Antibody that binds to OX40L and method of use thereof

Abstract

One of the new mechanisms in the treatment of atopic dermatitis (AD) is the targeting of OX40 or OX40L. OX40L is a ligand for OX40. This specification describes novel and improved antibodies that bind to OX40L and methods of use thereof. In certain embodiments, this specification describes methods for inhibiting the biological activity of OX40L. In certain embodiments, this specification describes pharmaceutical compositions comprising anti-OX40L antibodies. In certain embodiments, the antibodies and methods described herein are used to treat inflammatory diseases or disorders accompanied by elevated levels of OX40L.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims the benefits and priority thereunder of U.S. Provisional Patent Application No. 63 / 462,871 filed on 28 April 2023, U.S. Provisional Patent Application No. 63 / 529,631 filed on 28 July 2023, and U.S. Provisional Patent Application No. 63 / 561,037 filed on 4 March 2024, the entirety of which disclosures are incorporated herein by reference for all purposes. [Background technology]

[0002] One emerging mechanism in the treatment of atopic dermatitis (AD) involves targeting OX40 or OX40L. OX40L is a ligand for OX40. OX40L is expressed on antigen-presenting cells, and its interaction with OX40 induces T cell accumulation by providing survival signals. OX40L contributes to the excessive activation of the immune system in AD and other inflammatory conditions by activating T cells and reprogramming them into an inflammatory subset. Furthermore, OX40L-mediated activation of OX40 inhibits FOXP3 expression and the inhibitory function of regulatory T (Treg) cells. Treg cells suppress the immune response, thereby leading to the exacerbation of symptoms in inflammatory conditions. Therefore, blocking OX40L may yield clinical benefits in AD and other inflammatory conditions by first suppressing the activation of inflammatory T cells and then increasing Treg cell proliferation, which may help further reduce inflammatory cells. Both amriterimab, which targets OX40L, and locatinlimab, which targets OX40, have shown promising Phase 2 data in Alzheimer's disease (AD).

[0003] OX40L is a ligand for OX40 expressed on antigen-presenting cells. The interaction of OX40L with OX40 induces T cell accumulation by providing a survival signal. T cells are a crucial type of leukocyte in the immune system, playing a central role in the immune response. OX40L contributes to immune hyperactivation in AD and other inflammatory conditions, such as systemic lupus erythematosus, by activating T cells and reprogramming them into an inflammatory subset. Furthermore, OX40L-mediated activation of OX40 inhibits Foxp3 expression and the inhibitory function of regulatory T (Treg) cells. Treg cells can suppress the immune response, leading to exacerbation of inflammatory symptoms.

[0004] Therefore, there is a need in this field for improved therapeutic agents that target OX40L, such as recombinant antibodies. [Overview of the project]

[0005] In a first aspect, antibodies such as recombinant human antibodies that specifically bind to human OX40L are disclosed herein.

[0006] In certain embodiments, the herein describes an isolated antibody that binds to OX40L, comprising: 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 the amino acid sequence shown in any one of SEQ ID NOs: 1-69 and 740-747; and b. CDR-H2 comprises the amino acid sequence shown in any one of SEQ ID NOs: 70-174 and 748-762. An antibody is described that contains the following amino acid sequences: c. CDR-H3 contains the amino acid sequence shown in any one of SEQ ID NOs. 175-257 and 763-780; d. CDR-L1 contains the amino acid sequence shown in any one of SEQ ID NOs. 258-334 and 781-796; e. CDR-L2 contains the amino acid sequence shown in any one of SEQ ID NOs. 335-367 and 797-805; and f. CDR-L3 contains the amino acid sequence shown in any one of SEQ ID NOs. 268-393 and 806-811.

[0007] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 258, 286, and 311; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0008] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 2, 23, and 45; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 176, 204, and 224; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 259, 287, and 312; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 336 and 360; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 369 and 395.

[0009] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 3, 24, and 46; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 71, 112, and 143; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 177, 205, and 225; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 370 and 396.

[0010] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 261, 289, and 314; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0011] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 73, 114, and 145; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 262, 290, and 315; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 372 or 398.

[0012] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 6, 24, and 49; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 74, 115, and 146; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 180, 208, and 228; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 263, 291, and 316; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 339 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 373 or 399.

[0013] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 7, 25, and 50; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 75, 116, and 147; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 181, 209, and 229; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 264, 292, and 317; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340 and 363; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

[0014] In some embodiments, the antibodies provided herein comprise 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: 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.

[0015] In some embodiments, the antibodies provided herein comprise 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-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.

[0016] In some embodiments, the antibodies provided herein comprise 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-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.

[0017] In some embodiments, the antibodies provided herein comprise 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.

[0018] In some embodiments, the antibodies provided herein comprise 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.

[0019] In some embodiments, the antibodies provided herein comprise 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.

[0020] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 185, 213, and 233; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

[0021] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 9, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 77, 118, and 149; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 342 and 364; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0022] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 28, and 53; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 78, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 266, 286, and 311; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0023] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 186, 203, and 235; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 267, 294, and 319; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 344 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0024] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 80, 120, and 151; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 186, 203, and 235; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0025] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 11, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0026] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 11, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 81, 121, and 152; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0027] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 80, 120, and 151; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 187, 203, and 236; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0028] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 187, 203, and 236; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0029] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 268, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0030] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 12, 29, and 54; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0031] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 82, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 189, 214, and 238; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 345 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0032] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 83, 122, and 153; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 346 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 378 and 404.

[0033] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 13, 30, and 55; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 84, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0034] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 347 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0035] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 345 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0036] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 85, 123, and 154; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0037] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 270, 295, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0038] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 1, 31, and 56; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 379 and 405.

[0039] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 32, and 57; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0040] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 380 and 406.

[0041] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 14, 33, and 58; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0042] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0043] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0044] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 13, 30, and 55; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0045] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0046] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 348 and 366; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0047] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 381 and 405.

[0048] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0049] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 381 and 405.

[0050] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0051] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0052] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0053] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 78, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0054] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 2, 840, and 45; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 176, 204, and 224; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 259, 287, and 312; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 336 and 360; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 369 and 395.

[0055] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 15, 34, and 59; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 88, 125, and 156; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 349 and 365; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 382 and 407.

[0056] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 89, 126, and 157; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0057] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 4, 35, and 60; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 178, 206, and 241; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 271, 296, and 320; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 350 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 371 and 397.

[0058] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 90, 127, and 158; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 261, 289, and 314; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0059] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 16, 36, and 61; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 91, 128, and 159; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 191, 215, and 242; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

[0060] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 16, 36, and 61; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 91, 128, and 159; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0061] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 15, 27, and 62; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

[0062] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 15, 27, and 62; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 383 and 408.

[0063] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 37, and 63; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 92, 129, and 160; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 384 and 409.

[0064] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 93, 130, and 161; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 384 and 409.

[0065] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 192, 207, and 243; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 273, 298, and 322; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 385 and 410.

[0066] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 17, 38, and 64; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 95, 132, and 163; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 386 and 411.

[0067] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 96, 130, and 164; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 192, 207, and 243; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 274, 299, and 323; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 386 and 411.

[0068] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 97, 130, and 164; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 275, 300, and 324; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 386 and 411.

[0069] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 193, 216, and 244; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 276, 301, and 325; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0070] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 193, 216, and 245; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 277, 302, and 326; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0071] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 194, 217, and 246; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 276, 301, and 325; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0072] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 194, 217, and 247; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 276, 301, and 325; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 388 and 413.

[0073] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 19, 40, and 66; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 99, 133, and 165; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 278, 303, and 327; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 352 and 367; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0074] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 20, 41, and 67; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 100, 134, and 166; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 195, 218, and 249; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 279, 304, and 328; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 353 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

[0075] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 20, 840, and 48; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 101, 133, and 167; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 389 and 414.

[0076] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 102, 135, and 168; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 350 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 389 and 414.

[0077] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 103, 136, and 169; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 196, 218, and 250; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 354 and 367; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 390 and 415.

[0078] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 104, 137, and 170; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 197, 208, and 251; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 281, 306, and 330; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0079] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 105, 138, and 171; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 197, 208, and 251; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 281, 306, and 330; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0080] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 198, 219, and 252; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 282, 307, and 331; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 391 and 416.

[0081] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 20, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 195, 218, and 253; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 355 and 367; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0082] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0083] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 6, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 106, 137, and 170; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 195, 218, and 253; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0084] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 20, 41, and 67; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 107, 133, and 167; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

[0085] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 108, 139, and 172; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 181, 209, and 229; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 283, 308, and 332; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 356 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

[0086] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 21, 42, and 68; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 109, 140, and 173; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 199, 220, and 254; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

[0087] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 43, and 69; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 106, 137, and 170; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 200, 221, and 255; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 284, 309, and 333; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

[0088] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 43, and 69; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 201, 222, and 256; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 285, 310, and 334; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 357 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 392 and 417.

[0089] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 43, and 69; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 110, 141, and 174; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 202, 222, and 257; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 285, 310, and 334; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 358 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 393 and 418.

[0090] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 748, 116, and 758; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 763, 769, and 775; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 781, 787, and 792; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 797 and 802; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 806 and 812.

[0091] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 740, 742, and 745; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 749, 754, and 759; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 764, 770, and 776; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 782, 788, and 793; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 798 and 803; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 807 and 813.

[0092] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 17, 743, and 746; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 750, 133, and 165; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 765, 771, and 777; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 783, 298, and 322; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 799 and 804; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 808 and 814.

[0093] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 751, 755, and 760; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 766, 772, and 778; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 784, 789, and 794; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 809 and 815.

[0094] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 368 and 394.

[0095] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 752, 756, and 761; CDR-H3 containing the sequence shown in any one of SEQ ID NOs: 767, 773, and 779; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 785, 790, and 795; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 800 and 805; and CDR-L3 containing the sequences shown in SEQ ID NOs: 810 and 816.

[0096] In some embodiments, the antibodies provided herein include CDR-H1 containing the sequence shown in any one of SEQ ID NOs: 741, 744, and 747; CDR-H2 containing the sequence shown in any one of SEQ ID NOs: 753, 757, and 762; CDR-H3 containing the sequence shown in SEQ ID NOs: 768, 774, and 780; CDR-L1 containing the sequence shown in any one of SEQ ID NOs: 786, 791, and 796; CDR-L2 containing the sequence shown in any one of SEQ ID NOs: 801 and 360; and CDR-L3 containing the sequences shown in SEQ ID NOs: 811 and 817.

[0097] In some embodiments, the antibody contains a heavy chain variable domain (VH) sequence selected from the amino acid sequences shown in SEQ ID NOs. 419-488 and 818-824.

[0098] In some embodiments, the antibody includes a light chain variable domain (VL) sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 489-544 and 825-831.

[0099] In some embodiments, the antibody comprises a VH sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 419-488 and 818-824, and a VL sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 489-544 and 825-831.

[0100] In certain embodiments, the Specified Description of an isolated antibody that binds to OX40L comprises a VH sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 419-488 and 818-824, and a VL sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 489-544 and 825-831.

[0101] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 429 and the VL sequence shown in SEQ ID NO: 497.

[0102] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 429 and the VL sequence shown in SEQ ID NO: 498.

[0103] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 430 and a VL sequence shown in SEQ ID NO: 499.

[0104] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 431 and the VL sequence shown in SEQ ID NO: 500.

[0105] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 432 and the VL sequence shown in SEQ ID NO: 501.

[0106] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 433 and the VL sequence shown in SEQ ID NO: 502.

[0107] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 434 and the VL sequence shown in SEQ ID NO: 502.

[0108] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 435 and the VL sequence shown in SEQ ID NO: 502.

[0109] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 436 and the VL sequence shown in SEQ ID NO: 502.

[0110] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 437 and the VL sequence shown in SEQ ID NO: 502.

[0111] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 438 and a VL sequence shown in SEQ ID NO: 503.

[0112] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 439 and the VL sequence shown in SEQ ID NO: 502.

[0113] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 440 and the VL sequence shown in SEQ ID NO: 504.

[0114] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 441 and a VL sequence shown in SEQ ID NO: 505.

[0115] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 442 and the VL sequence shown in SEQ ID NO: 506.

[0116] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 443 and the VL sequence shown in SEQ ID NO: 507.

[0117] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 443 and a VL sequence shown in SEQ ID NO: 508.

[0118] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 444 and the VL sequence shown in SEQ ID NO: 506.

[0119] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 509.

[0120] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 446 and the VL sequence shown in SEQ ID NO: 510.

[0121] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 447 and the VL sequence shown in SEQ ID NO: 506.

[0122] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 445 and a VL sequence shown in SEQ ID NO: 511.

[0123] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 448 and a VL sequence shown in SEQ ID NO: 506.

[0124] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO: 502.

[0125] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO: 506.

[0126] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 450 and the VL sequence shown in SEQ ID NO: 506.

[0127] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 512.

[0128] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 449 and a VL sequence shown in SEQ ID NO: 513.

[0129] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 514.

[0130] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 515.

[0131] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 451 and a VL sequence shown in SEQ ID NO: 514.

[0132] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 451 and the VL sequence shown in SEQ ID NO: 506.

[0133] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 452 and the VL sequence shown in SEQ ID NO: 506.

[0134] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 438 and a VL sequence shown in SEQ ID NO: 506.

[0135] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 453 and a VL sequence shown in SEQ ID NO: 512.

[0136] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 454 and a VL sequence shown in SEQ ID NO: 490.

[0137] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 455 and the VL sequence shown in SEQ ID NO: 516.

[0138] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 456 and a VL sequence shown in SEQ ID NO: 517.

[0139] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 457 and a VL sequence shown in SEQ ID NO: 518.

[0140] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 458 and the VL sequence shown in SEQ ID NO: 492.

[0141] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 459 and the VL sequence shown in SEQ ID NO: 519.

[0142] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 460 and the VL sequence shown in SEQ ID NO: 520.

[0143] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 461 and a VL sequence shown in SEQ ID NO: 521.

[0144] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 461 and a VL sequence shown in SEQ ID NO: 522.

[0145] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 461 and a VL sequence shown in SEQ ID NO: 522.

[0146] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 462 and the VL sequence shown in SEQ ID NO: 523.

[0147] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 463 and a VL sequence shown in SEQ ID NO: 523.

[0148] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 464 and a VL sequence shown in SEQ ID NO: 524.

[0149] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 465 and the VL sequence shown in SEQ ID NO: 525.

