用方法
WO2024158824A1 (en) 2023-01-23 2024-08-02 Yale University Antibody oligonucleotide conjugates
WO2024163009A1 (en) 2023-01-31 2024-08-08 Genentech, Inc. Methods and compositions for treating urothelial bladder cancer
TW202436339A (zh) 2023-01-31 2024-09-16 瑞士商赫孚孟拉羅股份公司 治療選自非小細胞肺癌或三陰性乳癌的癌症之用途
WO2024173607A2 (en) 2023-02-14 2024-08-22 Evolveimmune Therapeutics, Inc. Combination of bispecific antibodies and chimeric antigen receptor t cells for treatment
WO2024170543A1 (en) 2023-02-14 2024-08-22 Institut National de la Santé et de la Recherche Médicale Anti-cd44 antibodies and uses thereof
WO2024182443A2 (en) 2023-02-27 2024-09-06 Compugen Ltd. Triple combination therapy with anti-pvrig antibodies, anti-tigit antibodies, and pembrolizumab
KR20250158054A (ko) 2023-03-02 2025-11-05 알로이 테라퓨틱스, 인크. 항-cd22 항체 및 이의 용도
EP4676975A1 (en) 2023-03-03 2026-01-14 Beone Medicines I GmbH Muc1 and cd16a antibodies and methods of use
AR132043A1 (es) 2023-03-03 2025-05-21 Beigene Switzerland Gmbh Anticuerpos muc1 y métodos de uso
KR20250167153A (ko) 2023-03-03 2025-11-28 셀덱스 쎄라퓨틱스, 인크. 항-줄기 세포 인자(scf) 및 항-흉선 기질 림포포이에틴(tslp) 항체, 및 이중특이적 구축물
JP2026506241A (ja) 2023-03-03 2026-02-20 ビーワン メディシンズ ワン ゲーエムベーハー Ｃｄ１６ａ抗体及び使用方法
WO2024184812A1 (en) 2023-03-06 2024-09-12 Beigene Switzerland Gmbh Anti-cldn6 antibodies and methods of use
WO2024184810A1 (en) 2023-03-06 2024-09-12 Beigene Switzerland Gmbh Anti-cldn6 and anti-cd3 multispecific antibodies and methods of use
TW202436345A (zh) 2023-03-06 2024-09-16 瑞士商百濟神州瑞士有限責任公司 抗ｃｄ３多特異性抗體及使用方法
EP4676596A1 (en) 2023-03-08 2026-01-14 AC Immune SA Anti-tdp-43 binding molecules and uses thereof
JP2026509243A (ja) 2023-03-10 2026-03-17 ジェネンテック， インコーポレイテッド プロテアーゼとの融合およびその使用
WO2024188965A1 (en) 2023-03-13 2024-09-19 F. Hoffmann-La Roche Ag Combination therapy employing a pd1-lag3 bispecific antibody and an hla-g t cell bispecific antibody
WO2024194685A2 (en) 2023-03-17 2024-09-26 Oxitope Pharma B.V. Anti-phosphocholine antibodies and methods of use thereof
KR20250173600A (ko) 2023-03-17 2025-12-10 옥시토프 파마 비.브이. 항-포스포콜린 항체 및 그 사용 방법
AU2024239150A1 (en) 2023-03-21 2025-10-02 Biograph 55, Inc. Cd19/cd38 multispecific antibodies
EP4683674A1 (en) 2023-03-23 2026-01-28 Yale University Compositions and methods for delivering antibody oligonucleotide conjugates for exon skipping
EP4688843A1 (en) 2023-03-30 2026-02-11 272Bio Limited Gnrh-binding polypeptides and uses thereof
WO2024206738A1 (en) 2023-03-31 2024-10-03 Immunai Inc. Humanized anti-trem2 antibodies
CN120936626A (zh) 2023-03-31 2025-11-11 基因泰克公司 抗αvβ8整合素抗体及使用方法
WO2024211235A1 (en) 2023-04-05 2024-10-10 Sorrento Therapeutics, Inc. Antibody-drug conjugates and uses thereof
CN121969397A (zh) 2023-04-05 2026-05-01 维硕公司 抗体偶联药物及其用途
CN121969398A (zh) 2023-04-05 2026-05-01 维硕公司 抗体偶联药物及其用途
CN121263432A (zh) 2023-04-12 2026-01-02 上海康抗生物技术有限公司 包含掩蔽型白介素12的多功能分子及使用方法
KR20260012304A (ko) 2023-04-17 2026-01-26 피크 바이오, 인크. 항체 및 항체-약물 접합체 및 사용 방법 및 합성 공정 및 중간체
WO2024226829A2 (en) 2023-04-26 2024-10-31 Yale University Enpp3-binding molecules, compositions formed therefrom, and methods of use thereof for the treatment of cancer
AU2024270495A1 (en) 2023-05-05 2025-10-09 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
EP4709752A1 (en) 2023-05-08 2026-03-18 F. Hoffmann-La Roche AG Targeted interferon alpha fusion proteins and methods of use
EP4709484A1 (en) 2023-05-10 2026-03-18 Genentech, Inc. Methods and compositions for treating cancer
AU2024273454A1 (en) 2023-05-16 2025-11-27 F. Hoffmann-La Roche Ag Pd-1-regulated il-2 immunocytokine and uses thereof
EP4713371A1 (en) 2023-05-17 2026-03-25 Institut National de la Santé et de la Recherche Médicale Anti-cathepsin-d antibodies
KR20260021689A (ko) 2023-06-08 2026-02-13 제넨테크, 인크. 림프종 진단 및 치료 방법을 위한 대식세포 시그니처
CN121311247A (zh) 2023-06-09 2026-01-09 舒泰神（北京）生物制药股份有限公司 特异性结合masp3的抗体以及特异性结合masp3和masp2的多特异性抗体
WO2024251884A1 (en) 2023-06-09 2024-12-12 Innate Pharma Nk cell engager proteins comprising anti-cd20 and ant-nkp46 antibody, linked to il-2 in treatment of r/r b-nhl
EP4477236A1 (en) 2023-06-14 2024-12-18 Inatherys Combination therapy for treating a tumor using adc comprising anti-cd71 antibodies and bh3 mimetics
CN121358781A (zh) 2023-06-16 2026-01-16 江苏贝捷泰生物科技有限公司 特异性识别因子XIIa的抗体及其应用
EP4731668A1 (en) 2023-06-22 2026-04-29 Genentech, Inc. Antibodies and uses thereof
