Dosage and administration of an Anti-ox40l antibody

Administering anti-OX40L antibodies in specific dosages and schedules addresses immune overactivation in inflammatory diseases by modulating T cell activity, providing effective treatment for conditions such as atopic dermatitis and asthma.

WO2025255353A1PCT designated stage Publication Date: 2025-12-11APOGEE THERAPEUTICS INC
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Patent Information

Application Number
PCT/US2025/032460
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2025-02-28
Filing Date
2025-06-05
Publication Date
2025-12-11

AI Technical Summary

Technical Problem

There is a need for improved therapeutics and methods of treatment that target OX40L to address immune overactivation in inflammatory conditions such as atopic dermatitis and asthma.

Method used

Administering an anti-OX40L antibody or its antigen binding fragment according to specific clinical dosage regimens, including doses of 75 mg, 150 mg, 300 mg, 600 mg, or 1200 mg, and dosing schedules such as every three or six months, to modulate T cell activity and regulate immune response.

Benefits of technology

The administration of anti-OX40L antibodies effectively targets OX40L, reducing immune overactivation and alleviating symptoms in inflammatory diseases like atopic dermatitis and asthma.

✦ Generated by Eureka AI based on patent content.

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Abstract

Provided are dosages and methods for clinical treatment of human patients using an anti-OX40L antibody, or antigen binding fragment thereof.
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Description

[0001] DOSAGE AND ADMINISTRATION OF AN ANTI-OX40L ANTIBODY

[0002] BACKGROUND

[0003] OX40L is the ligand for 0X40 expressed on antigen presenting cells. Its interaction with 0X40 causes the accumulation of T cells by providing a survival signal. T cells are important types of white blood cells of the immune system that play a central role in the immune response. OX40L, by playing a role in activating T cells and reprogramming them into inflammatory subsets, contributes to immune overactivation in atopic dermatitis (AD) and other inflammatory conditions. Additionally, OX40L activation of 0X40 inhibits the expression of Foxp3 and the inhibitory function of regulatory T (Treg) cells. Treg cells can suppress the immune response that leads to worsening symptoms in inflammatory conditions. Accordingly, there is a need in the art for improved therapeutics and methods of treatment that target OX40L. It is an object of the present disclosure to provide improved methods for treating patients wi th a variety of immunologic and inflammatory' diseases, such as AD and asthma.

[0004] SUMMARY

[0005] Provided herein are compositions and methods for treating a variety7of diseases and conditions (including immunologic and inflammatory7diseases) in a human patient comprising administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, wherein the anti-OX40L antibody, or antigen binding fragment thereof, is administered (or is for administration) according to a particular clinical dosage regimen (e.g., at a particular dose amount and according to a specific dosing schedule). In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, is administered at a dose of 75 mg, 150 mg, 300 mg, 600 mg, or 1200 mg. In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, is administered subcutaneously.

[0006] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 75 mg.

[0007] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 150 mg.

[0008] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 300 mg. In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 600 mg.

[0009] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 1200 mg.

[0010] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a maintenance dose every three months.

[0011] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a maintenance dose every' six months.

[0012] In one embodiment, the antibody is Antibody 114. Antibody 114 comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 489, and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738. A C-terminal lysine is present in SEQ ID NO: 854. which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 651. Accordingly, a composition comprising Antibody 114 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 854 or SEQ ID NO: 651, or a mixture thereof. In certain embodiments, Antibody 114 comprises the heavy chain sequence set forth in SEQ ID NO: 932 and the light chain sequence set forth in SEQ ID NO: 933. The C-terminal lysine in SEQ ID NO: 932 may not be present if cleavage occurs during manufacture or after administration.

[0013] In another embodiment, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1-69, 740-747, and 840; b. CDR-H2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 70-174 and 748-762; c. CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 175-257 and 763-780, d. CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 258-334 and 781-796, e. CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 335-367 and 797-805; and f. CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 268-393 and 806-811.

[0014] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0015] 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 258, 286, and 311; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0016] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2,

[0017] 23, and 45; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0018] 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 176, 204, and 224; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 259, 287, and 312; a CDR-L2 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 336 and 360; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 369 and 395.

[0019] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 3,

[0020] 24, and 46; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0021] 71, 112, and 143; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 177, 205, and 225; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 370 and 396.

[0022] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 22, and 47; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0023] 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206. and 226; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 261 , 289, and 314; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0024] 73, 114, and 145; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207, and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 262, 290, and 315; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 372 or 398.

[0025] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 6,

[0026] 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0027] 74, 115, and 146; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208. and 228; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 263, 291, and 316; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 339 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 373 and 399.

[0028] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 7,

[0029] 25, and 50; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0030] 75, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 181, 209. and 229; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 264. 292, and 317; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 and 363; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0031] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8,

[0032] 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0033] 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 182, 210, and 230; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 375 and 401 .

[0034] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51 ; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 183, 211. and 231; a CDR-Ll comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265. 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 376 and 402.

[0035] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26. and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 183, 211, and 231; a CDR-Ll comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 377 and 403.

[0036] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76. 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 184, 212, and 232; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 376 and 402.

[0037] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 184, 212, and 232; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 377 and 403.

[0038] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 185, 213, and 233; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 376 and 402.

[0039] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8,

[0040] 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0041] 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 185, 213. and 233; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 377 and 403.

[0042] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 9,

[0043] 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0044] 77, 118, and 149; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203. and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 342 and 364; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0045] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0046] 28, and 53; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0047] 78, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 266. 286, and 311; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0048] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10. 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 79, 1 19, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 186, 203, and 235; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 267, 294. and 319; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 344 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0049] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0050] 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 80, 120, and 151; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 186, 203, and 235; a CDR-L1 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0051] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0052] 11, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 79, 1 19, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0053] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 11, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 81. 121, and 152; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0054] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 80, 120, and 151; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 187. 203, and 236; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 79, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 187, 203, and 236; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0055] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188. 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 268, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0056] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 12, 29, and 54; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0057] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an ammo acid sequence set forth in any one of SEQ ID NOs: 82, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 189, 214, and 238; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 345 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0058] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 83, 122, and 153; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 346 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0059] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13. 30. and 55; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 84, 1 11, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 239; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0060] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 347 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0061] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 345 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0062] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 85, 123, and 154; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 239; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0063] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175. 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 270, 295, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0064] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0065] 31, and 56; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203. and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 379and 405.

[0066] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0067] 32, and 57; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 86, 124, and 155; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0068] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10. 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 1 11 , and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288. and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361 ; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 and 406.

[0069] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 14, 33, and 58; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0070] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87, 1 11, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0071] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0072] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13, 30, and 55; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175. 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0073] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175. 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 348 and 366; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0074] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 381 and 405.

[0075] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an ammo acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0076] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 86, 124, and 155; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203. and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 381 and 405.

[0077] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22. and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 86, 124, and 155; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0078] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 239; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0079] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0080] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 78, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0081] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2, 840, and 45; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 176, 204. and 224; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 259, 287, and 312; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 336 and 360; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 369 and 395.

[0082] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15, 34, and 59; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 88, 125, and 156; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190, 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 349 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 382 and 407.

[0083] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 22, and 47; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 89, 126, and 157; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206, and 226; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0084] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 35. and 60; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 72, 1 13, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206, and 241; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 271, 296, and 320; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 350 and 361 ; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0085] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 22, and 47; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 90, 127, and 1 8; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206, and 226; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 261, 289, and 314; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0086] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 16, 36, and 61; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 91, 128, and 159; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 191, 215, and 242; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 351 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 382 and 407.

[0087] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 16, 36, and 61; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 91. 128, and 159; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190, 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 351 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0088] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15, 27, and 62; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190. 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 382 and 407. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15, 27, and 62; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190, 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 351 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 383 and 408.

[0089] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 37, and 63; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0090] 92, 129, and 160; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207. and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 272, 297, and 321; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 384 and 409.

[0091] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0092] 93, 130, and 161; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207. and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 272. 297, and 321; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 384 and 409.

[0093] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0094] 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 192, 207, and 243; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 273, 298, and 322; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 385 and 410.

[0095] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 17, 38, and 64; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 95, 132, and 163; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207, and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 272, 297, and 321; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 386 and 411.

[0096] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 24. and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0097] 96, 130, and 164; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 192, 207, and 243; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 274, 299, and 323; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 386 and 411.

[0098] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0099] 97. 130, and 164; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207, and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 275, 300, and 324; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 386 and 411.

[0100] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0101] 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 193, 216, and 244; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 276, 301, and 325; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0102] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 193, 216, and 245; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 277, 302, and 326; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0103] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 194. 217, and 246; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 276, 301, and 325; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0104] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0105] 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 194, 217, and 247; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 276, 301, and 325; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 388 and 413.

[0106] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0107] 19, 40, and 66; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 99, 133, and 165; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 278, 303, and 327; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 352 and 367; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0108] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0109] 20, 41, and 67; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100, 134, and 166; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 218, and 249; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 279, 304. and 328; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 353 and 361 ; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0110] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 20, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 101, 133, and 167; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 389 and 414.

[0111] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0112] 102, 135, and 168; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 350 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 389 and 414.

[0113] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0114] 103, 136. and 169; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 196, 218, and 250; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 354 and 367; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 390 and 415.

[0115] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0116] 104, 137. and 170; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 197, 208. and 251; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 281 , 306, and 330; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 105, 138. and 171; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 197, 208, and 251; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 281, 306, and 330; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0117] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 198, 219. and 252; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 282, 307, and 331; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 391 and 416.

[0118] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 20, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 218, and 253; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 355 and 367; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0119] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0120] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 6, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 106, 137, and 170; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 218. and 253; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280. 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0121] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0122] 20. 41. and 67; a CDR-H2 compnsing an amino acid sequence set forth in any one of SEQ ID NOs: 107, 133, and 167; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0123] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 108, 139. and 172; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 181, 209, and 229; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 283, 308, and 332; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 356 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0124] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0125] 21, 42, and 68; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 109, 140. and 173; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 199, 220, and 254; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0126] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 43, and 69; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 106, 137, and 170; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 200, 221 , and 255; a CDR-Ll comprising an amino acid sequence set forth in any one of SEQ ID NOs: 284, 309, and 333; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0127] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 43, and 69; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 201, 222. and 256; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 285, 310, and 334; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 357 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 392 and 417.

[0128] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 43, and 69; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 110, 141, and 174; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 202, 222. and 257; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 285. 310, and 334; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 358 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 393 and 418.

[0129] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 748, 116, and 758; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 763, 769, and 775, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 781. 787, and 792; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 797 and 802; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 806 and 812.

[0130] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 740, 742. and 745; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 749, 754, and 759; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 764, 770, and 776, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 782, 788. and 793; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 798 and 803; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 807 and 813.

[0131] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 17, 743, and 746; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 750, 133, and 165; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 765, 771, and 777, a CDR-L1 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 783, 298, and 322; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 799 and 804; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 808 and 814.

[0132] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0133] 751, 755, and 760; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 766, 772, and 778, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 784, 789, and 794; a CDR-L2 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 809 and 815.

[0134] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0135] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0136] 752, 756. and 761; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 767, 773. and 779. a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 785, 790, and 795; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 800 and 805; and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NOs: 810 and 816. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 741, 744, and 747; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 753, 757. and 762; a CDR-H3 comprising an amino acid sequence set forth in SEQ ID NOs: 768, 774, and 780, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 786, 791, and 796; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 801 and 360; and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NOs: 811 and 817.

[0137] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable domain (VH) sequence selected from an amino acid sequence set forth in SEQ ID NOs: 419-488, 818-824, and 841.

[0138] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a light chain variable domain (VL) sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0139] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 419-488, 818-824, and 841, and a VL sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0140] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 419 and a VL sequence set forth in SEQ ID NO: 489.

[0141] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 420 and a VL sequence set forth in SEQ ID NO: 490.

[0142] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 421 and a VL sequence set forth in SEQ ID NO: 491.

[0143] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 422 and a VL sequence set forth in SEQ ID NO: 492.

[0144] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 423 and a VL sequence set forth in SEQ ID NO: 493. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 424 and a VL sequence set forth in SEQ ID NO: 494.

[0145] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 425 and a VL sequence set forth in SEQ ID NO: 495.

[0146] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 426 and a VL sequence set forth in SEQ ID NO: 496.

[0147] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 427 and a VL sequence set forth in SEQ ID NO: 497.

[0148] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 427 and a VL sequence set forth in SEQ ID NO: 498.

[0149] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 428 and a VL sequence set forth in SEQ ID NO: 497.

[0150] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 428 and a VL sequence set forth in SEQ ID NO: 498.

[0151] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 429 and a VL sequence set forth in SEQ ID NO: 497.

[0152] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 429 and a VL sequence set forth in SEQ ID NO: 498.

[0153] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 430 and a VL sequence set forth in SEQ ID NO: 499.

[0154] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 431 and a VL sequence set forth in SEQ ID NO: 500. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 432 and a VL sequence set forth in SEQ ID NO: 501.

[0155] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 433 and a VL sequence set forth in SEQ ID NO: 502.

[0156] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 434 and a VL sequence set forth in SEQ ID NO: 502.

[0157] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 435 and a VL sequence set forth in SEQ ID NO: 502.

[0158] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 436 and a VL sequence set forth in SEQ ID NO: 502.

[0159] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 437 and a VL sequence set forth in SEQ ID NO: 502.

[0160] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 438 and a VL sequence set forth in SEQ ID NO: 503.

[0161] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 439 and a VL sequence set forth in SEQ ID NO: 502.

[0162] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 440 and a VL sequence set forth in SEQ ID NO: 504.

[0163] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 441 and a VL sequence set forth in SEQ ID NO: 505.

[0164] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 442 and a VL sequence set forth in SEQ ID NO: 506. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 443 and a VL sequence set forth in SEQ ID NO: 507.

[0165] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 443 and a VL sequence set forth in SEQ ID NO: 508.

[0166] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 444 and a VL sequence set forth in SEQ ID NO: 506.

[0167] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 509.

[0168] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 446 and a VL sequence set forth in SEQ ID NO: 510.

[0169] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 447 and a VL sequence set forth in SEQ ID NO: 506.

[0170] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 511.

[0171] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 448 and a VL sequence set forth in SEQ ID NO: 506.

[0172] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 449 and a VL sequence set forth in SEQ ID NO: 502.

[0173] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 449 and a VL sequence set forth in SEQ ID NO: 506.

[0174] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 450 and a VL sequence set forth in SEQ ID NO: 506. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 512.

[0175] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 449 and a VL sequence set forth in SEQ ID NO: 513.

[0176] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 514.

[0177] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 515.

[0178] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 451 and a VL sequence set forth in SEQ ID NO: 514.

[0179] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 451 and a VL sequence set forth in SEQ ID NO: 506.

[0180] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 452 and a VL sequence set forth in SEQ ID NO: 506.

[0181] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 438 and a VL sequence set forth in SEQ ID NO: 506.

[0182] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 453 and a VL sequence set forth in SEQ ID NO: 512.

[0183] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 454 and a VL sequence set forth in SEQ ID NO: 490.

[0184] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 455 and a VL sequence set forth in SEQ ID NO: 516. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 456 and a VL sequence set forth in SEQ ID NO: 517.

[0185] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 457 and a VL sequence set forth in SEQ ID NO: 518.

[0186] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 458 and a VL sequence set forth in SEQ ID NO: 492.

[0187] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 459 and a VL sequence set forth in SEQ ID NO: 519.

[0188] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 460 and a VL sequence set forth in SEQ ID NO: 520.

[0189] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 461 and a VL sequence set forth in SEQ ID NO: 521.

[0190] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 461 and a VL sequence set forth in SEQ ID NO: 522.

[0191] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 461 and a VL sequence set forth in SEQ ID NO: 522.

[0192] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 462 and a VL sequence set forth in SEQ ID NO: 523.

[0193] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 463 and a VL sequence set forth in SEQ ID NO: 523.

[0194] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 464 and a VL sequence set forth in SEQ ID NO: 524. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 465 and a VL sequence set forth in SEQ ID NO: 525.

[0195] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 466 and a VL sequence set forth in SEQ ID NO: 526.

[0196] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 467 and a VL sequence set forth in SEQ ID NO: 527.

[0197] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 468 and a VL sequence set forth in SEQ ID NO: 528.