[0150] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 466 and a VL sequence shown in SEQ ID NO: 526.

[0151] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 467 and the VL sequence shown in SEQ ID NO: 527.

[0152] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 468 and a VL sequence shown in SEQ ID NO: 528.

[0153] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 469 and a VL sequence shown in SEQ ID NO: 529.

[0154] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 470 and a VL sequence shown in SEQ ID NO: 528.

[0155] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 471 and a VL sequence shown in SEQ ID NO: 530.

[0156] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 472 and a VL sequence shown in SEQ ID NO: 531.

[0157] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 473 and a VL sequence shown in SEQ ID NO: 532.

[0158] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 474 and a VL sequence shown in SEQ ID NO: 533.

[0159] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 475 and a VL sequence shown in SEQ ID NO: 534.

[0160] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 476 and the VL sequence shown in SEQ ID NO: 535.

[0161] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 477 and the VL sequence shown in SEQ ID NO: 536.

[0162] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 478 and a VL sequence shown in SEQ ID NO: 536.

[0163] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 479 and the VL sequence shown in SEQ ID NO: 537.

[0164] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 480 and a VL sequence shown in SEQ ID NO: 538.

[0165] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 481 and a VL sequence shown in SEQ ID NO: 539.

[0166] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 482 and a VL sequence shown in SEQ ID NO: 539.

[0167] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 483 and a VL sequence shown in SEQ ID NO: 539.

[0168] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 484 and a VL sequence shown in SEQ ID NO: 540.

[0169] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 485 and the VL sequence shown in SEQ ID NO: 541.

[0170] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 486 and a VL sequence shown in SEQ ID NO: 542.

[0171] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 487 and a VL sequence shown in SEQ ID NO: 543.

[0172] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 488 and a VL sequence shown in SEQ ID NO: 544.

[0173] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 818 and the VL sequence shown in SEQ ID NO: 825.

[0174] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 819 and the VL sequence shown in SEQ ID NO: 826.

[0175] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 820 and the VL sequence shown in SEQ ID NO: 827.

[0176] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 821 and the VL sequence shown in SEQ ID NO: 828.

[0177] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 822 and the VL sequence shown in SEQ ID NO: 829.

[0178] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 823 and the VL sequence shown in SEQ ID NO: 830.

[0179] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 824 and the VL sequence shown in SEQ ID NO: 831.

[0180] In some embodiments, the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

[0181] In some embodiments, the antibody is a humanized antibody.

[0182] In some embodiments, the antibody comprises a heavy-chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

[0183] In some embodiments, the human Fc region includes human heavy chain constant regions of the IgG class and subclasses selected from IgG1, IgG2, IgG3, and IgG4.

[0184] In some embodiments, the human Fc region includes human IgG1 Fc.

[0185] In some embodiments, the human Fc region includes human IgG4 Fc.

[0186] In some embodiments, the human Fc region includes human IgG2 Fc.

[0187] In some embodiments, the heavy chain includes a constant heavy chain sequence selected from the amino acid sequences shown in any one of SEQ ID NOs. 637 to 737, 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 includes a constant heavy chain sequence selected from the amino acid sequences shown 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.

[0188] In some embodiments, the light chain comprises a constant light chain sequence shown in Sequence 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.

[0189] In some embodiments, the heavy chain comprises a constant heavy chain sequence selected from the amino acid sequence shown in SEQ ID NO: 651, or amino acids 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 shown in SEQ ID NO: 738, or amino acid sequences 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.

[0190] In some embodiments, the Fc region includes one or more amino acid substitutions, and these substitutions result in an increase in one or more of the antibody half-life, ADCC activity, ADCP activity, and / or CDC activity compared to an Fc region without these substitutions.

[0191] In some embodiments, the Fc region includes one or more amino acid substitutions, where the one or more substitutions result in a decrease in one or more of the ADCC activity, ADCP activity, and / or CDC activity compared to an Fc region without the one or more substitutions.

[0192] In some embodiments, one or more amino acid substitutions result in an increased antibody half-life compared to antibodies containing the wild-type Fc region.

[0193] In some embodiments, one or more amino acid substitutions are selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W, and optionally, one or more amino acid substitutions are 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, L234A / L235A, M428L / N434AL234A / G237AL234A / L235A / G237A, L234A / L235A / P329G, D265A / YTE, LALA / YTE, LAGA / YTE, LAL AGA / YTE, LALAPG / YTE, N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D26 5A / 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 / N434 A, D265A / N434A, LALA / N434A, LAGA / N434A, LALAGA / N434A, LALAPG / N434A, N297A / N434W, D265 A / 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, LA LAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, T307Q / Q311V / A378V This is a combination of amino acid substitutions selected from the group consisting of (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.

[0194] In some embodiments, the Fc region binds to the fetal Fc receptor (FcRn).

[0195] In some embodiments, the Fc region binds to FcRn with higher affinity at pH 6.0 compared to antibodies containing the wild-type Fc region.

[0196] In some embodiments, the Fc region binds to FcRn at pH 6.0 with a KD of less than 1 × 10⁻⁷ M.

[0197] In some embodiments, the antibody is a monoclonal antibody.

[0198] In some embodiments, the antibody binds to the OX40L sequence shown in SEQ ID NO: 739.

[0199] In some embodiments, the antibody, when measured by surface plasmon resonance (SPR), has approximately 1, 2, 3, 4, 5, 6, 7, 8, 9 × 10¹⁶ units in the OX40L sequence shown in SEQ ID NO: 739. -9 Join with KD values ​​less than or equal to M.

[0200] In some embodiments, the antibody, when measured by surface plasmon resonance (SPR), is approximately 1 × 10¹⁶ of the OX40L sequence shown in SEQ ID NO: 739. -10 Join with KD values ​​less than or equal to M.

[0201] In some embodiments, the antibody, when measured by surface plasmon resonance (SPR), is approximately 1 × 10⁶ of human OX40L. -9 Join with KD values ​​less than or equal to M.

[0202] In some embodiments, the antibody exhibits a melting temperature above 68°C when measured by differential scanning fluorescence (DSF).

[0203] In some embodiments, the antibody exhibits a melting temperature above 75°C when measured by differential scanning fluorescence (DSF).

[0204] In some embodiments, the antibodies exhibit an agglutination temperature of 71.2°C or higher when measured by differential scanning fluorescence (DSF).

[0205] In some embodiments, the antibody has a retention time of 15.2 minutes or less when measured by hydrophobic chromatography.

[0206] In some embodiments, the antibody can inhibit OX40L-dependent IFNγ release in human cells, for example.

[0207] In certain embodiments, the antibody exhibits increased ability to bind to OX40L on the cell surface compared to anriterimab.

[0208] In some embodiments, the antibody does not have the heavy chain variable region sequence shown in SEQ ID NO: 113.

[0209] In some embodiments, the antibody does not have the heavy chain sequence shown in SEQ ID NO: 146.

[0210] In certain embodiments, the isolated antibody is used to treat inflammatory disorders or diseases. In certain embodiments, the isolated antibody is used to treat atopic dermatitis. In certain embodiments, the isolated antibody is used to treat idiopathic pulmonary fibrosis. In certain embodiments, the isolated antibody is used to treat alopecia areata. In certain embodiments, the isolated antibody is used to treat chronic sinusitis with nasal polyps. In certain embodiments, the isolated antibody is used to treat chronic sinusitis without nasal polyps (CRSsNP). In certain embodiments, the isolated antibody is used to treat eosinophilic esophagitis (EoE). In certain embodiments, the isolated antibody is used to treat eosinophilic gastrointestinal disorders or diseases (ENID) selected from the group consisting of eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), eosinophilic colitis (EoC), and eosinophilic gastroenteritis (EGE). In certain embodiments, the isolated antibody is used to treat Churg-Strauss syndrome / eosinophilic granulomatosis with polyangiitis (EGPA). In certain embodiments, the isolated antibody is used to treat prurigo nodularis (PN). In certain embodiments, the isolated antibody is used to treat chronic urticaria immobile (CSU). In certain embodiments, the isolated antibody is used to treat chronic pruritus of unknown cause (CPUO). In certain embodiments, the isolated antibody is used to treat bullous pemphigoid (BP). In certain embodiments, the isolated antibody is used to treat cold-induced urticaria (ColdU). In certain embodiments, the isolated antibody is used to treat allergic fungal rhinosinusitis (AFRS). In certain embodiments, the isolated antibody is used to treat allergic bronchopulmonary aspergillosis (ABPA). In certain embodiments, the isolated antibody is used to treat chronic obstructive pulmonary disease (COPD). In certain embodiments, the isolated antibody is used to treat inflammatory bowel diseases such as Crohn's disease or ulcerative colitis. In certain embodiments, the isolated antibody is used to treat psoriasis. In certain embodiments, the isolated antibody is used to treat lupus.In certain embodiments, the isolated antibody is used to treat rheumatoid arthritis. In certain embodiments, the isolated antibody is used to treat hidradenitis suppurativa. In certain embodiments, the isolated antibody is used to treat celiac disease. In certain embodiments, the isolated antibody is used to treat systemic scleroderma.

[0211] In certain embodiments, this specification discloses isolated polynucleotides or groups of polynucleotides encoding an antibody, its VH, its VL, its light chain, its heavy chain, or its antigen-binding portion, as described in any of the above claims, wherein the polynucleotides or groups of polynucleotides include cDNA.

[0212] In certain embodiments, this specification discloses vectors or groups of vectors comprising polynucleotides or groups of polynucleotides disclosed herein.

[0213] In certain embodiments, this specification discloses host cells containing polynucleotides or groups of polynucleotides or vectors or groups of vectors disclosed herein.

[0214] In certain embodiments, this specification discloses a method for producing an antibody, the method comprising expressing an antibody having a host cell disclosed herein and isolating the expressed antibody.

[0215] In certain embodiments, this specification discloses a pharmaceutical composition comprising one of the embodiments disclosed herein and a pharmaceutically acceptable excipient.

[0216] In certain embodiments, this specification discloses a kit comprising one of the embodiments disclosed herein, or a pharmaceutical composition disclosed herein, and instructions for use.

[0217] In certain embodiments, this specification describes a method for treating a disorder or disease in a mammalian subject requiring treatment of an inflammatory disorder or disease, comprising administering to the mammalian subject a therapeutically effective amount of an antibody or pharmaceutical composition described herein. In certain embodiments of the method 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 method 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 sinusitis 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 (ENID) 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 nodosa (PN). In certain embodiments, the inflammatory disorder or disease is chronic urticaria immaculateum (CSU). In certain embodiments, the inflammatory disorder or disease is chronic pruritus of unknown cause (CPUO). In certain embodiments, the inflammatory disorder or disease is bullous pemphigoid (BP). In certain embodiments, the inflammatory disorder or disease is cold-induced 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 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 of the methods described herein, the mammalian subject is human.

[0218] In certain embodiments, this specification discloses a method for treating a mammalian subject requiring treatment of a condition involving elevated OX40L levels, comprising administering to the mammalian subject a therapeutically effective amount of one of the embodiments of the herein disclosed antibody or a pharmaceutical composition disclosed herein. In certain embodiments of the method described herein, the mammalian subject is human.

[0219] In certain embodiments, this specification discloses a method for reducing the biological activity of OX40L in a mammalian subject requiring a reduction in its biological activity, the method comprising administering to the mammalian subject a therapeutically effective amount of one of the embodiments of the method disclosed herein or a pharmaceutical composition disclosed herein. In certain embodiments of the method disclosed herein, the mammalian subject is human.

[0220] In certain embodiments, this specification discloses a method for suppressing a TH2-type allergic reaction in a mammalian subject requiring suppression, the method comprising administering to the mammalian subject a therapeutically effective amount of one of the embodiments of the herein disclosed antibody or a pharmaceutical composition disclosed herein. In certain embodiments of the method herein, the mammalian subject is human.

[0221] In certain embodiments, this specification discloses a method for the prevention of an inflammatory disorder or disease in a mammalian subject requiring prevention, comprising administering to the mammalian subject a therapeutically effective amount of one of the embodiments of the herein disclosed antibody or a pharmaceutical composition disclosed herein. In certain embodiments of the method described herein, the mammalian subject is human. [Brief explanation of the drawing]

[0222] [Figure 1] This graph shows the ability of an exemplary anti-hOX40L antibody to bind to hOX40L-expressing CHO cells.

[0223] [Figure 2] This graph shows the OD450-540 values ​​when the concentration of the antibody is increased in the presence of hOX40L, in order to determine the ability of the antibody to block the binding of hOX40L to hOX40.

[0224] [Figure 3] This graph shows the amount of light luminescence (RLU) when the concentration of the antibody is increased in the presence of cells expressing hOX40, in order to determine the ability of the antibody to block the binding of hOX40L to hOX40 in cells.

[0225] [Figure 4] Graphs A and B show the inhibition rate (%) of OX40L and OX40L binding by the indicated antibody compared to the positive control.

[0226] [Figure 5A] This graph shows the inhibition of the IFN-gamma response in the PBMC-CD4 T-cell mixed lymphocyte reaction (MLR) by an antibody at a concentration of 100 nM. [Figure 5B] This graph shows the inhibition of the IFN-gamma response in the PBMC-CD4 T-cell mixed lymphocyte reaction (MLR) by an antibody at a concentration of 20 nM. [Figure 5C]This graph shows the inhibition of the IFN-gamma response in the PBMC-CD4 T-cell mixed lymphocyte reaction (MLR) by an antibody at a concentration of 4 nM.

[0227] [Figure 6] A and B are a pair of graphs showing the concentration of the antibody in the serum of cynomolgus monkeys over time after administration of a single dose of the antibody. [Modes for carrying out the invention]

[0228] definition Unless otherwise defined, all technical terms, notations, and other scientific terms used herein have meanings that are generally understood by those skilled in the art. Where applicable, terms that have generally understood meanings are defined herein for clarity and / or for immediate reference, and the inclusion of such definitions herein should not necessarily be construed as representing a difference beyond that which is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and are commonly employed by those skilled in the art using conventional methods, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual 4th ed. (2012), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Where necessary, procedures involving the use of commercially available kits and reagents are generally carried out according to the protocols and conditions defined by the manufacturers, unless otherwise noted.

[0229] As used herein, the singular forms "a," "an," and "the" include multiple subjects unless otherwise indicated.

[0230] It is understood that the aspects and embodiments of the present invention described herein include "including," "consisting of," and "essentially consisting of."