EP4731255A1 (en) 2023-06-22 2026-04-29 Genentech, Inc. Treatment of multiple myeloma
WO2024263195A1 (en) 2023-06-23 2024-12-26 Genentech, Inc. Methods for treatment of liver cancer
WO2024263904A1 (en) 2023-06-23 2024-12-26 Genentech, Inc. Methods for treatment of liver cancer
TW202515608A (zh) 2023-06-26 2025-04-16 以色列商坎布根有限公司 Ｉｌ—１８ｂｐ拮抗抗體及其於癌症治療之單一療法及組合療法的用途
AU2024309736A1 (en) 2023-06-30 2026-01-15 Evive Biotechnology (Shanghai) Ltd G-csf dimer for use in the treatment or prevention of chemotherapy or radiotherapy induced neutropenia
WO2025012417A1 (en) 2023-07-13 2025-01-16 Institut National de la Santé et de la Recherche Médicale Anti-neurotensin long fragment and anti-neuromedin n long fragment antibodies and uses thereof
WO2025015318A2 (en) 2023-07-13 2025-01-16 Iovance Biotherapeutics, Inc. Cytokine encoding lentiviral vectors and uses thereof for making tumor infiltrating lymphocytes
WO2025019790A1 (en) 2023-07-19 2025-01-23 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with trop-2 targeting adc
KR20260041867A (ko) 2023-07-21 2026-03-27 브리스톨-마이어스 스큅 컴퍼니 Pad4 조정제의 시트룰린화 및 활성을 평가하는 방법
WO2025022280A1 (en) 2023-07-21 2025-01-30 Astrazeneca Ab Treatment of neurodegenerative diseases
WO2025021790A2 (en) 2023-07-24 2025-01-30 F. Hoffmann-La Roche Ag Multispecific antibodies
WO2025034806A1 (en) 2023-08-08 2025-02-13 Wisconsin Alumni Research Foundation Single-domain antibodies and variants thereof against fibroblast activation protein
CN121620524A (zh) 2023-08-09 2026-03-06 豪夫迈·罗氏有限公司 抗A-β蛋白抗体、方法及其用途
WO2025032069A1 (en) 2023-08-09 2025-02-13 F. Hoffmann-La Roche Ag Mono and multispecific anti-trem2 antibodies, methods and uses thereof
KR20260051042A (ko) 2023-08-09 2026-04-15 에프. 호프만-라 로슈 아게 단일 및 다중특이성 항-trem2 항체, 그 방법 및 용도
WO2025041077A1 (en) 2023-08-23 2025-02-27 Sanofi Ctla-4-based lysosomal degraders and uses thereof
WO2025046298A2 (en) 2023-09-01 2025-03-06 iTeos Belgium SA Anti-trem2 antibodies and methods of use
WO2025049905A1 (en) 2023-09-01 2025-03-06 Gennao Bio, Inc. Dnase co-expression in host cells
WO2025045251A2 (en) 2023-09-03 2025-03-06 Kira Pharmaceuticals (Us) Llc Multispecific constructs comprising anti-factor d moiety
AU2024341660A1 (en) 2023-09-11 2026-03-12 Evolveimmune Therapeutics, Inc. Bispecific antibody fusion molecules targeting b7-h4 and cd3 and methods of use thereof
AU2024345039A1 (en) 2023-09-20 2026-03-19 Evolveimmune Therapeutics, Inc. Multispecific antibodies that bind cd3 and cd2 and methods of use thereof
WO2025064890A1 (en) 2023-09-20 2025-03-27 Evolveimmune Therapeutics, Inc. Bispecific antibody fusion molecules targeting cd180 and cd3 and methods of use thereof
AR133909A1 (es) 2023-09-25 2025-11-12 Hoffmann La Roche ANTICUERPO QUE SE UNE A C3bBb
US20250109187A1 (en) 2023-09-28 2025-04-03 Novavax, Inc. ANTI-SARS-CoV-2 SPIKE (S) ANTIBODIES AND THEIR USE IN TREATING COVID-19
WO2025068957A1 (en) 2023-09-29 2025-04-03 Novartis Ag Bispecific antibodies for use in lowering the risk of cardiovascular disease events in subjects known to be a carrier of clonal expansion of hematopoietic cell lines with somatic mutations
US20250109209A1 (en) 2023-10-03 2025-04-03 Absci Corporation Tl1a associated antibody compositions and methods of use
TW202517301A (zh) 2023-10-06 2025-05-01 美商思進公司 用ｂ７－ｈ４抗體－藥物結合物治療晚期實體腫瘤之方法
WO2025085489A1 (en) 2023-10-17 2025-04-24 Bristol-Myers Squibb Company Gspt1-degrading compounds, anti-cd33 antibodies and antibody-drug conjugates and uses thereof
WO2025101484A1 (en) 2023-11-06 2025-05-15 Iovance Biotherapeutics, Inc. Treatment of endometrial cancers with tumor infiltrating lymphocyte therapies
WO2025099120A1 (en) 2023-11-09 2025-05-15 F. Hoffmann-La Roche Ag Multispecific antibodies with conditional activity
WO2025106474A1 (en) 2023-11-14 2025-05-22 Genentech, Inc. Therapeutic and diagnostic methods for treating cancer with anti-fcrh5/anti-cd3 bispecific antibodies
WO2025114862A1 (en) 2023-11-27 2025-06-05 Glaxosmithkline Intellectual Property Development Limited Il-33 binding antibodies
WO2025120015A1 (en) 2023-12-06 2025-06-12 Institut National de la Santé et de la Recherche Médicale Cd5 targeting antibodies with depleting and t or b-cell activation effects
WO2025122885A1 (en) 2023-12-08 2025-06-12 Absci Corporation Anti-her2 associated antibody compositions designed by artificial intelligence and methods of use
