OA21947A - Angiopoietin-related protein 7-specific antibodies and uses thereof. - Google Patents

Abstract

This disclosure relates to the treatment and/or prevention of glaucoma and other diseases affecting the optic nerve and retinal ganglion cells. In particular, the present disclosure provides novel therapeutic antibodies, and related compositions and methods, that target angiopoietin-related protein 7 (ANGPTL7) to reduce intraocular pressure (lOP) in order to prevent optical nerve damage and restore vision.

Description

ANGIOPOIETIN-RELATED PROTEIN 7-SPECIFIC ANTIBODIES AND USESTHEREOF

CROSS REFERENCE TO RELATED APPLICATIONS

[0001I This application claims priority to and the benefît of U.S. Provisional Patent 5 Application No. 63/336,747 filed April 29, 2022, which is incorporated herein by reference in its entirety for ail purposes.

SEQUENCE LISTING

[0002] The text of the computer readable sequence listing filed herewith. titled “40185_601_SequenceListing,” created March 30, 2023, having a file size of 410,410 bytes, is 10 hereby incorporated by reference in its entirety.

FIELD

[0003] Embodiments of the présent disclosure relate to the treatment and/or prévention of glaucoma and other diseases affecting the optic nerve and retinal ganglion cells. In pa rticular, the présent disclosure provides novel therapeutic antibodies, and related compositions and methods, 15 that target angiopoietin-related protein 7 (ANGPTL7) to reduce intraocular pressure (IOP) in order to prevent optic nerve damage and restore vision.

BACKGROUND

[0004] Glaucoma is a group of optic neuropathies associated with characteristic structural changes at the optic nerve head that may lead to visual field loss and, ultimately, blindness.

Blindness is most commonly defined as 20/200 or worse visual acuity on a Snellen eye chart or a visual field of less than 20 degrees. Legal blindness refers to the fulfillment of these criteria by the better-seeing eye. By 2020, approximately 79.6 million people worldwide will hâve glaucoma and more than 11 million will be bilatérally blind from glaucoma. More than 2 million Americans 40 years and older hâve glaucoma, and studies of the U.S. population estimate that more than one25 half of these cases may be undiagnosed or untreated. Among black and Hispanic persons, glaucoma is the leading cause of irréversible blindness. Glaucoma accounts for more than 25% of cases of blindness in these groups, making it a more common cause of blindness than diabetic

retinopathy (accounting for 7.3% and 14.3% of cases in blacks and Hispanics, respectiveiy) and age-related macular degeneration (accounting for 4.4% and 14.3% of cases in blacks and Hispanics, respectiveiy). Among Hispanics, glaucoma causes blindness more often than cataracts do (28.6% vs. 14.3%). In 2009, Medicare beneficiaries spent $748 million on glaucoma-related 5 visits, testing, and procedures. Patients with glaucoma who are not blind may hâve functional limitations, leading to driving cessation and decreased ability to read.

|0005] The two most common forms of glaucoma are primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), with the former approximately seven times more common than the latter in the United States and Europe. When POAG and PACG are left untreated, 10 the typical disease course is chronic, progressive, and irréversible visual field loss, which may progress to tunnel vision and, ultimately, loss of central vision. Treatment that reduces intraocular pressure has been shown to improve outcomes in randomized clinical trials. The angle of the eye is the junction between the iris and cornea, where the trabecular meshwork drains aqueous humor from the anterior chamber of the eye. In POAG, the angle remains open as the trabecular meshwork 15 is unblocked by iris tissue. Intraocular pressure is transmitted to the axons of retinal ganglion cells at the optic nerve as mechanîcal stress, leading to cell death. However, about 50% of patients with glaucoma hâve intraocular pressure within the so-called “normal” range of 10 to 21 mm Hg at diagnosis. Only after 30% of retinal ganglion cells hâve been lost are visual field defects present on perimetric testing. In PACG, the peripheral iris obstructs normal aqueous outflow. This can 20 lead to increased intraocular pressure and optic nerve damage. Eyes that are at risk of PACG tend to be shorter with a shallower anterior chamber. Patients with PACG may expérience acute or subacute events that occur after a sudden rise in intraocular pressure or from chronic PACG that is insidious in onset and largely asymptomatic.

SUMMARY

[00061 Embodiments of the present disclosure include an antibody, or an antigen binding fragment thereof, which specifically binds human Angiopoietin-Like Protein 7 (ANGPTL7), optionally wherein said human ANGPTL7 is a polypeptide which comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 370 to 374.

10007] In some embodiments, the antibody, or an antigen binding fragment thereof, exhibits 30 any one or more the following functional characteristics: increases outflow facility compared to a

control when administered to the eye of a subject. optionally wherein the control is vehicle treatment, dexamethasone treatment. ANGPTL7 protein treatment, or ANGPTL7 protein with an isotype control antibody treatment; and/or binds to ANGPTL7 with a Kpof about l OOnM or lower; and/or binds to the same epitope on ANGPTL7 as an antibody comprising the VH and VL 5 sequences of any one of the exemplary antibodies the sequences of which are provided in Table

11; and/or competes for binding to ANGPTL7 with an antibody comprising the VH and VL sequences of any one of the exemplary antibodies the sequences of which are provided in Table 11.

[0008] In some embodiments, the antibody, or an antigen binding fragment thereof is 10 monoclonal, optionally recombinant. In some embodiments, the antibody, or an antigen binding fragment thereof, is human, humanized, or chimeric.

[0009] In some embodiments, the antibody, or an antigen binding fragment thereof, is a full length antibody, a single chain antibody, a single chain variable fragment (scFv), a variable fragment (Fv), a fragment antigen-binding région (Fab), a Fab-C, a Fab’-SH, a (Fab’)2, a single15 domain antibody (sdAb), a VH H antibody, a nanobody, a camelid-derived single-domain antibody, a shark IgNAR-derived single-domain antibody fragment (VNAR), a diabody, a triabody, an anticalin or an aptamer, optionally wherein the antibody is a full length antibody comprising an Fc région such as a human IgGl, IgG2, IgG3 or IgG4 région.

[0010] In some embodiments, the antibody, or an antigen binding fragment thereof, is 20 conjugated to at least one additional moiety, optionally selected from: an antigen binding moiety, such as an antibody or antigen-binding fragment thereof, which is capable of spécifie binding to a target which is not human ANGPTL7, preferably wherein said target is expressed in the human eye; a therapeutic or cytotoxic moiety; a détection moiety; a purification moiety; a half-life extension moiety, optionally a polypeptide that is at least 20 amino acids in length and comprises 25 any combination of G, A, S T, E, and P residue, which polypeptide is conjugated to the C- or Nterminus of the antibody.

|0011] In some embodiments, the antibody, or an antigen binding fragment thereof is a polypeptide comprising: one, two or ail three HCDRs of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also one, two or ail three of the 30 corresponding LCDRs of the exemplary antibody; and/or a VH sequence having at least 90% identity to the VH sequence of any one of the exemplary antibodies the sequences of which are

provided in Table 11, and optionally also a VL sequence having at least 90% identity to the corresponding VL sequence of the exemplary antibody, preferably wherein variation is not permitted in the HCDRs or LCDRs; and/or ail six CDRs of any of the exemplary antibodies exemplary antibodies the sequences of which are provided in Table 11; and/or the VH and VL 5 sequences of any one ofthe exemplary antibodies the sequences of which are provided in Table

11; and/or the full length heavy chain (VH + constant) sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also the corresponding full length light chain (VL + constant) sequence of the exemplary antibody.

[0012] Embodiments of the présent disclosure also include a polynucleotide encoding an 10 antibody, or an antigen binding fragment thereof, of any of the preceding paragraphs, optionally wherein said polynucleotide comprises or consists of a nucleic acid sequence having at least 70%, 80%, 90% or 100% identity to a nucleic acid sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11.

[0013| Embodiments of the présent disclosure also include an expression vector comprising 15 the polynucleotide of the preceding paragraph, which is optionally an adeno-associated virus (AAV) vector, a lentiviral (LV) vector, a herpes simplex virus (HSV) vector, or a retrovirus vector. [0014] Embodiments of the présent disclosure also include a pharmaceutical composition comprising an antibody, or an antigen binding fragment thereof, a polynucleotide, or a vector according to any one of the preceding paragraphs, and optionally: at least one pharmaceutically 20 acceptable carrier, diluent or preservative; and/or at least one additional active ingrédient. In some embodiments, the pharmaceutical composition is suitable for ocular administration to a subject, optionally by delivery using a conjunctival insert, a contact lens, a gel, a nanoparticle, a mucoadhesive polymer, an ointment, a solution, a suspension, eye drops, and/or an implant, preferably by injection into the vitreous fluid.

[00151 Embodiments of the présent disclosure also include the antibody, or an antigen binding fragment thereof, the polynucleotide, the vector, or the compositions of any of the preceding paragraphs, for use as a médicament, optionally for use in a method oftreating a disease ofthe eye in a subject. In some embodiments, the disease is characterized by increased intraocular pressure and/or reduced outflow facility in the eye of the subject. In some embodiments, the method 30 comprises ocular administration of the antibody, preferably by injection into the vitreous fluid. and wherein said administration preferably relieves at least one symptom in the subject selected from eye pain, eye pressure, headaches, rambow-colored halos around hghts, low vision, blurred vision, narrowed vision, impaired peripheral vision, blind spots, nausea. vomiting, and red eyes. In some embodiments, the disease is glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells, optionally wherein said glaucoma is primary or glucocorticoid-induced glaucoma.

[0016] Embodiments of the présent disclosure include antibodies against Angiopoietin-Like Protein 7 (ANGPTL7) peptides, or an antigen-binding fragment thereof, comprising a heavy chain variable région (VH) comprising complementarity determining régions (CDRs) HCDR1, HCDR2, and HCDR3, and a light chain variable région (VL) comprising complementarity determining régions (CDRs) LCDR1, LCDR2, and LCDR3. In some embodiments, the HCDR1 comprises one of the following amino acid sequences: (a) Χ1ΥΧ2ΙΧ3 (SEQ ID NO: 1), wherein X, is S or D; X₂ is G or Y; X3 is S or H; (b) TSGVGVG (SEQ ID NO: 18); (c) X1X2X3MX4 (SEQ ID NO: 27), wherein X, is V, S, D, or T; X2 is Y, H, or F; X3 is D, G, S, or A; X4 is H, S, or N; or (d) SX1SX2YWX3 (SEQ ID NO: 74), wherein Xi is S or G; X₂ is S or Y; X3 is G or S. In some embodiments, the HCDR2 comprises one of the following amino acid sequences: (a) W1XiX2X3X4GX5TX₆YAQX7XkX9G (SEQ ID NO: 7), wherein X, is S, I, or N; X₂ is A or P; X3 is Y or N; Χ4 is N or T; X$ is N or A; Xg is N or K; X₇ is N or K; Xg is L or F; Χς> is R or Q; (b) LIYWNDDKXiYSPSLKS (SEQ ID NO: 21), wherein Xi is R or Q; (c) XiX2X3X4X5XftX7X_sX9X 10X11X12X13X14X15G (SEQ ID NO: 43), wherein X, is G, T, S, A, V, H, or 1; X₂ is I or M; X₃ is D, N, T, S, or G; X₄ is P, W, S, G, or Y; X₅ is D, A, N, S, or Y; X₆ is G or S; X₇ is D, G, Y, S, 1, or N; X₈ is T, S, N, 1, Y, or D; X9 is Y, T, F, Μ. K, G, or I; Xi₀ is Y, G, or F; X11 is P, Y, or A; X12 îs G, D, or A; X_]3 is S or D; X_[4 is V, L, or S; X15 is K or M; or (d) X1IYYSGSTX2SNPSLKS (SEQ ID NO: 78) wherein X| is S, or Y; X₂ is Y or S. In some embodiments, the HCDR3 comprises one ofthe following amino acid sequences: (a) SEQ ID NOs: 13-17; (b) X1X2X3X4X5X6FFDX7 (SEQ IDNO: 24) wherein X, is S, D, or N; X₂ is Y or P; X3 is G or D; X₄ is D or Y; X₅ is Y or G; X₆ is W or D; X₇ is L or Y; (c) SEQ ID NOs: 59-73; or (d) X1X2X3X4GX5X6X7X8X9Y (SEQ ID NO: 82) wherein X, is Q or A; X₂ is Y or K; X₃ is I or W; X4 is S or E; X5 is T or D; Xg is E or Y; X₇ is Y or F; Xg is F or D; Xg is Q or Y.

|0017| In accordance with the above embodiments, the LCDR1 of the anti-ANGPTL7 antibodies of the présent disclosure includes an amino acid sequences of any of SEQ ID NOs: 8797, SEQ ID NOs: 123-127, or SEQ ID NOs: 141-149; the LCDR2 comprises an amino acid sequence ofany of SEQ IDNOs: 99-109, SEQ ID NOs: 129-133, or SEQ ID NOs 151-159; and the LCDR3 comprises an amino acid sequence of any of SEQ ID NOs: 11 I-I2I, SEQ ID NOs: I35-139, or SEQ IDNOs: I6I-169.

(0018] In some embodiments, the présent disclosure provides antibodies directed against ANGPTL7 peptides, or an antigen-binding fragment thereof, that include a VH comprising complementarity determining régions HCDRI, HCDR2, and HCDR3, and a VL comprising corn pie mentarity determining régions LCDR1, LCDR2, and LCDR3, wherein the LCDR1 comprises one of the following amino acid sequences: (a) RASQX1IX2X3X4LX5 (SEQ ID NO: 86), wherein Xi is G or S; X2 is S, R, or Y; Xj is S, N, or 1; X4 is W, D, or Y; X5 is A, G, or N; (b) RSSQSLX!X2SX3X4X5X6YLX7 (SEQ ID NO: 122), wherein Xi is L or V; X2 is H, Y, or F; X₃ is N or D; X₄ is R or G; X₅ is Y or N; X₆ is N or T; X₇ is D or N; or (c) RASQSVSX1X2X3X4A (SEQ ID NO: 140), wherein Xi is S, N, or R; X2 is Y or S; X3 is L or Y; X4 is A or L. In some embodiments, the LCDR2 comprises one of the following amino acid sequences: (a) AX1SSLX2S (SEQ ID NO: 98), wherein Xi is A or T; X₂ is Q or P; (b) X1X2SNRX3S (SEQ ID NO: 128), wherein Xi is L, K, or E; X2 is G or V; X₃ is A or D; or (c) X1ASX2RAT (SEQ ID NO: 150), wherein Xi is D or G; X2 is N, S, or T. In some embodiments, the LCDR3 comprises one of the following amino acid sequences: (a) XiQX2X₃X4X5PX&X₇ (SEQ ID NO: 110), wherein Xi is L or Q; X2 is A, H, S, or D; X3 is N, F, or Y; X₄ is S, T, or N; X₅ is F, Y, or T; X₆ is W, L, I, P, or Y; X₇ is T or Y; (b) MQX1X2X3X4PX5T (SEQ ID NO: 134), wherein X, is T or G; X₂ is L or T; X₃ is Q or H; X₄ is T or W; X₅ is Y or W; or (c) QQX1X2X3X4X5X01 (SEQ ID NO: 160), wherein X, is R, Y, or G; X₃ is S, G, or Q; X₃ is N, S, or V; X₄ is W, S, or I; X₅ is P or L; Χ_ή is L, S, P, or T.

[0019] In accordance with the above embodiments, the HCDR1 of the anti-ANGPTL7 antibodies of the présent disclosure includes an amino acid sequences of any of SEQ ID NOs: 26, SEQ ID NOs: 19-20, SEQ ID NOs: 28-42, or SEQ ID NOs: 75-77; the HCDR2 comprises an amino acid sequence of any of SEQ ID NOs: 8-12, SEQ ID NOs: 22-23, SEQ ID NOs 44-58, or SEQ ID NOs: 79-81 ; and the HCDR3 comprises an amino acid sequence of any of SEQ ID NOs: 13-17, SEQ IDNOs: 25-26, SEQ ID NOs: 59-73, or SEQ ID NOs: 83-85.

[0020] In some embodiments, the HCDRI comprises the amino acid sequence of SEQ ID NO: 2; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 8; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13. In some embodiments, the HCDRI comprises the amino acid sequence of SEQ ID NO: 3; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 9; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 14. In some embodiments, the HCDRl comprises the ammo acid sequence of SEQ ID NO: 4; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 10; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 5; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 11 ; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 6; the HCDR2 comprises the amino acid sequence of SEQ ID NO: I2; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 7; the HCDR2 comprises the amino acid sequence of SEQ ID NO. 14; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 19; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 22; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 20; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 23; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 26. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 28; the HCDR2 comprises the amino acid sequence of SEQ IDNO: 44; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 59. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 29; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 45; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 60. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 30; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 46; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6I. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 31; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 47; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 62. In some embodiments, the HCDRI comprises the amino acid sequence of SEQ ID NO: 32; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 48; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 63. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 33; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 49; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 34; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 50; and the HCDR3 comprises the amino acid sequence of

SEQ ID NO: 65. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 35; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5I; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 66. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 36; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 52; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 67. In some embodiments, the HCDRI comprises the amino acid sequence of SEQ ID NO: 37; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 53; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 68. In some embodiments, the HCDR l comprises the amino acid sequence of SEQ ID NO: 38; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 54; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 39; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 55; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 70. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 40; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 56; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 71. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 41; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 57; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 72. !n some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 42; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 58; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 73. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 75; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 79; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 76; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 80; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the HCDRl comprises the amino acid sequence of SEQ ID NO: 77; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 81 ; and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 85. In some embodiments, the LCDRl comprises the amino acid sequence of SEQ ID NO: 87; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 99; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: lll. In some embodiments, the LCDRl comprises the amino acid sequence of SEQ ID NO: 88; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 100; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: i 12. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 89; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 101 ; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 90; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 102; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: Il4. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 91; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 103; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 115. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 92; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 104; and the LCDR3 comprises the amino acid sequence of SEQIDNO: Il 6. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 93; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 105; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 117. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 94; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 106; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: I 18. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 95; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 107; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 119. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 96; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 108; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 120. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 97; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 109; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: I2l. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 123; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 129; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 135. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 124; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 130; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 136. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO: 125; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 131; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 137. In some embodiments, the LCDRI comprises the amino acid sequence of SEQ ID NO; 126; the LCDR2

ΙΟ comprises the amino acid sequence of SEQ IDNO: 132; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 138. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 127; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 133; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 139. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 141; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 151 ; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 161. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 142; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 152; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 162. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 143; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 153; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 163. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 144; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 154; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 164. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 145; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 155; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 165. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 146; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 156; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 166. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 147; the LCDR2 comprises theaminoacid sequence of SEQ IDNO: 157; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 167. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 148; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 158; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 168. In some embodiments, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 149; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 159; and the LCDR3 comprises the amino acid sequence of SEQ IDNO: 169.

[0021] In some embodiments, the VH of the anti-ANGPTL7 antibodies of the présent disclosure includes an amino acid sequence that is at least 90% identical to any of: (a) SEQ ID NOs: 170-174; (b) SEQ ID NOs: 190-191; (c) SEQ ID NOs: 198-212; or (d) SEQ ID NOs: 258260. In some embodiments, the VL of the anti-ANGPTL7 antibodies of the présent disclosure includes an amino acid sequence thaï is at least 90% identical to any of: (a) SEQ ID NOs: 180184; (b) SEQ ID NOs: 194-195; (c) SEQ ID NOs; 228-242; or (d) SEQ ID NOs: 264-266. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: I70 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID 5 NO: 180. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: I7l and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 181. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 172 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 182. In some embodiments, the VH comprises an 10 amino acid sequence that is at least 90% identical to SEQ ID NO: 173 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 183. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 174 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 184. In some embodiments. the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID

I5 NO: 190 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: I94. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: I9l and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: I95. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: I98 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 228. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 199 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 229. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 200 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 230. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 201 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 231. In some embodiments. the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 202 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 232. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 203 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 233. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 204 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 234. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 205 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 235. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 206 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 236. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 207 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 237. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 208 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 238. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 209 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 239. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 210 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 240. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 211 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 241. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 212 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 242. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 258 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 264. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 259 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 265. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 260 and the VL comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 266.

[0022) In accordance with the above embodiments, the présent disclosure provides antiANGPTL7 antibodies comprising various functional characteristics. In some embodiments, the anti-ANGPTL7 antibodies described herein bind ANGPTL7 (or a fragment thereof) and increase outflow facility compared to a control. In some embodiments, the control is selected from the group consisting of vehicle treatment, dexamethasone treatment, ANGPTL7 protein treatment, and

ANGPTL7 protein with an isotype control antibody treatment. In some embodiments. the antiANGPTL7 antibody comprises: (a) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 210 and a VL comprising an amino acid sequence thaï is at least 90% identical to SEQ ID NO: 240; (b) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 200 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 230; (c) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 258 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 264; (d) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 207 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 237; (e) a VH comprising an amino acid sequence thaï is at least 90% identical to SEQ ID NO: 204 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 234; (f) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 260 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 266; (g) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 205 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 235; (h) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 206 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 236 (i) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 208 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 238; (j) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: I9l and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 195; (k) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 203 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 233; (!) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 212 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 242; (m) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 198 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 228; (n) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 190 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 194; (o) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 202 and a VL comprising an amino acid sequence that is at least 90%

I4 identical to SEQ ID NO: 232; (p) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 211 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 241; or (q) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 199 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 229.

[0023] In some embodiments, the anti-ANGPTL7 antibody comprises:(a) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 210 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 240; (b) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 200 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 230; or (c) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 258 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 264.

|0024| In sonie embodiments. the anti-ANGPTL7 antibody comprises: (a) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 207 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 237; (b) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 204 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 234; (c) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 260 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 266; (d) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 205 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 235; (e) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 206 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 236 (f) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 208 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 238; (g) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 191 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 195; (h) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 203 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 233; (i) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 212 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 242; (j) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 198 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 228; or (k) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: I90 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 194.

[0025] In some embodiments, the anti-ANGPTL7 antibody comprises:(a) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 202 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 232; (b) a VH comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 211 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 241; or (c) a VH comprising an 10 amino acid sequence that is at least 90% identical to SEQ ID NO: 199 and a VL comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 229.

[0026] In accordance with the above embodiments, the anti-ANGPTL7 antibodies of the présent disclosure can be a monoclonal antibody, a human antibody, a humanized antibody, and/or a chimeric antibody. In some embodiments, the antibody is a fragment selected from the group I5 consisting of Fab, Fab-C, Fab'-SH, Fv, scFv, and (Fab')? fragments. In some embodiments, the anti-ANGPTL7 antibody is a monospecific antibody. In some embodiments, the anti-ANGPTL7 antibody is a bispecific antibody. In some embodiments, the anti-ANGPTL7 antibody comprises two or more single-domain antibodies that form a bivalent antibody, a trivalent antibody, or a tetravalent antibody that recognizes different epitopes on the same or different antigens.

[0027] In some embodiments, the antibody comprises a détection moiety. In some embodiments, the antibody comprises a purification moiety. In some embodiments, the antibody comprises a half-life extension moiety. In some embodiments, the half-life extension moiety comprises a polypeptide that is at least 20 amino acids in length and comprises any combination of G, A, S T, E, and P residues. In some embodiments, the half-life extension polypeptide is 25 attached to the C-terminus or N-terminus of the antibody.

[0028] The anti-ANGPTL7 antibodies of the présent disclosure can be administered as part of a pharmaceutîcal composition in a therapeutically effective amount to treat an eye disease (e.g., glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells). In some embodiments, the composition is suitable forocular administration. In some embodiments, ocular 30 administration comprises injection into vitreous fluid. In some embodiments, ocular administration comprises delivering the antibody using a conjunctival insert, a contact lens, a gel, a nanoparticle, a mucoadhesive polymer, an ointment, a solution, a suspension, eye drops, and/or an implant.

[0029] Embodiments of the présent disclosure also include methods of treating glaucoma and/or a disease affecting the optic nerve and/or retina! ganglion cells. In accordance with these 5 embodiments, the methods include administering a pharmaceutical composition comprising a therapeutically effective amount of an anti-ANGPTL7 antibody of the présent disclosure. In some embodiments, the pharmaceutical composition is administered ocularly and treats at least one symptom associated with glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells. In some embodiments, the at least one symptom associated with glaucoma and/or a disease 10 affecting the optic nerve or retinal ganglion cells comprises eye pain, eye pressure, headaches, rainbow-colored halos around lights, low vision, blurred vision, narrowed vision, impaired peripheral vision, blind spots, nausea, vomiting, and red eyes. In some embodiments, administering the pharmaceutical composition atténuâtes intraocular pressure and/or increases outflow facility in the subject’s eye. In some embodiments, the pharmaceutical composition is 15 administered at a dose ranging from about 0.0001 mg/dose to about 100 mg/dose. In some embodiments, the pharmaceutical composition is administered at a dose ranging from about 0.0001 mg/ml to about 100 mg/ml.

|0030| Embodiments of the présent disclosure also include a polynucleotide encoding any of the anti-ANGPTL7 antibodies of the présent disclosure. In some embodiments, the polynucleotide 20 comprises a sequence that is at least 70% identical to any of the following nucleic acid sequences:

(a) SEQ ID NOs: 175-179; (b) SEQ ID NOs: 192-193; (c) SEQ ID NOs: 213-227; or (d) SEQ ID NOs; 261-263. In some embodiments, the polynucleotide comprises a sequence that is at least 70% identical to any of the following nucleic acid sequences: (a) SEQ ID NOs: 185-189; (b) SEQ ID NOs: 196-197; (c) SEQ ID NOs: 243-257; or (d) SEQ ID NOs: 267-269. In some embodiments, 25 the polynucleotide comprises a sequence that is at least 80% identical to any of the following nucleic acid sequences: (a) SEQ ID NOs: 175-179; (b) SEQ ID NOs: 192-193; (c) SEQ ID NOs: 213-227; or (d) SEQ ID NOs: 261-263. In some embodiments, the polynucleotide comprises a sequence that is at least 80% identical to any of the following nucleic acid sequences: (a) SEQ ID NOs: 185-189; (b) SEQ ID NOs: 196-197; (c) SEQ ID NOs: 243-257; or (d) SEQ IDNOs: 26730 269.

[0031] In some embodiments, the polynucleotide encodmg an anti-ANGPTL7 antibody of the présent disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 175 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 185; (b) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 176 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 186; (c) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 177 and a nucleic acid sequence that is at least 70% identical to SEQ IDNO: 187; (d) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 1 78 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 188; or (e) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 179 and a nucleic acid sequence that is at least 70% identical to SEQ IDNO: 189.

[0032] In some embodiments, the polynucleotide encoding an anti-ANGPTL7 antibody of the présent disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 192 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 196; or (b) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 193 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 197.

[0033] In some embodiments, the polynucleotide encoding an anti-ANGPTL7 antibody of the présent disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 213 and a nucleic acid sequence that isat least 70% identical to SEQ IDNO: 243; (b)a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 214 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 244; (c) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 215 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 245; (d) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 216 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 246; (e) a nucleic acid sequence that is at least 70% identical to SEQ IDNO: 217 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 247; (f) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 218 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 248; (g) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 219 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 249; (h) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 220 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 250; (i) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 221 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 251; (j) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 222 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 252; or (k) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 223 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 253; (I) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 224 and a nucleic acid sequence that is 5 at least 70% identical to SEQ ID NO: 254; (m) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 225 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 255; (n) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 226 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 256; or (o) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 227 and a nucleic acid sequence that is at least 70% identical I0 to SEQ IDNO: 257.

[0034] In some embodiments, the polynucleotide encoding an anti-ANGPTL7 antibody of the present disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 261 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 267; (b) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 262 and a nucleic acid sequence that is 15 at least 70% identical to SEQ ID NO: 268; or (c) a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 263 and a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 269.

[0035] In accordance with these embodiments, the present disclosure includes an expression vector comprising any of the polynucleotides encoding an anti-ANGPTL7 antibody of the present 20 disclosure. In some embodiments, the expression vector is suitable for manufacturing an antiANGPTL7 antibody of the present disclosure for delivery of the antibody to a subject. In some embodiments, the expression vector is suitable for use in gene therapy (e.g., an expression vector for delivering a polynucleotide encoding an anti-ANGPTL7 antibody of the present disclosure to a subject). In some embodiments, the expression vector is an adeno-associated virus (AAV) vector, 25 or comprises an AAV backbone. In some embodiments, the expression vector is a lentiviral vector (LV), or comprises an LV backbone. In some embodiments, the expression vector is a herpes simplex virus (HSV) vector, or a retrovirus vector.

[0036] In accordance with these embodiments. the present disclosure also provides a method of administering ocular gene therapy to a subject in need thereof comprising injecting a 30 pharmaceutical composition comprising an effective amount of an expression vector described herein (e.g., an expression vector comprising a polynucleotides encoding an anti-ANGPTL7 i

antibody of the présent disclosure). In accordance with these embodiments, the présent disclosure also provides a method of treating glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells comprising administering a pharmaceutical composition comprising an effective amount of an expression vector described herein (e.g., an expression vector comprising a polynucleotides encoding an anti-ANGPTL7 antibody of the présent disclosure). In some embodiments, administering the pharmaceutical composition treats at least one symptom of glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells.

[0037] In accordance with the above embodiments, the anti-ANGPTL7 antibodies of the présent disclosure bind an epitope from an ANGPTL7 polypeptide having any amino acid sequence of SEQ IDNOs: 370-374, or a variant thereof. In some embodiments, the anti-ANGPTL7 antibodies of the présent disclosure bind an epitope from an ANGPTL7 polypeptide w ith a Kd of about I00 nM or lower.

BRIEF DESCRIPTION OF THE DRAWING(S)

[0038] FIG. 1: Représentative data demonstrating the levels of ANGTPL7 gene expression relative to control following treatment with déxaméthasone for 5 days.

[0039] FIG. 2: Représentative data of treatment-induced gene changes from 3 days of ANGPTL7 (50 mg/ml) treatment in human TM and SC cells using an RNAseq panel.

[0040| FIGS. 3A-3C: Représentative schematic diagram of 3D-HTM scaffolding technology (Glauconix) used as an ex-vivo human eye tissue model to assess the effects of ANGPTL7 on outflow facility (FIG. 3A). FIG. 3B includes représentative data demonstrating outflow facility for 3D-HTM donor 2 treated with vehicle (DMSO), 500nM Dexamethasone, 50 ng/mL of ANGPTL7. Samples were analyzed using One-way ANOVA (GraphPad Prism Software, Inc., La Jolla, CA), *P<0.05, **P<.0.0l, ***P<.001 N=4 per treatment group. FIG. 3C includes représentative data । demonstrating outflow facility for 3D-HTM donor 3 treated with vehicle (DMSO), 500nM

Dexamethasone, 50 ng/mL of ANGPTL7. Samples were analyzed using One-way ANOVA (GraphPad Prism Software, Inc., La Jolla, CA), *P<0.05, **P<.0.0l, ***P<,00l N=4 pertreatment group.

[0041] FIGS. 4A-4C: FIG. 4A includes représentative data demonstrating outflow facility for donor 1 treated with vehicle (DMSO), 500nM Dexamethasone, or 25, 50, 150 ng/mL of

ANGPTL7. Samples were analyzed using One-way ANOVA (GraphPad Prism Software, Inc., La

Joila, CA), *P<0.05, **P<.0.0l, ***P<.00I N=3 per treatment group. FIG. 4B includes représentative data demonstrating outflow facîlity for donor 2 treated with vehicle (DMSO), 500nM Dexamethasone, or 25, 50, 150 ng/mL of ANGPTL7. Samples were analyzed using Oneway ANOVA (GraphPad Prism Software, Inc., La Joila, CA), *P<0.05, **P<.0.0l, ***P<.00l N=3 per treatment group. FIG. 4C includes représentative data demonstrating outflow facîlity for donor 3 treated with vehicle (DMSO), 500nM Dexamethasone, or 25, 50, 150 ng/mL of ANGPTL7. Samples were analyzed using One-way ANOVA (GraphPad Prism Software, lnc„ La Joila, CA), *P<0.05, **P<.0.0l, ***P<.00l N=3 per treatment group. (See FIG. 3A for schematic diagram of 3D-HTM scaffolding technology used to generate data in FIGS. 4A-4C.)

[0042] FIGS. 5A-5D: Représentative ELISA results used to détermine antigen positive sérum titers of mice immunized with ANGPTL7, according to four different immunization protocols/cohorts (FIG. 5A —Cohort I ; FIG. 5B — Cohort 2; FIG. 5C — Cohort 3; FIG. 5D - Cohort 4).

[0043] FIGS. 6A-6I: Représentative results of ANGPTL7 antibody cross-blockîng experiments, including data from a représentative heatmap analyzing the ability of the antibodies to block one another for binding to the antigen (FIG. 6A), and représentative dendrograms, which progressively group antibodies with similar compétition profiles. FIG. 6B includes data from a granular binning network. FIG. 6C: includes data from a combined binary dendrogram (color indicates bins in the Community binning network). FIG. 6D includes data from a community binning network. FIG. 6E includes binning data based on affinity for huANGPTL7-his (P62). FIG. 6F includes binning data based on antibody source (hybridoma or phage). FIG. 6G includes binning data based on fibrinogen domain (P60P) binding. FIG. 6H includes binning data based on rabbit ANGPTL7 (p66) binding. FIG. 6I includes binning data based on mouse ANGPTL7 binding.

[0044] FIGA. 7: Représentative results of the effects of anti-ANGPTL7 antibodies on conventional outflow facîlity using a 3D HTM/HSC Tissue Model (see FIG. 3A). Outflow facîlity of one donor cell line treated with vehicle (DMSO), 500 nM Dexamethasone, 50 ng/mL ANGPTL7 (L l nM) alone, 50 ng ANGPTL7 + an isotype control Antibody (330) at l L l nM, and twenty different Anti-ANGPTL7 antibodies at ll.l nM together with 50 ng/mL ANGPTL7. Samples were analyzed for effects against isotype control (330) using One-way ANOVA (GraphPad Prism Software, Inc., La Jolla, CA), *P<0.05, **P<.0.0l, ***P<.00l, ****P<.000l N=3 per treatment group.

[0045] FIGS. 8A-8C: Représentative data of the effects of dexamethasone-induced ocular hypertension in ANGPTL7 knockout mice. FIG. 8A includes body weight data of mice post- implantation surgery; dexamethasone impaired weight gain in male mice compared to PBS-treated mice, thereby confirming the proper functioning of the dexamethasone osmotic pumps. FIG. 8B includes intraocular pressure (IOP) data of ANGPTL7 WT and ANGPTL7 KO mice dosed with PBS control or Dexamethasone (4 mg/kg/day); osmotic pumps were implanted on day 0. FIG. 8C includes représentative data of the changes in IOP of ANGPTL7 WT and ANGPTL7 KO mice implanted with osmotic pumps containing PBS vehicle or dexamethasone (4 mg/kg/day) over 28 days. Ail IOP values were normalized to baseline (day 0) readings.

[0046] FIGS. 9A-9R: Représentative data demonstrating the in vivo tolerability of antiANGPTL7 antibodies using single intravitreal (IVT) injections in New Zealand White Rabbits.

The anti-ANGPTL7 antibodies indicated were injected at either a 0.5 mg dose (FIGS. 9C, 9D, 9G,

9H, 9K, 9L, 90, 9P) or a 2.0 mg dose (FIGS. 9E, 9F, 91, 9J, 9M, 9N, 9Q, 9R) in the right eye (OD), or with a corresponding vehicle dose in the left eye (OS). (FIGS. 9A and 9B include data from Controls at 2 mg doses). Intraocular pressure (IOP) measurements (FIGS. 9A, 9C, 9E, 9G, 91, 9K. 9M, 90, 9Q) and changes in IOP (FIGS. 9B, 9D, 9F, 9H, 9J, 9L, 9N, 9P, 9R) were taken at the indicated time points over a 21 -day period.

(0047] FIGS. 10A-I0C: Représentative pharmacokinetic (PK) data for ANGPTL7 antibody,

ATX-P-424, including intraocular pressure (IOP) measurements at 0.5 mg or 2.0 mg (OU) doses compared to vehicle (FIG. 10A); changes in IOP compared to baseline (FIG. I0B); and total ocular examination scores (OE) (FIG. 10C).

[0048| FIGS. 11A-11C: Représentative pharmacokinetic (PK) data for ANGPTL7 antibody,

ATX-P-439, including intraocular pressure (IOP) measurements at 0.5 mg or 2.0 mg (OU) doses compared to vehicle (FIG. 11 A); changes in IOP compared to baseline (FIG. 11 B); and total ocular examination scores (OE) (FIG. 1 IC).

[0049] FIGS. I2A-12C: Représentative pharmacokinetic (PK) data for ANGPTL7 antibody, ATX-P-448, including intraocular pressure (IOP) measurements at 0.5 mg or 2.0 mg (OU) doses compared to vehicle (FIG. 12A); changes in IOP compared to baseline (FIG. 12B); and total ocular examination scores (OE) (FIG. I2C).

[0050] FIGS. 13A-13: Représentative data demonstrating the in vivo tolerabihty of antiANGPTL7 antibodies usîng single intravitreal (IVT) injections in African Green Monkeys. Data includes absolute IOP values at baseline (day 3) and on day 10, 6 hours post topîcal administration of saline and Latanoprost (FIG. 13A); changes in IOP 6 hours post topical administration of either saline (day 3) or Latanoprost (day 10) (FIG. 13B); and changes in IOP between vehicle and Latanoprost administration (FIG I3C).

[0051) FIGS. I4A-14H: Représentative IOP measurements (FIGS. 14A, 14C, 14E, and 14G) and changes in IOP (FIGS. 14B, 14D, 14F, and 14H) in African Green Monkeys dosed with 2 mg of the indicated anti-ANGPTL7 antibody compared to an isotype control (BTX-330) and a single vehicle eye.

[0052] FIG. 15: Représentative clinical scores of ocular examinations (OE) across ail the dosed groups in FIGS. 14A-14H.

DETAILED DESCRIPTION

[0053J Embodiments of the présent disclosure relate to the treatment and/or prévention of glaucoma and other ocular diseases affecting the optic nerve and retinal ganglion cells. In particular, the présent disclosure provides novel therapeutic antibodies that target angiopoietinrelated protein 7 (ANGPTL7) as a means for reducing intraocular pressure (IOP) and/or increasing outflow facility, thereby preventing optic nerve damage and/or restoring vision.

[0054] Angiopoietin-like proteins (ANGPTL) are a family of proteins that hâve structural similarity to angiopoietin proteins. Seven proteins hâve been initially grouped into this family (ANGPTL 1-7), and more recently, another protein called ANGPTL8 has been identified. ANGPTL proteins hâve an amino-terminal coiled-coil domain as well as a carboxyl-terminal fîbrinogen-like domain, except ANGPTL8, which lacks the later domain. ANGPTL proteins are not known to bind tyrosine kinase receptors such as Tie 1 and Tie 2, distinguishing them from angiopoietin proteins. ANGPTL proteins hâve been shown to play different physiological rôles in metabolism, inflammation and cancer. Increasing evidence is connecting these proteins to obesity and insulin résistance. ANGPTL2, for example, has been shown to associate with adiposity and insulin résistance as well as the development of type 2 diabètes. ANGPTL3, 4, and 8 hâve been shown to play a major rôle in regulating lipid metabolism through their inhibition of lipoprotein lipase. Similarly, ANGPTL6 has been shown to be higher in subjects with metabolic syndrome and to positively associate with HDL level. The levels of ANGPTL8 has been shown to be higher in obese and diabetic subjects and to positively associate with insulin résistance and fasting blood glucose in non-diabetic subjects.

[0055] ANGPTL7, however, is a poorly studied member of the ANGPTL protein family that 5 has been initially discovered in the stromal layer of the cornea. Levels of ANGPTL7 hâve been shown to be elevated in glaucoma and its overexpression increases the collagen expression level while, its induction by glucocorticoids caused the up-regulation of important glaucoma-related proteins including fîbronectin, myocilin and MMPI. These data suggest that ANGPTL7 may coordînate the trabecular meshwork’s extracellular matrix and its response to steroids.

Additionally, ANGPTL7 has been associated with various cancers potentially through its interaction with the WNT/-beta-catenin signaling pathway. Currently, there are no therapeutic approaches that target ANGPTL7.

[0056] Glaucoma is a leading cause of worldwide irréversible vision loss, characterized by progressive optic neuropathy. The most common form of glaucoma is primary open-angle 15 glaucoma (POAG), which is always accompanied by high intraocular pressure (IOP), the key risk factor for the pathogenesis of POAG. In some cases, prolonged useof dexamethasone (DEX) poses a high risk of elevated IOP and results in secondary glaucoma, which has many common characteristics with POAG. The pathogenesis of POAG can be deduced from the mechanisms underlying DEX-induced ocular hypertension. Understanding the DEX-induced molecular 20 mechanisms may assist in developing thérapies for glucocorticoid-induced glaucoma and POAG.

Additionally, high IOP is caused by increased outflow résistance of aqueous humor (AH). Accumulating evidence suggests that actin cytoskeletal rearrangement of the trabecular meshwork (TM) forming cross-linked actin networks is a crucial contributor to this increased résistance. Previous studies hâve found that the concentration of angiopoietin-like 7 (ANGPTL7) is increased 25 in glaucomatous AH and that overexpression of ANGPTL7 in the TM alters the components of the extracellular matrix (ECM). A recent study found that ANGPTL7 protein-altering variants exert a strong protective effect on glaucoma and suggested ANGPTL7 as a therapeutic target for glaucoma. Thus, ANGPTL7 may play a vital rôle in modulating TM’s ECM and regulating IOP.

[0057] In light of this, experiments were performed to détermine the rôle that ANGPTL7 may 30 play in the etiology of glaucoma and other related diseases affecting the optic nerve and retinal ganglion cells, and concomitantly, to develop a therapeutic platform based on modulating ANGPTL7 activity using anti-ANGPTL7 antibodies.

Définitions

[0058] To facilitate an understanding of the présent technology, a number of terms and phrases are defined below. Additional définitions are set forth throughout the detailed description.

[0059] The use of the terms “a” and “an” and “the” and “at least one” and similar referents in the context of describing the embodiments of the présent disclosure (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The use of the term “at least one” foilowed by a list of one or more items (for example, “at least one of A and B”) is to be construed to mean one item selected from the listed items (A or B) or any combination of two or more of the listed items (A and B), unless otherwise indicated herein or clearly contradicted by context. The ternis “comprising,” “having,” “including,” and “contaîning” are to be construed as open-ended terms (Le., meaning “including, but not limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the spécification as if it were individually recited herein. AU methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and ail examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the various embodiments ofthe présent disclosure, and does not pose a limitation on the scope of these embodiment unless otherwise claimed. No language in the spécification should be construed as indicating any nonclaimed element as essential to the practice of the various embodiments of the présent disclosure. [0060) As used herein, the term “or” is an inclusive “or” operator and is équivalent to the term “and/or” unless the context clearly dictâtes otherwise. The term “based on” is not exclusive and allows for being based on additional factors not described, unless the context clearly dictâtes otherwise. In addition, throughout the spécification, the meaning of “a,” “an,” and “the” include plural references. The meaning of “in” includes “in” and “on.”

[0061] The transitional phrase “consisting essentially of’ as used in claims in the présent application limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention, as discussed in In re Herz, 537 F,2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976). For example, a composition “consisting essentially of’ recited éléments may contain an unrecited contaminant at a level such that, though présent, the contaminant does not alter the function of the recited composition as compared to a pure composition, i.e., a composition “consisting of’ the recited components.

[0062] The term “one or more,” as used herein, refers to a number higher than one. For example, the term “one or more” encompasses any of the following: two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fïfteen or more, twenty or more, fifty or more, 100 or more, or an even greater number.

[0063] The term “one or more but less than a higher number,” “two or more but less than a higher number,” “three or more but less than a higher number,” “four or more but less than a higher number,” “five or more but less than a higher number,” “six or more but less than a higher number,” “seven or more but less than a higher number,” “eight or more but less than a higher number,” “nine or more but less than a higher number,” “ten or more but less than a higher 15 number,” “eleven or more but less than a higher number,” “twelve or more but less than a higher number,” “thirteen or more but less than a higher number,” “fourteen or more but less than a higher number,” or “fïfteen or more but less than a higher number” is not limited to a higher number. For example, the higher number can be 10,000, 1,000, 100, 50, etc. For example, the higher number can be approximately 50 (e.g., 50,49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 20 32,31,32,30,29,28,27,26,25,24,23,22,21,20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10,9,8,7,

6, 5, 4, 3 or 2).

[0064] The term “immunoglobulin” or “antibody,” as used herein, refers to a protein that is found in blood or other bodily fluids of vertebrates, which is used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. Typically, an immunoglobulin or 25 antibody is a protein that comprises at least one complementarity determining région (CDR). The CDRs form the “hypervariable région” of an antibody, which is responsible for antigen binding (discussed further below). A whole antibody typically consists of four polypeptides: two identical copies of a heavy (H) chain polypeptide and two identical copies ofa light (L) chain polypeptide. Each of the heavy chains contains one N-terminal variable (Vh) région and three C-terminal 30 constant (Chi, Ch2, and Chî) régions, and each light chain contains one N-terminal variable (Vl) région and one C-terminal constant (Cl) région. The light chains of antibodies can be assigned to one of two distinct types, either kappa (k) or lambda (λ), based upon the amino acid sequences of their constant domains. In a typical antibody, each light chain is linked to a heavy chain by disulfide bonds, and the two heavy chains are linked to each other by disulfide bonds. The light chain variable région is aligned with the variable région of the heavy chain, and the light chain 5 constant région is aligned with the first constant région of the heavy chain. The remaining constant régions of the heavy chains are aligned with each other.

|0065] The variable régions of each pair of light and heavy chains form the antigen binding site of an antibody. The Vu and Vl régions hâve the same general structure, with each région comprising four Framework (FW or FR) régions. The term “Framework région,” as used herein, 10 reFers to the relatively conserved amino acid sequences within the variable région which are located between the CDRs. There are Four Framework régions in each variable domain, which are desîgnated FRI, FRT, FR3, and FR4. The Framework régions Form the β sheets that provide the structural Framework oFthe variable région (see, e.g., C. A. Janeway et al. (eds.), Immunobiology, 5th Ed., Garland Publishing, New York, N.Y. (2001 )).