[0231] All compositions described herein, and all methods using such compositions, may include or "essentially consist of" the listed components or steps. Where a composition is described as "essentially consisting of" the listed components, it contains the listed components and may contain other components that do not substantially affect the condition being treated, but does not contain any other components that substantially affect the condition being treated, other than those explicitly listed. Alternatively, where a composition contains additional components other than those explicitly listed that substantially affect the condition being treated, it does not contain additional components in concentrations or amounts sufficient to substantially affect the condition being treated. Where a method is described as "essentially consisting of" the listed steps, it includes the listed steps and may contain other steps that do not substantially affect the condition being treated, but does not contain any other steps that substantially affect the condition being treated, other than those explicitly listed. As a non-limiting example, where a composition is described as "essentially consisting of" a certain component, that composition may further contain any amount of pharmaceutically acceptable carriers, media, or diluents, and other such components that do not substantially affect the condition being treated.

[0232] As used herein, the term “vector” refers to a nucleic acid molecule capable of propagating another nucleic acid it is linked to. This term includes vectors as self-replicating nucleic acid structures, as well as vectors integrated into the genome of a host cell into which they are introduced. Certain vectors can operatively induce the expression of linked nucleic acids. Such vectors are referred to herein as “expression vectors.”

[0233] The terms “host cell,” “host cell line,” and “host cell culture” are used synonymously and refer to cells into which exogenous nucleic acids have been introduced, and the offspring of such cells. Host cells include “transformers” (or “transformed cells”) and “transferers” (or “transferred cells”), which include primary transformed cells or transferred cells and their offspring, respectively. Such offspring may not be completely identical to the parent cells in nucleic acid content and may contain mutations. “Recombinant host cell” or “host cell” refers to a cell containing exogenous polynucleotides, regardless of the method used for insertion, such as direct uptake, transduction, f-conjugation, or other methods known in the art to produce recombinant host cells.

[0234] As used herein, the term “eukaryote” refers to organisms belonging to the phylogenetic domain Eucarya, such as animals (including, but not limited to, mammals, insects, reptiles, and birds), ciliates, plants (including, but not limited to, monocots, dicots, and algae), fungi, yeasts, flagellates, microsporids, protists, and so on.

[0235] As used herein, the term “prokaryote” refers to a prokaryotic organism. For example, non-eukaryotes may belong to the phylogenetic domain of Eubacteria (including, but not limited to, Escherichia coli, Thermus thermophilus, Bacillus stearothermophilus, Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas putida, etc.) or the phylogenetic domain of Archaea (including, but not limited to, halophilic bacteria such as Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Haloferax volcanii, and halophilic species NRC-1, Archaeeoglobus fulgidus, Pyrococcus furiosus, Pyrococcus horikoshii, Aeuropyrum pernix, etc.).

[0236] As used herein, “effective dose” or “therapeutic effective dose” refers to the amount of a therapeutic compound, such as an anti-OX40L antibody, administered to an individual, either as a single dose or as part of a series of doses, which is effective in producing or contributing to a desired therapeutic effect, either alone or in combination with another mode of therapy. Examples of desired therapeutic effects include enhancement of the immune response, slowing or delaying tumor development, stabilization of a disease, or improvement of one or more symptoms. An effective dose may be administered in one or more doses.

[0237] The term “to treat” (and its variations such as “to treat” or “to cure”) refers to a clinical intervention in an attempt to alter the natural course of a disease or condition in an object that requires such alteration. Treatment may be carried out in the course of clinicopathology. Desired effects of treatment include prevention of disease recurrence, relief of symptoms, reduction of any direct or indirect pathological consequences of the disease, prevention of metastasis, slowing of the rate of disease progression, recovery or reduction of the condition, and remission or improved prognosis.

[0238] The term "sufficient amount" means an amount sufficient to produce the desired effect, for example, an amount sufficient to modulate the immune response in the subject.

[0239] As used herein, the terms “subject” or “individual” mean a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cattle, horses, camels, goats, rabbits, and sheep. In certain embodiments, the subject is a human. In some embodiments, the subject has a disease or condition that can be treated with antibodies provided herein. In some embodiments, the disease or condition is cancer. In some embodiments, the disease or condition is a viral infection.

[0240] The term "in vitro" refers to processes that occur in living cells that are growing independently of the living organism, such as growth in tissue culture.

[0241] The term "in vivo" refers to processes that occur in living organisms.

[0242] The term “package insert” is used to refer to the instructions typically included in the commercial packaging (e.g., a kit) of a therapeutic or diagnostic agent, which contain information about the indications, use, dosage, administration, combination therapy, contraindications, and / or warnings regarding its use.

[0243] The term "pharmaceutical composition" refers to a preparation in which the biological activity of the active ingredient contained therein is effective in treating the target, and which does not contain any additional ingredients that are unacceptably toxic to the target in the amount provided in the pharmaceutical composition.

[0244] The terms “co-administration,” “to co-administer,” and “in combination with” include administering two or more therapeutic agents simultaneously, all at once, or sequentially without specific time constraints. In one embodiment, each agent is present simultaneously within cells or in the body of the subject, or exerts a simultaneous biological or therapeutic effect. In one embodiment, the therapeutic agents are in the same composition or unit dosage form. In other embodiments, the therapeutic agents are in different compositions or unit dosage forms. In certain embodiments, the first agent may be administered before the administration of the second therapeutic agent.

[0245] The terms "to regulate" and "to adjust" refer to reducing or inhibiting the listed variables, or activating or increasing them as an alternative.

[0246] The terms “increase” and “activate” refer to increases of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2x, 3x, 4x, 5x, 10x, 20x, 50x, 100x, or more in the listed variables.

[0247] The terms “reduce” and “inhibit” refer to reductions of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 1 / 2, 1 / 3, 1 / 4, 1 / 5, 1 / 10, 1 / 20, 1 / 50, 1 / 100, or more in the listed variables.

[0248] The term "approximately" indicates and encompasses the given value and its upper and lower range. In certain embodiments, the term "approximately" indicates a specified value ± 10%, ± 5%, or ± 1%. In certain embodiments, where applicable, the term "approximately" indicates the specified value(s) ± one standard deviation of that value(s).

[0249] The term "stimulate" refers to the activation of receptor signaling pathways to induce a biological response associated with receptor activation. A "stimulant" is an entity that binds to and stimulates a receptor.

[0250] The term "antagonism" refers to the inhibition of receptor signaling, which inhibits biological responses related to receptor activation. An "antagonist" is an entity that binds to and antagonizes a receptor.

[0251] For any structural or functional characteristics described herein, the methods for determining these characteristics are known in the art.

[0252] The term "depending on the case," when used consecutively, means to include all of the given combinations, taking into account all subcombinations.

[0253] The term "amino acid" refers to, for example, 20 common naturally occurring amino acids. These naturally occurring amino acids include alanine (Ala, A), arginine (Arg, R), asparagine (Asn, N), aspartic acid (Asp, D), cysteine ​​(Cys, C), glutamic acid (Glu, E), glutamine (Gln, Q), glycine (Gly, G), histidine (His, H), isoleucine (Ile, I), leucine (Leu, L), lysine (Lys, K), methionine (Met, M), phenylalanine (Phe, F), proline (Pro, P), serine (Ser, S), threonine (Thr, T), tryptophan (Trp, W), tyrosine (Tyr, Y), and valine (Val, V).

[0254] The term "affinity" refers to the combined strength of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or epitope). Unless otherwise indicated herein, "affinity" refers to the intrinsic binding affinity that reflects the 1:1 interaction between the elements of a binding pair (e.g., an antibody and an antigen or epitope).

[0255] As used herein, the term "kd" (seconds-1) refers to the dissociation rate constant of a particular antibody-antigen interaction. This value is also known as the koff value.

[0256] As used herein, the term "kd" (M-1 × sec-1) refers to the association rate constant of a particular antibody-antigen interaction. This value is also known as the kon value.

[0257] As used herein, the term "KD" (M) refers to the dissociation equilibrium constant of a particular antibody-antigen interaction. KD = kd / ka. In some embodiments, the affinity of an antibody is described in terms of the KD of the interaction between such antibody and its antigen. For clarity, as is known in the art, a smaller KD value indicates a higher affinity interaction, and a larger KD value indicates a lower affinity interaction.

[0258] As used herein, the term "KA" (M-1) refers to the association equilibrium constant of a particular antibody-antigen interaction. KA = ka / kd.

[0259] The term “antibody” is used herein in its broadest sense and includes certain types of immunoglobulin molecules that contain one or more antigen-binding domains that specifically bind to an antigen or epitope. Specifically, antibodies include intact antibodies (e.g., intact immunoglobulins), antibody fragments, and multispecific antibodies.

[0260] "Anti-OX40L antibody," "OX40L antibody," or "OX40L-specific antibody" refers to an antibody provided herein that specifically binds to the antigen OX40L.

[0261] The term "epitope" refers to the portion of an antigen that specifically binds to an antibody.

[0262] As used herein, the terms “hypervariable region” or “HVR” refer to each region of an antibody-variable domain whose sequence is hypervariable and / or which forms a structurally defined loop (“hypervariable loop”).

[0263] The term "antigen-binding domain" refers to the portion of an antibody that can specifically bind to an antigen or epitope.

[0264] The term "chimeric antibody" refers to an antibody in which part of the heavy chain and / or light chain originates from a specific source or species, while the rest of the heavy chain and / or light chain originates from a different source or species.

[0265] The term "human antibody" refers to an antibody produced by a human or human cell, or an antibody having an amino acid sequence that corresponds to the amino acid sequence of an antibody derived from a non-human source using the human antibody repertoire or a human antibody coding sequence (e.g., obtained from or newly designed from a human source). Strictly speaking, human antibodies exclude humanized antibodies.

[0266] The term "humanized antibody" refers to a protein that has a different sequence from that of an antibody derived from a non-human species, due to the substitution, deletion, and / or addition of one or more amino acids. As a result, when administered to a human subject, a humanized antibody is less likely to induce an immune response and / or induces a less severe immune response compared to an antibody from a non-human species.

[0267] The term "multispecific antibody" refers to an antibody that contains two or more different antigen-binding domains that collectively and specifically bind to two or more different epitopes.

[0268] A "monospecific antibody" is an antibody that contains one or more binding sites that specifically bind to a single epitope. An example of a monospecific antibody is the naturally occurring IgG molecule, which is bivalent (i.e., has two antigen-binding domains) but recognizes the same epitope in each of its two antigen-binding domains. Binding specificity can exist at any appropriate valency.

[0269] The term "monoclonal antibody" refers to an antibody from a population of substantially homogeneous antibodies. This population of substantially homogeneous antibodies is substantially similar, except for variants that may normally occur during the production of monoclonal antibodies, and includes antibodies that bind to the same epitope(s). Such variants are generally present only in small amounts. Monoclonal antibodies are typically obtained by a process involving the selection of a single antibody from multiple antibodies. For example, the selection process could be the selection of a specific clone from multiple clones, such as a hybridoma clone, phage clone, yeast clone, bacterial clone, or a pool of other recombinant DNA clones. The selected antibody can be further modified, for example, to improve its affinity for a target ("affinity maturation"), to humanize the antibody, to improve its production in cell culture, and / or to reduce its immunogenicity in a target.

[0270] The term "single-chain" refers to a molecule containing amino acid monomers linearly linked by peptide bonds. In certain such embodiments, the C-terminus of the Fab light chain is connected to the N-terminus of the Fab heavy chain in a single-chain Fab molecule. As described in more detail herein, the scFv is such that the C-terminus of the variable domain (VL) of the light chain is connected to the N-terminus of the variable domain (VH) of the heavy chain by a polypeptide chain. Alternatively, the scFv consists of a polypeptide chain to which the C-terminus of VH is connected to the N-terminus of VL by a polypeptide chain.

[0271] A "Fab fragment" (also called a fragment antigen-binding fragment) includes a constant domain (CL) of the light chain and a first constant domain (CH1) of the heavy chain, as well as variable regions VL and VH on the light and heavy chains, respectively. The variable domains contain a complementation-determining loop (CDR, also called a hypervariable region) involved in antigen binding. The Fab' fragment differs from the Fab fragment in that it has several residues added to the carboxyl terminus of the heavy chain CH1 domain, which contains one or more cysteines derived from the antibody hinge region.

[0272] The "F(ab')2" fragment contains two Fab' fragments linked by a disulfide bond near the hinge region. The F(ab')2 fragment can be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab') fragment can be dissociated, for example, by treatment with β-mercaptoethanol.

[0273] The "Fv" fragment contains a non-covalent dimer of one heavy chain variable domain and one light chain variable domain.

[0274] A "single-stranded Fv," "sFv," or "scFv" comprises the VH and VL domains of an antibody, where these domains reside within a single polypeptide chain. In one embodiment, the Fv polypeptide further includes a polypeptide linker between the VH and VL domains, which allows the scFv to form a structure desirable for antigen binding. For an overview of scFv, see, for example, 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. Patent No. 5,571,894, and U.S. Patent No. 5,587,458.

[0275] The “scFv-Fc” fragment comprises an scFv bound to an Fc domain. For example, the Fc domain may be bound to the C-terminus of the scFv. The Fc domain may follow VH or VL depending on the orientation of the variable domain of the scFv (i.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 includes an IgG4 Fc domain.

[0276] 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. For single domain antibodies and fragments thereof, the entire content is incorporated herein by reference to Arabi Ghahroudi et al., FEBS Letters, 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sci., 2001, 26:230-245, which are hereby incorporated by reference in their entirety. Single domain antibodies are also known as sdAbs or nanobodies. SdAbs are relatively stable and are easily expressed as fusion partners 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 Biotechnol.77(1):13-22).

[0277] The terms "full-length antibody", "intact antibody", and "whole antibody" are used synonymously herein to refer to an antibody having a structure substantially similar to the naturally occurring antibody structure and having a heavy chain containing an Fc region. For example, when used to refer to an IgG molecule, a "full-length antibody" is an antibody that includes two heavy chains and two light chains.

[0278] The term "antibody fragment" refers to an antibody that includes a portion of an intact antibody, such as an antigen-binding region and / 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.

[0279] The term "Fc domain" or "Fc region" as used herein is defined as the C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. This term includes natural sequence Fc regions and variant Fc regions.