US20250197511A1 (en) 2023-12-13 2025-06-19 Horizon Therapeutics Ireland Dac Methods for the treatment of thyroid eye disease
WO2025133707A1 (en) 2023-12-19 2025-06-26 Vectory Therapeutics B.V. Anti-tdp-43 antibodies and uses thereof
GB202319605D0 (en) 2023-12-20 2024-01-31 argenx BV Monovalent binding molecules and methods of use
WO2025133694A1 (en) 2023-12-20 2025-06-26 argenx BV Fcrn/hsa-binding molecules and methods of use
WO2025132503A1 (en) 2023-12-20 2025-06-26 F. Hoffmann-La Roche Ag Antibodies binding to ceacam5
WO2025133042A2 (en) 2023-12-22 2025-06-26 F. Hoffmann-La Roche Ag Activatable fusion proteins and methods of use
WO2025147696A1 (en) 2024-01-05 2025-07-10 Resolve Therapeutics, Llc Treatment of symptoms associated with sars-cov viral infection or a prior sars-cov viral infection with nuclease agents
JP2026508860A (ja) 2024-01-05 2026-03-13 ビーワン メディシンズ ワン ゲーエムベーハー 抗ＦＧＦＲ２ｂ抗体、コンジュゲート、及び使用方法
WO2025149633A1 (en) 2024-01-12 2025-07-17 Laigo Bio B.V. Bispecific antigen binding proteins
WO2025149947A1 (en) 2024-01-12 2025-07-17 Seagen Inc. Antibody-drug conjugates
WO2025155877A2 (en) 2024-01-18 2025-07-24 The Regents Of The University Of California Antibodies binding to pad4 and uses thereof
US12319742B1 (en) 2024-01-24 2025-06-03 Shattuck Labs, Inc. Antibodies that bind TNFRSF25
JP2025115976A (ja) 2024-01-26 2025-08-07 フューチャージェン・バイオファーマシューティカル（ベイジン）カンパニー・リミテッド Ｔｌ１ａに特異的に結合できる抗体及びその使用
WO2025171182A1 (en) 2024-02-08 2025-08-14 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with cancer vaccine
WO2025174974A1 (en) 2024-02-14 2025-08-21 Bristol-Myers Squibb Company Anti-cd33 antibodies and uses thereof
WO2025172924A1 (en) 2024-02-15 2025-08-21 Janssen Biotech, Inc. Anti-transferrin receptor compositions and methods thereof
US12521446B2 (en) 2024-02-27 2026-01-13 Bristol-Myers Squibb Company Anti-CEACAM5 antibody drug conjugates
WO2025184208A1 (en) 2024-02-27 2025-09-04 Bristol-Myers Squibb Company Anti-ceacam5 antibodies and uses thereof
WO2025186332A1 (en) 2024-03-05 2025-09-12 Ac Immune Sa Vectorized anti-tdp-43 antibodies
CA3249015A1 (en) 2024-03-20 2025-10-31 Janssen Biotech, Inc. Methods of treating crohn’s disease with anti-il23 specific antibody
WO2025196639A1 (en) 2024-03-21 2025-09-25 Seagen Inc. Cd25 antibodies, antibody-drug conjugates, and uses thereof
WO2025215060A1 (en) 2024-04-11 2025-10-16 F. Hoffmann-La Roche Ag Antibodies that specifically bind modified oligonucleotides
WO2025226603A1 (en) 2024-04-22 2025-10-30 Surface Oncology, LLC Methods for treating cancer using anti-ccr8 antibodies
WO2025226808A1 (en) 2024-04-24 2025-10-30 Genentech, Inc. Compositions and methods of treating lupus nephritis
WO2025224297A1 (en) 2024-04-26 2025-10-30 Institut National de la Santé et de la Recherche Médicale Antibodies having specificity to tgfbi and uses thereof
EP4644413A1 (en) 2024-05-03 2025-11-05 Genmab B.V. Binding agents having altered fc-mediated effector functions
WO2025242732A1 (en) 2024-05-21 2025-11-27 Institut National de la Santé et de la Recherche Médicale Pan antibodies against sars-cov-2 spike protein and uses thereof for therapeutical purposes
WO2025245176A1 (en) 2024-05-22 2025-11-27 Bristol-Myers Squibb Company Multispecific antibody constructs
WO2025250969A1 (en) 2024-05-31 2025-12-04 Vertex Pharmaceuticals Incorporated Anti-cd74 antibodies, conjugates and uses thereof
WO2025254987A1 (en) 2024-06-03 2025-12-11 Alector Llc Siglec-9 ecd fusion molecule variants and methods of use thereof
WO2025255349A1 (en) 2024-06-06 2025-12-11 Bristol-Myers Squibb Company Multispecific anti-cd40 / anti-fap antibodies and uses thereof
WO2025255405A1 (en) 2024-06-06 2025-12-11 Bristol-Myers Squibb Company Anti-fap antibodies and uses thereof
WO2025257181A1 (en) 2024-06-11 2025-12-18 Institut National de la Santé et de la Recherche Médicale Antibodies targeting trans-active response dna-binding protein-43 (tdp-43)
WO2025262604A1 (en) 2024-06-17 2025-12-26 Janssen Biotech, Inc. Methods of treating crohn's disease with anti-il23 specific antibody
US20260008843A1 (en) 2024-06-21 2026-01-08 Glaxosmithkline Intellectual Property Development Limited Multispecific antigen binding proteins
WO2026006494A1 (en) 2024-06-25 2026-01-02 Alloy Therapeutics, Inc. Anti-cd3 antibodies and uses thereof