[0198] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 469 and a VL sequence set forth in SEQ ID NO: 529.

[0199] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 470 and a VL sequence set forth in SEQ ID NO: 528.

[0200] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 471 and a VL sequence set forth in SEQ ID NO: 530.

[0201] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 472 and a VL sequence set forth in SEQ ID NO: 531.

[0202] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 473 and a VL sequence set forth in SEQ ID NO: 532

[0203] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 474 and a VL sequence set forth in SEQ ID NO: 533.

[0204] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 475 and a VL sequence set forth in SEQ ID NO: 534. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 476 and a VL sequence set forth in SEQ ID NO: 535.

[0205] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 477 and a VL sequence set forth in SEQ ID NO: 536.

[0206] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 478 and a VL sequence set forth in SEQ ID NO: 536.

[0207] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 479 and a VL sequence set forth in SEQ ID NO: 537.

[0208] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 480 and a VL sequence set forth in SEQ ID NO: 538.

[0209] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 481 and a VL sequence set forth in SEQ ID NO: 539.

[0210] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 482 and a VL sequence set forth in SEQ ID NO: 539.

[0211] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 483 and a VL sequence set forth in SEQ ID NO: 539.

[0212] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 484 and a VL sequence set forth in SEQ ID NO: 540.

[0213] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 485 and a VL sequence set forth in SEQ ID NO: 541.

[0214] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 486 and a VL sequence set forth in SEQ ID NO: 542. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 487 and a VL sequence set forth in SEQ ID NO: 543.

[0215] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 488 and a VL sequence set forth in SEQ ID NO: 544.

[0216] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 818 and a VL sequence set forth in SEQ ID NO: 825.

[0217] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 819 and a VL sequence set forth in SEQ ID NO: 826.

[0218] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 820 and a VL sequence set forth in SEQ ID NO: 827.

[0219] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 821 and a VL sequence set forth in SEQ ID NO: 828.

[0220] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 822 and a VL sequence set forth in SEQ ID NO: 829.

[0221] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 823 and a VL sequence set forth in SEQ ID NO: 830.

[0222] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 824 and a VL sequence set forth in SEQ ID NO: 831.

[0223] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 841 and a VL sequence set forth in SEQ ID NO: 842.

[0224] In another embodiment, the antibody, or antigen binding fragment thereof, is a humanized, human, or chimeric antibody.

[0225] In another embodiment, the antibody, or antigen binding fragment thereof, is a humanized antibody. In another embodiment, antibody, or antigen binding fragment thereof, comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

[0226] In another embodiment, the antibody , or antigen binding fragment thereof, comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgGl, IgG2, IgG3, and IgG4.

[0227] In another embodiment, the human Fc region comprises a human IgGl Fc region.

[0228] In another embodiment, the human Fc region comprises a human IgG4 Fc region.

[0229] In another embodiment, the human Fc region comprises a human IgG2 Fc region.

[0230] In another embodiment, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a constant heavy chain sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 637-737 and 843-931, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In some embodiments, the heavy chain comprises a constant heavy chain sequence selected from an amino acid sequence set forth in SEQ ID NO: 651, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In some embodiments, the heavy chain comprises a constant heavy chain sequence selected from an amino acid sequence set forth in SEQ ID NO: 854. or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0231] In another embodiment, the antibody, or antigen binding fragment thereof, comprises a light chain comprising a constant light chain sequence set forth in SEQ ID NO: 738, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0232] In another embodiment, the heavy chain comprises a constant heavy chain sequence selected from an amino acid sequence set forth in SEQ ID NO: 651, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity' thereto and the light chain comprises a constant light chain sequence set forth in SEQ ID NO: 738, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0233] In another embodiment, the heavy chain comprises a constant heavy chain sequence selected from an amino acid sequence set forth in SEQ ID NO: 854, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto and the light chain comprises a constant light chain sequence set forth in SEQ ID NO: 738, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0234] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 651 and / or a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489, and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738.

[0235] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 489, and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738.

[0236] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 489. and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738.

[0237] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO:

[0238] 932 or an amino acid sequence having at least 90%. at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0239] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a light chain sequence comprising an amino acid sequence set forth in SEQ ID NO:

[0240] 933 or an amino acid sequence having at least 90%. at least 91%. at least 92%. at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 932 or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto and a light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 933, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0241] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 932 and a light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 933.

[0242] In another embodiment, the antibody , or antigen binding fragment thereof, comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, and / or CDC activity7compared with the Fc region without the one or more substitutions.

[0243] In another embodiment, the antibody , or antigen binding fragment thereof, comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of ADCC activity', ADCP activity, and / or CDC activity7compared with the Fc region without the one or more substitutions.

[0244] In another embodiment, the one or more amino acid substitutions results in increased antibody half-life compared to an antibody comprising a wild-type Fc region.

[0245] In another embodiment, the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q31 IV, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions is a combination of amino acid substitutions selected from the group consisting of M428L / N434S (LS); M252Y / S254T / T256E (YTE); T250Q / M428L; T307A / E380A / N434A; T256D / T307Q (DQ); T256D / T307W (DW); M252Y / T256D (YD); T307Q / Q311V / A378V (QVV); T256D / H285D / T307R / Q311V / A378V (DDRVV); L309D / Q311H / N434S (DHS); S228P / L235E (SPLE); L234A / L235A (LALA); M428L / N434A (LA); L235A / G237A (LAGA); L234A / L235A / G237A (LALAGA); L234A / L235A / P329G (LALAPG); D265A / YTE; LALA / YTE; LAGA / YTE; LALAGA / YTE; LALAPG / YTE; N297A / LS; D265A / LS; LALA / LS; LALAGA / LS; LALAPG / LS; N297A / DHS; D265A / DHS; LALA / DHS; LAGA / DHS;

[0246] LALAGA / DHS; LALAPG / DHS; SP / YTE; SPLE / YTE; SP / LS; SPLE / LS; SP / DHS; SPLE / DHS; N297A / LA; D265A / LA; LALA / LA; LAGA / LA; LALAGA / LA; LALAPG / LA; N297A / N434A; D265A / N434A; LALA / N434A; LAGA / N434A; LALAGA / N434A; LALAPG / N434A; N297A / N434W; D265A / N434W; LALA / N434W; LAGA / N434W; LALAGA / N434W; LALAPG / N434W; N297A / DQ, D265A / DQ; LALA / DQ; LAGA / DQ; LALAGA / DQ; LALAPG / DQ; N297A / DW; D265A / DW; LALA / DW; LAGA / DW; LALAGA / DW;

[0247] LALAPG / DW; N297A / YD; D265A / YD; LALA / YD; LAGA / YD; LALAGA / YD; LALAPG / YD; T307Q / Q311V / A378V (QVV); N297A / QVV; D265A / QVV; LALA / QVV; LAGA / QVV;

[0248] LALAGA / QVV; LALAPG / QVV; DDRVV; N297A / DDRVV; D265A / DDRVV;

[0249] LALA / DDRVV; LAGA / DDRVV; LALAGA / DDRV V; and LALAPG / DDRVV. In some embodiments, the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q / M428L, T307A / E380A / N434A, DQ, DW, YD, QVV, DHS, LA, D265A / YTE, LALA / YTE, LAGA / YTE, LALAGA / YTE. LALAPG / YTE. N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D265A / DHS. LALA / DHS. LAGA / DHS, LALAGA / DHS, LALAPG / DHS, SP / YTE, SPLE / YTE, SP / LS, SPLE / LS, SP / DHS, SPLE / DHS, N297A / LA, D265A / LA, LALA / LA, LAGA / LA, LALAGA / LA, LALAPG / LA, N297A / DQ, D265A / DQ, LALA / DQ, LAGA / DQ, LALAGA / DQ, LALAPG / DQ, N297A / DW, D265A / DW, LALA / DW, LAGA / DW, LALAGA / DW, LALAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, N297A / QVV. D265A / QVV, LALA / QVV. LAGA / QVV, LALAGA / QVV, and LALAPG / QVV.

[0250] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody, or antigen binding fragment thereof, described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236. In certain embodiments, the OX40L antibody, or antigen binding fragment thereof, described herein comprises the heavy and light chain variable regions of Antibody 114 and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively.

[0251] In certain embodiments the human Fc region comprises a human IgGl Fc with LALA mutations. In certain embodiments the human Fc region comprises a human IgGl Fc with YTE mutations. In certain embodiments the human Fc region comprises a human IgGl Fc with LALA and YTE mutations. In certain embodiments, the Fc region of the OX40L antibody, or antigen binding fragment thereof, comprises a human IgGl Fc with LALA or YTE mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. In certain embodiments, the LALA mutations are at positions 234 and 235 and the YTE mutations are at positions 252, 254 and 256 (EU numbering). In certain embodiments, the LALA mutations are at positions 235 and 236 (L235A / L236A) and the YTE mutations are at positions 253, 255, and 257 (M253Y / S255T / T257E) (direct numbering). In another embodiment, the Fc region binds to Neonatal Fc receptor (FcRn).

[0252] In another embodiment, the Fc region binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.

[0253] In another embodiment, the Fc region binds to FcRn with a KD of <1 x 10-7 M at pH 6.0. In another embodiment, the antibody, or antigen binding fragment thereof, is a monoclonal antibody.

[0254] In another embodiment, the antibody, or antigen binding fragment thereof, binds an OX40L sequence set forth in SEQ ID NO: 739.

[0255] In another embodiment, the antibody, or antigen binding fragment thereof, binds to an OX40L sequence set forth in SEQ ID NO: 739 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7. 8. or 9 x 10-9M, as measured by surface plasmon resonance (SPR).

[0256] In another embodiment, the antibody, or antigen binding fragment thereof, binds to an OX40L sequence set forth in SEQ ID NO: 739 with a KD of less than or equal to about 1 x IO'10M, as measured by surface plasmon resonance (SPR).

[0257] In another embodiment, the antibody, or antigen binding fragment thereof, binds to human OX40L with a KD of less than or equal to about 1 x 10'9M, as measured by surface plasmon resonance (SPR).

[0258] In another embodiment, the antibody, or antigen binding fragment thereof, exhibits a melting temperature greater than 68°C as measured by Differential Scanning Fluorometry (DSF).

[0259] In another embodiment, the antibody, or antigen binding fragment thereof, exhibits a melting temperature greater than 75°C as measured by Differential Scanning Fluorometry (DSF).

[0260] In another embodiment, the antibody, or antigen binding fragment thereof, exhibits an aggregation temperature equal to or greater than 71.2°C as measured by Differential Scanning Fluorometry (DSF).

[0261] In another embodiment, the antibody, or antigen binding fragment thereof, has a retention time of 15.2 minutes or less as measured by hydrophobic interaction chromatography. In another embodiment, the antibody, or antigen binding fragment thereof, can inhibit OX40L dependent IFNy release, for example, in a human cell. In some embodiments, the antibody, or antigen binding fragment thereof, can inhibit OX40L dependent IFNy release, for example, in a human.

[0262] In another embodiment, the antibody, or antigen binding fragment thereof, has an increased capacity to bind cell surface OX40L as compared to amlitelimab.

[0263] In another embodiment, the antibody , or antigen binding fragment thereof, does not have a heavy chain variable region sequence set forth in SEQ ID NO: 832.

[0264] In another embodiment, the antibody, or antigen binding fragment thereof, does not have a light chain variable region sequence set forth in SEQ ID NO: 833.

[0265] In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, has a half-life of about 60 days.

[0266] In one embodiment, administration of the anti-OX40L antibody, or antigen binding fragment thereof, inhibits Type 1, Type 2, and / or Type 3 inflammation.

[0267] In one embodiment, administration of the anti-OX40L antibody, or antigen binding fragment thereof, reduces expression of one or more non-Type 2 inflammatory markers selected from the group consisting of TNFa, NFKBI. and NFKBIA.

[0268] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of an inflammatory disorder or disease. In certain embodiments, the anti- OX40L antibody, or antigen binding fragment thereof, is used in the treatment of atopic dermatitis. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of idiopathic pulmonary’ fibrosis. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of alopecia areata. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of chronic sinusitis with nasal polyps. In certain embodiments, the anti- OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of eosinophilic esophagitis (EoE). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN). Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Churg-Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Prurigo Nodularis (PN). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Chronic Spontaneous Urticaria (CSU). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Chronic Pruritis of Unknown Origin (CPUO). In certain embodiments, the anti- OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Bullous Pemphigoid (BP). In certain embodiments, the anti-OX40L antibody , or antigen binding fragment thereof, is used in the treatment of Cold Inducible Urticaria (ColdU). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Allergic Fungal Rhinosinusitis (AFRS). In certain embodiments, the anti-OX40U antibody, or antigen binding fragment thereof, is used in the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of Chronic Obstructive Pulmonary Disease (COPD). In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of psoriasis. In certain embodiments, the anti- OX40L antibody, or antigen binding fragment thereof, is used in the treatment of lupus. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of rheumatoid arthritis. In certain embodiments, the anti-OX40U antibody, or antigen binding fragment thereof, is used in the treatment of hi dradenitis suppurativa. In certain embodiments, the anti-OX40U antibody, or antigen binding fragment thereof, is used in the treatment of celiac disease. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of systemic sclerosis. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of allergic rhinitis. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of eosinophilic fasciitis. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of scleromyxedema. In certain embodiments, the anti-OX40U antibody, or antigen binding fragment thereof, is used in the treatment of scleredema. In certain embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, is used in the treatment of and nephrogenic systemic fibrosis.

[0269] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, is used in a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount an antibody, or antigen binding fragment thereof, described herein or a pharmaceutical composition described herein. In certain embodiments of the methods described herein, the inflammatory disorder or disease is atopic dermatitis. In certain embodiments, the inflammatory’ disorder or disease is asthma. In certain embodiments, the inflammatory disorder or disease is idiopathic pulmonary fibrosis. In certain embodiments of the methods described herein, the inflammatory’ disorder or disease is alopecia areata. In certain embodiments, the inflammatory' disorder or disease is chronic sinusitis with nasal polyps. In certain embodiments, the inflammatory disorder or disease is Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In certain embodiments, the inflammatory disorder or disease is eosinophilic esophagitis (EoE). In certain embodiments, the inflammatory disorder or disease is an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE). In certain embodiments, the inflammatory disorder or disease is Churg-Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA). In certain embodiments, the inflammatory' disorder or disease is Prurigo Nodularis (PN). In certain embodiments, the inflammatory' disorder or disease is Chronic Spontaneous Urticaria (CSU). In certain embodiments, the inflammatory disorder or disease is Chronic Pruritis of Unknown Origin (CPUO). In certain embodiments, the inflammatory disorder or disease is Bullous Pemphigoid (BP). In certain embodiments, the inflammatory disorder or disease is Cold Inducible Urticaria (ColdU). In certain embodiments, the inflammatory disorder or disease is Allergic Fungal Rhinosinusitis (AFRS). In certain embodiments, the inflammatory disorder or disease is Allergic Bronchopulmonary Aspergillosis (ABPA). In certain embodiments, the inflammatory disorder or disease is Chronic Obstructive Pulmonary Disease (COPD). In certain embodiments, the inflammatory' disorder or disease is an inflammatory' bowel disease, such as Crohn’s disease or ulcerative colitis. In certain embodiments, the inflammatory' disorder or disease is psoriasis. In certain embodiments, the inflammatory disorder or disease is lupus. In certain embodiments, the inflammatory' disorder or disease is rheumatoid arthritis. In certain embodiments, the inflammatory' disorder or disease is celiac disease. In certain embodiments, the inflammatory disorder or disease is hidradenitis suppurativa. In certain embodiments, the inflammatory' disorder or disease is systemic sclerosis. In certain embodiments, the inflammatory disorder or disease is allergic rhinitis. In certain embodiments, the inflammatory disorder or disease is eosinophilic fasciitis. In certain embodiments, the inflammatory disorder or disease is scleromyxedema. In certain embodiments, the inflammatory' disorder or disease is scleredema. In certain embodiments, the inflammatory disorder or disease is nephrogenic systemic fibrosis. In certain embodiments of the methods described herein, the mammalian subject is a human.

[0270] BRIEF DESCRIPTION OF THE DRAWINGS

[0271] FIG. 1 is a schematic of the Single Ascending Dose (SAD) Study Schema. Thec'*’’ represents the planned dose level (z.e., 1200 mg SC x 1 dose). However, different doses may be used, based on emerging data.