I5 [0066] The Framework régions are connected by three CDRs. As discussed above, the three CDRs, known as CDRl, CDR2, and CDR3, Form the “hypervariable région” oFan antibody, which is responsible For antigen binding. The CDRs Form loops connecting, and in some cases comprising part oF, the beta-sheet structure Formed by the Framework régions. While the constant régions oF the light and heavy chains are not directly involved in binding oF the antibody to an antigen, the 20 constant régions can influence the orientation oF the variable régions. The constant régions also exhibit various eFFector fonctions, such as participation in antibody-dependent complementmediated lysis or antibody-dependent cellular toxicity via interactions with eFFector molécules and cells.

[0067] As used herein, when an antibody or other entity (e.g., antigen binding domain) 25 “specifically recognizes” or “specifically binds” an antigen or epitope, it preFerentially recognizes the antigen in a complex mixture oF proteins and/or macromolecules, and binds the antigen or epitope with aFflnity which is substantially higher than to other entities not displaying the antigen or epitope. In this regard, “aFFinity which is substantially higher” means aFfinity that is high enough to enable détection oF an antigen or epitope which is distinguished From entities using a desîred 30 assay or measurement apparatus. Typically, it means binding aFflnity having a binding constant (Ka)oFat least I0⁷ M'¹ (e.g.,>10⁷ Μ-',>10⁸ M'¹, >IO^,,J Μ'',>Ι0¹¹ M’¹, >10¹² M’¹, >10¹³

M'¹, etc.). In certain such embodiments, an antibody is capable of binding different antigens so long as the different antigens comprise that particular epitope. In certain instances, for example, homologous proteins from different species may comprise the same epitope.

[0068| The terms “fragment of an antibody,” “antibody fragment,” and “antigen-binding 5 fragment” of an antibody are used interchangeably herein to refer to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (see, generally, Holliger et al., Nat. Biotech., 23(9): 1126-1129 (2005)). Any antigen-binding fragment of the antibody described herein is within the scope of the present disclosure. The antibody fragment desirably comprises, for example, one or more CDRs, the variable région (or portions thereof), the constant région (or portions thereof), or combinations thereof. Examples of antibody fragments include, but are not limited to, (i) a Fab fragment, which is a monovalent fragment consisting ofthe Vl, Vh, Cl, and Chi domains, (ii) a F(ab’)2 fragment, which is a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge région, (iii) a Fv fragment consisting of the V, and Vh domains of a single arm of an antibody, (iv) a Fab’ fragment, which results from breaking the disulfide bridge of an F(ab’)2 fragment using mild reducing conditions, (v) a disulflde-stabilized Fv fragment (dsFv), and (vi) a domain antibody (dAb), which is an antibody single variable région domain (Vu or Vl) polypeptide that specifically binds antigen.

|0069] The term “monoclonal antibody,” as used herein, refers to an antibody produced by a single clone of B lymphocytes that is directed against a single epitope on an antigen. Monoclonal antibodies typically are produced using hybridoma technology, as first described in Kohler and Milstein. Eur. J. Immunol., 5: 511-519 (1976). Monoclonal antibodies may also be produced using recombinant DNA methods (see, e.g., U.S. Patent 4,816,567), isolated from phage display antibody libraries (see, e.g., Clackson et al. Nature, 352: 624-628 (1991)); and Marks et al., J. Mo!. Biol., 222: 581-597 (1991)), or produced from transgenic mice carrying a fully human immunoglobulin system (see, e.g., Lonberg, Nat. Biotechnol., 23(9): 1117-25 (2005), and Lonberg, Handb. Exp. Pharmacol., 181: 69-97 (2008)). In contrast, “polyclonal” antibodies are antibodies that are secreted by different B cell lineages within an animal. Polyclonal antibodies are a collection of immunoglobulin molécules that recogntze multiple epitopes on the same antigen.

[0070] The terms “nucleic acid,” “polynucleotïde,” “nucléotide sequence,” and “oligonucleotide” are used interchangeably herein and refer to a polymer or oligomer of pyrimidine and/or purine bases, preferably cytosine, thymine, and uracil, and adenine and guanine,

respectively (See Albert L. Lehninger, Principies of Biochemistry, at 793-800 (Worth Pub. 1982)). The terms encompass any deoxyribonucleotide, ribonucleotide, or peptide nucleic acid component, and any Chemical variants thereof, such as methylated, hydroxymethylated, or glycosylated fornns of these bases. The polymers or oligomers may be heterogenous or 5 homogenous in composition, may be isolated from naturally occurring sources, or may be artificially or synthetically produced. In addition, the nucleic acids may be DNA or RNA. or a mixture thereof, and may exist permanently or transitionally in single-stranded or double-stranded form, including homoduplex, heteroduplex, and hybrid States. In some embodiments, a nucleic acid or nucleic acid sequence comprises other kinds of nucleic acid structures such as, for instance, 10 a DNA/RNA hélix, peptide nucleic acid (PNA), morpholino nucleic acid (see, e.g., Braasch and

Corey, Biochemistry, 7/(14): 4503-4510 (2002) and U.S. Patent 5,034,506), locked nucleic acid (LNA; see Wahlestedt et al., Proc. Natl. Acad. Sci. U.S.A., 97: 5633-5638 (2000)), cyclohexenyl nucleic acids (see Wang, J. Am. Chem. Soc., 122: 8595-8602 (2000)), and/or a ribozyme. The terms “nucleic acid” and “nucleic acid sequence” may also encompass a chain comprising non15 natural nucléotides, modified nucléotides, and/or non-nucleotide building blocks that can exhibit the same function as natural nucléotides (e.g., “nucléotide analogs”).

[0071 j The terms “peptide,” “polypeptide,” and “protein” are used interchangeably herein and refer to a polymeric form of amino acids of any length, which can include coded and non-coded amino acids, chemically or biochemically modified or derivatized amino acids, and polypeptides 20 having modified peptide backbones.

[0072] As used herein, a “nucleic acid” or “nucleic acid molécule” generally refers to any ribonucleic acid or deoxyribonucleic acid, which may be unmodified or modified DNA or RNA. “Nucleic acids” include, without limitation, single- and double-stranded nucleic acids. As used herein, the term “nucleic acid” also includes DNA as described above that contains one or more 25 modified bases. Thus, DNA with a backbone modified for stability or for other reasons is a “nucleic acid.” The term “nucleic acid” as it is used herein embraces such chemically, enzymatically, or metabolically modified forms of nucleic acids, as well as the Chemical forms of DNA characteristic of viruses and cells, including for example, simple and complex cells.

10073] The terms “oligonucleotide” or “polynucleotide” or “nucléotide” or “nucleic acid” refer to a molécule having two or more deoxyribonucleotides or ribonucleotides, preferably more than three, and usually more than ten. The exact size will dépend on many factors, which in turn dépends on the ultimate function or use of the oligonucleotide. The oligonucleotide may be generated in any manner, including Chemical synthesis, DNA réplication, reverse transcription, or a combination thereof. Typical deoxyribonucleotides for DNA are thymine, adenine, cytosine, and guanine. Typical ribonucleotides for RNA are uracil, adenine, cytosine, and guanine.

[0074| The terms “complementary” and “complementarity” refer to nucléotides (e.g., I nucléotide) or polynucleotides (e.g., a sequence of nucléotides) related by the base-pairing rules. For example, the sequence 5’-A-G-T-3’ is complementary to the sequence 3'-T-C-A-5'. Complementarity may be “partial,” in which only some of the nucleic acids’ bases are matched according to the base pairing rules. Or, there may be “complété” or “total” complementarity between the nucleic acids. The degree of complementarity between nucleic acid strands affects the efficiency and strength of hybridization between nucleic acid strands. This is of particular importance in amplification reactions and in détection methods that dépend upon binding between nucleic acids.

[0075| The terni “gene” refers to a nucleic acid (e.g., DNA or RNA) sequence that comprises coding sequences necessary for the production of an RNA, or of a polypeptide or its precursor. A functional polypeptide can be encoded by a full-length coding sequence or by any portion of the coding sequence as long as the desired activity or functional properties (e.g., enzymatic activity, ligand binding, signal transduction, etc.) of the polypeptide are retained. The terni “portion” when used in reference to a gene refers to fragments of that gene. The fragments may range in size from a few nucléotides to the entire gene sequence minus one nucléotide. Thus, “a nucléotide comprising at least a portion of a “gene” may comprise fragments of the gene or the entire gene. |0076| The term “gene” also encompasses the coding régions of a structural gene and includes sequences located adjacent to the coding région on both the 5' and 3' ends, e.g., for a distance of about l kb on either end, such that the gene corresponds to the length of the full-length mRNA (e.g., comprising coding, regulatory, structural and other sequences). The sequences that are located 5' of the coding région and that are présent on the mRNA are referred to as 5' non-translated or untranslated sequences. The sequences that are located 3' or downstream of the coding région and that are présent on the mRNA are referred to as 3' non-translated or 3' untranslated sequences. The term “gene” encompasses both cDNA and genomic forms of a gene. In some organisms (e.g., eukaryotes), a genomic form or clone of a gene contains the coding région interrupted with noncoding sequences termed “introns” or “intervening régions” or “intervening sequences.” Introns are segments of a gene that are transcnbed into nuclear RNA (hnRNA); introns may contain regulatory éléments such as enhancers. Introns are removed or “spliced out” from the nuclear or primary transcript; introns therefore are absent in the messenger RNA (mRNA) transcript. The mRNA functions during translation to specify the sequence or order of amino acids in a nascent polypeptide.

|00771 In addition to containing introns, genomic forms of a gene may also include sequences located on both the 5' and 3' ends of the sequences that are present on the RNA transcript. These sequences are referred to as “flanking” sequences or régions (these flanking sequences are located 5' or 3' to the non-translated sequences present on the mRNA transcript). The 5’ flanking région may contain regulatory sequences such as promoters and enhancers that control or influence the transcription of the gene. The 3* flanking région may contain sequences that direct the termination of transcription, posttranscriptional cleavage, and polyadenylation.

[00781 The term “wild-type” when made in reference to a gene refers to a gene that has the characteristics of a gene isolated from a naturally occurring source. The term “wild-type” when made in reference to a gene product refers to a gene product that has the characteristics of a gene product isolated from a naturally occurring source. The term “wild-type” when made in reference to a protein refers to a protein that has the characteristics of a naturally occurring protein. The term “naturally-occurring” as applied to an object refers to the fact that an object can be found in nature. For example, a polypeptide or polynucleotide sequence that is present in an organism (including viruses) that can be isolated from a source in nature, and which has not been intentionally modified by the hand of a person in the laboratory is naturally-occurring, A wild-type gene is often that gene or allele that is most frequently observed in a population and is thus arbitrarily desîgnated the “normal” or “wild-type” form of the gene. In contrast, the term “modified” or “mutant” when made in reference to a gene or to a gene product refers, respectively, to a gene or to a gene product that display s modifications in sequence and/or functional properties (e.g., altered characteristics) when compared to the wild-type gene or gene product. It is noted that naturally-occurring mutants can be isolated; these are identified by the fact that they hâve altered characteristics when compared to the wild-type gene or gene product.

[0079] The term “allele” refers to a variation of a gene; the variations include but are not limited to variants and mutants, polymorphie loci, and single nucléotide polymorphie loci, frameshift. and splice mutations. An allele may occur naturally in a population, or it might arise during the lifetime of any particular îndividual of the population.

[0080| Thus, the terms “variant” and “mutant” when used in reference to a nucléotide sequence refer to a nucleic acid sequence that differs by one or more nucléotides from another, usually 5 related, nucléotide acid sequence. A “variation” is a différence between two different nucléotide sequences; typically, one sequence is a reference sequence.

|00811 The terms “immunogen” and “antigen” are used interchangeably herein and refer to any molécule, compound, or substance that induces an immune response in an animal (e.g., a mammal). An “immune response” can entail, for example, antibody production and/or the activation of immune effector cells. An antigen in the context of the disclosure can comprise any subunit, fragment, or epitope of any proteinaceous or non-proteinaceous (e.g., carbohydrate or lipid) molécule that provokes an immune response in a mammal. The term “epitope” refers to a sequence of an antigen that is recognized by an antibody or an antigen receptor. Epitopes also are referred to in the art as “antigenic déterminants.” In certain embodiments, an epitope is a région of

I5 an antigen that is specifically bound by an antibody. In certain embodiments, an epitope may include chemically active surface groupings of molécules such as amino acids, sugar side chains, phosphoryl, or sulfonyl groups. In certain embodiments, an epitope may hâve spécifie threedimensional structural characteristics (e.g., a “conformational” epitope) and/or spécifie charge characteristics. The antigen can be a protein or peptide of viral, bacterial, parasitic, fungal, 20 protozoan. prion, cellular, or extracellular orîgin, which provokes an immune response in a mammal, preferably leading to protective immunity.

10082] A “pharmaceutically acceptable carrier” as used herein generally refers to an ingrédient in a pharmaceutical formulation, other than an active ingrédient, which is nontoxic to a subject. A pharmaceutically acceptable carrier includes. but is not limited to, a buffer, excipient, stabilizer, 25 or preservative.

|00831 The term “pharmaceutical formulation” as used herein generally refers to a préparation which is in such form as to permit the biological activity of an active ingrédient (e.g., an antiANGPTL7 antibody, an antibody conjugale, a fusion protein, or a polymeric formulation) contained therein to be effective, and which contains no additional components which are 30 unacceptably toxic to a subject to which the formulation would be administered.

|0084| As used herein, “treatment” (and grammatical variations thereof such as “treat” or “treating”) generally refers to clinical intervention in an attempt to alter the natural course of the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Désirable effects of treatment include, but are not limited to, preventing 5 occurrence or récurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological conséquences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease State, and remission or improved prognosis. In some embodiments, anti-ANGPTL7 antibodies of the présent disclosure or other compositions that include an anti-ANGPTL7 antibody of the présent disclosure (e.g., an antibody 10 conjugale, a fusion protein. or a polymeric formulation) are used to delay development of a disease or to slow the progression of a disease.

[0085] The term “half-life” as used herein generally refers to the time required for the concentration of a substance (e.g., an anti-ANGPTL7 antibody, an antibody conjugale, a fusion protein (e.g., a Fab fusion protein), or a polymeric formulation) to decrease by one-half, in vivo 15 (e.g., in the eye (e.g., the vitreous)) or in vitro.

[0086] An “effective amount” of an agent, e.g., a pharmaceutical formulation, as used herein generally refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic resuit.

[0087] An “individual” or “subject” is a mammal. Mammals include, but are not limited to, 20 domesticated animais (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and nonhuman primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the individual or subject is a human. A “subject” may be a “patient.”

Anti-ANGPTL7 Antibodies

[0088| Embodiments of the présent disclosure relate to the treatment and/or prévention of 25 glaucoma and other ocular diseases affecting the optic nerve and retinal ganglion cells. In particular, the présent disclosure provides novel therapeutic antibodies that target angiopoietinrelated protein 7 (ANGPTL7) as a means for reducing intraocular pressure (IOP) and/or increasing outflow facility, lhereby preventing optic nerve damage and/or restoring vision.

[0089] As described further herein, embodiments of the présent disclosure include an antibody, 30 or an antigen binding fragment thereof, which specifîcally binds human Angiopoietin-Like Protein (ANGPTL7), optionally wherein said human ANGPTL7 is a polypeptide which comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 370 to 374.

[0090] In some embodiments, the antibody, or an antigen binding fragment thereof, exhibits any one or more the following functional characteristics: increases outflow facility compared to a control when administered to the eye of a subject, optionally wherein the control is vehicle treatment. dexamethasone treatment. ANGPTL7 protein treatment. or ANGPTL7 protein with an isotype control antibody treatment; and/or binds to ANGPTL7 with a Kdoî about l OOnM or lower; and/or binds to the same epitope on ANGPTL7 as an antibody comprising the VH and VL sequences of any one of the exemplary antibodies the sequences of which are provided in Table 11; and/or competes for binding to ANGPTL7 with an antibody comprising the VH and VL sequences of any one of the exemplary antibodies the sequences of which are provided in Table IL

[0091] In some embodiments, the antibody, or an antigen binding fragment thereof, is monoclonal, optionally recombinant. In some embodiments, the antibody, or an antigen binding fragment thereof, is human, humanized, or chimeric.

[0092] In some embodiments, the antibody, or an antigen binding fragment thereof, is a full length antibody, a single chain antibody, a single chain variable fragment (scFv), a variable fragment (Fv), a fragment antigen-binding région (Fab), a Fab-C, a Fab’-SH, a (Fab’)2, a singledomain antibody (sdAb), a VHH antibody, a nanobody, acamelid-derived single-domain antibody, a shark IgNAR-derived single-domain antibody fragment (VNAR), a diabody, a triabody, an anticalin or an aptamer, optionally wherein the antibody is a full length antibody comprising an Fc région such as a human IgG 1, IgG2, lgG3 or IgG4 région.

|0093| In some embodiments, the antibody, or an antigen binding fragment thereof, is conjugated to at least one additional moiety, optionally selected from: an antigen binding moiety, such as an antibody or antigen-binding fragment thereof, which is capable of spécifie binding to a target which is not human ANGPTL7, preferably wherein said target is expressed in the human eye; a therapeutic or cytotoxic moiety; a détection moiety; a purification moiety; a half-life extension moiety, optionally a polypeptide that is at least 20 amino acids in length and comprises any combination of G, A, S T, E, and P residue, which polypeptide is conjugated to the C- or Nterminus of the antibody.

[0094] In some embodiments, the antibody, or an antigen binding fragment thereof is a polypeptide comprising: one, two or ail three HCDRs of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also one, two or ail three of the corresponding LCDRs of the exemplary antibody; and/or a VH sequence havîng at least 90% 5 identity to the VH sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also a VL sequence having at least 90% identity to the corresponding VL sequence of the exemplary antibody, preferably wherein variation is not permitted in the HCDRs or LCDRs; and/or ail six CDRs of any of the exemplary antibodies exemplary antibodies the sequences of which are provided in Table 11; and/or the VH and VL 10 sequences of any one of the exemplary antibodies the sequences of which are provided in Table

11; and/or the full length heavy chain (VH + constant) sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also the corresponding full length light chain (VL + constant) sequence of the exemplary' antibody.

[0095] Embodiments of the présent disclosure also include a polynucleotide encoding an 15 antibody, or an antigen binding fragment thereof, of any of the preceding paragraphe, optionally wherein said polynucleotide comprises or consists of a nucleic acid sequence having at least 70%, 80%, 90% or 100% identity to a nucleic acid sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11.

[0096] Embodiments of the présent disclosure also include an expression vector comprising 20 the polynucleotide of the preceding paragraph, which is optionally an adeno-associated virus (AAV) vector, a lentiviral (LV) vector, a herpes simplex virus (HSV) vector, or a retrovirus vector. |0097| Embodiments of the présent disclosure also include a pharmaceutical composition comprising an antibody, or an antigen binding fragment thereof, a polynucleotide, or a vector according to any one of the preceding paragraphs, and optionally: at least one pharmaceutically 25 acceptable carrier, diluent or preservative; and/or at least one additional active ingrédient. In some embodiments, the pharmaceutical composition is suitable for ocular administration to a subject, optionally by delivery using a conjunctival insert, a contact lens, a gel, a nanoparticle, a mucoadhesîve polymer, an ointment, a solution, a suspension, eye drops, and/or an implant, preferably by injection into the vitreous fluid.

|0098| Embodiments of the présent disclosure also include the antibody, or an antigen binding fragment thereof, the polynucleotide, the vector, or the compositions of any of the preceding paragraphs, for use as a médicament, optionally for use in a method of treating a disease of the eye in a subject. In some embodiments, the disease is characterized by increased intraocular pressure and/or reduced outflow facility in the eye of the subject. In some embodiments, the method comprises ocular administration of the antibody, preferably by injection into the vitreous fluid. and wherein said administration preferably relieves at least one symptom in the subject selected from eye pain, eye pressure, headaches, rainbow-colored halos around lights, low vision, blurred vision, narrowed vision, impaired peripheral vision, blind spots, nausea, vomiting, and red eyes. In some embodiments, the disease is glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells, optionally wherein said glaucoma is primary or glucocorticoid-induced glaucoma.

[0099] As described further herein, anti-ANGPTL7 antibodies were generated, and their structural and functional properties were elucidated. Based on these data, embodiments of the présent disclosure include anti-ANGPTL7 antibodies, or antigen-binding fragments thereof. that are comprised of a heavy chain variable région (VH) comprising complementarity determining régions (CDRs) HCDRI, HCDR2, and HCDR3, and a light chain variable région (VL) comprising complementarity determining régions (CDRs) LCDRl, LCDR2, and LCDR3. In some embodiments, the HCDRl comprises one of the following amino acid sequences: (a) X|YX₂IX₃ (SEQ ID NO: l ), wherein Xi is S or D; X₂ is G or Y; X3 is S or H; (b) TSGVGVG (SEQ ID NO: 18); (c) X1X2X3MX4 (SEQ ID NO: 27), wherein X, is V, S, D, or T; X₂ is Y, H, or F; X₃ is D, G, S, or A; X4 is H, S, or N; or (d) SX1SX2YWX3 (SEQ ID NO: 74), wherein Xi is S or G; X₂ is S or Y; X₃ is G or S. In some embodiments, the HCDR2 comprises one of the following amino acid sequences: (a) WIX1X2X3X4GX5TX6YAQX7X8X9G (SEQ IDNO: 7), wherein Xi is S, I, or N; X₂ is A or P; X₃ is Y or N; X4 is N or T; X5 is N or A; Xô is N or K; X7 is N or K; Xs is L or F; Xg is R or Q; (b) LIYWNDDKXiYSPSLKS (SEQ ID NO: 21), wherein Xi is R or Q; (c) XiX₂X₃X4X5X6X7X8X9XioXi 1X12X13X14X15G (SEQ ID NO: 43), wherein X] is G, T, S, A, V, H, or I; X? is 1 or M; X₃ is D, N, T, S, or G; X₄ is P, W, S, G, or Y; X₅ is D, A, N, S, or Y; X₆ is G or S; X₇ is D, G, Y, S, I, or N; X₈ is T, S, N, I, Y, or D; X₉ is Y, T, F, Μ. K, G, or I; X10 is Y, G, or F; Xi। is P, Y, or A; X|₂ is G, D, or A; X[₃ is S or D; X14 is V, L, or S; X15 is K or M; or (d) X1IYYSGSTX2SNPSLKS (SEQ ID NO: 78) wherein Xi is S, or Y; X₂ is Y or S. In some embodiments, the HCDR3 comprises one ofthe following amino acid sequences: (a) SEQ ID NOs: 13-17; (b) X)X2X₃X4X5X6FFDX7 (SEQ ID NO: 24) wherein Xi is S, D, or N; X₂ is Y or P; X₃ is G or D; X4 is D or Y; X; is Y or G; Xô is W or D; X7 is L or Y; (c) SEQ ID NOs: 59-73; or (d) * 36

X1X2X3X4GX5X6X7X8X9Y (SEQ ID NO: 82) wherein X, is Q or A; X₂ is Y or K; X₃ is I or W;

X4 is S or E; X5 is T or D; X& is E or Y; X₇ is Y or F; Xs is F or D; Xg is Q or Y.

|00100] In addition to the above HCDRl, HCDR.2, and HCDR3 sequences, anti-ANGPTL7 antibodies of the présent disclosure include an LCDRl comprising an amino acid sequence of any 5 ofSEQIDNOs: 87-97, SEQ ID NOs: 123-I27, or SEQ ID NOs: I4I-149; the LCDR2 comprises an amino acid sequence of any of SEQ ID NOs: 99-109, SEQ ID NOs: 129-I33, or SEQ IDNOs 151-159; and the LCDR3 comprises an amino acid sequence of any of SEQ ID NOs: 111-121, SEQ IDNOs: I35-I39, or SEQ ID NOs: 16I-169.

|00101| In some embodiments, the présent disclosure provides anti-ANGPTL7 antibodies, or I0 antigen-binding fragments thereof, that include a VH comprising complementarity determining régions HCDRl, HCDR2, and HCDR3, and a VL comprising complementarity determining régions LCDRl, LCDR2, and LCDR3. In some embodiments, the LCDRl comprises one of the following amino acid sequences: (a) RASQX1IX2X3X4LX5 (SEQ ID NO: 86), wherein Xj is G or S; X2 is S, R, or Y; X₃ is S, N, or I; X₄ is W, D, or Y; X₅ is A, G, or N; (b) 15 RSSQSLX1X2SX3X4X5X6YLX7 (SEQ ID NO: 122), wherein Xi is L or V; X₂ is H, Y, or F; X3 is

N or D; X₄ is R or G; X₅ is Y or N; X₆ is N or T; X₇ is D or N; or (c) RASQSVSXÆX3X4A (SEQ ID NO: 140), wherein Xi is S, N, or R; X₂ is Y or S; X₃ is L or Y; X₄ is A or L. In some embodiments, the LCDR2 comprises one ofthe following amino acid sequences: (a) AX1SSLX2S (SEQ ID NO: 98), wherein Xi is A or T; X₂ is Q or P; (b) X1X2SNRX3S (SEQ ID NO: 128), 20 wherein X, is L, K, or E; X₂ is G or V; X₃ is A or D; or (c) X1ASX2RAT (SEQ ID NO: 150), wherein X; is D or G; X2 is N, S, or T. In some embodiments, the LCDR3 comprises one of the following amino acid sequences: (a) X1QX2X3X4X5PX6X7 (SEQ ID NO: 110), wherein Xi is L or Q; X₂ is A, H, S, or D; X₃ is N, F, or Y; X₄ is S, T, or N; X₅ is F, Y, or T; X₆ is W, L, I, P, or Y; X₇ is T or Y; (b) MQXiX2X₃X₄PX₅T (SEQ ID NO: 134), wherein Xi is T or G; X₂ is L or T; X₃ is 25 Q or H; X₄ is T or W; X₅ is Y or W; or (c) QQXiX2X₃X₄XsXôT (SEQ ID NO: 160), wherein Xi is

R, Y, or G; X₂ is S, G, or Q; X₃ is N, S, or V; X₄ is W, S, or I; Xs is P or L; X₆ is L, S, P, or T.

[00102| In addition to the above LCDRl, LCDR2, and LCDR3 sequences, anti-ANGPTL7 antibodies of the présent disclosure include an HCDRl comprising an amino acid sequence of any of SEQ ID NOs: 2-6, SEQ ID NOs: 19-20, SEQ ID NOs: 28-42, or SEQ ID NOs: 75-77; the 30 HCDR2 comprises an amino acid sequence of any of SEQ ID NOs: 8-12, SEQ ID NOs: 22-23,

SEQ ID NOs 44-58, or SEQ ID NOs: 79-81; and the HCDR3 comprises an amino acid sequence ofany ofSEQ ID NOs: 13-17, SEQ IDNOs: 25-26, SEQ IDNOs: 59-73, or SEQ ID NOs: 83-85. [00103] In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 2, the HCDR2 ofSEQ IDNO: 8, and the HCDR3 ofSEQ IDNO: 13. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 3, the HCDR2 ofSEQ ID NO: 9, and the HCDR3 of SEQ ID NO: I4. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 4, the HCDR2 of SEQ ID NO: 10, and the HCDR3 of SEQ ID NO: 15. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 5, the HCDR2 ofSEQ ID NO: 11, and the HCDR3 ofSEQ ID NO: 16. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 6, the HCDR2 ofSEQ ID NO: 12, and the HCDR3 of SEQ ID NO: 17. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 7, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 14, and the HCDR3 of SEQ ID NO: 20. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 19, the HCDR2 comprises the amino acid sequence ofSEQ ID NO: 22, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 20, the HCDR2 ofSEQ ID NO: 23, and the HCDR3 ofSEQ ID NO: 26. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 28, the HCDR2 ofSEQ ID NO: 44, and the HCDR3 of SEQ ID NO: 59. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 29, the HCDR2 ofSEQ ID NO: 45, and the HCDR3 of SEQ ID NO: 60. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 30, the HCDR2 ofSEQ IDNO: 46, and the HCDR3 ofSEQ ID NO: 61. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDR I ofSEQ ID NO: 31, the HCDR2 ofSEQ IDNO: 47, and the HCDR3 ofSEQ IDNO: 62. In someembodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 32, the HCDR2 of SEQ ID NO: 48, and the HCDR3 ofSEQ ID NO: 63. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ IDNO: 33, the HCDR2 ofSEQ IDNO: 49, and the HCDR3 ofSEQ IDNO: 64. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI ofSEQ ID NO: 34, the HCDR2 of SEQ ID NO: 50, and the HCDR3 of SEQ ID NO: 65. In some embodiments, an antiANGPTL7 antibody comprises the HCDRI ofSEQ IDNO: 35, the HCDR2 ofSEQ IDNO: 5I, and the HCDR3 ofSEQ ID NO: 66. In some embodiments, an anti-ANGPTL7 antibody comprises

the HCDRl of SEQ ID NO: 36, the HCDR2 of SEQ ID NO: 52, and the HCDR3 of SEQ ID NO: 67. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRI of SEQ ID NO: 37, the HCDR2 of SEQ ID NO: 53, and the HCDR3 of SEQ ID NO: 68. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 38, the HCDR2 of SEQ ID NO:

54, and the HCDR3 of SEQ ID NO: 69. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 39, the HCDR2 of SEQ ID NO: 55, and the HCDR3 of SEQ ID NO: 70. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 40, the HCDR2 of SEQ ID NO: 56, and the HCDR3 of SEQ ID NO: 7I. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 41, the HCDR2 10 of SEQ ID NO: 57, and the HCDR3 of SEQ ID NO: 72. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 42, the HCDR2 of SEQ ID NO: 58, and the HCDR3 of SEQ ID NO: 73. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 75, the HCDR2 of SEQ ID NO: 79, and the HCDR3 of SEQ ID NO: 83. In some embodiments, an anti-ANGPTL7 antibody comprises the HCDR l of SEQ ID NO: 76, the 15 HCDR2 of SEQ ID NO: 80, and the HCDR3 of SEQ ID NO: 84. In some embodiments, an antiANGPTL7 antibody comprises the HCDRl of SEQ ID NO: 77, the HCDR2 of SEQ ID NO: 8I and the HCDR3 of SEQ ID NO: 85.

[00104J In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO: 87, the LCDR2 of SEQ ID NO: 99, and the LCDR3 of SEQ ID NO: lll. In some 20 embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO: 88, the LCDR2 of SEQ ID NO: I00, and the LCDR3 of SEQ ID NO: Il2. In some embodiments, an antiANGPTL7 antibody comprises the LCDRl of SEQ ID NO: 89, the LCDR2 of SEQ ID NO: 101, and the LCDR3 of SEQ ID NO: Il3. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO. 90, the LCDR2 of SEQ ID NO: 102, and the LCDR3 of 25 SEQ ID NO: 114. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ IDNO: 91, the LCDR2 of SEQ IDNO: 103, and the LCDR3 ofSEQ ID NO: 115. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl ofSEQ ID NO: 92, the LCDR2 of SEQ ID NO: 104, and the LCDR3 of SEQ ID NO: 116. In some embodiments, an antiANGPTL7 antibody comprises the LCDRl ofSEQ ID NO: 93, the LCDR2 ofSEQ IDNO: 105, 30 and the LCDR3 of SEQ ID NO: 117. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl ofSEQ IDNO: 94, the LCDR2 ofSEQ IDNO: 106, and the LCDR3 of

SEQ ID NO: 118. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQIDNO: 95, the LCDR2 ofSEQ ID NO: 107, and the LCDR3 ofSEQIDNO: l 19. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO: 96, the LCDR2 of SEQ ID NO: 108, and the LCDR3 of SEQ ID NO: 120. In some embodiments, an antiANGPTL7 antibody comprises the LCDRl of SEQ ID NO: 97, the LCDR2 of SEQ ID NO: 109, and the LCDR3 of SEQ ID NO: I2l. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRI of SEQ ID NO: 123, the LCDR2 of SEQ ID NO: 129, and the LCDR3 of SEQ ID NO: I35. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO: I24, the LCDR2 of SEQ ID NO: 130, and the LCDR3 of SEQ ID NO: 136. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ IDNO: 125, the HCDR2 of SEQ ID NO: I3l, and the LCDR3 of SEQ ID NO: 137. In some embodiments, an antiANGPTL7 antibody comprises the LCDRl of SEQ ID NO: I26, the LCDR2 of SEQ ID NO: 132, and the LCDR3 of SEQ ID NO: 138. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl ofSEQIDNO: I27, the LCDR2 ofSEQ IDNO: I33, andthe LCDR3 of SEQ ID NO: 139. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQIDNO: I4l, the LCDR2 of SEQ ID NO: I5l,and the LCDR3 of SEQ ID NO: I6l. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDR I of SEQ ID NO: I42, the LCDR2 of SEQ ID NO: 152, and the LCDR3 of SEQ ID NO: 162. In some embodiments, an antiANGPTL7 antibody comprises the LCDRl ofSEQIDNO: 143, the LCDR2 ofSEQIDNO: 153, and the LCDR3 of SEQ ID NO: 163. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO: I44, the LCDR2 of SEQ ID NO: 154, and the LCDR3 of SEQ ID NO: 164. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQ ID NO: I45, the LCDR2 of SEQ ID NO: 155, and the LCDR3 SEQ ID NO: 165. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl ofSEQ IDNO: 146, the LCDR2 of SEQ ID NO: 156, and the LCDR3 of SEQ ID NO; I66. In some embodiments, an antiANGPTL7 antibody comprises the LCDRl ofSEQIDNO: 147, the LCDR2 ofSEQ IDNO: 157, and the LCDR3 of SEQ ID NO: 167. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl ofSEQ ID NO: 148, the LCDR2 ofSEQ IDNO: 158, and the LCDR3 of SEQ ID NO: 168. In some embodiments, an anti-ANGPTL7 antibody comprises the LCDRl of SEQIDNO: 149, the LCDR2 ofSEQ ID NO: 159, and the LCDR3 ofSEQ ID NO: 169.

[00105] In some embodiments, the VH of the anti-ANGPTL7 antibodies of the présent disclosure includes an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to any of: (a) SEQ ID NOs: 170-174; (b) SEQ ID NOs: 190-191; (c) SEQ ID NOs: 198-212; or (d) SEQ ID NOs: 258-260. In some embodiments, the VL ofthe anti-ANGPTL7 antibodies of the présent disclosure includes an amino acid sequence that is at least 90% identical (e.g., at least 9] %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to any of: (a) SEQ ID NOs: 180-184; (b) SEQ ID NOs: 194-195; (c) SEQ ID NOs: 228-242; or (d) SEQ ID NOs: 264-266.

(00106] In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 170 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 180. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%. at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 171 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 181. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 172 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 182. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 173 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 183. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%,

4l at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 174 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 184. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 190 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 194. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 191 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 195. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 198 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%. at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 228. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 199 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 229. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 200 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 230. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 201 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 231. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 202 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 232. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 203 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 233. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 204 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 234. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 205 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 235. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 206 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 236. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 207 and the VL comprises an atnino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 237. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 208 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 238. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 209 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 239. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 210 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 240. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%. or 100% identical) to SEQ ID NO: 211 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 241. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%. at least 92%, at least 93%. at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 212 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 242. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 258 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 264. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91 %. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 259 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%. at least 99%, or 100% identical) to SEQ ID NO: 265. In some embodiments, the VH comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 260 and the VL comprises an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ IDNO:266.

[00107] Nucleic acid or amino acid sequence “identity,” as described herein, can be determined by comparing a nucleic acid or amino acid sequence of interest to a reference nucleic acid or amino acid sequence. A number of mathematical algorithms for obtaining the optimal alignment and calculating identity between two or more sequences are known and incorporated into a number of available software programs. Examples of such programs include CLUSTAL-W, T-Coffee, and ALIGN (for alignment of nucleic acid and amino acid sequences), BLAST programs (e.g., BLAST 2.1, BL2SEQ, and later versions thereof) and FASTA programs (e.g., FASTA3x, FAS™, and SSEARCH) (for sequence alignment and sequence similarity searches). Sequence alignment algorithms also are disclosed in, for example, Altschul et al., J. Molecular Biol., 215(3): 403-410 (1990), Beigert et al., Proc. Natl. Acad. Sci. USA, 106(10): 3770-3775 (2009), Durbin et al., eds., Biological Sequence Analysis: Probahilistic Models of Proteins and Nucleic Acids, Cambridge University Press, Cambridge, UK (2009), Soding. Bioinformatics, 21(7): 951 -960 (2005), Altschul et al., Nucleic Acids Res., 25(17): 3389-3402 (1997), and Gusfield, Algorithms on Strings, Trees andSequences, Cambridge University Press, Cambridge UK (1997)).

[00108] As would be recognized by one of ordinaiy skill in the art based on the présent disclosure. one or more amino acids of the aforementioned anti-ANGPTL7 antibodies, or antigen fragments thereof, can be replaced or substituted with a different amino acid. An amino acid “replacement” or “substitution” refers to the replacement of one amino acid at a given position or residue by another amino acid at the same position or residue within a polypeptide sequence. Amino acids are broadly grouped as “aromatic” or “aliphatic.” An aromatic amino acid includes an aromatic ring. Examples of “aromatic” amino acids include histidîne (H or His), phenylalanine (F or Phe), tyrosine (Y or Tyr), and tryptophan (W or Trp). Non-aromatic amino acids are broadly grouped as “aliphatic.” Examples of “aliphatic” amino acids include glycine (G or Gly), alanine (A or Ala), valine (V or Val), leucine (L or Leu), isoleucine (I or Ile), méthionine (M or Met), serine (S or Ser), threonine (T or Thr), cysteine (C or Cys), proline (P or Pro), glutamic acid (E or Glu), aspartic acid (A or Asp), asparagine (N or Asn), glutamine (Q or Gin), lysine (K or Lys), and arginine (R or Arg). Aliphatic amino acids may be sub-divided into four sub-groups. The “large aliphatic non-polar sub-group” consists of valine, leucine, and isoleucine. The “aliphatic slightlypolar sub-group” consists of méthionine, serine, threonine, and cysteine. The “aliphatic polar/charged sub-group” consists of glutamic acid, aspartic acid, asparagine, glutamine, lysine, and arginine. The “small-residue sub-group” consists of glycine and alanine. The group of charged/polar amino acids may be sub-divided into three sub-groups: the “positively-charged subgroup” consisting of lysine and arginine, the “negatively-charged sub-group” consisting of glutamic acid and aspartic acid, and the “polar sub-group” consisting of asparagine and glutamine. Aromatic amino acids may be sub-divided into two sub-groups: the “nitrogen ring sub-group” consisting of histidîne and tryptophan and the “phenyl sub-group” consisting of phenylalanine and tyrosine.

|00109] The amino acid replacement or substitution can be conservative, semi-conservative, or non-conservative. The phrase “conservative amino acid substitution” or “conservative mutation” refers to the replacement of one amino acid by another amino acid with a common property. A functional way to define common properties between individual amino acids is to analyze the normalized frequencies of amino acid changes between corresponding proteins of homologous organisms (Schulz and Schirmer, Principles of Protein Structure, Springer-Verlag, New York (1979)). According to such analyses, groups of amino acids may be defined where amino acids within a group exchange preferentially with each other, and therefore resemble each other most in their impact on the overall protein structure. Examples of conservative amino acid substitutions include substitutions of amino acids within the sub-groups described above, for example, lysine for arginine and vice versa such that a positive charge may be maintained, glutamic acid for aspartic acid and vice versa such that a négative charge may be maintained, serine for threonine such that a free -OH can be maintained, and glutamine for asparagine such that a free -NH₂ can be maintained. “Semi-conservative mutations” include amino acid substitutions of amino acids within the same groups listed above, but not within the same sub-group. For example, the substitution of aspartic acid for asparagine, or asparagine for lysine, involves amino acids within the same group, but different sub-groups. “Non-conservative mutations” involve amino acid substitutions between different groups, for example, lysine for tryptophan, or phenylalanine for serine, etc.

[00110] In addition, one or more amino acids can be inserted into the anti-ANGPTL7 antibodies, or antigen-binding fragments thereof (e.g., insertion into the heavy and/or light chain variable région amino acid sequence). Any number of suitable amino acids can be inserted into the amino acid sequence of the antibody or antigen-binding fragment thereof. In this respect, at least one amino acid (e.g., 2 or more, 5 or more, or 10 or more amino acids), but not more than 20 amino acids (e.g., 18 or less, 15 or less, or 12 or less amino acids), can be inserted into the amino acid sequence of the antibody or antigen-binding fragment thereof. For example, I -10 amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids) may be inserted into the amino acid sequence ofthe monoclonal antibody or antigen-binding fragment thereof. In this respect, the amino acid(s) can be inserted into an antibody or antigen-binding fragment thereof in any suitable location. Preferably, the amino acid(s) are inserted into a CDR (e.g., CDR1, CDR2, or CDR3) of the antibody or antigen-binding fragment thereof.

[00111] The amino acid sequences of the anti-ANGPTL7 antibodies, or antigen-binding fragments thereof, are not limited to the spécifie amino acid sequences described herein. Indeed, an anti-ANGPTL7 antibody or antigen-binding fragment thereof can comprise any heavy chain polypeptide or light chain polypeptide that competes with the anti-ANGPTL7 antibodies or antigen-binding fragments thereof for conformational binding to ANGPTL7. Antibody compétition can be assayed using routine peptide compétition assays such as, for example, ELISA, Western blot, or immunohistochemistry methods (see, e.g., U.S. Patents 4,828,981 and 8,568,992; and Braitbard et al., Proteome Sci., 4: 12 (2006)),

[00112] An anti-ANGPTL7 antibody of the present disclosure may be a whole antibody, or an antigen-binding fragment of a whole antibody. As defined herein, antigen-binding antibody fragments encompassed by the present disclosure include, but are not limited to, F(ab’)₂, Fab’,

Fab, Fv, scFv, dsFv, dAb, and single chain binding polypeptides. Antibody fragments and their therapeutic utility are further described in. e.g., Nelson, A.L., MAbs. 2010 Jan-Feb; 2(l): 77-83; Joosten et al., Microbial Cell Factories volume 2, Article number: l (2003); and Bâtes A, Power CA., Antibodies (Basel). 2019;8(2):28; doi:l0.3390/antib8020028). In some embodiments. the anti-ANGPTL7 antigen-binding fragment is a single-chain variable fragment (scFv), which is an engineered antibody generated by the fusion of the heavy (VH) and light chains (VL) of immunoglobulins through a short polypeptide linker. Single chain variable domain (Fv) fragments (scFv) are used in the art in a variety of clinical and therapeutic applications, primarily due to their improved pharmacokinetic properties as compared to the parent monoclonal antibodies and the relative ease of producing them in large quantities at low cost (Monnier et al., Antibodies 2013, 2(2), 193-208; doi.org/IO.339O/antib2O20193; Safdari et al., Mol Med. 2016; 22: 258-270; and Lu, R., Hwang, Y., Liu, I. et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 27, l (2020). https://doi.org/IOJ 186/sl 2929-019-0592-z).

|00113] An anti-ANGPTL7 antibody of the présent disclosure may be a diabody. Diabodies are antibody fragments with two antigen-binding sites that may be bivalent or bispecific. See, for example, EP 404,097; WO 1993/0! 161; Hudson et al., Nat. Med. 9:129-134 (2003); and Hollinger et al., Proc. Natl. Acad. Sci. USA 90: 6444-6448 (1993). Triabodies and tetrabodies are also described in Hudson et al., Nat. Med. 9:129-134 (2003). An anti-ANGPTL7 antibody of the présent disclosure may be a single-domain antibody (also referred to as a nanobody). Singledomain antibodies are antibody fragments comprising ail or a portion of the heavy chain variable domain or ail or a portion of the light chain variable domain of an antibody. In certain embodiments, a single-domain antibody is a human single-domain antibody (Domantis, Inc., Waltham. Mass.; see, e.g., U.S. Pat. No. 6,248,516 Bl). Antibody fragments can be made by various techniques, including but not Iimited to proteolytic digestion of an intact antibody as well as production by recombinant host cells (e.g., E. coli or phage), as described herein.

100114] In other embodiments, the anti-ANGPTL7 antibody is a whole antibody. As defined herein. a whole antibody comprises two identical copies of a heavy (H) chain polypeptide and two identical copies of a light (L) chain polypeptide. Each of the heavy chains contains one N-terminal variable (Vh) région and three C-terminal constant (Cm, Ch2, and Chî) régions, and each light chain contains one N-terminal variable (Vl) région and one C-terminal constant (Cl). The heavy chain C-terminal constant région contains the fragment crystallizable (Fc) domain, which

détermines antibody class and is responsible for humoral and cellular effector functions. Antibodies are divided into five major classes (or “isotypes”), IgG, IgM, IgA, IgD and IgE, which differ in their function in the immune System. IgGs are the most abundant immunoglobulins in the blood, representing 60% of total sérum antibodies in humans. IgG antibodies may be subclassified as IgG l, IgG2, IgG3, and IgG4, named in order of their abundance in sérum (IgG I being the most abundant) (Vidarsson et al., Frontiers in Immunology. 5: 520 (2014)). A whole anti-ANGPTL7 monoclonal antibody described herein may be of any suîtable class and/or subclass. In some embodiments, the monoclonal antibody is of class IgG (e.g., IgG l, lgG2, IgG3, or IgG4). For example, the monoclonal antibody may bean IgG I antibody.