WO2026006492A2 (en) 2024-06-25 2026-01-02 Ypsilon Therapeutics, Inc. Anti-prame/hla-a2 antibodies and uses thereof
WO2026006495A1 (en) 2024-06-25 2026-01-02 Alloy Therapeutics, Inc. Anti-wt1/hla-a2 antibody and uses thereof
CA3258952A1 (en) 2024-06-27 2026-03-01 Janssen Biotech, Inc. Methods of treating ulcerative colitis with anti-il23 specific antibody
WO2026006784A1 (en) 2024-06-28 2026-01-02 Iovance Biotherapeutics, Inc. Methods of making tumor reactive peripheral blood lymphocytes (trpbl)
WO2026013218A1 (en) 2024-07-10 2026-01-15 Ac Immune Sa Anti-tdp-43 vectors, binding molecules and uses thereof
WO2026021476A1 (en) 2024-07-24 2026-01-29 Beone Guangzhou Biologics Manufacturing Co., Ltd. Anti-cmet and anti-egfr multispecific antibody drug conjugates
WO2026030464A1 (en) 2024-07-30 2026-02-05 Genentech, Inc. Dosage regimen for reducing cytokine release syndrome (crs) with anti-fcrh5/anti-cd3 bispecific antibodies in multiple myeloma therapy
WO2026035866A1 (en) 2024-08-07 2026-02-12 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with a lag-3 inhibitor and a pd-1 inhibitor
WO2026039779A1 (en) 2024-08-15 2026-02-19 Yale University Humanized 3e10 antibodies and antigen binding fragments optimized for rad51 binding
WO2026044000A1 (en) 2024-08-20 2026-02-26 Ethyreal Bio, Inc. Multispecific antibodies and methods of use thereof
WO2026052839A1 (en) 2024-09-06 2026-03-12 Hone Bio Limited Targeting fusion proteins
WO2026062582A1 (en) 2024-09-20 2026-03-26 Novartis Ag Methods of treatment using anti-trem2 antibodies
WO2026062585A1 (en) 2024-09-20 2026-03-26 Novartis Ag Methods of treatment using anti-trem2 antibodies
WO2026068504A2 (en) 2024-09-24 2026-04-02 The University Of Bristol Novel protein conjugates
WO2026072685A1 (en) 2024-09-25 2026-04-02 Genentech, Inc. Compositions and methods of treating lupus nephritis
WO2026072794A2 (en) 2024-09-26 2026-04-02 Iovance Biotherapeutics, Inc. Expansion processes for til product enriched with neoantigen- reactive t cells (narts)
WO2026078029A1 (en) 2024-10-10 2026-04-16 F. Hoffmann-La Roche Ag Splitted interleukin-2 prodrugs and uses thereof
CN119552212B (zh) * 2025-01-26 2025-04-25 杭州康源食品科技有限公司 一种具有降尿酸活性的三肽lfp及其应用

Citations (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4490473A (en) * 1983-03-28 1984-12-25 Panab Labeled antibodies and methods
US4752601A (en) * 1983-08-12 1988-06-21 Immunetech Pharmaceuticals Method of blocking immune complex binding to immunoglobulin FC receptors
US5204244A (en) * 1987-10-27 1993-04-20 Oncogen Production of chimeric antibodies by homologous recombination
US5348876A (en) * 1989-07-18 1994-09-20 Dynal As IgG3 antibodies with shortened hinge region and a complement activation test
US5419904A (en) * 1990-11-05 1995-05-30 The Regents Of The University Of California Human B-lymphoblastoid cell line secreting anti-ganglioside antibody
US5576184A (en) * 1988-09-06 1996-11-19 Xoma Corporation Production of chimeric mouse-human antibodies with specificity to human tumor antigens
US5624821A (en) * 1987-03-18 1997-04-29 Scotgen Biopharmaceuticals Incorporated Antibodies with altered effector functions
US5698449A (en) * 1990-10-16 1997-12-16 Northwestern University Synthetic peptide and its uses
US5731168A (en) * 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5736137A (en) * 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US5834597A (en) * 1996-05-20 1998-11-10 Protein Design Labs, Inc. Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same
US5985599A (en) * 1986-05-29 1999-11-16 The Austin Research Institute FC receptor for immunoglobulin
US6136310A (en) * 1991-07-25 2000-10-24 Idec Pharmaceuticals Corporation Recombinant anti-CD4 antibodies for human therapy
US6165745A (en) * 1992-04-24 2000-12-26 Board Of Regents, The University Of Texas System Recombinant production of immunoglobulin-like domains in prokaryotic cells
US6194551B1 (en) * 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
US6242195B1 (en) * 1998-04-02 2001-06-05 Genentech, Inc. Methods for determining binding of an analyte to a receptor
US6277375B1 (en) * 1997-03-03 2001-08-21 Board Of Regents, The University Of Texas System Immunoglobulin-like domains with increased half-lives
US20010036459A1 (en) * 2000-04-13 2001-11-01 Ravetch Jeffrey V. Enhancement of antibody-mediated immune responses