[0280] The term "substantially purified" refers to a construct or variant thereof described herein that may be substantially or essentially free of components normally associated with or interacting with the protein in its native environment, i.e., in natural cells or, in certain embodiments, in a recombinant-produced heteromultimer substantially free of cellular material, such as found in the host cell, and includes preparations of proteins 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% contaminating protein (by dry weight).

[0281] The term "percent identity" in the context of two or more nucleic acid or polypeptide sequences refers to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same when aligned and compared using one of the following sequence comparison algorithms (e.g., publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software, or an algorithm available to one of ordinary skill in the art) or by visual inspection to maximize matches. Software for performing BLAST analysis is generally available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). One of ordinary skill in the art can determine appropriate parameters for sequence alignment, including any algorithm necessary to achieve the maximum alignment over the full length of the sequences being compared. Depending on the application, the percent "identity" can exist over a region of the sequences being compared, e.g., over a functional domain, or alternatively, over the full length of the two sequences being compared.

[0282] To perform a sequence comparison, typically one sequence acts as a reference sequence, which is then compared to the test sequence. When using a sequence comparison algorithm, the test sequence and reference sequence are entered into a computer, subsequence coordinates are specified as needed, and the sequence algorithm program parameters are specified. The sequence comparison algorithm then calculates the sequence identity percentage (%) for the test sequence(s) relative to the reference sequence based on the specified program parameters.

[0283] The optimal alignment of sequences for comparison can be performed, for example, by the local homology algorithm of Smith & Waterman Adv. Appl. Math. 2:482 (1981), the homology alignment algorithm of Needleman & Wunsch J.Mol.Biol.48:443 (1970), the similarity search method of Pearson & Lipman Proc.Nat'l. Acad.Sci.USA85:2444 (1988), by computer implementation of these algorithms (GAP, BESTFIT, FASTA, and TFASTA from Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see Ausubel et al., (cited above)).

[0284] The ranges listed herein are understood to be abbreviated notations of all values ​​within that range, including the listed endpoints. For example, the range 1 to 50 is understood to include any number, combination of numbers, or subrange from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50.

[0285] It should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless otherwise explicitly indicated by the context.

[0286] Anti-OX40L antibody Antibody structure This application provides an antibody that binds to OX40L and a composition containing the antibody.

[0287] The recognized immunoglobulin genes include kappa constant region genes, lambda constant region genes, alpha constant region genes, gamma constant region genes, delta constant region genes, epsilon constant region genes, and mu constant region genes, as well as a vast number of immunoglobulin variable region genes. The light chain is classified as either kappa or lambda. The "class" of an antibody or immunoglobulin refers to the type of constant domain or constant region held by its heavy chain. Antibodies have five main classes: IgA, IgD, IgE, IgG, and IgM, some of which can be further classified into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains corresponding to different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively.

[0288] The structural unit of an exemplary immunoglobulin (antibody) consists of two pairs of polypeptide chains, each having one “light” chain (approximately 25 kD) and one “heavy” chain (approximately 50–70 kD). The N-terminal domain of each chain defines a variable region of approximately 100–110 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 IgG1 heavy chain consists of the VH domain, CH1 domain, CH2 domain, and CH3 domain from the N-terminus to the C-terminus, respectively. The light chain contains the VL and CL domains from the N-terminus to the C-terminus. The IgG1 heavy chain contains a hinge between the CH1 and CH2 domains. In certain embodiments, the immunoglobulin construct includes at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE linked to a therapeutic polypeptide. In some embodiments, the immunoglobulin domains found in the antibodies provided herein are from or derived from an immunoglobulin-based construct such as a diabody or nanobody. In certain embodiments, the immunoglobulin construct described herein comprises at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody. In certain embodiments, the immunoglobulin construct provided herein comprises at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, human antibody, camelid antibody, mouse antibody, or chimeric antibody.

[0289] In some embodiments, the antibodies provided herein include a heavy chain. In one embodiment, the heavy chain is IgA. In one embodiment, the heavy chain is IgD. In one embodiment, the heavy chain is IgE. In one embodiment, the heavy chain is IgG. In one embodiment, the heavy chain is IgM. In one embodiment, the heavy chain is IgG1. In one embodiment, the heavy chain is IgG2. In one embodiment, the heavy chain is IgG3. In one embodiment, the heavy chain is IgG4. In one embodiment, the heavy chain is IgA1. In one embodiment, the heavy chain is IgA2.

[0290] In some embodiments, the antibody is an IgG1 antibody. In some embodiments, the antibody is an IgG3 antibody. In some embodiments, the antibody is an IgG2 antibody. In some embodiments, the antibody is an IgG4 antibody.

[0291] Generally, natural quadruple-chain antibodies contain six HVRs, three in the VH (H1, H2, H3) and three in the VL (L1, L2, L3). HVRs generally contain amino acid residues from the hypervariable loop and / or complementarity-determining region (CDR), the latter having the highest sequence variability and / or being involved in antigen recognition. Except for CDR1 in the VH, CDRs generally contain amino acid residues that form the hypervariable loop. The hypervariable region (HVR) is also called the “complementarity-determining region” (CDR), and these terms are used interchangeably herein to refer to the portion of the variable region that forms the antigen-binding region. This particular region is described in Kabat et al., USD ept. of Health and Human Services, Sequences of Proteins of Immunological Interest (1983), and Chothia et al., J Mol Biol 196:901-917 (1987), where the definition includes overlaps or subsets of amino acid residues when compared to each other. However, the application of any definition referring to an antibody CDR or its variants is intended to be within the scope of the terms defined and used herein. The exact residue numbers comprising a particular CDR vary depending on the sequence and size of the CDR. Those skilled in the art can determine by conventional methods which residues constitute a particular CDR by considering the variable region amino acid sequence of the antibody.

[0292] The amino acid sequence boundaries of CDRs can be determined by those skilled in the art using one of many known numbering schemes, including those described in Kabat et al. (see above) ("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 Pluckthun, J.Mol.Biol., 2001, 309:657-70 ("aHo" numbering scheme) (each of these is referenced in full).

[0293] Table 1 shows the locations 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.

[0294] CDRs can be specified using antibody numbering software such as Abnum, which is available, for example, at www.bioinf.org.uk / abs / abnum / and whose full details are referenced by Abhinandan and Martin, (2008) Immunology, 2008, 45:3832-3839. [Table 1]

[0295] The "EU numbering scheme" is generally used when referring to residues within the constant region of the antibody heavy chain (as reported, for example, in Kabat et al. (above)). Unless otherwise specified, the EU numbering scheme is used to refer to residues within the constant region of the antibody heavy chain as described herein.

[0296] One example of an antigen-binding domain is the one formed by the VH-VL dimer of an antibody. Another example of an antigen-binding domain is the one formed by the diversification of a specific loop from the tenth fibronectin type III domain of adnectin. The antigen-binding domain can contain CDR1, 2, and 3 from the heavy chain in that order, and CDR1, 2, and 3 from the light chain in that order.

[0297] Epitopes often consist of surface-accessible amino acid residues and / or sugar side chains and may possess specific three-dimensional structural and charge properties. Conformational and non-conformational epitopes are distinguished in that binding to the former is lost in the presence of a denaturing solvent, while binding to the latter is not. Epitopes may include amino acid residues directly involved in binding and other amino acid residues not directly involved in binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination, such as testing antibody binding to OX40L variants with different point mutations or to chimeric OX40L variants.

[0298] To screen for antibodies that bind to epitopes on a target antigen conjugated by the antibody of interest (e.g., OX40L), a conventional 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.

[0299] A chimeric antibody is an antibody in which a portion of the heavy chain and / or light chain is derived from a particular source or species, while the remaining portion of the heavy chain and / or light chain is derived from a different source or species.

[0300] A human antibody is an antibody produced by a human or human cell, or an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody derived from a non-human source using a human antibody repertoire or human antibody coding sequence (e.g., obtained from a human-derived source or newly designed). Human antibodies strictly exclude humanized antibodies.

[0301] A humanized antibody has a sequence different from the sequence of an antibody derived from a non-human species by substituting, deleting, and / or adding one or more amino acids. As a result, when administered to a human subject, the humanized antibody is less likely to induce an immune response and / or induces a less severe immune response compared to an antibody of a non-human species. In one embodiment, certain amino acids within the framework and constant domains of the heavy chain and / or light chain of a non-human species antibody are mutated to produce a humanized antibody. In another embodiment, the constant domain(s) derived from a human antibody is 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 such that when administered to a human subject, the immunogenic potential of the non-human antibody is reduced, and the amino acid residues being changed are not important for the immunospecific binding of the antibody to the antigen or the change made to the amino acid sequence is a conservative change so 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 methods for making humanized antibodies can be found in U.S. Patent Nos. 6,054,297, 5,886,152, and 5,877,293. For further details, see, for example, Jones et al., Nature 1986, 321:522-525, Riechmann et al., Nature 1988, 332:323-329, and Presta, Curr., each of which is incorporated by reference in its entirety.

[0302] Two or more different epitopes may be epitopes on the same antigen (e.g., a single OX40L) or on different antigens (e.g., different OX40L molecules, or an OX40L molecule and a non-OX40L molecule). In some embodiments, the multispecific antibody binds to two different epitopes (i.e., a "bispecific antibody"). In some embodiments, the multispecific antibody binds to three different epitopes (i.e., a "triplespecific antibody").

[0303] Examples of anti-IL antibodies include those described herein, such as clones shown in the drawings and / or tables. In some embodiments, the antibody includes an alternative skeleton. In some embodiments, the antibody consists of an alternative skeleton. In some embodiments, the antibody is essentially made up of an alternative skeleton. In some embodiments, the antibody includes an antibody fragment. In some embodiments, the antibody consists of an antibody fragment. In some embodiments, the antibody is essentially made up of an antibody fragment.

[0304] In some embodiments, the antibody is a monoclonal antibody.

[0305] In some embodiments, the antibody is a polyclonal antibody.

[0306] In some embodiments, antibodies are produced by hybridomas. In other embodiments, antibodies are produced by recombinant cells engineered to express desired variable and constant domains.

[0307] In some embodiments, the antibody may be a single-chain antibody or other antibody derivative that retains antigen specificity and a lower hinge region or variants thereof.

[0308] In some embodiments, the antibody may be a multifunctional antibody, a recombinant antibody, a human antibody, a humanized antibody, or a fragment or variant thereof. In certain embodiments, the antibody fragment or its derivative may be selected from Fab fragments, Fab'2 fragments, CDRs, and scFvs.

[0309] In some embodiments, antibodies can form immune complexes. For example, the immune complexes may be tumor cells coated with the antibody.

[0310] To perform a sequence comparison, typically one sequence acts as a reference sequence, which is then compared to the test sequence. When using a sequence comparison algorithm, the test sequence and reference sequence are entered into a computer, subsequence coordinates are specified as needed, and the sequence algorithm program parameters are specified. The sequence comparison algorithm then calculates the sequence identity percentage (%) for the test sequence(s) relative to the reference sequence based on the specified program parameters.

[0311] The optimal alignment of sequences for comparison can be performed, for example, by the local homology algorithm of Smith & Waterman Adv. Appl. Math. 2:482 (1981), the homology alignment algorithm of Needleman & Wunsch J.Mol.Biol.48:443 (1970), the similarity search method of Pearson & Lipman Proc.Nat'l. Acad.Sci.USA85:2444 (1988), by computer implementation of these algorithms (GAP, BESTFIT, FASTA, and TFASTA from Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see Ausubel et al., (cited above)).

[0312] An example of a suitable algorithm for determining sequence identity (%) and sequence similarity (%) is the BLAST algorithm, which is described in Altschul et al. J.Mol.Biol.215:403-410 (1990). Software for performing BLAST analysis is generally available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov / ). [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] Table 2-12 Table 2-13 Table 2-14 Table 2-15 Table 2-16 Table 2-17 Table 2-18 Table 2-19 Table 2-20 Table 2-21 Table 2-22 Table 2-23 Table 2-24 Table 2-25 [Table 2-26] [Table 2-27] [Table 2-28] [Table 2-29] [Table 2-30] [Table 2-31]

[0313] V H domain In some embodiments, the antibodies provided herein include a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841.

[0314] In some embodiments, the antibodies provided herein include a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with an exemplary VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841. In some embodiments, the antibodies provided herein include a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841, having 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. HThe sequence is included. 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 the sequences provided herein by, for example, 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 the sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0315] V L domain In some embodiments, the antibodies provided herein include a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0316] In some embodiments, the antibodies provided herein include a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with a VL sequence selected from any one of SEQ ID NOs. 489-544, 825-831, and 842. In some embodiments, the antibodies provided herein include a VL sequence selected from any one of SEQ ID NOs. 489-544, 825-831, and 842, having 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0317] VH-VL combination In some embodiments, the antibodies provided herein include 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.

[0318] In certain embodiments, the antibodies provided herein may be configured such that a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841 is combined with a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842.

[0319] In certain embodiments, the antibodies provided herein include the VH and VL sequences of the constructs shown in Table 2.

[0320] In some embodiments, the antibodies provided herein include a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with 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%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with a VL sequence selected from any one of SEQ ID NOs: 489-544, 825-831, and 842. In some embodiments, the antibodies provided herein comprise a VH sequence selected from any one of SEQ ID NOs: 419-488, 818-824, and 841, having 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, having 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0321] In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 419 and the VL sequence shown in SEQ ID NO: 489. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 420 and the VL sequence shown in SEQ ID NO: 490. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 421 and the VL sequence shown in SEQ ID NO: 491. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 422 and the VL sequence shown in SEQ ID NO: 492. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 423 and the VL sequence shown in SEQ ID NO: 493.

[0322] In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 424 and the VL sequence shown in SEQ ID NO: 494. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 425 and the VL sequence shown in SEQ ID NO: 495. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 426 and the VL sequence shown in SEQ ID NO: 496. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 427 and the VL sequence shown in SEQ ID NO: 497. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 427 and the VL sequence shown in SEQ ID NO: 498. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 428 and the VL sequence shown in SEQ ID NO: 497. In certain embodiments, the antibody includes the VH sequence shown in SEQ ID NO: 428 and the VL sequence shown in SEQ ID NO: 498.

[0323] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 429 and the VL sequence shown in SEQ ID NO: 497.

[0324] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 429 and the VL sequence shown in SEQ ID NO: 498.

[0325] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 430 and a VL sequence shown in SEQ ID NO: 499.

[0326] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 431 and the VL sequence shown in SEQ ID NO: 500.

[0327] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 432 and the VL sequence shown in SEQ ID NO: 501.

[0328] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 433 and the VL sequence shown in SEQ ID NO: 502.

[0329] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 434 and the VL sequence shown in SEQ ID NO: 502.

[0330] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 435 and the VL sequence shown in SEQ ID NO: 502.

[0331] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 436 and the VL sequence shown in SEQ ID NO: 502.

[0332] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 437 and the VL sequence shown in SEQ ID NO: 502.

[0333] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 438 and a VL sequence shown in SEQ ID NO: 503.

[0334] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 439 and the VL sequence shown in SEQ ID NO: 502.

[0335] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 440 and the VL sequence shown in SEQ ID NO: 504.

[0336] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 441 and a VL sequence shown in SEQ ID NO: 505.

[0337] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 442 and the VL sequence shown in SEQ ID NO: 506.

[0338] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 443 and the VL sequence shown in SEQ ID NO: 507.

[0339] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 443 and a VL sequence shown in SEQ ID NO: 508.

[0340] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 444 and the VL sequence shown in SEQ ID NO: 506.

[0341] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 509.

[0342] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 446 and the VL sequence shown in SEQ ID NO: 510.

[0343] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 447 and the VL sequence shown in SEQ ID NO: 506.

[0344] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 445 and a VL sequence shown in SEQ ID NO: 511.

[0345] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 448 and a VL sequence shown in SEQ ID NO: 506.

[0346] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO: 502.

[0347] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO: 506.

[0348] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 450 and the VL sequence shown in SEQ ID NO: 506.

[0349] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 512.

[0350] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 449 and a VL sequence shown in SEQ ID NO: 513.

[0351] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 514.

[0352] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO: 515.

[0353] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 451 and a VL sequence shown in SEQ ID NO: 514.

[0354] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 451 and the VL sequence shown in SEQ ID NO: 506.

[0355] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 452 and the VL sequence shown in SEQ ID NO: 506.

[0356] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 438 and a VL sequence shown in SEQ ID NO: 506.

[0357] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 453 and a VL sequence shown in SEQ ID NO: 512.

[0358] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 454 and a VL sequence shown in SEQ ID NO: 490.

[0359] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 455 and the VL sequence shown in SEQ ID NO: 516.

[0360] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 456 and a VL sequence shown in SEQ ID NO: 517.

[0361] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 457 and a VL sequence shown in SEQ ID NO: 518.

[0362] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 458 and the VL sequence shown in SEQ ID NO: 492.

[0363] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 459 and the VL sequence shown in SEQ ID NO: 519.

[0364] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 460 and the VL sequence shown in SEQ ID NO: 520.

[0365] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 461 and a VL sequence shown in SEQ ID NO: 521.

[0366] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 461 and a VL sequence shown in SEQ ID NO: 522.

[0367] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 461 and a VL sequence shown in SEQ ID NO: 522.

[0368] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 462 and the VL sequence shown in SEQ ID NO: 523.

[0369] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 463 and a VL sequence shown in SEQ ID NO: 523.

[0370] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 464 and a VL sequence shown in SEQ ID NO: 524.

[0371] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 465 and the VL sequence shown in SEQ ID NO: 525.

[0372] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 466 and a VL sequence shown in SEQ ID NO: 526.

[0373] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 467 and the VL sequence shown in SEQ ID NO: 527.

[0374] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 468 and a VL sequence shown in SEQ ID NO: 528.

[0375] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 469 and a VL sequence shown in SEQ ID NO: 529.

[0376] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 470 and a VL sequence shown in SEQ ID NO: 528.

[0377] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 471 and a VL sequence shown in SEQ ID NO: 530.

[0378] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 472 and a VL sequence shown in SEQ ID NO: 531.

[0379] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 473 and a VL sequence shown in SEQ ID NO: 532.

[0380] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 474 and a VL sequence shown in SEQ ID NO: 533.

[0381] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 475 and a VL sequence shown in SEQ ID NO: 534.

[0382] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 476 and the VL sequence shown in SEQ ID NO: 535.

[0383] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 477 and the VL sequence shown in SEQ ID NO: 536.

[0384] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 478 and a VL sequence shown in SEQ ID NO: 536.

[0385] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 479 and the VL sequence shown in SEQ ID NO: 537.

[0386] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 480 and a VL sequence shown in SEQ ID NO: 538.

[0387] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 481 and a VL sequence shown in SEQ ID NO: 539.

[0388] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 482 and a VL sequence shown in SEQ ID NO: 539.

[0389] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 483 and a VL sequence shown in SEQ ID NO: 539.

[0390] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 484 and a VL sequence shown in SEQ ID NO: 540.

[0391] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 485 and the VL sequence shown in SEQ ID NO: 541.

[0392] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 486 and a VL sequence shown in SEQ ID NO: 542.

[0393] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 487 and a VL sequence shown in SEQ ID NO: 543.

[0394] In a particular embodiment, the antibody comprises a VH sequence shown in SEQ ID NO: 488 and a VL sequence shown in SEQ ID NO: 544.

[0395] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 818 and the VL sequence shown in SEQ ID NO: 825.

[0396] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 819 and the VL sequence shown in SEQ ID NO: 826.

[0397] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 820 and the VL sequence shown in SEQ ID NO: 827.

[0398] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 821 and the VL sequence shown in SEQ ID NO: 828.

[0399] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 822 and the VL sequence shown in SEQ ID NO: 829.

[0400] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 823 and the VL sequence shown in SEQ ID NO: 830.

[0401] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 824 and the VL sequence shown in SEQ ID NO: 831.

[0402] In a particular embodiment, the antibody comprises the VH sequence shown in SEQ ID NO: 841 and the VL sequence shown in SEQ ID NO: 842.

[0403] In certain embodiments, the antibody comprises one of the above combinations of VH and VL and further comprises a heavy chain containing a human IgG sequence selected from the sequences shown in SEQ ID NOs. 637-737 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto. In certain embodiments, the antibody comprises one of the above combinations of VH and VL and further comprises a heavy chain containing a heavy chain sequence shown in SEQ ID NO. 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto. In a particular embodiment, the antibody comprises one of the above combinations of VH and VL, and further comprises the human light chain sequence shown in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto. In a particular embodiment, the antibody comprises one of the above combinations of VH and VL, and further comprises the heavy chain sequence shown in SEQ ID NO: 651 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and the human light chain sequence shown in SEQ ID NO: 738 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto.

[0404] In some embodiments, the antibodies provided herein include CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 258, 286, and 311; and the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359. The sequence includes CDR-L2 containing an acid sequence, CDR-L3 containing the sequence shown in any one of SEQ ID NOs: 368 and 394, the heavy chain sequence shown in SEQ ID NO: 651 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and the human light chain sequence shown in SEQ ID NO: 738 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto.

[0405] In a particular embodiment, the antibody is a VH containing a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with sequence number 419, a VL containing a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with sequence number 489, The sequence includes the heavy chain sequence shown in Sequence ID No. 651 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and the human light chain sequence shown in Sequence ID No. 738 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto.

[0406] In some embodiments, the antibodies provided herein include CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; and the amino acid sequence shown in any one of SEQ ID NOs: 347 and 365. The molecules include CDR-L2, CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404, the heavy chain sequence shown in SEQ ID NO: 651 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and the human light chain sequence shown in SEQ ID NO: 738 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto.

[0407] In certain embodiments, the antibody is VH containing a sequence of sequence number 841 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, VL containing a sequence of sequence number 842 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto. The sequence includes the heavy chain sequence shown in Sequence ID No. 651 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and the human light chain sequence shown in Sequence ID No. 738 or a sequence having at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto.

[0408] CDR In some embodiments, antibodies comprising one, two, three, four, five, or six of the CDRs from Table 2 or Table 3 are disclosed herein. In some embodiments, six of the Kabat CDRs from Table 2 or Table 3, six of the Chothia CDRs from Table 2 or Table 3, or six of the IMGT CDRs from Table 2 or Table 3 are disclosed herein.

[0409] In some embodiments, the antibodies provided herein contain one to three CDRs of VH domains selected from SEQ ID NOs: 419-488, 818-824, and 840. H The CDR contains two to three domains. In some embodiments, the antibodies provided herein contain three VH domain CDRs selected from SEQ ID NOs: 419-488, 818-824, and 840. In some embodiments, the CDR is an exemplary CDR. In some embodiments, the CDR is a Kabat CDR. In some embodiments, the CDR is a Chothia CDR. In some embodiments, the CDR is an IMGT CDR. In some embodiments, the CDR is an AbM CDR. In some embodiments, the CDR is a Contact CDR.

[0410] In some embodiments, the CDR is a CDR having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with CDR-H1, CDR-H2, or CDR-H3 of SEQ ID NOs. 1-257 and 740-780. In some embodiments, CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs. 419-488, 818-824, and 840, having up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, CDR-H2 is a CDR-H2 of a VH domain selected from SEQ ID NOs. 419-488, 818-824, and 840, having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 419-488, 818-824, and 840, having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0411] In some embodiments, the antibodies provided herein contain one to three CDRs of VH domains selected from SEQ ID NOs: 489-544 and SEQ ID NOs: 825-831. In some embodiments, the antibodies provided herein contain two to three CDRs of VH domains selected from SEQ ID NOs: 489-544 and SEQ ID NOs: 825-831. In some embodiments, the antibodies provided herein contain three CDRs of VH domains selected from SEQ ID NOs: 489-544 and SEQ ID NOs: 825-831. In some embodiments, the CDR is an exemplary CDR. In some embodiments, the CDR is a Kabat CDR. In some embodiments, the CDR is a Chothia CDR. In some embodiments, the CDR is an IMGT CDR. In some embodiments, the CDR is an AbM CDR. In some embodiments, the CDR is a Contact CDR.

[0412] In some embodiments, the CDR is a CDR having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with CDR-L1, CDR-L2, or CDR-L3 of SEQ ID NOs. 258-393 and SEQ ID NOs. 781-811. In some embodiments, CDR-L1 is a CDR-L1 of a VL domain selected from SEQ ID NOs. 489-544 and SEQ ID NOs. 825-831, having up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, CDR-L2 is a CDR-L2 of a VL domain selected from SEQ ID NOs. 489-544 and SEQ ID NOs. 825-831, having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, CDR-L3 is a CDR-L3 of a VL domain selected from SEQ ID NOs: 489-544 and SEQ ID NOs: 825-831, having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0413] In some embodiments, the antibodies provided herein include one to three CDRs of VH domains selected from SEQ ID NOs: 419-488, 818-824, and 840, and one to three CDRs of VL domains selected from SEQ ID NOs: 489-544 and 825-831. In some embodiments, the antibodies provided herein include two to three CDRs of VH domains selected from SEQ ID NOs: 419-488, 818-824, and 840, and two to three CDRs of VL domains selected from SEQ ID NOs: 489-544 and 825-831. In some embodiments, the antibodies provided herein include three CDRs of VH domains selected from SEQ ID NOs: 419-488, 818-824, and 840, and three CDRs of VL domains selected from SEQ ID NOs: 489-544 and 825-831. In some embodiments, the CDRs are exemplary CDRs. In some embodiments, the CDR is a Kabat CDR. In some embodiments, the CDR is a Chothia CDR. In some embodiments, the CDR is an IMGT CDR. In some embodiments, the CDR is an AbM CDR. In some embodiments, the CDR is a Contact CDR.

[0414] In some embodiments, the antibodies provided herein comprise CDR-H3 selected from SEQ ID NOs: 175-257 and 763-780. In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175-257 and 763-780. In some embodiments, CDR-H3 is CDR-H3 selected from SEQ ID NOs: 175-257 and 763-780 having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0415] In some embodiments, the antibodies provided herein comprise CDR-H1 selected from SEQ ID NOs: 1-69, 740-747, and 840. In some embodiments, CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 1-69, 740-747, and 840. In some embodiments, CDR-H1 is CDR-H1 selected from SEQ ID NOs: 1-69, 740-747, and 840 having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0416] In some embodiments, the antibodies provided herein include CDR-H2 selected from SEQ ID NOs: 70-174 and SEQ ID NOs: 748-762. In some embodiments, CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70-174 and SEQ ID NOs: 748-762. In some embodiments, CDR-H2 is CDR-H2 selected from SEQ ID NOs: 70-174 and SEQ ID NOs: 748-762 having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0417] In some embodiments, the antibodies provided herein include CDR-L3 selected from SEQ ID NOs: 268-393 and 806-811. In some embodiments, CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs: 268-393 and 806-811. In some embodiments, CDR-L3 is CDR-L3 selected from SEQ ID NOs: 268-393 and 806-811 having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0418] In some embodiments, the antibodies provided herein include CDR-L2 selected from SEQ ID NOs: 335-367 and 797-805. In some embodiments, CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs: 335-367 and 797-805. In some embodiments, CDR-L2 is CDR-L2 selected from SEQ ID NOs: 335-367 and 797-805 having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0419] In some embodiments, the antibodies provided herein comprise CDR-L1 selected from SEQ ID NOs. 258-334 and SEQ ID NOs. 781-796. In some embodiments, CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 258-334 and SEQ ID NOs. 781-796. In some embodiments, CDR-L1 is CDR-L1 selected from SEQ ID NOs. 258-334 and SEQ ID NOs. 781-796, having up to 1, 2, 3, 4, 5, 6, 7, or 8 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 sequences provided herein by, for example, 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 sequences provided herein and may be newly isolated, for example, according to a method provided herein to obtain an antibody.

[0420] In some embodiments, the antibodies provided herein include CDR-H3 selected from SEQ ID NOs: 175-257 and 763-780, CDR-H2 selected from SEQ ID NOs: 70-174 and 748-762, CDR-H1 selected from SEQ ID NOs: 1-69 and 740-747, CDR-L3 selected from SEQ ID NOs: 268-393 and 806-811, CDR-L2 selected from SEQ ID NOs: 335-367 and 797-805, and CDR-L1 selected from SEQ ID NOs: 258-334 and 781-796. In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 175-257 and SEQ ID NOs. 763-780; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70-174 and SEQ ID NOs. 748-762; CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 1-69 and SEQ ID NOs. 740-747. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 268-393 and 806-811, and CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 335-367 and 797-805. CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 258-334 and 781-796.In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175-257 and 763-780 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70-174 and 748-762 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 1-69 and 740-747 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is a CDR-L3 selected from SEQ ID NOs. 268-393 and 806-811, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is a CDR-L2 selected from SEQ ID NOs. 335-367 and 797-805, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is a CDR-L1 selected from SEQ ID NOs. 258-334 and 781-796, having up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0421] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 258, 286, and 311; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359; and CDR-L3 comprising the sequence shown in any one of SEQ ID NOs: 368 and 394.

[0422] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 17 and 91; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 5, 71, and 79; CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 1, 67, and 187. CDR-L3 has 99% identity, CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 shown in SEQ ID NO: 53, CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs: 41 and 108, and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs: 26 and 100. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 17 and 91 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 5, 71, and 79 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 1, 67, and 187 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from the above, CDR-L3 is CDR-L3 as shown in SEQ ID NO: 53, having up to 1, 2, 3, 4, or 5 amino acid substitutions, CDR-L2 is CDR-L2 selected from SEQ ID NOs: 41 and 108, having up to 1, 2, 3, or 4 amino acid substitutions, and CDR-L1 is CDR-L1 selected from SEQ ID NOs: 26 and 100, having up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0423] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 1, 22, and 44. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 368 and 394; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 335 and 359; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 258, 286, and 311.In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223, having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142, having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 1, 22, and 44, having up to 1, 2, 3, 4, or 5 amino acid substitutions. The selected CDR-H1 is CDR-L3, CDR-L3 is CDR-L3 selected from SEQ ID NOs: 368 and 394, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is CDR-L2 selected from SEQ ID NOs: 335 and 359, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is CDR-L1 selected from SEQ ID NOs: 258, 286, and 311, having up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0424] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 258, 286, and 311; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0425] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 176, 204, and 224; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 2, 23, and 45. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 369 or 395; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 336 or 360; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 259, 287, and 312. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 176, 204, and 224 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions, CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions, and CDR-H1 has up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from SEQ ID NOs: 2, 23, and 45; CDR-L3 is selected from SEQ ID NOs: 369 and 395, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from SEQ ID NOs: 336 and 360, having up to 1, 2, 3, and 4 amino acid substitutions; and CDR-L1 is selected from SEQ ID NOs: 259, 287, and 312.

[0426] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 2, 23, and 45; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 176, 204, and 224; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 259, 287, and 312; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 336 and 360; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 369 and 395.

[0427] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 177, 205, and 225; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 71, 112, and 143; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 3, 24, and 46. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 370 and 396; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 177, 205, and 225 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 71, 112, and 143 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 3, 24, and 46; CDR-L3 is selected from sequence numbers 370 and 396, having a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0428] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 3, 24, and 46; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 71, 112, and 143; CDR-H3 comprising the sequence shown in any one of SEQ ID NOs: 177, 205, and 225; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 370 and 396.

[0429] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 178, 206, and 226; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 72, 113, and 144; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 4, 22, and 47. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 371 and 397; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 261, 289, and 314. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 178, 206, and 226 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 72, 113, and 144 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 4, 22, and 47; CDR-L3 is selected from sequence numbers 371 and 397 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 261, 289, and 314.

[0430] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 261, 289, and 314; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0431] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 179, 207, and 227; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 73, 114, and 145; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 5, 840, and 48. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 372 and 398; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 338 and 362; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 262, 290, and 315. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 179, 207, and 227 having up to 1, 2, 3, 4, 5, 6, 7, and 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 73, 114, and 145 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a sequence having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from numbers 5, 840, and 48; CDR-L3 is selected from sequence numbers 372 and 398 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 338 and 362 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 262, 290, and 315.

[0432] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 73, 114, and 145; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 262, 290, and 315; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 372 and 398.

[0433] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 180, 208, and 228; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 74, 115, and 146; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 6, 24, and 49. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 373 and 399; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 339 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 263, 291, and 316. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 180, 208, and 228 having up to 1, 2, 3, 4, 5, 6, 7, and 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 74, 115, and 146 having up to 1, 2, 3, 4, 5, 6, 7, and 8 amino acid substitutions; and CDR-H1 is a sequence having up to 1, 2, 3, 4, and 5 amino acid substitutions. CDR-H1 is selected from numbers 6, 24, and 49; CDR-L3 is selected from sequence numbers 373 and 399 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 339 and 361 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 263, 291, and 316.

[0434] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 6, 24, and 49; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 74, 115, and 146; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 228; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 263, 291, and 316; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 339 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 373 and 399.

[0435] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 181, 209, and 229; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 75, 116, and 147; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 7, 25, and 50. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 374 and 400; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 340 and 363; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 264, 292, and 317. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 181, 209, and 229 having up to 1, 2, 3, 4, 5, 6, 7, and 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 75, 116, and 147 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 4, 25, and 50; CDR-L3 is selected from sequence numbers 374 and 400, having a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 340 and 363, having a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 264, 292, and 317.

[0436] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 7, 25, and 50; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 75, 116, and 147; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 181, 209, and 229; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 264, 292, and 317; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340 and 363; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

[0437] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 182, 210, and 230; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 375 and 401; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 341 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 182, 210, and 230 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H2 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 8, 26, and 51; CDR-L3 is selected from sequence numbers 375 and 401, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 265, 293, and 318.

[0438] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 182, 210, and 230; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 375 and 401.

[0439] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 183, 211, and 231; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 376 and 402; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 341 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 183, 211, and 231 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 8, 26, and 51; CDR-L3 is selected from sequence numbers 376 and 402, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 265, 293, and 318.

[0440] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 183, 211, and 231; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 376 and 402.

[0441] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 183, 211, and 231; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 377 and 403; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 341 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 183, 211, or 231 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions, CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions, and CDR-H1 has up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from SEQ ID NOs: 8, 26, and 51; CDR-L3 is selected from SEQ ID NOs: 377 and 403, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from SEQ ID NOs: 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from SEQ ID NOs: 265, 293, and 318.

[0442] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 183, 211, and 231; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

[0443] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 184, 212, and 232; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 376 and 402; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 341 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 184, 212, and 232 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 8, 26, and 51; CDR-L3 is selected from sequence numbers 376 and 402, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 265, 293, and 318.

[0444] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 184, 212, and 232; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 376 and 402.

[0445] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 184, 212, and 232; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 377 and 403; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 341 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 184, 212, and 232 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 8, 26, and 51; CDR-L3 is selected from sequence numbers 377 and 403, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 265, 293, and 318.

[0446] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 184, 212, and 232; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

[0447] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 185, 213, and 233; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 376 and 402; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 341 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 185, 213, and 233 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 8, 26, and 51; CDR-L3 is selected from sequence numbers 376 and 402, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 265, 293, and 318.

[0448] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 185, 213, and 233; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 376 and 402.

[0449] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 185, 213, and 233; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 76, 117, and 148; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 8, 26, and 51. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 377 and 403; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 341 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 265, 293, and 318. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 185, 213, and 233 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 76, 117, and 148 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 8, 26, and 51; CDR-L3 is selected from sequence numbers 377 and 403, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 341 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 265, 293, and 318.

[0450] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 185, 213, and 233; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

[0451] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 234; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 77, 118, and 149; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 9, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 368 and 394; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 342 and 364; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 234 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 77, 118, and 149 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H2 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 9, 27, and 52; CDR-L3 is selected from sequence numbers 368 and 394 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 342 and 364 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0452] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 9, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 77, 118, and 149; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 342 and 364; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0453] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 78, 119, and 150; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 1, 28, and 53. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 266, 286, and 311. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 78, 119, and 150 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 1, 28, and 53; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 266, 286, and 311.

[0454] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 28, and 53; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 78, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 266, 286, and 311; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0455] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 186, 203, and 235; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 79, 119, and 150; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 344 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 267, 294, and 319. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 186, 203, and 235 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 79, 119, and 150 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 344 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 267, 294, and 319.

[0456] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 186, 203, and 235; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 267, 294, and 319; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 344 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0457] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 186, 203, and 235; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 80, 120, and 151; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 186, 203, and 235 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 80, 120, and 151 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0458] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 80, 120, and 151; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 186, 203, and 235; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0459] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 79, 119, and 150; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 11, 27, or 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 or 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 79, 119, and 150 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 11, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0460] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 11, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0461] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 81, 121, and 152; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 11, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 81, 121, and 152 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 81, 121, and 152 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 11, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0462] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 11, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 81, 121, and 152; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0463] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 187, 203, and 236; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 80, 120, and 151; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 187, 203, and 236 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 80, 120, and 151 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H2 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0464] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 80, 120, and 151; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 187, 203, and 236; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0465] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 187, 203, and 236; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 79, 119, and 150; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 187, 203, and 236 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 79, 119, and 150 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0466] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 187, 203, and 236; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0467] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 188, 203, and 237; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 368 and 394; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 268, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 237 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 368 and 394, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 268, 288, and 313.

[0468] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 268, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0469] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 188, 203, and 237; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 12, 29, and 54. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 237 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 12, 29, and 54; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0470] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 12, 29, and 54; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0471] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 189, 214, and 238; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 82, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 345 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 269, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 189, 214, and 238 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 82, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 345 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 269, 288, and 313.

[0472] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 82, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 189, 214, and 238; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 345 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0473] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 175, 203, and 234; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 83, 122, and 153; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 346 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 234 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 83, 122, and 153 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 346 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0474] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 83, 122, and 153; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 346 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0475] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 188, 203, and 239; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 84, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 13, 30, and 55. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 239 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 84, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 13, 30, and 55; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0476] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 13, 30, and 55; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 84, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0477] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 175, 203, and 234; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 347 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 234 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 347 and 365 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0478] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 347 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0479] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 175, 203, and 234; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 345 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 234 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 345 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0480] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 345 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0481] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 188, 203, and 239; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 85, 123, and 154; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 239 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 85, 123, and 154 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0482] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 85, 123, and 154; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0483] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 270, 295, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 270, 295, and 313.

[0484] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 270, 295, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0485] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 175, 203, or 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 1, 31, and 56. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 379 and 405; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 1, 31, and 56; CDR-L3 is selected from sequence numbers 379 and 405, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0486] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 31, and 56; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 379 and 405.

[0487] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 86, 124, and 155; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 1, 32, and 57. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 86, 124, and 155 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 1, 32, and 57; CDR-L3 is selected from sequence numbers 378 and 404 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0488] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 32, and 57; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0489] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 380 and 406; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 380 and 406, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0490] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380 and 406.

[0491] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 14, 33, and 58. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 14, 33, and 58; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0492] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 14, 33, and 58; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0493] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 87, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 343 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 343 and 365, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0494] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0495] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 87, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0496] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0497] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 87, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 13, 30, and 55. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 13, 30, and 55; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0498] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 13, 30, and 55; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0499] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 368 and 394; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 368 and 394, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0500] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0501] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 87, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 348 and 366; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 87, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 348 and 366, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0502] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 348 and 366; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0503] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 381 and 405; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 381 and 405 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0504] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 381 and 405.

[0505] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 368 and 394; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 335 and 359; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 368 and 394, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 335 and 359, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0506] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0507] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 86, 124, and 155; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 1, 22, and 44. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 381 and 405; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 86, 124, and 155 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 1, 22, and 44; CDR-L3 is selected from sequence numbers 381 and 405, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0508] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, or 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 381 and 405.

[0509] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 175, 203, and 223; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 86, 124, and 155; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 1, 22, and 44. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 175, 203, and 223 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 86, 124, and 155 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 1, 22, and 44; CDR-L3 is selected from sequence numbers 378 and 404 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0510] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0511] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 188, 203, and 239; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 239 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0512] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0513] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 188, 203, and 237; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 378 and 404; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 237 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 378 and 404, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0514] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

[0515] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 188, 203, and 237; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 78, 119, and 150; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 10, 27, and 52. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 368 and 394; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 188, 203, and 237 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 78, 119, and 150 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H2 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 10, 27, and 52; CDR-L3 is selected from sequence numbers 368 and 394, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0516] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 78, 119, and 150; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

[0517] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 176, 204, and 224; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 70, 111, and 142; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 2, 23, and 45. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 369 and 395; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 336 and 360; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 259, 287, and 312. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 176, 204, and 224 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 70, 111, and 142 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 2, 23, and 45; CDR-L3 is selected from sequence numbers 369 and 395 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 336 and 360 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 259, 287, and 312.

[0518] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 2, 23, and 45; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 176, 204, and 224; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 259, 287, and 312; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 336 and 360; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 369 and 395.

[0519] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 190, 215, and 240; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 88, 125, and 156; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 15, 34, and 59. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 382 and 407; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 349 and 365; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 269, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 190, 215, and 240 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 88, 125, and 156 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 15, 34, and 59; CDR-L3 is selected from sequence numbers 382 and 407 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 349 and 365 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 269, 288, and 313.

[0520] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 15, 34, and 59; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 88, 125, and 156; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 349 and 365; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

[0521] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 178, 206, and 226; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 89, 126, and 157; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 4, 22, and 47. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 371 and 397; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 260, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 178, 206, and 226 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 89, 126, and 157 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H2 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 4, 22, and 47; CDR-L3 is selected from sequence numbers 371 and 397, having a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361, having a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 260, 288, and 313.

[0522] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 89, 126, and 157; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0523] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 178, 206, and 241; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 72, 113, and 144; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 4, 35, and 60. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 371 and 397; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 350 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 271, 296, and 320. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 178, 206, and 241 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 72, 113, and 144 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 4, 35, and 60; CDR-L3 is selected from sequence numbers 371 and 397 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 350 and 361 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 271, 296, and 320.

[0524] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 35, and 60; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 241; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 271, 296, and 320; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 350 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0525] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 178, 206, and 226; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 90, 127, and 158; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 4, 22, and 47. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 371 or 397; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 261, 289, and 314. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 178, 206, and 226 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 90, 127, and 158 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 4, 22, and 47; CDR-L3 is selected from sequence numbers 371 and 397 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 261, 289, and 314.

[0526] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 90, 127, and 158; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 261, 289, and 314; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0527] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 191, 215, and 242; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 91, 128, and 159; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 16, 36, and 61. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from SEQ ID NOs. 382 and 407; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from SEQ ID NOs. 351 or 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from SEQ ID NOs. 269, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 191, 215, and 242 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 91, 128, and 159 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 16, 36, and 61; CDR-L3 is selected from sequence numbers 382 and 407 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 351 and 361 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 269, 288, and 313.