[0272] FIG. 2 summarizes demographics for all the cohorts.

[0273] FIG. 3 summarizes treatment emergent adverse events (TEAEs) for all participant groups.

[0274] FIG. 4 is a graph depicting the single-dose concentration-time profile (mean (SD) profiles) for Antibody 114 at 75 mg, 150 mg, 300 mg. and 600 mg.

[0275] FIGS. 5A-5B are modeled concentration predictions based on Antibody 114 Phase 1 PK for 3-month (50 mg; FIG. 5A) and 6-month (200 mg; FIG. 5B) exposures. The solid line represents population PK (PPK) model predicted median concentrations of Antibody 114 for Q3M or Q6M dosing regimen and the shaded area represents 90% prediction interval (PI).

[0276] FIG. 6 depicts median serum TARC percent change from Baseline in a preliminary’ blinded PD summary- of Antibody 114 from SAD Cohort 1 (75 mg), Cohort 2 (150 mg), Cohort 3 (300 mg). Cohort 4 (600 mg), and Cohort 5 (1200 mg).

[0277] FIG. 7 depicts median percent change from Baseline for TNF-a for the Placebo group and all four Cohorts.

[0278] FIG. 8 depicts median percent change from Baseline for IL-22 for the Placebo group, Cohort 1 (75 mg), Cohort 2 (150 mg), Cohort 3 (300 mg), and Cohort 4 (600 mg).

[0279] FIG. 9 depicts serum IgE median percent change from Baseline for the Placebo group, Cohort 1 (75 mg), Cohort 2 (150 mg), Cohort 3 (300 mg), Cohort 4 (600 mg), and Cohort 5 (1200 mg).

[0280] FIG. 10 depicts periostin median percent change from Baseline for the Placebo group. Cohort 1 (75 mg), Cohort 2 (150 mg), Cohort 3 (300 mg), Cohort 4 (600 mg), and Cohort 5 (1200 mg).

[0281] FIG. 11 depicts serum LDH median percent change from Baseline for the Placebo group, Cohort 1 (75 mg), Cohort 2 (150 mg). Cohort 3 (300 mg). Cohort 4 (600 mg), and Cohort 5 (1200 mg). FIGs. 12A-12J set forth a targeted transcriptomic dataset generated using NanoString nCounter Immunology V2 panel to profile 579 I&I-related gene targets in Cohorts 1, 2, and 3 up to Day 29.

[0282] FIG. 13 is a graph depicting the concentration-time profile (mean (SD) PK profiles by cohort) for Antibody 1 14 at 75 mg, 150 mg, 300 mg, 600 mg, and 1200 mg.

[0283] FIG. 14 depicts serum IgE median percent change from Baseline for the Placebo group, Cohort 1 (75 mg), Cohort 2 (150 mg), Cohort 3 (300 mg), Cohort 4 (600 mg), and Cohort 5 (1200 mg).

[0284] DETAILED DESCRIPTION

[0285] I. Definitions

[0286] As used herein, the term “subject” or “patient” is a human patient.

[0287] As used herein, the term “adult” patient is a human patient that has been classified by a physician or caretaker as such, e.g, one who is not a newborn, infant, child or adolescent, e.g., based on age, developmental status, physiological features, etc. Typically, adult patients are patients who are 18 years of age or older (>18 years of age).

[0288] As used herein, “effective treatment” refers to treatment producing a beneficial effect, e.g., amelioration of at least one symptom of a disease or disorder. A beneficial effect can take the form of an improvement over baseline, e.g, an improvement over a measurement or observation made prior to initiation of therapy according to the method. Effective treatment may refer to alleviation of at least one symptom.

[0289] The term “effective amount” refers to an amount of an agent that provides the desired biological, therapeutic and / or prophylactic result. That result can be reduction, amelioration, palliation, lessening, delaying and / or alleviation of one or more of the signs, symptoms or causes of a disease, or any other desired alteration of a biological system. In one example, an “effective amount” is the amount of anti-OX40L antibody, or antigen binding fragment thereof, clinically proven to alleviate at least one symptom. An effective amount can be administered in one or more administrations. In certain embodiments, treatment is continued as long as clinical benefit is observed or until unmanageable toxicity' or disease progression occurs.

[0290] As used herein, “administration” refers to providing or giving a subject a therapeutic agent (e.g.. an OX40L antibody described herein) by any effective route. Exemplary routes of administration are described herein below.

[0291] As used herein, the terms “conservative mutation,” “conservative substitution,” and “conservative amino acid substitution” refer to a substitution of one or more amino acids for one or more different amino acids that exhibit similar physicochemical properties, such as polarity, electrostatic charge, and steric volume. These properties are summarized for each of the tw enty naturally occurring amino acids in Table 1 below. Table 1. Representative physicochemical properties of naturally occurring amino acids From this table it is appreciated that the conservative amino acid families include (i) G, A, V, L and I; (ii) D and E; (iii) C, S and T; (iv) H, K and R; (v) N and Q; and (vi) F, Y and W. A conservative mutation or substitution is therefore one that substitutes one amino acid for a member of the same amino acid family (e.g., a substitution of Ser for Thr or Lys for Arg).

[0292] As used herein, the term '‘serum trough level” refers to the lowest level that the agent (e.g., the anti-OX40L antibody, or antigen binding fragment thereof) or medicine is present in the serum. In contrast, a “peak serum level,” refers to the highest level of the agent in the serum. The “average serum level,” refers to the mean level of the agent in the serum over time.

[0293] The term “antibody” describes a polypeptide comprising at least one antibody-derived antigen binding site (e.g., VH / VL region or Fv, or CDR). Antibodies include known forms of antibodies and antibody fragments, e.g., the antibody can be a human antibody, a humanized antibody, a bispecific antibody or a chimeric antibody. The antibody also can be a Fab, Fab'2. ScFv, SM1P. Affibody®. nanobody or a single-domain antibody. The antibody also can be of any of the following isotypes: IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgAsec, IgD, IgE or combinations thereof. The antibody can be a naturally occurring antibody or an antibody that has been altered by a protein engineering technique (e.g, by mutation, deletion, substitution, conjugation to a nonantibody moiety). An antibody can include, for example, one or more variant amino acids (compared to a naturally occurring antibody) that change a property (e.g.. a functional property) of the antibody. Numerous such alterations are known in the art that affect, e.g., half-life, effector function, and / or immune responses to the antibody in a patient. The term antibody also includes artificial or engineered polypeptide constructs that comprise at least one antibody derived antigen binding site.

[0294] A “anti-OX40L antibody,” “OX40L antibody,” or “OX40L specific antibody” is an antibody, as provided herein, which specifically binds to the antigen OX40L.

[0295] The term “epitope” means a portion of an antigen that specifically binds to an antibody. Epitopes frequently consist of surface-accessible amino acid residues and / or sugar side chains and may have specific three-dimensional structural characteristics, as w ell as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter may be lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to OX40L variants with different point-mutations, or to chimeric OX40L variants. To screen for antibodies which bind to an epitope on a target antigen bound by an antibody of interest (e.g., OX40L), a routine cross-blocking assay such as that described in Antibodies, A Laboratory' Manual, Cold Spring Harbor Laboratory', Ed Harlow and David Lane (1988), can be performed. Alternatively, or additionally, epitope mapping can be performed by methods known in the art.

[0296] The term “hypervariable region” or “HVR”, as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and / or form structurally defined loops (“hypervariable loops”).

[0297] The term “antigen-binding domain” means the portion of an antibody that is capable of specifically binding to an antigen or epitope.

[0298] The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. The “class” of an antibody or immunoglobulin refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, 5, e. y, and p. respectively.

[0299] An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about SOO kD). The N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains respectively. The IgGl heavy chain comprises of the VH, CHI, CH2 and CH3 domains respectively from the N to C-terminus. The light chain comprises of the VL and CL domains from N to C terminus. The IgGl heavy' chain comprises a hinge between the CHI and CH2 domains. In certain embodiments, the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide. In some embodiments, the immunoglobulin domain found in an antibody provided herein, is from or derived from an immunoglobulin-based construct such as a diabody, or a nanobody. In certain embodiments, the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody. In certain embodiments, the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody or any chimeric antibody. Generally, native four-chain antibodies comprise six HVRs; three in the VH (Hl , H2, H3), and three in the VL (LI, L2, L3). HVRs generally comprise amino acid residues from the hypervariable loops and / or from the complementarity determining regions (CDRs), the latter being of highest sequence variability and / or involved in antigen recognition. With the exception of CDR1 in VH, CDRs generally comprise the amino acid residues that form the hypervariable loops. Hypervariable regions (HVRs) are also referred to as “complementarity determining regions” (CDRs), and these terms are used herein interchangeably in reference to portions of the variable region that form the antigen-binding regions. This particular region has been described by Kabat et o / .. U.S. Dept. ofHealth and Human Services, Sequences of Proteins of Immunological Interest (1983) and by Chothia et al., J Mol Biol 196:901-917 (1987), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or variants thereof is intended to be within the scope of the term as defined and used herein. The exact residue numbers which encompass a particular CDR will vary depending on the sequence and size of the CDR. Those skilled in the art can routinely determine which residues comprise a particular CDR given the variable region amino acid sequence of the antibody.

[0300] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol. 262:732-745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Pltickthun. J. Mol. Biol., 2001, 309:657-70 (“aHo” numbering scheme); each of which is incorporated by reference in its entirety.

[0301] Table 2 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes.

[0302] CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available at www.bioinf.org.uk / abs / abnum / , and described in Abhinandan and Martin, Immunology7, 2008, 45:3832-3839, incorporated by reference in its entirety7.

[0303] Table 2. Residues in CDRs according to Kabat and Chothia numbering schemes.

[0304] * The C-terminus of CDR-H1. when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR.

[0305] The “EU numbering scheme” is generally used when referring to a residue in an antibody heavy chain constant region (e.g, as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein.

[0306] One example of an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer of an antibody. Another example of an antigen-binding domain is an antigenbinding domain formed by diversification of certain loops from the tenth fibronectin type III domain of an Adnectin. An antigen-binding domain can include CDRs 1, 2, and 3 from a heavy chain in that order; and CDRs 1 , 2, and 3 from a light chain in that order.

[0307] The term “chimeric antibody” refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0308] The term “human antibody” refers to an antibody which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.

[0309] The term “humanized antibody” refers to a protein having a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and / or additions, such that the humanized antibody is less likely to induce an immune response, and / or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject. In one embodiment, certain amino acids in the framework and constant domains of the heavy and / or light chains of the non-human species antibody are mutated to produce the humanized antibody. In another embodiment, the constant domain(s) from a human antibody are fused to the variable domain(s) of a non-human species. In another embodiment, one or more amino acid residues in one or more CDR sequences of a non-human antibody are changed to reduce the likely immunogenicity of the non-human antibody when it is administered to a human subject, wherein the changed amino acid residues either are not critical for immunospecific binding of the antibody to its antigen, or the changes to the amino acid sequence that are made are conservative changes, such that the binding of the humanized antibody to the antigen is not significantly worse than the binding of the non-human antibody to the antigen. Examples of how to make humanized antibodies can be found in U.S. Pat. Nos. 6,054,297, 5,886,152 and 5,877,293. For further details, see Jones et al.. Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323- 329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated by reference in its entirety.

[0310] The term “multispecific antibody” refers to an antibody that comprises two or more different antigen-binding domains that collectively specifically bind two or more different epitopes.

[0311] A “monospecific antibody” is an antibody that comprises one or more binding sites that specifically bind to a single epitope. An example of a monospecific antibody is a naturally occurring IgG molecule which, while divalent (i.e. , having two antigen-binding domains), recognizes the same epitope at each of the two antigen-binding domains. The binding specificity may be present in any suitable valency .

[0312] The term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies compnses antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and / or to reduce its immunogenicity in a subject.

[0313] The term “single-chain” refers to a molecule comprising amino acid monomers linearly linked by peptide bonds. In a particular such embodiment, the C-terminus of the Fab light chain is connected to the N-terminus of the Fab heavy chain in the single-chain Fab molecule. As described in more detail herein, an scFv has a variable domain of light chain (VL) connected from its C-terminus to the N-terminal end of a variable domain of heavy chain (VH) by a polypeptide chain. Alternately the scFv comprises of polypeptide chain where in the C-terminal end of the VH is connected to the N-terminal end of VL by a polypeptide chain. The “Fab fragment’’ (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CHI) of the heavy chain along with the variable domains VL and VH on the light and heavy chains respectively. The variable domains comprise the complementarity determining loops (CDR. also referred to as hypervariable region) that are involved in antigen-binding. Fab' fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH 1 domain including one or more cysteines from the antibody hinge region.

[0314] “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds. F(ab’)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab’) fragments can be dissociated, for example, by treatment with B-mercaptoethanol.

[0315] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.

[0316] “Single-chain Fv” or “sFv” or “scFv” includes the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. In one embodiment, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding. For a review of scFv see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113. Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994). HER2 antibody scFv fragments are described in WO93 / 16185; U.S. Pat. No. 5,571,894; and U.S. Pat. No. 5,587,458.

[0317] “scFv-Fc” fragments comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminal of the scFv. The Fc domain may follow the VH or VL, depending on the orientation of the variable domains in the scFv (z.e., VH -VL or VL -VH). Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain comprises an IgG4 Fc domain.

[0318] The term “single domain antibody” or “sdAb” refers to a molecule in which one variable domain of an antibody specifically binds to an antigen without the presence of the other variable domain. Single domain antibodies, and fragments thereof, are described in Arabi Ghahroudi et al., FEB S Letters, 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sei., 2001, 26:230-245, each of which is incorporated by reference in its entirety. Single domain antibodies are also known as sdAbs or nanobodies. SdAbs are fairly stable and easy to express as fusion partner with the Fc chain of an antibody (Harmsen MM, De Haard HJ (2007). “Properties, production, and applications of camelid single-domain antibody fragments”. Appl. Microbiol The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a naturally occurring antibody structure and having heavy chains that comprise an Fc region. For example, when used to refer to an IgG molecule, a “full length antibody” is an antibody that comprises two heavy chains and two light chains.

[0319] The term “antibody fragment” refers to an antibody that comprises a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments. Fab fragments, F(ab’)2 fragments, Fab' fragments, scFv (sFv) fragments, and scFv-Fc fragments.

[0320] The term “Fc domain” or “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy' chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions.

[0321] The term “substantially purified” refers to a construct described herein, or variant thereof that may be substantially or essentially free of components that normally accompany or interact with the protein as found in its naturally occurring environment, i.e. a native cell, or host cell in the case of recombinantly produced heteromultimer that in certain embodiments, is substantially free of cellular material includes preparations of protein having less than about 30%, less than about 25%. less than about 20%. less than about 15%. less than about 10%. less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% (by dry weight) of contaminating protein.

[0322] II. Anti-OX40L Antibodies

[0323] Anti-OX40L antibodies (or VH / VL domains derived therefrom) suitable for use in the methods described herein can be generated using methods known in the art. Alternatively, art recognized anti-OX40L antibodies can be used. Antibodies that compete for binding to OX40L with any of these art recognized antibodies or antibodies described herein can also be used.

[0324] The exact boundaries of CDRs are defined differently according to different methods. In some embodiments, the positions of the CDRs or framework regions within a light or heavy chain variable domain are as defined by Kabat et al. [(1991) “Sequences of Proteins of Immunological Interest.” NIH Publication No. 91-3242, U.S. Department of Health and Human Services. Bethesda, MD], In such cases, the CDRs can be referred to as “Kabat CDRs” (e.g, “Kabat LCDR2” or “Kabat HCDR1 ”). In some embodiments, the positions of the CDRs of a light or heavy chain variable region are as defined by Chothia et al. (Nature, 342:877-83, 1989). Accordingly, these regions can be referred to as “Chothia CDRs” (e.g., “Chothia LCDR2” or “Chothia HCDR3”) Tn some embodiments, the positions of the CDRs of the light and heavy chain variable regions can be defined by a Kabat-Chothia combined definition. In such embodiments, these regions can be referred to as “combined Kabat-Chothia CDRs.” Thomas, C. et al. (Mol. Immunol., 33: 1389-401, 1996) exemplifies the identification of CDR boundaries according to Kabat and Chothia numbering schemes.