US6491916B1 (en) * 1994-06-01 2002-12-10 Tolerance Therapeutics, Inc. Methods and materials for modulation of the immunosuppresive activity and toxicity of monoclonal antibodies
US6528624B1 (en) * 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
US20030190311A1 (en) * 2000-12-12 2003-10-09 Dall'acqua William Molecules with extended half-lives, compositions and uses thereof
US20040002587A1 (en) * 2002-02-20 2004-01-01 Watkins Jeffry D. Fc region variants
US6676927B1 (en) * 1999-01-20 2004-01-13 The Rockefeller University Animal model and methods for its use in the selection of cytotoxic antibodies
US6706265B1 (en) * 1992-03-24 2004-03-16 Btg International Limited Humanized anti-CD3 specific antibodies
US6737056B1 (en) * 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US20040191265A1 (en) * 2003-01-06 2004-09-30 Schenerman Mark A. Stabilized glycoproteins

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
USRE30985E (en) 1978-01-01 1982-06-29 Serum-free cell culture media
FR2413974A1 (fr) 1978-01-06 1979-08-03 David Bernard Sechoir pour feuilles imprimees par serigraphie
US4275149A (en) 1978-11-24 1981-06-23 Syva Company Macromolecular environment control in specific receptor assays
US4318980A (en) 1978-04-10 1982-03-09 Miles Laboratories, Inc. Heterogenous specific binding assay employing a cycling reactant as label
US4419446A (en) 1980-12-31 1983-12-06 The United States Of America As Represented By The Department Of Health And Human Services Recombinant DNA process utilizing a papilloma virus DNA as a vector
NZ201705A (en) 1981-08-31 1986-03-14 Genentech Inc Recombinant dna method for production of hepatitis b surface antigen in yeast
US4601978A (en) 1982-11-24 1986-07-22 The Regents Of The University Of California Mammalian metallothionein promoter system
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
DD266710A3 (de) 1983-06-06 1989-04-12 Ve Forschungszentrum Biotechnologie Verfahren zur biotechnischen Herstellung van alkalischer Phosphatase
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
US4965199A (en) 1984-04-20 1990-10-23 Genentech, Inc. Preparation of functional human factor VIII in mammalian cells using methotrexate based selection
US4879231A (en) 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US5091178A (en) 1986-02-21 1992-02-25 Oncogen Tumor therapy with biologically active anti-tumor antibodies
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
GB8610600D0 (en) 1986-04-30 1986-06-04 Novo Industri As Transformation of trichoderma
ATE135397T1 (de) 1988-09-23 1996-03-15 Cetus Oncology Corp Zellenzuchtmedium für erhöhtes zellenwachstum, zur erhöhung der langlebigkeit und expression der produkte
FR2646437B1 (fr) 1989-04-28 1991-08-30 Transgene Sa Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant
EP0402226A1 (en) 1989-06-06 1990-12-12 Institut National De La Recherche Agronomique Transformation vectors for yeast yarrowia
ES2096590T3 (es) 1989-06-29 1997-03-16 Medarex Inc Reactivos biespecificos para la terapia del sida.
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
WO1992020373A1 (en) 1991-05-14 1992-11-26 Repligen Corporation Heteroconjugate antibodies for treatment of hiv infection
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
CA2140280A1 (en) 1992-08-17 1994-03-03 Avi J. Ashkenazi Bispecific immunoadhesins
DK0752248T3 (da) 1992-11-13 2000-11-13 Idec Pharma Corp Terapeutisk anvendelse af kimæriske og radioaktivt mærkede antistoffer mod humant B-lymfocytbegrænset differentieringsantig
US5885573A (en) * 1993-06-01 1999-03-23 Arch Development Corporation Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
US5730977A (en) * 1995-08-21 1998-03-24 Mitsui Toatsu Chemicals, Inc. Anti-VEGF human monoclonal antibody
US6750334B1 (en) 1996-02-02 2004-06-15 Repligen Corporation CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor
JP4046354B2 (ja) 1996-03-18 2008-02-13 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム 増大した半減期を有する免疫グロブリン様ドメイン
WO1998023289A1 (en) * 1996-11-27 1998-06-04 The General Hospital Corporation MODULATION OF IgG BINDING TO FcRn
DE19721700C1 (de) 1997-05-23 1998-11-19 Deutsches Krebsforsch Mutierter OKT3-Antikörper
ES2244066T3 (es) * 1997-06-24 2005-12-01 Genentech, Inc. Procedimiento y composiciones de glicoproteinas galactosiladas.