I0 [00115] As discussed above, the Fc domain médiates several effector functions of antibodies, such as binding to receptors on target cells and complément fixation (triggering effector functions that eliminate the antigen). In some embodiments, the Fc domain may be modified or engineered to alter its effector functions. For example, Fc domains may be modified to improve antibodydependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), 15 and to control sérum half-life. In some embodiments, the Fc domain of the anti-ANGPTL7 antibody may be engineered to inodulate affinity for an Fc receptor, such as Fcy receptors (FcyRs) and the néonatal Fc receptor (FcRn). Indeed, optimization of the interactions between antibodies and FcyRs has emerged as a promising approach for enhancing the actîvity of therapeutic antibodies forthetreatmentofvariousdiseases(Mimotoetal.,Curr. Pharm. Biotechnol. 17, 129820 1314(2016); Lazar et al., Proc. Natl Acad. Sci. USA 103,4005-4010(2006); Richards et al., Mol.

Cancer Ther. 7, 2517-2527 (2008); Nordstrom et al., Breast Cancer Res. 13, R123 (2011); and Kang, T.H., Jung, S.T., Exp Mol Med 51, 1-9 (2019)). The Fc domain also may be modified to improve sérum half-life, e.g., by engineering IgG Fc forhigher FcRn binding (Zalevsky et al., Nat. Biotechnol. 28, 157-159 (2010); and Dall’Acqua et al., J. Immunol. 169, 5171-5180 (2002)). In other embodiments, the Fc domain may be modified to create monovalency or antibody bispecificity for tmproving therapeutic potency. For example, an Fc domain may be generated that does not form a homodimer but remains as a soluble monomer, mFc, that exhibits high affinity for FcyRI but no détectable binding to FcyRIIIa. In other embodiments, a heterodimeric Fc domain may be generated to obtain bispecific properties for antigen binding to circumvent homodimer formation. Engineered Fc domains may be generated by inducing point mutations or by modifying glycosylation of the Fc domain (Saunders, K.O., Front Immunol. 2019; 10:1296; Kelley, R.F.,

Meng, Y.G., Liu et al., J Biol Chem. 2014;289:3571-90; Monnet et al., MAbs. 2014;6:422-36; Li et al., Proc Natl Acad Sci USA. 2017;! 14:3485-90; and Lin et al., Proc Natl Acad Sci USA. 2015; 112:10611-6; Kang and Jung, supra).

Multispecific Anti-ANGPTL7 Antibodies

[00116J As described above, the anti-ANGPTL7 antibodies of the présent disclosure can be a monoclonal antibody, a human antibody, a humanized antibody, and/or a chimeric antibody. In some embodiments, the antibody is a fragment selected from the group consisting of Fab, Fab-C, Fab'-SH, Fv, scFv, and (Fab')? fragments. In some embodiments, the anti-ANGPTL7 antibody is a monospecific antibody. In some embodiments, the anti-ANGPTL7 antibody is a bispecific 10 antibody. In some embodiments, the anti-ANGPTL7 antibody comprises two or more singledomain antibodies that form a bivalent antibody, a tri valent antibody, or a tetravalent antibody that recognizes different epitopes on the same or different antigens.

|00117] In some embodiments, an anti-ANGPTL7 antibody provided herein is a chimeric antibody. Certain chimeric antibodies are described, for example, in U.S. Pat. No. 4,816,567; and 15 Morrison et al., Proc. Natl. Acad. Sci. USA. 81:6851-6855 (1984). In one example, a chimeric antibody comprises a non-human variable région (e.g., a variable domain derived from a mouse, rat, hamster, rabbit, or non-human primate, such as a monkey) and a human constant domain. In a further example, a chimeric antibody is a “class switched” antibody in which the class or subclass has been changed from that of the parent antibody. Chimeric antibodies include antigen-binding 20 fragments thereof.

[00118] In certain embodiments, a chimeric antibody is a humanized antibody. Typically, a non-human antibody is humanized to reduce immunogenicity to humans, while retaining the speciflcity and affinity of the parental non-human antibody. Generally, a humanized antibody comprises one or more variable domains in which H VRs, for example, CDRs, (or portions thereof) 25 are derived from a non-human antibody, and FRs (or portions thereof) are derived from human antibody sequences. A humanized antibody optionally will also comprise at least a portion of a human constant région. In some embodiments, some FR residues in a humanized antibody are substituted with corresponding residues from a non-human antibody (e.g., the antibody from which the HVR residues are derived), e.g., to restore or improve antibody specificity or affinity.

[00119] Humanized antibodies and inethods of making them are reviewed, for example, in

Almagro and Fransson. Front. Biosci. 13:1619-1633 (2008), and are further described, for example, in Riechmann et al., Nature 332:323-329 (1988); Queen et al., Proc. Nat'l Acad. Sci. USA 86:10029-10033 (1989); U.S. Pat. Nos. 5,821,337, 7,527,791, 6,982,321, and 7,087,409; Kashmiri et al., Methods 36:25-34 (2005) (describing specificity determining région (SDR) grafting); Padlan, Mol. Immunol. 28:489-498 (1991) (describing “resurfacing”); Dall'Acqua et 5 al., Methods 36:43-60 (2005) (describing “FR shuffling”); and Osboum et aL, Methods 36:61-68 (2005) and Klimka et al., Br. J. Cancer, 83:252-260 (2000) (describing the “guided sélection” approach to FR shuffling).

(001201 In accordance with the above embodiments, an anti-ANGPTL7 antibody of the présent disclosure can be made into bivalent, trivalent, or tetravalent formats. For example, an anti10 ANGPTL7 antibody of the présent disclosure can be a bivalent, bispecific antibody with heteromeric heavy chains (e.g., Triomab, knobs-into-holes (K.IH), Duobody, etc). An antiANGPTL7 antibody of the présent disclosure can be a tetravalent multispecific antibody comprised of IgGs with other binding domains fused to either the N- or C-termini of either the heavy or light chains (e.g., dual variable domain [DVD|, IgG-scFv fusion, Mabtyrin (IgG with 15 non-antibody binding scafïbld “centyrin” fused to C-terminal end of heavy chains). An antiANGPTL7 antibody of the présent disclosure can be comprised of IgGs to which additional antigen combining sites hâve been added within the structure (e.g., two-in-one antibodies, MAT “Modular Antibody Technology” platform from F-Star). An anti-ANGPTL7 antibody of the présent disclosure can be an engineered antibody fragment linked by short peptide linkers which 20 can be made into bivalent, trivalent, or tetravalent formats addressing two to three targets (e.g., bispecific T-cell engager (BiTE), Nanobody platform, dual- affinity re-targeting (DART) antibodies, “tandem antibody” structures (TandAbs)). And an anti-ANGPTL7 antibody of the présent disclosure can be comprised of chemically coupled IgGs.

(00121| In some embodiments, an anti-ANGPTL7 antibody of the présent disclosure is a 25 multispecific antibody, such as a bispecific antibody, which hâve binding specificities for at least two different antigens. In some embodiments, the anti-ANGPTL7 antibodies of the présent disclosure, or antigen-binding fragments thereof, can be used to form one arm (e.g., antigenbinding portion) of a bispecific antibody, whereas the other arm of the bispecific antibody can be spécifie fora different antigen. In some embodiments, the other antigen includes, but is not limited 30 to, interleukin-1 beta (IL-Ιβ), interleukin-6 (IL-6); interleukin-6 receptor (IL-6R); interleukin-13 (IL-13); IL-13 receptor (IL-13R); PDGF (e.g., PDGF-BB); angiopoietin; angiopoietin 2 (Ang2);

5l

Tie2; SIP; integrins ανβ3, ανβ5, and α5β1; betacellulin; apelin/APJ; erythropoietin; complément factor D; TNFa; HtrAl; a VEGF receptor (e.g., VEGFR1, VEGFR2, VEGFR3, membrane-bound VEGF-receptor (mbVEGFR), or soluble VEGF receptor (sVEGFR)); ST-2 receptor; and proteins genetically linked to age-related macular degeneration (AMD) risk, such as complément pathway components C2, factor B, factor H, CFHR3, C3b, C5, C5a, and C3a; HtrAl; ARMS2; TIMP3; HLA; interleukin-8 (IL-8); CX3CRI; TLR3; TLR4; CETP; LIPC; COLIOAI; and TNFRSFIOA. [001221 In some embodiments, a bispecific antibody of the présent disclosure includes an antiANGPTL7 antibody, or an antigen-binding fragment thereof, and an anti-VEGF antibody, or an antigen-binding fragment thereof. Such bispecific antibodies can be used to target different mechanisms. and thus provide additional therapeutic benefits. For example, the anti-ANGPTL7 arm can be any of the anti-ANGPTL7 antibodies of the présent disclosure, and the anti-VEGF arm can be any VEGF antagonist. including but not lîmîted to, anti-VEGF antibodies (e.g., bevacizumab, sevacizumab, and ranibizumab), anti-VEGFR2 antibodies and related molécules (e.g., ramucirumab, tanibirumab, aflibercept), anti-VEGFR 1 antibodies and related molécules (e.g., icrucumab, aflibercept (VEGF Trap-Eye; EYLEA®), and ziv-aflibercept (VEGF Trap; ZALTRAP®)), anti-VEGF arms of VEGF bispecific antibodies (e.g., MP-0250, vanucîzumab (VEGF-ANG2)), including anti-VEGF, anti-VEGFRl, and anti-VEGFR2 arms.

Functional Characteristics of Anti-ANGPTL7 Antibodies

[00123] In accordance with the above embodiments, the présent disclosure provides antiANGPTL7 antibodies comprising various functional characteristics. In some embodiments. the anti-ANGPTL7 antibodies described herein bind an antigen on ANGPTL7 (SEQ ID NO: 370), or a variant or isoform thereof, via interaction with its antigenic déterminants (epitopes). In some embodiments, the anti-ANGPTL7 antibodies described herein bind an antigen/epitope from a human ANGPTL7 fibrinogen domain (e.g., ATX-P-60; SEQ ID NO: 373), an antigen/epitope from a full length human ANGPTL7 monomeric variant L59P L84P (ATX-P-62; SEQ ID NO: 371), an antigen/epitope from a full length human ANGPTL7 monomeric variant L59 GGPGG (ATXP-63; SEQ ID NO: 372), an antigen/epitope from a human wild type ANGPTL7 multimer (PExt1; SEQ IDNO: 374).

[00124] In some embodiments, binding of an anti-ANGPTL7 antibody to an ANGPTL7 polypeptide reduces intraocular pressure and/or increases outflow facility (see, e.g., Example 9 and FIG. 7). In some embodiments, the anti-ANGPTL7 antibody binds an epitope on human

ANGPTL7 with a Ko of about 100 nM or lower (see, e.g., Example 10). In some embodiments, the anti-ANGPTL7 antibodies described herein bind ANGPTL7 (or a fragment thereof) and increase outflow facility compared to a control. In some embodiments, the control is selected from the group consisting of vehicle treatment, dexamethasone treatment. ANGPTL7 protein treatment, and treatment with an ANGPTL7 protein/polypeptide and an isotype control antibody (see, e.g., FIG. 7). In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 210 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 240. In some embodiments, the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 200 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 230. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%. at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ IDNO: 258 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%. or 100% identical) to SEQ ID NO: 264. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 207 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 237. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 204 and a VL comprising an amino acid sequence

that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 234. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 5 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to

SEQ ID NO: 260 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 266. In some embodiments, the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% 10 identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 205 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 235. In some embodiments, the anti-ANGPTL7 antibody comprises a VH 15 comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 206 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 236. In some 20 embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 208 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 25 99%, or 100% identical) to SEQ ID NO: 238. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 191 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 30 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO:

195. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino

acid sequence that is at least 90% identical (e.g., at least 9I%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 203 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at 5 least 98%, at least 99%, or 100% identical) to SEQ ID NO: 233. In some embodiments, the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 212 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, 10 at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 242. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 198 and a VL comprising an amino acid sequence that is at least 15 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least

96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 228. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 190 20 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 194. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, 25 at least 99%, or 100% identical) to SEQ ID NO: 202 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 232. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 30 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to

SEQ ID NO: 211 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 241. In some embodiments, the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 199 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ IDNO: 229.

[00125] In some embodiments, the anti-ANGPTL7 antibodies described herein bind ANGPTL7 (or a fragment thereof) and increase outflow facîlity compared to a control. In some embodiments, the control is any of vehicle treatment, dexamethasone treatment, ANGPTL7 protein treatment, and/or treatment with an ANGPTL7 protein/polypeptide and an isotype control antibody. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 210 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 240. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 200 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 230. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 258 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 264.

|00126] In some embodiments, the anti-ANGPTL7 antibodies described herein bind ANGPTL7 (or a fragment thereof) and increase outflow facîlity compared to a control. In some embodiments, the control is any of dexamethasone treatment, ANGPTL7 protein treatment, and/or treatment with an ANGPTL7 protein/polypeptide and an isotype control antibody. In some embodiments, the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at 5 least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 207 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 237. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, 10 at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 204 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 234. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence 1 5 that is at least 90% identical (e.g., at least 91%. at least 92%, at least 93%, at least 94%, at least

95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 260 and a VL comprising an amino acid sequence that is at least 90% identical (e.g,, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 266. In some embodiments, the anti-ANGPTL7 antibody 20 comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 205 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO:

235. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 206 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at 30 least 98%, at least 99%, or 100% identical) to SEQ ID NO: 236. In some embodiments. the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 208 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%. at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 238. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 191 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 195. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 203 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%. at least 99%, or 100% identical) to SEQ ID NO: 233. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ IDNO: 212 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 242. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ IDNO: 198 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 228. In some embodiments, the antiANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 190 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ IDNO: 194.

[00127] In some embodiments, the anti-ANGPTL7 antibodies described herein bind ANGPTL7 (or a fragment thereof) and increase outflow facility compared to a control. In some embodiments, the control is any of dexamethasone treatment and/or ANGPTL7 protein treatment. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 202 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 232. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 211 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 241. In some embodiments, the anti-ANGPTL7 antibody comprises a VH comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 199 and a VL comprising an amino acid sequence that is at least 90% identical (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 229.

Polypeptides and Expression Vectors

J00128] Embodiments of the présent disclosure also inciude a polynucleotide encoding any of the anti-ANGPTL7 antibodies of the présent disclosure. In some embodiments, the polynucleotide comprises a sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 175-179; (b) SEQ ID NOs: 192-193; (c) SEQ IDNOs: 213-227; or (d) SEQ ID NOs: 261-263. In some embodiments, the polynucleotide comprises a sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ IDNOs:

I85-189; (b) SEQ ID NOs: 196-197; (c) SEQ IDNOs: 243-257; or (d) SEQ ID NOs: 267-269. In some embodiments, the polynucleotide comprises a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 175-179; (b) SEQ ID NOs: 192-193; (c) SEQ ID NOs: 213-227; or (d) SEQ ID NOs: 261-263. In some embodiments, the polynucleotide comprises a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 185-189; (b) SEQ ID NOs: 196-197; (c) SEQ ID NOs: 243-257; or (d) SEQ ID NOs: 267-269. In some embodiments, the polynucleotide comprises a sequence that is at least 85% identical (e.g., at least 85%, at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 1 75-179; (b) SEQ ID NOs: 192-193; (c) SEQ ID NOs: 213-227; or (d) SEQ ID NOs: 261-263. In some embodiments, the polynucleotide comprises a sequence that is at least 85% identical (e.g., at least 85%, at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 185-189; (b) SEQ ID NOs: 196-197; (c) SEQ IDNOs: 243-257; or (d) SEQ ID NOs: 267-269. In some embodiments, the polynucleotide comprises a sequence that is at least 90% identical (e.g., at least 90%, at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 175-179; (b) SEQ ID NOs: 192-193; (c) SEQ IDNOs: 213-227;or (d) SEQ IDNOs: 261-263. In someembodiments, the polynucleotide comprises a sequence that is at least 90% identical (e.g., at least 90%, at least 95%. or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 185-189; (b) SEQ ID NOs: 196-197; (c) SEQ ID NOs: 243-257; or (d) SEQ ID NOs: 267-269. In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical (e.g., at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 175-179; (b) SEQ ID NOs: 192-193; (c) SEQ ID NOs: 213-227; or (d) SEQ ID NOs: 261-263. In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical (e.g., at least 95%, or 100% identical) to any of the following nucleic acid sequences: (a) SEQ ID NOs: 185-189; (b) SEQ ID NOs: 196-197; (c) SEQ ID NOs: 243-257; or (d) SEQ ID NOs: 267-269.

[00129] In some embodiments, the polynucleotide encoding an anti-ANGPTL7 antibody of the présent disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 175 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%. at least 95%, or 100% identical) to SEQ ID NO: 185; (b) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 176 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%. at least 90%. at least 95%, or 100% identical) to SEQ ID NO: 186; (c) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%. at least 80%, at least 85%. at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 177 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 187; (d) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 178 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%. or 100% identical) to SEQ ID NO: 188; (e) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 179 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 189.

100130] In some embodiments, the polynucleotide encoding an anti-ANGPTL7 antibody of the présent disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 213 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%. at least 95%. or 100% identical) to SEQ ID NO: 243; (b) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 214 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 244; (c) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 215 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 245; (d) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%. at least 75%, at least 80%, at least 85%, at least 90%, at least

6l

95%. or 100% identical) to SEQ ID NO: 216 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 246; (e) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 21 7 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%. or 100% identical) to SEQ ID NO: 247; (f) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 218 and a nucleic acid sequence that is at least 70% identical (e.g.. at least 70%. at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 248; (g) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 219 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%. or 100% identical) to SEQ ID NO: 249; (h) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 220 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%. at least 75%, at least 80%. at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ IDNO: 250; (i) a nucleic acid sequence that isat least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 221 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%. or 100% identical) to SEQ ID NO: 251; or (j) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 222 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%. at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ IDNO: 252; (k) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%. at least 85%, at least 90%. at least 95%, or 100% identical) to SEQ IDNO: 223 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 253; (I) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 224 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 254; or (m) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 225 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 255; (n) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 226 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 256; or (o) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 227 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%. at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 257.

[00131] In some embodiments, the polynucleotide encoding an anti-ANGPTL7 antibody of the présent disclosure comprises: (a) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 261 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%. or 100% identical) to SEQ ID NO: 267; (b) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 262 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 268; (c) a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 263 and a nucleic acid sequence that is at least 70% identical (e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical) to SEQ ID NO: 269.

[00132] In accordance with these embodiments, the présent disclosure includes an expression vector comprising any of the polynucleotides encoding an anti-ANGPTL7 antibody of the présent disclosure. In some embodiments, the expression vector is suitable for manufacturing an antiANGPTL7 antibody of the présent disclosure for delivery of the antibody to a subject. In certain embodiments, the nucleic acid sequence is in the form of a vector. The vector can be, for example, a plasmid, episome, cosmid, viral vector (e.g., retroviral or adénoviral), or phage. Suitable vectors and methods of vector préparation are well known in the art (see, e.g., Sambrook et al., Molecular Cioning. a Laboratory Manual, 4th édition, Cold Spring Harbor Press. Cold Spring Harbor, N.Y. (2012), and Ausubel et al., Current Protocols in Molecular Biology, Greene PubIishing Associates and John Wiley & Sons, New York, N.Y. ( 1994)).

|00133] In addition to the nucleic acid encoding an anti-ANGPTL7 antibody or antigen-binding fragment thereof, the vector desirably comprises expression control sequences, such as promoters. enhancers, polyadenylation signais, transcription terminators, internai ribosome entry sites (IRES), and the like, that provide for the expression of the antibody-encoding nucleic sequence in a host cell. Exemplary expression control sequences are known in the art and described in, for example, Goeddel, Gene Expression Technology: Methods in Enzymology, Vol. 185, Academie Press, San Diego, Calif. ( 1990).

[00134| A vector comprising a nucleic acid sequence encoding an anti-ANGPTL7 antibody or antigen-binding fragment thereof may be introduced into a host cell that is capable of expressing the polypeptides encoded thereby, including any suitable prokaryotic or eukaryotic cell. Examples of suitable prokaryotic cells include, but are not limited to, cells from the généra Bacillus (such as Bacillus suhtilis and Bacillus brevis), Escherichia (such as E. coli), Pseudomonas, Streptomyces, Salmonella, and Erwinia. Particularly useful prokaryotic cells include the varîous strains of Escherichia coli (e.g., Kl2, HB101 (ATCC No. 33694), DH5a, DH 10, MC 1061 (ATCC No. 53338), and CC102). Suitable eukaryotic cells are known in the art and include, for example, yeast cells, insect cells, and mammalian cells. Examples of suitable yeast cells include those from the généra Hansenula, Kluyveromyces, Pichia, Rhinosporidium, Saccharomyces, and Schizosaccharomyces. Suitable insect cells include Sf-9 and HIS cells (Invitrogen, Carlsbad, Calif.) and are described in. for example, Kitts et al.. Biotechniques, 14'. 810-817 (1993); Lucklow, Curr. Opin. Biotechnol., 4\ 564-572 (1993); and Lucklow et al., J. Virol., 67·. 4566-4579 (1993). Examples of suitable mammalian cells include, but are not limited to, Chinese hamster ovary cells (CHO) (ATCC No. CCL61), CHO DHFR-cells (Urlaub et al., Proc. Natl. Acad. Sci. USA, 97: 4216-4220 (1980)), human embryonic kidney (HEK) 293 or 293T cells (ATCC No. CRLI573), and 3T3 cells (ATCC No. CCL92). Other suitable mammalian cell lines are the monkey COS-I (ATCC No. CRL1650) and COS-7 cell lines (ATCC No. CRLI65I), as well as the CV-I cell line (ATCC No. CCL70). Further exemplary' mammalian host cells include primate cell lines and

rodent cell lines, including transformed cell lines. Normal diploid cells, cell strains derived from in vitro culture of primary tissue, as well as primary expiants also are suitable. Other suitable mammalian cell lines include, but are not limited to, mouse neuroblastoma N2A cells, HeLa, mouse L-929 cells, and BHK or HaK hamster cell lines, ail of which are availabié from the ATCC.

Methods for selecting suitable mammalian host cells and methods for transformation, culture, amplification, screening, and purification of such cells are well known in the art (see, e.g., Ausubel et al., eds., Short Protocols in Molecular Biology, 5th ed., John Wiley & Sons, Inc., Hoboken, NJ. (2002)). Preferably, the mammalian cell is a human cell.

[00135] In some embodiments, the vector can include means for attaching a détection moiety 10 to an anti-ANGPTL7 antibody of the présent disclosure. In some embodiments, the vector can include means for attaching a purification moiety to an anti-ANGPTL7 antibody of the présent disclosure. Exemplary détection and/or purification moieties/tags that can be coupled to an antiANGPTL7 antibody of the présent disclosure includes, but is not limited to, hemagglutinin (HA), c-Myc, V5, DYK.DDDDK, His tag (e.g., 6.X-HIS), Glutathione S-Transferase (GST), Maltose 15 Binding Protein (MBP), a fluorophore (e.g., Green Fluorescent Protein (GFP), Red Fluorescent

Protein (RFP), mCherry, a chromophore, and/or a luminescent peptide (e.g., luciferase).

[00136| In some embodiments, the expression vector is suitable for use in gene therapy (e.g., an expression vector for delivering a polynucleotide encoding an anti-ANGPTL7 antibody of the présent disclosure to a subject). In some embodiments, the expression vector is a herpes simplex 20 virus (HSV) vector, or a retrovirus vector. In some embodiments, the expression vector is an adeno-associated virus (AAV) vector, or comprises an AAV backbone. For example, AAV vectors hâve been designed, produced and used to médiate gene delivery in human subjects, including for therapeutic purposes. Typically, AAV vectors for use in gene transfer comprise a réplication defective AAV genome lacking functional Rep and Cap coding viral sequences. Such 25 réplication defective AAV vectors more preferably lack most or ail of the Rep and Cap coding sequences, and essentially retain one or two AAV ITR sequences and a packaging sequence. The defective genome is packaged in a viral particle, to form a defective, recombined AAV virus, also termed “AAV vector.” Methods of producing such AAV vectors hâve been disclosed in the literature, including using packaging cells, auxiliary viruses or plasmids, and/or baculovirus 30 Systems (Samulski et al., (1989) J. Virology 63, 3822; Xiao et al., (1998) J. Virology 72, 2224;

Inoue et al., (1998) J. Virol. 72, 7024; WO98/22607; W02005/072364). Methods of producing

pseudotyped AAV vectors hâve also been reported (e.g., WO00/28004), as well as varions modifications or formulations of AAV vectors, to reduce their immunogenicity upon in vivo administration (see e.g., W001/23001; WOOO/733I6; WO04/I I2727; W005/Q056I0; WO99/06562). AAV vectors may be prepared or derived from varions serotypes of AAVs, which may be even mixed together or with other types of viruses to produce chimeric (e.g., pseudotyped) AAV viruses. Examples of tAAVs are human AAV4 vectors, human AAV7 vectors, human AAV9 vectors, human AAVIO vectors, or bovine AAV vectors. The AAV vector may be derived from a single AAV serotype or comprise sequences or components originating from at least two distinct AAV serotypes (pseudotyped AAV vector), e.g., an AAV vector comprising an AAV genome derived from one AAV serotype (for example AAV9), and a capsid derived at least in part from a distinct AAV serotype. An AAV vector, as used herein, is a vector which comprises at least one component part derivable from an adeno-associated virus. Preferably, that component part is involved in the biological mechanisms by which the vector infects or transduces target cells and expresses an anti-ANGPTL7 antibody of the present disclosure (e.g., ocular delivery/expression).

[00137] In other embodiments, the expression vector is a lentiviral vector (LV), or comprises an LV backbone. Lentiviruses are part of a larger group of retroviruses. A detailed list of lentiviruses may be found in Cofïîn et al (1997) “Retroviruses” Cold Spring Harbour Laboratory Press Eds: JM Coffin. SM Hughes, HE Varmus pp 758-763). For example, lentiviruses can be divided into primate and non-primate groups. Examples of primate lentiviruses include but are not limited to: the human immunodeficiency virus (HIV), the causative agent of human auto immunodeficiency syndrome (AIDS), and the simian immunodeficiency virus (SIV). The nonprimate lentiviral group includes the prototype “slow virus” visna/maedi virus (VMV), as well as the related caprine arthritis-encephalitis virus (CAEV), equine infectious anaemia virus (E1AV), feline immunodeficiency virus (FIV), Maedi visna virus (MW) and bovine immunodeficiency virus (BIV). In one embodiment, the lentiviral vector is derived from HIV- 1, HIV-2, SIV, FIV, B1V, EIAV, CAEV or Visna lentivirus. The lentivirus family differs from retroviruses in that lentiviruses hâve the capability to infect both dividing and non-dividing cells (Lewis et al (1992) EM BO J 11 (8): 3053-3058 and Lewis and Emerman (1994) J Virol 68 (1):510-516). In contrast, other retroviruses, such as MLV, are unable to infect non-dividing or slowly dividing cells such as those that make up, for example, muscle, brain, lung and liver tissue. A lentiviral vector, as used herein, is a vector which comprises at least one component part derivable from a lentivirus.

Preferably, that component part is involved in the biological mechanisms by which the vector infects or transduces target cells and expresses an anti-ANGPTL7 antibody of the présent disclosure (e.g., ocular deiivery/expression).

|00138| Additional compositions and methods for ocular gene therapy can be found in, e.g.,

Bordet, T., and Behar-Cohen, F., “Ocular gene thérapies in clinical practice: viral vectors and nonviral alternatives,” Drug Discovery Today. Volume 24, Issue 8, August 2019, Pages 1685I693). In some embodiments. gene therapy platforms, methods, and compositions that can be used to deliver an anti-ANGPTL7 antibody of the présent disclosure to a subject (e.g., ocular deiivery) includes the platforms. methods, and compositions disclosed in US20220025396,

US20220011308, US20210371877, US20210363I92, US20190078099, US20190038724, and

US 10494646B2, which are incorporated herein by reference. In other embodiments, gene therapy platforms, methods, and compositions that can be used to deliver an anti-ANGPTL7 antibody of the présent disclosure to a subject (e.g., ocular deiivery) includes the platforms, methods, and compositions based on HMR59 (Hemera Biosciences), which through its protein product soluble

CD59, blocks the membrane attack complex that forms during the terminal step in the complément cascade. HMR59 is designed to be administered as a single intraocular injection.

|001391 In accordance with these embodiments, the présent disclosure also provides a method of administering ocular gene therapy to a subject in need thereof comprising injecting a pharmaceutical composition comprising an effective amount of an expression vector described herein (e.g., an expression vector comprising a polynucleotides encoding an anti-ANGPTL7 antibody of the présent disclosure). As described further below, the présent disclosure also provides a method of treating glaucoma and other ocular diseases affecting the optic nerve and retinal ganglion cells. In some embodiments, the method comprises administering a pharmaceutical composition comprising an effective amount of an expression vector described herein (e.g., an expression vector comprising a polynucleotides encoding an anti-ANGPTL7 antibody of the présent disclosure). In some embodiments, administering the pharmaceutical composition treats at least one symptom of glaucoma or other ocular diseases affecting the optic nerve and retinal ganglion cells.

Compositions and Methods of Treatment |00140] The anti-ANGPTL7 antibodies of the présent disclosure can be administered as part of a pharmaceutical composition in a therapeutically effective amount to treat an eye disease (e.g., glaucoma). In some embodiments, the composition is suitable for ocular administration. In some embodiments, ocular administration comprises injection into vitreous fluid. In some embodiments, ocular administration comprises delivering the antibody using a conjunctival insert, a contact lens, a gel, a nanoparticle, a mucoadhesive polymer, an ointment, a solution, a suspension, eye drops, 5 and/or an implant (e.g., Susvimo™). Recent methods and formulations for ocular administration can be found in, e.g., Souto, E.B., et al. “Advanced Formulation Approaches for Ocular Drug Delivery: State-Of-The-Art and Recent Patents,” Pharmaceutics, 2019 Sep; l l(9): 460).

[00141] In accordance with these embodiments, the methods include administering a pharmaceutical composition comprising a therapeutically effective amount of an anti-ANGPTL7 10 antibody of the present disclosure. In some embodiments, the pharmaceutical composition is administered ocularly and treats at least one symptom of glaucoma or other ocular diseases affecting the optic nerve and retinal ganglion cells. In some embodiments, the at least one symptom comprises eye pain, eye pressure, headaches, rainbow-colored halos around lights, low vision, blurred vision, narrowed vision, impaired peripheral vision, blind spots, nausea, vomiting, and red 15 eyes. In some embodiments, administering the pharmaceutical composition reduces or atténuâtes intraocular pressure and/or increases or enhances outflow facility in the subject’s eye.

[00142] In some embodiments, the pharmaceutical composition comprising a therapeutically effective amount of an anti-ANGPTL7 antibody of the present disclosure is administered at a dose ranging from about 0.0001 mg/dose to about 100 mg/dose. In some embodiments, the anti20 ANGPTL7 antibody is administered at a dose ranging from about 0.001 mg/dose to about 100 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.01 mg/dose to about 100 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.1 mg/dose to about 100 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 1.0 25 mg/dose to about 100 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 10 mg/dose to about 100 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/dose to about 10 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/dose to about 1.0 mg/dose. In some embodiments, the 30 anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/dose to about

0.1 mg/dose. in some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/dose to about 0.001 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.01 mg/dose to about 10 mg/dose. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.001 mg/dose to about 1.0 mg/dose. In some embodiments. the anti-ANGPTL7 antibody is administered 5 at a dose ranging from about 0.1 mg/dose to about 10 mg/dose.

|00l43| In some embodiments, the pharmaceutical composition comprising a therapeutically effective amount of an anti-ANGPTL7 antibody of the présent disclosure is administered at a dose ranging from about 0.0001 mg/ml to about 100 mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.001 mg/ml to about I00 mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.01 mg/ml to about 100 mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.1 mg/ml to about I00 mg/ml. In some embodiments, the antiANGPTL7 antibody is administered at a dose ranging from about l.O mg/ml to about I00 mg/ml.

In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about

10 mg/ml to about 100 mg/ml. In some embodiments. the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/ml to about !0 mg/ml. In some embodiments, the antiANGPTL7 antibody is administered at a dose ranging from about 0.000I mg/ml to about l.O mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/ml to about 0.1 mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/ml to about 0.01 mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.0001 mg/ml to about 0.001 mg/ml. In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.01 mg/ml to about 10 mg/ml. In some embodiments, the antiANGPTL7 antibody is administered at a dose ranging from about 0.001 mg/ml to about l .0 mg/ml.

In some embodiments, the anti-ANGPTL7 antibody is administered at a dose ranging from about 0.1 mg/ml to about 10 mg/ml.

[00144] As used herein, the terms “treatment,” “treating,” and the like refer to obtaining a desired pharmacologie and/or physiologie effect. In some embodiments, the effect is therapeutic.

i .e., the effect partially or completely cures a disease and/or adverse symptom attributable to the disease. To this end, the methods of the présent disclosure comprise administering a “therapeutically effective amount” of an anti-ANGPTL7 antibody, or composition comprising an anti-ANGPTL7 antibody. A “therapeutically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic resuit. The therapeutically effective amount may vary according to factors such as the disease State, âge, sex, and weight of the îndividual, and the ability of the monoclonal antibody to elicit a desired response in the îndividual. For example, a therapeutically effective amount of an anti-ANGPTL7 antibody of the présent disclosure is an amount that treats at least one symptom of glaucoma or other ocular diseases affecting the optic nerve and retinal ganglion cells in a subject. In some embodiments, the pharmacologie and/or physiologie effect may be prophylactic, i.e., the effect completely or partially prevents a disease or symptom thereof. In this respect, the methods of the présent disclosure comprise administering a “prophylactically effective amount” of an anti-ANGPTL7 antibody or composition comprising an anti-ANGPTL7 antibody. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired prophylactic resuit (e.g., prévention of glaucoma or at least one symptom associated with glaucoma).

|00l45| A typical dose of a therapeutically effective amount of an anti-ANGPTL7 antibody of the present disclosure can range from, for example, about 0.0001 mg/dose to about 100 mg/dose for each eye to be treated. In some embodiments, a therapeutically effective amount of an antiANGPTL7 antibody of the present disclosure can range from about 0.001 mg/dose to about I00 mg/dose, from about 0.01 mg/dose to about I00 mg/dose, from about 0.05 mg/dose to about 50 mg/dose, from about 0.1 mg/dose to about 10 mg/dose, from about 0.5 mg/dose to about 5 mg/dose, and from about I mg/dose to about 10 mg/dose. In some embodiments, a therapeutically effective concentration of an anti-ANGPTL7 antibody of the present disclosure can range from, for example, about 0.0001 mg to about 100 mg of the antibody per milliliterof solution. In some embodiments, a therapeutically effective concentration of an anti-ANGPTL7 antibody of the present disclosure can range from about 0.001 mg/ml to about I00 mg/ml, from about 0.01 mg/ml to about 100 mg/ml, from about 0.I mg/ml to about 100 ing/ml, from about l.O mg/ml and about 100 mg/ml, from about 0.001 mg/ml and about 50 mg/ml, from about 0.01 mg/ml and about 50 mg/ml, from about 0.1 mg/ml and about 50 mg/ml, from about 0.1 mg/ml and about 25 mg/ml, from about 0.1 mg/ml and about 10 mg/ml, and from about l.O mg/ml and about 10 mg/ml. In some embodiments, a therapeutically effective dose of an anti-ANGPTL7 antibody of the présent disclosure can be, exactly or approximately, 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.35 mg, 0.4 mg.

0.45 mg. 0.5 mg. 0.55 mg, 0.6 mg, 0.65 mg, 0.7 mg, 0.75 mg, 0.8 mg, 0.85 mg, 0.9 mg, 0.95 mg, l .0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 10.0 mg, 15.0 mg, 20.0 mg. or 25.0 mg, or can fall within a range delimited by any two of the foregoing values. For example, in certain embodiments, a sustained release formulation, (e.g., an ocular implant) can be, exactly or approximately, 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.35 mg, 0.4 mg, 0.45 mg, 0.5 mg, 0.55 mg, 0.6 mg, 0.65 mg, 0.7 mg, 0.75 mg, 0.8 mg, 0.85 mg, 0.9 mg, 0.95 mg, l .0 mg. 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 10.0 mg. I5.0 mg, 20.0 mg, or 25.0 mg of an anti-ANGPTL7 antibody, or an amount that falls within a range delimited by any two of the foregoing values.

[00146] Therapeutic or prophylactîc efficacy can be monitored by periodic assessment of treated patients. For repeated administrations over several days or longer, depending on the condition, the treatment is repeated until a desired suppression of disease symptoms occurs. However, other dosage regimens may be useful and are within the scope of the présent disclosure. The desired dosage can be delivered by a single bolus administration of the composition, by multiple bolus administrations of the composition, or by continuous infusion administration of the composition. The composition comprising an anti-ANGPTL7 antibody, or antigen-binding fragment thereof, can be administered to a mammal using standard administration techniques, including ocular, oral, intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration. The composition preferably is suitable for ocular administration.

[00147] In accordance with the compositions and methods of treatment described herein, embodiments of the présent disclosure include anti-ANGPTL7 antibodies that hâve enhanced halflife (e.g., after ocular administration), such that the anti-ANGPTL7 antibody can be administered less often to a subject. In some embodiments, the antibody comprises a half-life extension moiety. In some embodiments, the half-life extension moiety comprises a polypeptide that can be coupled to an anti-ANGPTL7 antibody ofthe présent disclosure by any means known in the art (e.g., génération of a fusion protein). In some embodiments, the polypeptide that can be coupled to an anti-ANGPTL7 antibody of the présent disclosure is at least 20 amino acids in length and comprises any combination of G, A, S T, E, and P residues. In some embodiments, the half-life extension polypeptide is attached to the C-terminus or N-terminus of the antibody. In some embodiments, this îs referred to as “XTENylation,” as described further in US8933197,

7l

US7846445, US7855279, US8492530, US9938331, US8673860, US937I369, US9926351, US10961287, US10172953, and US 10953073.

[00148] The présent disclosure also provides a composition comprising any of the antiANGPTL7 antibodies or antigen-binding fragments thereof described herein. The composition desirably is a pharmaceutically acceptable (e.g., physiologically acceptable) composition, which comprises a carrier, preferably a pharmaceutically acceptable (e.g., physiologically acceptable) carrier, and the anti-ANGPTL7 antibody or antigen-binding fragment thereof. Any suitable carrier can be used within the context of the présent disclosure, and such carriers are well known in the art. For example, the composition may contain preservatives, such as, for example, methylparaben, propylparaben. sodium benzoate, and benzalkonium chloride. A mixture of two or more preservatives optionally may be used. In addition, buffering agents may be included in the composition. Suitable buffering agents include, for example, citric acid, sodium citrate, phosphoric acid, potassium phosphate, and various other acids and salts. A mixture of two or more buffering agents optionally may be used. Methods for preparing compositions for pharmaceutical use are known to those ski lied in the art and are described in, for example, Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins; 2 Ist ed. (May 1,2005).

[00149| Once administered to a mammal (e.g., a human), the biological activity of the antiANGPTL7 antibody, or antigen-binding fragment thereof, can be measured by any suitable method known in the art. For example, the biological activity can be assessed by determining the stability of the anti-ANGPTL7 antibody. The biological activity of the anti-ANGPTL7 antibody also can be assessed by determining its binding affinity to ANGPTL7 peptides and/or by assessing its binding affinity to peptides with which it may cross-react. The term “affinity” refers to the equilîbrium constant for the réversible binding of two agents and is expressed as the dissociation constant (Kd). Affinity of a binding agent to a ligand, such as affinity of an antibody for an epitope, can be, for example, from about 1 femtomolar (fM) to about 1 millimolar (mM) (e.g., from about 1 picomolar (pM) to about 1 nanomolar (nM), or from about 1 nM to about 1 micromolar (μΜ)). In some embodiments, the affinity of an anti-ANGPTL7 antibody may be from about 1 nm to about 20 nm, and desirably from about 5 nm to about 10 nm. Antibody affinity for an antigen or epitope of interest can be measured using any art-recognized assay. Such methods include, for example, fluorescence activated cell sorting (FACS), separable beads (e.g., magnetic beads), antigen panning, and/or ELISA (see, e.g., Janeway et al. (eds.), Immunobiology, 5th ed., Garland Publishing. New York. N.Y., 200I).

(00150| In some embodiments. an anti-ANGPTL7 antibody, or composition comprising an antiANGPTL7 antibody, may be administered alone or in combination with other drugs/therapeutic agents. For example, the anti-ANGPTL7 antibody can be administered in combination with other agents for the treatment or prévention of glaucoma or other ocular disease affecting the optic nerve or retinal ganglion cells. as disclosed herein. For example, anti-ANGPTL7 antibodies of the présent disclosure, or antibody conjugales, fusion proteins, or polymeric formulations thereof, can be used either alone or in combination with other agents in a therapy. For instance, an anti10 ANGPTL7 antibody may be co-administered with at least one additional therapeutic agent. In certain embodiments, an additional therapeutic agent is another antibody, a chemotherapeutic agent, a cytotoxic agent, an anti-angiogenic agent, an immunosuppressive agent, a prodrug, a cytokine, a cytokine antagonist, cytotoxic radiotherapy, a corticosteroid, an anti-emetic, a cancer vaccine, an analgésie, a growth-inhibitory agent, or combinations thereof.

[00l5l| In certain embodiments, an anti-ANGPTL7 antibody of the présent disclosure is administered with a drug/therapeutic agent that treats/prevents glaucoma or other ocular disease that affects the optic nerve or retinal ganglion cells. Any suitable glaucoma therapeutic agent can be administered as an additional therapeutic agent in combination with an anti-ANGPTL7 antibody of the présent disclosure, or an antibody conjugale, fusion protein, and/or polymeric formulation thereof, for treatment of an ocular disorder (e.g., e.g., glaucoma or other disease associated with or affecting the optic nerve or retinal ganglion cells). For example, in some embodiments, an anti-ANGPTL7 antibody of the présent disclosure can be administered with an agent that lowers intraocuiar pressure by promoting the drainage of fluid from the eye, including but not limited to, prostaglandins (e.g., Xalatan (latanoprost), Travatan Z (travoprost), Zioptan (tafluprost), and Lumigan (bimatoprost)), Rho kinase inhibitors (e.g., Rhopressa (netarsudil)), nitric oxides (e.g., Vyzulta (latanoprostene bunod), and miotic or cholinergic agents (e.g., Isopto Carpine (pilocarpine)). In some embodiments, an anti-ANGPTL7 antibody of the présent disclosure can be administered with an agent that lowers intraocuiar pressure by reducing the amount of fluid produced in the eye, including but not limited to, alpha-adrenergic agonists (e.g., lopidine (apraclonidine) and Alphagan P or Qoliana (brimonidine)), beta blockers (e.g.,

Betoptic (betaxolol) and Betimol, Istalol, or Timoptic (timolol)), and carbonic anhydrase inhibitors (e.g., Trusopt (dorzolamide) and Azopt (brinzolamide)). Additionally, one or more ot these therapeutic agents can be administered with an anti-ANGPTL7 antibody of the présent disclosure, in conjunction with other treatments, such as laser treatment (e.g., trabeculoplasty) and surgery (e.g., glaucoma implant surgery, and minimally invasive glaucoma surgery (MIGS)).

[00152] In some embodiments, an anti-ANGPTL7 antibody, antibody conjugate, fusion protein, or polymeric formulation of the présent disclosure is administered simultaneously with an additional therapeutic agent. In some embodiments, an anti-ANGPTL7 antibody, antibody conjugate, fusion protein, or polymeric formulation of the présent disclosure is administered before or after an additional therapeutic agent. In some embodiments, the additional therapeutic agent(s) binds to a second biological molécule selected from the group consisting of VEGF, IL-Ιβ; IL-6; IL-6R; IL-13; IL-13R; PDGF; angiopoietin; Ang2; Tie2; SIP; integrins ανβ3, ανβ5, and α5β!; betacellulin; apelin/APJ; erythropoietin; complément factor D; TNFa; HtrAl; a VEGF receptor; ST-2 receptor; and proteins genetically linked to AMD risk, such as complément pathway components C2, factor B, factor H, CFHR3, C3b, C5, C5a, and C3a; HtrAl; ARMS2; TIMP3; HLA; interleukin-8 (IL-8); CX3CRI; TLR3; TLR4; CETP; LIPC; COLIOAI; and TNFRSFIOA. In some embodiments, the additional therapeutic agent is an antibody or antigen-binding fragment thereof. In some embodiments according to (or as applied to) any of the embodiments above, the ocular disorder is an intraocular neovascular disease selected from the group consisting of proliférative rétinopathies, choroidal neovascularization (CNV), glaucoma, diseases affecting the optic nerve, diseases affecting the retinal ganglion cells, diabetic and other ischemia-related rétinopathies, diabetic macular edema, pathological myopia, von Hippel-Lindau disease, histoplasmosis of the eye, retinal vein occlusion (RVO), including CRVO and BRVO, corneal neovascularization, retinal neovascularization, and retinopathy of prematurity (ROP).