[0325] Methods for determining whether an antibody binds to a protein antigen and / or the affinity for an antibody to a protein antigen are known in the art. The binding of an antibody to a protein antigen, for example, can be detected and / or quantified using a variety of techniques such as, but not limited to, Western blot, dot blot, surface plasmon resonance (SPR) detection (e.g, BIAcore system; Pharmacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.), or enzyme-linked immunosorbent assay (ELISA; Benny K. C. Lo (2004) “Antibody Engineering: Methods and Protocols,” Humana Press (ISBN: 1588290921); Johne, B. et al. , J. Immunol. Meth., 160: 191-8, 1993; Jonsson, U. et al., Ann. Biol. Clin.. 51 : 19-26, 1993; Jonsson, U. et al.. Biotechniques, 11:620-7, 1991). In addition, methods for measuring the affinity (e.g. dissociation and association constants) are set forth in the working examples.

[0326] As used herein, the term “ka” refers to the rate constant for association of an antibody to an antigen. The term “ka” refers to the rate constant for dissociation of an antibody from the antibody / antigen complex. And the term “KD” refers to the equilibrium dissociation constant of an antibody-antigen interaction. The equilibrium dissociation constant is deduced from the ratio of the kinetic rate constants, KD = ka / ka. The kinetics of antibody binding to human OX40L can be determined, for example, at pH 8.0. 7.4, 7.0, 6.5 and 6.0 via SPR on a BIAcore 3000 instrument using an anti-Fc capture method to immobilize the antibody.

[0327] In one embodiment, the antibody, or antigen binding fragment thereof, competes for binding with, and / or binds to the same epitope on OX40L as an antibody described herein. The term “binds to the same epitope” with reference to two or more antibodies means that the antibodies bind to the same segment of amino acid residues, as determined by a given method. Techniques for determining whether antibodies bind to the same epitope on OX40L with an antibody described herein include, for example, epitope mapping methods, such as, x-ray analyses of cry stals of antigen: antibody complexes, and hydrogen / deuterium exchange mass spectrometry (HDX-MS). Other methods monitor the binding of the antibody to peptide antigen fragments or mutated variations of the antigen where loss of binding due to a modification of an amino acid residue within the antigen sequence is often considered an indication of an epitope component. In addition, computational combinatorial methods for epitope mapping can also be used. These methods rely on the ability of the antibody of interest to affinity isolate specific short peptides from combinatorial phage display peptide libraries. Antibodies having the same VH and VL or the same CDR1, CDR2 and CDR3 sequences are expected to bind to the same epitope.

[0328] Antibodies that ‘"compete with another antibody for binding to a target” refer to antibodies that inhibit (partially or completely) the binding of the other antibody to the target. Whether two antibodies compete with each other for binding to a target, i.e., whether and to what extent one antibody inhibits the binding of the other antibody to a target, may be determined using known competition experiments. In certain embodiments, an antibody competes with, and inhibits binding of another antibody to a target by at least 10%. 20%. 30%. 40%. 50%. 60%. 70%, 80%, 90% or 100%. The level of inhibition or competition may be different depending on which antibody is the “blocking antibody” (i.e., the antibody that is incubated first with the target). Competing antibodies can bind to, for example, the same epitope, an overlapping epitope or to adjacent epitopes (e.g., as evidenced by steric hindrance).

[0329] Anti-OX40L antibodies, or antigen-binding fragments thereof described herein, used in the methods described herein can be generated using a variety of art-recognized- techniques. Monoclonal antibodies can be obtained by various techniques familiar to those skilled in the art. Briefly, spleen cells from an animal immunized with a desired antigen are immortalized, commonly by fusion with a myeloma cell (Kohler, G. & Milstein, C.. Eur. J. Immunol., 6:511-9. 1976)). Methods of immortalization include transformation with Epstein Barr Virus, oncogenes, or retroviruses or other methods known in the art. Colonies arising from single immortalized cells are screened for production of antibodies of the desired specificity and affinity for the antigen, and yield of the monoclonal antibodies produced by such cells may be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host. Alternatively, one may isolate DNA sequences that encode a monoclonal antibody or a binding fragment thereof by screening a DNA library from human B cells (Huse, W. et al., Science, 246: 1275-81, 1989). a. Exemplary Constructs

[0330] Exemplary anti-OX40L antibodies are set forth in Table 3. In one embodiment, the antibody is Antibody 114. Antibody 114 comprises the VH, VL, and CDR sequences set forth in the table below, and comprises a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 854 and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738. Exemplary’ anti-OX40L antibodies are described in International Application Publication No. WO2024227174A2, which is incorporated herein by reference.

[0331] Table 3. Sequences of OX40L Antibody Constructs - VH, VL, and Associated CDRs b. VH Domains

[0332] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an illustrative VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. c. VL Domains

[0333] In some embodiments, an antibody , or antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0334] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 489- 544, 825-831, and 842. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 489-544, 825- 831, and 842, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 ammo acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. d. VH-V Combinations

[0335] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841; and a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0336] In some embodiments, a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841 can be combined with a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0337] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in Table 3.

[0338] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 419- 488, 818-824, and 841; and a VL sequence having at least about 80%, 85%. 90%. 91%. 92%. 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841. with up to 1, 2, 3, 4, 5. 6, 7, 8, 9, 10, 11. 12. 13, 14, 15. 16. 17, 18, 19, or 20 amino acid substitutions, and a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants / ’ In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may. for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0339] In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable domain (VH) sequence selected from an amino acid sequence set forth in SEQ ID NOs: 419-488, 818-824, and 841.

[0340] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a light chain variable domain (VL) sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 489-544, 825-831, and 842. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 419-488, 818-824, and 841, and a VL sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0341] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 419 and a VL sequence set forth in SEQ ID NO: 489.

[0342] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 420 and a VL sequence set forth in SEQ ID NO: 490.

[0343] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 421 and a VL sequence set forth in SEQ ID NO: 491.

[0344] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 422 and a VL sequence set forth in SEQ ID NO: 492.

[0345] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 423 and a VL sequence set forth in SEQ ID NO: 493.

[0346] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 424 and a VL sequence set forth in SEQ ID NO: 494.

[0347] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 425 and a VL sequence set forth in SEQ ID NO: 495.

[0348] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 426 and a VL sequence set forth in SEQ ID NO: 496.

[0349] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 427 and a VL sequence set forth in SEQ ID NO: 497.

[0350] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 427 and a VL sequence set forth in SEQ ID NO: 498. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 428 and a VL sequence set forth in SEQ ID NO: 497.

[0351] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 428 and a VL sequence set forth in SEQ ID NO: 498.

[0352] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 429 and a VL sequence set forth in SEQ ID NO: 497.

[0353] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 429 and a VL sequence set forth in SEQ ID NO: 498.

[0354] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 430 and a VL sequence set forth in SEQ ID NO: 499.

[0355] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 431 and a VL sequence set forth in SEQ ID NO: 500.

[0356] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 432 and a VL sequence set forth in SEQ ID NO: 501.

[0357] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 433 and a VL sequence set forth in SEQ ID NO: 502.

[0358] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 434 and a VL sequence set forth in SEQ ID NO: 502.

[0359] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 435 and a VL sequence set forth in SEQ ID NO: 502.

[0360] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 436 and a VL sequence set forth in SEQ ID NO: 502. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 437 and a VL sequence set forth in SEQ ID NO: 502.

[0361] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 438 and a VL sequence set forth in SEQ ID NO: 503.

[0362] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 439 and a VL sequence set forth in SEQ ID NO: 502.

[0363] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 440 and a VL sequence set forth in SEQ ID NO: 504.

[0364] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 441 and a VL sequence set forth in SEQ ID NO: 505.

[0365] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 442 and a VL sequence set forth in SEQ ID NO: 506.

[0366] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 443 and a VL sequence set forth in SEQ ID NO: 507.

[0367] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 443 and a VL sequence set forth in SEQ ID NO: 508.

[0368] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 444 and a VL sequence set forth in SEQ ID NO: 506.

[0369] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 509.

[0370] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 446 and a VL sequence set forth in SEQ ID NO: 510. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 447 and a VL sequence set forth in SEQ ID NO: 506.

[0371] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 511.

[0372] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 448 and a VL sequence set forth in SEQ ID NO: 506.

[0373] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 449 and a VL sequence set forth in SEQ ID NO: 502.

[0374] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 449 and a VL sequence set forth in SEQ ID NO: 506.

[0375] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 450 and a VL sequence set forth in SEQ ID NO: 506.

[0376] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 512.

[0377] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 449 and a VL sequence set forth in SEQ ID NO: 513.

[0378] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 514.

[0379] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 445 and a VL sequence set forth in SEQ ID NO: 515.

[0380] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 451 and a VL sequence set forth in SEQ ID NO: 514. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 451 and a VL sequence set forth in SEQ ID NO: 506.

[0381] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 452 and a VL sequence set forth in SEQ ID NO: 506.

[0382] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 438 and a VL sequence set forth in SEQ ID NO: 506.

[0383] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 453 and a VL sequence set forth in SEQ ID NO: 512.

[0384] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 454 and a VL sequence set forth in SEQ ID NO: 490.

[0385] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 455 and a VL sequence set forth in SEQ ID NO: 516.

[0386] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 456 and a VL sequence set forth in SEQ ID NO: 517.

[0387] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 457 and a VL sequence set forth in SEQ ID NO: 518.

[0388] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 458 and a VL sequence set forth in SEQ ID NO: 492.

[0389] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 459 and a VL sequence set forth in SEQ ID NO: 519.

[0390] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 460 and a VL sequence set forth in SEQ ID NO: 520. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 461 and a VL sequence set forth in SEQ ID NO: 521.

[0391] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 461 and a VL sequence set forth in SEQ ID NO: 522.

[0392] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 461 and a VL sequence set forth in SEQ ID NO: 522.

[0393] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 462 and a VL sequence set forth in SEQ ID NO: 523.

[0394] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 463 and a VL sequence set forth in SEQ ID NO: 523.

[0395] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 464 and a VL sequence set forth in SEQ ID NO: 524.

[0396] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 465 and a VL sequence set forth in SEQ ID NO: 525.

[0397] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 466 and a VL sequence set forth in SEQ ID NO: 526.

[0398] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 467 and a VL sequence set forth in SEQ ID NO: 527.

[0399] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 468 and a VL sequence set forth in SEQ ID NO: 528.

[0400] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 469 and a VL sequence set forth in SEQ ID NO: 529. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 470 and a VL sequence set forth in SEQ ID NO: 528.

[0401] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 471 and a VL sequence set forth in SEQ ID NO: 530.

[0402] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 472 and a VL sequence set forth in SEQ ID NO: 531.

[0403] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 473 and a VL sequence set forth in SEQ ID NO: 532

[0404] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 474 and a VL sequence set forth in SEQ ID NO: 533.

[0405] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 475 and a VL sequence set forth in SEQ ID NO: 534.

[0406] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 476 and a VL sequence set forth in SEQ ID NO: 535.

[0407] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 477 and a VL sequence set forth in SEQ ID NO: 536.

[0408] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 478 and a VL sequence set forth in SEQ ID NO: 536.

[0409] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 479 and a VL sequence set forth in SEQ ID NO: 537.

[0410] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 480 and a VL sequence set forth in SEQ ID NO: 538. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 481 and a VL sequence set forth in SEQ ID NO: 539.

[0411] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 482 and a VL sequence set forth in SEQ ID NO: 539.

[0412] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 483 and a VL sequence set forth in SEQ ID NO: 539.

[0413] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 484 and a VL sequence set forth in SEQ ID NO: 540.

[0414] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 485 and a VL sequence set forth in SEQ ID NO: 541.

[0415] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 486 and a VL sequence set forth in SEQ ID NO: 542.

[0416] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 487 and a VL sequence set forth in SEQ ID NO: 543.

[0417] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 488 and a VL sequence set forth in SEQ ID NO: 544.

[0418] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 818 and a VL sequence set forth in SEQ ID NO: 825.

[0419] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 819 and a VL sequence set forth in SEQ ID NO: 826.

[0420] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 820 and a VL sequence set forth in SEQ ID NO: 827. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 821 and a VL sequence set forth in SEQ ID NO: 828.

[0421] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 822 and a VL sequence set forth in SEQ ID NO: 829.

[0422] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 823 and a VL sequence set forth in SEQ ID NO: 830.

[0423] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 824 and a VL sequence set forth in SEQ ID NO: 831.

[0424] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 841 and a VL sequence set forth in SEQ ID NO: 842.

[0425] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22. and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 1 11, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 258, 286, and 311 ; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; a CDR-L3 comprising the sequence set forth in any one of SEQ ID NOs: 368 and 394, a constant heavy chain sequence set forth in SEQ ID NO: 651 and / or SEQ ID NO: 854 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0426] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 258, 286, and 311; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; a CDR-L3 comprising the sequence set forth in any one of SEQ ID NOs: 368 and 394, a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%. 85%. 90%. 91%. 92%. 93%. 94%. 95%. 96%. 97%, 98% or 99% identity thereto.

[0427] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 258, 286, and 311; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; a CDR-L3 comprising the sequence set forth in any one of SEQ ID NOs: 368 and 394. a constant heavy chain sequence set forth in SEQ ID NO: 854 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0428] In some embodiments, an antibody, or antigen binding fragment thereof, comprises a VH comprising SEQ ID NO: 419 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, a VL comprising SEQ ID NO: 489 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, a constant heavy chain sequence set forth in SEQ ID NO: 651 and / or SEQ ID NO: 854 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0429] In some embodiments, an antibody, or antigen binding fragment thereof, comprises a VH comprising SEQ ID NO: 419 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, a VL comprising SEQ ID NO: 489 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity’ thereto, a constant heavy chain sequence set forth in SEQ ID NO: 651 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0430] In some embodiments, an antibody, or antigen binding fragment thereof, comprises a VH comprising SEQ ID NO: 419 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, a VL comprising SEQ ID NO: 489 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, a constant heavy chain sequence set forth in SEQ ID NO: 854 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto and a human constant light chain sequence set forth in SEQ ID NO: 738 or a sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity' thereto. e. CDRs

[0431] In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of Table 3 or Table 4. In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 6 of the Kabat CDRs of Table 3 or Table 4, 6 of the Chothia CDRs of Table 3 or Table 4, or 6 of the IMGT CDRs of Table 3 or Table 4.

[0432] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from SEQ ID NOs: 419-488, 818-824, and 840. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VH domain selected from SEQ ID NOs: 419-488, 818- 824, and 840. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 419-488, 818-824, and 840. In some aspects, the CDRs are exemplary' CDRs. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0433] In one embodiment, the antibody, or antigen binding fragment thereof, that binds OX40L comprises a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1 , CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1-69 and 740-747; b. CDR-H2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 70-174 and 748-762; c. CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 175-257 and 763-780, d. CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 258-334 and 781-796, e. CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 335-367 and 797-805; and f. CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 268-393 and 806-811.

[0434] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0435] 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0436] 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 258, 286, and 311; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0437] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2,

[0438] 23, and 45; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0439] 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 176, 204. and 224; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 259, 287, and 312; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 336 and 360; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 369 and 395.

[0440] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 3,

[0441] 24, and 46; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0442] 71, 112, and 143; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 177, 205. and 225; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 370 and 396.

[0443] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 22, and 47; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0444] 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206, and 226; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 261 , 289, and 314; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0445] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0446] 73, 114, and 145; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207. and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 262. 290, and 315; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 372 or 398.

[0447] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 6,

[0448] 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0449] 74, 115, and 146; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 228; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 263, 291, and 316; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 339 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 373 and 399.

[0450] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 7,

[0451] 25, and 50; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0452] 75, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 181, 209, and 229; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 264, 292, and 317; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 and 363; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0453] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8,

[0454] 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0455] 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 182, 210, and 230; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361 ; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 375 and 401.

[0456] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 183, 211, and 231; a CDR-Ll comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 376 and 402.

[0457] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 183, 211, and 231; a CDR-Ll comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 377 and 403.

[0458] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 184, 212, and 232; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 376 and 402.

[0459] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 184, 212. and 232; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 377 and 403. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 185, 213, and 233; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 376 and 402.

[0460] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8,

[0461] 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0462] 76, 117, and 148; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 185, 213. and 233; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 265, 293, and 318; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 377 and 403.