HUP0100813A3 (en) 1998-02-25 2003-08-28 Lexigen Pharmaceuticals Corp L Enhancing the circulating half-life of antibody-based fusion proteins
ATE375365T1 (de) * 1998-04-02 2007-10-15 Genentech Inc Antikörper varianten und fragmente davon
GB9809951D0 (en) 1998-05-08 1998-07-08 Univ Cambridge Tech Binding molecules
EP1105427A2 (en) 1998-08-17 2001-06-13 Abgenix, Inc. Generation of modified molecules with increased serum half-lives
US7183387B1 (en) * 1999-01-15 2007-02-27 Genentech, Inc. Polypeptide variants with altered effector function
PL209392B1 (pl) 1999-01-15 2011-08-31 Genentech Inc Przeciwciało, komórka gospodarza, sposób wytwarzania przeciwciała oraz zastosowanie przeciwciała
HUP0204475A2 (en) 2000-02-11 2003-04-28 Merck Patent Gmbh Enhancing the circulating half-life of antibody-based fusion proteins
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
EP1572091A4 (en) 2002-07-09 2008-03-05 Genentech Inc COMPOSITIONS AND METHODS FOR TUMOR DIAGNOSIS AND TREATMENT
EP1553975B8 (en) 2002-09-27 2023-04-12 Xencor, Inc. Optimized fc variants and methods for their generation
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
DK1562972T3 (da) 2002-10-15 2010-12-06 Facet Biotech Corp Modifikation af FcRn-bindingsaffiniteter eller serumhalveringstider for antistoffer ved mutagenese
CA2512729C (en) 2003-01-09 2014-09-16 Macrogenics, Inc. Identification and engineering of antibodies with variant fc regions and methods of using same
WO2005037867A1 (en) 2003-10-15 2005-04-28 Pdl Biopharma, Inc. ALTERATION OF Fc-FUSION PROTEIN SERUM HALF-LIVES BY MUTAGENESIS OF POSITIONS 250, 314 AND/OR 428 OF THE HEAVY CHAIN CONSTANT REGION OF IG
AU2005285347A1 (en) * 2004-08-19 2006-03-23 Genentech, Inc. Polypeptide variants with altered effector function
DOP2006000029A (es) * 2005-02-07 2006-08-15 Genentech Inc Antibody variants and uses thereof. (variantes de un anticuerpo y usos de las mismas)

Patent Citations (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4490473A (en) * 1983-03-28 1984-12-25 Panab Labeled antibodies and methods
US4752601A (en) * 1983-08-12 1988-06-21 Immunetech Pharmaceuticals Method of blocking immune complex binding to immunoglobulin FC receptors
US5985599A (en) * 1986-05-29 1999-11-16 The Austin Research Institute FC receptor for immunoglobulin
US5624821A (en) * 1987-03-18 1997-04-29 Scotgen Biopharmaceuticals Incorporated Antibodies with altered effector functions
US5648260A (en) * 1987-03-18 1997-07-15 Scotgen Biopharmaceuticals Incorporated DNA encoding antibodies with altered effector functions
US5204244A (en) * 1987-10-27 1993-04-20 Oncogen Production of chimeric antibodies by homologous recombination
US5576184A (en) * 1988-09-06 1996-11-19 Xoma Corporation Production of chimeric mouse-human antibodies with specificity to human tumor antigens
US5348876A (en) * 1989-07-18 1994-09-20 Dynal As IgG3 antibodies with shortened hinge region and a complement activation test
US5698449A (en) * 1990-10-16 1997-12-16 Northwestern University Synthetic peptide and its uses
US5419904A (en) * 1990-11-05 1995-05-30 The Regents Of The University Of California Human B-lymphoblastoid cell line secreting anti-ganglioside antibody
US6136310A (en) * 1991-07-25 2000-10-24 Idec Pharmaceuticals Corporation Recombinant anti-CD4 antibodies for human therapy
US6706265B1 (en) * 1992-03-24 2004-03-16 Btg International Limited Humanized anti-CD3 specific antibodies
US6165745A (en) * 1992-04-24 2000-12-26 Board Of Regents, The University Of Texas System Recombinant production of immunoglobulin-like domains in prokaryotic cells
US5736137A (en) * 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US6491916B1 (en) * 1994-06-01 2002-12-10 Tolerance Therapeutics, Inc. Methods and materials for modulation of the immunosuppresive activity and toxicity of monoclonal antibodies
US5731168A (en) * 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5834597A (en) * 1996-05-20 1998-11-10 Protein Design Labs, Inc. Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same
US6821505B2 (en) * 1997-03-03 2004-11-23 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
US6277375B1 (en) * 1997-03-03 2001-08-21 Board Of Regents, The University Of Texas System Immunoglobulin-like domains with increased half-lives
US20020098193A1 (en) * 1997-03-03 2002-07-25 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
US6528624B1 (en) * 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
US6538124B1 (en) * 1998-04-02 2003-03-25 Genentech, Inc. Polypeptide variants
US20030158389A1 (en) * 1998-04-02 2003-08-21 Genentech, Inc. Polypeptide variants
US20030166868A1 (en) * 1998-04-02 2003-09-04 Genentech, Inc. Polypeptide variants
US6242195B1 (en) * 1998-04-02 2001-06-05 Genentech, Inc. Methods for determining binding of an analyte to a receptor
US6194551B1 (en) * 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
US20050233382A1 (en) * 1999-01-15 2005-10-20 Genentech, Inc. Polypeptide variants with altered effector function
US20050118174A1 (en) * 1999-01-15 2005-06-02 Genentech, Inc. Polypeptide variants with altered effector function