[00153] In some embodiments, an anti-ANGPTL7 antibody of the présent disclosure, or an antibody conjugate, fusion protein, and/or polymeric formulation thereof, may be administered in combination with at least one additional therapeutic agent for treatment of an ocular disorder, for example, an ocular disorder described herein (e.g., glaucoma or other disease associated with or affecting the optic nerve or retinal ganglion cells). Exemplary additional therapeutic agents for combination therapy for treatment of ocular disorders include, without limitation, anti-angiogenic agents, such as VEGF antagonists, including, for example, anti-VEGF antibodies (e.g., the antiVEGF Fab LUCENTIS® (ranibizumab)), soluble receptor fusion proteins (e.g., the recombinant soluble receptor fusion protein EYLEA® (aflibercept, also known as VEGF Trap Eye; Regeneron/Aventis)), aptamers (e.g., the anti-VEGF pegylated aptamer MACUGEN® (pegaptanib sodium; NeXstar Pharmaceuticals/OSI Pharmaceuticals)), and VEGFR tyrosine kinase inhibitors (e.g., 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-( I -methylpiperidin-4y lmethoxy)quinazoline (ZD6474), 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3pyrrolidin-l-ylpropoxy)quinazoline (AZD2I71), vatalanib (PTK.787), semaxaminib (SU54I6; SUGEN), and SUTENT® (sunitinib)); Tryptophanyl-tRNA synthetase (TrpRS); squalamine; RETAANE® (anecortave acetate for depot suspension; Alcon, Inc.); Combretastatin A4 Prodrug (CA4P); MIFEPREX® (mifepristone-ru486); subtenon triamcinolone acetonide; intravitreal crystalline triamcinolone acetonide; matrix metalloproteinase inhibitors (e.g., Prinomastat (AG3340; Pfizer)); fluocinolone acetonide (including fluocinolone intraocular implant; Bausch & Lomb/Control Delivery Systems); linomide; inhibitors of integrin β3 function; angiostatin, and combinations thereof, |00154] Further examples of additional therapeutic agents that can be used in combination with an anti-ANGPTL7 antibody of the présent disclosure, or an antibody conjugale, fusion protein, and/or polymeric formulation thereof, for treatment of an ocular disorder (e.g., glaucoma or other disease associated with or affecting the optic nerve or retinal ganglion cells), include, but are not limited to, VISUDYNE® (verteporfin; a light-activated drug that is ty pically used in conjunction with photodynamîc therapy with a non-thermal laser), PKC412, Endovion (NS 3728; NeuroSearch A/S), neurotrophic factors (e.g., glial derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF)), diltiazem, dorzolamide, PHOTOTROP®, 9-cis-retinal, eye médication (e.g., phospholine iodide, echothiophate, or carbonic anhydrase inhibitors), veovastat (AE-941 ; AEterna Laboratories, Inc.), Sirna-027 (AGF-745; Sirna Therapeutics, Inc.), neurotrophins (including, by way of example only, NT-4/5, Genentech), Cand5 (Acuity Pharmaceuticals), INS-3721 7 (Inspire Pharmaceuticals), integrin antagonists (including those from Jerini AG and Abbott Laboratories), EG-3306 (Ark Therapeutics Ltd.), BDM-E (BioDiem Ltd.), thalîdomide (as used, for example, by EntreMed, Inc.), cardiotrophin-l (Genentech), 2-methoxyestradiol (Allergan/Oculex), DL-8234 (Toray Industries), NTC-200 (Neurotech), tetrathiomolybdate (University of Michigan), LYN-002 (Lynkeus Biotech), microalgal compound (Aquasearch/Albany, Mera Pharmaceuticals), D-9I20 (Celitech Group pic), ATX-SIO (Hamamatsu Photonics), TGF-beta 2 (Genzyme/Celtrix), ty rosine kinase inhibitors (e.g., those from Allergan. SUGEN, or Pfizer), NX-278-L (NeXstar

Pharmaceuticals/Gilead Sciences), Opt-24 (OPTIS France SA), retinal cell ganglion neuroprotectants (Cogent Neurosciences), N-nitropyrazole dérivatives (Texas A&M University System), KP-I02 (Krenitsky Pharmaceuticals), cyclosporin A, therapeutic agents used in photodynamic therapy (e.g., VISLJDYNE®; receptor-targeted PDT, Bristol-Myers Squibb, Co.; porfimer sodium for injection with PDT; verteporfin, QLT Inc.; rostaporfin with PDT, Miravent Medical Technologies; talaporfin sodium with PDT, Nippon Petroleum; and motexafin lutetium, Pharmacyclics, Inc.), antîsense oligonucleotides (including, by way of example, products tested by Novagali Pharma SA and ISIS-13650, Isis Pharmaceuticals), and combinations thereof.

100155] An anti-ANGPTL7 antibody of the présent disclosure, or an antibody conjugale, fusion protein, and/or polymeric formulation thereof, may be administered in combination with a therapy or surgical procedure for treatment of an ocular disorder (e.g., glaucoma or other disease associated with or affecting the optic nerve or retinal ganglion cells), including, for example, laser photocoagulation (e.g., panretinal photocoagulation (PRP)), drusen lasering, macular hole surgery, macular translocation surgery, implantable miniature télescopes, PHI-motion angiography (also known as micro-laser therapy and feeder vessel treatment), proton beam therapy, microstimulation therapy, retinal detachment and vitreous surgery, scierai buckle, submacular surgery, transpupillary thermotherapy, photosystem I therapy, use of RNA interférence (RNAi), extracorporeal rheopheresis (also known as membrane differential filtration and rheotherapy), microchip implantation, stem cell therapy, gene replacement therapy, ribozyme gene therapy (including gene therapy for hypoxia response element. Oxford Biomedica; Lentipak, Genetix; and PDEF gene therapy, GenVec), photoreceptor/retinal cells transplantation (including transplantable retinal épithélial cells, Diacrin, Inc.; retinal cell transplant, Cell Genesys, Inc.), acupuncture, and combinations thereof (00156| In some embodiments, an anti-ANGPTL7 antibody of the présent disclosure, or an antibody conjugale, fusion protein. and/or polymeric formulation thereof, can be administered in combination with an anti-angiogenic agent for treatment of an ocular disorder (e.g., glaucoma or other disease associated with or affecting the optic nerve or retinal ganglion cells). Any suitable anti-angiogenic agent can be used in combination with an antibody of the présent disclosure, including, but not limited to, those listed by Carmeliet et al. Nature 407:249-257, 2000. In some embodiments, the anti-angiogenic agent is a VEGF antagonist. including, but not limited to, an anti-VEGF antibody (e.g., the anti-VEGF Fab LUCENT1S® (ranibizumab), RTH-258 (formerly

ESBA-1008, an anti-VEGF single-chain antibody fragment; Novartis), or a bispecific anti-VEGF antibody (e.g., an anti-VEGF/anti-angiopoietin 2 bispecific antibody such as RG-77I6; Roche)), a soluble recombinant receptor fusion protein (e.g., EYLEA® (aflibercept)), a VEGF variant, a soluble VEGFR fragment, an aptamer capable of blocking VEGF (e.g., pegaptanib) or VEGFR, a neutralizing anti-VEGFR antibody, a small molécule inhibitor of VEGFR tyrosine kinases, an antiVEGF DARPin® (e.g., abicipar pegol), a small interfering RNAs which inhibits expression of VEGF or VEGFR, a VEGFR tyrosine kinase inhibitor (e.g., 4-(4-bromo-2-fluoroanilino)-6methoxy-7-( l -methylpiperidin-4-ylmethoxy)quinazoline (ZD6474), 4-(4-fluoro-2-methylindol-5yloxy)-6-methoxy-7-(3-pyrrolidin-l-ylpropoxy)quinazoline (AZD2I7I), vatalanib (PTK787), semaxaminib (SU5416; SUGEN), and SUTENT® (sunitinib)), and combinations thereof.

[00157] Other suitable anti-angiogenic agents that may be administered in combination with an antibody of the présent disclosure, or an antibody conjugale, fusion protein, and/or polymeric formulation thereof, for treatment of an ocular disorder (e.g., glaucoma or other disease associated with or affecting the optîc nerve or retinal ganglion cells) include cortîcosteroids, angiostatic steroids, anecortave acetate, angiostatin. endostatin, tyrosine kinase inhibitors, matrix metalloproteinase (MMP) inhibitors, insulin-like growth factor-binding protein 3 (IGFBP3), stromal derived factor (SDF-1) antagonists (e.g., anti-SDF-1 antibodies), pigment epitheliumderived factor (PEDF), gamma-secretase, Delta-like ligand 4, integrin antagonists. hypoxiainducible factor (HIF)-la antagonists, protein kinase CK2 antagonists, agents that inhibit stem cell (e.g., endothélial progenitor cell) homing to the site of neovascularizatîon (e.g., an anti-vascular endothélial cadherin (CD-144) antibody and/or an anti-SDF-1 antibody), and combinations thereof.

[00158| In some embodiments, an anti-ANGPTL7 antibody of the présent disclosure, or an antibody conjugale, fusion protein, and/or polymeric formulation thereof, can be administered in combination with an agent that has activity against neovascularizatîon for treatment of an ocular disorder (e.g., glaucoma or other disease associated with or affecting the optic nerve or retinal ganglion cells), such as an anti-inflammatory drug, a mammalian target of rapamycin (mTOR) inhibitor (e.g., rapamycin, AFINITOR® (everolimus), and TORISEL® (temsirolimus)), cyclosporine, a tumor necrosis factor (TNF) antagonist (e.g., an anti-TNFa antibody or antigenbinding fragment thereof (e.g., infliximab, adalimumab, certolizumab pegol, and golimumab) or a soluble receptor fusion protein (e.g., etanercept)), an anti-complement agent, a nonsteroidal antiinflammatory agent (NSAID), or combinations thereof.

[00159| In addition to therapeutic uses, an anti-ANGPTL7 antibody or antigen-binding fragment, described herein can be used in diagnostic or research applications. Research applications include, for example, methods that utilize the anti-ANGPTL7 antibody and a label to detect an ANGPTL7 polypeptide or protein in a sample (e.g., in a human body fluid or in a cell or tissue extract). The anti-ANGPTL7 antibody or antigen-binding fragment thereof may be employed in any suitable assay for measuring ANGPTL7 in a sample for diagnostic and/or research purposes. Such assays include, but are not limited to, sandwich immunoassays, enzyme immunoassays (EIA), enzyme-linked immunosorbent assays (ELISA), latéral flow assays, compétitive inhibition immunoassays (e.g., forward and reverse), compétitive binding assays, Forster résonance energy transfer (FRET), one-step antibody détection assays, single molécule détection assays, radioimmunoassays (RIA), and FACS. Such methods are disclosed in, for example, U.S. Patents 6,143,576; 6,113,855; 6,019,944; 5,985,579; 5,947,124; 5,939,272; 5,922.615; 5,885,527; 5,851,776; 5,824,799; 5,679,526; 5,525,524; and 5,480,792; and Adamczyk et al.. Anal. Chim. Acta, 579(1): 61-67 (2006).

[00160] The anti-ANGPTL7 antibody or antigen-binding fragment thereof can be provided in a kit, e.g., a packaged combination of reagents in predetermined amounts with instructions for performing an assay using the antibody (e.g., an assay that detects ANGPTL7). As such. the disclosure provides a kit comprising the antibody or antigen-binding fragment described herein and instructions for use thereof. The instructions can be in paper form or computer-readable form. such as a disk, CD, DVD, etc. Altematively or additionally, the kit can comprise a calibrator or control, and/or at least one container (e.g., tube, microtiter plates, or strips) for conducting an assay, and/or a buffer, such as an assay buffer or a wash buffer. Idéally, the kit comprises ail components, i.e., reagents, standards, buffets, dîluents, etc., which are necessary to perform the assay. Other additives may be included in the kit. such as stabilizers, buffers (e.g., a blocking buffer or lysis buffer), and the like. The relative amounts of the various reagents can be varied to provide for concentrations in solution of the reagents which substantially optimize the sensitivity of the assay. The reagents may be provided as dry powders (typically lyophi 1 ized), including excipients which on dissolution will provide a reagent solution having the appropriate concentration.

[00161] The following examples further illustrate the various embodiments of the present disclosure but should not be construed as in any way limiting ils scope.

EXAMPLES

[00162] It will be readîly apparent to those skilled in the art that other suitable modifications and adaptations of the methods of the present disclosure described herein are readily applicable and appréciable, and may be made using suitable équivalents without departing from the scope of the present disclosure or the aspects and embodiments disclosed herein. Having now described the present disclosure in detail, the same will be more clearly understood by référencé to the following examples, which are merely intended only to illustrate some aspects and embodiments of the disclosure, and should not be viewed as limiting to the scope of the disclosure. The disclosures of ail journal référencés, U.S. patents, and publications referred to herein are hereby incorporated by référencé in their entireties.

[00163] The present disclosure has multiple aspects, illustrated by the following non-limiting examples.

EXAMPLE 1 |00164] This example describes dexamethasone-induced changes in gene expression in primary human trabecular meshwork cells. Primary trabecular meshwork cells isolated from post-mortem human donors were treated with dexamethasone (DEX). Changes in ANGTPL7 gene expression relative to vehicle were quantified using qPCR, as shown in FIG. 1. Using these data, strong DEX responders were selected for future studies, such as RNAseq.

|00165| In particuiar, primary human trabecular meshwork cells were passed in DMEM with 10% fêtai bovine sérum (FBS) and 1% penicillin/streptomycin. Cells were plated in 96-well plates at 20,000 cells/well. Media was changed 3 times a week. After 1 week, cells were further differentiated using DMEM with 1% FBS and 1% penicillin/streptomycin. Cells were incubated with low sérum for a minimum of 1 additional week, with media changes 3 times a week.

[00166] For dexamethasone (DEX) treatment, media were removed and replaced with media containing 100 nM DEX or 0.1% éthanol (EtOH, vehicle). Media was refreshed after 2-3 days, and cells were harvested for qPCR on day 5 using the Cells to Ct kit. qPCR was run using an

ANGPTL7 TaqMan assay from Life Technologies on a Quantstudioô qPCR machine. Gene expression was normalized to the EtOH control.

EXAMPLE 2

[00167] This example describes RNAseq of ANGPTL7 treatment-induced changes in gene expression of human trabecular meshwork(TM) and Schlemm’s Canal (SC) cells (FIG. 2). Briefly, primary human trabecular meshwork and Schlemm’s canal cells were passed in DMEM with 10% fêtai bovine sérum (PBS) with 1% penicillin/streptomycin. Cells were seeded at 200k cells/well in 6-well formats. Cells were differentiated in low sérum for a week with media changes 3 times a week. For ANGPTL7 treatment, media were removed and replaced with media containing 50 ng/mL of ANGPTL7 protein made from BIORTUS. Treatment media was refreshed daily for three days. After three days, cells were spun down and frozen into a pellet and then stored into a -80C freezer until shipment to SeqMatic for processing.

EXAMPLE 3

100168] Experiments were conducted to détermine the effects of ANGPTL7 on outflow facility in a bioengineered ex vivo human eye tissue model. Glauconix developed a proprietary technology allowing multi-layer growth of bioengineered 3D human trabecular meshwork (HTM) cells cocultured with human Schlemms’ canal (HSC) cells, thereby mimicking the architecture of the tissues responsible for pressure build-up in the human eye (FIG. 3A). This allows endpoint analyses relevant to IOP-modulation. This scaffolding of cells is used to compare treatment effects of vehicle (DMSO), dexamethasone (a steroid known to elevate IOP), and human ANGPTL7 protein on outflow facility.

[00169| Briefly, HTM cells were thawed and allowed to grow for about 7 days (media changes every 2 days). The HTM cells were seeded onto scaffolds and HSC cells were thawed on the same day; the HTM cells were allowed to grow for 7 days on the scaffolds with media changes every 2 days. HSCs were co-cultured on the back side of the HTM scaffolds and grown for 10-12 days with media changes every 2 days. HTM/HSC constructs were sérum starved the in a 1% medium the day before treatment. The first day of treatment was called Day 0. On Day 3, supernatants were collected, re-treated, and this process was repeated on Days 6 and 9. Perfusion was donc on Day 10.

I I )00170] FIG. 3B includes représentative data demonstrating outflow facîlity for 3D-HTM donor 2 treated with vehicle (DMSO), 500nM Dexamethasone, 50 ng/mL of ANGPTL7. Samples were analyzed using One-way ANOVA (GraphPad Prism Software, Inc., La Jolla. CA), *P<0.05, **P<.0.0l, ***P<.001 N=4 per treatment group. FIG. 3C includes représentative data 5 demonstrating outflow facîlity for 3D-HTM donor 3 treated with vehicle (DMSO), 500nM

Dexamethasone, 50 ng/mL of ANGPTL7. Samples were analyzed using One-way ANOVA (GraphPad Prism Software, Inc., La Jolla, CA), *P<0.05, **P<.0.01, ***P<.001 N=4 pertreatment group. These data demonstrate that ANGPTL7 treatment reduced outflow facîlity for hoth donors, similar to DEX treatment.

EXAMPLE 4 |001711 Experiments were conducted to détermine the effects of ANGPTL7 on outflow facîlity using a bioengineered ex vivo human eye tissue model. Glauconix developed a proprietary technology allowing multi-layer growth of bioengineered 3D human trabecular meshwork (HTM) cells co-cultured with human Schlemms’ canal (HSC) cells, thereby mimicking the architecture of 15 the tissues responsible for pressure build-up in the human eye (FIG. 3A; see also exemplary protocol in Example 3). This allows endpoint analyses relevant to lOP-modulation.

|00172] This experîment compared three different doses (25, 50, and 150 ug/ml) of ANGPTL7 protein on outflow facîlity in three different donor HTM cell lines (FIGS. 4A-4C). In this example, experiments were focused on the reproducibility of ANGPTL7 effects on outflow facîlity (from 20 SOW l ) and dose response effects in three different I ITM donors.

EXAMPLE 5

[00173] Génération of recombinant ANGPTL7 proteins. Recombinant protein préparations were undertaken to produce spécifie proteins which could be used as immunogens/antigens, screening reagents, and/or control reagents. Ail efforts were made in service of the goal of 25 generating a panel of anti-ANGPTL7 antibodies with the desired properties. In this particular example, outsourced material produced by Biortus was used for the human ANGPTL7 multimer, while protein engineering work was used to produce mutant human monomers. Truncated but nonengineered wild type fibrinogen domain only human ANGPTL7 monomer was also produced.

8l

[00174] Proteins with the sequence corresponding to human, African green monkey, and rabbit ANGPTL7 were produced. The human and African green monkey sequences were engineered to favor the production of monomeric material, while the rabbit protein was a mixture of monomer, trimer, and hexamer. When finished, ail protein préparations exceeded 90% purity by analytical methods and were less than <l endotoxin unit per milliliter.

[00175] Beginnîng with in silico analysis, appropriate wild type amino acid sequences of human, rabbit, and African green monkey ANGPTL7 were located and extracted from publicly available databases. The sequences were then further analyzed and modified manually using Geneious Prime software in accordance with the experimental plan. Specifically, in regard to the production of monomeric ANGPTL7, the mechanism of multimerization was examined closely. Structurally, ANGPTL7 consists of two domains, a small N-terminal coiled coil domain and a larger C-terminal fibrînogen like domain. Given the similarîties to fibrinogen protein at the domain level, previously published works, and the well documented biological function of coiled coil domains, the N-terminal région was identified as the area on which to focus in order to engineer monomeric mutants. Coiled coil domains follow a well-defined heptad repeat of hydrophobie and charged amino acids. This repeat, in conjugation with the property of approximately seven amino acids per two turns of an alpha hélix, and the aqueous environment of either the extra or intracellular space, favor packing ofthe hydrophobie side chains into the interior of the coil while the charged amino acids face the aqueous environment. Dimerization, trimerization or other higher order multimers resuit as each linear alpha hélix is dépendent on others to reach the energetically favorable “packed” State. Approaches which disrupt linearity and/or the hydrophobie and charged heptad could lead to monomers. Two strategies were designed upon this theoretical Framework. Constructs with substitutions of proline for leucine at both amino acid position 59 and 84 or with leucine at position 59 replaced with glycine-glycine-proline-glycîne-glycine were built in silico and added to the panel of sequences designed for the project. The replacement of leucine at position 59 with five amino acids proved most successful. A version In addition, a truncated form of human ANGPTL7 corresponding to only the C-terminal Fibrinogen like domain sequence was added to the panel of sequences.

[00176] Ail Sequences were examined for liabilities and modified to add further amino acid sequence which encoded for “tags” to facilitate purification, lower immunogenicity, or simplify analytical screening. Examples of protein tags used in this work include the HIS tag and the Avi tag. Tags were separated from each other and from the ANGPTL7 sequences with short linker sequences. Ail tags were added to the C-terminal end of the sequences. Additionally, the native signal peptide was removed and replaced with a signal peptide conducive to recombinant expression.

[00177| After ail modifications were complété, the amino acid sequences were back translated into DNA sequences and optimized for the codon biases found in the human genome. These optimized DNA sequences were sent to Integrated DNA Technologies and produced as DNA fragment(s) with DNA overhangs added to the 5’ and 3’ ends. Utilizîng the DNA overhangs and the Gibson cloning method, these DNA fragments were assembled into the expected sequence and cloned into a mammalian expression plasmid driven by a CMV promoter. The plasmid was propagated in E. coli with appropriate antibiotic sélection and prepared, at a scale useful for recombinant expression, utilizîng commercially available préparation kits purchased from Qiagen. The sequence of the plasmid and the expression gene was then confirmed using Sanger sequencing. [00178] Using polyethylenimine, the sequence verified plasmid was transfected into human embryonic kidney cells adapted for recombinant expression. One day after transfection. the cells were supplemented with Chemicals and nutrients designed to increase recombinant protein expression. These suppléments include sodium propionate, valproic acid, glucose, glutamine, and a variety of yeast lysâtes. Five days after transfection, the expressing cell cultures were harvested. As the recombinant protein is secreted into the growth medium, the cells, cell fragments, and cell débris, were removed via centrifugation and filtration through a membrane with pores no greater than 0.22 microns. The clarified culture medium, conditioned with the recombinant protein, was now ready for purification. Using a FPLC (Fast pressure liquid chromatography) and the appropriate commercially available pre-packed affinity chromatography column for the Cterminal tag(s) the protein of interest was purified from the cell culture medium and immobilized on the chromatography column. For HIS tagged proteins, a Ni-NTA agarose column was used. Multiple column washes followed, each spécifie for the type of column/tag/chromatography. The protein of interest was eluted from the column with 300 mM of imidazole for HIS tagged proteins. [00179] Protein quality and quantity were assessed using a combination of SDS-PAGE gel electrophoresis, spectrophotometry, and analytical-SEC (size exclusion chromatography). Most proteins for this project required further purification. To further polish the proteins, the FPLC and a second chromatography column were employed. Séparation by size, accomplished with a size exclusion column, enabled increased protein punties up to >90%. SEC also enabled buffer exchange out of the affinity chromatography elution buffer and into the final buffer of choice (PBS). The protein sample then moved onto quality control. If, at any point during purification, protein concentration needed to be increased, Amicon Ultra molecular weight cutoff (MWCO) filtration units were used to concentrate protein by separating protein from buffer. MWCO was chosen to ensure compatibility with the size of the protein of interest. Before moving to final quality control, ail final samples were concentrated to > I milligram per milliliter.

|00l80| Endotoxin contamination in the final protein sample was assayed using Charles River’s Endosafe PTS system. Spectrophotometry determined the final protein concentration. Three micrograms of the final sample were ïnjected onto an analytical SEC column (YMC Diol 300) to détermine its final purity. Additionally, sometimes SDS-PAGE electrophoresis was performed to détermine final quality. Once ail final metrics passed, the protein was sterilized in a biosafety cabinet using a stérile 0.22 micron filter. This was followed by stérile aliquoting and flash freezing in liquid nitrogen before storage at -80°C.

EXAMPLE 6

[001811 Recovery of ANGPTL7 antibody sequences from immunized mice. ANGPTL7 Immunization: Four cohorts of Alloy Therapeutic transgenic humanized mice, ATX-GK, were immunized with various human ANGPTL7 antigens using a standard 5-week R1MMS protocol: 10 gg subeutaneous dosing of antigen emulsified in complété Freund’s adjuvant followed by 5 weekly subeutaneous dosing of antigen emulsified in incomplète Freund’s adjuvant.

[00182] Cohort 1 : Three ATX-GK mice immunized with human ANGPTL7 fibrinogen domain (ATX-P-60; SEQ ID NO: 373). Cohort 2: Three ATX-GK mice immunized with full length human ANGPTL7 monomeric variant L59P L84P (ATX-P-62; SEQ IDNO: 371). Cohort 3: Three ATXGK mice immunized with full length human ANGPTL7 monomeric variant L59 GGPGG (ATXP-63; SEQ ID NO: 372). Cohort 4: Three ATX-GK mice immunized with human wild type ANGPTL7 multimer (PExt-1; SEQ ID NO: 374).

|00183[ Sample bleeds were taken at week four and tested for antigen positive sérum titer and purification tag négative sérum titer by ELISA. ELISA plates were coated with either lug/ml of ANGPTL7 immunogen or an irrelevant protein with the same purification tag as the immunogen. Antigen coated plates were incubated with seven 10-fold serial dilutions of sera starting at 1:300.

Antibodies bound to antigen were detected by anti-mouse IgG HRP secondary antibody and one step TMB solution. The absorbance signal at 450 nm was measured with an ELISA microplate reader (FIGS. 5A-5D).

[00184| Hybridoma: Immune tissues from high titer mice were harvested and preserved for 5 antibody discovery. Hybridoma cell lines producing ANGPTL7 antibodies were produced by fusion of single B Cells from spleen and lymph nodes of titer positive mice with myeloma cells. Twenty 96 well plates of hybridoma fusions were generated and expanded. Hybridomas expressing ANGPTL7 spécifie antibodies were detected by antigen binding by ELISA. Affinity of antibodies in the hybridoma supernatants were measured by SPR using the Octet instrument. ANGPTL7 10 antibodies in hybridoma supematant were loaded on a biosensor. Response was measured as a nm shift in the interférence pattern and was proportional to the number of antibodies bound to the surface of the biosensor. The binding interaction of ANGPTL7 to the immobilized antibodies was measured as association (kon). Following analyte association, the biosensor was dipped into PBS without ANGPTL7, and the bound antigen was allowed to dissociate from the antibody (kdis). KD 15 (M), or affinity of the antibodies for ANGPTL7 was measured as kdis/kon.

[00185] Heavy and light chains from validated hybridomas were sequenced, RNA was isolated from ANGPTL7 antibody secreting hybridomas and heavy and light chain variable régions were cloned by reverse transcription using gene spécifie primers followed by PCR amplification with variable chain gene spécifie primers. PCR products were sequenced by standard Sanger 20 sequencing methods.

[00186] Phage Display. Variable heavy and light chains were amplified from the spleen of high titer immunized mice by reverse transcription using gene spécifie primers followed by PCR amplification with variable chain gene spécifie primers. Variable régions were cloned into a phage display vector designed to express Fabs on phage g3p protein. Libraries of phage expressing 25 unique Fabs were amplified and purified. Phage were allowed to bind to biotinylated ANGPTL7 antigens captured on streptavidin magnetic beads. Phage remaining bound to antigen beads after several stringent washes was eluted using a basic triethylamine solution and neutralized with Tris buffer pH 8.0. Eluted phages were reinfected into TGI bacterial cells, amplified by co-infection with M13 helper phage, and purified by PEG précipitation. Purified phages expressing Fabs were 30 selected for antigen binding as described. Phage from the second round were diluted and infected into TGI cells. Polyclonal pools of phage output from two rounds of panning were tested by

ELISA to confîrm that the pools contained ANGPTL7-specific phage. Variable heavy and light chain régions were sequenced from single infected bacterial colonies using a rolling circle amplification and standard Sanger sequencing.

[00187] Antibody Sequencing: Unique variable heavy and light chain pairs from hybridoma and phage display campaigns were cloned into vectors designed to express full length antibodies as IgGs in HEK293 cells under the control of a CMV promoter. Antibody expression vectors were complexed with polyethylenimine and transfected into HEK293 cultures. After 5 days of shakîng at 37 °C in 293 cell culture media, antibodies were captured on agarose-based protein A resin. After several stringent washes, antibodies were eluted in glycine solution, pH 3, neutralized with Hepes, pH 9, and buffer exchanged into PBS.

EXAMPLE 7

[00188| Human ANGPTL7 monoclonal antibody differential scanning fluorimetry (DSF). Development of effective monoclonal antibodies dépends not only on their biological activity but also on their physicochemical properties, such as homogeneity and stability. mAb stability can be affected by their formulation. Among the inany techniques used to study the stability of mAbs, differential scanning fluorimetry (DSF) offers both excellent throughput and minimal material consumption. DSF measures the température of the protein unfolding transition (Tm) based on the change in fluorescence intensîty of an environmentally sensitive dye.

[00189] Experiments were conducted to assess the thermal stability of the human ANGPTL7 monoclonal antibodies (“ATX” antibodies) of the présent disclosure by determining the melting température. Thermal stability was assessed via differential scanning fluorimetry (DSF) utilizing the Protein Thermal Shift (PTS) assay from Applied Biosystems. The assay was performed according to the manufacturer’s instruction. Briefly, the antibody to be evaluated was prepared in triplicate by mixing with Protein Thermal Shift dye and buffer; a real-time melt experiment from 25 °C to 95 °C was run on QuantStudio 3. Data was analyzed by using Protein Thermal Shift Software and the melting température (Tm) was calculated from the melt curve (Table 1).

[00190] Table I: DSF analysis of human anti-ANGPTL7 monoclonal antibodies.

Protein Thermal Shift Assay Results
Sample ID	Tm D - Mean	Tm 2 - Mean
ATX-P-423	62.50
ATX-P-424	62.69	73.14

ATX-P-425	62.97	7I.94
ATX-P-427	62.78	67.87
ATX-P-428	62.62	79.24
ATX-P-429	62.64	80.49
ATX-P-430	62.59
ΛΤΧ-Ρ-43 I	60.77
ATX-P-432	62.82
ΛΤΧ-Ρ-433	62.68	72.49
ATX-P-434	62.82	75.29
ΛΤΧ-Ρ-435	62.68	78.38
ATX-P-436	62.33	80.83
ΛΤΧ-Ρ-437	62.42
ATX-P-438	62.63	81.09
ATX-P-439	62.77	83.42
ΛΤΧ-Ρ-440	62.58	79.68
ATX-P-442	62.44	85.lü
ATX-P-443	62.45
ATX-P-444	62.10
ATX-P-445	62.61
ATX-P-446	62.10
ATX-P-447	62.31
ATX-P-448	62.33	72.19
ATX-P-449	62.24	80.41

EXAMPLE 8

[001911 ANGPTL7 Antibody Cross-Blocking. High-throughput epitope binning experîments were conducted on real-time label-free biosensors (Carterra LSA) to sort large panels of mAbs 5 into bins based on their ability to block one another for binding to the antigen. In a pairwise epitope binning analysis, antigen and antibody 2 (analyte antibody) are sequentially applied to the sensor chip (HC200M) covalently pre-loaded with antibody I (ligand antibody). An increase in response upon exposure to the analyte antibody indicates non-competition between the two antibodies, whereas a lack of change in the signal indicates compétition. Antibodies having the same blocking 10 profiles towards others in the test set are grouped into one bin. Community network plots are used to explore clustering of mAbs that share similar but not necessarily identical compétition profiles. [00192] Rather than relying strictly on the sandwiching/blocking assignments in the heat map (FIG. 6A), as the Bin network plots do, hierarchical clustering was applied to the sorted heat map to generate various dendrograms and network plots, which progressively group mAbs based on 15 various binning parameters. (FIGS. 6B-6I). FIG. 6B includes data from a granular binning network. FIG. 6C: includes data from a combined binary dendrogram (color indicates bins in the Community binning network). FIG. 6D includes data from a community binning network. FIG.

6E includes binning data based on affinity for huANGPTL7-his (P62). FIG. 6F includes binning data based on antibody source (hybridoma or phage). FIG. 6G includes binning data based on fibrinogen domain (P60P) binding. FIG. 6H includes binning data based on rabbit ANGPTL7 (p66) binding. FIG. 6I includes binning data based on mouse ANGPTL7 binding.

EXAMPLE 9

[00193] ANGPTL7 Functional Evaluation. Experiments were conducted to test the effects of anti-ANGPTL7 antibodies on conventional outflow facility using a 3D HTM/HSC Tissue Model (see FIG. 3A/Example 3). The purpose of this study is to screen antibodies that bînd ANGPTL7 to détermine whether they are able to block ANGPTL7’s dépréssion of outflow facility in an organoid model of the aqueous outflow tract. Antibodies that are capable of increasing outflow facility by blocking ANGPTL7’s activity are drug candidates for further study.

[00194] The studies were carried out using a bioengineered ex vivo human outflow tract model described above. G lançon ix developed a proprietary technology allowing multi-layer growth of bioengineered 3D human trabecular meshwork (HTM) cells co-cultured with human Schlemms’ canal (HSC) cells, thereby mimicking the architecture of the tissues responsible for pressure buildup in the human eye. This allows endpoint analyses relevant to IOP-modulation. Previous experiments described above showed both dexamethasone and ANGPTL7 significantly decreased outflow facility in the 3D human tissue model. In this experiment, the effects of 20 anti-ANGPTL7 antibodies on outflow facility with ANGPTL7 treatment were investigated.

[00195] As show in FIG. 7, outflow facility of one donor cell line treated with vehicle (DMSO),

500 nM Dexamethasone, 50 ng/mL ANGPTL7 (1.1 nM) alone, 50 ng ANGPTL7 + an isotype control Antibody (330) at 11.1 nM, and 20 different Anti-ANGPTL7 antibodies at 11.1 nM together with 50 ng/mL ANGPTL7. Samples were analyzed for effects against isotype control (330) using One-way ANOVA (GraphPad Prism Software, Inc., La Jolla, CA), *P<0.05, **P<.0.01, ***P<.00l, ****P<.000l N=3 per treatment group. These data clearly demonstrate that the efficacy of the anti-ANGPTL7 antibodies of the present disclosure to restore outflow faci lity.

EX AMPLE 10

[00196] ANGPTL7 Antibody Kinetics. Experiments were conducted to détermine the reactivity and dissociation constants (Kd) of anti-ANGPTL7 antibodies with the human fibrinogen domain of the ANGPTL7 protein. Binding experiments were performed on Octet HTX (ForteBio) in Ix PBS, pH 7.4, 0.1 mg/ml BSA, 0.05% Sodium Azide, and 0.02% Tween 20. Antibodies at a concentration of 50 nM were loaded on pre-hydrated AHC biosensors for 5 min. The loaded sensors were dipped into monovalent P60 (huANGPTL7-Fibrinogen-his) at a concentration of 200 nM for 5 min association, followed by 10 min dissociation. Results were analyzed with ForteBio Data Analysis 11.1 and fit to a 1:1 binding mode! to détermine the monovalent Kd. Responses (nm) at the end of association were also determined (Table 2).

[00197] Table 2: Reactivity of anti-AbJGPTL7 antibodies with the human fibrinogen domain of the ANGPTL7 protein.

	AHC > Antibody > P60 (ftuANGPTL 7-Fibrinogen-his) @ 200 nM
Ab ID	Response	KD (M)	kon(lZMs)	kdis( 1/s)	Full RA2
ATX-P-423	0.69	1.83E-O8	1.96E+05	3.60E-03	0.99
ATX-P-424	0.41	1.06E-07	1.11E+05	1.18E-02	0.99
ATX-P-425	0.36	3.Ü5E-07	7.04E+04	2.14E-02	1.00
ATX-P-427	0.50	6.5IE-08	1.55E+05	1.0IE-02	0.96
ATX-P-428	0.02	N.B.	N.B.	N.B.	0.42
ATX-P-429	0.52	7.53 E-08	4.23E+04	3.18E-O3	1.00
ATX-P-430	0.13	N.B.	N.B.	N.B.	0.99
ATX-P-43 1	0.11	N.B.	N.B.	N.B.	0.90
ATX-P-432	0.10	N.B.	N.B.	N.B.	0.95
ATX-P-433	0.66	1.09E-08	2.23E+05	2.43E-03	0.96
ATX-P-434	0.53	4.63E-10	2.58E+05	1.20E-04	0.99
ATX-P-435	0.45	7.70E-08	2.52E+04	1.94E-03	1.00
ATX-P-436	0.14	N.B.	N.B.	N.B.	0.99
ATX-P-437	0.60	6.58E-10	2.13E+05	1.40E-04	1.00
ATX-P-438	0.08	N.B.	N.B.	N.B.	0.99
ATX-P-439	0.28	P.F.	P.F.	P.F.	0.75
ATX-P-440	0.39	5.58E-08	4.65Ε+Ό4	2.60E-03	0.97
ATX-P-442	0.69	4.62E-09	3.4IE+05	1.58E-03	0.96
ATX-P-443	0.01	N.B.	N.B.	N.B.	0.41
ATX-P-444	0.14	N.B.	N.B.	N.B.	1.00
ATX-P-445	0.12	N.B.	N.B.	N.B.	0.99
ATX-P-446	0.09	N.B.	N.B.	N.B.	0.90

ATX-P-447	0.08	N.B.	N.B.	N.B.	0.94
ATX-P-448	0.54	4.69E-09	9.47E+04	4.44E-04	0.97
ATX-P-449	0.08	N.B.	N.B.	N.B.	0.67

|00198] Experiments were also conducted to détermine the reactivity and dissociation constants (Kd) of anti-ANGPTL7 antibodies with the human ANGPTL7-his protein. Binding experiments were performed on Octet HTX (ForteBio) in Ix PBS, pH 7.4, 0.1 mg/ml BSA, 0.05% Sodium

Azide, and 0.02% Tween 20. To measure monovalent binding kinetics, antibodies at a concentration of 50 nM were loaded on pre-hydrated AHC biosensors for 5 min. The loaded sensors were dipped into monovalent P62 (huANGPTL7-his) at a range of concentration from 0.343-250 nM (a serial 3-fold dilution) for 5 min association, followed by 10 min dissociation. Results were analyzed with ForteBio Data Analysis 11.1 and fit globally to a 1:1 binding model to détermine the monovalent Kd (Table 3).

|00199] Table 3: Reactivity of anti-ANGPTL7 antibodies with the human ANGPTL7-his protein.

	AHC > Antibody > P62 (huANGPTL7-his) @ 250 nM, 3X dilution
Ab ID	KD(M)	kon(l/Ms)	k<lis( 1 /s) or (kofT)	Full RA2
ATX-P-423	3.58E-O8	1.48E+05	5.30E-03	1.00
ATX-P-424	1.64E-07	5.30E+04	8.68E-03	0.99
ATX-P-425	2.19E-07	6.50E+04	1.42E-02	0.98
ATX-P-427	3.97E-07	6.60Ε+Ό4	2.62E-02	1.00
ATX-P-428	N.B.	N.B.	N.B.	0.00
ATX-P-429	9.27E-08	3.75Ε+Ό4	3.48E-03	0.99
ATX-P-430	6.56E-08	1.33E+O5	8.73E-O3	0.92
ATX-P-431	N.B.	N.B.	N.B.	0.00
ATX-P-432	N.B.	N.B.	N.B.	0.00
ATX-P-433	1.3OE-O9	4.3IE+O5	5.60E-04	0.99
ATX-P-434	6.71E-10	2.62E+05	I.76E-04	1.00
ATX-P-43 5	3.51E-08	3.89E+O4	1.37E-03	0.98
ATX-P-436	N.B.	N.B.	N.B.	0.00
ATX-P-43 7	Very low KD	Very low KD	Slow KofT	1.00
ATX-P-43 8	7.8IE-08	1.28E+O5	1.00E-02	0.98
ATX-P-43 9	4.1 IE-10	1.02E+06	4.18E-04	1.00
ATX-P-440	8.4OE-O8	3.96E+04	3.32E-03	0.98
ATX-P-442	1.2IE-09	4.68E+05	5.68E-04	0.99

ΛΤΧ-Ρ-443	N.B.	N.B.	N.B.	0.00
ATX-P-444	2.17E-10	3.57E+O5	7.72E-05	I.00
ATX-P-445	4.24E-10	6.49E+05	2.75E-04	0.99
ATX-P-446	1.57E-10	4.00E+05	6.28E-05	I.00
ATX-P-447	Low KD	Low KD	Slow, drifting	0.99
ATX-P-448	9.83E-11	3.27E+O5	3.22E-05	I.00
ATX-P-449	Very W.B.	Very W.B.	Very W.B.	0.00

(00200J Experiments were also conducted to détermine the reactivity and dissociation constants (Kd) of anti-ANGPTL7 antibodies with the human ANGPTL7 GGPGG_sub-hîs protein. Binding experiments were performed on Octet HTX (ForteBio) in I x PBS, pH 7.4, 0.1 mg/ml BSA, 0.05% 5 Sodium Azide, and 0.02% Tween 20. Antibodies at a concentration of 50 nM were loaded on prehydrated AHC biosensors for 5 min. The loaded sensors were dipped into monovalent P63 (huANGTPL7-GGPGG_sub-his) at a concentration of I00 nM for 5 min of association, followed by 10 min ofdissociation. Results were analyzed with ForteBio Data Analysis ll.l and fit to a l:l binding model to determine the monovalent Kd. Responses (nm) at the end of association were 10 also determined (Table 4).

|0020l] Table 4: Reactivity of anti-ANGPTL7 antibodies with the human ANGPTL7 GGPGG_sub-his protein.

	AHC > Antibody > P63 (huANGTPL7-GGPGG_sub-his) @ 100 nM
Ab ID	Response	KD(M)	kon(l/Ms)	kdis( 1/s)	Full RA2
ATX-P-423	0.73	2.82E-08	1.29E+05	3.63E-03	0.98
ATX-P-424	0.43	5.45E-08	9.62E+04	5.24E-03	0.96
ATX-P-425	0.35	1.31E-07	8.04E+04	1.05E-02	0.97
ATX-P-427	0.45	P.F.	P.F.	P.F.	0.89
ATX-P-428	0.03	N.B.	N.B.	N.B.	0.75
ATX-P-429	0.46	8.31E-08	4.06E+04	3.37E-03	1.00
ΛΤΧ-Ρ-430	0.14	N.B.	N.B.	N.B.	0.97
ATX-P-431	0.11	N.B.	N.B.	N.B.	0.91
ATX-P-432	0.09	N.B.	N.B.	N.B.	0.95
ATX-P-433	0.71	1.89E-08	1.34E+O5	2.53E-03	0.96
ATX-P-434	0.70	I.50E-09	1.4OE+O5	2.10E-04	0.99
ATX-P-43 5	0.36	6.48E-08	3.07E+04	1.99E-03	0.99
ATX-P-436	0.13	N.B.	N.B.	N.B.	0.98
ATX-P-43 7	0.73	1.37E-09	I.29E+05	I.77E-04	0.99
ATX-P-43 8	0.19	N.B.	N.B.	N.B.	0.95

•	ATX-P-439	0.31	P.F.	91 P.F.	P.F.	0.80
ATX-P-440	0.38	6.37E-08	4.33E+04	2.76E-03	0.97
ATX-P-442	0.82	9.67E-09	1.85E+O5	I.79E-03	0.97
ATX-P-443	0.02	N.B.	N.B.	N.B.	0.80
ATX-P-444	0.56	7.07E-10	4.76E+05	3.37E-04	0.96
ATX-P-445	0.64	P.F.	P.F.	P.F.	0.90
ATX-P-446	0.56	6.48E-I0	4.97E+05	3.22E-04	0.94
ATX-P-447	0.7 I	I.32E-09	4.65E+05	6.15E-04	0.93
ATX-P-448	0.53	6.02E-09	8.34E+04	5.02 E-04	0.97
ΛΤΧ-Ρ-449	0.15	N.B.	N.B.	N.B.	0.84

1002021 Experiments were also conducted to détermine the reactivity and dissociation constants (Kd) of anti-ANGPTL7 antibodies with the mouse ANGPTL7 protein. Binding experiments were performed on Octet IITX (ForteBio) in Ix PBS, pH 7.4, O.l mg/ml BSA, 0.05% Sodium Azide, 5 and 0.02% Tween 20. Antibodies at a concentration of 50 nM were loaded on pre-hydrated AHC biosensors for 5 min. The loaded sensors were dipped into monovalent muANGPTL7-his (R&D Systems) at a concentration of 200 nM for 5 min of association, followed by 10 min of dissociation. Results were analyzed with ForteBio Data Analysis ll.l and fit to a kl binding model to déterminé the monovalent Kd. Responses (nm) at the end of association were also determined 10 (Table 5).

(00203] Table 5: Reactivity of anti-ANGPTL7 antibodies with the mouse ANGPTL7 protein.

	AHO	Antibody > muANGPTL7-his (R&D Systems) @ 200 nM
	Ab ID	Response	KD (M)	kon(l/N1s)	kdis(l/s)	Full RA2
	ATX-P-423	0.14	N.B.	N.B.	N.B.	0.89
	ATX-P-424	0.I4	N.B.	N.B.	N.B.	0.91
	ATX-P-425	0.20	P.F. ! L.R.	P.F. / L.R.	P.F. / L.R.	0.85
	ATX-P-427	0.48	1.03E-08	1.20E+05	1.23E-03	0.90
	ΛΤΧ-Ρ-428	0.04	N.B.	N.B.	N.B.	0.90
	ATX-P-429	0.00	N.B.	N.B.	N.B.	0.70
	ATX-P-43 0	0.01	N.B.	N.B.	N.B.	0.47
	ATX-P-431	0.04	N.B.	N.B.	N.B.	0.94
	ATX-P-432	0.03	N.B.	N.B.	N.B.	0.85
	ATX-P-433	0.17	P.F./L.R.	P.F./L.R.	P.F./L.R.	0.89
	ATX-P-434	0.54	7.28E-09	L4IE+05	I.03E-03	0.92
	ATX-P-435	0.01	N.B.	N.B.	N.B.	0.76
	ATX-P-436	0.01	N.B.	N.B.	N.B.	0.85
	ATX-P-43 7	0.02	N.B.	N.B.	N.B.	0.96

ATX-P-438	0.01	N.B.	N.B.	N.B.	0.89
ATX-P-439	0.53	P.F.	P.F.	P.F.	0.89
ATX-P-440	0.2!	5.53E-O8	1.66E+04	9.15E-04	0.99
ATX-P-442	0.32	P.F.	P.F.	P.F.	0.84
ATX-P-443	0.02	N.B.	N.B.	N.B.	0.86
ATX-P-444	0.01	N.B.	N.B.	N.B.	0.45
ATX-P-445	0.01	N.B.	N.B.	N.B.	0.62
ATX-P-446	0.05	N.B.	N.B.	N.B.	0.99
ATX-P-447	0.12	N.B.	N.B.	N.B.	0.94
ATX-P-448	0.69	Low KD	Low KD	Slow Koff	0.99
ATX-P-449	0.75	8.57E-1O	8.I6E+04	7.00E-05	0.99

(00204] Experiments were also conducted to détermine the reactivity and dissociation constants (Kd) of anti-ANGPTL7 antibodies with the rabbit ANGPTL7 protein. Binding experiments were performed on Octet HTX (ForteBio) in Ix PBS, pH 7.4, O.l mg/ml BSA, 0.05% Sodium Azide, 5 and 0.02% Tween 20. Antibodies at a concentration of 50 nM were loaded on pre-hydrated AHC biosensors for 5 min. The loaded sensors were dipped into monovalent P66 (rabbit ANGPTL7his) at a concentration of 200 nM for 5 min of association, followed by 10 min of dissociation. Results were analyzed with ForteBio Data Analysis 11.1 and fit to a l : l binding mode! to détermine the monovalent KD. Responses (nm) at the end of association were also determined 10 (Table 6).

[00205] Table 6: Reactivity of anti-ANGPTL7 antibodies with the rabbit ANGPTL7 protein.

	AHC > Antibody > P66 (rabbit ANGPTL7-his) @ 200 nM
AblD	Response	KD(M)	kon(l/Ms)	kdis( l/s>	Full RA2
ATX-P-423	1.02	6.69E-09	8.29E+04	5.54E-04	0.99
ATX-P-424	0.93	4.65E-09	5.24E+04	2.44E-04	0.99
ATX-P-425	0.95	2.38E-09	4.I2E+04	9.79E-05	l.OO
ATX-P-427	0.93	3.2IE-09	4.16E+04	L33E-04	l.OO
ATX-P-428	0.04	N.B.	N.B.	N.B.	0.81
ATX-P-429	0.04	N.B.	N.B.	N.B.	0.92
ATX-P-430	0.21	N.B.	N.B.	N.B.	0.96
ΛΤΧ-Ρ-431	O.l l	N.B.	N.B.	N.B.	0.86
ATX-P-432	0.09	N.B.	N.B.	N.B.	0.70
ATX-P-433	0.90	7.02E-09	L04E+05	7.27E-04	0.99
ATX-P-434	0.81	Low KD	Low KD	Slow Koff	0.99
ATX-P-435	0.01	N.B.	N.B.	N.B.	0.67
ATX-P-436	0.02	N.B.	N.B.	N.B.	0.70

•	ATX-P-437	0.80	7.86E-I0	93 1.27E+05	1.00E-04	0.99
ATX-P-438	0.42	7.16E-09	6.79E+04	4.86E-04	0.98
ATX-P-439	0.92	2.95E-09	I.01E+05	2.98E-04	0.98
ATX-P-440	0.57	6.27E-09	5.07E+04	3.18E-04	0.98
ATX-P-442	0.95	3.38E-09	1.44E+05	4.87E-04	0.99
ATX-P-443	0.03	N.B.	N.B.	N.B.	0.85
ATX-P-444	0.30	N.B.	N.B.	N.B.	0.96
ATX-P-445	0.26	N.B.	N.B.	N.B.	0.96
ATX-P-446	0.41	3.19E-09	L08E+05	3.46E-04	0.98
ATX-P-447	0.65	3.33E-09	8.31E+O4	2.77E-04	0.99
ATX-P-448	0.75	9.49E-10	4.77E+04	4.52E-05	0.99
ATX-P-449	0.74	6.26E-10	6.53E+04	4.08E-05	0.99

[00206] Experiments were also conducted to détermine the reactivity and dissociation constants (Ko) of anti-ANGPTL7 antibodies with the human ANGPTL7 multimer protein. Binding experiments were performed on Octet HTX (ForteBio) in Ix PBS, pH 7.4, O.l mg/ml BSA, 0.05% 5 Sodium Azide, and 0.02% Tween 20. Antibodies at a concentration of 50 nM were loaded on prehydrated AHC biosensors for 5 min. The loaded sensors were dipped into Pext-0l (huANGTPL7FLAG) at a concentration of 100 nM for 5 min of association, followed by 10 min of dissociation. Results were analyzed with ForteBio Data Analysis ll.l and fit to a l:l binding model to détermine the apparent KD. Responses (nm) at the end of association were also determined (Table 10 7).

[00207] Table 7: Reactivity ofanti-ANGPTL7 antibodies with the human ANGPTL7 multimer protein.

	AHC > Antibody > Pext-01 (huANGTPL7-FLAG multimer) @ 100 nM
AblD	Response	KD (M)	kon(l/Ms)	kdis(1/s)	Full RA2
ATX-P-423	0.87	Low Kit	Low KD	Slow Koff	0.99
ATX-P-424	0.76	Low KD	Low KD	Slow Koff	1.00
ATX-P-425	0.83	Low KD	Low KD	Slow Koff	1.00
ATX-P-427	0.82	Low KD	Low KD	Slow Koff	1.00
ΛΤΧ-Ρ-428	0.05	N.B.	N.B.	N.B.	0.95
ATX-P-429	0.58	Low KD	Low KD	Slow Koff	1.00
ATX-P-430	0.20	N.B.	N.B.	N.B.	0.98
ATX-P-431	0.21	N.B.	N.B.	N.B.	1.00
ATX-P-432	0.22	N.B.	N.B.	N.B.	1.00
ATX-P-433	0.72	Low KD	Low KD	Slow Koff	0.99

ATX-P-434	0.68	Low KD	Low KD	Slow Kofï	0.98
AIX-P-435	0.45	Low KD	Low KD	Slow Koff	0.99
ATX-P-436	0.16	N.B.	N.B.	N.B.	0.97
ATX-P-437	0.71	Low KD	Low KD	Slow Kofï	0.98
ATX-P-438	0.60	6.53E-08	3.7IE+04	2.42E-O3	0.99
ATX-P-439	0.87	1.28E-08	7.98E+04	1.02E-03	1.00
ATX-P-440	0.61	Low KD	Low KD	Slow Koff	1.00
ATX-P-442	0.79	Low KD	Low KD	Slow Koff	0.98
ÀTX-P-443	0.03	N.B.	N.B.	N.B.	0.92
ATX-P-444	0.70	Low KD	Low KD	Slow Koff	0.97
ATX-P-445	0.80	Low KD	Low KD	Slow Koff	0.97
ATX-P-446	0.75	Low KD	Low KD	Slow Koff	0.97
ATX-P-447	0.91	Low KD	Low KD	Slow Koff	0.96
ATX-P-448	0.58	Low KD	Low KD	Slow Koff	0.99
ATX-P-449	0.65	Low KD	Low KD	Slow Koff	0.98

EXAMPLE 11 |00208] ANGPTL7 is a member of the ANGPTL family though its fonction is poorly characterized. Previous studies hâve shown that loss-of-function variants in the ANGPTL7 gene are associated with protection from glaucoma and reduced intraocular pressure (IOP). Therefore, 5 experiments were conducted to investigate the rôle of ANGPTL7 in IOP homeostasis and its potential as a target for the development of therapeutics.

[00209] Briefly, an ANGPTL7 knockout model was generated by Lexicon therapeutics in 129SvEv-C57BL/6 mixed genetic background. ANGPTL7 WT (N=14) and ANGPTL7 KO (N=17) mice were implanted with osmotic pumps filled with PBS or dexamethasone-cyclodextrin 10 solution (4 mg/kg/day) for 28 days. Body weight and IOP measurements were taken weekly. Alzet osmotic pumps (Model 1004) were sterile-filied with PBS or 45.45 mg/mL of dexamethasonecyclodextrin solution to provide a dose of 4 mgs/kg/day for the average 30g mouse. The pumps were then incubated in 0.9% normal saline at 37°C for 48 hours before implantation. On Day 0, body weight and IOP measurements were taken and then used to randomize the mice into the 15 following 4 treatment groups: Angptl7 KO + PBS, N-8; Angpit7 KO + Dexamethasone, N=9;

Angptl7 WT + PBS, N=5; and Angptl7 WT + Dexamethasone, N=14. PBS or dexamethasone pumps were subcutaneously implanted into the mouse. IOP and body weight were taken weekly on days 7, 14,21, and 28. On day 28, final body weight and IOP measurements were taken. OS/OD were enucleated and snap frozen in liquid nitrogen. Mice were euthanized followmg humane lACUC procedures.

(00210] Représentative results of the effects of dexamethasone-induced ocular hypertension in ANGPTL7 knockout mice are provided in FIGS. 8A-8C. FIG. 8A includes body weight data of mice post-implantation surgery; dexamethasone impaired weight gain in male mice compared to PBS-treated mice, thereby confirming the proper functioning of the dexamethasone osmotic pumps. FIG. 8B includes intraocuiar pressure (IOP) data of ANGPTL7 WT and ANGPTL7 KO mice dosed with PB S control or Dexamethasone (4 mg/kg/day); osmotic pumps were implanted on day 0. FIG. 8C includes représentative data of the changes in IOP of ANGPTL7 WT and ANGPTL 7 KO mice implanted with osmotic pumps containing PBS vehicle or dexamethasone (4 mg/kg/day) over 28 days. Ail IOP values were normalized to baseline (day 0) readings.

EXAMPLE 12

[00211| In Vivo Tolerability. Experiments were conducted to test the in vivo tolerability of anti-ANGPTL7 antibodies using single intravitreal (IVT) injections in New Zealand White Rabbits. Représentative data is provided in FIGS. 9A-9R. The anti-ANGPTL7 antibodies indicated (“BTX” labels are interchangeable with “ATX-P“ labels) were injected at either a 0.5 mg dose (FIGS. 9C, 9D, 9G, 9H, 9K, 9L, 90, 9P) or a 2.0 mg dose (FIGS. 9E, 9F, 91, 9J, 9M, 9N, 9Q, 9R) in the right eye (OD), or with a corresponding vehicle dose in the left eye (OS). (FIGS. 9A and 9B include data from Controls at 2 mg doses). Intraocuiar pressure (IOP) measurements (FIGS. 9A, 9C, 9E, 9G, 91, 9K, 9M, 90, 9Q) and changes in IOP (FIGS. 9B, 9D, 9F, 9H, 9J, 9L, 9N, 9P, 9R) were taken at the indicated time points over a 21 -day period.

[00212] Briefly, animais were dosed at Day 0, and IOP was normalized to Day -3 (N = 3 per treatment group; p < 0.05). Animais were dosed on Day 0. Experimental eyes (OD) were compared to vehicle eyes (OS) using two-way ANOVA. For the intravitreal injections (Day 0), rabbits underwent dilation with 1% tropicamide HCl, and were given buprénorphine (0.01-0.05 mg/kg) SC. Rabbits were sedated using a ketamine/xylazine cocktail (4-10/20-50 mg/kg) IM and the eyes were aseptically prepared using topical 5% betadine solution, followed by rinsing with stérile eye wash, and application of one drop of 0.5% proparacaine HCl. The conjunctiva were gently grasped with Colibri forceps, and the injection was made using a 27-30 G needle, 2-3 mm posterior to the superior limbus (through the pars plana), with the needle pointing slightly posteriorly to avoid contact with the lens. After dispensing the syringe contents, the needle was slowly withdrawn. Following the injection procedure, l drop of antibiotic ophthalmic solution was applied topically to the ocular surface. For each injection group, baseline ocular examinations and IOP measurements were obtained 24 hrs post-dose and at Days 3, 8, 14, and 2I. Terminal blood 5 collections for PK analysis (see below) were obtained on Day 21.

[00213] Intraocular pressure (IOP) was measured in both eyes of ail animais at the timepoints indicated. The measurements were taken using a Tonovet probe (iCare Tonometer, Espoo, Finland) without use of topical anesthetic. The tip of the Tonovet probe was directed to gently contact the central cornea. Six consecutive measurements were obtained. After the sixth 10 measurement, the average IOP shown was recorded. Animais did not require tranquilization for the procedure.

EXAMPLE 13

[00214| Pharmacokinetic (PK) Evaluation. Previous studies (described above) demonstrated that both 0.5 mg and 2.0 mg doses of several novel anti-ANGPTL7 antibodies were well tolerated 15 in rabbits over a 21-day period. Thus, experiments were conducted to evaluate the pharmacokinetics (PK) of several of the well tolerated anti-ANGPTL7 antibodies. New Zealand White Rabbits received a single bilateral (OU) injection of each of ATX-P-424 (FIGS. 10A-10C), ATX-P-439 (FIGS. 1IA-I1C), and ATX-P-448 (FIGS. 12A-12C). (“BTX” labels are interchangeable with “ATX-P“ labels.) Représentative pharmacokinetic (PK) data for the 20 ANGPTL7 antibody indicated included intraocular pressure (IOP) measurements dosed at 0.5 mg or 2.0 mg (OU) compared to vehicle (FIGS. Ι0Α, 1 IA, and 12A); changes in IOP compared to baseline (FIGS. Ι0Β, 1 IB, and 12B); and total ocular examination score (OE) (FIGS. 10C, 1 IC, and I2C).

[00215] Briefly, at least I mL of whole blood was drawn from the marginal ear vein or via 25 cardîac puncture (terminal bleed only) and placed into plastic red top tubes (no anti-coagulant or with sérum separator gel) for sérum acquisition at the timepoints indicated. Altematively, the centra! auricular artery was utilized if the vein is inaccessible or suboptimal for reuse for further collections. A thin layer of lidocaine 5% ointment was applied topically to the skin overlying the vessel prior to needle insertion. Oil of wintergreen was also applied to facilitate vasodilation as 30 needed. After collection, the tubes were gently mixed by inverting 3-5 times. Blood samples were stored at room température for between 30 and 60 minutes prior to processing. The whole blood samples were centrifuged at 4°C for 10 minutes at 2,000 x g in a refrigerated centrifuge. Immediately after centrifugation, the clear sérum was aliquoted into four (4) 200 μΐ, samples and stored frozen at-80°C until shipment for analysis. Additionally, a veterînaty ophthalmologist 5 performed complété ocular examinations using a slit lamp biomicroscope and indirect ophthalmoscope to evaluate ocular surface morphology and anterior and posterior segment inflammation on ail animais prior to dosing to serve as a baseline and at the timepoints indicated. Ail animais received normal ocular examinations to be considered for this study. The modified Hackett and McDonald ocular grading System, with additional scoring parameters for the ocular 10 posterior segment were used for scoring.

|002l6| For analysis of ATX-P-424 at 0.5 mg. animais were dosed in two different cohorts (N=6 and N=4) staggered by one day. Animais were dosed on Day 0 and euthanized (N=2 per time point) at 24h. and Day 7, 14, and 21. Number of eyes per measurement included N=20 on day 0 and l, N= 12 eyes on day 7, N=8 on day 14, and N=4 on day 21. For analysis of ATX-P-424 at 2.0 15 mg. on day 0, rabbits (N=6) exhibited OE scores of above 20 and were euthanized. For analysis of ATX-P-439, measurements included N=20 eyes at day 0 and I. Animais dosed with ATX-P-439 at both doses (N=6 per group) exhibited OE scores of above 20 after 24 hours and were euthanized. No further animais were dosed from the second cohort. For analysis of ATX-P-448, animais were dosed in two different cohorts N=6 and N=4 staggered by one day. Animais were dosed on Day 0 20 and euthanized 09=2 per time point) at 24h, and Day 7, 14, and 21. Number of eyes per measurement included N=20 on day 0 and l, N=l2 eyes on day 7, N=8 eyes on day 14, and N=4 eyes on day 21.

EXAMPLE 14 |00217| In Vivo Tolerability (Non-Human Primates). Experîments were also conducted to test the in vivo tolerability of anti-ANGPTL7 antibodies using single intravitreal (IVT) injections in Non-human primates (African Green Monkeys). FIGS. I3A-13C include représentative data of absolute IOP values at baseline (day 3) and on day 10, 6 hours post topical administration of saline and Latanoprost (FIG. 13A); changes in IOP 6 hours post topical administration of either saline (day 3) or Latanoprost (day 10) (FIG. I3B); and changes in IOP between vehicle and Latanoprost administration (FIG 13C). FIGS. 14A-I4H include représentative IOP measurements (FIGS. 14A,

14C, 14E, and I4G) and changes in IOP (FIGS. 14B, I4D, 14F, and 14H) in African Green Monkeys dosed with 2 mg of the indicated anti-ANGPTL7 antibody compared to an isotype control (BTX-330) and a single vehicle eye. And FIG. 15 includes représentative clinical scores of ocular examinations (OE) across ail the dosed groups.

[00218) Briefly, monkeys underwent prescreening to identify animais with basal IOP values greater than 16 mmHg and below 26 mmHg. For prescreening monkeys were sedated with ketamine/xylazine (8 mg/kg and 1.6 mg/kg, respectively) between 8:00-10:00AM for IOP measures using a rebound tonometer (Tonovet®). In the event animais were not fully sedated additional ketamine/xylazine was administered to effect. Any animal requiring greater than 25% over target dose for IOP measurements was preferentially targeted for exclusion. Measurement of IOP were performed 5-10 minutes after initial sédation (T=0). Animais were placed in a supine position one minute prior to IOP measurement (OS will be analyzed immediately prior to OD) and prone at ail other times while sedated. The sédation, body positioning and IOP measurement procedure was repeated in identical fashion 6 hours after initial prescreen assessments (Γ6 hour).

Any monkey demonstrating a greater than 5 mmHg drop in IOP between T=0 and T=6 hour (IOP sensitivity to sédation) was excluded from the study. Following completion of T=6 hour IOP measurements monkeys underwent ophthalmic screening to assess ocular and general Health by slit lamp biomicroscopy, fundoscopy, and color fundus photography (CFP). Monkeys with normal exam findings were enrolled into the study and randomized to treatment groups based on prescreen

T=0 IOP.

[00219] A minimum of 7 days after completion of screening activities and at least 7 days prior to initiation of Phase 2, animais were sedated and IOP assessed using the same methods employed for screening. Immediately after completion of T=0 IOP measures, one eye was dosed with 1 gtt (~35 pL) of latanoprost 0.005% ophthalmic solution (Xalatan® or équivalent) and the other with

0.9% saline. Dosing was performed between 8:00 AM and 10:00 AM. Follow up IOP assessments were performed at T=6 hour to détermine IOP lowering response for each animal. The absolute change in IOP between T=0 and T=6 h during screening and Phase 1 was calculated for each eye and subsequently the percent différence in ΔΙΟΡ between sédation alone and latanoprost (%ΔΔΙΟΡ) was determined using the formula:

100 àIOP(screemng) ΔΙΟΡ (phase 1) x 100)

[00220] Animais were subsequently ranked based on average %ΔΔΙΟΡ in response to timolol. Animais demonstrating minimal impact of sédation on IOP and response to timolol administration compared with sédation alone (“timolol responders”) were enrolled in the study. In the event less than 15 animais were identified for recruitment based on these criteria up to 8 additional animais 5 were screened in identical fashion to complété study enrolment.

[00221 ] For IVT dosing, topical proparacaine 0.5% was administered, allowing 30 seconds to take effect. and an eye spéculum placed, then the ocular surface was rinsed with 5% Betadine solution followed by stérile 0.9% saline. IVT injections were performed in both eyes (OU) according to the treatment assignaient using a 3l-gauge 5/16-inch needle/syringe (Ulticare VetRx l() U-100, or équivalent) inserted inferotemporally at the level of the ora serrata -2 mm posterior to the limbus. Following injection, a topical antibiotic ophthalmic ointment (neomycin, polymyxin, bacitracin or équivalent) was administered.

[00222] At the indicated time points, intraocular pressure (IOP) measurements were collected using a TonoVet (iCare. Finland) tonometer set to the dog (d) calibration setting. The TonoVet 15 rebound tonometer was well tolerated and required no additional local analgesia. AU IOP measures were performed while animais were sedated with ketamine and xylazine. Animais were sedated 5I0 minutes prior to each scheduled measure and placed in a supine position one minute prior to each IOP measurement (OS will be analyzed immediately prior to OD) and prone at ail other times while sedated. After completion of each IOP assessment animais were shifted to a prone position 20 and maintained in this position until recovered from sédation. Three measures were taken from each eye at each time point and the mean value employed for IOP analysis.

[00223] Additîonally, at the designated time points, both eyes (OU) were examined by slit lamp biomicroscopy. Scoring was applied to qualitative clinical ophthalmic findings using a nonhuman primate ophthalmic scoring system and summary score derived from exam components. At the 25 designated time points, bilateral color fundus images of the retina were captured with 50° of view centered on the fovea using a Topcon TRC-50EX retinal caméra with Canon 6D digital imaging hardware and New Vision Fundus Image Analysis System software. At designated time points, blood samples (0.5-1 mL) were collected and transferred to KiEDTA lavender top Vacutainers, gently inverted several times and retained on ice until CBC with differential analysis on an Abaxis 30 VetScan HM5 hematology analyzer. Whole blood (3 ml.) was collected via the fémoral or saphenous vein at the designated time points. Blood was transferred to vacutainer tubes (in the

ιοο absence of anticoagulant) and incubated at room température for approximately l hour before centrifugation 4000 rpm for I0 minutes at 4°C and isolation of sérum aliquots (~0.5 mL * 2 aliquots per time point). Aliquots were stored and shipped below -70°C to a designated laboratory for NAb analysis. At the designated timepoints, topical proparacaine 0.5% was administered, 5 allowing 30 seconds to take effect. an eye spéculum placed, then the ocular surface rinsed with 5%

Betadine solution followed by a stérile 0.9% saline rinse. Aqueous humor (50 pL) was sampled with a 0.3 mL insulin syringe with a 3l-gauge needle advance into the anterior chamber ~2 mm anterior to the temporal limbus. Aqueous samples were transferred to cryotubes, flash frozen and stored and shipped below^r -70°C to the Sponsor, or to a Sponsor designated laboratory for analysis.

Subjects were additionally assessed at cage-side twice daily for general wellbeing and evidence of ocular pathology. Data generated from protocol-defined endpoints were collated, summarized, and analyzed. Specified statistical analyses were performed where data meets required assumptions. If data failed to meet assumptions for defined statistical methods alternative methods were employed where possible. P values <0.05 will be considered statistically significant.

I5

Séquences

[00224] The various amino acid sequences and nucleic acid sequences referenced herein are provided below.

[00225] Table 8: Anti-ANGPTL7 antibodies (CDR sequences)

SEQ ID NO:	Antibody Name:	Descriptor:	Sequence:
VH Family: IGHV1
l	-	HCDRI Consensus	X|YX2]X3 (X| is S or D; X2 is G or Y; X3 is S or 11)
2	ATX-P-428	HCDRI	SYGIS
3	ATX-P-429	HCDRI	SYGIS
4	ATX-P-443	HCDRI	SYGIS
5	ATX-P-431	HCDRI	DYYIH
6	ATX-P-432	HCDRI	DYYIH
7	-	HCDR2 Consensus	WIXiX^XjXoGXsTXôYAQXtXsXqG (Xi is S, l, or N; X2 is A or P; Xj is Y or N; X4 is N or T; X5 is N or A: Xè is N or K; X? is N or K; Xg is L or F; Xo is R or Q)
8	ATX-P-428	HCDR2	WiSAYNGNTNYAQNLRG
9	ATX-P-429	HCDR2	W l SAYNGNTNYAQNL RG
10	ATX-P-443	HCDR2	W1IAYNGNTNYAQKLQG
11	ATX-P-431	HCDR2	WINPNTGATKYAQK.FQG
12	ATX-P-432	11CDR2	WINPNTGATKYAQKFQG
13	ATX-P-428	HCDR3	VSLVWFGELPRGFDY
14	ATX-P-429	HCDR3	VSLVWFGELPRGFDY
15	ATX-P-443	HCDR3	DTGFSFDY

ΙΟΙ

16	ATX-P-431	HCDR3	EDNGNYGDVI DI
17	ATX-P-432	HCDR3	EDNGNYGDVFDI
VH Family: IGHV2
18	-	l (CDR I Consensus	TSGVGVG
!9	ATX-P-442	HCDRI	TSGVGVG
20	ATX-P-437	HCDRI	TSGVGVG
2I	-	HCDR2 Consensus	LlYWNDDKXiYSPSLKS (Xi is R or Q)
22	ATX-P-442	HCDR2	LIYWNDDKRYSPSLKS
23	ATX-P-437	HCDR2	LIYWNDDKQYSPSLKS
24	-	HCDR3 Consensus	X1X2X3X4X5X6FFDX7 (Xi is S, D, or N; X; is Y or P; Xi is G or D; X4 is D or Y; X$ is Y or G: X6 is W or D; X? is L or Y )
25	ATX-P-442	HCDR3	DYGDYWFFDL
26	ATX-P-437	HCDR3	NPDYGDFFDY
VH Family: 1GHV3
27	-	HCDRI Consensus	X1X2X3MX4 (X1 is V. S, D, or T; X: is Y. H, or F; X3 is D, G, S, or A; X4 is H. S. or N)
28	ATX-P-444	HCDRI	VYDMH
29	ATX-P-445	HCDRI	SHDMH
30	ATX-P-446	HCDRI	SYDMH
3I	ATX-P-447	HCDRI	DYDMH
32	ATX-P-427	HCDRI	DYGMS
33	ATX-P-440	HCDRI	DYGMS
34	ATX-P-424	HCDRI	SYSMN
35	ΛΤΧ-Ρ-425	HCDRI	TYSMN
36	ATX-P-430	HCDRI	SYAMS
37	ATX-P-439	HCDRI	SYAMS
38	ATX-P-449	HCDRI	SYGMH
39	ATX-P-448	HCDRI	SYGMH
40	ATX-P-423	HCDRI	SYGMH
41	ATX-P-438	HCDRI	SYGMH
42	ATX-P-433	HCDRI	DFAMH
43	-	HCDR2 Consensus	X| X:X3X4X5X6X7X8X9X|0X11 X1 ;X 13X14X1SG (X1 is G, T, S, A, V, H. or 1; X2 is I or M; X3 is D, N, T, S, or G; X4 is P, W, S, G, or Y; X5 is D, A. N, S, or Y; Xi is G or S; X7 is D, G. Y, S, 1, or N; X8 is T, S, N, 1. Y, or D; X, is Y, T, F, Μ, K, G. or I; X10 is Y, G, or F; Xn is P, Y, or A; X12 is G, D, or A; X13 is S or D; X|4 is V, L. or S; X15 is K or M)
44	ATX-P-444	IICDR2	G1DPDGDTYYPGSVKG
45	ATX-P-445	HCDR2	G1DPAGDTYYPDSVKG
46	ATX-P-446	HCDR2	GIDPDGD'I YYPGSVKG
47	ATX-P-447	HCDR2	G1DPDGDTYYPGSLKG
48	ATX-P-427	HCDR2	GINWNGGSTGYADSVKG
49	ATX-P-440	HCDR2	TINWNGGNTGYADSVKG
50	ATX-P-424	HCDR2	SITSSSYIFYADSLKG
5I	ATX-P-425	HCDR2	SITSSSSYMFYADSVMG
52	ATX-P-430	HCDR2	A1SGSGGSTYYADSVKG
53	ATX-P-439	HCDR2	A1SGSGGST Y Y ADS VKG
54	ATX-P-449	HCDR2	VISYYGSNKYYADSVKG
55	ATX-P-448	HCDR2	VMSYDGINGYYADSVKG
56	ATX-P-423	HCDR2	H1TYDGSDKYYGDSVKG

102

57	ATX-P-438	HCDR2	IISYDGNNKYYADSVKG
58	ATX-P-433	HCDR2	GIGWNSGSIGYADSVKG
59	ATX-P-444	HCDR3	GEESNSSEDGFDI
60	ATX-P-445	HCDR3	GEASSSSEDAFDl
6I	ATX-P-446	HCDR3	GEDNSSSEDAFDl
62	ATX-P-447	HCDR3	GEDSSSSEDAFDI
63	ATX-P-427	HCDR3	YSGSFRDAFDl
64	ATX-P-440	HCDR3	DEGAAGLGYYFDY
65	ATX-P-424	HCDR3	DSNWGEAFDl
66	ATX-P-425	HCDR3	DSNWGEAFDt
67	ATX-P-430	HCDR3	DGDYYYYYMDV
68	ATX-P-439	HCDR3	VERDMVRGHYYYYMDV
69	ATX-P-449	HCDR3	GITMDV
70	ΛΤΧ-Ρ-448	HCDR3	LVYADDAFDI
71	ATX-P-423	HCDR3	DGYSSGWWYFDY
72	ATX-P-438	HCDR3	ERGYSSSSGYYYYYMDV
73	ATX-P-433	HCDR3	APDYGDYYI DY
VH Family: IGHV4
74	-	HCDRI Consensus	SXiSXjYWXj (Xi is S or G; X; is S or Y; Xj is G or S)
75	ATX-P-434	HCDRl	SSSSYWG
76	ATX-P-435	HCDRI	SSSSYWG
77	ATX-P-436	HCDRl	SGSYYWS
78	-	HCDR2 Consensus	X1IYYSGSTX2SNPSLKS (Xi is S. or Y; X? is Y or S)
79	ATX-P-434	HCDR2	SIYYSGSTYSNPSLKS
80	ATX-P-435	HCDR2	SIYYSGSTYSNPSLKS
8I	ATX-P-436	HCDR2	YIYYSGSTSYNPSLKS
82	-	HCDR3 Consensus	XÆXjXiGXsXoXvXsXoY (Xi is Q or A; X; is Y or K: X3 is 1 or W; X.i is S or E; Xs is T or D: X<, is E or Y: X7 is Y or F; X8 is F or D; X» is Q or Y)
83	ATX-P-434	HCDR3	QY1SGTEY1-QY
84	ATX-P-435	HCDR3	QY1SGTEYFQY
85	ATX-P-436	HCDR3	AKWEGDYFDY
VH Family: 1GKVI
86	-	LCDRI Consensus	RASQX|IX2X3X4LX5 (X| is G or S; X2 is S, R. or Y; X3 is S, N, or I; X4 is W, D, or Y; Xs is Λ. G. or N)
87	ATX-P-439	LCDRI	RASQG1SSWLA
88	ATX-P-424	LCDRI	RASQGIRNDLG
89	ATX-P-425	LCDRI	RASQGIR1DLG
90	ATX-P-423	LCDRI	RASQGIRNDLG
9l	ATX-P-442	LCDRI	RASQGISSYLA
92	ATX-P-437	LCDRI	RASQS1SSYLN
93	ATX-P-440	LCDRI	RASQSISSWLA
94	ATX-P-433	LCDRI	RASQSISIYLN
95	ATX-P-436	LCDRI	RASQSISSYLN
96	ATX-P-434	LCDRI	RASQSIYSYLN
97	ATX-P-427	LCDRI	RASQGIRNDLG
98	-	LCDR2 Consensus	AX1SSLX2S (Xi is A or T; X2 is Q or P)
99	ATX-P-439	LCDR2	AASSLQS
100	ATX-P-424	LCDR2	AASSLPS
10!	ΛΤΧ-Ρ-425	LCDR2	AASSLPS

103

I02	ATX-P-423	LCDR2	AASSLQS
103	ATX-P-442	LCDR2	AASSLQS
104	ATX-P-437	LCDR2	AASSLQS
105	ATX-P-440	LCDR2	ATSSLQS
106	ATX-P-433	LCDR2	AASSLQS
107	ATX-P-436	LCDR2	AASSLQS
ί 08	ATX-P-434	LCDR2	AASSLQS
109	ATX-P-427	LCDR2	AASSLQS
l ΙΟ	-	LCDR3 Consensus	XiQX:X3X4XsPX(1X7 (Xi is L or Q; X2 is A, H. S, or D; X3 is N, F, or Y; X4 is S, T, or N; X5 is F. Y, or T; X6 is W. L. L P. or Y; X7 is T or Y)
I 11	ATX-P-439	LCDR3	QQANSFPWT
Il2	ATX-P-424	LCDR3	LQHNSYPWT
113	ATX-P-425	LCDR3	LQHNSYPWT
Il4	ATX-P-423	LCDR3	LQHNSYPLT
H5	ATX-P-442	LCDR3	QQSFSTPLT
116	ATX-P-437	LCDR3	QQSFSTPLT
H7	ATX-P-440	LCDR3	QQSYSTPIT
H8	ATX-P-433	LCDR3	QQSYTTPLT
H9	ATX-P-436	LCDR3	QQSYSTPLT
120	ATX-P-434	LCDR3	QQSYSTPPYT
I2l	ATX-P-427	LCDR3	LQDYNYPYT
VH Family: IGKV2
122	-	L.CDRI Consensus	RSSQSLXiXîSXjXjXsXôYLX? (Xi is L or V; X2 is H, Y, or F; X3 is N or D; X4 is R or G; Xs is Y or N; X6 is N or T; X? is D or N)
123	ATX-P-429	LCDRI	RSSQSLLHSNRYNYLD
I24	ATX-P-444	LCDRI	RSSQSLVYSDGNTYLN
125	ATX-P-445	LCDRI	RSSQSLVYSDGNTYLN
126	ATX-P-446	LCDRI	RSSQSLVFSDGNTYLN
127	ATX-P-447	LCDRI	RSSQSLVYSDGNTYLN
I28	-	LCDR2 Consensus	X]X2SNRX3S (Xi is L. K, or E; X2 is G or V: Xj is A or D)
I29	ATX-P-429	LCDR2	LGSNRAS
130	ATX-P-444	LCDR2	KVSNRDS
I3l	ATX-P-445	LCDR2	EVSNRDS
132	ATX-P-446	LCDR2	KVSNRDS
133	ATX-P-447	LCDR2	EVSNRDS
134	-	LCDR3 Consensus	MQXiX2X3X4PXsT (Xi is T or G; X2 is L or T; Xj is Q or H; X4 is T or W; X5 is Y or W)
135	ATX-P-429	LCDR3	MQTLQTPYT
I36	ATX-P-444	LCDR3	MQGTHWPWT
I37	ATX-P-445	LCDR3	MQGTHWPWT
138	ATX-P-446	LCDR3	MQGTHWPWT
139	ATX-P-447	LCDR3	MQGTHWPWT
VH Family: IGKV3
140	-	LCDRI Consensus	RASQSVSXiXÆXjA (Xi is S, N. or R; X2 is Y or S: Xi is L or Y; X4 is A or L)
141	ATX-P-449	LCDRI	RASQSVSSYLA
142	ATX-P-448	LCDRI	RASQSVSSYLA
143	ATX-P-435	LCDRI	RASQSVSNYLA
144	ATX-P-428	LCDRI	RASQSVSSSYLA
145	ATX-P-443	LCDRI	RASQSVSSSYLA

] 04

146	ATX-P-431	LCDRl	RASQSVSSSYLA
147	ATX-P-432	LCDRl	RASQSVSSSYLA
148	ATX-P-430	LCDRl	RASQSVSSSYLA
149	ATX-P-438	LCDRl	RASQSVSRSYLA
150	-	LCDR2 Consensus	XiASXiRAT ( X । is D or G; X3 is N, S, or T)
151	ATX-P-449	LCDR2	DAS NRAT
152	ATX-P-448	L.CDR2	DAS NRAT
153	ATX-P-435	LCDR2	DASNRAT
154	ATX-P-428	LCDR2	GAS SRAT
155	ATX-P-443	LCDR2	GAS SRAT
156	ATX-P-431	LCDR2	GAS SRAT
157	ATX-P-432	LCDR2	GAS SRAT
158	ATX-P-430	LCDR2	GAS SRAT
159	ATX-P-438	LCDR2	GASIRAT
160	-	LCDR3 Consensus	QQX|X:X3X4X5X6T (Xi is R. Y, or G; X2 is S, G. or Q; X3 is N, S, or V; X.< is W. S, or 1; X5 is P or L; X& is L, S. P. or T)
161	ATX-P-449	LCDR3	QQRSNWPLT
162	ATX-P-448	LCDR3	QQRSNWPLT
163	ATX-P-435	LCDR3	QQRSNWPS
164	ATX-P-428	LCDR3	QQYGSSPPT
165	ATX-P-443	LCDR3	QQYGSSLT
166	ATX-P-431	LCDR3	QQYGSSPPT
167	ATX-P-432	LCDR3	QQYGSSPPT
168	ATX-P-430	LCDR3	QQYGSSPPT
169	ATX-P-438	LCDR3	QQGQVIPPT

|00226| Table 9: Anti-ANGPTL7 antibodies (VH and VL sequences)

SEQ ID NO:	Antibody Name:	Descriptor:	Sequence:
170	ATX-P-428	VH	QVQLVQSGAEVKKPGASVKVSCKASGYTFSSYGISWVRQAPGQG LEWMGW1SAYNGN TNYAQNLRGRVAMTTDTSTTTA YMELRSLR SDDTAVYYCARVSLVWFGELPRGFDYWGQGTLVTVSS
171	ATX-P-443	VII	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ GLEWMGWIIAYNGNTNYAQKLQGRITMTTNTSTNTAYMELRSL RSDDTAVYYCGRDTGFSFDYWGQGTLVTVSS
172	ATX-P-429	VH	QVQLVQSGAEVKKPGASVKVSCKASGYTFSSYG1SWVRQAPGQG LEWMGWISAYNGNTNYAQNLRGRVAMTTDTSTTTAYMELRSLR SDDTAVYYCARVSLVWFGELPRGFDYWGQGTLVTVSS
173	ATX-P-431	VH	QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYY1HWVRQAPGP GLEWLGW1NPNTGATKYAQKFQGRVTMTRDTSISTAYMELSRLR SDDTAVYYWAREDNGNYGDVFDIWGQGTMVTVSS
174	ATX-P-432	VH	QVQLVQSGAEVK.KPGASVKVSCKASGYTFTDYY1HWVRQAPGP GLEWLGWINPNTGATKYAQKFQGRVTMTRDTSISTAYMELSRLR SDDTAVYYCARF.DNGNYGDVFDIWGQGTMVTVSS
175	ATX-P-428	VH - nucléotide	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCT GGGGCCTC AGTGAAGGTCTCCTGCA AGGC TTCTGG FTACACCT TTTCCAGCTATGGTATCAGCTGGGTGCGACAGGCCCCTGGACA AGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAA CACAAACTATGCACAGAACCTCCGGGGCAGAGTCGCCAIGAC CACAGACACATCCACGACCACAGCCTACATGGAGTTGAGGAG CCTGAGATCTGACG ACACGGCCG TGI ATTACTGTGCGAGAGTT

105

			TCATTAGTATGGTTTGGGGAATTACCCAGGGGTTTTGACTACT GGGGCCAGGGAACCCTGGTCACCGTCTCCTCA
176	ATX-P-443	VH — nucléotide	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCT GGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGTTACACCT TTACCAGCTATGGTATCAGCTGGGTGCGACAGGCCCCTGGACA AGGGCTTGAGTGGATGGGATGGATCATCGCl TACAATGGTAAC ACAAACTATGCACAGAAGCTCCAGGGCAGAATCACCATGACC ACAAACACATCCACGAACACAGCCTACATGGAGCTGAGGAGC CTGAGATCTGACGACACGGCCGTGTATTACTGTGGGAGAGATA CGGGGTTTTCTTTTGACTACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCA
177	ATX-P-429	VH - nucléotide	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCT GGGGCCTCAGTGAAGG TCTCC TGCAAGGCTTCTGGTTACACCT TTTCCAGCTATGG I ATCAGCTGGGTGCGACAGGCCCCTGGACA AGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAA CACAAACTATGCACAGAACCTCCGGGGCAGAGTCGCCATGAC CACAGACACATCCACGACCACAGCCTACATGGAGTTGAGGAG CCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGTT TC ATT AGT ATGGTTTGG GG A A TTACCC A GGGGTTTTG ACTACT GGGGCCAGGGAACCCTGGTCACCGTCTCCTCA
I78	ATX-P-431	VH - nucléotide	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCT GGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCT TCACCGACTACTATATACACTGGGTGCGACAGGCCCCTGGGCC AGGGCTTGAGTGGTTGGGCTGGATCAACCCTAACACTGGTGCC ACAAAGTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACC AGGGACACGTCCATCAGCACAGCCTATATGGAGCTGAGCAGG CTGAGATCTGACGACACGGCCGTATATTATTGGGCGAGAGAA GATAATGGGAACTACGGGGATGTTTTTGATATCTGGGGACAAG GGACAATGGTCACCGTCTCTTCA
179	ATX-P-432	VH - nucléotide	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCT GGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCT TCACCGACTACTATATACACTGGGTGCGACAGGCCCCTGGGCC AGGGCT1GAGIGGTTGGGCTGGATCAACCCTAACACTGGTGCC ACAA AGTATGCA C AG A AGT1TC AGGGCAGGGIC ACC ATG A CC AGGGACACGTCCATCAGCACAGCCIATATGG AGCTGAGCAGG CTGAGATCTGACGACACGGCCGTATATTATTGTGCGAGAGAAG ATAATGGGAACTACGGGGAl GTTT TTGATATCIGGGGACA AGG GACAATGGTCACCGTCTCTTCA
180	ATX-P-428	VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA^QQKPGQAP RLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQ YGSSPPTFGGGTKVEIK
I8l	ATX-P-443	VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAP RLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQ YGSSLTFGGGTKVDIK
182	ATX-P-429	VL	DIVMTQSPLSLPVTPGEPASISCRSSQSLLIISNRYNYLDWYLQKPG QSPQLLIYLGSNRASGVPDRFSGSGSGTDl-Ί LQISRVEAEDVGVY YCMQTLQTPYTFGQGTKLEIK
183	ATX-P-431	VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAP RLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQ YGSSPPTFGGGTKVEIK.
184	ATX-P-432	VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAP RLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQ YGSSPPTFGGGTK VEl K
185	ATX-P-428	VL — nucléotide	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT

106

			TAGCAGCAGCTAC il AGCC TGGTACCAGCAGAAACCTGGCCA GGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACT GGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAG TGTATTACTGTCAGCAGTATGGTAGCTCACCTCCCACTTTCGGC GGAGGGACCAAGGTGGAGATCAAA
186	ATX-P-443	VL - nucléotide	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCA GGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACT GGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAG TGTATTACTGTCAGCAGTATGGTAGCTCACTCACTTTCGGCGG AGGGACCAAAGTGGATATCAAA
187	ATX-P-429	VL - nucléotide	GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCC TGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTC CTGCATAGTAATAGATACAACTATTTGGATTGGTACCTGCAGA AGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAA TCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCA GGCACAGATTTTACACTGCAAATCAGCAGAGTGGAGGCTGAG GATGTTGGGGTTTATTACTGCATGCAAACTCTACAAACTCCGT ACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA
I88	ATX-P-431	VL - nucléotide	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCA GGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACT GGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAG TGTATTACTGTCAGCAGTATGGTAGCTCACCTCCCACTTTCGGC GGAGGGACCAAGGTGGAAATCAAA
189	ATX-P-43 2	VL - nucléotide	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAG TGT TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCA GGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACT GGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAG TGTATTACTGTCAGCAGTATGGTAGCTCACCTCCCACllTCGGC GGAGGGACCAAGGTGGAAATCAAA
190	ATX-P-437	VH	QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKA LEWLALIYWNDDKQYSPSLKSRLTITKDTSKNQVVLTMTNMDP MDTATYYCAHNPDYGDFFDYWGQGTLVTVSS
I9l	ATX-P-442	VH	QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKA LEWLALIYWNDDKRYSPSLKSRLTITKDTSKNLVVLTMTNMDPV DTATYYCARDYGDYWFFDLWGRGTPVTVSS
192	ATX-P-437	VII - nucléotide	CAG A TC ACCTTG A A GG A GTCTGGTCCT ACGCTG GTGA A ACCC A CACAGACCCTCACGTTGACCTGCACCTTCTCTGGGTTCTCACTC AGCACTAGTGGCGTGGGTGTGGGCTGGATCCGTCAGCCCCCAG GAAAGGCCCTGGAGTGGCTTGCACTCATTTATTGGAATGATGA TAAACAGTACAGCCCTTCTCTGAAGAGCAGGCTCACCATCACC AAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAAC ATGGACCCTATGGACACAGCCACATA T TACTGTGCACACAACC CTGACTACGGTGACTTCTTTGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA
193	ATX-P-442	VH - nucléotide	CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAAACCCA CACAGACCCTCACGCTGACCTGCACCTTCTCTGGGTTCTCACTC

107

			AGCACTAGTGGAGTGGGTGTGGGCTGGATCCGTCAGCCCCCA GGAAAGGCCCTGGAGTGGC l TGCACTCATTTATTGGAATGATG ATAAGCGCTACAGCCCATCTCTGAAGAGCAGGCTCACCATCAC CAAGGACACCTCCAAAAACCTGGTGGTCCTTACAATGACCAAC ATGGACCCTGTGGACACAGCCACATATTACTGTGCACGTGACT ACGGTGACTACTGGTTCTTCGATCTCTGGGGCCGTGGCACCCC GGTCACCGTCTCCTCA
I94	ATX-P-437	VL	DIQMTQSPSSLSASVGDRVTITCRASQS1SSYLNWYQQKPGKAPK LL1YAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFATYYCQQSF STPLTFGGGTKLEIK
195	ATX-P-442	VL	DIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPK LLIYAASSLQSGVPSRFSGSGSGTDI l'LTISSLQPEDFATYYCQQSF STPLTFGGGTKLEIK
196	ATX-P-437	VL —nucléotide	G AC ATCCAG ATG ACCC AGTCTCC ATC CTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCAT TAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGC CCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGG GTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCA TTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTA CTACTGTCAACAGAGTTTCAGTACCCCGCTCACTTTCGGCGGA GGGACCAAGCTGGAAATCAAA
197	ATX-P-442	VL — nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGGGCAT TAGCAGTTATTTAGCCTGGTATCAGCAAAAACCAGGGAAAGC CCCTAAGCTCCTGA TCTATGCTGCATCCAGTTTGCAAAGTGGG GTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCA CTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTA CTACTGTCAACAGAGTTTCAGTACCCCGCTCACTTTCGGCGGA GGGACCAAGCTGGAGATCAAA
198	ATX-P-444	VH	EVQLVESGGGLVQPGGSLRLSCAASGI 'TLSVYDMHWVRQVSGK GLEWVSGJDPDGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRV GDTAVYYCLRGEESNSSEDGFDIWGQGTMVTVSS
199	ATX-P-445	VH	EVQLVESGGGLVQPGGSLRLSCAASGFTFSSHDMHWVRQVTGK GLEWVSG1DPAGDTYYPDSVKGRFTISRENAKNSLYLQMNSLRA GDI AVYYCTRGEASSSSEDAFD1WGQGTMV1 VSS
200	ATX-P-446	VH	EVQLVESGGGLVQPGGSLRLSCAASGI Ί LSSYDMHWVRQVIGKG LEWVSGIDPDGDTYYPGSVKGRFTISREDAKNSLYLQMNSLRAG DTAVYYCTRGEDNSSSEDAFD1WGQGTMVTVSS
201	ATX-P-447	VH	EVQLVESGGGLVQPGGSLRLSCAASGFTISDYDMHWVRQTTGKG LEWVSG1DPDGDTYYPGSLKGRFT1SRENAKNSLYLQMNSLRAG DTAVYYCTRGEDSSSSEDAFDIWGQGTMVTVSS*
202	ATX-P-427	VH	EVQLVESGGGVVRPGGSLRLSCAASGFSFDDYGMSWVRQVPGK GLEWVSGINWNGGSTGYADSVKGRFTISRDNAKNSLYLQMSSLR AEDTALYYCASYSGSFRDAFD1WGQGTMVTVSS
203	ATX-P-440	VH	EVQLVESGGGVVRPGGSLRLSCAASGFTFDDYGMSWVRQAPGK GLEWVST1NWNGGNTGYADSVKGRFT1SRDNAKNSLYLQMNSL RAEDTALYYCARDEGAAGLGYYFDYWGQGTLVTVSS
204	ATX-P-424	VH	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKG LEWVSSITSSSYIFYADSLKGRFTISRDNAKNSLFLQMNSLRAEDT AVYYCARDSNWGEAFDI WGQGTMVTVSS
205	ATX-P-425	VH	EVQLVESGGGLVKPGGSLRLSCAASGFTFSTYSMNWVRQAPGKG LEWVSSITSSSSYMFYADSVMGRJ TISRDNAKNSLYLQMNSLRAE DTADYYCARDSN WGEAFDI WGQGTMVTVSS

108

206	ATX-P-430	VH	EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKG LEWVSAISGSGGSTYYADSVKGRFT1SRDNSKNTLYLQMNSLRAE DTAVYYCAKDGDYYYYYMDVWGKGTTVTVSS
207	ATX-P-439	VH	EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKG LEWVSAISGSGGSTYYADSVKGRFT1SRDNSKNTLYLQMNSLRAE DTAVYYCAKVERDMVRGHYYYYMDVWGKGTTVTVSS
208	ATX-P-423	VH	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK GLEWVSHITYDGSDKYYGDSVKGRFTISRDNSKNTLYLQMNSTR AEDTAVYYCAKDGYSSGWWYFDYWGQGTLVTVSS
209	ATX-P-438	VH	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK GLEWVAIISYDGN'NKYYADSVKGRF'11SRDNSKNTLYLQMNSLR DEDTAVYYCAKERGYSSSSGYYYYYMDVWGKGTTVTVSS
210	ATX-P-448	VH	QVQLVESGGGVVQPGRSLRLSCAASGFPFSSYGMHWVRQAPGK GLEWVAVMSYDGINGYYADSVKGRI TISRDNSKNTLYLQMNSL RAED TAVYYCARLVYADDAFDIWGQGTTVTVSS
2ll	ATX-P-449	VH	QVQLVESGGGVVQPGRSLRLSCAASGFAFSSYGMHWVRQAPGK GLEWVAVISYYGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLR AEDTAVYHCARGITMDVWGKGTTVTVSS
212	ATX-P-433	VH	EVQLVESGGGLVQPGRSLRLSCAASGFTFDDFAMHWVRQGPGK GLEWVSGIGWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLR AEDTALYYCAKAPDYGDYYFDYWGQGTLVTVSS
213	ATX-P-444	VH - nucléotide	GAGGTGCAGCTGGTGGAGTCGGGGGGAGGCTTGGTACAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCC TCAGTGTCTACGACATGCACTGGGTCCGCCAAGTTTCAGGAAA AGGTCTGGAGTGGGTCTCAGGTATTGATCCTGATGGTGACACA TACTATCCCGGCTCCGTGAAGGGCCGATTCACCATCTCCAGAG AAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAG AGTCGGGGACACGGCTGTGTATTA1TGTC TAAGAGGGGAGGA AAGCAACTCGTCCGAGGATGGTTTTGATATATGGGGACAAGG GACAATGGTCACCGTCTCCTCA
214	ATX-P-445	VH - nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TCAGTAGCCACGACATGCACTGGGTCCGCCAAGTTACAGGAA AAGGTCTGGAGTGGGTCTCAGGTATTGATCCTGCTGGTGACAC ATAC1ATCCAGAC TCCGTGAAGGGCCGATTCACCATCTCTAGA GAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGA GAGCCGGGGACACGGCTGTGTATTACTGTACAAGAGGAGAGG CTAGTAGTTCGTCCGAGGATGCTTTTGATATCTGGGGACAAGG GACAATGGTCACTGTCTCCTCA
215	ATX-P-446	VH - nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCC TCAGTAGCTACGACATGCACTGGGTCCGCCAAGTTATAGGAAA AGGTCTGGAGTGGGTCTCAGGTATTGATCCTGATGGTGACACA TACTATCCAGGCTCCGTGAAGGGCCGATTCACCATCTCCAGAG AAGATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAG AGCCGGGGACACGGCTGTGTATTACTGTACAAGAGGAGAGGA TAACAGCTCGTCCGAGGATGCTTTTGATATCTGGGGACAAGGG ACAATGGTCACTGTCTCCTCA
216	ΛΤΧ-Ρ-447	VH — nucléotide	GAGGTCCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCG GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCA TCAGTGACTACGACATGCACTGGGTCCGCCAAACTACAGGAA AAGGTCTAGAATGGGTCTCAGGTATTGATCCTGATGGCGACAC ATATTATCCAGGCTCCTTGAAGGGGCGATTCACCATCTCCAGA GAAAATGCCAAGAATTCTTTGTATCTTCAAATGAACAGTCTGA GAGCCGGGGACACGGCTGTGTATTACTGTACAAGAGGAGAGG

109

			ATAGTAGTTCGTCCGAGGATGCTTTTGATATCTGGGGACAAGG GACAATGGTCACCGTCTCCTCA
217	ATX-P-427	VH - nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGTGTGGTACGGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCAGCT TTGATGATTATGGCATGAGCTGGGTCCGCCAAGTTCCAGGGAA GGGGCTGGAGTGGGTCTCTGGTATTAATTGGAATGGTGGTAGT ACAGGTTATGCAGACTCTGTGAAGGGCCGATTCACCATCTCCA GAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAGCAGTCT GAGAGCCGAGGACACGGCCTTGTATTACTGTGGGAGCTATAGT GGGAGCTTCCG TGAT GCTTTTGATATCTGGGGACAAGGGACAA TGGTCACCGTCTCTTCA
218	AIX-P-440	VH — nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGTGTGGTACGGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TTGATGATTATGGCATGAGCTGGGTCCGCCAAGCTCCAGGGAA GGGGCTGGAGTGGGTCTCTACTATTAATTGGAATGGTGGTAAC ACAGGTTATGCAGACTCTGTGAAGGGCCGATTCACCATCTCCA GAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCT GAGAGCCGAGGACACGGCCTTGTATTACTGTGCGAGAGATGA AGGAGCAGCTGGACTTGGATACTACTTTGACTACTGGGGCCAG GGAACCCTGGTCACCGTCTCCTCA
2I9	ATX-P-424	VH — nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCAAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TCAGTAGCTATAGCATGAACTGGGTCCGCCAGGCTCCAGGGA AGGGGC'I GGAGTGGGTCTCATCCATTACTAG l AGTAGTTACAT ATTCT ACG C AG ACTC ATTG A A GGGCCG ATT C ACC ATCTC C AG A GACAACGCCAAGAACTCACTGTTTCTGCAAATGAACAGCCTGA GAGCCGAGGACACAGCTGTTTATTACTGTGCGAGAGATTCTAA CTGGGGCGAGGCTTTTGATATCTGGGGACAAGGGACAATGGT CACCGTCTCTTCA
220	ATX-P-425	VH — nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCAAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGTTTCACCT TCAGTACTTATAGCATGAACTGGGTCCGCCAGGCTCCAGGGAA GGGGCTGGAGTGGGTCTCATCCATTACTAGTAGTAGTAGTTAC ATGTTCTACGCAGACTCAGTGATGGGCCGATTCACCATCTCCA GAGACAACGCCAAGAACTCACTGTACCTACAAATGAACAGCC TGAGAGCCGAGGACACAGCTGATTATTACTGTGCGAGAGATTC TAATTGGGGGGAGGCTTTTGATATCTGGGGACAAGGGACAAT GGTCACCGTCTCTTCA
221	ATX-P-430	VH —nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAA GGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCA GAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC TGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGACG GTGACTACTACTACTACTACATGGACGTCTGGGGCAAAGGGAC CACGGTC A CCGTCTCCTC A
222	ATX-P-439	VH — nucléotide	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCT GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAA GGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCA GAGACAATT CCAAGAACACGCTGTATCTGCAAATGAACAGCC TGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGTGG AAAGGGATATGGTT CGGGGCCACTACTACTACTACATGGACGT CTGGGGCAAAGGGACCACGGTCACCGTCTCTTCA

HO

223	ATX-P-423	VII — nucléotide	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCT GGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAA GGGGCTGGAGTGGGTGTCACATATAACATATGATGGAAGTGA TAAATACTATGGAGACTCCGTGAAGGGCCGA T TCACCATCTCC AGAGACAAl’TCCAAGAATACGCTGTATCTGCAAATGAACAGC CTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGAT GGGTATAGCAGTGGCTGGTGGTACTTTGACTACTGGGGCCAGG GAACCCTGGTCACCGTCTCCTCA
224	ATX-P-438	VH - nucléotide	CAGGTGCAGCTGGTGGAGTCCGGGGGAGGCGTGGTCCAGCCT GGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAA GGGGCTGGAGTGGGTGGCAATTA TA TCATATGA TGGAAATAA TAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCC AGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGC CTGAGAGATGAGGACACGGCTGTTTATTATTGTGCGAAAGAG AGGGGGTATAGCAGCTCGTCCGGCTACTACTACTACTACATGG ACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCA
225	AIX-P-448	VH - nucléotide	CAAGTGCAATTGGTGGAGTCCGGTGGAGGAGTAGTACAGCCG GGA AGGTC ACTG AG A CTTTCC TGCGC TGCT AGTGG ATTCCC A T TTAGCTCCTACGGGATGCACTGGGTTCGCCAAGCGCCAGGTAA GGGACTGGAATGGGTGGCTGTCATGAGTTACGATGGAATTAA CGGCTATTATGCCGATAGCGTCAAAGGCCGGTTCACGATCTCA AGAGACAACTCTAAGAACACGCTCTACTTGCAGATGAACAGT CTCCGCGCA GA A G ATACGG CCGTGTATT A CTGTGCG A G ATTGG TGTATGCCGATGATGCTTTTGATATCTGGGGACAAGGGACCAC GGTCACCGTCTCCTCA
226	ATX-P-449	VH - nucléotide	CAAGTGCAATTGGTGGAGTCCGGTGGAGGAGTAGTACAGCCG GGAAGGTCACTGAGACTTTCCTGCGCTGCTAGTGGATTCGCCT TTAGTTCCTACGGCATGCACTGGGTTCGCCAAGCGCCAGGTAA GGGACTGGAATGGGTGGCTGTCATCTCCTACTACGGATCTAAT AAATATTATGCCGATAGCGTCAAAGGCCGGTTCACGATCTCAA GAGACAACTCTAAGAACACGCTCTACTTGCAGATGAACAGTCT CCGCGCAGAAGATACGGCCGTGTATCACTGTGCGAGAGGGAT TACTA TGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCC TCA
227	ΛΤΧ-Ρ-433	VH - nucléotide	GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCT GGCAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT TTGATGATTTTGCCATGCACTGGGTCCGGCAAGGTCCAGGGAA GGGCCTGGAGTGGGTCTCAGGTATTGGTTGGAATAGTGGTAGC ATCGGCTATGCGGACTCTGTGAAGGGCCGATTCACCATCTCCA GAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCT GAGAGCTGAGGACACGGCCTTATATTACTGTGCAAAAGCCCCT GACTACGGTGACTACTACTTTGACTACTGGGGCCAGGGAACCC TGGTCACCGTCTCCTCA
228	ATX-P-444	VL	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRP GQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISKVEAEDVGIY YCMQGTHWPWTFGQGTKVDIK
229	ATX-P-445	VL	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRP GQSPRRLIHEVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGV YYCMQGTHWPWTFGQGTKVDIK
230	ATX-P-446	VL	DVVMTQSPLSLPVTLGQPASJSCRSSQSLVFSDGNTYLNWFQQRP GQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGV YYCMQGTHWPWTFGQGTKVDIK

231	ATX-P-447	VL	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRP GQSPRRLIHEVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGV YYCMQGTHWPWTFGQGTKVDIK
232	ATX-P-427	VL	AIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPK LLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQDY NYPYTFGQGTKLEIK
233	ATX-P-440	VL	DlQMTQSPSTLSASVGDRVlITCRASQSISSW'LAWYQQKPGKAPK LL1YATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSY STP1TFGQGTRLEIK
234	ATX-P-424	VL	D1QMTQSPSSLSASVGDRVTITCRASQGIRND1.GWYQQKPGKAPK RLIYAASSLPSGVPSRFSGSGSGTEFTLTISSLQPEDFAIYYCLQHN SYPWTFGQGTKVEIK
235	ATX-P-425	VL	DIQMTQSPSSLSASVGDRVT1TCRASQGIRIDLGWFQQKPGKAPK RL1YAASSLPSGVPSRFSGSGSGTEFTLHSSLQPEDFATYYCLQI1N SYPWTFGQGTKVEIK
236	ATX-P-430	VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYL.AWYQQKPGQAP RLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPF.DFAVYYCQQ YGSSPPTFGGG'l KVEIK
237	ATX-P-439	VL	D1QMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPK LLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQA NSFPWTFGQGTKVDIK
238	ATX-P-423	VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPK RLIYAASSLQSGVPSRFSGSGSGTEFALTISSLQPEDFATYYCLQH NSYPLTFGGGTKLE1K
239	ATX-P-438	VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSRSYLAWYQQKPGQAP RLL11GASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQG QVIPPTFGQGTKVEIK
240	ATX-P-448	VL	EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRS NWPLTFGGGTKVEIK
241	ATX-P-449	VL	E1VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR LL1YDASNRATGIPARFSGSGSGTDFTLT1SSLEPEDFAVYYCQQRS NWPLTFGGGTKVEIK
242	ATX-P-433	VL	DIQMTQSPSSLSASVGDRVT1TCRASQSISIYLNWYQQKPGTAPKL LIYAASSLQSGVPSRFSGSGSGTDFTLTISSI.QPEDFAAYYCQQSY TTPLTFGGGTKVE1K
243	ATX-P-444	VL — nucléotide	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCT TGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCTC GTATACAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAGA GGCC AG GCC A ATCTCC A AGGCGCCT A ATI T ATA AGGTTTCTA A CCGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTC AGGCACTGATTTCACACTGAAAATCAGCAAGGTGGAGGCTGA GGATGTTGGGATTTATTACTGCATGCAAGGTACACACTGGCCG TGGACGTTCGGCCAAGGGACCAAAGTGGATATCAAA
244	ATX-P-445	VL - nucieotide	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCT TGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCTC GTATACAGTGATGGAAACACCTACTTGAATTGGl TTCAGCAGA GGCCAGGCCAATCTCCAAGGCGCCTAATTCATGAGGTTTCTAA CCGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTC AGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGA GGATGTTGGGGTTTATTACTGCATGCAAGGTACACACTGGCCG TGGACGTTCGGCCAAGGGACCAAAGTGGATATCAAA
245	ATX-P-446	VL - nucieotide	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCT TGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCTC GTA'n'CAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAGA

112

			GGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTAA CCGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTC AGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGA GGATGTTGGGGTTTATTACTGCATGCAAGGTACACACTGGCCG TGGACGTTCGGCCAAGGGACCAAAGTGGATATCAAA
246	ATX-P-447	VL - nucléotide	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCT TGGACAGCCGGCCTCCATCTCCTGCAGG l CTAGTCAAAGCCTC GTATACAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAGA GGCCAGGCCAATCTCCAAGGCGCCTAATTCATGAGGT'rrCTAA CCGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTC AGGCACTGATT l CACACTGAAAATCAGCAGGGTGGAGGC IGA GGATGTTGGGGTTTATTACTGCATGCAAGGTACACACTGGCCG TGGACGTTCGGCCAAGGGACCAAAGTGGATATCAAA
247	ATX-P-427	VL - nucléotide	GCCATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCAT TAG A A A TGATTT AGGCTG GT ATC AGC AG A A AC C AGG G A A AGC CCCTAAGCTCCTGATCTATGCTGCATCCAGTTTACAAAGTGGG GTCCCATCAAGGTTCAGCGGCAGTGGATCTGGCACAGATTTCA CTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTA TTACTGTCTACAAGATTACAATTACCCGTACACTTTTGGCCAG GGGACCAAGCTGGAGATCAAA
248	ATX-P-440	VL — nucléotide	GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTAT TAGTAGCTGGT TGGCCTGGTATCAGCAGAAACCAGGGAAAGC CCCTAAGCTCCTGATCTATGCTACATCCAGTTTGCAAAGTGGG GTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCA C TC TCACCA TCAGCAGTCTGCAACCTGA AGATTTl GCAACT TA CTACTGTCAACAGAGTTACAGTACCCCGATCACCTTCGGCCAA GGGACACGACTGGAGATTAAA
249	ATX-P-424	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCAT TAGAAATGATTTAGGCTGGTATCAGCAGAAACCAGGGAAAGC CCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCCAAGTGGG GTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCA CTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAATTTA TTACTGTCTACAGCATAATAGTTACCCGTGGACGTTCGGCCAA GGGACC AAG GTGGAAATCAAA
250	ATX-P-425	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCCGCATCTG TAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCA TTAGAATTGATTTAGGCTGGTTTCAGCAGAAACCAGGGAAAGC CCCTAAGCGCCTCATCTATGCTGCATCCAGTTTGCCAAGTGGG GTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCA CTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTA TTACTGTCTACAGCATAATAGTTACCCGTGGACGTTCGGCCAA GGGACCAAGGTGGAGATCAAA
251	ATX-P-430	VL - nucléotide	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCA GGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACT GGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAG TGTATTACTGTCAGCAGTATGGTAGCTCACCTCCCACTTTCGGC GGAGGGACCAAGGTGGAAATCAAA
252	ATX-P-439	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGTAT

H3

			TAGCAGCTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGC CCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGG GTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCA CTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTA CTATTGTCAACAGGCTAACAGTTTCCCGTGGACGTTCGGCCAA GGGACCAAAGTGGATATCAAA
253	ATX-P-423	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCAT TAGAAATGATTTAGGCTGGTATCAGCAGAAACCAGGGAAAGC CCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGG GTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCG CTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTA TTACTGTCTACAGCATAATAGTTACCCTCTCACTTTCGGCGGA GGGACCAAGCTGGAGATCAAA
254	ATX-P-438	VL - nucléotide	GAAATTGTGCTGACTCAGTCTCCCGGCACACTGTCTCTTAGCC CTGGCGAAAGAGCCACACTGAGCTGTAGAGCCAGCCAGAGCG TGTCCAGAAGCTACCTGGCTTGGTATCAGCAGAAGCCCGGACA GGCTCCCAGACTGCTGATCATCGGAGCCTCTACAAGAGCCACC GGCATTCCCGATAGATTCAGCGGCTCTGGCAGCGGCACCGATT TCACCCTGACAATCAGCAGACTGGAACCCGAGGACTTCGCCGT GTACTACTGTCAGCAGGGCCAAGTGATCCCTCCTACCTTTGGC CAGGGCACCAAGGTGGAAATCAAA
255	ATX-P-448	VL — nucléotide	GAAATTGTGTTGACGCAGTCTCCAGCCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT TAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCT CCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCA TCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCAC TCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAGTTTAT TACTGTCAGCAGCGTAGCAACTGGCCTCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAA
256	ATX-P-449	VL - nucléotide	GAAATTGTGTTGACGCAGTCTCCAGCCACCCTGTCTTTGTCTCC AGGGGAA AGAGCCACCCTCTCCTGCAGGGCCAGTCAGAG TGT TAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCT CCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACI GGCA TCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCAC TCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAGTTTAT TACTGTCAGCAGCGTAGCAACTGGCCTCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAA
257	ATX-P-43 3	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCAT TAGCATCTATTTAAATTGGTATCAGCAGAAACCAGGGACAGCC CCT A AGCTCCTG A TCT ATGCTGC ATCCAGTTTG CAA AGTGGGG TCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCAC TCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAGCTTAC TACTGTCAACAGAGTTACACTACCCCGCTCACTTTCGGCGGAG GGACCAAGGTGGAAATCAAA
258	ATX-P-43 5	VH	QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSSYWGWIRQPPGKG LEWIGSIYYSGSTYSNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCARQYISGTEYFQYWGQGTLVTVSS
259	ATX-P-436	VH	QLQEQESGPGLVKPSETLSLTCTVSGGSISSSSSYWGWIRQPPGKG LEWIGSIYYSGSTYSNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCARQYISGTEYFQYWGQGTLVTVSS
260	ATX-P-434	VH	QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGSYYWSWIRQPPGK GLEWIGYIYYSGSTSYNPSLKSRVSISVDTSKNQFSLKLSSVTAAD TAVFYCARAKWEGDYFDYW'GQGTLVTVSS

H4

261	ATX-P-435	VH — nucléotide	CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCT TCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGTTCCAT CAGCAGTAGTAGTTCCTACTGGGGCTGGATCCGCCAGCCCCCA GGGAAGGGACTGGAGTGGATTGGGAGTATCTATTATAGTGGG AGCACCTACTCCAACCCGTCCCTCAAGAGTCGAGTCACCATAT CCGTAGACACGTCCAAGAATCAGTTCTCCCTGAAGCTGAGCTC TGTGACCGCCGCAGACACGGCTGTGTATTACTGTGCGAGACAG TATATAAGTGGAACTGAATACTTCCAGTACTGGGGCCAGGGCA CCCTGGTCACCGTCTCCTCA
262	ATX-P-436	VH - nucléotide	CAGC'l GCAGCl GCAGGAG TCGGGCCCAGGACTGGTGAAGCCT TCGGAGACCCTG TCCCTCACCTGCAC TGTCTCTGGTGGTTCCAT CAGCAGTAGTAGTTCCTACTGGGGCTGGA TCCGCCAGCCCCCA GGGA AGGGACTGGAGTGGATTGGGAG TATC TA TTA TAGTGGG AGCACCTACTCCAACCCGTCCCTCAAGAGTCGAGTCACCATAT CCGTAGACACGTCCAAGAATCAGTTCTCCCTGAAGCTGAGCTC TGTGACCGCCGCAGACACGGCTGTGTATTACTGTGCGAGACAG TATATAAGTGGAACTGAATACTTCCAGTACTGGGGCCAGGGCA CCCTGGTCACCGTCTCCTCA
263	ATX-P-434	VH - nucléotide	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCT TCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCGT cagcagtggtagttactactggagctggatccggcagccccca GGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGG AGCACCAGCTACAACCCCTCCCTCAAGAGTCGAGTCTCCATAT CAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTC tgtgaccgctgcggacacggccgtgttttactgtgcgagagct AAGTGGGAAGGGGACTACTTTGACTACTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCA
264	ATX-P-435	VL	El VL TQSPA TLSLSPGERA TLSCRASQSVSNYLA WYQQKPGQAPR LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRS NWPSFGQG! RLEIK
265	ATX-P-436	VL	DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPK LLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSY STPLTFGGGTKVEIK
266	ATX-P-434	VL	DIQMTQSPSSLSASVGDRVTITCRASQSIYSYLNWYQQKPGKAPN HLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLHPEDFATYYCQQS YSTPPYTFGQGTKVEIK
267	ATX-P-435	VL - nucléotide	GΑΑΑΤΊ GTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCC AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT TAGCAACTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCT CCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCA TCCCAGCCAGATTCAGTGGCAGTGGGTCTGGGACAGACTTCAC TCTCACCATCAGCAGCCTGGAGCCTGAAGATTTTGCAGTTTAT TACTGTCAGCAGCGTAGCAACTGGCCCTCCTTCGGCCAAGGGA CACGACTGGAGATTAAA
268	ATX-P-436	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCAT TAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGC CCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGG GTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCA CTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTA CTACTGTCAACAGAGTTACAGTACCCCGCTCACTHCGGCGGA GGGACCAAGGTGGAAATCAAA
269	ATX-P-434	VL - nucléotide	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCAT TTACAGCTAITJAAATTGGTATCAGCAGAAACCAGGGAAAGCC

l 15

CCTAATCACCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGG TCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCAC TCTCACCATCAGCAGTCTGCACCCTGAAGATTTTGCAACTTAC TACTGTCAACAGAGTTACAGTACCCCTCCGTACACTTTTGGCC AGGGGACCAAGGTGGAAATCAAA

[00227J Table ΙΟ: Anti-ANGPTL7 antibodies (HC IgGI Fc and LC Kappa sequences)

SEQ ID NO:	Antibody Naine:	Descriptor:	Sequence:
270	ATX-P-428	Variable HC + Constant hlgGl-Agly-Fc	QVQLVQSGAEVKKPGASVKVSCKASGYTFSSYGISWVRQ APGQGLEWMGWISAYNGNTNYAQNLRGRVAMTTDTSTT TAYMELRSLRSDDTAVYYCARVSLVWFGELPRGFDYWGQ GTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQ'ÏYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYASTYRWSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPG
271	ATX-P-443	Variable HC + Constant hlgGl-Agly-Fc	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQ APGQGLEWMGWIIAYNGNTNYAQKLQGRITMTYNTSTNT AYMELRSLRSDDTAVYYCGRDTGFSFDYWGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPG
272	ATX-P-429	Variable HC + Constant hlgGl-Agly-Fc	QVQLVQSGAEVKKPGASVKVSCKASGYTFSSYGISWVRQ APGQGLEWMGWISAYNGNTNYAQNLRGRVAMTTDTSTT TAYMELRSLRSDDTA VYYCARVSLVWFGELPRGFDYWGQ GTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPG
273	ATX-P-43 l	Variable HC + Constant hlgGl-Agly-Fc	QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIHWVRQ APGPGLEWLGWINPNTGATKYAQKFQGRVTMTRDTSISTA YMELSRLRSDDTAVYYWAREDNGNYGDVFDIWGQGTMV TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYIPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

H6

			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPG
274	ATX-P-432	Variable UC + Constant hlgGl-Agly-Fc	QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIH WVRQ APGPGLEWLGWINPNTGATKYAQKFQGRVTMTRDTSISTA YMELSRLRSDDTAVYYCAREDNGNYGDVFDIWGQGTMV TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSR EEMIKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSITLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPG
275	ATX-P-428	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAA GCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGG TTACACCTTTTCCAGCTATGGTATCAGCTGGGTGCGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCA GCGCTTACAATGGTAACACAAACTATGCACAGAACCTC CGGGGCAGAGTCGCCATGACCACAGACACATCCACGAC CACAGCCTACATGGAGTTGAGGAGCCTGAGATCTGACG ACACGGCCGTGTATTACTGTGCGAGAGTTTCATTAGTAT GGTTTGGGGAATTACCCAGGGGTTTTGACTACTGGGGCC AGGGAACCCTGGTCACCGTCTCCTCAGCTAGCACTAAA GGGCC TTC! ’GTATTTCCCT TGGCCCCGTCCAGCAAATCG ACCTCGGGAGGGACAGCCGCCCTGGGTTGCCTTGTGAA AGATTATTTCCCTGAGCCAGTTACCGTAAGTTGGAACAG TGGGGCGCTGACAAGTGGTGTGCACACGTTTCCTGCCGT CCTGCAATCATCGGGCTTGTATAGCCTCAGCTCTGTGGT CACTGTCCCAAGTTCATCGCTGGGCACTCAGACGTATAT TTGCAATGTGAACCACAAACCTTCAAATACAAAAGTGG ATAAACGCGTAGAACCGAAATCGTGTGATAAAACTCAC ACATGCCCGCCATGCCCGGCACCTGAACTGCTTGGTGGT CCCAGCGTGTTCCTGTTCCCGCCGAAGCCTAAAGATACT CTAATGATCAGCCGTACGCCAGAGGTGACATGTGTCGT GGTTGACGTGTCCCACGAAGATCCCGAAGTTAAGTTCA ATTGGTATGTTGATGGTGTAGAGGTACACAATGCTAAG ACTAAACCTCGCGAGGAGCAGTACGCCTCGACCTATCG TGTCGTGAGCGTTCTGACCGTCCTTCACCAAGATTGGCT TAACGGCAAAGAATATAAGTGCAAGGTAAGCAATAAAG CACTTCCGGCCCCAATCGAGAAAACCATTTCCAAGGCC AAAGGTCAACCAAGAGAACCCCAGGTGTATACTCTTCC GCCTTCTCGTGAGGAAATGACTAAAAATCAAGTATCCCT TACGTGTCTGGTTAAAGGTTTTTATCCTAGCGATATTGC TGTTGAATGGGAATCGAACGGTCAGCCGGAGAATAATT ATAAA ACAACGCCACCCG'l CCI GGATAGCGACGGCl CA ΊΤ1TTTCTGTATAGCAAACTGACTGTAGATAAATCACGG TGGCAGCAGGGCAATGTATTCAGTTGCTCCGn'ATGCAT GAAGCGTTACATAATCAC'I ACACGCAGA AATCTC TTAGT CTTTCACCCGGT
276	ATX-P-443	Variable HC + Constant hlgGl-Agly-Fc (nudeotide)	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAA GCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGG TTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCA TCGCTTACAATGGTAACACAAACTATGCACAGAAGCTC

			CAGGGCAGAATCACCATGACCACAAACACATCCACGAA CACAGCCTACATGGAGCTGAGÜAGCCTGAGATCTGACG ACACGGCCGTGTATTACTGTGGGAGAGATACGGGGTTTT CTT H’GACTACTGGGGCC AGGGA ACCCTGGTCACCG TCT CCTC A GCT AGCACTA AA GGGCCTTCTGTA TTTCCCTTGG CCCCGTCCAGCAAATCGACCTCCjCjGAGGGACAGCCGCC CTGGGTTGCCTTGTGAAAGATTATTTCCCTGAGCCAGTT ACCGTAAGTTGGAACAGTGGGGCGCTGACAAGTGGTGT GCACACGTTTCCTGCCGTCCTGCAATCATCGGGCTTGTA TAGCCTCAGCTCTGTGGTCACTGTCCCAAGTTCATCGCT GGGCACTCAGACGTATATTTGCAATGTGAACCACAAAC CTTCAAATACAAAAGTGGATAAACGCGTAGAACCGAAA TCGTGTGATAAAACTCACACATGCCCGCCATGCCCGGCA CCTGAACTGCTTGGTGGTCCCAGCGTGTTCCTGTTCCCG CCGAAGCCTAAAGATACTCTAATGATCAGCCGTACGCC AGAGGTGACATGTGTCGTGGTTGACGTGTCCCACGAAG ATCCCGAAGTTAAGTTCAATTGGTATGTTGATGGTGTAG AGGTACACAATGCTAAGACTAAACCTCGCGAGGAGCAG TACGCCTCGACCTATCGTGTCGTGAGCGTTCTGACCGTC CTTCACCAAGATTGGCTTAACGGCAAAGAATATAAGTG CAAGGTAAGCAATAAAGCACTTCCGGCCCCAATCGAGA AAACCATTTCCAAGGCCAAAGGTCAACCAAGAGAACCC CAGGTGTATACTCTTCCGCCTTCTCGTGAGGAAATGACT AAAAATCAAGTATCCCTTACGTGTCTGGTTAAAGGTTTT TATCCTAGCGATATTGCTGTTGAATGGGAATCGAACGGT CAGCCGGAGAATAATTATAAAACAACGCCACCCGTCCT GGATAGCGACGGCTCATTTTTTCTGTATAGCAAACTGAC TGTAGATAAATCACGGTGGCAGCAGGGCAATGIAriCA GTTGCTCCGTÏ’ATGCATGAAGCGn'ACATAATCACTACA CGCAGAAATCTCTTAGTCTTTCACCCGGT
277	ATX-P-429	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAA GCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGG TTACACCTTTTCCAGCTATGGTATCAGCTGGGTGCGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCA GCGCTTACAATGGTAACACAAACTATGCACAGAACCTC CGGGGCAGAGTCGCCATGACCACAGACACATCCACGAC CACAGCCTACATGGAGTTGAGGAGCCTGAGATCTGACG ACACGGCCGTGTATTACTGTGCGAGAGTTTCATTAGTAT GGTTTGGGGAATTACCCAGGGGTTTTGACTACTGGGGCC AGGGAACCCTGGTCACCGTCTCCTCAGCTAGCACTAAA GGGCCTTCTGTATTTCCCTTGGCCCCGTCCAGCAAATCG ACCTCGGGAGGGACAGCCGCCCTGGGTTGCCTTGTGAA AGATTATTTCCCTGAGCCAGTTACCGTAAGTTGGAACAG TGGGGCGCTGACAAGTGGTGTGCACACGTTTCCTGCCGT CCTGCAATCATCGGGCTTGTATAGCCTCAGCTCTGTGGT cactgtcccaagttcatcgctoggcactcagacgtatat TTGCAATGTGAACCACAAACCTTCAAATACAAAAGTGG ATAAACGCGTAGAACCGAAATCGTGTGATAAAACTCAC ACATGCCCGCCATGCCCGGCACCTGAACTGCTTGGTGGT CCCAGCGTGTTCCTGTTCCCGCCGAAGCCTAAAGATACT CTAATGATCAGCCGTACGCCAGAGGTGACATGTGTCGT GGTTGACGTGTCCCACGAAGATCCCGAAGTTAAGTTCA ATTGGTATGTTGATGGTGTAGAGGTACACAATGCTAAG ACTAAACCTCGCGAGGAGCAGTACGCCTCGACCTATCG TGTCGTGAGCGTTCTGACCGTCCTTCACCAAGATTGGCT TAACGGCAAAGAATATAAGTGCAAGGTAAGCAATAAAG

			CAC1 FCCGGCCCCAAl CGAGAAAACCATTTCCAAGGCC AAAGGTCAACCAAGAGAACCCCAGGTGTATACTCTTCC GCCTTCTCGTGAGGAAATGACTAAAAATCAAGTATCCCT TACGTGTCTGGTTAAAGGTTTTTATCCTAGCGATATTGC TGTTGAATGGGAATCGAACGGTCAGCCGGAGAATAATT ATAAAACAACGCCACCCGTCCTGGATAGCGACGGCTCA TTTTTTCTGTATAGCAAACTGACTGTAGATAAATCACGG Ί GGCAGCAGGGCAATG FATTCAGTTGCTCCGTTATGCAT GAAGCGTTACATAATCACTACACGCAGAAATCTCTTAGT CTTTCACCCGGT
278	ATX-P-43 l	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAA GCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGG ATACACCTTCACCGACTACTATATACACTGGGTGCGACA GGCCCCTGGGCCAGGGCTTGAGTGGTTGGGCTGGATCA ACCCTAACACTGGTGCCACAAAGTATGCACAGAAGTTT CAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAG CACAGCCTATATGGAGCTGAGCAGGCTGAGATCTGACG ACACGGCCGTATATTATTGGGCGAGAGAAGATAATGGG AACTACGGGGATGTTTTTGATATCTGGGGACAAGGGAC AATGGTCACCGTCTCTTCAGCTAGCACTAAAGGGCCTTC TGTATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGG AGGGACAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTT CCCTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGC TGACAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAAT CATCGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCC CAAGTTCATCGCTGGGCACTCAGACGTATATTTGCAATG TGAACCACAAACCTTCAAATACAAAAGTGGATAAACGC GT AG A ACCG A AATCG TG TG ATAAAACTCACA C A TGCCC GCCATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGT GTTCCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGAT CAGCCGTACGCCAGAGGTGACATGTGTCGTGGTTGACG TGTCCCACGAAGATCCCGAAGTTAAGTTCAATTGGTATG TTGATGGTGTAGAGGTACACAATGCTAAGACTAAACCT CGCGAGGAGCAGTACGCCTCGACCTATCGTGTCGTGAG CGTTCTGACCGTCCTTCACCAAGATTGGCTTAACGGCAA AGAATATAAGTGCAAGGTAAGCAATAAAGCACTTCCGG CCCCAATCGAGAAAACCATTTCCAAGGCCAAAGGTCAA CCAAGAGAACCCCAGGTGTATACTCTTCCGCCTTCTCGT GAGGAAATGACTAAAAATCAAGTATCCCTTACGTGTCT GGTTAAAGGTTTTTATCCTAGCGATATTGCTGTTGAATG GGAATCGAACGGTCAGCCGGAGAATAATTATAAAACAA CGCCACCCGTCCTGGATAGCGACGGCTCATTTTTTCTGT ATAGCAAACTGACTGTAGATAAATCACGGTGGCAGCAG GGCAATGTATTCAGTTGCTCCGTTATGCATGAAGCGTTA CATAATCACTACACGCAGAAATCTCTTAGTCTTTCACCC GGT
279	ATX-P-432	Variable UC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAA GCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGG ATACACCTTCACCGACTACTATATACACTGGGTGCGACA GGCCCCTGGGCCAGGGCTTGAGTGGTTGGGCTGGATCA ACCCTAACACTGGTGCCACAAAGTATGCACAGAAGTTT CAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAG CACAGCCTATATGGAGCTGAGCAGGCTGAGATCTGACG ACACGGCCGTATATTATTGTGCGAGAGAAGATAATGGG AACTACGGGGATGTTTTTGATATCTGGGGACAAGGGAC AATGGTCACCGTCTCITCAGC'IAGCACTAAAGGGCCTTC

119

			TGTATTTCCCITGGCCCCGTCCAGCAAATCGACCTCGGG AGGGACAGCCGCCCTGGGTTGCCTIG l GA AAGA T ΓΛΤΤΤ CCCTGAGCCAGTTACCG TAAG1TGGAACAGTGGGGCGC TGACAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAAT CATCGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCC CA AGT TC A TCGCTGGGC ACTC AG A CGT ATA TTTGC AATG TGAACCACAAACCTTCAAATACAAAAGTGGATAAACGC GTAGAACCGAAATCGTGTGA'IΛΑΛΑΕΙ CACACATGCCC GCCATGCCCGGCACC1GAAC TGC IT GGTGGTCCCAGCGT GTTCCTGTTCCCGCCGAAGCC TA AAGATACTCTAATGAT CAGCCG l ACGCCAGAGG TGACA TG TGTCGTGGTTGACG 1 GTCCCACGAAGATCCCGAAGl Ί AAGTTCAAITGGTATG TTGATGGTGTAGAGGTACACAATGClAAGACTAAACCT CGCGAGGAGCAGl ACGCC1CGACC TA TCG TG TCG TGAG CGTTCTGACCGTCCTTCACCAAGA'I 1GGCT I AACGGCAA AGAATATAAGTGCAAGGIAAGCAATAAAGCACTTCCGG CCCCAATCGAGAAAACCAl T TCCAAGGCCAAAGGTCAA CCAAGAGAACCCCAGGTGTATAC TC TTCCGCC TIC 1 CGI GAGGAAATGACTAAAA ATCAAG TA 1 CCCTTACG TG 1 CT GGTTAAAGGTTTTTATCC1AGCGAΤΑΊ TGCTGTTGA AT G GGAATCGAACGGTCAGCCGGAGAATAATTATAAAACAA CGCCACCCGTCCTGGATAGCGACGGCTCATTTTTTCTGT ATAGCAAACTGACTGTAGATAAATCACGGTGGCAGCAG GGCAATGTATTCAGTTGCTCCG ΊΊ A TGCAIGAAGCGTTA CATAATCACTACACGCAGAAATCTCTTAGTCTTTCACCC GGT
280	ATX-P-428	Variable LC + Kappa Constant	E1VLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GQAPRLL1YGASSRATG1PDRESGSGSGTDFTLT1SRLEPEDF AVYYCQQYGSSPPTFGGGTKVEIKRTVAAPSVF1FPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC
28I	ATX-P-443	Variable LC + Kappa Constant	EIVLTQSPGTLSLSPGERA TLSCRASQSVSSSYLAWYQQKP GQAPRLLIYGASSRATGIPDRI-SGSGSG I DFTLTISRLEPEDF AVYYCQQYGSSLTFGGGTKVDIKRTVAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP VTKSFNRGEC
282	ATX-P-429	Variable LC + Kappa Constant	DIVMTQSPLSLPVTPGEPAS1SCRSSQSLI.HSNRYNYLDWY LQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLQISRV EAEDVGVYYCMQTLQTPYTFGQGTKLEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNIYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC
283	ATX-P-431	Variable LC + Kappa Constant	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GQAPRLLIYGASSRATGlPDRl-SGSGSGrDFTLTlSRLEPEDl· AVYYCQQYGSSPPTFGGGTKVE1KRTVAAPSVF1FPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC
284	ATX-P-432	Variable LC + Kappa Constant	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GQAPRLL1YGASSRATG1PDRFSGSGSGTDFTLT1SRLEPEDF AVYYCQQYGSSPPTFGGGTKVEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC

120

285	ATX-P-428	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGC TCCTCATCTA TGGTGC ATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGIG GCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGC AGTATGGTAGCTCACCTCCCACTTTCGGCGGAGGGACCA AGGTGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTT TTATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGA CCGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCG TGAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGC AGTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGAT TCTAAAGATTCCACATATTCACTCAGCTCCACCCTTACA CTGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGC ATGTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCA CAAAATCGTTTAACCGCGGTGAGTGT
286	ATX-P-443	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTC TTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGC TCCTCATCTATGGTGC ATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTG GCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGC AGTATGGTAGCTCACTCACTTTCGGCGGAGGGACCAAA GTGGATATCAAACGTACGGTAGCTGCCCCTTCAGTTTTT ATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGACC GCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGTG AGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCAG TCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTC TAAAGATTCCACATATTCACTCAGCTCCACCCTTACACT GAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCAT GTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCACA AAATCGTTTAACCGCGGTGAGTGT
287	ATX-P-429	Variable LC + Kappa Constant (nucléotide)	GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTC ACCCCTGGAGAGCCGGCCTCCATC f CCTGCAGGTCTAGT CAGAGCCTCCTGCATAGTAATAGATACAACTATTTGGAT TGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCT GATCTATTTGGGTTCTAATCGGGCCTCCGGGGTCCCTGA CAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACT GCAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTT ATTACTGCATGCAAACTCTACAAACTCCGTACACTTTTG GCCAGGGGACCAAGCTGGAGATCAAACGTACGGTAGCT GCCCCTTCAGTTTTTATCTTTCCGCCGTCTGACGAGCAGT TAAAATCCGGGACCGCTTCTGTAGTTTGCCTGCTGAATA ATTTTTATCCGCGTGAGGCTAAAGTACAATGGAAAGTCG ACAATGCTTTGCAGTCGGGAAATTCACAGGAAAGTGTT ACGGAGCAGGATTCTAAAGATTCCACATATTCACTCAGC TCCACCCTTACACTGAGCAAAGCCGACTATGAAAAACA TAAAGTTTACGCATGTGAGGTGACGCACCAAGGATTAT CCAGTCCGGTCACAAAATCGTTTAACCGCGGTGAGTGT
288	ATX-P-431	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGC ATCCAGCAGGGCCAC TGGCAICCCAGACAGGTTCAGTG

I2l

			GCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGC AGTATGG I AGCTCACCTCCCAC Π TCGGCGGAGGGACCA AGGTGGAAATCAAACGTACGGTAGCTGCCCCTTCAGTTT HAT CTTTCCGCCGTCTGACGAGCAGTTAA AATCCGGGA CCGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCG TGAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGC AGTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGAT TCTAAAGATTCCACATATTCACTCAGCTCCACCCTTACA CTGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGC ATGTGAGCiTGACGCACCAAGGATTATCCAGTCCGGTCA CAAAATCGTTTAACCGCGGTGAGTGT
289	ATX-P-432	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGC ATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTG GCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGC AGTATGGTAGCTCACCTCCCACTTTCGGCGGAGGGACCA AGGTGGAAATCAAACGTACGGTAGCTGCCCCTTCAGTTT TTATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGA CCGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCG TGAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGC AGTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGAT TCTAAAGATTCCACATATTCACTCAGCTCCACCCTTACA CTGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGC ATGTGAGG l GACGCACCAAGGAITATCCAGTCCGG l'CA CAAAATCGTTTAACCGCGGTGAGTGT
290	ATX-P-437	Variable HC + Constant hlgGl-Agly-Fc	QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQP PGKALEWLALIYWNDDKQYSPSLKSRLTITKDTSKNQVVL TMTNMDPMD TATYYCAFINPDYGDFFDYWGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSIIEDPEVKI’NWYVD GVEVHNAKTKPREEQYASTYRVVSVl.TVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIA VEWESNGQPENNYK i TPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPG
291	ATX-P-442	Variable HC + Constant hlgGl-Agly-Lc	QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQP PGKALEWLALIYWNDDKRYSPSLKSRLTITKDTSKNLVVL TMTN'MDPVDTATYYCARDYGDYWTFDLWGRGTPVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTI.MISRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKT KPREEQYASTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM T KNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPG
292	ATX-P-437	Variable HC + Constant hlgG!-Agly-Fc (nucleolide)	CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAA ACCCACACAGACCCTCACGTTGACCTGCACCTTCTCTGG GTTCTCACTCAGCACTAGTGGCGTGGGTGTGGGCTGGAT

122

			CCGTCAGCCCCCAGGAAAGGCCCTGGAGTGGCTTGCAC TCA ITT A TI GGAATGATGATAAACAGTACAGCCCTTCTC TGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAA AACCAGGTGGTCCTTACAATGACCAACATGGACCCTAT GGACACAGCCACATATTACTGTGCACACAACCCTGACT ACGGTGACTTCTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGTAT TTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGA CAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCCCTG AGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGACA AGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCATCG GGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAAGT tcatcgctgggcactcagacgtatatttgcaatgtgaac CACAAACCTTCAAATACÀAAAGTGGATAAACGCGTAGA ACCGAAATCGTGTGATAAAACTCACACATGCCCGCCAT GCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCC TGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCC GTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTCCC ACGAAGATCCCGAAGTTAAGTTCAATTGGTATGTTGATG GTGTAGAGGTACACAATGCTAAGACTAAACCTCGCGAG GAGCAGTACGCCTCGACCTATCGTGTCGTGAGCGTTCTG ACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAATAT AAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCAAT CGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAG AACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGAAA TGACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAAAG GTTTTTATCCTAGCGATATTGCTGTTGAATGGGAATCGA ACGGTCAGCCGGAGAATAATTATAAAACAACGCCACCC GTCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCAAA CTGACTGTAGATAAATCACGGTGGCAGCAGGGCAATGT ΑΊ ’TCAG Tl GCl CCGTTATGCA TGAAGCGTTACATAATCA CTACACGCAGAAATCTCTTAGTCTn'CACCCGGT
293	ATX-P-442	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAA ACCCACACAGACCCTCACGCTGACCTGCACCTTCTCTGG GTTCTCACTCAGCACTAGTGGAGTGGGTGTGGGCTGGAT CCGTCAGCCCCCAGGAAAGGCCCTGGAGTGGCTTGCAC TCATTTATTGGAATGATGATAAGCGCTACAGCCCATCTC TGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAA AACCTGGTGGTCCTTACAATGACCAACATGGACCCTGTG GACACAGCCACATATTACTGTGCACGTGACTACGGTGA CTACTGGTTCTTCGATCTCTGGGGCCGTGGCACCCCGGT CACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGTATT TCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGA CAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCCCTG AGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGACA AGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCATCG GGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAAGT TCATCGCTGGGCACTCAGACGTATATTTGCAATGTGAAC CACAAACCTTCAAATACAAAAGTGGATAAACGCGTAGA ACCGAAATCGTGTGATAAAACTCACACATGCCCGCCAT GCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCC TGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCC GTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTCCC ACGAAGATCCCGAAGTTAAGTTCAATTGGTATGTTGATG GTGTAGAGGTACACAATGCTAAGACTAAACCTCGCGAG GAGCAGTACGCCTCGACCTATCGTGTCGTGAGCGTTCTG

123

			ACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAATAT AAGTGCAAGG’I AAGCAATAAAGCACTTCCGGCCCCAAT CGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAG AACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGAAA TGACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAAAG GTTTTT ATCCTAG CG ATA TTGCTGTTG A ATG GG A ATCGA ACGGTCAGCCGGAGAATAATTATAAAACAACGCCACCC GTCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCAAA CTGACTGTAGATAAATCACGGTGGCAGCAGGGCAATGT ATTCAGTTGCTCCGTTATGCATGAAGCGTTACATAATCA CTACACGCAGAAATCTCTl AGTCTTTCACCCGG T
294	ATX-P-437	Variable LC + Kappa Constant	DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPG KAPKLLIYAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFA TYYCQQSFSTPLTFGGGTKLEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC
295	ATX-P-442	Variable LC + Kappa Constant	DIQM TQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPG KAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF ATYYCQQSFSTPLTFGGGTKLEIKRTVAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP VTKSFNRGEC
296	ATX-P-437	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATC CAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCA GTGGATCTGGGACAGATTTCATTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGA GTTTCAGTACCCCGCTCACTTTCGGCGGAGGGACCAAGC TGGA A ATC A A AC GTACG GT AGCTGC CCCTTC A GTTTTTA TCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGACCG CTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGTGA GGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCAGT CGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTCT AAAGATTCCACATATTCACTCAGCTCCACCCTTACACTG AGCAAAGCCGACTATGAAAAACATAAAGTTTACGCATG TGAGGTGACGCACCAAGGA T TATCCAGTCCGGTCACAA AATCGTTTAACCGCGG TGAG l GT
297	ATX-P-442	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAG TCAGGGCATTAGCAGTTATTTAGCCTGGTATCAGCAAAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATC CAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCA GTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGA GTTTCAGTACCCCGCTCACTTTCGGCGGAGGGACCAAGC TGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTTTTA TCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGACCG CTTCTGTAG TTTGCCTGCTGAA TAAT m'TATCCGCGTGA GGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCAGT CGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTCT AAAGATTCCACATATTCACTCAGCTCCACCCTTACACTG AGCAAAGCCGACTATGAAAAACATAAAGTTTACGCATG

I24

			TGAGGTGACGCACCAAGGATTATCCAGTCCGGTCACAA AATCGTTTAACCGCGGTGAGTGT
298	ATX-P-444	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVQPGGSLRLSCAASGFTLSVYDMHWVRQ VSGKGLEWVSGIDPDGDIYYPGSVKGRFTISRENAKNSLY LQMNSLRVGDTAVYYCLRGEESNSSEDGFDl WGQGTMVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG
299	ATX-P-445	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVQPGGSLRLSCAASGFTFSSHDMHWVRQ VTGKGLEWVSGIDPAGDTYYPDSVKGRFTISRENAKNSLY LQMNSLRAGDTAVYYCTRGEASSSSEDAFDIWGQGTMVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNIIKPSNTK VDKRVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVIINAKTKPREEQYASTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG
300	ATX-P-446	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVQPGGSLRLSCAASGFTLSSYDMl IWVRQ VIGKGLEWVSGIDPDGDTYYPGSVKGRFTISREDAKNSLYL QMNSLRAGDTAVYYCÎRGEDNSSSEDAFDIWGQGTMVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVH1 FPAVLQSSGLYSLSSVVTVPSSSLG TQT YICNVNHKPSNTKVDKRVEPKSCDKTIITCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKUSKAKGQPREPQVY l LPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPG
30 i	ATX-P-447	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVQPGGSLRLSCAASGFTISDYDMHWVRQ TTGKGLEWVSGIDPDGDTYYPGSLKGRFTISRENAKNSLY LQMNSLRAGDTAVYYCTRGEDSSSSEDAFDIWGQGTMVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAK TKPREEQYASTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFL YSKLFVDKSRWQQGN VFSCS VMHEALl INI l YTQKSLSLSPG
302	ATX-P-427	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGVVRPGGSLRLSCAASGFSFDDYGMSWVRQ VPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNAKNS LYLQMSSLRAEDTALYYCASYSGSERDAFDIWGQGTMVT VSSASTKGPSVFPLAPSSKSTSGGTAAI.GCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG

I25

			GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW Y VDG VEVI IN AK IKPREEQY ASTYR VVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKT1SKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGIYPSDIAVEWESNGQPENNYKTTPP Vl.DSDGSI FLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG
303	ATX-P-440	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGVVRPGGSl.Rl.SCAASGFTFDDYGMSWVRQ APGKGLEWVSTINWNGGNTGYADSVKGRFTISRDNAKNS LYLQMNSLRAEDTALYYCARDEGAAGLGYYFDYWGQGT LVTVSSAS l KGPSVFPI.APSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVI.QSSGI.YSLSSVV I VPSSSL GTQIYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYASTYRVVSVl.TVLHQD WLNGKEYKCKVSNKAEPAPIEK TJSKAKGQPREPQVYTLP PSREEMI KNQVSLTCLVKGFYPSDJAVEWESNGQPENNYK TTPPVl.DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHY TQKSLSLSPG
304	ATX-P-424	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQ APGKGLEWVSSITSSSYlFYADSLKGRF'lISRDNAKNSLFLQ MNSLRAEDTAVYYCARDSNWGEAFDIWGQGTMVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICN VNHKPSN l KVDKRVEPKSCDKTI li’CPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAK TKPREEQYAS l'YRVVSVL IVLHQDWLNGKEY KCKVSNKAl.PAPlEKTISKAKGQPREPQVYTLPPSREEMl K NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSK[/ΓVDKSRWQQGNVl·'SCSVMHEALHNI^YTQK SLSLSPG
305	ATX-P-425	Variable I IC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVKPGGSLRLSCAASGFTFSTYSMNWVRQ APGKGLEWVSSITSSSSYMI YADSVMGRl l ISRDNAKNSL YLQMNSLRAEDTADYYCARDSNWGEAFDIWGQGTMVTV SSAS TKGPSVFPl.APSSKS TSGGTAAI.GCLVKDYFPEPVTV SWNSGALTSGVH J FPA VLQSSGI.YSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTl.MISR TPEVTCVVVDVSHEDPEVKFNWY VDGVEVI INA K l KPREEQYAS I YRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFl. YSKLTVDKSR WQQGN VFSCSVMHEALI INI IY TQKSLSLSPG
306	ATX-P-430	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGLVQPGGSLR1.SCAASGFTFSSYAMSWVRQ APGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL YLQMNSLRAEDTAVYYCAKDGDYYYYYMDVWGKGTTV TVSSAS IKGPSVFPLAPSSKSTSGGIAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRI PEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEK3 ISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN H YTQKSLSLSPG
307	ATX-P-439	Variable HC + Constant hlgGl-Agly-Fc	EVQLVESGGGl.VQPGGSLRLSCAASGFTFSSYAMSWVRQ APGKGLEWVSAISGSGGS TYYADSVKGRFTISRDNSKNTL

I26

			YLQMNSLRAEDTAVYYCAKVERDMVRGHYYYYMDVWG KGTI VTVSSASTKGPSVFPI.APSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVIITFPA VLQSSGLYSLSSVVTVPS SSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVIINAKTKPREEQYASTYRVVSVL l’VI J l QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHY TQKSLSLSPG
308	A I X-P-423	Variable HC + Constant hlgGl-Agly-Fc	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQ APGKGLEWVSHITYDGSDKYYGDSVKGRF'HSRDNSKNTL YLQMNSLRAEDTAVYYCAKDGYSSGWWYFDYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGG TAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLl IQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY I LPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK FTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPG
309	ATX-P-438	Variable HC + Constant hlgGl-Agly-Fc	QVQLVESGGGVVQPGRSLRLSC AASGFTFSSYGMHWVRQ APGKGLEWVAIISYDGNNKYYADSVKGRFTISRDNSKNTL YLQMNSLRDEDTAVYYCAKERGYSSSSGYYYYYMDVWG KGTTVTVSSASTKGPSVFPI.APSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPS SSLGTQTYICN VNHKPSNTK VDKR VEPKSCDKTHTCPPCP APEI.LGGPSVFLFPPKPKD I LMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAK I KPREEQYASTYRVVSVL l’VLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYI LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFl.YSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPG
310	ATX-P-448	Variable I IC + Constant hlgGl-Agly-Fc	QVQL VESGGGVVQPGRSLRLSC AASGFPFSSYGMHWVRQ APGKGLEWVAVMSYDGINGYYADSVKGRFTISRDNSKNT LYLQMNSLRAEDTAVYYCARl.VYADDAFDIWGQGLTVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDl I.MISE I PEV rCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWl.N GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAI.HNI I YTQKSLSLSPG
311	ATX-P-449	Variable HC + Constant hlgGl-Agly-Fc	QVQLVESGGGVVQPGRSLRI.SCAASGFAFSSYGMHWVRQ APGKGLEWVAVISYYGSNKYYADSVKGRFTISRDNSKNTL YLQMNSLRAEDTAVYHCARGITMDVWGKGTTVTVSSAST KGPSVFPI.APSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKRVEPKSCDK THTCPPCPAPELLGGPSVF LFPPKPKDTl.MISRTPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDlAVEWESNGQPENNYKTTPPVLE)S

I27

			DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPG
312	âTX-P-433	Variable HC + Constant hlgGI-Agly-Fc	EVQLVESGGGLVQPGRSLRLSCAASGFTFDDFAMHWVRQ GPGKGLEWVSGIGWNSGSIGYADSVKGRFTISRDNAKNSL YLQMNSLRAED TALYYCAKAPDYGDYYFDY WGQGTLVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG GPSVFLI-PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAK.TKPREEQYASTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT l PP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG
313	ATX-P-444	Variable HC + Constant hlgG l-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCGGGGGGAGGCTTGGTACA GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCCTCAGTGTCTACGACATGCACTGGGTCCGCCA AGTTTCAGGAAAAGGTCTGGAGTGGGTCTCAGGTATTG ATCCTGATGGTGACACATACTATCCCGGCTCCGTGAAGG GCCGATTCACCATCTCCAGAGAAAATGCCAAGAACTCC TTGTATCTTCAAATGAACAGCCTGAGAGTCGGGGACAC GGCTGTGTATTATTGTCTAAGAGGGGAGGAAAGCAACT CGTCCGAGGATGGTTTTGATATATGGGGACAAGGGACA ATGGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCT GTATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGA GGGACAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTC CCTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCT GACAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATC ATCGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCC AAGTTCATCGCTGGGCACTCAGACGTATATTTGCAATGT GAACCACAAACC'rTCAAATACAAAAGTGGATAAACGCG TAGAACCGAAATCGTGTGATAAAACTCACACATGCCCG CCATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTG ΊΊ CCTGTICCCGCCGAAGCCTAAAGATACTCTAATGATC AGCCGTACGCCAGAGGTGACATGTGTCGTGGTTGACGT GTCCCACGAAGATCCCGAAGTTAAGTTCAATTGGTATGT TGATGGTGTAGAGGTACACAATGCTAAGACTAAACCTC GCGAGGAGCAGTACGCCTCGACCTATCGTGTCGTGAGC GTTCTGACCGTCCTTCACCAAGATTGGCTTAACGGCAAA GAATATAAGTGCAAGGTAAGCAATAAAGCACTTCCGGC CCCAATCGAGAAAACCATTTCCAAGGCCAAAGGTCAAC CAAGAGAACCCCAGGTGTATACTCTTCCGCCTTCTCGTG AGGAAATGACTAAAAATCAAGTATCCCTTACGTGTCTG GTTAAAGGTTTTTATCCTAGCGATATTGCTGTTGAATGG GAATCGAACGGTCAGCCGGAGAATAATTATAAAACAAC GCCACCCGTCCTGGATAGCGACGGCTCATTTTTTCTGTA TAGCAAACTGACTGTAGATAAATCACGGTGGCAGCAGG GCAATGTATTCAGTTGCTCCGTTATGCATGAAGCGTTAC ATAATCACTACACGCAGAAATCTCTTAGTCTTTCACCCG GT
314	ATX-P-445	Variable HC + Constant hlgGI-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACA GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG AT TCACCl TCAGl AGCCACGACATGCACTGGGTCCGCCA AGTTACAGGAAAAGGTCTGGAGTGGGTCTCAGGTATTG ATCCTGCTGGTGACACATACTATCCAGACTCCGTGAAGG GCCGATTCACCATCTCTAGAGAAAATGCCAAGAACTCCT

128

			TGTATCTTCAAATGAACAGCCTGAGAGCCGGGGACACG GCTGTGTATTACTGTACAAGAGGAGAGGCTAGTAG'l l C GTCCGAGGATGCTTTTGATATCTGGGGACAAGGGACAA TGGTCACTGTCTCCTCAGCTAGCACTAAAGGGCCTTCTG TATTl cccn GGCCCCG TCCAGCAAATCGACCTCGGGAG GGACAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCC CTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTG ACAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCA TCGGGC TTGTATAGCCTCAGC ICI G'I GG TCAC TGTCCCA AGTTCATCGCTGGGCACTCAGACGTATA H TGCAATGTG AACCACAAACCTTCAAATACAAAAGTGGATAAACGCGT AGAACCGAAATCGTGTGATAAAACTCACACATGCCCGC CATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGT l’CCTGTTCCCGCCGAAGCCTAAAGATAC I C I AA lGATCA GCCGTACGCCAGAGGTGACATGTG l’CGTGG TTGACG TGI CCCACGAAGATCCCGAAGTTAAGTTCAATTGGTATGTTG ATGGTGTAGAGGTACACAATGCTAAGACTAAACCTCGC GAGGAGCAGTACGCCTCGACCTATCG'I G! CGTGAGCG IT CTGACCGTCCTTCACCAAGATTGGCΙΊ AACGGCAAAGA ATATAAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCC CAATCGAGAAAACCATTTCCAAGGCCAAAGGTCAACCA AGAGAACCCCAGGTGTATACTCTTCCGCCTTCTCCi I GAG GAAATGACTAAAAATCAAGTATCCCTTACGTGTCTGGTT AAAGGTTTTTATCCTAGCGATATTGCTGTTGAATGGGAA ICGAACGGTCAGCCGGAGAATAATTATAAAACAACGCC ACCCGTCCTGGATAGCGACGGCTCATTT1ΊΊΤΊ GΤΑΊ AG CAAACTGACTGTAGATAAATCACGGTGGCAGCAGGGCA ATGTATTCAGTTGCTCCGTTATGCATGAAGCGTTACATA ATCACTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
315	ATX-P-446	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGIACA GCC'I GGGGGGICCC TGAGACIC TCCTGTGCAGCCTCTGG ATTCACCCTCAGTAGCTACGACATGCACTGGGTCCGCCA AGTTATAGGAAAAGGTCTGGAGTGGGTCTCAGGTATTG A FCC’i'GA'l GG I GACACATAC l A l’CCAGGCTCCGTGAAGG GCCGATTCACCATCTCCAGAGAAGATGCCAAGAACTCC TTGTATCl TCAAATGAACAGCCTGAGAGCCGGGGACAC GGCTGTGTATTACTGTACAAGAGGAGAGGA I AACAGCI CGTCCOAGGATGCTTTTGATATCTGGGGACAAGGGACA ΛIGGTCACTGTCTCCTCAGCl AGCACTAAAGGGCCTTCT GTATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGA GGGACAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTC CCTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCT GACAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATC ATCGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCC AAGTTCATCGCTGGGCACTCAGACGTATATTTGCAA 1 GT GAACCACAAACCTTCAAATACAAAAGTGGATAAACGCG TAGAACCGAAATCGTGTGATAAAACTCACACATGCCCG CCATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTG TTCCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGATC AGCCGTACGCCAGAGGTGACATGTGTCGTGGTTGACGT GTCCCACGAAGATCCCGAAGTTAAGTTCAATTGGTATGT TGATGGTGTAGAGGTACACAATGCTAAGACTAAACCTC GCGAGGAGCAGTACGCCTCGACCTATCGTGTCGTGAGC GTTCTGACCGTCCTTCACCAAGA Π GGCTTAACGGCAAA GAATATAAGTGCAAGGTAAGCAA'l AAAGCAC I l’CCGGC CCCAATCGAGAAAACCATTTCCAAGGCCAAAGGTCAAC

I29

			CAAGAGAACCCCAGG [ GTATAC'I CTTCCGCCTTCTCGTG AGGAAATGACTAAAAATCAAGTATCCCTTACGTGTCTG GTTAAAGGTTTTTATCCTAGCGATATTGCTGTTGAATGG GAATCGAACGGTCAGCCGGAGAATAATTATAAAACAAC GCCACCCGTCCTGGATAGCGACGGCTCAmTTTCTG TA TAGCAAACTGACTGTAGATAAATCACGGTGGCAGCAGG GCAA1GTATTCAGTTGCTCCGTTATGCATGAAGCGTTAC ATAATCACTACACGCAGAAATCTCTTAGTCTTTCACCCG GT
316	ATX-P-447	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	GAGGTCCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACA GCCGGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCATCAGTGACTACGACATGCACTGGGTCCGCCA AACTACAGGAAAAGGTCTAGAATGGGTCTCAGGTATTG ATCCTGATGGCGACACATATTATCCAGGCTCCTTGAAGG GGCGATTCACCATCTCCAGAGAAAATGCCAAGAATTCTT TGTATC l TCAAATGAACAGTCTGAGAGCCGGGGACACG GCTGTGTATTACTGTACAAGAGGAGAGGATAGTAGTTC GTCCGAGGATGCTTTTGATATCTGGGGACAAGGGACAA TGGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTG TA FΠ CCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAG GGACAGCCGCCCTGGGT TGCC1T'GTGAAAGATT ’ATTTCC CTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTG ACAAGTGGTG TGCACACGTTTCCTGCCGTCCTGCAATCA TCGGG CTTGTATAG CCTCA GCTCTGTGGTCA CTGTCCC A AGTTCATCGCTGGGCACTCAGACGTATAT TTGCAATGTG AACCACAAACCTTCAAATACAAAAGTGGATAAACGCGT AGAACCGAAATCGTGTGATAAAACTCACACATGCCCGC CATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGT TCCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCA GCCGTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGT CCCACGAAGATCCCGAAGTTAAGT1CAATTGGTATGTl G ATGGTGTAGAGGTACACAATGCTAAGACTAAACCTCGC GAGGAGCAGTACGCCTCGACCTATCGTGTCGTGAGCGTT CTGACCGTCCTTCACCAAGAT1 GGCT l AACGGCAAAGA ATATAAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCC CAATCGAGAA AACCATTTCCAAGGCCAAAGG TCAACCA AGAGAACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAG GAAATGACTAAAAATCAAGTATCCCTTACGTGTCTGGTT AAAGGTTTTTATCCTAGCGATATTGCTGTTGAATGGGAA TCGAACGGTCAGCCGGAGAATAATTATAAAACAACGCC ACCCGTCCTGGATAGCGACGGCTCATTTTTTCTGTATAG CAAACTGACTGTAGATAAATCACGGTGGCAGCAGGGCA ATGTATTCAGTTGCTCCGTTATGCATGAAGCGTTACATA ATCACTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
317	ATX-P-427	Variable l IC + Constant h!gGI-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGTGTGGTACG GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCI GG ATTC AG CTTTG ATG ATTATGGC ATG AGCTGG GTCCGCC A AGTTCCAGGGAAGGGGCTGGAGTGGGTCTCTGGTATTA ATTGGAATGGTGGTAGTACAGGTTATGCAGACTCTGTGA AGGGCCGA l I CACCAl CTCCAGAGACAACGCCAAGAAC TCCCTGTATCTGCAAATGAGCAGTCTGAGAGCCGAGGA CACGGCCII’G 1 AT 1ACTG TGCGAGC1ATAGTGGGAGCTT CCGTGATGCTTTTGATATCTGGGGACAAGGGACAATGGT CACCGTCTCTTCAGCTAGCACTAAAGGGCCTTCTGTATT TCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGA CAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCCCTG

130

			AGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGACA AGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCATCG GGCTTGTATAGCCTCAGCTCTG TGGTCACTGTCCCAAGT TCATCGCTGGGCACTCAGACGTATATTTGCAATGTGAAC CACAAACC1Ί CAAATACAAAAG l'GGA IAAACGCG I AGA ACCGAAATCGTGTGATAAAACTCACACATGCCCGCCAT GCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCC TGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCC GTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTCCC ACGAAGATCCCGAAGTTAAGTICAATIGGTATGTTGATG GTGTAGAGGTACACAATGCTAAGACTAAACCTCGCGAG GAGCAGTACGCCTCGACCTA l CG I GI CGTGAGCGTTCTG ACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAATAT AAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCAAT CGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAG AACCCCAGGTGTATACTCTTCCGCCITCTCGTGAGGAAA TGACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAAAG GTTTTTATCCTAGCGATATl GCTGTTGAATGGGAATCGA ACGGTCAGCCGGAGAATAATTATAAAACAACGCCACCC GTCCTGGATAGCGACGGCTCATnTTICTGTATAGCAAA CTGACTGTAGATAAATCACGGTGGCAGCAGGGCAATGT ATTCAGTTGCTCCGTTAIGCAΊ GAAGCGTFACATAATCA CTACACGCAGAAATCTCTTAGTC ΊΤΙCACCCGGT
318	ATX-P-440	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGTGTGGTACG GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACC1TTGATGA ΓΓΑΊ GGCA IGAGCTGGGTCCGCCA AGC TCCAGGGAAGGGGCIGGAGTGGGTCTCTACTATTA ATTGGAATGGTGGTAACACAGGT TATGCAGACTCTGTG AAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAA CTCCCTGTATCTGCAAATGAACAGTCTGAGAGCCGAGG ACACGGCCTTGTATTACTGTGCGAGAGATGAAGGAGCA GCTGGA CTTGGAT ACTAC TTTGACTACTG GGGCC AGGG A ACCCTGGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCT TCTGTATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCG GGAGGGACAGCCGCCCTGGGT tgccii gtgaaagatt a TTTCCCTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGC GCTGACAAGTGGTGTGCACACGTFTCCTGCCGTCCTGCA ATCATCGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGT CCCAAGTTCATCGCTGGGCACTCAGACGTATATTTGCAA TGTGAACCACAAACCTTCAAATACAAAAGTGGATAAAC GCGTAGAACCGAAATCGTGTGATAAAACTCACACATGC CCGCCATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGC GTGTTCCTGTTCCCGCCGAAGCCTAAAGATACTCTAATG ATCAGCCGTACGCCAGAGGTGACATG3 GTCGTGG TI GA CGTGTCCC ACGAAGATCCCGA AGITA AG ITCAATTGGIA TGTTGATGGTGTAGAGGTACACAATGCTAAGACTAAAC CTCGCGAGGAGCAGTACGCCTCGACCTATCGTGTCGTGA GCGTTCTGACCGTCCTTCACCAAGATTGGCTTAACGGCA AAGAATATAAGTGCAAGGTAAGCAATAAAGCACTTCCG GCCCCAATCGAGAAAACCA ΙΊ TCCAAGGCCAAAGGTCA ACCAAGAGAACCCCAGGTGTATAC'I CTTCCGCCTTCTCG TGAGGAAATGACTAAAAATCAAG3 ATCCC'n ACGTGTCT GGTTAAAGGTTTTTATCCTAGCGATATTGCTGTTGAATG GGAATCGAACGGTCAGCCGGAGAATAATTATAAAACAA CGCCACCCGTCCTGGA TAGCGACGGCTCATT1 ITFCTGT ATAGCAAACTGACTGTAGATAAATCACGGTGGCAGCAG

			GGCAATGTA] TCAGTTGCTCCGTTATGCATGAAGCGTTA CAT A A TC A Cl A C ACGC AG A A ATCTCTTA GTCTTTC ACCC GGT
319	ATX-P-424	Variable I IC + Constant hlgGl-Agly-Fc (nucieotide)	G A GG TGC AGCTG GTGG AGTCTGGGGG AGG CCTGGTC A A GCCTGGGGGG TCCCTGAGACTC T'CCTG TGCAGCCTCTGG ATTCACCTTCAGTAGCTATAGCA'J GAACTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCATCCATTA CTAGTAGTAGTTACATATTCTACGCAGACTCATTGAAGG GCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCA CTGTTTCTGCAAATGAACAGCCTGAGAGCCGAGGACAC AGCTGTTTATTACTGTGCGAGAGATTCTAACTGGGGCGA GGCTTTTGATATCTGGGGACAAGGGACAATGGTCACCG TCTCTTCAGCTAGCACTAA AGGGCCTTCTG l A TT TCCCTT GGCCCCGTCCAGCAAATCGACCTCGGGAGGGACAGCCG CCCTGGGTTGCCTTGTG AAAGA ΓΊ A Π T CCCTGAGCCAG TTACCGTAAGTTGGAACAGTGGGGCGCTGACAAGTGGT GTGCACACGTTTCCTGCCGTCCIGCAATCATCGGGCTTG TATAGCCTCAGCTCTGTGGTCACTGTCCCAAGTTCATCG CTGGGCACTCAGACGTATATTT GCAATGTGAACCACAA ACCTTCAAATACAAAAGTGGATAAACGCGTAGAACCGA AATCGTGTGATAAAACTCACACATGCCCGCCATGCCCG GCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCCTGTTC CCGCCGAAGCC l AAAGATACTCTAATGATCAGCCGTAC GCCAGAGG1GACATGTGTCGTGGl1GACGTGTCCCACG AAGATCCCGAAGTTAAGTTCAATTGGTA TGTTGATGGTG TAGAGGTACACAATGCTAAGACTAAACCTCGCGAGGAG CAGTACGCCTCGACCTATCGIGTCG1GAGCGTTCTGACC GTCC1 rCACCAAGATTGGCTTAACGGCAAAGAATATAA GTGCAAGGTAAGCAATA AAGCACT1CCGGCCCCAATCG AGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAGAA CCCCAGGTGTATACTCTTCCGCCn CTCGTGAGGAAATG ACTAAAAATCAAGTA TCCCTT ACGTGTCTGGTTAAAGGT TTTTATCCTAGCGA TATTGCTGITGAA TGGGAATCGAAC GGTCAGCCGGAGAATAATTATAAAACAACGCCACCCGT CCTGGA1AGCGACGGCTCATTT ΠΊ CTGTATAGCAAACT GACTGTAGATAAATCACGGTGGCAGCAGGGCAATGTAT TCAGTTGCTCCGTTATGCATGAAGCGTTACATAATCACT ACACGCAGAAATCTCTTAGTCmCACCCGGT
320	ATX-P-425	Variable HC + Constant hlgGl-Agly-Fc (nucieotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCAA GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG TTTCACCTTCAGTACTTATAGCA [ GAACTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAG TGGG TCTCATCCA TT A CTAGTAGl AGTAGTTACATGT i'Cl ACGCAGACTCAGI GA TGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAAC TCACTGTACCTACAAATGAACAGCCTGAGAGCCGAGGA CACAGCTGATTATTACTGTGCGAGAGATTCTAATTGGGG GGAGGCTTTTGATATCTGGGGACAAGGGACAATGGTCA CCGTCTCTTC AGCT AGCACT AA A GG GCCTTCTGTA TTTC CCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGACA GCCGCCC TGGGTTGCCTTGTG A A A GA TT ATTTCC CTG AG CCAGT IACCGTAAGTTGGAACAGTGGGGCGCTGACAAG TGGTG'I GCACACGTTTCCTGCCG i CCTGCA ATCATCGGG CTTGTATAGCCICAGCTCTGTGGTCAClGTCCCAAGTTC ATCGCTGGGCACTCAGACGTATATTTGCAATGTGAACCA CAAACCTTCAAATACAAAAG [ GGA ï AAACGCGTAGAAC CGAAATCGTGTGATAAAACTCACACATGCCCGCCATGC

132

			CCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCCTG TTCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCCGT ACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTCCCAC GAAGATCCCGAAGTTAAGTTCAATTGGTATGTTGATGGT GTAGAGGTACACAATGCTAAGACTAAACCTCGCGAGGA GCAGTACGCCTCGACCTATCGTGTCGTGAGCGTTCTGAC CGTCCTTCACCAAGATTGGCTTAACGGCAAAGAATATA AGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCAATC GAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAGA ACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGAAAT GACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAAAGG TTTTTATCCTAGCGATATTGCTGTTGAATGGGAATCGAA CGGTCAGCCGGAGAATAATTATAAAACAACGCCACCCG TCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCAAAC TGACTGTAGATAAATCACGGTGGCAGCAGGGCAATGTA TTCAGTTGCTCCGTTATGCATGAAGCGTTACATAATCAC TACACGCAGAAATCTCTTAGTCTTTCACCCGGT
32l	ATX-P-43Ü	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACA GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTA GTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTG AAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAA CACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGG ACACGGCCGTATATTACTGTGCGAAAGACGGTGACTAC TACTACTACTACATGGACGTCTGGGGCAAAGGGACCAC GGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGT ATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGG GACAGCCGCCCTGGG TTGCC TTGTGAAAGATTATTTCCC TGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGA CAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCAT CGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAA GTTC ATCGCTGGG CACTC A G ACG T A Γ ATI TGC A A TGTG A ACCACAAACCTTCAAATACAAAAGTGGATAAACGCGTA GAACCGAAATCGTGTGATAAAACTCACACATGCCCGCC ATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTT CCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAG CCGTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTC CCACGAAGATCCCGAAGTTAAGTTCAATTGGTATGTTGA TGGTGTAGAGGTACACAATGClAAGAClAAACCTCGCG AGGAGCAOTACGCCTCGACCTA TCGTGTCGTGAGCGT TC TGACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAAT ATAAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCA ATCGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAG AGAACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGA AATGACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAA AGGTTTTTATCCTAGCGATATTGCTGTTGAATGGGAATC GAACGGTCAGCCGGAGAATAATTATAAAACAACGCCAC CCG TCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCA AACTGACTGTAGATAAATCACGGTGGCAGCAGGGCAAT GTATTCAGTTGCTCCGTTATGCATGAAGCGTTACATAAT CACTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
322	ATX-P-439	Variable I IC + Constant hlgGl-Agly-Fc (nucléotide)	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACA GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTA

133

			GTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTG AAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAA CACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGG ACACGGCCGTATATTACTGTGCGAAAGTGGAAAGGGAT ATGGTTCGGGGCCACIACTACTACTACATGGACG I C I GG GGCAAAGGGACCACGGTCACCGTCTCTTCAGCTAGCAC TAAAGGGCCTTCTGTATTTCCCTTGGCCCCGTCCAGCAA ATCGACCTCGGGAGGGACAGCCGCCCTGGGTTGCCTTGT GAAAGATTATTTCCCTGAGCCAGTTACCGTAAGTTGGAA CAGTGGGGCGCTGACAAGTGGTGTGCACACGTTTCCTGC CGTCCTGCAATCATCGGGCTTGTATAGCCTCAGCTCTGT GGTCACTGTCCCAAGTTCATCGCTGGGCACTCAGACGTA TATTTGCAATGTGAACCACAAACCTTCAAATACAAAAGT GGATAAACGCGTAGAACCGAAATCGTGTGATAAAACTC ACACATGCCCGCCATGCCCGGCACCTGAACTGCTTGGTG GTCCCAGCGT GTTC CTGTTCCCGCCG A AGCCTA A AG A TA ctctaatgatcagccgtacgccagaggtgacatgtgtcg TGGTTGACGTGTCCCACGAAGATCCCGAAGTTAAGTTCA ATTGGTATGTTGATGGTGTAGAGGTACACAATGCTAAG ACTAAACCTCGCGAGGAGCAGTACGCCTCGACCTATCG TGTCGTGAGCGTTCTGACCGTCCTTCACCAAGATTGGCT TAACGGCAAAGAATATAAGTGCAAGGTAAGCAATAAAG CACTTCCGGCCCCAATCGAGAAAACCATTTCCAAGGCC AAAGGTCAACCAAGAGAACCCCAGGTGTATACTCTTCC GCCTTCTCGTGAGGAAATGAC'l AAAAA TCAAGTATCCCT TACGTGTCTGGTTAAAGGTTTTTATCCTAGCGATATTGC TGTTGAATGGGAATCGAACGGTCAGCCGGAGAATAATT ATAAAACAACGCCACCCGTCCTGGATAGCGACGGCTCA TTTTTTCTGTATAGCAAACTGACTGTAGATAAATCACGG TGGC AGCAGGGCAA IG TA T TCAG T TGCT CCG T TATGCAT GAAGCGTTACATAATCACTACACGCAGAAATCTCTTAGT CTTTCACCCGGT
323	ATX-P-423	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCA GCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCA GGCTCCAGGCAAGGGGCTGGAGTGGGTGTCACATATAA CATATGATGGAAGTGATAAATACTATGGAGACTCCGTG AAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAA TACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGG ACACGGCTGTGTATTACTGTGCGAAAGATGGGTATAGC AGTGGCTGGTGGTACTTTGACTACTGGGGCCAGGGAAC CCTGGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTC TGTATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGG AGGGACAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTT CCCTGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGC TGACAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAAT CATCGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCC CAAGTTCATCGCTGGGCACTCAGACGTATATTTGCAATG TGAACCACAAACCTTCAAATACAAAAGTGGATAAACGC GTAGAACCGAAATCGTGTGATAAAACTCACACATGCCC GCCATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGT GTTCCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGAT CAGCCGTACGCCAGAGGTGACATGTGTCGTGGTTGACG TGTCCCACGAAGATCCCGAAGTTAAGTTCAATTGGTATG TTGATGGTGTAGAGGTACACAATGCTAAGACTAAACCT CGCGAGGAGCAGTACGCCTCGACCTATCGTGTCGTGAG

I34

			CGTTCTGACCGTCCTTCACCAAGATTGGCTTAACGGCAA AGAA TATAAG TGCAAGGTAAGCAATAAAGCACTTCCGCi CCCCAATCGAGAAAACCATTTCCAAGGCCAAAGGTCAA CCAAGAGAACCCCAGGTGTATAC TC'TI CCGCCTTCTCG T GAGGAAA TGACTAAAAATCAAG'I Λ TCCCTTACGTGTCT GGTTAAAGGTTTTTATCCTAGCGA! ATTGCTGÏ TGAATG GGAATCGAACGGTCAGCCGGAGAAIAATTATAAAACAA CGCCACCCGTCCTGGATAGCGACGGCTCATTTTTTCTGT ATAGCAAACTGACTGTAGATAAATCACGGTGGCAGCAG GGCAATGTATTCAGTTGCTCCG Tl ATGCATGAAGCGTTA CATAATCAC TACACGCAGAAATCTC Π AGTCTTTCACCC GGT
324	ATX-P-438	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTGCAGCTGGTGGAGTCCGGGGGAGGCGTGGTCCA GCCTGGGAGGTCCCTGAGACTCTCC IG TGCAGCCTCTGG ATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCA GGCTCCAGGCAAGGGGCTGGAGIGGGTGGCAATTATAT CATATGA TGG AAATAATAA AT ACTATGCAGACTCCGTG AAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAA CACGCTGTATCTGCAAATGAACAGCCTGAGAGATGAGG ACACGGCTGTTTATTATTGTGCGAAAGAGAGGGGGTAT AGCAGCTCGTCCGGCTACTACTACTACTACATGGACGTC TGGGGCAAAGGGACCACGGTCACCGTCTCCTCAGCTAG CACTAAAGGGCC l TCTGTATTTCCCTl GGCCCCGTCCAG CAAATCGACCTCGGGAGGGACAGCCGCCCTGGGTTGCC TTGTGAAAGATTATTTCCCTGAGCCAGTTACCGTAAGTT GGAACAGTGGGGCGCTGACAAGTGGTGTGCACACGTTT CCTGCCG TCCTGCAATCATCGGGCT l’GTATAGCCTCAGC TCTGTGGICACTGTCCCAAGTTCATCGCTGGGCACTCAG ACGTATATTl GCAATGTGAACCACA AACCTTCAAATACA AAAGTGGATAAACGCGTAGAACCGAAATCGTGTGATAA AACTCACACATGCCCGCCATGCCCGGCACCTGAACTGCT TGGTGGTCCCAGCGTGTTCCTGTTCCCGCCGAAGCCTAA AGATACTCTAATGATCAGCCGTACGCCAGAGGTGACAT GTG TCGTGG II GACGTGTCCCACGAAGATCCCGAAGTTA AGTTCAATIGGTATGTTGATGGTG I AGAGGTACACAATG CTAAGAC l AAACCTCGCGAGGAGCAGTACGCCTCGACC TATCGTGTCGTGAGCGTTCTGACCG TCCTTCACCAAGAT TGGCTTAACGGCAAAGAATATAAGTGCAAGGTAAGCAA TAAAGCACTTCCGGCCCCAATCGAGAAAACCATTTCCA AGGCCAAAGG TCAACCAAGAGAACCCCAGGTGTATACT CTTCCGCCTTCTCGTGAGGAAATGACTAAAAATCAAGTA TCCCTTACOTGTCTGGTTAAAGGTTTJTATCCTAGCGAT ATTGCTGTT GAATGGGAATCGAACGGTCAGCCGGAGAA TAATTATAAAACAACGCCACCCGTCCTGGATAGCGACG GCTCATTITl ICTGTATAGCAAACTGACTGTAGATAAAT CACGGTGGCAGCAGGGCAATGTATTCAGTTGCTCCGTTA TGCATGAAGCGTTACATAATCACTACACGCAGAAATCTC TTAGTCTTICACCCGGT
325	ATX-P-448	Variable UC + Constant hlgGl-Agly-Fc (nucieotide)	CAAGTGCAATTGGTGGAGTCCGGTGGAGGAGTAGTACA GCCGGGAAGGTCACTGAGACTTTCCTGCGCTGCTAGTGG ATTCCCA TTTAGCTCCTACGGGATGCACTGGGTTCGCCA AGCGCCAGG TAAGGGACTGGAA TGGGTGGCTGTCATGA GTTACGATGGAA TTAACGGCl ΛΊ TATGCCGATAGCGTCA AAGGCCGGTTCACGATCTCAAGAGACAACTCTAAGAAC ACGCTCTACTTGCAGATGAACAGTCTCCGCGCAGAAGA TACGGCCGTGTATTACTGTGCGAGA I IGGTGTATGCCGA

135

			TGATGCTTTTGATATCTGGGGACAAGGGACCACGGTCAC CGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGTATTTCC CTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGACAG CCGCCCTGGGTTGCCTTGTGA AAGAU ATTTCCCTGAGC CAGTTACCGTAAGTTGGAACAGTGGGGCGCTGACAAGT GGTGTGCACACGTTTCCTGCCGTCCTGCAATCATCGGGC TTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAAGTTCA TCGCTGGGCACTCAGACGTATATTTGCAATGTGAACCAC AAACCTTCAAATACAAAAGTGGATAAACGCGTAGAACC GAAATCGTGTGATAAAACTCACACATGCCCGCCATGCC CGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCCTGT TCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCCGTA CGCCAGAGGTGACATGTGTCGTGGTTGACGTGTCCCACG AAGATCCCGAAGTTAAGTTCAATTGGTATGTTGATGGTG TAGAGGTACACAATGCTAAGACTAAACCTCGCGAGGAG CAGTACGCCTCGACCTATCGTGTCGTGAGCGTTCTGACC GTCCTTCACCAAGATTGGCTTAACGGCAAAGAATATAA GTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCAATCG AGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAGAA CCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGAAATG ACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAAAGGT TTTTATCCTAGCGATATTGCTGTTGAATGGGAATCGAAC GGTCAGCCGGAGAATAATTATAAAACAACGCCACCCGT CCTGGATAGCGACGGCTCATTTTTTCTGTATAGCAAACT GACTGTAGATAAATCACGGTGGCAGCAGGGCAATGTAT TCAGTTGCTCCGTTATGCATGAAGCGTTACATAATCACT ACACGCAGAAATCTCTTAGTCTTTCACCCGGT
326	ATX-P-449	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAAGTGCAATTGGTGGAGTCCGGTGGAGGAGTAGTACA GCCGGGAAGGTCACTGAGACTTTCCTGCGCTGCTAGTGG ATTCGCCTTTAGTTCCTACGGCATGCACTGGGTTCGCCA AGCGCCAGGTAAGGGACTGGAATGGGTGGCTGTCATCT CCTACTACGGATCTAATAAATATTATGCCGATAGCGTCA AAGGCCGGTTCACGATCTCAAGAGACAACTCTAAGAAC ACGCTCTACTTGCAGATGAACAGTCTCCGCGCAGAAGA TACGGCCGTGTATCACTGTGCGAGAGGGATTACTATGG ACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCA GCTAGCACTAAAGGGCCTTCTGTATTTCCCTTGGCCCCG TCCAGCAAATCGACCTCGGGAGGGACAGCCGCCCTGGG TTGCCTTGTGAAAGATTATTTCCCTGAGCCAGTTACCGT AAGTTGGAACAGTGGGGCGCTGACAAGTGGTGTGCACA CGTTTCCTGCCGTCCTGCAATCATCGGGCTTGTATAGCC TCAGCTCTGTGGTCACTGTCCCAAGTTCATCGCTGGGCA CTCAGACGTATATTTGCAATGTGAACCACAAACCTTCAA ATACAAAAGTGGATAAACGCGTAGAACCGAAATCGTGT GATAAAACTCACACATGCCCGCCATGCCCGGCACCTGA ACTGCTTGGTGGTCCCAGCGTGTTCCTGTTCCCGCCGAA GCCTAAAGATACTCTAATGATCAGCCGTACGCCAGAGG TGACATGTGTCGTGGTTGACGTGTCCCACGAAGATCCCG AAGTTAAGTTCAATTGGTATGTTGATGGTGTAGAGGTAC ACAATGCTAAGACTAAACCTCGCGAGGAGCAGTACGCC TCGACCTATCGTGTCGTGAGCGTTCTGACCGTCCTTCAC CAAGATTGGCTTAACGGCAAAGAATATAAGTGCAAGGT AAGCAATAAAGCACTTCCGGCCCCAATCGAGAAAACCA TTTCCAAGGCCAAAGGTCAACCAAGAGAACCCCAGGTG TATACTCTTCCGCCTTCTCGTGAGGAAATGACTAAAAAT CAAGTATCCCTTACGTGTCTGGTTAAAGGTTTTTATCCT

136

			AGCGAT ATTGCTGTTG A A TGGG A A T CG A ACGGTC AGCC GGAGAA'l ΑΑΊΊ ATAAAACAACGCCACCCGTCCTGGATA GCGACGGC l CA'ITTTTTCTGTATAGCAAACTGACTGTAG ATAAATCACGG TGGCAGCAGGGCAATGTATTCAGTTGC TCCGTTATGCATGAAGCGTTACATAATCACTACACGCAG AAATCTCTI AG TCTTTCACCCGG T
327	ATX-P-433	Variable l IC + Constant hlgGl-Agly-Fc (nucléotide)	GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACA GCCTGGCAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACC T TI GATGATTTTGCCATGCACTGGGTCCGGCA AGGTCCAGGG A AGGG CCTGG AGTGGGTCTC AGGT ATTG G H GG A A [ AGTGGT AGC ATCG GCT ATGC GG A CTCTGTG A AGGGCCGA TTCACCATCTCCAGAGACAACGCCAAGAAC ICC CTGT A TCTGCAA ATG A AC AGTC TG A GA GCTG AGG A CACGGCC ΤΊ ATATTACTGTGCAAAAGCCCCTGACTACGG TGACTACTACTTTGACTACTGGGGCCAGGGAACCCTGGT CACCGTCTCC TCAGCTAGCAC'I AAAGGGCCTTCTGTATT TCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGA CAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCCCTG AGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGACA AGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCATCG GGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAAGT TC ATCGCTGGGC ACTCAG ACGT AT A TTTGC A A TGTG A AC CACAAACCT I CAAATACAAAAGTGGA'l AAACGCGTAGA ACCGAAATCGTGTGATAAAACTCACACATGCCCGCCAT GCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCC TGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCC GTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTCCC ACGAAGATCCCGAAGTTAAGTTCAATTGGIATGTTGA TG GTGTAGAGGTACACAATGCTAAGACTAAACCTCGCGAG GAGCAGTACGCCTCGACCTATCG l’GTCGTGAGCGTTCTG ACCG1 CC ( TCACCAAGATTGGCTFAACGGCAAAGAATAT AAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCAAT CGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAG AACCCCAGGTGTATACTCTTCCGCCFI Cl CGTGAGGAAA TGACTAAAAATCAAGTATCCCTl ACG l GTC4 GGTTAAAG G T T Π T AICCTA GCG A T ATTGCTG TTG A A TGGG A ATCG A ACGGTCAGCCGGAGAATAATTATAAAACAACGCCACCC GTCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCAAA CTGACTGTAGATAAATCACGGTGGCAGCAGGGCAATGT ATTCAGTTGCTCCGTTATGCATGAAGCGTTACATAATCA CTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
328	ATX-P-444	Variable LC + Kappa Constant	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWF QQRPGQSPRRL1YKVSNRDSGVPDRISGSGSGTDFTLKISK VEAEDVGIYYCMQGTH WPWTFGQG TKVDIKRTVAAPSVF 1FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQES VTEQDSKDSTYSLSS 1 ’L I LSKADYEKHKVYACEV THQGLSSPVTKSFNRGEC
329	ATX-P-445	Variable LC + Kappa Constant	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWF QQRPGQSPRRLIHEVSNRDSGVPDRFSGSGSGTDFTLK1SR VEAEDVGVY YCMQGTH WPWT1GQGTK VDIKRTVAAPSV HFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAl.Q SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC
330	ATX-P-446	Variable LC + Kappa Constant	DVVMTQSPLSLPV TLGQPASISCRSSQSLVFSDGNTYLNWF QQRPGQSPRRL1YKVSNRDSGVPDRFSGSGSGTDFTLKISR VEAEDVGVYYCMQGTHWPWTFGQGTKVDIKRTVAAPSV

137

			FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC
33I	ATX-P-447	Variable LC + Kappa Constant	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWF QQRPGQSPRRLIHEVSNRDSGVPDRFSGSGSGTDFTLKISR VEAEDVGVYYCMQGTHWPWTFGQGTKVDIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC
332	ATX-P-427	Variable LC + Kappa Constant	AIQM TQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKP GKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPED FATYYCLQDYNYPYTFGQGTKLEIKR TVAAPSVFIFPPSDE Ql.KSGTASVVCLLNNFYPRF.AKVQWKVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC
333	ΛΤΧ-Ρ-440	Variable LC + Kappa Constant	DIQM TQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPG KAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSTPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC
334	ATX-P-424	Variable LC + Kappa Constant	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKP GKAPKRLIYAASSLPSGVPSRFSGSGSGTEFTLTISSLQPEDF AIYYCLQHNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC
335	ATX-P-425	Variable LC + Kappa Constant	DIQMTQSPSSLSASVGDRVTITCRASQGIRIDLGWFQQKPG KAPKRLIYAASSLPSGVPSRFSGSGSGTEFTLTISSLQPEDFA TYYCLQFINSYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP VTKSFNRGEC
336	ATX-P-43 0	Variable LC + Kappa Constant	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPPTFGGGTKVEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC
337	ATX-P-439	Variable LC + Kappa Constant	DIQMTQSPSSVSASVGDRVTITCRASQGtSSWLAWYQQKP GKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPED FATYYCQQANSFPWTFGQGTKVDIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKi IKVYACEV H [QGLS SPVTKSFNRGEC
338	ATX-P-423	Variable LC + Kappa Constant	DiQMTQSPSSLSASVGDRVTiTCRASQGIRNDLGWYQQKP GKAPKRLIYAASSLQSGVPSRFSGSGSGTEFALTISSLQPED FATYYCLQHNSYPLTFGGGTKLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTIIQGLSS PVTKSFNRGEC
339	ATX-P-438	Variable LC + Kappa Constant	EÏVLTQSPGTLSLSPGERATLSCRASQSVSRSYLAWYQQKP GQAPRLLIIGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQGQVIPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV

138

			TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC
340	ATX-P-448	Variable LC + Kappa Constant	EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPG QAPRLLIYDASNRA l GIPARFSGSGSGI DFTLTISSLEPEDFA VYYCQQRSNWPLTFGGGTKVEIKRJ VAAPSVFIFPPSDEQL KSGTASVVCLl.NNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTUQGLSSP VTKSFNRGEC
341	ΑΤΧ-Ρ-449	Variable LC + Kappa Constant	EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPG QAPRLLIYDASNRATGIPARFSGSGSGI DFTLTISSLEPEDFA VYYCQQRSNWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKl IKVYACEVTl IQGLSSP VTKSFNRGEC
342	ΑΤΧ-Ρ-433	Variable LC + Kappa Constant	DIQMTQSPSSLSASVGDRVTITCRASQSISIYLNWYQQKPG TAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA AYYCQQSYTTPLTFGGGTKVEIKRl VAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP VTKSFNRGEC
343	ΑΤΧ-Ρ-444	Variable LC + Kappa Constant (nucléotide)	GATGTTGTGAlGACTCAGTCTCCACTCTCCCTGCCCGTC ACCCTFGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGT CAAAGCCTCGTATACAGTGATGGAAACACCTACTTGAA TTGGTl TCAGCAGAGGCCAGGCCAATCTCCAAGGCGCCT ΑΑΠ TATAAGG'I ITCTAACCGGGACTCTGGGGTCCCAGA CAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACT GAAAA TCAGC AAGGTGGAGGCTGAGGATGTTGGGATTT ATTACTGCATGCAAGGTACACACTGGCCGTGGACGTTCG GCCAAGGGACCAAAGTGGATATCAAACGTACGGTAGCT GCCCCTTCAGTTTTTATCTTTCCGCCGTCTGACGAGCAGT TAAAATCCGGGACCGCTTCTG PAG ITIGCCTGCTG AATA ATTTTTATCCGCGTGAGGCTAAAGTACAATGGAAAGTCG ACAATGCTn’GCAGTCGGGAAATTCACAGGAAAGTGTT ACGGAGCAGGAIΊ CTA AAGATI’CCACATATTCACTCAGC TCCACCCTTACACTGAGCAAAGCCGACTATGAAAAACA TAAAGTIΊACGCATGTGAGGTGACGCACCAAGGATTAT CCAGTCCGGTCACAAAATCGTTTAACCGCGGTGAGTGT
344	ΑΤΧ-Ρ-445	Variable LC + Kappa Constant (nucléotide)	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTC ACCCTTGGACAGCCGGCCTCCATCICC TGCAGGTCTAGT CAAAGCCTCGTATACAGTGATGGAAACACCTACTTGAA TTGGTTTCAGCAGAGGCCAGGCCAATCTCCAAGGCGCCT AATTCATGAGGTTTCTAACCGGGACTCTGGGGTCCCAGA CAGATTCAGCGGCAGTGGGl CAGGCAC'I GATTTCACACT GAAAA'I CAGCAGGGTGGAGGC l GAGGAIG I I GGGGTTT ATTACTGCATGCAAGGTACACAClGGCCGTGGACGTTCG GCCAAGGGACCAAAGTGGATATCAAACGTACGGTAGCT GCCCCTTCAGTTTTTATCTTTCCGCCGTCTGACGAGCAGT TAAAATCCGGGACCGCTTCTGTAG'm'GCCTGCTGAATA ATTTTTATCCGCGTGAGGCTAAAGTACAATGGAAAGTCG ACAATGCriT'GCAGTCGGGAAATTCACAGGAAAGTGTT ACGGAGCAGGATTCTAAAGATTCCACATATTCACTCAGC TCCACCCl TACACTGAGCAAAGCCGAC TATGAAAAACA TAAAGT I'['ACGCATGTGAGGTGACGCACCAAGGATTAT CCAGTCCGGTCACAAAATCGTTTAACCGCGGTGAGTGT
345	ΑΤΧ-Ρ-446	Variable LC + Kappa Constant (nucléotide)	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTC ACCCT'I GGACAGCCGGCCTCCATCTCCTGCAGGTCTAGT

			CAAAGCCTCGTATTCAGTGATGGAAACACCTACTTGAAT TGGTTTCAGCAGAGGCCAGGCCAATCTCCAAGGCGCC T AATTTATAAGGTTTCTAACCGGGACTCTGGGGTCCCAGA CAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACT GAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGGGTTT AT l ACTGCAIGCAAGGTACACACTGGCCGTGGACGTTCG GCCAAGGGACCAAAGTGGATATCAAACGTACGGTAGCT GCCCCT TCAGTTTTTATCTTTCCGCCGTCTGACGAGCAGT TAAAATCCGGGACCGCTTCTGTAGTTTGCCTGCTGAATA ATTTTTATCCGCGTGAGGCTAAAGTACAATGGAAAGTCG ACAATGCTTTGCAGTCGGGAAATTCACAGGAAAGTGTT ACGGAGCAGGATTCTAAAGATTCCACATATTCACTCAGC TCCACCCTTACACTGAGCAAAGCCGACTATGAAAAACA TAAAGTTTACGCATGTGAGGTGACGCACCAAGGATTAT CCAGTCCGGTCACAAAATCGTTTAACCGCGGTGAGTGT
346	ATX-P-447	Variable LC + Kappa Constant (nucléotide)	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTC ACCCTTGGACAGCCGGCCTCCA TCTCCTGCAGGTCTAGT CAAAGCCTCGTATACAGTGATGGAAACACCTACTTGAA TTGGTT TCAGCAGAGGCCAGGCCAATCTCCAAGGCGCCT AATTCATGAGGTTTCTAACCGGGACTCTGGGGTCCCAGA CAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACT GAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGGGTTT ATTACTGCATGCAAGGTACACACTGGCCGTGGACGTTCG GCCAAGGGACCAAAGTGGATATCAAACGTACGGTAGCT GCCCCTTCAGTTTTTATCTTTCCGCCGTCTGACGAGCAGT T A A A A TC CGGG A CCG CTTCTGTAGTTTGCCTGCTG A AT A ATTTTTATCCGCGTGAGGCTAAAGTACAATGGAAAGTCG ACAATGCTTTGCAGTCGGGAAATTCACAGGAAAGTGTT ACGGAGCAGGATTCTAAAGATTCCACATATTCACTCAGC TCCACCCTTACACTGAGCAAAGCCGACTATGAAAAACA TAAAGTTTACGCATGTGAGGTGACGCACCAAGGATTAT CCAGTCCGGTCACAAAATCGTTTAACCGCGGTGAGTGT
347	ΛΤΧ-Ρ-427	Variable LC + Kappa Constant (nucléotide)	GCCATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGGGCATTAGAAATGATTTAGGCTGGTATCAGCAGA AACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAT CCAGTTTACAAAGTGGGGTCCCATCAAGGTTCAGCGGC AGTGGATCTGGCACAGATTTCACTCTCACCATCAGCAGC CTGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAA GAITACAATTACCCGTACACTTTTGGCCAGGGGACCAAG CTGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTTTT ATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGACC GCTTCTGT A GTTTGCCTGCTGA ATA ATTTTTATCCGCGTG AGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCAG TCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTC TAAAGATTCCACATATTCACTCAGCTCCACCCTTACACT GAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCAT GTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCACA AAATCG1 TI AACCGCGGTGAGTGT
348	ATX-P-440	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAG TCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTACATC CAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCA GTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGA

140

			GTT ACAG TACCCCGATCACCTTCGGCCAAGGGACACGA CTGGAG A I T A AACGTACGGTAGC TGCCCCTTC AGTTTTT ATCTTTCCGCCGTCTGACGAGCAG H AAAATCCGGGACC GCTTCTGTAGTn GCCTGCTGAATAA TTTTTATCCGCGTG AGGCI AAAGTACAATGGAAAGTCGACAATGCTTTGCAG TCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTC TAAAGATTCCACATATTCACTCAGCTCCACCCTTACACT GAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCAT GTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCACA AAATCGTITAACCGCGGTGAG TOT
349	ATX-P-424	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGGGCATTAGAAATGATTTAGGCTGGTATCAGCAGA AACCAGGGAAAGCCCCTAAGCGCCTGATCTATOCTGCA TCCAG l TT GCCAAG TGGGG1 CCCATCAAGGTTCAGCGGC AGTGGATC'l GGGACAGAATTCACTCTCACAATCAGCAG CCTGCAGCC TGAAGATTT TGCAA TTTATTACTGTCTACA GCATAA TAGTTACCCGTGGACGTTCGGCCAAGGGACCA AGGTGGAAATCAAACGTACGGTAGCTGCCCCTTCAGTTT TTATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGA CCGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCG TGAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGC AGTCGGGAAATTCACAGGAAAGTG'rTACGGAGCAGGAT TCTAAAGATTCCACATATTCACTCAGCTCCACCCTTACA CTGAGCAAAGCCGACTATGAAAAACA'l AAAGTTTACGC ATGTGAGG TGACGCACCAAGG ATTATCCAGTCCGGTCA CAAAATCGTTTAACCGCGGTGAGTGT
350	ΛΤΧ-Ρ-425	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCCGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGGGCA LI AGAATTGATTT AGGCTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCC TCATCTATGCTGCA TC CAGTTTGCCAAGTGGGGTCCCAlCAAGGTTCAGCGGCA GTGGATC l’GGGACAGAATTCACTCI CACAATCAGCAGC CTGCAGCCTGAAGAI 1 1 1GCAACTTA TT ACTGTCTACAG CATAATACi T TACCCGTGGACGTTCGGCCAAGGGACCAA GGTGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTTT TATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGAC CGCTTCl GIAGTTTGCCTGCTGAATAATTTTTATCCGCGT GAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCA GTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATT CTAAAGATTCCACATATTCACTCAGCTCCACCCTTACAC TGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCA TGTGAGGIGACGCACCAAGGATTATCCAGTCCGGTCAC AAAATCGTHAACCGCGGTGAGTGT
351	ATX-P-430	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCA TCTATGGT GC ATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTG GCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGT GTATTACTGTCAGC AGTATGGTAGCTCACCTCCCAC Π TCGGCGGAGGGACCA AGGTGGAAATCAAACGTACGGTAGCTGCCCCTTCAGTTT TTATCTTT CCGCCGTCTGACGAGCAG ΓΓΑΑ AATCCGGGA CCGCTTCTGTAGTTTGCCTGCTGAATAA ΊΤΠΊ ATCCGCG TGAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGC

I4l

			AGTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGAT TCTAAAGATTCCACATATTCACTCAGCTCCACCCTTACA CTGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGC ATGTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCA CAAAATCGTTTAACCGCGGTGAGTGT
352	ATX-P-439	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCA TCTGTAGGAGACAGAG TCACCA TCACTTGTCGGGCGAG TCAGGGTATTAGCAGCTGGITAGCCTGGIATCAGCAGA AACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAT CCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGC AGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGC CTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAG GCTAACAGTTTCCCGTGGACGTTCGGCCAAGGGACCAA AGTGGATATCAAACGTACGGTAGCTGCCCCTTCAGTTTT TATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGAC CGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGT GAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCA GTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATT CTAAAGATTCCACATATTCACTCAGCTCCACCCTTACAC TGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCA TGTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCAC AA A ATCGTTTA ACCGCGGTG AGTGT
353	ATX-P-423	Variable LC + Kappa Constant (nucléotide)	G ACATCC A GATG ACC C A GTCTCC A TC CTCCCTGTCTG CA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGGGCATTAGAAATGATTTAGGCTGGTATCAGCAGA AACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA TCCAG'l TTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGC AGTGGATCTGGGACAGAATTCGCTCTCACAATCAGCAG CCTG C A GCCTG A A G ATTTTGC A ACTT A TT ACTGTCT AC A GCA'I ’AATAGTTACCCTC TCAC'T Γ TCGGCGG AGGGACCA A GCTGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTTT TATCTT TCCGCCGTCTGACGAGCAG1TAAAATCCGGGAC CGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGT GAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCA GTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATT CTAAAGATTCCACATATTCACTCAGCTCCACCCTTACAC TGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCA IGTGAGG TGACGCACCA AGGAT TA! CCAGTCCGG TCAC AAAATCGT TTAACCGCGGTGAGTGT
354	ATX-P-438	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGCTGACTCAGTCTCCCGGCACACTGTCTCTT AGCCCTGGCGAAAGAGCCACACTGAGCTGTAGAGCCAG CCAGAGCGTGTCCAGAAGCTACCTGGCTTGGTATCAGC AGAAGCCCGGACAGGCTCCCAGACTGCTGATCATCGGA GCCTCTACAAGAGCCACCGGCATTCCCGATAGATTCAGC GGCTCTGGCAGCGGCACCGATTTCACCCTGACAATCAGC AGACTGGAACCCGAGGACTTCGCCGTGTACTACTGTCA GCAGGGCCAAGTGATCCCTCCTACCTTTGGCCAGGGCAC CAAGGTGGAAATCAAACGTACGG TAGCTGCCCCI ’TCAG ITT 1TATC l I ’TCCGCCG TCTGACGAGCAG T TA AAA TCCG GGACCGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCC GCGTGAGGCTAAAGTACAATGGAAAGTCGACAATGCTT TGCAGTCGGGAAATTCACAGGAAAGTGTTACGGAGCAG GATTCTAAAGATTCCACATATTCACTCAGCTCCACCCTT ACACTGAGCAAAGCCGACTATGAAAAACATAAAGTTTA CGCATGTGAGGTGACGCACCAAGGATTATCCAGTCCGG TCACAAAATCGTT TAACCGCGG TGAG TGT

I42

355	ATX-P-448	Variable LC + Kappa Constant (nucléotide)	GAAATTGTG T TGACGC AGTCTCCAGCCACCCTGTC TT TG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGA AACC TGGCCAGGC TCCCAGGC ICC TCATCTATGA TGCAT CCAACAGGGCCACTGGCATCCCAGCCAGGTTCAGTGGC AG TGGGTC TGGGACAGAC T TCAC'I Cl CACCATCAGCAGC CTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAG CGTAGCAACTGGCCTCTCACTTTCGGCGGAGGGACCAA GGTGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTTT TATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGAC CGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGT GAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCA GTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATT CTAAAGA ITCCACATATTCACTCAGCTCCACCCTTACAC TGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCA TGTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCAC AAAATCGTTTAACCGCGGTGAGTGT
356	ATX-P-449	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACGCAGTCTCCAGCCACCCTGTCTTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGA AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGATGCAT CCAACAGGGCCACTGGCATCCCAGCCAGGTTCAGTGGC AGI GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGC CTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAG CGTAGCAACTGGCCTCTCACTTTCGGCGGAGGGACCAA GGTGGAGATCAAACGTACGGTAGCTGCCCCTTCAGTTTT TATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGAC CGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGT GAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCA GTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATT CTAAAGATTCCACATATTCACTCAGCTCCACCCTTACAC TGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCA TGI GAGGTGACGCACCAAGGAT1ATCCAGTCCGGTCAC AAAATCGTTTAACCGCGGTGAGTGT
357	ATX-P-433	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGAGCATTAGCATCTATTTAAATTGGTATCAGCAGAA ACCAGGGACAGCCCCTAAGCTCCTGATCTATGCTGCATC CAG TTTGCAAAGTGGGGTCCCATCAAGGl TCAGTGGCA GTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAGCTTACTACTGTCAACAGA GTTACACTACCCCGCTCACTTTCGGCGGAGGGACCAAG GTGGAAATCAAACGTACGGTAGCTGCCCCTTCAGTTTTT ATC'm CCGCCG TCTGACGAGCAG TTAAAATCCGGGACC GC'l rCFGI AGTTTGCCTGCTGAATAATTTTTATCCGCGTG AGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCAG TCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTC TAAAGATTCCACATATTCACTCAGCTCCACCCTTACACT GAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCAT GTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCACA AAA'I CGI’I TAACCGCGGTGAGTG T
358	ATX-P-435	Variable HC + Constant hlgGl-Agly-Fc	QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSSYWGWIRQP PGKGLEW1GS1YYSGSTYSNPSLKSRVT1SVDTSKNQFSLKL SSVTAADTAVYYCARQYISGTEYFQYWGQGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGV11TFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

143

			VNHKPSNTKVDKRVEPKSCDK Π Π CPPCPAPELLGGPSVF LFPPKPKD TLMISR TPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAK I KPREEQYASTYRVVSVl I VLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVY'l l.PPSREEM ΓΚ NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGN VFSCSVMI lEALHNHYI QK SLSLSPG
359	ATX-P-436	Variable HC + Constant hlgGl-Agly-Fc	QLQ1.QESGPGLVKPSETLSLTCTVSGGS1SSSSSYWGWIRQP PGKGLEWIGSIYYSGSTYSNPSLKSRVT1SVDTSKNQFSLKL SSVTAADIAVYYCARQYISGTEYFQYWGQGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVV 1 VPSSSLG TQTY1CN VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAK1KPREEQYASTYRVVSVL TVLIIQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSREEMTK NQVSLTCLVKGFYPSD1AVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPG
360	ATX-P-434	Variable UC + Constant hlgGl-Agly-Fc	QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGSYYWSW1R QPPGKGLEW1GYIYYSGSTSYNPSLK.SRVS1SVDTSK.NQFSL KLSSVTAADTAVFYCARAKWEGDYFDYWGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGAL'l SGV1ITFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSN1KVDKRVEPKSCDKTH1CPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKI KPREEQYASTYRVVSVLTVLHQDWLNGKE YKCKVSNKAI.PAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKL I VDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPG
361	ATX-P-435	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAA GCCTTCGGAGACCCTGTCCCTCACCrGCACIGTCTCTGG TGGTTCCATCAÜCAGTAGTAGTTCCJACTGGGGCTGGAT CCGCCAGCCCCCAGGGAAGGGAC1GGAGTGGA TTGGGA GTATCTATTATAGTGGGAGCACCTACTCCAACCCGTCCC TCAAGAG1CGAGTCACCATATCCGTAGACACGTCCAAG AATCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCA GACACGGCTG TGTATTACTGTGCGAGACAG ΤΑΤΑΊ AAG T GGAACTGAATACTTCCAGTACTGGGGCCAGGGCACCCT GGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGT ATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGG GACAGCCGCCCIGGGTTGCCTTGTGAAAGA TTATTTCCC TGAGCCAGTTACCGTAAG Π GGAACAG1GGGGCGC I GA CAAGTGGTGTGCACACGTT ICCTGCCGTCCTGCAATCAT CGGGCTTGTATAGCCTCAGCTC1G I GGTCACTGTCCCAA GTTCATCGCIGGGCACTCAGACG TA IA ΓΠ GCAATGTGA ACCACAAACCTTCAAATACAAAAGTGGATAAACGCGTA GAACCGAAATCGTGTGATAAAACTCACACATGCCCGCC ATGCCCGGCACCTGAACTGCT1GGTGGTCCCAGCGTGTT CCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAG CCGTACGCCAGAGGTGACATGl GTCGTGGTTGACGTGTC CCACGAAGATCCCGAAGTTAAGITCAATTGGTATGTTGA TGGTGTAGAGGTACACAATGC1AAGACTAAACCTCGCG AGGAGCAGTACGCCTCGACCl ATCGTGTCGTGAGCGTTC TGACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAAT

144

			ATAAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCA ATCGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAG AGAACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGA AATGACTAAAAATCAAGTATCCCTTACGTGTCTGGTTAA AGGTTTTTATCCTAGCGA'I ATTGCTGTTGAATGGGAATC GAACGGTCAGCCGGAGAA TAATTATAAAACAACGCCAC CCGTCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCA AACTGACTGTAGATAAATCACGGTGGCAGCAGGGCAAT GT ATTC AGTTGCTCCGTTATGCATG A A GCGTT A C AT A AT CACTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
362	ATX-P-436	Variable HC + Constant hlgGl-Agly-Fc (nucléotide)	CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAA GCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGG TGGTTCCATCAGCAGTAGTAGTTCCTACTGGGGCTGGAT CCGCCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGA GTATCTATTATAGTGGGAGCACCTACTCCAACCCGTCCC TCAAGAGTCGAGTCACCATATCCGTAGACACGTCCAAG AATCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCA GACACGGCTGTGTATTACTGTGCGAGACAGTATATAAGT GGAACTGAATACTTCCAGTACTGGGGCCAGGGCACCCT GGTCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGT ATTTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGG GACAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCCC TGAGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGA CAAGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCAT CGGGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAA GTTCATCGCTGGGCACTCAGACGTATATTTGCAATGTGA ACCACAAACCTTCAAATACAAAAGTGGATAAACGCGTA GAACCGAAATCGTGTGATAAAACTCACACATGCCCGCC ATGCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTT CCTGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAG CCGTACGCCAGAGGTGACATGTGTCGTGGTTGACGTGTC CCACGAAGATCCCGAAGTTAAGTTCAATTGGTATGTTGA TGGTGTAGAGGTACACAATGCTAAGACTAAACCTCGCG AGGAGCAGTACGCCTCGACCTATCGTGTCGTGAGCGTTC TGACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAAT ATAAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCA ATCGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAG AGAACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGA AATGACTAAAAATCAAGTATCCCTTACGTGTCTGG TTAA AGGTTTTTATCCTAGCGATATTGCTGTTGAATGGGAATC GAACGGTCAGCCGGAGAATAATTATAAAACAACGCCAC CCGTCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCA AACTGACTGTAGATAAATCACGGTGGCAGCAGGGCAAT GTATTCAGTTGCTCCGTTATGCATGAAGCGTTACATAAT CACTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
363	ATX-P-434	Variable I IC + Constant hlgGl-Agly-Fc (nucléotide)	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAA GCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGG TGGCTC CG TC AGCAGTGG TAGTTACTACTGGA GCTGGAT CCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGT ATATCTATTACAGTGGGAGCACCAGCTACAACCCCTCCC TC A AG AGTCG AGTCTCC A TATC AGTAG A C A CGTCC A AG AACCAGT rCFCCCTGAAGCTGAGCTCTGTGACCGCTGCG GACACGGCCGTGTTTTACTGTGCGAGAGCTAAGTGGGA AGGGGACTACTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCAGCTAGCACTAAAGGGCCTTCTGTAT TTCCCTTGGCCCCGTCCAGCAAATCGACCTCGGGAGGGA

145

			CAGCCGCCCTGGGTTGCCTTGTGAAAGATTATTTCCCTG AGCCAGTTACCGTAAGTTGGAACAGTGGGGCGCTGACA AGTGGTGTGCACACGTTTCCTGCCGTCCTGCAATCATCG GGCTTGTATAGCCTCAGCTCTGTGGTCACTGTCCCAAGT TCATCGCTGGGCACTCAGACGTATATTTGCAATGTGAAC CACAAACCTTCAAATACAAAAGTGGATAAACGCGTAGA ACCGAAATCGTGTGATAAAACTCACACATGCCCGCCAT GCCCGGCACCTGAACTGCTTGGTGGTCCCAGCGTGTTCC TGTTCCCGCCGAAGCCTAAAGATACTCTAATGATCAGCC GTACGCC A G A GGTG AC ATGTGTCGTGGTTG ACGTGTCCC ACGAAGATCCCGAAGTTAAGTTCAATTGGTATGTTGATG GTGTAGAGG TACACAAl GCTAAGACTAAACCTCGCGAG GAGCAG1ACGCCTCGACCTATCGTGTCGTGAGCGTTCTG ACCGTCCTTCACCAAGATTGGCTTAACGGCAAAGAATAT AAGTGCAAGGTAAGCAATAAAGCACTTCCGGCCCCAAT CGAGAAAACCATTTCCAAGGCCAAAGGTCAACCAAGAG AACCCCAGGTGTATACTCTTCCGCCTTCTCGTGAGGAAA TGACTAAAAATCAAGTATCCCTTACGTGTCTGGIΊ AAAG GTTTTTATCCTAGCGATATTGCTGTTGAATGGGAATCGA ACGGTCAGCCGGAGAATAATTATAAAACAACGCCACCC GTCCTGGATAGCGACGGCTCATTTTTTCTGTATAGCAAA CTGACTGTAGATAAATCACGGTGGCAGCAGGGCAATGT ATTCAGTTGCTCCGTTATGCATGAAGCGTTACATAATCA CTACACGCAGAAATCTCTTAGTCTTTCACCCGGT
364	ATX-P-435	Variable LC + Kappa Constant	E1VLTQSPATLSLSPGERATLSCRASQSVSNYLAWYQQKPG QAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFA VYYCQQRSNWPSFGQGTRLEIKRTVAAPSVF1FPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC
365	ATX-P-436	Variable LC + Kappa Constant	DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPG KAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLT1SSLQPEDF ATYYCQQSYSTPLTFGGGTKVE1KRTVAAPSVF1FPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT F.QDSKDSTYSLSSTLTLSKADYEKI IKVYACEVTHQGLSSP VTKSFNRGEC
366	ATX-P-434	Variable LC + Kappa Constant	DIQMTQSPSSLSASVGDRVTITCRASQSIYSYLNWYQQKPG KAPNHLIYAASSLQSGVPSRFSGSGSGTDFTLT1SSL1IPEDF ATYYCQQSYSTPPYTFGQGTKVEIKRTVAAPSVF1FPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC
367	ATX-P-435	Variable LC + Kappa Constant (nucléotide)	GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTG TCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TCAGAGTGTTAGCAACTACTTAGCCTGGTACCAACAGA AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGATGCAT CCAACAGGGCCACTGGCATCCCAGCCAGATTCAGTGGC AGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGC CTGGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAG CGTAGCAACTGGCCCTCCTTCGGCCAAGGGACACGACT GGAGAT'l AAACGTACGGTAGCTGCCCCTTCAGTTTTTAT CTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGACCGC TTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGTGAG GCTAAAG TACAATGGAAAGTCGACAATGCTTTGCAGTC GGGAAA TTCACAGGAAAGTGTTACGGAGCAGGATTCTA AAGATTCCACATATTCACICAGC1CCACCCTTACACTGA

I46

			GCAAAGCCGACTATGAAAAACATAAAGTTTACGCATGT GAGGTGACGCACCAAGGATTATCCAGTCCGGTCACAAA ATCGT H AACCGCGGTGAGTGT
368	ATX-P-436	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCTCC'I ’GATCTATGCTGCATC CAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCA GTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGA GTTACAGTACCCCGCTCACTTTCGGCGGAGGGACCAAG GTGGAAATCAAACGTACGGTAGCTGCCCCTTCAGTTTTT ATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGACC GCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCGTG AGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGCAG TCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGATTC TAAAGATTCCACATATTCACTCAGCTCCACCCTTACACT GAGCAAAGCCGACTATGAAAAACATAAAGTTTACGCAT GTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCACA AAATCGTTT AACCGCGGTGAGTGT
369	ATX-P-434	Variable LC + Kappa Constant (nucléotide)	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCA TCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAG TCAGAGCATTTACAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAATCACCTGATCTATGCTGCATC CAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCA GTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCACCCTGAAGATTTTGCAACTTACTACTG TCAACAGA GTTACAGTACCCCTCCGTACACTTTTGGCCAGGGGACCA AGGTGGAAATCAAACGTACGG TAGC [ GCCCCTTCAGTTT TTATCTTTCCGCCGTCTGACGAGCAGTTAAAATCCGGGA CCGCTTCTGTAGTTTGCCTGCTGAATAATTTTTATCCGCG TGAGGCTAAAGTACAATGGAAAGTCGACAATGCTTTGC AGTCGGGAAATTCACAGGAAAGTGTTACGGAGCAGGAT TCTAAAGATTCCACATATTCAC TCAGC TCCACCCTTACA CTGAGCAAAGCCGACTATGAAAAACATAAAGTTTACGC ATGTGAGGTGACGCACCAAGGATTATCCAGTCCGGTCA C A AA ATC GTTT A A CCGCG GTGAGTGT

[00228] Human Angiopoietin-related protein 7 (UniProt Accession No. 043827): MLKKPLSAVTWLCIFIVAFVSHPAWLQKLSKHKTPAQPQLKAANCCEEVKELKAQVAN LSSLLSELNKKQERDWVSVVMQVMELESNSKRMESRLTDAESKYSEMNNQIDIMQLQA

AQTVTQTSADAIYDCSSLYQKNYRISGVYKLPPDDFLGSPELEVFCDMETSGGGWTIIQR RKSGLVSFYRDWKQYKQGFGSIRGDFWLGNEHIHRLSRQPTRLRVEMEDWEGNLRYAE YSHFVLGNELNSYRLFLGNYTGNVGNDALQYHNNTAFSTKDKDNDNCLDKCAQLRKG GYWYNCCTDSNLNGVYYRLGEHNKHLDGITWYGWHGSTYSLKRVEMKIRPEDFKP (SEQ IDNO: 370).

147 |00229] Human Angiopoietin-related protein 7 L59PL84P variant (ATX-P-62): MLKKPLSAVTWLCIFIVAFVSHPAWLQKLSKHKTPAQPQLKAANCCEEVKELKAQVAN PSSLLSELNKKQERDWVSVVMQVMEPESNSKRMESRLTDAESKYSEMNNQIDIMQLQA AQTVTQTSADAIYDCSSLYQKNYRISGVYKLPPDDFLGSPELEVFCDMETSGGGWTIIQR

RKSGLVSFYRDWKQYKQGFGSIRGDFWLGNEHIHRLSRQPTRLRVEMEDWEGNLRYAE YSHFVLGNELNSYRLFLGNYTGNVGNDALQYHNNTAFSTKDKDNDNCLDKCAQLRKG GYWYNCCTDSNLNGVYYRLGEHNKHLDGITWYGWHGSTYSLKRVEMKIRPEDFKP (SEQ IDNO: 371).

[00230] Human Angiopoietin-related protein 7 L59 GGPGG variant (ATX-P-63):

MLKKPLSAVTWLCIFIVAFVSHPAWLQKLSKHKTPAQPQLKAANCCEEVKELKAQVAN GGPGGSSLLSELNKKOERDWVSVVMOVMELESNSKRMESRLTDAESKYSEMNNQIDI MQLQAAQTVTQTSADAIYDCSSLYQKNYRISGVYKLPPDDFLGSPELEVFCDMETSGGG WTIIQRRKSGLVSFYRDWKQYKQGFGSIRGDFWLGNEHIHRLSRQPTRLRVEMEDWEG NLRYAEYSHFVLGNELNSYRLFLGNYTGNVGNDALQYHNNTAFSTKDKDNDNCLDKC

AQLRKGGYWYNCCTDSNLNGVYYRLGEHNKHLDGITWYG WHGSTYSLKRVEMKIRPE DFKP (SEQ ID NO: 372).

[00231] Human Angiopoietin-related protein 7 fibrinogen domain (ATX-P-60): YDCSSLYQKNYRISGVYKLPPDDFLGSPELEVFCDMETSGGGWTI1QRRKSGLVSFYRD WKQYKQGFGSIRGDFWLGNEHIHRLSRQPTRLRVEMEDWEGNLRYAEYSHFVLGNELN

SYRLFLGNYTGNVGNDALQYHNNTAFSTKDKDNDNCLDKCAQLRKGGYWYNCCTDS NLNGVYYRLGEHNKHLDGITWYGWHGSTYSLKRVEMKIRPED (SEQ IDNO: 373).

[00232] Human Angiopoietin-related protein 7 wild type multimer (PExt-l):

|00233] MLKKPLSAVTWLCIFIVAFVSHPAWLQKLSKHKTPAQPQLKAANCCEEVKEL KAQVANLSSLLSELNKKQERDWVSVVMQVMELESNSKRMESRLTDAESKYSEMNNQ1 25 DIMQLQAAQTVTQTSADAIYDCSSLYQKNYRISGVYKLPPDDFLGSPELEVFCDMETSG

GGWT1IQRRKSGLVSFYRDWKQYKQGFGSIRGDFWLGNEHIHRLSRQPTRLRVEMEDW EGNLRYAEYSHFVLGNELNSYRLFLGNYTGNVGNDALQYHNNTAFSTKDKDNDNCLD KCAQLRKGGYWYNCCTDSNLNGVYYRLGEHNKHLDGITWYGWHGSTYSLKRVEMKI RPEDFKP (SEQ ID NO: 374).

148

[00234] Table 11 : Summary of SEQ ID NOs for individual exemplary antibodies of the présent disclosure.

Antibody Name	HCDRs 1,23 (aa)	LCDRs 1,2,3 (aa)	VH (aa)	VH (nucléotide)	VL (aa)	VL (nucléotide)	VH + constant (aa)	VH + constant (nucléotide)	VL + constant (aa)	VL + constant (nucléotide)
ATX-P-423	40,56,71	90,102,114	208	223	238	253	308	323	338	353
ATX-P-424	34,50,65	88,100,112	204	219	234	249	304	319	333	349
ATX-P-425	35,51,66	89,101,113	205	220	235	250	305	320	335	350
ATX-P-427	32,48,63	97,109,121	202	217	232	247	302	317	332	347
ATX-P-428	2,8,13	144,154,164	170	175	180	185	270	275	280	285
ATX-P-429	3,9,14	123,129,135	172	177	182	187	272	277	282	287
ATX-P-430	36,52,67	148,158,168	206	221	236	251	306	321	336	351
ATX-P-431	5,11,16	146,156,166	173	178	183	188	273	278	283	188
ATX-P-432	6,12,17	147,157,167	174	179	184	189	274	279	284	289
ATX-P-433	42,58,73	94,106,118	212	227	242	257	312	327	342	357
ATX-P-434	75, 79, 83	96,108,120	260	263	266	269	360	363	366	369
ATX-P-435	76, 80, 84	143,153,163	258	261	264	267	358	361	364	367
ATX-P-436	77, 81,85	95,107,119	259	262	265	268	359	362	365	368
ATX-P-437	20,23,26	92,104,116	190	192	194	196	290	292	294	296
ATX-P-438	41,57,72	149,159,169	209	224	239	254	309	324	339	354
ATX-P-439	37,53,68	87,99,111	207	222	237	252	307	322	337	352
ATX-P-440	33,49,64	93,105,117	203	218	233	248	303	318	333	348
ATX-P-442	19,22,25	91,103,115	191	193	195	197	291	293	295	297
ATX-P-443	4,10,15	145,155,165	171	176	181	186	271	276	281	286
ATX-P-444	28,44,59	124,130,136	198	213	228	243	298	313	328	343
ATX-P-445	29,45,60	125,131,137	199	214	229	244	299	314	329	344
ATX-P-446	30,46,61	126,132,138	200	215	230	245	300	315	330	345
ATX-P-447	31,47,62	127,133,139	201	216	231	246	301	316	331	346
ATX-P-448	39,55,70	142,152,162	210	225	240	255	310	325	340	355
ATX-P-449	38,54,69	141,151,161	211	226	241	256	311	326	341	356

KEY: aa = amino acid; HCDR l, 2, 3 = heavy chain CDRs l, 2, and 3 (in numerical order); LCDRs l, 2, 3 = light chain CDRs 1, 2, and 3 (in numerical order); VH = heavy chain variable région; VL = light chain variable région; VH + constant = heavy chain variable région sequence with an exemplary human heavy chain constant région sequence (typically IgG 1 ); VL + constant = light chain variable région sequence with an exemplary 5 human light chain constant région sequence (typically kappa). Ail numbers except in “Antibody Name” correspond to SEQ ID NOs in the sequence listing and Tables 8, 9, and 10.

149 |00235] Various embodiments of the présent disclosure are described herein. Variations of those embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the various embodiments of the présent disclosure to be 5 practiced otherwise than as specifically described herein. Accordingly, embodiments of the présent disclosure include ail modifications and équivalents of the subject matter recited in the daims appended hereto as permitted by applicable law. Moreover, any combination of the abovedescribed éléments in ail possible variations thereof is encompassed by the various embodiments of the présent disclosure unless otherwise indîcated herein or otherwise clearly contradicted by 10 context.

Claims (15)

1. l An antibody, or an antigen binding fragment thereof, which specifically bïnds human Angiopoietin-Like Protein 7 (ANGPTL7), optionally wherein said human ANGPTL7 is a polypeptide which comprises or consists ofthe amino acid sequence of any one of SEQ ID NOs: 370 to 374.
2. 2. The antibody, or an antigen binding fragment thereof, of claim l, which exhibits any one or more the following functional characteristics:

   a. increases outflow facility compared to a control when administered to the eye of a subject, optionally wherein the control is vehicle treatment, dexamethasone treatment, ANGPTL7 protein treatment, or ANGPTL7 protein with an isotype control antibody treatment; and/or

   b. binds to ANGPTL7 with a KdoÎ about lOOnM or lower; and/or

   c. binds to the same epitope on ANGPTL7 as an antibody comprising the VH and VL sequences of any one of the exemplary antibodies the sequences of which are provided in Table 11; and/or

   d. competes for binding to ANGPTL7 with an antibody comprising the VH and VL sequences of any one of the exemplary antibodies the sequences of which are provided in Table 11.
3. 3. The antibody, or an antigen binding fragment thereof, of claim I or claim 2, which is monoclonal, optionally recombinant.
4. 4. The antibody, or an antigen binding fragment thereof, of any one of claims l to 3, which is human, humanîzed or chimeric.
5. 5. The antibody, or an antigen binding fragment thereof, of any one of claims I to 4, which is a full length antibody, a single chain antibody, a single chain variable fragment (scFv), a variable fragment (Fv), a fragment antigen-binding région (Fab), a Fab-C, a Fab’-SH, a (Fab’)2, i

   i i

   a single-domain antibody (sdAb), a VHH antibody, a nanobody, a camelid-derived singledomain antibody, a shark IgNAR-derived single-domain antibody fragment (VNAR), a diabody, a triabody, an antical in or an aptamer, optionally wherein the antibody is a full length antibody comprising an Fc région such as a human IgG l, lgG2, IgG3 or IgG4 région.
6. 6. The antibody, or an antigen binding fragment thereof, of any one of claims I to 5, which is conjugated to at least one additional moiety, optionally selected from:

   a. an antigen binding moiety, such as an antibody or antigen-binding fragment thereof, which is capable of spécifie binding to a target which is not human ANGPTL7, I0 preferably wherein said target is expressed in the human eye;

   b. a therapeutic or cytotoxic moiety;

   c. a détection moiety;

   d. a purification moiety;

   e. a half-life extension moiety, optionally a polypeptide that is at least 20 amino acids in 15 length and comprises any combination of G, A, S T, E, and P residue, which polypeptide is conjugated to the C- or N- terminus of the antibody.
7. 7. The antibody, or an antigen binding fragment thereof, of any one of claims l to 6, which is a polypeptide comprising:

   20 a. one, two or ail three HCDRs of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also one, two or ail three of the corresponding LCDRs of said exemplary antibody; and/or

   b. a VH sequence having at least 90% identity to the VH sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally

   25 also a VL sequence having at least 90% identity to the corresponding VL sequence of said exemplary antibody, preferably wherein variation is not permitted in the HCDRs or LCDRs; and/or

   c. ail six CDRs of any one of the exemplary antibodies the sequences of which are provided in Table 11; and/or

   30 d. the VH and VL sequences of any one of the exemplary antibodies the sequences of which are provided in Table 11; and/or

   152

   e. the full length heavy chain (VH + constant) sequence of any one of the exemplary antibodies the sequences of which are provided in Table 11, and optionally also the corresponding full length light chain (VL + constant) sequence of said exemplary antibody.
8. 8. A polynucleotide encoding an antibody, or an antigen binding fragment thereof, of any one of claims l to 7, optionally wherein said polynucleotide comprises or consists of a nucleic acid sequence having at least 70%, 80%, 90% or 100% identity to a nucleic acid sequence of any one of the exemplary antibodies the sequences of which are provided in Table I I.
9. 9. An expression vector comprising the polynucleotide of claim 8, which is optionally an adeno-associated virus (AAV) vector, a lentiviral (LV) vector, a herpes simplex virus (HSV) vector, or a retrovirus vector.
10. 10. A pharmaceutical composition comprising an antibody, or an antigen binding fragment thereof, a polynucleotide, or a vector according to any one of the preceding claims, and optionally:

    a. at least one pharmaceutically acceptable carrier, diluent or preservative; and/or b. at least one additional active ingrédient.
11. 11. The pharmaceutical composition of claim 10, which is suitable for ocular administration to a subject, optionally by delivery using a conjunctival insert. a contact lens, a gel, a nanoparticle, a mucoadhesîve polymer, an ointment, a solution, a suspension, eye drops, and/or an implant, preferably by injection into the vitreous fluid.
12. 12. The antibody, or an antigen binding fragment thereof, according to any one of claims 1 to 7, the polynucleotide of claim 8, the vector of claim 9, or the composition of claim 10 or 11, for use as a médicament, optionally for use in a method of treating a disease of the eye in a subject.

    153
13. 13. The antibody, fragment, polynucleotide, vector, or composition for use according to claim I2, wherein said disease is characterized by increased intraocular pressure and/or reduced outflow facility in the eye of the subject.

    5
14. 14. The antibody, fragment, polynucleotide, vector or composition for use according to claim

    12 or 13, wherein the method comprises ocular administration of the antibody, preferably by injection into the vitreous fluid. and wherein said administration preferably relieves at least one symptom in the subject selected from eye pain, eye pressure, headaches, rainbow-colored halos around lights, low vision, blurred vision, narrowed vision, impaired peripheral vision, blind

    10 spots, nausea, vomiting. and red eyes.
15. 15. The antibody, fragment, polynucleotide, vector or composition for use according to any one of claims 12 to I4, where the disease is glaucoma and/or a disease affecting the optic nerve or retinal ganglion cells, optionally wherein said glaucoma is primary or glucocorticoid-induced 15 glaucoma.