[0463] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 9,

[0464] 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0465] 77, 118, and 149; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203. and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 342 and 364; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0466] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0467] 28, and 53; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0468] 78, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 266, 286, and 311; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0469] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 79, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 186, 203, and 235; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 267, 294, and 319; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 344 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0470] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0471] 10. 27. and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 80, 120, and 151; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 186, 203, and 235; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0472] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0473] 11, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 79. 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0474] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 11, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 81, 121, and 152; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0475] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 80, 120, and 151; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 187, 203, and 236; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0476] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 79, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 187. 203, and 236; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0477] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 268, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0478] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 12, 29, and 54; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0479] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10. 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 82, 1 11 , and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 189, 214, and 238; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288. and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 345 and 361 ; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0480] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 83, 122, and 153; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 234; a CDR-L1 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 346 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0481] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13, 30, and 55; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 84, 1 11, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 239; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0482] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 347 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0483] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175. 203, and 234; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 345 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 85, 123, and 154; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 239; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0484] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175. 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 270, 295, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0485] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0486] 31, and 56; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203. and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260. 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 379and 405.

[0487] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1,

[0488] 32, and 57; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 86, 124, and 155; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0489] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 and 406.

[0490] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 14. 33. and 58; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 1 11, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0491] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 343 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0492] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0493] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13, 30, and 55; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0494] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175. 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0495] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 87, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 348 and 366; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0496] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 381 and 405.

[0497] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10. 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 1 11 , and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288. and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 335 and 359; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0498] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 86, 124, and 155; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 381 and 405.

[0499] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 22, and 44; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 86, 124, and 155; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0500] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70. I l l, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 239; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404.

[0501] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188. 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 378 and 404. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 78, 119, and 150; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 188, 203, and 237; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0502] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2, 840, and 45; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 176, 204. and 224; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 259, 287, and 312; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 336 and 360; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 369and 395.

[0503] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15, 34, and 59; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 88, 125, and 156; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190, 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 349 and 365; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 382 and 407.

[0504] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 22, and 47; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 89, 126, and 157; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206, and 226; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0505] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 35, and 60; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206. and 241; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 271. 296, and 320; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 350 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0506] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 4, 22. and 47; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 90, 127, and 158; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 178, 206, and 226; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 261, 289, and 314; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0507] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 16, 36, and 61; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 91. 128, and 159; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 191, 215, and 242; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 351 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 382 and 407.

[0508] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 16, 36, and 61; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 91, 128, and 159; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190, 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 351 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 371 and 397.

[0509] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15, 27, and 62; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190, 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 382 and 407.

[0510] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15, 27, and 62; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 72, 113, and 144; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190. 215, and 240; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 269, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 351 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 383 and 408.

[0511] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 37, and 63; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0512] 92, 129, and 160; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207. and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 272. 297, and 321; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 384 and 409.

[0513] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0514] 93, 130, and 161; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207, and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 272. 297, and 321; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 384 and 409.

[0515] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0516] 94, 131 , and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 192, 207, and 243; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 273, 298, and 322; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 385 and 410.

[0517] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0518] 17, 38, and 64; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 95, 132, and 163; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207, and 227; a CDR-L1 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 272, 297, and 321; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 386 and 411.

[0519] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0520] 96, 130, and 164; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 192, 207, and 243; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 274, 299, and 323; a CDR-L2 comprising an amino acid sequence set forth in anyone of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 386 and 411.

[0521] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 24, and 49; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0522] 97, 130, and 164; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 179, 207, and 227; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 275, 300, and 324; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 338 and 362; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 386 and 411.

[0523] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0524] 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 193. 216, and 244; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 276, 301 , and 325; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 193, 216, and 245; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 277, 302, and 326; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0525] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 194. 217, and 246; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 276, 301, and 325; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0526] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0527] 18, 39, and 65; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 98, 116, and 147; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 194, 217, and 247; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 276, 301, and 325; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 388 and 413.

[0528] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0529] 19, 40, and 66; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 99, 133, and 165; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 278, 303, and 327; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 352 and 367; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0530] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 20, 41, and 67; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100, 134, and 166; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 218, and 249; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 279, 304, and 328; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 353 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0531] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 20. 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 101, 133, and 167; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 389 and 414.

[0532] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0533] 102, 135. and 168; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 350 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 389 and 414.

[0534] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0535] 103, 136. and 169; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 196, 218, and 250; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 354 and 367; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 390 and 415.

[0536] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0537] 104, 137, and 170; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 197, 208, and 251 ; a CDR-L 1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 281, 306, and 330; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0538] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 105, 138. and 171; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 197, 208. and 251; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 281, 306, and 330; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0539] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 198, 219. and 252; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 282. 307, and 331; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 391 and 416.

[0540] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 20, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 218, and 253; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 355 and 367; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0541] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131 , and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361 ; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0542] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 6, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 106, 137, and 170; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 218, and 253; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0543] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0544] 20, 41, and 67; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 107, 133, and 167; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180, 208, and 248; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 387 and 412.

[0545] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 108, 139. and 172; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 181, 209, and 229; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 283, 308, and 332; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 356 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0546] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs:

[0547] 21, 42, and 68; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 109, 140. and 173; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 199. 220, and 254; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 280, 305, and 329; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 43, and 69; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 106, 137. and 170; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 200, 221, and 255; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 284, 309, and 333; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 337 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 374 and 400.

[0548] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 43, and 69; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 94, 131, and 162; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 201, 222. and 256; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 285, 310, and 334; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 357 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 392 and 417.

[0549] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 43, and 69; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 110, 141, and 174; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 202, 222. and 257; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 285. 310, and 334; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 358 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 393 and 418.

[0550] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 748, 116, and 758; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 763, 769, and 775, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 781, 787, and 792; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 797 and 802; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 806 and 812.

[0551] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 740, 742, and 745; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 749, 754, and 759; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 764, 770, and 776, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 782, 788, and 793; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 798 and 803; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 807 and 813.

[0552] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 17. 743, and 746; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 750, 133, and 165; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 765, 771, and 777, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 783, 298, and 322; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 799 and 804; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 808 and 814.

[0553] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 5, 840, and 48; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 751, 755. and 760; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 766, 772, and 778, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 784, 789, and 794; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 809 and 815.

[0554] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 27, and 52; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 70, 111, and 142; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 175, 203, and 223, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 260, 288, and 313; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 341 and 361; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 368 and 394.

[0555] In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 8, 26, and 51; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 752, 756, and 761; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 767, 773, and 779, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 785, 790, and 795; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 800 and 805; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 810 and 816. In another embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 741, 744, and 747; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 753, 757, and 762; a CDR-H3 comprising an amino acid sequence set forth in SEQ ID NOs: 768, 774. and 780. a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 786, 791, and 796; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 801 and 360; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 811 and 817.

[0556] Table 4. Consensus Sequences of Clones

[0557] Il l

[0558]

[0559] In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0560] In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. f. Fc Region

[0561] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder et al., (2010) Allergy Clin. Immunol.

[0562] 125: S41 -52, incorporated by reference in its entirety. The Fc region may be a naturally occurring Fc region, or an Fc region modified as described in the art or elsewhere in this disclosure.

[0563] Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al, Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Sen-ice, National Institutes of Health, Bethesda, MD, 1991. An "Fc polypeptide" of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e. a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association. For example, an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence. An Fc can be of the class IgA, TgD, IgE, IgG, and TgM, and several of these may be further divided into subclasses (isotypes), e.g, IgGi, IgGz, IgGs. IgG4, IgAi, and IgA2.

[0564] The terms "Fc receptor’ and “FcR” are used to describe a receptor that binds to the Fc region of an antibody. For example, an FcR can be a native sequence human FcR. Generally, an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcyRI, FcyRII, and FcyRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcyRII receptors include FcyRIIA (an "‘activating receptor”) and FcyRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology, the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)). Activating receptor FcyRIIA contains an immunoreceptor tyrosine-based activation motif (IT AM) in its cytoplasmic domain. Inhibiting receptor FcyRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Daeron, Annu. Rev. Immunol. 15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas etal.,J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term “FcR” herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol. 117:587 (1976); and Kim et al., J. Immunol. 24:249 (1994)).

[0565] Modifications in the CH2 domain can affect the binding of FcRs to the Fc. A number of amino acid modifications in the Fc region are known in the art for selectively altering the affinity of the Fc for different Fcgamma receptors. In some aspects, the Fc comprises one or more modifications to promote selective binding of Fc-gamma receptors.

[0566] Exemplary mutations that may alter the binding of FcRs to the Fc are listed below (in EU numbering format):

[0567] • S298A / E333A / K334A, S298A / E333A / K334A / K326A (Lu Y, Vernes JM, Chiang N, et al..

[0568] J Immunol Methods . 2011 Feb 28;365(l-2): 132-41);

[0569] • F243L / R292P / Y300L / V305I / P396L, F243L / R292P / Y300L / L235V / P396L (Stavenhagen

[0570] JB, Gorlatov S, Tuaillon N, et al.. Cancer Res. 2007 Sep 15;67(18):8882-90; Nordstrom JL, Gorlatov S, Zhang W, et al., Breast Cancer Res. 2011 Nov 30;13(6):R123); • F243L (Stewart R, Thom G, Levens M, et al., Protein Eng Des Sei. 2011 Sep;24(9):671-

[0571] 8.), S298A / E333A / K334A (Shields RL, Namenuk AK, Hong K, et al., J Biol Chem. 2001 Mar 2;276(9):6591-604);

[0572] • S239D / I332E / A330L, S239D / I332E (Lazar etal., (2006) Proc Natl Acad Sci USA.

[0573] 103(11):4005-10);

[0574] • S239D / S267E, S267E / L328F (Chu etcz / ., (2008) Mol Immunol. 45(15):3926-33);

[0575] • S239D / D265S / S298A / I332E, S239E / S298A / K326A / A327H, G237F / S298A / A330L / I332E

[0576] , S239D / I332E / S298A, S239D / K326E / A330L / I332E / S298A, G236A / S239D / D270L / I33 2E, S239E / S267E / H268D, L234F / S267E / N325L, G237F / V266L / S267D and other mutations listed in WO2011 / 120134 and WO2011 / 120135, herein incorporated by reference. Therapeutic Antibody Engineering (by William R. Strohl and Lila M. Strohl, Woodhead Publishing series in Biomedicine No 11, ISBN 1 907568 37 9, Oct 2012) lists mutations on page 283.

[0577] In some embodiments, the heavy chain comprises a constant heavy chain sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 637-737 and 843- 931, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%. at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In some embodiments, the heavy chain comprises a constant heavy chain sequence set forth in SEQ ID NO: 651, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity' thereto. In some embodiments, the heavy chain comprises a constant heavy chain sequence set forth in SEQ ID NO: 854, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In some embodiments, the light chain comprises a constant light chain sequence set forth in SEQ ID NO: 738, or an amino acid sequence having at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In some embodiments, the heavy chain comprises a constant heavy chain sequence set forth in SEQ ID NO: 651, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity' thereto and the light chain comprises a constant light chain sequence set forth in SEQ ID NO: 738, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto. In some embodiments, the heavy chain comprises a constant heavy chain sequence set forth in SEQ ID NO: 854, or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto and the light chain comprises a constant light chain sequence set forth in SEQ ID NO: 738. or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.

[0578] In some embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 651 and / or a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489. and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738.

[0579] In some embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489. and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738.

[0580] In some embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489, and a constant light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 738.

[0581] The C-terminal Lys330 of the constant heavy chain sequence of SEQ ID NO: 854 may or may not be present. The disclosure specifically contemplates SEQ ID NO: 854 that does not include the C-terminal Lys corresponding to Lys330 (as set forth in SEQ ID NO: 651). A polypeptide comprising SEQ ID NO: 854 may be expressed including a C-terminal Lys330 which may then be proteolytically cleaved upon expression of the polypeptide (e.g, the polypeptide of SEQ ID NO: 854 is expressed using a nucleic acid construct encoding the polypeptide including a C-terminal lysine residue, which may then be removed via cleavage to produce the polypeptide of SEQ ID NO: 651). Accordingly, the anti-OX40L antibody that is administered can have the constant heavy chain sequence of SEQ ID NO: 854, SEQ ID NO: 651, or a mixture thereof {e.g., a composition comprising anti-OX40L antibodies may contain a mixture of antibodies having either a constant heavy chain sequence of SEQ ID NO: 854 or a constant heavy chain sequence of SEQ ID NO: 651 and / or antibodies containing both constant heavy chain sequences (e.g., in a single antibody containing two constant heavy chain sequences)).

[0582] In some embodiments, the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 932 and a light chain sequence comprising an amino acid sequence set forth in SEQ ID NO: 933.

[0583] In some embodiments, an antibody described herein includes modifications intended to improve its ability to mediate effector function. Such modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards Clq for CDC. Table 5 summarizes various designs reported in the literature for effector function engineering.

[0584] Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art. The GlymaX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody production. This prevents the addition of the sugar “fucose’7to the N-linked antibody carbohydrate part by antibody -producing cells, (von Horsten et al. (2010) Glycobiology. 20 (12): 1607-18). Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4- hexylose reductase (RMD) {see von Horsten et al. (2010) supra) or Lee 13 CHO cells, which are deficient in protein fucosylation see Ripka et n / . (1986) Arch. Biochem. Biophys. 249:533-545; U.S. Pat. Pub. No. 2003 / 0157108; WO 2004 / 056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha-1, 6-fucosyltransferase gene or FUT8 knockout CHO cells {see Yamane-Ohnuki et al. (2004) Biotech. Bioeng. 87: 614-622; Kanda et al. (2006) Biotechnol. Bioeng. 94:680-688; and WO 2003 / 085107; each of which is incorporated by reference in its entirety). Another approach to obtaining antibodies with lowered levels of fucosylation can be found in U.S. patent 8,409,572, which teaches selecting cell lines for antibody production for their ability to yield lower levels of fucosylation on antibodies.

[0585] Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system.

[0586] In some aspects, an antibody provided herein comprises an IgGl domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgGl domain. Such Fc domains are known to have improved ADCC. See Shields et al., (2002) J. Biol. Chem. 277:26733-26740, incorporated by reference in its entirety. In some aspects, such antibodies do not comprise any fucose at position Asn 297. The amount of fucose may be determined using any suitable method, for example as described in WO 2008 / 077546, incorporated by reference in its entirety.

[0587] In certain embodiments, an antibody provided herein comprises an Fc region with one or more amino acid substitutions which may improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region. In some embodiments, an antibody provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al., (2006) Proc. Natl. Acad. Sci. USA 103:4005-4010, incorporated by reference in its entirety.

[0588] Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub. Nos. 2003 / 0157108, 2004 / 0093621. 2003 / 0157108. 2003 / 0115614, 2002 / 0164328, 2004 / 0093621, 2004 / 0132140, 2004 / 0110704, 2004 / 0110282, 2004 / 0109865; International Pat. Pub. Nos. 2000 / 61739, 2001 / 29246, 2003 / 085119, 2003 / 084570, 2005 / 035586, 2005 / 035778; 2005 / 053742, 2002 / 031140; Okazaki et al. , J. Mol. Biol., 2004, 336:1239-1249; and Yamane-Ohnuki et al. (2004) supra', each of which is incorporated by reference in its entirety.

[0589] In some embodiments, an antibody provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997 / 30087; WO 1998 / 58964; and WO 1999 / 22764; each of which is incorporated by reference in its entirety.

[0590] Thus, in one embodiment, an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in Table 5 that may confer improved effector function. In another embodiment, the antibody can be afucosylated to improve effector function.

[0591] Table 5. CH2 Domains and Effector Function Engineering

[0592] Fc modifications that can reduce FcgR and / or complement binding and / or effector function are known in the art. Recent publications describe strategies that have been used to engineer antibodies with reduced or silenced effector activity (see Strohl, WR (2009) Curr Opin Biotech 20:685-691, and Strohl, WR and Strohl LM, ‘"Antibody Fc engineering for optimal antibody performance’’ In Therapeutic Antibody Engineering, Cambridge: Woodhead Publishing (2012), pp 225-249). These strategies include reduction of effector function through modification of glycosylation, use of IgG2 / IgG4 scaffolds, or the introduction of mutations in the hinge or CH2 regions of the Fc. For example. U.S. Patent Publication No. 2011 / 0212087 (Strohl), International Patent Publication No. WO 2006 / 105338 (Xencor), U.S. Patent Publication No. 2012 / 0225058 (Xencor), U.S. Patent Publication No. 2012 / 0251531 (Genentech), and Strop et al ((2012) J. Mol. Biol. 420: 204-219), each of which is incorporated by reference in its entirety, describe specific modifications to reduce FcgR or complement binding to the Fc. Specific, non-limiting examples of known amino acid modifications that are intended to reduce FcgR or complement binding to the Fc include those identified in the follow ing Table 6.

[0593] Table 6. Modifications to Reduce FcgR or Complement Binding to the Fc

[0594] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one or more alterations that may improve or diminish Clq binding and / or CDC. See U.S. Pat. No. 6,194,551; WO 99 / 51642; and Idusogie et al. (2000) J. Immunol. 164:4178-4184; each of which is incorporated by reference in its entirety.

[0595] In certain embodiments, the heavy chain comprises a constant heavy chain sequence selected from the sequences set forth in SEQ ID NOs: 637-737. In certain embodiments, the constant heavy chain sequence, (e.g., a constant heavy’ chain sequence selected from SEQ ID NOs: 637-737) further comprises a C-terminal lysine (SEQ ID NOs: 843-931). Although a C- terminal lysine may be present in the corresponding coding sequence of the constant heavy7chain region, it may be cleaved off during manufacture or after administration. Accordingly, sequences of heavy chain constant regions with and without the C-terminal lysine are provided herein.

[0596] In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in Table 7 with a heavy chain constant region described herein (e.g., a constant heavy chain sequence selected from the sequences set forth in SEQ ID NOs: 637-737 and 843-931, such as a constant heavy chain sequence of SEQ ID NO: 651 or 854). In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in Table 7 with a heavy chain constant region and a light chain constant region described herein (e.g., a constant heavy chain sequence selected from the sequences set forth in SEQ ID NOs: 637-737 and 843-931, such as a constant heavy chain sequence of SEQ ID NO: 651 or 854, and a constant light chain sequence set forth in SEQ ID NO: 738).

[0597] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc region without the one or more substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is about 10,000-fold, 1,000-fold. 500-fold. 100-fold, 50-fold, 20-fold. 10-fold, 9-fold, 8-fold. 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75- fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an antibody comprising a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is about 10.000-fold. 1.000-fold. 500-fold. 100-fold. 50-fold, 20-fold. 10-fold, 9-fold. 8-fold. 7- fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85- fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold. 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05 -fold longer compared to amlitelimab.

[0598] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in a decrease in one or more of ADCC activity7, ADCP activity, or CDC activity compared with the Fc region without the one or more substitutions.

[0599] In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A. L235A, and N434W. In certain embodiments, the one or more amino acid substitutions comprises a specific combination of amino acid substitutions selected from the group consisting of M428L / N434S (LS); M252Y / S254T / T256E (YTE); T250Q / M428L; T307A / E380A / N434A; T256D / T307Q (DQ); T256D / T307W (DW); M252Y / T256D (YD); T307Q / Q311V / A378V (QVV); T256D / H285D / T307R / Q311V / A378V (DDRVV); L309D / Q31 1H / N434S (DHS); S228P / L235E (SPLE); L234A / L235A (LAL A); M428L / N434A (LA); L235A / G237A (LAGA); L234A / L235A / G237A (LALAGA); L234A / L235A / P329G (LALAPG); D265A / YTE; LALA / YTE; LAGA / YTE; LALAGA / YTE; LALAPG / YTE; N297A / LS; D265A / LS; LALA / LS; LALAGA / LS; LALAPG / LS; N297A / DHS; D265A / DHS; LALA / DHS; LAGA / DHS; LALAGA / DHS; LALAPG / DHS; SP / YTE; SPLE / YTE; SP / LS; SPLE / LS; SP / DHS; SPLE / DHS; N297A / LA; D265A / LA; LALA / LA; LAGA / LA;

[0600] LALAGA / LA; LALAPG / LA; N297A / N434A; D265A / N434A; LALA / N434A; LAGA / N434A; LALAGA / N434A; LALAPG / N434A; N297A / N434W; D265A / N434W; LALA / N434W; LAGA / N434W; LALAGA / N434W; LALAPG / N434W; N297A / DQ; D265A / DQ; LALA / DQ; LAGA / DQ; LALAGA / DQ; LALAPG / DQ; N297A / DW; D265A / DW; LALA / DW; LAGA / DW; LALAGA / DW; LALAPG / DW; N297A / YD; D265A / YD; LALA / YD; LAGA / YD: LALAGA / YD; LALAPG / YD; T307Q / Q311V / A378V (QVV); N297A / QVV; D265A / QVV; LALA / QVV; LAGA / QVV; LALAGA / QVV; LALAPG / QVV; DDRVV; N297A / DDRVV;

[0601] D265A / DDRVV; LALA / DDRVV; LAGA / DDRVV; LAL AGA / DDRVV; and LALAPG / DDRVV.

[0602] In certain embodiments, the Fc region binds an Fey Receptor selected from the group consisting of: FcyRI. FcyRIIa, FcyRIIb, FcyRIIc, FcyRIIIa, and FcyRIIIb. In certain embodiments, the Fc region binds an Fey Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.

[0603] In some embodiments, an antibody, or antigen binding fragment thereof, disclosed herein comprises a VH and / or VL sequence from Table 7. In some embodiments, an antibody, or antigen binding fragment thereof, containing a VH and / or VL sequence of Table 7 also comprises one or more amino acid substitutions, e.g, substitutions in the Fc region, disclosed herein. In some embodiments, an antibody, or antigen binding fragment thereof, containing a VH and / or VL sequence of Table 7 comprises a constant heavy chain sequence selected from the sequences set forth in SEQ ID NOs: 637-737 and 843-931. In some embodiments, an antibody, or antigen binding fragment thereof, comprising a VH and / or VL sequence of Table 7 comprises one or more amino acid substitutions in the Fc region selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W. In certain embodiments, an antibody, or antigen binding fragment thereof, containing a VH and / or VL sequence of Table 7 comprises a specific combination of amino acid substitutions in the Fc region selected from the group consisting of M428L / N434S (LS); M252Y / S254T / T256E (YTE); T250Q / M428L; T307A / E380A / N434A; T256D / T307Q (DQ); T256D / T307W (DW); M252Y / T256D (YD); T307Q / Q311 V / A378V (QVV); T256D / H285D / T307R / Q311V / A378V (DDRVV); L309D / Q311H / N434S (DHS); S228P / L235E (SPLE); L234A / L235A (LALA); M428L / N434A (LA); L235A / G237A (LAGA); L234A / L235A / G237A (LALAGA); L234A / L235A / P329G (LALAPG); D265A / YTE; LALA / YTE; LAGA / YTE; LALAGA / YTE; LALAPG / YTE; N297A / LS; D265A / LS; LALA / LS; LALAGA / LS; LALAPG / LS; N297A / DHS; D265A / DHS; LALA / DHS; LAGA / DHS; LALAGA / DHS; LALAPG / DHS; SP / YTE; SPLE / YTE; SP / LS; SPLE / LS; SP / DHS; SPLE / DHS; N297A / LA; D265A / LA; LALA / LA; LAGA / LA; LALAGA / LA; LALAPG / LA; N297A / N434A; D265A / N434A; LALA / N434A; LAGA / N434A; LALAGA / N434A; LALAPG / N434A; N297A / N434W; D265A / N434W; LALA / N434W; LAGA / N434W; LALAGA / N434W; LALAPG / N434W; N297A / DQ; D265A / DQ; LALA / DQ; LAGA / DQ; LALAGA / DQ; LALAPG / DQ; N297A / DW; D265A / DW; LALA / DW; LAGA / DW; LALAGA / DW;

[0604] LALAPG / DW; N297A / YD; D265A / YD; LALA / YD; LAGA / YD; LALAGA / YD; LALAPG / YD; T307Q / Q311V / A378V (QVV); N297A / QVV; D265A / QVV; LALA / QVV; LAGA / QVV; LALAGA / QVV; LALAPG / QVV; DDRVV; N297A / DDRVV; D265A / DDRVV; LALA / DDRVV; LAGA / DDRVV; LALAGA / DDRVV; and LALAPG / DDRVV.

[0605] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody, or antigen binding fragment thereof, described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257. In certain embodiments, an antibody, or antigen binding fragment thereof, described herein comprises an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, an antibody, or antigen binding fragment thereof, described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236. In certain embodiments, the OX40L antibody, or antigen binding fragment thereof, described herein comprises the heavy and light chain variable regions of Antibody 114 and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively.

[0606] In certain embodiments the human Fc region comprises a human IgGl Fc w ith LALA mutations. In certain embodiments the human Fc region comprises a human IgGl Fc with YTE mutations. In certain embodiments the human Fc region comprises a human IgGl Fc with LALA and YTE mutations. In certain embodiments, the Fc region of the OX40L antibody, or antigen binding fragment thereof, comprises a human IgGl Fc with LALA or YTE mutations. In certain embodiments, when direct numbering is used these "YTE " and ‘‘LALA” mutations can be located at different amino acid position numbers. In certain embodiments, the LALA mutations are at positions 234 and 235 and the YTE mutations are at positions 252, 254 and 256 (EU numbering). In certain embodiments, the LALA mutations are at positions 235 and 236 (L235A / L236A) and the YTE mutations are at positions 253, 255, and 257 (M253Y / S255T / T257E) (direct numbering).

[0607] Table 7. VH and VL Sequences of Anti-OX40L Antibodies

[0608] In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, has a half- life of about 30 days to about 90 days (e.g., a half-life of about 30 days to about 90 days, about

[0609] 30 days to about 75 days, about 30 days to about 60 days, about 30 days to about 45 days, about

[0610] 45 days to about 90 days, about 45 days to about 75 days, about 45 days to about 60 days, about 60 days to about 90 days, about 60 days to about 75 days, about 75 days to about 90 days, about 30 days, about 35 days, about 40 days, about 45 days, about 50 days, about 55 days, about 60 days, about 65 days, about 70 days, about 75 days, about 80 days, about 85 days, or about 90 days). In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, has a half-life of about 60 days.

[0611] III. Compositions

[0612] Also provided herein are compositions comprising an anti-OX40L antibody, or antigen binding fragment thereof. The compositions can be formulated as a pharmaceutical solution, e.g., for administration to a subject for treatment. The pharmaceutical compositions generally include a pharmaceutically acceptable carrier. As used herein, a “pharmaceutically acceptable carrier’7refers to. and includes, any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. The compositions can include a pharmaceutically acceptable salt, e.g., an acid addition salt or a base addition salt, sugars, carbohydrates, polyols and / or tonicity modifiers.

[0613] The compositions can be formulated according to standard methods. Pharmaceutical formulation is an established art (see, for example, Gennaro (2000) “Remington: The Science and Practice of Pharmacy,” 20thEdition, Lippincott, Williams & Wilkins (ISBN: 0683306472); Ansel et al. (1999) “Pharmaceutical Dosage Forms and Drug Delivery Systems,” 7thEdition, Lippincott Williams & Wilkins Publishers (ISBN: 0683305727); and Kibbe (2000) “Handbook of Pharmaceutical Excipients American Pharmaceutical Association,” 3rdEdition (ISBN: 091733096X)). In some embodiments, a composition can be formulated, for example, as a buffered solution at a suitable concentration and suitable for storage at 2-8 °C (e.g., 4 °C). In some embodiments, a composition can be formulated for storage at a temperature below 0 °C (e.g, -20 °C or -80 °C). In some embodiments, the composition can be formulated for storage for up to 2 years (e.g.. 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, I’ / years or 2 years) at 2-8 °C (e.g., 4 °C). Thus, in some embodiments, the compositions described herein are stable in storage for at least 1 year at 2-8 °C (e.g., 4 °C).

[0614] The pharmaceutical compositions can be in a variety’ of forms. These forms include, e.g., liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories. The preferred form depends, in part, on the intended mode of administration and therapeutic application. Compositions containing a composition intended for systemic or local delivery, for example, can be in the form of injectable or infusible solutions. Accordingly, the compositions can be formulated for administration by a parenteral mode (e.g, intravenous, subcutaneous, intraperitoneal, or intramuscular injection). “Parenteral administration,” “administered parenterally” and other grammatically equivalent phrases, as used herein, refer to modes of administration other than enteral and topical administration, usually by injection, and include, without limitation, intravenous, intranasal, intraocular, pulmonary, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intrapulmonary, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural, intracerebral, intracranial, intracarotid and intracistemal injection and infusion.

[0615] IV. Methods

[0616] Provided herein are methods for treating a variety of immunologic and inflammatory diseases in a human patient comprising administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, wherein the anti-OX40L antibody, or antigen binding fragment thereof, is administered (or is for administration) according to a particular clinical dosage regimen (e.g., at a particular dose amount and according to a specific dosing schedule). In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, is administered at a dose of 75 mg. 150 mg, 300 mg. 600 mg, or 1200 mg.

[0617] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 75 mg.

[0618] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 150 mg.

[0619] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 300 mg.

[0620] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 600 mg.

[0621] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 1200 mg. In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a maintenance dose every' three months.

[0622] In one embodiment, a method of treating a disease or condition in a human patient is provided, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a maintenance dose every six months. In one embodiment, the anti-OX40L antibody, or antigen binding fragment thereof, is administered subcutaneously.

[0623] In one embodiment, the disease or condition to be treated with an anti-OX40L antibody, or antigen binding fragment thereof, described herein is an inflammatory disorder or disease. In certain embodiments, the inflammatory disorder or disease is atopic dermatitis, asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic Bronchopulmonary Aspergillosis (ABPA), Chronic Obstructive Pulmonary Disease (COPD), an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis, psoriasis, lupus, rheumatoid arthritis, hidradenitis suppurativa, systemic sclerosis, allergic rhinitis, eosinophilic fasciitis, scleromyxedema, scleredema, or nephrogenic systemic fibrosis.

[0624] V. Outcomes

[0625] In one embodiment, patients treated according to the disclosed methods maintain a serum trough concentration of the anti-OX40L antibody, or antigen binding fragment thereof, of at least 150, 155, 160, 165, 170, 175, 180, 185, 190, 200, 205, 210, 215, 220, 225, 230, 240, 245, 250,

[0626] 255, 260, 265, 270, 280, 290, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, 355, 360,

[0627] 365, 370, 375, 380, 385, 390, 395 or 400 pg / mL or greater. In one embodiment, patients treated according to the disclosed methods maintain a serum trough concentration of the anti-OX40L antibody, or antigen binding fragment thereof, of at least 175 pg / mL or greater.

[0628] In one embodiment, the treatment results in a shift towards normal levels of one or more biomarkers compared to baseline. In another embodiment, the treatment results in a reduction or cessation in one or more symptoms compared to baseline.

[0629] In another embodiment, the treatment results in an improvement in the patient’s quality of life, as assessed by one or more art-recognized assessments.

[0630] In one embodiment, administration of the anti-OX40L antibody, or antigen binding fragment thereof, inhibits Type 1, Type 2, and / or Type 3 inflammation.

[0631] In one embodiment, administration of the anti-OX40L antibody, or antigen binding fragment thereof, reduces expression of one or more non-Type 2 inflammatory markers selected from the group consisting of TNFa, NFKBI. and NFKBIA.

[0632] VI. Kits and Unit Dosage Forms

[0633] Also provided herein are kits that include a pharmaceutical composition containing an anti-OX40L antibody or antigen binding fragment thereof, and a pharmaceutically acceptable carrier, in a therapeutically effective amount adapted for use in the preceding methods. The kits optionally also can include instructions, e.g., comprising administration schedules, to allow a practitioner (e.g., a physician, nurse, or patient) to administer the composition contained therein to administer the composition to a patient. The kit also can include a syringe.

[0634] Optionally, the kits include multiple packages of the single-dose pharmaceutical compositions each containing an effective amount of the anti-OX40L antibody, or antigen binding fragment thereof, for a single administration in accordance with the methods provided above. Instruments or devices necessary for administering the pharmaceutical composition(s) also may be included in the kits. For instance, a kit may provide one or more prefilled syringes containing an amount of the anti-OX40L antibody, or antigen binding fragment thereof.

[0635] The following example is merely illustrative and should not be construed as limiting the scope of this disclosure in any way as many variations and equivalents will become apparent to those skilled in the art upon reading the present disclosure. The contents of all references, Genbank entries, patents and published patent applications cited throughout this application are expressly incorporated herein by reference.

[0636] EXAMPLES

[0637] EXAMPLE 1: A Phase 1, Randomized, Blinded, Placebo-Controlled, Single Ascending Dose, First-In-Human Study of the Safety, Tolerability, and Pharmacokinetics of Antibody 114 in Healthy Participants This first-in-human (FIH) Phase 1 study is conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-drug antibodies (AD As) of Antibody 114 (an anti-OX40L antibody comprising a heavy chain variable region sequence set forth in SEQ ID NO: 419, a light chain variable region sequence set forth in SEQ ID NO: 489, a constant heavy chain sequence set forth in SEQ ID NO: 854, and a constant light chain sequence set forth in SEQ ID NO: 738 (i.e., an anti-OX40L antibody comprising a heavy chain sequence set forth in SEQ ID NO: 932 and a light chain sequence set forth in SEQ ID NO: 933)) in healthy participants. The results help inform drug dosing and therapeutic regimen for subsequent clinical studies in the intended patient population.

[0638] Healthy participants are chosen for this study to avoid any disease-related confounding factors that could impact the interpretation of safety' and tolerability' data. The inclusion and exclusion criteria help ensure that only healthy participants are included in the study to property monitor the safety and well-being of participants, while minimizing study-related risks.

[0639] A stepwise dose escalation is used to allow evaluation of the safety of Antibody 114 with minimal risk to participants. The use of a placebo control (0.9% sodium chloride) administered via subcutaneous injection helps distinguish any potential effects between Antibody 114 itself and other effects not related to Antibody 114, with minimal bias. Participants are randomized to Antibody 1 14 or placebo in a 6:2 ratio, which is an accepted standard used in early phase PK studies.

[0640] As is common practice for Phase 1 studies, participants remain confined to the study center after dosing with Antibody 114 or placebo. A confinement period of 4 consecutive days allows for rigorous monitoring for any acute events related to initial Antibody 114 dosing (e.g., anaphylaxis). The safety assessment period prior to dose escalation (14 days), which includes outpatient visits approximately every 7 days initially, then monthly after confinement ends, sufficiently covers potential safety liabilities associated with an immunomodulatory antibody and includes the Cmax. based on non-human primate (NHP) data and antibody analogs, where safetyevents are most likely to be seen. Regular outpatient visits continue to Day 225, which allows for long-term safety monitoring, as well as continued PK, PD, and ADA analyses. This follow-up period spans approximately 5 half-lives.

[0641] The safety monitoring practices used in this protocol (e.g., a, vital sign measurements, clinical laboratory tests, and physical examinations) are those used conventionally to monitor participants’ safety and are designed to detect treatment-emergent adverse events (TEAEs). The study population and study design are intended to minimize risk to healthy participants in the study while allowing for evaluation of safety, tolerability, PK, PD, and AD As of Antibody 114. 1. Objectives and Endpoints

[0642] The primary' objective of the study is to evaluate the safety' and tolerability' of single doses of Antibody 114 in healthy participants (e.g., as assessed by incidence of AEs, incidence of abnormal laboratory findings, incidence of abnormal vital signs, electrocardiograms (ECGs), and physical examination findings).

[0643] Secondary' objectives include: (1) characterizing the single dose pharmacokinetics (PK) of Antibody 114 in healthy participants (e.g.. as assessed by Maximum observed serum concentration (Cmax). time to Cmax (tmax). terminal elimination rate constant (kz), terminal elimination half-life (ti / 2), area under the serum concentration versus time curve (AUC) from time 0 to the last quantifiable time point (AUCo-iast), AUC from time 0 extrapolated to infinity7(AUCo-inf), apparent clearance (CL / F), and apparent volume of distribution (Vz / F)) and (2) evaluating the presence of anti-drug antibodies (ADAs) after single doses of Antibody 114 in healthy participants (e.g., via incidence of ADAs and pharmacokinetic (PK) parameters (e.g., Cmax and area under the serum concentration-time curve (AUC)) for participants with versus without ADAs). ADA analysis is performed using a validated ADA assay in 3-tier format (screen, confirm, titer) and neutralizing antibody (Nab) assay in samples that have positive titers for ADA. Serum samples are used to assess ADA outcomes.

[0644] The exploratory objective is to explore potential changes in biomarkers after single doses of Antibody 114 in healthy participants (e.g., as assessed by changes in time in phosphorylated signal transducer and activator of transcription 6 (pSTAT6), thymus- and activation-regulated chemokine (TARC), and other markers).

[0645] 2. Overall Study Design

[0646] This is a Phase 1, randomized, blinded, placebo-controlled, single ascending dose (SAD), first-in-human (FIH) study of Antibody 114 in healthy participants. Antibody 114 is administered subcutaneously (SC) in single ascending doses (SAD). Up to a maximum of 5 SAD cohorts are investigated in this study. Participants only participate in 1 cohort of the study. A schematic of the SAD Study Schema is set forth in FIG. 1.

[0647] The starting dose is 75 mg and there are 4 ascending dose levels (150, 300, 600, and 1,200 mg), with actual dose levels beyond the starting dose at the discretion of the Safety- Review Committee (SRC) based on emerging data. The first 2 participants in each SAD cohort (sentinel participants) are randomized 1 : 1 (active: placebo) in a blinded fashion. After at least 24 hours of post-dose safety and tolerability monitoring, the remainder of the cohort is randomized 5: 1 (active:placebo).

[0648] Participants are screened within 42 days prior to dosing to assess eligibility for study entry and are admitted to the clinical research unit (CRU) 1 day prior to dosing (Day -1). On Day 1 (day of dosing), participants receive a single SC dose of Antibody 114 or placebo. Assessments include, but are not limited to, vital signs, ECG, evaluation of AEs / SAEs, concomitant medications, and blood draws for PK, PD, and safety laboratory tests.

[0649] On Day 4 (72 hours post-dose) participants are discharged from the CRU after completion of all in-clinic assessments on that day. The duration of confinement in the CRU is to monitor for acute events (e g., anaphylaxis) and to ensure quality data. The duration of CRU stay can be adjusted based on SRC decision for Cohorts 2 and beyond based on emerging data from previous cohorts.

[0650] After completion of CRU confinement (through Day 4). participants return for outpatient visits (spanning approximately 5 times the expected half-life of Antibody 114) on Days 8, 11, 15, 22, 29, 57, 85, 113, 141, 169, and 197 followed by an end-of-study (EOS) visit on Day 225. The follow-up visit schedule, PK sampling times and frequency (up to 3 additional PK samples may be added), and duration of study can be adjusted based on SRC decision depending on the safety and / or PK results from prior cohorts.

[0651] The SRC makes the determination to escalate and to which dose based on at least 14 days of post-dose (Day 15) safety data from the previous dose level and in consideration of any emergent safety data from prior cohorts. Specifically, the SRC determines whether any protocol-defined dose-limiting toxicities occurred through Day 15 in participants who received Antibody 114 in the current cohort and whether any stopping rules were met. At least 5 of the 8 participants in the cohort have Day 15 safety data for the SRC to convene. In addition, available PK results are reviewed to assess the appropriateness of the next planned dose and to guide revisions of the next dose to be evaluated, if necessary.

[0652] Dose escalation in subsequent cohorts does not exceed a 2-fold increase in dose relative to the previous cohort. The highest single dose tested does not exceed 1,200 mg.

[0653] 3. Selection and Withdrawal of Patients

[0654] Approximately 40 participants are enrolled in this study (with 8 participants in each of 5 cohorts).

[0655] Participants meet all the following criteria at Screening and upon admission to the CRU (on Day -1): A. Healthy men and women, as determined by physical examination, laboratory screening tests, and medical history’ ;

[0656] B. 18 to 65 years of age (inclusive) with a body mass index of 18.0 to 32.0 kg / m2(inclusive), weight < 120 kg;

[0657] C. Willing and able to speak, read, and understand English, and provide written informed consent after the nature of the study has been explained and prior to the start of any study procedures;

[0658] D. Willing and able to attend the necessary visits to the CRU, and comply with all testing and requirements defined in the protocol;

[0659] E. Willing and able to remain at the study site unit for the duration of the confinement period and return for the outpatient visit(s) defined in the protocol;

[0660] F. Willing to use a highly effective method of contraception from 30 days prior to admission through 30 days after EOS or 5 half-lives after the last administration of study drug, whichever is longer;

[0661] G. Willing to abstain from alcohol and tobacco use for 48 hours prior to admission to the CRU (Day -1) and during inpatient period, and any illicit drug abuse for > 48 hours prior to admission to the CRU (Day -1);

[0662] H. Non-tattooed, clear injection site (e.g.. absence of dermatologic conditions, such as scarring or rash, that may impact the ability to assess injection site reactions) suitable for SC injection and monitoring; and

[0663] I. Agrees to comply with the drawing of blood samples for the PK and PD assessments.

[0664] Participants do not meet any of the following criteria at Screening or upon admission to the CRU (on Day -1):

[0665] A. Evidence of clinically significant abnormalities or disease: a. Diagnosis of diabetes mellitus (history of gestational diabetes mellitus, fully resolved, permitted); b. Positive test for human immunodeficiency virus (HIV) antibody; c. Acute or chronic hepatitis B or C as evidenced by hepatitis B surface antigen (HBsAg) and / or hepatitis C antibody (HCV Ab); evidence of resolved infection or status post-vaccination with the presence of antibodies or documented absence of viral deoxyribonucleic acid on polymerase chain reaction is allowed; d. Diagnosis or suspected diagnosis of immunodeficiency or autoimmune diseases, or undergoing immunosuppressive therapy such as anticancer chemotherapy or radiotherapy before the study, or has received systemic corticosteroid treatment (topical corticosteroids are acceptable) within the past 120 days before dosing; e. Significant history or clinical manifestation of any metabolic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, acute or chronic infectious diseases and malignancies; f. History or presence of conditions which, are known to interfere with the absorption, distribution, metabolism, or excretion of drugs; g. Liver function tests (i.e., alanine aminotransferase, aspartate aminotransferase) > 1.5 times the upper limit of normal; elevated bilirubin is not allowed unless due to Gilbert's syndrome; h. Neutrophils > 1.5 times the upper limit of normal; i. Impaired renal function defined as an estimated glomerular filtration rate

[0666] < 60 mL / min / 1.73 m2at Screening; j . Any other laboratory, vital sign (e.g., hypertension that could be unsafe for study drug administration per Investigator assessment), ECG abnormality (e.g., QTc corrected using Fridericia’s formula [QTcF] prolongation), clinically significant medical condition (e.g., cardiac failure), or finding that, is likely to unfavorably alter the risk of study participation, confound study results, or interfere with the study conduct or compliance; participants can be rescreened and tests may be repeated at the Investigator's discretion. Note: participants with history ofnon- clinically significant disease (e.g., childhood asthma, migraines, non-hospitalized depression, Gilbert syndrome, cholecystectomy) that is not likely to unfavorably alter the risk of study participation, confound study results, or interfere with the study conduct or compliance may be eligible for the study;

[0667] B. History of any of the following: a. Clinically significant opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia) within 5 years prior to Screening; b. Serious local infection (e.g., cellulitis) or systemic infection (e.g., septicemia) within 3 months prior to Screening;

[0668] C. Poor peripheral venous access;

[0669] D. Fever (> 38.0°C) within 14 days before study drug administration

[0670] E. Positive COVID-19 test at admission to the CRU; F. Known history of illicit drug abuse, harmful alcohol use (defined as an average of

[0671] > 10 standard drinks per week) or alcoholism, and / or heavy tobacco use (defined as > 5 cigarettes per day or equivalent) within 2 years prior to Screening; positive screen for drugs of abuse (except tetrahydrocannabinol [THC]), or alcohol breath test at Screening or admission to the CRU, and participants must abstain from cigarette smoking for the duration of their stay in the CRU. Participants may be rescreened for drugs of abuse or alcohol breath test;

[0672] G. History of severe allergic reactions or hypersensitivity (i.e., anaphylaxis);

[0673] H. Known or suspected intolerance or hypersensitivity to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies, or antibody fragments, or to any components of the formulation of Antibody 114 and its excipients used in this study;

[0674] I. If female, nursing, lactating, pregnant, or plans to become pregnant within 30 days of EOS or 5 half-lives (whichever is longer) of last study drug administration;

[0675] J. Donation or loss of > 1 unit (450 mL) of whole blood within 1 month prior to dosing or plasma donations within 7 days of dosing;

[0676] K. Use of any prescription or nonprescription medication 7 days prior to dosing through CRU discharge Day 4 (exception: contraceptives, hormone replacement therapy, vitamins, over-the-counter [OTC] antihistamines, OTC topical steroids, or acetaminophen / paracetamol up to 2 g per day prior to dosing is permitted);

[0677] L. Vaccination within 30 days prior to administration of Antibody 114;

[0678] M. Use of any investigational drug therapy within 30 days or 5 half-lives (whichever is longer) prior to study drug dosing through 5 half-lives after the last dose of study drug

[0679] N. Use of any depot injection or implant for 3 months prior to dosing; or

[0680] O. Unable to comply with study requirements.

[0681] 4. Dose Limiting Toxicities and Stopping Rules

[0682] A dose-limiting toxicity (DLT) is defined as any Grade 3 or higher drug-related AE, a drug-related SAE, or any other finding (symptoms, physical exam, laboratory') deemed to constitute a DLT.

[0683] Any drug-related Grade > 3 or serious adverse reaction prompts a safety assessment to determine whether dosing may proceed in additional participants, and whether changes to the study protocol are needed, such as a dosing adjustment.

[0684] Dose escalation stopping rules are as follows: a. If DLTs occur in > 2 participants receiving a given dose of Antibody 114 and no participants receiving placebo, dose escalation is stopped. b. If a DLT occurs in both participants receiving Antibody 114 and placebo or in only 1 participant receiving Antibody 114. dose escalation proceeds with the dose increment. c. Progression to the next higher dose level cannot proceed if one or more participants has a drug-related SAE or a drug-related clinically significant AE and these warrant discontinuation of dose escalation.

[0685] 5. Description of Study Drug and Concomitant Medicines

[0686] Participants receive a single subcutaneous (SC) dose of either Antibody 114 or placebo, administered by the investigational staff on Day 1. A summary of the investigational product is set forth in Table 8.

[0687] Table 8. Investigational Product

[0688] Antibody 114 is a fully human immunoglobulin G1 (IgGl) monoclonal antibody that binds OX40L with high affinity (described in International Application Publication No. WO2024227174A2, which is incorporated herein by reference). Antibody 114 comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419 and a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489. The constant heavy and light chain sequences of Antibody 114 are set forth in SEQ ID NO: 854 and SEQ ID NO: 738, respectively. Consequently, Antibody 114 comprises a heavy chain sequence of SEQ ID NO: 923 and a light chain sequence of SEQ ID NO: 933. A C-terminal lysine is present in SEQ ID NO: 854 (which corresponds to the C- terminal lysine in SEQ ID NO: 932), which may be cleaved off during manufacture or after administration, resulting in the constant heavy chain sequence of SEQ ID NO: 651. Accordingly, the Antibody 1 14 composition that is administered to participants may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 854 or SEQ ID NO: 651, or a mixture thereof. Antibody 114 includes 2 sets of amino-acid modifications in the fragment crystallizable (Fc) region: M253Y / S255T / T257E (YTE) and L235A / L236A (LALA) (by direct numbering). YTE modifications are designed to extend the half-life of monoclonal antibodies in humans (see Dall'Acqua WF, et al., J. Biol. Chem. 2006; 281(33):23514-24). LALA modifications are designed to significantly reduce binding to Fc gamma receptors (FcyR) and complement protein Clq, which are intended to ablate the effector function of a human IgGl antibody.

[0689] Antibody 114 binds to human OX40L, preventing inflammatory signaling. This pathway is well described in the pathology of AD as well as other inflammatory and immunologic conditions (see Furue M and Furue M., J. Clin. Med. 2021; 10(12); 2578; Cortini A, et al., Ann. Rheum. Dis. 2017;76(12):2095-103; and Siddiqui S, etal., Chest. 2010;137(4):797-804. doi: 10. 1378 / chest.09-1839).

[0690] Antibody 114 is supplied as a sterile solution in glass vials.

[0691] Placebo is commercially approved and sourced sterile 0.9% NaCl solution for injection. Antibody 1 14 and placebo doses are masked by the pharmacy for blinding purposes as they are not color-matched.

[0692] Antibody 114 drug product is inspected prior to use. Damaged vials or vials exhibiting particulate are not used.

[0693] The Antibody 114 drug product dosage is withdrawn into a syringe that is covered and remains blinded prior to dosing. Antibody 114 drug product can be held in the vial at room temperature for up to 8 hours before drawing the dosage into the syringe and is administered within 8 hours of drawing the dosage into the syringe.

[0694] Study drug is administered as a SC injection. The site of injection is marked and documented for later observation (e.g., injection site reaction). The preferred SC injection site is the abdomen and is used as the primary site. The upper arm or thigh can be used if there is a rationale. In the case of a need for multiple injections, SC injection sites are at least 2 inches apart.

[0695] The use of any prescription or non-prescription medication (except for contraceptives, hormone replacement therapy, vitamins, OTC antihistamines, OTC topical steroids, or acetaminophen / paracetamol up to 2 g / day) is prohibited 7 days prior to dosing through CRU discharge Day 4. After this time, medications are allowed per Investigator discretion.

[0696] If it is medically necessary to initiate any concomitant medication during the study (i.e., treatment of a TEAE), it is recorded on the case report form (CRF). Permitted medications include contraceptives, hormone replacement therapy, vitamins, OTC antihistamines, OTC topical steroids, or acetaminophen / paracetamol up to 2 g / day at all times during the study. Outside of the timing of 48 hours prior to dosing through CRU discharge on Day 4, medications are allowed per Investigator discretion.

[0697] 6. Pharmacokinetic, Pharmacodynamic, and Anti-Drug Antibody (ADA) Assessments Blood samples are collected from all participants to determine serum concentrations of

[0698] Antibody 114, changes in PD biomarkers, and presence of AD As. Blood samples are collected at the times noted in the Schedules of Assessments set forth in Tables 9 and 10. PK sampling times and frequency (up to 3 additional PK samples may be added) can be adjusted depending on the safety and / or PK results from prior cohorts.

[0699] Table 9. Schedule of Assessments: SAD - Screening Through Discharge AE = adverse event; CRU = clinical research unit; ECG = electrocardiogram; FSH = follicle stimulating hormone; h = hour; HIV = human immunodeficiency virus; IgE = immunoglobulin E; LDH = lactate dehydrogenase; PE = physical examination; SAE = serious adverse eventaIncluding smoking, drinking and illicit drug use history, allergy history, and blood donation historybHeart rate, blood pressure, body temperature, and respiratory rate.cWomen only: pregnancy test for women of childbearing potential; FSH to document postmenopausal status for women who are < 55 years of age at Screening only (only required 1 time during Screening); serum pregnancy testing at Screening between Day -42 and -2, then urine pregnancy testing thereafter.dCOVID-19 test: rapid antigen or PCR test. Done at CRU check-in.eSerology testing for HIV, hepatitis B virus, and hepatitis C virus.fPerformed in triplicate (approximately 1 to 3 minutes apart).

[0700] 8Prior to dose.hCan also occur before dosing on Day 1.

[0701] 1Performed by a trained healthcare provider.

[0702] ' Serum samples; for pharmacokinetics and pharmacodynamics: serum biomarkers.kThe reporting period for AEs and SAEs begins after the ICF is signed.

[0703] Table 10. Schedule of Assessments: SAD - Outpatient Post-Treatment Monitoring Through End of Study

[0704] AE = adverse event; d = day; ECG = electrocardiogram; EOS = end of study; ET = early termination; h = hour; SAE = serious adverse eventaEOS assessments are followed at the ET visit, which occur if a participant is not followed to the EOS visit.bHeart rate, blood pressure, body temperature, and respiratory rate.cWomen only: urine pregnancy test for women of childbearing potential.dPerform in triplicate (approximately 1 to 3 minutes apart).ePerformed by a trained healthcare provider.fIf an injection site reaction persists at Day 8. the reaction is monitored and recorded until resolved.gSerum samples; for pharmacokinetics and pharmacodynamics: serum biomarkers. Table 11. Pharmacokinetic Parameters to be Estimated for Antibody 114

[0705] The PK parameters set forth in Table 11 are determined for Antibody 114 as appropriate and as data permit. Dose-normalized Cmax and AUC parameters are also determined, as applicable.

[0706] The following PD parameters are determined, as appropriate and as data permit:

[0707] 1. pSTAT6 changes over time and from baseline, both absolute and percent;

[0708] 2. Other blood biomarkers, including, but not limited to, TARC, changes over time and from baseline, both absolute and percent; and

[0709] 3. Whole blood transcriptome assessment using RNA sequencing (RNA-Seq).

[0710] Samples are collected for analysis of immunogenic response to determine presence / absence and titers of AD As as applicable. Samples can also be characterized for neutralizing antibodies (NAb) against Antibody 114 and other associated parameters, as appropriate. The presence of AD As and the possible impact that their presence has on PK parameters or safety can be investigated as appropriate and as data permit.

[0711] Samples from participants are assayed even if the participants do not complete the study. Samples are analyzed for Antibody 114 concentrations, AD As, and NAbs using validated bioanalytical methods. Samples for PD biomarkers are assessed using fit-for-purpose validated bioanalytical methods. Analysis of ADA samples is performed using a validated assay in a 3-tier format (screen, confirm, titer). 7. Safety Assessments

[0712] All adverse events occurring after the participant signs the ICF through the End of Study (EOS) visit are documented in the source and recorded on the appropriate CRF. Adverse events are determined based on volunteered signs or symptoms and by clinical observation and assessments during study visits. Spontaneously reported adverse events are recorded as such, and adverse events are elicited by clinical site staff using non-leading questions at designated time points.

[0713] All serious adverse events and unresolved adverse events related to the study drug are followed with appropriate medical management until resolution, return to baseline, or a stable status has been achieved.

[0714] Pre-existing conditions, diseases, or disorders are not considered treatment emergent adverse events (TEAEs) unless there is a change in intensity', frequency, or quality following study drug administration. Injection site reactions are considered an adverse event.

[0715] Clinical laboratory tests are provided in Table 12. Additional tests can be performed at any time during the study. Laboratory tests are performed at a local laboratory.

[0716] Table 12. Clinical Laboratory Tests

[0717] ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; eGFR = estimated glomerular filtration rate; GGT = gamma glutamyl transferase; IgE = immunoglobulin E; LDH = lactate dehydrogenase; MCH = mean cell hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean cell volume; MPV = mean platelet volume; WBC = white blood cellaLDH and IgE are PD markers, but are collected as part of the safety laboratory assessments

[0718] 8. Adverse Events and Serious Adverse Events An adverse event is any undesirable event or any untoward medical occurrence that occurs to a participant during the study, or the protocol-defined time after study termination, whether or not that event is considered study drug-related. A treatment emergent adverse event is an event that occurs following the receipt of any amount of study drug. Examples of adverse events include: A. Any treatment-emergent signs and symptoms (including events that are marked by a change from the participant’s baseline / entiy status [e.g., an increase in severity or frequency of pre-existing abnormality or disorder]); B. All reactions from study drug, abuse of drug, withdrawal phenomena, sensitivity, or toxicity to study drug;

[0719] C. Apparent unrelated illnesses;

[0720] D. Injuries or accidents;

[0721] E. Extensions or exacerbations of symptomatology, subjective participant-reported events, new clinically significant abnormalities in clinical laboratory, physiological testing, or physical examination;

[0722] F. Abnormal laboratory findings considered to be clinically significant, and that represent a worsening from baseline, are reported as an adverse event. An abnormal laboratory value is recorded as an adverse event if it is associated with clinical signs or symptoms, meets Grade 2 criteria whether symptomatic or not, requires an intervention, results in a serious adverse event, or results in study termination or interrupt! on / discontinuati on of study treatment.

[0723] A serious adverse event is any adverse event, occurring at any dose and regardless of causality, that:

[0724] A. Results in death.

[0725] B. Is life-threatening. Life-threatening means that the participant was at immediate risk of death from the reaction as it occurred (i.e., it does not include a reaction that hypothetically might have caused death had it occurred in a more severe form).

[0726] C. Requires inpatient hospitalization or prolongation of existing hospitalization. Hospitalization admissions and / or surgical operations scheduled to occur during the study period, but planned before the signing of the ICF, are not considered adverse events if the illness or disease existed before the participant was enrolled in the study, provided that it did not deteriorate in an unexpected manner during the study (e.g., surgery performed earlier than planned).

[0727] D. Results in persistent or significant disability / incapacity. Disability is defined as a substantial disruption of a person’s ability to conduct normal life functions.

[0728] E. Is a congenital anomaly / birth defect.

[0729] F. Is an important medical event. An important medical event is an event that may not result in death, be life-threatening, or require hospitalization but may be considered an S AE when, based upon appropriate medical judgment, it may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in the definitions for serious adverse events. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.

[0730] A distinction is between the terms “serious"’ and “severe”, since they are not synonymous. The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as severe headache). This is not the same as “serious,” which is based on participant / event outcome or action criteria usually associated with events that pose a threat to a participant’s life or functioning. A severe adverse event does not necessarily need to be considered serious. For example, persistent nausea of several hours duration may be considered severe nausea but not a serious adverse event if the event does not meet the serious criteria. On the other hand, a stroke resulting in only a minor degree of disability may be considered mild but would be defined as a serious adverse event based on the above noted serious criteria. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.

[0731] The Investigator or designee review each event (including injection site reactions) and assess its severity based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). version 5.0. If a participant has an adverse event not listed in the CTCAE, the following grading system is used to assess severity:

[0732] A. Grade 1 : mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

[0733] B. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.

[0734] C. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living.

[0735] D. Grade 4: life-threatening consequences; urgent intervention indicated.

[0736] E. Grade 5: death related to adverse event.

[0737] A mild, moderate, or severe adverse event may or may not be serious. These terms are used to describe the intensity of a specific event. Medical judgment should be used on a case- by-case basis.

[0738] The Investigator is obligated to assess the relationship between study drug and each adverse event / serious adverse event. The adverse event / serious adverse event is characterized as related or not related according to the following criteria: A. Related: The temporal relationship between the event and the administration of the study interve...

Claims

CLAIMS1. A method of treating a disease or condition in a human patient, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 75 mg.

2. A method of treating a disease or condition in a human patient, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 150 mg.

3. A method of treating a disease or condition in a human patient, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 300 mg.

4. A method of treating a disease or condition in a human patient, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 600 mg.

5. A method of treating a disease or condition in a human patient, wherein the method comprises administering to the patient an anti-OX40L antibody, or antigen binding fragment thereof, at a dose of 1200 mg.

6. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, is administered subcutaneously.

7. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, is administered at a maintenance dose every three months.

8. The method of any one of claims 1-6, wherein the anti-OX40L antibody, or antigen binding fragment thereof, is administered at a maintenance dose every' six months.

9. The method of any one of the preceding claims, wherein the disease is an immunologic and / or inflammatory disease.

10. The method of claim(). wherein the disease is atopic dermatitis (AD).

11. The method of claim 9, wherein the disease is asthma.

12. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:

489. and an Fc region comprising one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, M428L / N434S (LS). M252Y / S254T / T256E (YTE). T250Q / M428L, T307A / E380A / N434A. T256D / T307Q (DQ), T256D / T307W (DW), M252Y / T256D (YD), T307Q / Q311V / A378V (QVV), T256D / H285D / T307R / Q311V / A378V (DDRVV), L309D / Q311H / N434S (DHS), S228P / L235E (SPLE), L234A / L235A (LALA), M428L / N434A (LA), L235A / G237A (LAGA), L234AL235AG237A (LALAGA), L234A / L235A / P329G (LALAPG), D265AYTE, LALAYTE. LAGAYTE. LALAGAYTE. LALAPGYTE, N297ALS, D265ALS. LALALS. LALAGALS, LALAPG / LS, N297ADHS, D265ADHS, LALADHS, LAGADHS, LALAGADHS, LALAPG / DHS, SPYTE, SPLEYTE, SP / LS, SPLE / LS, SP / DHS, SPLE / DHS, N297ALA, D265ALA, LALALA. LAGALA, LALAGALA, LALAPG / LA, N297A / N434A, D265A / N434A, LALA / N434A, LAGA / N434A LALAGA / N434A, LALAPG / N434A N297A / N434W, D265A / N434W, LALA / N434W, LAGA / N434W, LALAGA / N434W, LALAPG / N434W, N297 ADQ, D265ADQ, LALADQ, LAGADQ, LALAGADQ, LALAPG / DQ, N297ADW, D265 ADW, LALADW, LAGADW, LALAGADW, LALAPG / DW. N297AYD, D265AYD, LALAYD, LAGAYD, LALAGAYD, LALAPGYD, N297AQVV, D265AQVV, LALAQVV, LAGAQVV, LALAGAQVV, LALAPG / QVV, DDRVV, N297 ADDRVV, D265 ADDRVV, LALADDRVV, LAGADDRVV, LALAGADDRVV, and LALAPG / DDRVV.

13. The method of claim 12, wherein the Fc region is a human IgGl Fc region.

14. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489, and a human IgGl Fc region comprising one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q / M428L, T307A / E380A / N434A, DQ, DW, YD, QVV, DHS, LA, D265A / YTE, LALA / YTE, LAGA / YTE. LALAGA / YTE. LALAPG / YTE. N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D265A / DHS. LALA / DHS. LAGA / DHS, LALAGA / DHS. LALAPG / DHS, SP / YTE, SPLE / YTE. SP / LS. SPLE / LS, SP / DHS, SPLE / DHS. N297A / LA, D265A / LA, LALA / LA, LAGA / LA, LALAGA / LA, LALAPG / LA, N297A / DQ, D265A / DQ, LALA / DQ, LAGA / DQ, LALAGA / DQ, LALAPG / DQ, N297A / DW, D265A / DW, LALA / DW, LAGA / DW, LALAGA / DW, LALAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, N297A / QVV. D265A / QVV, LALA / QVV. LAGA / QVV, LALAGA / QVV, and LALAPG / QVV.

15. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489, and a human IgGl Fc region comprising LALA and YTE substitutions.

16. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence set forth in SEQ ID NO: 651 and / or a constant heavy chain sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:

489. and a constant light chain sequence set forth in SEQ ID NO: 738.

17. The method of claim 16, wherein the anti-OX40L antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:

419. a constant heavy chain sequence set forth in SEQ ID NO: 854, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489, and a constant light chain sequence set forth in SEQ ID NO: 738.

18. The method of claim 16, wherein the anti-OX40L antibody, or antigen binding fragment thereof comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:419, a constant heavy chain sequence set forth in SEQ ID NO: 651, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO:489, and a constant light chain sequence set forth in SEQ ID NO: 738.

19. The method of any one of the preceding claims, wherein the anti-OX40L antibody, or antigen binding fragment thereof, has a half-life of about 60 days.

20. The method of any one of the preceding claims, wherein administration of the anti- OX40L antibody, or antigen binding fragment thereof, inhibits Type 1, Type 2, and / or Type 3 inflammation.

21. The method of any one of the preceding claims, wherein administration of the anti- OX40L antibody, or antigen binding fragment thereof, reduces expression of one or more nonType 2 inflammatory markers selected from the group consisting of TNFa, NFKBI, and NFKBIA.

22. The method of any one of the preceding claims, wherein the treatment results in a reduction or cessation in one or more symptoms of the disease or condition.

23. A kit for treating a disease or condition in a human patient, the kit comprising:(a) a dose of an anti-OX40L antibody, or antigen binding fragment thereof; and(b) instructions for using the anti-OX40L antibody, or antigen binding fragment thereof, in the method of any one of the preceding claims.

24. The kit of claim 23, wherein the dose is 75 mg, 150 mg, 300 mg, 600 mg, or 1200 mg.

25. The kit of claim 23 or 24, wherein the disease is an immunologic and / or inflammatory disease.

26. The kit of claim 25, wherein the disease is atopic dermatitis (AD) or asthma.

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