US20040191244A1 (en) * 1999-01-15 2004-09-30 Genentech, Inc. Polypeptide variants with altered effector function
US6737056B1 (en) * 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US20040228856A1 (en) * 1999-01-15 2004-11-18 Genentech, Inc. Polypeptide variants with altered effector function
US6676927B1 (en) * 1999-01-20 2004-01-13 The Rockefeller University Animal model and methods for its use in the selection of cytotoxic antibodies
US20010036459A1 (en) * 2000-04-13 2001-11-01 Ravetch Jeffrey V. Enhancement of antibody-mediated immune responses
US20030190311A1 (en) * 2000-12-12 2003-10-09 Dall'acqua William Molecules with extended half-lives, compositions and uses thereof
US20040002587A1 (en) * 2002-02-20 2004-01-01 Watkins Jeffry D. Fc region variants
US20040191265A1 (en) * 2003-01-06 2004-09-30 Schenerman Mark A. Stabilized glycoproteins

Cited By (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7785791B2 (en) 1999-01-15 2010-08-31 Genentech, Inc. Polypeptide variants with altered effector function
US20050233382A1 (en) * 1999-01-15 2005-10-20 Genentech, Inc. Polypeptide variants with altered effector function
US20040228856A1 (en) * 1999-01-15 2004-11-18 Genentech, Inc. Polypeptide variants with altered effector function
US20060194291A1 (en) * 1999-01-15 2006-08-31 Genentech, Inc. Polypeptide variants with altered effector function
US20060194957A1 (en) * 1999-01-15 2006-08-31 Genentech, Inc. Polypeptide variants with altered effector function
US8674083B2 (en) 1999-01-15 2014-03-18 Genentech, Inc. Polypeptide variants with altered effector function
US7332581B2 (en) 1999-01-15 2008-02-19 Genentech, Inc. Polypeptide variants with altered effector function
US7335742B2 (en) 1999-01-15 2008-02-26 Genentech, Inc. Polypeptide variants with altered effector function
US7371826B2 (en) 1999-01-15 2008-05-13 Genentech, Inc. Polypeptide variants with altered effector function
US7416727B2 (en) 1999-01-15 2008-08-26 Genentech, Inc. Polypeptide variants with altered effector function
US20080274105A1 (en) * 1999-01-15 2008-11-06 Genentech, Inc. Polypeptide variants with altered effector function
US20080274506A1 (en) * 1999-01-15 2008-11-06 Genentech, Inc. Polypeptide variants with altered effector function
US20080274108A1 (en) * 1999-01-15 2008-11-06 Genentech, Inc. Polypeptide variants with altered effector function
US8163882B2 (en) 1999-01-15 2012-04-24 Genentech, Inc. Polypeptide variants with altered effector function
US7790858B2 (en) 1999-01-15 2010-09-07 Genentech, Inc. Polypeptide variants with altered effector function
US7820161B1 (en) 1999-05-07 2010-10-26 Biogen Idec, Inc. Treatment of autoimmune diseases
US9993550B2 (en) 1999-05-07 2018-06-12 Genentech, Inc. Treatment of pemphigus
US8545843B2 (en) 1999-05-07 2013-10-01 Genentech, Inc. Treatment of vasculitis
US20100203046A1 (en) * 2003-11-12 2010-08-12 Biogen Idec Ma Inc. Fc gamma receptor-binding polypeptide variants and methods related thereto
US20060275283A1 (en) * 2003-11-12 2006-12-07 Biogen Idec Ma Inc. Fcgamma receptor-binding polypeptide variants and methods related thereto
US20060067930A1 (en) * 2004-08-19 2006-03-30 Genentech, Inc. Polypeptide variants with altered effector function
EP3524626A1 (en) 2007-03-22 2019-08-14 Biogen MA Inc. Binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind cd154 and uses thereof
US10725037B2 (en) 2007-05-01 2020-07-28 Research Development Foundation Immunoglobulin Fc libraries
US20090136936A1 (en) * 2007-05-01 2009-05-28 George Georgiou Immunoglobulin fc libraries
US8629245B2 (en) 2007-05-01 2014-01-14 Research Development Foundation Immunoglobulin Fc libraries
EP4364800A2 (en) 2008-09-16 2024-05-08 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
EP3747464A1 (en) 2008-09-16 2020-12-09 F. Hoffmann-La Roche AG Methods for treating progessive multiple sclerosis using an anti-cd20 antibody
US9994642B2 (en) 2008-09-16 2018-06-12 Genentech, Inc. Methods for treating progressive multiple sclerosis
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
US9683047B2 (en) 2008-09-16 2017-06-20 Genentech, Inc. Methods for treating progressive multiple sclerosis
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
US9238878B2 (en) 2009-02-17 2016-01-19 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
US9879249B2 (en) 2009-02-17 2018-01-30 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
US8679493B2 (en) 2009-06-30 2014-03-25 Research Development Foundation Immunoglobulin Fc polypeptides
US20100330076A1 (en) * 2009-06-30 2010-12-30 George Georgiou Immunoglobulin fc polypeptides
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
US10183998B2 (en) 2011-01-14 2019-01-22 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof
US9540438B2 (en) 2011-01-14 2017-01-10 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof
US8969526B2 (en) 2011-03-29 2015-03-03 Roche Glycart Ag Antibody Fc variants
US10654916B2 (en) 2011-04-21 2020-05-19 The Regents Of The University Of California, A California Corporation Compositions and methods for the treatment of neuromyelitis optica