[0528] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 16, 36, and 61; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 91, 128, and 159; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 191, 215, and 242; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

[0529] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 190, 215, and 240; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 91, 128, and 159; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 16, 36, and 61. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 371 and 397; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 351 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 269, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 190, 215, and 240 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 91, 128, and 159 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 16, 36, and 61; CDR-L3 is selected from sequence numbers 371 and 397 and has a maximum of 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 351 and 361 and has a maximum of 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 269, 288, and 313.

[0530] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 16, 36, and 61; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 91, 128, and 159; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

[0531] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 190, 215, and 240; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 72, 113, and 144; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 15, 27, and 62. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 382 and 407; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 337 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 269, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 190, 215, and 240 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 72, 113, and 144 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 15, 27, and 62; CDR-L3 is selected from sequence numbers 382 and 407 and has up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 337 and 361 and has up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 269, 288, and 313.

[0532] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 15, 27, and 62; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

[0533] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 190, 215, and 240; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 72, 113, and 144; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 15, 27, and 62. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 383 and 408; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 351 and 361; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 269, 288, and 313. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 190, 215, and 240 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 72, 113, and 144 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 15, 27, and 62; CDR-L3 is selected from sequence numbers 383 and 408, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 351 and 361, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 269, 288, and 313.

[0534] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 15, 27, and 62; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 383 and 408.

[0535] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 179, 207, and 227; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 92, 129, and 160; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 5, 37, and 63. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 384 and 409; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 338 and 362; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 272, 297, and 321. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 179, 207, and 227 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 92, 129, and 160 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 5, 37, and 63; CDR-L3 is selected from sequence numbers 384 and 409, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 338 and 362, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 272, 297, and 321.

[0536] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 37, and 63; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 92, 129, and 160; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 384 and 409.

[0537] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 179, 207, and 227; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 93, 130, and 161; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 5, 24, and 49. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 384 and 409; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 338 and 362; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 272, 297, and 321. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 179, 207, and 227 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 93, 130, and 161 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H3 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 5, 24, and 49; CDR-L3 is selected from sequence numbers 384 and 409, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 338 and 362, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 272, 297, and 321.

[0538] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 93, 130, and 161; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 384 and 409.

[0539] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs. 192, 207, and 243; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs. 94, 131, and 162; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs. 5, 840, and 48. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 385 and 410; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 338 and 362; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 273, 298, and 322. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 192, 207, and 243 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected from SEQ ID NOs: 94, 131, and 162 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; and CDR-H1 is a CDR-H2 having up to 1, 2, 3, 4, or 5 amino acid substitutions. CDR-H1 is selected from sequence numbers 5, 840, and 48; CDR-L3 is selected from sequence numbers 385 and 410, having up to 1, 2, 3, 4, or 5 amino acid substitutions; CDR-L2 is selected from sequence numbers 338 and 362, having up to 1, 2, 3, or 4 amino acid substitutions; and CDR-L1 is selected from sequence numbers 273, 298, and 322.

[0540] In some embodiments, the antibodies provided herein include CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 192, 207, and 243; CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 273, 298, and 322; CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 385 and 410.

[0541] In some embodiments, CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H3 selected from SEQ ID NOs: 179, 207, and 227; CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H2 selected from SEQ ID NOs: 95, 132, and 163; and CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-H1 selected from SEQ ID NOs: 17, 38, and 64. CDR-L3 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L3 selected from sequence numbers 386 and 411; CDR-L2 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L2 selected from sequence numbers 338 and 362; and CDR-L1 has at least approximately 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with CDR-L1 selected from sequence numbers 272, 297, and 321. In some embodiments, CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 179, 207, and 227 having up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; CDR-H2 is a CDR-H2 selected ...

Claims

1. An isolated antibody that binds to 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. a. CDR-H1 contains the amino acid sequence shown in any one of SEQ ID NOs: 1-69, 740-747, and 840. b. CDR-H2 contains the amino acid sequence shown in any one of SEQ ID NOs: 70-174 and 748-762. c. CDR-H3 contains the amino acid sequence shown in any one of SEQ ID NOs: 175-257 and 763-780. d. CDR-L1 contains the amino acid sequence shown in any one of SEQ ID NOs. 258-334 and 781-796. e. CDR-L2 contains the amino acid sequence shown in any one of SEQ ID NOs: 335-367 and 797-805. f. CDR-L3 is the isolated antibody comprising the amino acid sequence shown in any one of SEQ ID NOs. 268-393 and 806-811.

2. a. CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1-21, 740, and 741, b. CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70-110 and 748-753, c. CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175-202 and 763-768, d. CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs. 258-285 and 781-786, e. CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 335-358 and 797-801, f. An isolated antibody according to claim 1, comprising CDR-L3 having an amino acid sequence shown in any one of SEQ ID NOs: 368-393 and 806-811.

3. a. CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 22-43, 742-744, and 840, b. CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 111-141 and 754-757, c. CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs. 203-222 and 769-774, d. CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 286-310 and 787-791, e. CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 359-367 and 802-805, f. An isolated antibody according to claim 1, comprising CDR-L3 having an amino acid sequence shown in any one of SEQ ID NOs: 394-418 and 812-817.

4. a. CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 44-69 and 745-747, b. CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 142-174 and 758-762, c. CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 223-257 and 775-780, d. CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 311-334 and 792-796, e. CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 359-367 and 802-805, f. An isolated antibody according to claim 1, comprising CDR-L3 having an amino acid sequence shown in any one of SEQ ID NOs: 368-393 and 806-811.

5. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 258, 286, and 311; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 359; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

6. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 2, 23, and 45; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 176, 204, and 224; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 259, 287, and 312; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 336 and 360; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 369 and 395.

7. CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 3, 24, and 46, and SEQ ID NOs: 71, 112, and 143; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 177, 205, and 225; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 370 and 396.

8. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 261, 289, and 314; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

9. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 73, 114, and 145; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 262, 290, and 315; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 372 and 398.

10. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 6, 24, and 49; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 74, 115, and 146; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 228; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 263, 291, and 316; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 339 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 373 and 399.

11. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 7, 25, and 50; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 75, 116, and 147; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 181, 209, and 229; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 264, 292, and 317; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 340 and 363; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

12. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 182, 210, and 230; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 375 and 401.

13. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 183, 211, and 231; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 376 and 402.

14. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 183, 211, and 231; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

15. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 184, 212, and 232; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 376 and 402.

16. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 184, 212, and 232; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

17. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 185, 213, and 233; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 376 and 402.

18. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 76, 117, and 148; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 185, 213, and 233; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 265, 293, and 318; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 377 and 403.

19. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 9, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 77, 118, and 149; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 342 and 364; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

20. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 28, and 53; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 78, 119, and 150; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 266, 286, and 311; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

21. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 186, 203, and 235; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 267, 294, and 319; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 344 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

22. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 80, 120, and 151; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 186, 203, and 235; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

23. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 11, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

24. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 11, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 81, 121, and 152; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

25. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 80, 120, and 151; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 187, 203, and 236; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

26. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 79, 119, and 150; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 187, 203, and 236; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

27. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 268, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

28. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 12, 29, and 54; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

29. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 82, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 189, 214, and 238; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 345 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

30. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 83, 122, and 153; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 346 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

31. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 13, 30, and 55; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 84, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

32. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 347 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

33. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 345 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

34. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 85, 123, and 154; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

35. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 270, 295, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

36. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 31, and 56; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 379 and 405.

37. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 32, and 57; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

38. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 380 and 406.

39. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 14, 33, and 58; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

40. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 343 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

41. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

42. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 13, 30, and 55; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

43. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

44. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 87, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 348 and 366; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

45. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 381 and 405.

46. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 335 and 359; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

47. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 381 and 405.

48. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 1, 22, and 44; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 86, 124, and 155; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

49. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 239; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

50. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

51. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 78, 119, and 150; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 188, 203, and 237; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

52. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 2, 23, and 45; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 176, 204, and 224; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 259, 287, and 312; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 336 and 360; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 369 and 395.

53. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 15, 34, and 59; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 88, 125, and 156; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 349 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

54. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 89, 126, and 157; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

55. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 4, 35, and 60; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 241; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 271, 296, and 320; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 350 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

56. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 4, 22, and 47; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 90, 127, and 158; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 178, 206, and 226; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 261, 289, and 314; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

57. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 16, 36, and 61; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 91, 128, and 159; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 191, 215, and 242; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

58. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 16, 36, and 61; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 91, 128, and 159; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 371 and 397.

59. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 15, 27, and 62; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 382 and 407.

60. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 15, 27, and 62; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 72, 113, and 144; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 190, 215, and 240; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 269, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 351 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 383 and 408.

61. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 37, and 63; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 92, 129, and 160; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 384 and 409.

62. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 93, 130, and 161; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 384 and 409.

63. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 192, 207, and 243; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 273, 298, and 322; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 385 and 410.

64. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 17, 38, and 64; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 95, 132, and 163; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 272, 297, and 321; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 386 and 411.

65. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 96, 130, and 164; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 192, 207, and 243; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 274, 299, and 323; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 386 and 411.

66. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 24, and 49; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 97, 130, and 164; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 179, 207, and 227; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 275, 300, and 324; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 338 and 362; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 386 and 411.

67. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 193, 216, and 244; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 276, 301, and 325; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

68. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 193, 216, and 245; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 277, 302, and 326; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

69. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 194, 217, and 246; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 276, 301, and 325; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

70. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 18, 39, and 65; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 98, 116, and 147; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 194, 217, and 247; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 276, 301, and 325; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 388 and 413.

71. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 19, 40, and 66; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 99, 133, and 165; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 278, 303, and 327; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 352 and 367; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

72. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 20, 41, and 67; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 100, 134, and 166; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 195, 218, and 249; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 279, 304, and 328; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 353 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

73. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 20, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 101, 133, and 167; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 389 and 414.

74. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 102, 135, and 168; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 350 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 389 and 414.

75. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 103, 136, and 169; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 196, 218, and 250; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 354 and 367; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 390 and 415.

76. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 104, 137, and 170; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 197, 208, and 251; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 281, 306, and 330; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

77. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 105, 138, and 171; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 197, 208, and 251; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 281, 306, and 330; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

78. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 198, 219, and 252; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 282, 307, and 331; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 391 and 416.

79. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 20, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 195, 218, and 253; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 355 and 367; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

80. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

81. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 6, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 106, 137, and 170; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 195, 218, and 253; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

82. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 20, 41, and 67; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 107, 133, and 167; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 180, 208, and 248; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 387 and 412.

83. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 108, 139, and 172; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 181, 209, and 229; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 283, 308, and 332; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 356 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

84. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 21, 42, and 68; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 109, 140, and 173; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 199, 220, and 254; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 280, 305, and 329; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

85. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 43, and 69; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 106, 137, and 170; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 200, 221, and 255; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 284, 309, and 333; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 337 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 374 and 400.

86. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 43, and 69; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 94, 131, and 162; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 201, 222, and 256; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 285, 310, and 334; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 357 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 392 and 417.

87. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 43, and 69; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 110, 141, and 174; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 202, 222, and 257; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 285, 310, and 334; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 358 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 393 and 418.

88. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 748, 116, and 758; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 763, 769, and 775; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 781, 787, and 792; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 797 and 802; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 806 and 812.

89. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 740, 742, and 745; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 749, 754, and 759; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 764, 770, and 776; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 782, 788, and 793; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 798 and 803; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 807 and 813.

90. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 17, 743, and 746; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 750, 133, and 165; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 765, 771, and 777; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 783, 298, and 322; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 799 and 804; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 808 and 814.

91. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 5, 840, and 48; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 751, 755, and 760; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 766, 772, and 778; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 784, 789, and 794; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 809 and 815.

92. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 223; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 341 and 361; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 368 and 394.

93. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 8, 26, and 51; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 752, 756, and 761; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 767, 773, and 779; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 785, 790, and 795; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 800 and 805; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 810 and 816.

94. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 741, 744, and 747; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 753, 757, and 762; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 768, 774, and 780; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 786, 791, and 796; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 801 and 360; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 811 and 817.

95. An isolated antibody according to any one of claims 1 to 4, comprising CDR-H1 containing the amino acid sequence shown in any one of SEQ ID NOs: 10, 27, and 52; CDR-H2 containing the amino acid sequence shown in any one of SEQ ID NOs: 70, 111, and 142; CDR-H3 containing the amino acid sequence shown in any one of SEQ ID NOs: 175, 203, and 234; CDR-L1 containing the amino acid sequence shown in any one of SEQ ID NOs: 260, 288, and 313; CDR-L2 containing the amino acid sequence shown in any one of SEQ ID NOs: 347 and 365; and CDR-L3 containing the amino acid sequence shown in any one of SEQ ID NOs: 378 and 404.

96. An isolated antibody according to any one of the prior claims, comprising a heavy chain variable domain (VH) sequence selected from the sequences indicated by SEQ ID NOs: 419-488, 818-824, and 841.

97. An isolated antibody according to any one of the prior claims, comprising a light chain variable domain (VL) sequence selected from the sequences indicated by SEQ ID NOs: 489-544, 825-831, and 842.

98. An isolated antibody according to any one of the prior claims, comprising a VH sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 419-488, 818-824, and 841, and a VL sequence selected from the amino acid sequences shown in any one of SEQ ID NOs: 489-544, 825-831, and 842.

99. An isolated antibody that binds to OX40L, comprising a VH sequence selected from any one of the amino acid sequences shown in SEQ ID NOs: 419-488, 818-824, and 841, and a VL sequence selected from any one of the amino acid sequences shown in SEQ ID NOs: 489-544, 825-831, and 842.

100. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 419 and the VL sequence shown in SEQ ID NO:

489.

101. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 420 and the VL sequence shown in SEQ ID NO:

490.

102. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 421 and the VL sequence shown in SEQ ID NO:

491.

103. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 422 and the VL sequence shown in SEQ ID NO:

492.

104. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 423 and the VL sequence shown in SEQ ID NO:

493.

105. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 424 and the VL sequence shown in SEQ ID NO:

494.

106. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 425 and the VL sequence shown in SEQ ID NO:

495.

107. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 426 and the VL sequence shown in SEQ ID NO:

496.

108. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 427 and the VL sequence shown in SEQ ID NO:

497.

109. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 427 and the VL sequence shown in SEQ ID NO:

498.

110. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 428 and the VL sequence shown in SEQ ID NO:

497.

111. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 428 and the VL sequence shown in SEQ ID NO:

498.

112. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 429 and the VL sequence shown in SEQ ID NO:

497.

113. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 429 and the VL sequence shown in SEQ ID NO:

498.

114. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 430 and the VL sequence shown in SEQ ID NO:

499.

115. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 431 and the VL sequence shown in SEQ ID NO:

500.

116. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 432 and the VL sequence shown in SEQ ID NO:

501.

117. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 433 and the VL sequence shown in SEQ ID NO:

502.

118. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 434 and the VL sequence shown in SEQ ID NO:

502.

119. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 435 and the VL sequence shown in SEQ ID NO:

502.

120. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 436 and the VL sequence shown in SEQ ID NO:

502.

121. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 437 and the VL sequence shown in SEQ ID NO:

502.

122. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 438 and the VL sequence shown in SEQ ID NO:

503.

123. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 439 and the VL sequence shown in SEQ ID NO:

502.

124. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 440 and the VL sequence shown in SEQ ID NO:

504.

125. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 441 and the VL sequence shown in SEQ ID NO:

505.

126. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 442 and the VL sequence shown in SEQ ID NO:

506.

127. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 443 and the VL sequence shown in SEQ ID NO:

507.

128. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 443 and the VL sequence shown in SEQ ID NO:

508.

129. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 444 and the VL sequence shown in SEQ ID NO:

506.

130. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO:

509.

131. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 446 and the VL sequence shown in SEQ ID NO:

510.

132. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 447 and the VL sequence shown in SEQ ID NO:

506.

133. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO:

511.

134. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 448 and the VL sequence shown in SEQ ID NO:

506.

135. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO:

502.

136. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO:

506.

137. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 450 and the VL sequence shown in SEQ ID NO:

506.

138. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO:

512.

139. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 449 and the VL sequence shown in SEQ ID NO:

513.

140. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO:

514.

141. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 445 and the VL sequence shown in SEQ ID NO:

515.

142. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 451 and the VL sequence shown in SEQ ID NO:

514.

143. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 451 and the VL sequence shown in SEQ ID NO:

506.

144. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 452 and the VL sequence shown in SEQ ID NO:

506.

145. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 438 and the VL sequence shown in SEQ ID NO:

506.

146. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 453 and the VL sequence shown in SEQ ID NO:

512.

147. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 454 and the VL sequence shown in SEQ ID NO:

490.

148. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 455 and the VL sequence shown in SEQ ID NO:

516.

149. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 456 and the VL sequence shown in SEQ ID NO:

517.

150. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 457 and the VL sequence shown in SEQ ID NO:

518.

151. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 458 and the VL sequence shown in SEQ ID NO:

492.

152. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 459 and the VL sequence shown in SEQ ID NO:

519.

153. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 460 and the VL sequence shown in SEQ ID NO:

520.

154. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 461 and the VL sequence shown in SEQ ID NO:

521.

155. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 461 and the VL sequence shown in SEQ ID NO:

522.

156. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 461 and the VL sequence shown in SEQ ID NO:

522.

157. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 462 and the VL sequence shown in SEQ ID NO:

523.

158. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 463 and the VL sequence shown in SEQ ID NO:

523.

159. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 464 and the VL sequence shown in SEQ ID NO:

524.

160. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 465 and the VL sequence shown in SEQ ID NO:

525.

161. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 466 and the VL sequence shown in SEQ ID NO:

526.

162. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 467 and the VL sequence shown in SEQ ID NO:

527.

163. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 468 and the VL sequence shown in SEQ ID NO:

528.

164. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 469 and the VL sequence shown in SEQ ID NO:

529.

165. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 470 and the VL sequence shown in SEQ ID NO:

528.

166. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 471 and the VL sequence shown in SEQ ID NO:

530.

167. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 472 and the VL sequence shown in SEQ ID NO:

531.

168. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 473 and the VL sequence shown in SEQ ID NO:

532.

169. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 474 and the VL sequence shown in SEQ ID NO:

533.

170. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 475 and the VL sequence shown in SEQ ID NO:

534.

171. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 476 and the VL sequence shown in SEQ ID NO:

535.

172. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 477 and the VL sequence shown in SEQ ID NO:

536.

173. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 478 and the VL sequence shown in SEQ ID NO:

536.

174. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 479 and the VL sequence shown in SEQ ID NO:

537.

175. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 480 and the VL sequence shown in SEQ ID NO:

538.

176. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 481 and the VL sequence shown in SEQ ID NO:

539.

177. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 482 and the VL sequence shown in SEQ ID NO:

539.

178. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 483 and the VL sequence shown in SEQ ID NO:

539.

179. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 484 and the VL sequence shown in SEQ ID NO:

540.

180. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 485 and the VL sequence shown in SEQ ID NO:

541.

181. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 486 and the VL sequence shown in SEQ ID NO:

542.

182. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 487 and the VL sequence shown in SEQ ID NO:

543.

183. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 488 and the VL sequence shown in SEQ ID NO:

544.

184. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 818 and the VL sequence shown in SEQ ID NO:

825.

185. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 819 and the VL sequence shown in SEQ ID NO:

826.

186. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 820 and the VL sequence shown in SEQ ID NO:

827.

187. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 821 and the VL sequence shown in SEQ ID NO:

828.

188. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 822 and the VL sequence shown in SEQ ID NO:

829.

189. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 823 and the VL sequence shown in SEQ ID NO:

830.

190. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 824 and the VL sequence shown in SEQ ID NO:

831.

191. An isolated antibody according to claim 98 or 99, comprising the VH sequence shown in SEQ ID NO: 841 and the VL sequence shown in SEQ ID NO:

842.

192. An isolated antibody according to any one of the prior claims, which is a humanized antibody, a human antibody, or a chimeric antibody.

193. An isolated antibody according to any one of the prior claims, which is a humanized antibody.

194. An isolated antibody according to any one of the prior claims, comprising a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

195. The isolated antibody according to any one of the prior claims, wherein the human Fc region comprises a human heavy chain constant region of the IgG class and a subclass selected from IgG1, IgG2, IgG3, and IgG4.

196. The isolated antibody according to claim 195, wherein the human Fc region comprises human IgG1 Fc.

197. The isolated antibody according to claim 195, wherein the human Fc region comprises human IgG4 Fc.

198. The isolated antibody according to claim 195, wherein the human Fc region comprises human IgG2 Fc.

199. The isolated antibody according to any one of the prior claims, wherein the heavy chain comprises a constant heavy chain sequence selected from the sequences shown in SEQ ID NOs: 637 to 737.

200. The isolated antibody according to any one of the prior claims, wherein the light chain comprises the constant light chain sequence shown in Sequence ID No.

738.

201. The isolated antibody according to any one of the prior claims, wherein the Fc region comprises one or more amino acid substitutions, and the one or more substitutions result in an increase in one or more of the antibody half-life, ADCC activity, ADCP activity, or CDC activity compared to the Fc region without the one or more substitutions.

202. The isolated antibody according to any one of claims 1 to 198, wherein the Fc region comprises one or more amino acid substitutions, and the one or more substitutions result in a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared to an antibody containing a wild-type Fc region.

203. The one or more amino acid substitutions are selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W, and in some cases, the one or more amino acid substitutions are 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, L234A / L235A, M428L / N434A23442223722342 2377.2342234 2017, 2465, 145, ALA / YTE、LAGAYTE、66 A9A / TE、;A;,7 / !E、 82977.2652.

265. / A / T、LA;AG / 6S、LA 2019772426 The The A / / DHSSS / 6EE600EE / TE、S\ / TS、S:E / 6SS / / DHS、S,6 / D00、8297 A / A、D265A / LA、;;; / : The / ALAPG / 0A、829778434 AD2266A / 8434A、:A6 843442、,23442 3.344.2000 342、82977294347、4265 844347、,2347、 / AGA / / 444W、LA4A7 / / 4 347、,12,200194747、82 97.265.

244. / DQ、LAGA / QQ DQ、LAQAPM / QQ、82977 / D 7、42657、,267、 / AGA / DW、LA,7W / WW、6A 47,829,700,000 65, 21, 100, 100,000,000 D、:A,AG, / (,4A0000 / 14、43007444311166:23786 (#66)、82977:466、42656 66、LA0AQQ66、L6MMMQV6,000 2.66、,2666、4426 6、82977266、426526 6、,266、,271666 、LAPAG / DD266B DRVF ( ) ( ) ( ) ( ) () The 2000-year-old woman was born in 2000.

204. The isolated antibody according to any one of the prior claims, wherein the Fc region binds to the fetal Fc receptor (FcRn).

205. The isolated antibody according to claim 202, wherein the Fc region binds to FcRn with higher affinity at pH 6.0 compared to an antibody containing a wild-type Fc region.

206. The Fc region is 1 × 10 at pH 6.

0. －７ K less than M Ｄ The isolated antibody according to claim 202 or 203, which binds to FcRn.

207. An isolated antibody according to any one of the prior claims, which is a monoclonal antibody.

208. An isolated antibody according to any one of the prior claims, which binds to the OX40L sequence shown in Sequence ID No.

739.

209. An isolated antibody according to any one of the prior claims, for use in the treatment of an inflammatory disorder or disease.

210. An isolated antibody according to claim 209 for use in the treatment of atopic dermatitis (AD).

211. The isolated antibody according to claim 210, wherein the treatment reduces the severity of the disease in the patient, and the severity of the disease is assessed by a disease severity outcome scale for atopic dermatitis.

212. An isolated antibody according to claim 209 for use in the treatment of asthma.

213. An isolated antibody according to claim 209 for use in the treatment of chronic sinusitis with nasal polyps.

214. An isolated antibody according to claim 209 for use in the treatment of chronic sinusitis without nasal polyps (CRSsNP).

215. An isolated antibody according to claim 209 for use in the treatment of eosinophilic esophagitis (EoE).

216. An isolated antibody according to claim 209 for use in the treatment of an eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), eosinophilic colitis (EoC), and eosinophilic gastroenteritis (EGE).

217. An isolated antibody according to claim 209 for use in the treatment of Churg-Strauss syndrome / eosinophilic granulomatosis with polyangiitis (EGPA).

218. An isolated antibody according to claim 209 for use in the treatment of nodular prurigo (PN).

219. An isolated antibody according to claim 209 for use in the treatment of chronic urticaria subitum (CSU).

220. An isolated antibody according to claim 209 for use in the treatment of chronic pruritus of unknown cause (CPUO).

221. An isolated antibody according to claim 209 for use in the treatment of bullous pemphigoid (BP).

222. An isolated antibody according to claim 209 for use in the treatment of cold-induced urticaria (ColdU).

223. An isolated antibody according to claim 209 for use in the treatment of allergic fungal rhinosinusitis (AFRS).

224. An isolated antibody according to claim 209 for use in the treatment of allergic bronchopulmonary aspergillosis (ABPA).

225. An isolated antibody according to claim 209 for use in the treatment of chronic obstructive pulmonary disease (COPD).

226. An isolated antibody according to claim 209 for use in the treatment of Crohn's disease.

227. An isolated antibody according to claim 209 for use in the treatment of lupus.

228. An isolated antibody according to claim 209 for use in the treatment of rheumatoid arthritis (RA).

229. An isolated antibody according to claim 209 for use in the treatment of psoriasis.

230. An isolated antibody according to claim 209 for use in the treatment of ulcerative colitis.

231. An isolated antibody according to claim 209 for use in the treatment of hidradenitis suppurativa.

232. An isolated antibody according to claim 209 for use in the treatment of celiac disease.

233. An isolated antibody according to claim 209 for use in the treatment of systemic sclerosis.

234. An isolated polynucleotide or group of polynucleotides encoding an antibody according to any one of the prior claims, its VH, its VL, its light chain, its heavy chain, or its antigen-binding portion, wherein the polynucleotide or group of polynucleotides optionally includes cDNA.

235. A vector or group of vectors comprising a polynucleotide or group of polynucleotides as described in claim 234.

236. A host cell comprising a polynucleotide or group of polynucleotides as described in claim 231, or a vector or group of vectors as described in claim 235.

237. A method for producing an antibody, comprising expressing the antibody having a host cell as described in claim 236, and isolating the expressed antibody.

238. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 206 and a pharmaceutically acceptable excipient.

239. A kit comprising an antibody according to any one of claims 1 to 206 or a pharmaceutical composition according to claim 238, and instructions for use.

240. A method for treating an inflammatory disorder or disease in a mammal requiring treatment of an inflammatory disorder or disease, comprising administering to the mammal an effective amount of an antibody according to any one of claims 1 to 206 or a pharmaceutical composition according to claim 238.

241. The method according to claim 240, wherein the mammal subject is a human.

242. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is atopic dermatitis.

243. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is asthma.

244. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is chronic sinusitis with nasal polyps.

245. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is chronic sinusitis without nasal polyps (CRSsNP).

246. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is eosinophilic esophagitis (EoE).

247. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is an eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), eosinophilic colitis (EoC), and eosinophilic gastroenteritis (EGE).

248. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is Churg-Strauss syndrome / eosinophilic granulomatosis with polyangiitis (EGPA).

249. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is nodular prurigo (PN).

250. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is chronic urticaria immobile (CSU).

251. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is chronic pruritus of unknown cause (CPUO).

252. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is bullous pemphigoid (BP).

253. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is cold-induced urticaria (ColdU).

254. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is allergic fungal rhinosinusitis (AFRS).

255. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is allergic bronchopulmonary aspergillosis (ABPA).

256. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is chronic obstructive pulmonary disease (COPD).

257. The method according to claim 240 or 241, wherein the inflammatory disorder or disease is celiac disease.

258. A method for treating a condition in a mammal requiring treatment for an elevated OX40L level, comprising administering to the mammal an effective amount of the antibody described in any one of claims 1 to 206 or the pharmaceutical composition described in claim 238.

259. A method for reducing the biological activity of OX40L in a mammalian subject requiring a reduction in its biological activity, the method comprising administering to the mammalian subject a therapeutically effective amount of the antibody according to any one of claims 1 to 206 or the pharmaceutical composition according to claim 238.

260. A method for treating an inflammatory disorder or disease in a mammal requiring treatment of an inflammatory disorder or disease, comprising administering to the mammal a therapeutically effective amount of an antibody according to any one of claims 1 to 206 or a pharmaceutical composition according to claim 238.

261. The method according to any one of claims 258 to 260, wherein the mammal subject is a human.

262. The method according to claim 261, wherein the antibody can inhibit OX40L-dependent IFNγ release in humans.

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