US11390667B2 (en) 2011-04-21 2022-07-19 The Regents Of The University Of California Compositions and methods for the treatment of neuromyelitis optica
US9695233B2 (en) 2012-07-13 2017-07-04 Roche Glycart Ag Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases
US10683345B2 (en) 2012-07-13 2020-06-16 Roche Glycart Ag Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases
WO2014093396A1 (en) 2012-12-10 2014-06-19 Biogen Idec Ma Inc. Anti-blood dendritic cell antigen 2 antibodies and uses thereof
EP3686218A1 (en) 2012-12-10 2020-07-29 Biogen MA Inc. Anti-blood dendritic cell antigen 2 antibodies and uses thereof
WO2014151680A1 (en) 2013-03-15 2014-09-25 Biogen Idec Ma Inc. Treatment and prevention of acute kidney injury using anti-alpha v beta 5 antibodies
WO2014144466A1 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anti-alpha v beta 6 antibodies and uses thereof
WO2014143739A2 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anti-alpha v beta 6 antibodies and uses thereof
EP3901176A1 (en) 2014-11-10 2021-10-27 MedImmune Limited Binding molecules specific for cd73 and uses thereof
WO2016075099A1 (en) 2014-11-10 2016-05-19 Medimmune Limited Binding molecules specific for cd73 and uses thereof
US10184001B2 (en) * 2014-11-26 2019-01-22 Adventist Health System/Sunbelt Inc. Effector-deficient anti-CD32a antibodies
US10457737B2 (en) 2015-02-09 2019-10-29 Research Development Foundation Engineered immunoglobulin Fc polypeptides displaying improved complement activation
US11332538B2 (en) 2015-02-09 2022-05-17 Research Development Foundation Engineered immunoglobulin Fc polypeptides displaying improved complement activation
US11208632B2 (en) 2016-04-26 2021-12-28 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
US11788066B2 (en) 2016-04-26 2023-10-17 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
WO2018022479A1 (en) 2016-07-25 2018-02-01 Biogen Ma Inc. Anti-hspa5 (grp78) antibodies and uses thereof
US12503503B2 (en) 2018-10-29 2025-12-23 Hoffmann-La Roche Inc. Bispecific anti-VEGF/ANG2 antibody formulation
US11447551B2 (en) 2018-12-28 2022-09-20 Sparx Bioscience Limited Binding molecules specific for claudin 18.2, compositions and methods thereof, for the treatment of cancer and other diseases
US12460005B2 (en) 2018-12-28 2025-11-04 Sparx Bioscience Limited Binding molecules specific for claudin 18.2, compositions and methods thereof, for treatment of cancer and other diseases
WO2020210358A1 (en) 2019-04-08 2020-10-15 Biogen Ma Inc. Anti-integrin antibodies and uses thereof

Also Published As

Publication number Publication date
JP2016136951A (ja) 2016-08-04
CA2359067A1 (en) 2000-07-20
JP6230257B2 (ja) 2017-11-15
EP2364997A2 (en) 2011-09-14
KR101077001B1 (ko) 2011-10-26
HUP0104865A2 (hu) 2002-04-29
EP1141024B1 (en) 2018-08-08
JP2003512019A (ja) 2003-04-02
EP2366713A2 (en) 2011-09-21
IL223048A0 (en) 2012-12-31
IL223047A (en) 2016-10-31
KR100940380B1 (ko) 2010-02-02
IL144056A (en) 2014-04-30
CN1763097B (zh) 2011-04-13
PL220113B1 (pl) 2015-08-31
JP2013166770A (ja) 2013-08-29
CA2359067C (en) 2017-03-14
MXPA01007170A (es) 2002-07-30
KR20080090572A (ko) 2008-10-08
EP2386574A2 (en) 2011-11-16
HUP0104865A3 (en) 2004-07-28
CN1237076C (zh) 2006-01-18
US7785791B2 (en) 2010-08-31
PL209786B1 (pl) 2011-10-31
EP1141024A2 (en) 2001-10-10
US20080274105A1 (en) 2008-11-06
AU2008229968B2 (en) 2012-08-09
EP2364997A3 (en) 2012-07-04
BR0008758A (pt) 2001-12-04
US20080274506A1 (en) 2008-11-06
PL394232A1 (pl) 2011-07-04
HU230769B1 (hu) 2018-03-28
PL349770A1 (en) 2002-09-09
AU778683B2 (en) 2004-12-16
AU2850500A (en) 2000-08-01
KR101155191B1 (ko) 2012-06-13
IL222149B (en) 2018-11-29
US7790858B2 (en) 2010-09-07
KR20090078369A (ko) 2009-07-17
IL223048A (en) 2016-09-29
ZA200105484B (en) 2002-07-29
KR20060067983A (ko) 2006-06-20
MX353234B (es) 2018-01-08
PL209392B1 (pl) 2011-08-31
JP6312092B2 (ja) 2018-04-18
KR20010102976A (ko) 2001-11-17
WO2000042072A2 (en) 2000-07-20
KR100887482B1 (ko) 2009-03-10
HK1090066A1 (en) 2006-12-15
US20060194291A1 (en) 2006-08-31
WO2000042072A3 (en) 2000-11-30
JP5335735B2 (ja) 2013-11-06
NZ539776A (en) 2006-12-22
EP2366713A3 (en) 2012-06-27
IL144056A0 (en) 2002-04-21
JP2010227116A (ja) 2010-10-14
EP2386574A3 (en) 2012-06-27
ES2694002T3 (es) 2018-12-17
CN1763097A (zh) 2006-04-26
US7371826B2 (en) 2008-05-13
CN1343221A (zh) 2002-04-03
HUP1500355A2 (en) 2002-04-29
IL223047A0 (en) 2012-12-31
AU2008229968A1 (en) 2008-11-06
KR20100045527A (ko) 2010-05-03

Similar Documents

Publication Publication Date Title
US7335742B2 (en) Polypeptide variants with altered effector function
US7790858B2 (en) Polypeptide variants with altered effector function
US8674083B2 (en) Polypeptide variants with altered effector function
AU2012211437B2 (en) Polypeptide variants with altered effector function
AU2004233493B2 (en) Polypeptide variants with altered effector function
HK1162530A (en) Polypeptide variants with altered effector function
HK1162535A (en) Polypeptide variants with altered effector function

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION