Anti-CD30l antibodies and uses thereof

Abstract

To provide antibodies for targeted therapies available to IBD patients, especially those patients who may be non-responsive or lose response to existing IBD therapies.SOLUTION: The present invention provides an antibody or antigen binding fragment thereof that binds to CD30L, wherein the antibody or antigen binding fragment thereof comprises CDR-H1 comprising a specific amino acid sequence, CDR-H2 comprising a specific amino acid sequence, CDR-H3 comprising a specific amino acid sequence, CDR-L1 comprising a specific amino acid sequence, CDR-L2 comprising a specific amino acid sequence, and / or CDR-L3 comprising a specific amino acid sequence.SELECTED DRAWING: Figure 1-1

Description

[Technical Field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 150,373, filed February 17, 2021, which is incorporated herein by reference in its entirety.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in ASCII format, which is incorporated herein by reference in its entirety. The ASCII copy, created on February 14, 2022, is named 56884-786_601_SL.txt and is 256,626 bytes in size. [Background technology]

[0003] 1. Background technology Autoimmune diseases develop when immune tolerance to self-reactive immune cells breaks down, causing the immune system to attack self-molecules. Many autoimmune disorders are strongly associated with genetic, infectious, and / or environmental predispositions and result in multiple disorders and symptoms ranging from organ-specific to systemic dysfunction. Inflammatory bowel disease (IBD) refers to a group of intestinal disorders that cause inflammatory conditions in the digestive tract. The main types of IBD are ulcerative colitis (UC) and Crohn's disease (CD). These diseases are common, with approximately 1.86 million people diagnosed with UC and approximately 1.3 million people diagnosed with CD worldwide. Severe forms of IBD can result in or be characterized by intestinal fibrosis, which leads to the accumulation of scar tissue in the intestinal wall. The pathogenesis of IBD is thought to involve an uncontrolled immune response, and certain environmental factors may trigger such an immune response in genetically susceptible hosts. The heterogeneity in disease etiology and clinical course, combined with the variable response to treatment and its associated side effects, suggests that targeted therapeutic approaches are a desirable strategy for treating these diseases. However, very few targeted therapies are available for IBD patients, especially those who are non-responsive or at risk of losing their response to existing IBD treatments. Summary of the Invention

[0004] 2. Summary of the invention Provided herein are antibodies that bind to CD30 ligand (also referred to as CD30L, CD153, and TNFSF8) and are useful for treating autoimmune disorders, such as IBD. Generally, in certain embodiments, the antibodies described herein inhibit the interaction between CD30L and CD30, effectively reducing, inhibiting, or preventing immune activation (e.g., inflammatory responses). Furthermore, the anti-CD30L antibodies described herein possess properties useful for therapeutic applications, including, for example, reduced and / or hypoimmunogenicity. The antibodies described herein inhibit the expression / secretion of certain inflammatory cytokines (e.g., interleukin-6 and interleukin-8), which play important roles in inflammatory and autoimmune diseases, such as inflammatory bowel disease, Crohn's disease, and ulcerative colitis.

[0005] Thus, in one embodiment, the present specification provides an antibody or antigen-binding fragment that binds to CD30L, the antibody or antigen-binding fragment comprising: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; or (c) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743. (d) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; (d) an immunoglobulin light chain CDR2 (CDR-L2) comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and / or (e) an immunoglobulin light chain CDR3 (CDR-L3) comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.

[0006] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 109, 628, 635, and 712 to 723; (b) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 149, 642, 649, and 724 to 735; or (c) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 189, 656, 663, and 736 to 743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 309, 670, 677, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 349, 684, 691, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 389, 698, 705, and 760 to 765.

[0007] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 105-109, 628, 635, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 145-149, 642, 649, and 724-735; or (c) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 185-189, 656, 663, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 305 to 309, 670, 677, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 345 to 349, 684, 691, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 385 to 389, 698, 705, and 760 to 765.

[0008] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to CD30L, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO:34.

[0009] In some embodiments, the antibody or antigen-binding fragment thereof is selected from the group consisting of: (i) any one amino acid in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64; (ii) any two amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64; (iii) any three amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64; (iv) K16 , S21, R30, K48, R63 and Y64; (ii) any four amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63 and Y64; or (ii) any five amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63 and Y64; or (ii) K16, S21, R30, K48, R63 and Y64 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO:34.

[0010] In some embodiments, the antibody or antigen-binding fragment thereof binds to an epitope comprising K16 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 34. In some embodiments, the epitope further comprises S21 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 34. In some embodiments, the epitope further comprises R30 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 34. In some embodiments, the epitope further comprises K48 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 34. In some embodiments, the epitope further comprises R63 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 34. In some embodiments, the epitope further comprises Y64 in CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 34.

[0011] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 110 to 119, 629, 636, and 712 to 723; (b) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 150 to 159, 643, 650, and 724 to 735; or (c) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 190 to 199, 657, 664, and 736 to 743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 310 to 319, 671, 678, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 350 to 359, 685, 692, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 390 to 399, 699, 706, and 760 to 765.

[0012] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 115-119, 629, 636, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 155-159, 643, 650, and 724-735; or (c) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 195-199, 657, 664, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 315 to 319, 671, 678, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 355 to 359, 685, 692, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 395 to 399, 699, 706, and 760 to 765.

[0013] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 120-129 and 712-723; (b) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 160-169 and 724-735; (c) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 200-209 and 736-743; (d) a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 320-329 and 744-751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 360-369 and 752-759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 400-409 and 760-765.

[0014] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 125-129 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 165-169 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 205-209 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 325-329 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 365-369 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 405-409 and 760-765.

[0015] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 130-139 and 712-723; (b) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 170-179 and 724-735; (c) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 210-219 and 736-743; (d) a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 330-339 and 744-751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 370-379 and 752-759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 410-419 and 760-765.

[0016] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 130 to 134; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 170 to 174; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 210 to 214; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 330 to 334; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 370 to 374; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 410 to 414.

[0017] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 135-139 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 175-179 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 215-219 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 335-339 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 375-379 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 415-419 and 760-765.

[0018] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 220-224 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 235-239 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 250-254 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 420-424 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 435-439 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 450-454 and 760-765.

[0019] In some embodiments, the antibody or antigen-binding fragment thereof comprises an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein (a) the immunoglobulin variable region heavy chain (VH) comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 17, and / or (b) the immunoglobulin variable region light chain (VL) comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 18.

[0020] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 225-229 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 240-244 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 255-259 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 425-429 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 440-444 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 455-459 and 760-765.

[0021] In some embodiments, the antibody or antigen-binding fragment thereof comprises an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein (a) the VH comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 19, and / or (b) the VL comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 20.

[0022] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 230-234 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 245-249 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 260-264 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 430-434 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 445-449 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 460-464 and 760-765.

[0023] In some embodiments, the antibody or antigen-binding fragment thereof comprises an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein (a) the VH comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 21, and / or (b) the VL comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 22.

[0024] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 465-469, 631, 638, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 490-494, 645, 652, and 724-735; or (c) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 528-532, 659, 666, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 553 to 557, 673, 680, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 578 to 582, 687, 694, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 603 to 607, 701, 708, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 470-474, 632, 639, and 712-723; (b) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 495-499, 646, 653, and 724-735; or (c) a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 533-537, 660, 667, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 558 to 562, 674, 681, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 583 to 587, 688, 695, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 608 to 612, 702, 709, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 475-479, 633, 640, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 513-517, 647, 654, and 724-735; or (c) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 538-542, 661, 668, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 563 to 567, 675, 682, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 588 to 592, 689, 696, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 613 to 617, 703, 710, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 480-484, 630, 637, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 518-522, 644, 651, and 724-735; or (c) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 543-547, 658, 665, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 568 to 572, 672, 679 and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 593 to 597, 686, 693 and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 618 to 622, 700, 707 and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 485-489, 634, 641, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 523-527, 648, 655, and 724-735; or (c) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 548-552, 662, 669, and 736-743. (d) CDR-L1 having an amino acid sequence set forth in any one of SEQ ID NOs: 573 to 577, 676, 683, and 744 to 751; (e) CDR-L2 having an amino acid sequence set forth in any one of SEQ ID NOs: 598 to 602, 690, 697, and 752 to 759; and / or (f) CDR-L3 having an amino acid sequence set forth in any one of SEQ ID NOs: 623 to 627, 704, 711, and 760 to 765.

[0025] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724 to 735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712, 714, 716, 718, 720, and 722; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724, 726, 728, 730, 732, and 734; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736, 738, 740, and 742; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744, 746, 748, and 750; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752, 754, 756, and 758; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760, 762, and 764.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 713, 715, 717, 719, 721, and 723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 725, 727, 729, 731, 733, and 735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 737, 739, 741, and 743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 745, 747, 749, and 751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 753, 755, 757, and 759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 761, 763, and 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 712, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 730, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (v) (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 713, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 731, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 712, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 724, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 713, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 725, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 714, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 726, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 715, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 727, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 716, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 728, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 717, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 729, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 718, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 730, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 738, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 746, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 754, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 762. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 719, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 731, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 739, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 747, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 755, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 763.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 720, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 732, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 740, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 748, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 756, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 721, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 733, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 741, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 749, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 757, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 722, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 734, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 742, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 750, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 758, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 764. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 723, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 735, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 743, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 751, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 759, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 765.

[0026] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 635, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 649, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 663, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 677, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 691, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 705. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 107, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 147, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 187, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 307, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 347, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 387. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 105, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 145, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 185, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 305, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 345, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 385. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 106, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 146, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 186, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 306, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 346, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 386.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 108, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 148, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 188, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 308, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 348, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 388. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 109, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 149, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 189, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 309, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 349, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 389. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 628, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 642, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 656, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 670, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 684, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 698.

[0027] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 636, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 650, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 664, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 678, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 692, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 706. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 117, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 157, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 197, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 317, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 357, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 397. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 115, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 155, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 195, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 315, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 355, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 395. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 116, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 156, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 196, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 316, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 356, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 396.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 118, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 158, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 198, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 318, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 358, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 398. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 159, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 199, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 319, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 359, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 399. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 629, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 643, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 657, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 671, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 685, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 699.

[0028] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 637, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 651, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 665, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 679, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 693, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 707. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 482, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 520, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 545, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 570, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 595, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 620. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 480, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 518, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 543, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 568, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 593, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 618. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 481; (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 519; (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 544; (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 569; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 594; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 619.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 483, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 521, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 546, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 571, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 596, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 621. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 484, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 522, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 547, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 572, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 597, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 622. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 630, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 644, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 658, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 672, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 686, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 700.

[0029] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 638, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 652, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 666, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 680, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 694, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 708. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 467, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 492, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 530, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 555, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 580, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 605. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 465, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 490, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 528, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 553, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 578, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 603. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 466, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 491, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 529, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 554, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 579, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 604.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 468, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 493, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 531, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 556, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 581, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 606. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 469, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 494, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 532, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 557, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 582, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 607. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 631; (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 645; (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 659; (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 673; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 687; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 701.

[0030] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 639, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 653, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 667, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 681, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 695, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 709. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 472, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 497, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 535, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 560, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 585, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 610. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 470, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 495, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 533, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 558, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 583, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 608. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 471; (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 496; (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 534; (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 559; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 584; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 609.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 473, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 498, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 536, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 561, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 586, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 611. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 474, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 499, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 537, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 562, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 587, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 612. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 632, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 646, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 660, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 674, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 688, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 702.

[0031] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 640, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 654, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 668, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 682, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 696, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 710. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 477, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 515, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 540, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 565, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 590, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 615. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 475, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 513, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 538, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 563, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 588, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 613. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 476, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 514, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 539, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 564, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 589, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 614.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 478, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 516, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 541, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 566, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 591, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 616. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 479, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 517, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 542, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 567, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 592, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 617. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 633, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 647, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 661, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 675, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 689, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 703.

[0032] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 641, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 655, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 669, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 683, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 711. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 487, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 525, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 550, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 575, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 600, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 625. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 485, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 523, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 548, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 573, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 598, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 623. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 486, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 524, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 549, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 574, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 599, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 624.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 488, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 526, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 551, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 576, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 601, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 626. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 489, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 527, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 552, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 577, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 602, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 627. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 634, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 648, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 662, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 676, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 690, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 704.

[0033] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin variable region heavy chain (VH) comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 1, 2, 5, 6, 9, 10, 13, 14, 17, 19, 21, 23, 25, 27, 29, and 31; and / or (b) an immunoglobulin variable region light chain (VL) comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 3, 4, 7, 8, 11, 12, 15, 16, 18, 20, 22, 24, 26, 28, and 30. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 1, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 3. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 2, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 4. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 5, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 7. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 6, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 8.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 9, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 10, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 12. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 13, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 15. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 14, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 16. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 23, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 24. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 25, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 26.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 27, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 28. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 29, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 30. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 31, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 32.

[0034] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1, 2, 5, 6, 9, 10, 13, 14, 17, 19, 21, 23, 25, 27, 29, and 31, and / or (b) a VL comprising the amino acid sequence set forth in any one of SEQ ID NOs: 3, 4, 7, 8, 11, 12, 15, 16, 18, 20, 22, 24, 26, 28, and 30. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 1, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 2, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 4. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:5, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO:7. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:6, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO:8. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:9, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO:11. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:10, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO:12. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:13, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO:15. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 14, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 16. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 23, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 24.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 25, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 27, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 28. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 29, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 30. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 31, and / or (a) a VL comprising the amino acid sequence set forth in SEQ ID NO: 32.

[0035] In some embodiments, the antibody or antigen-binding fragment thereof further comprises an IgG constant region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises an IgG constant region with reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG and / or reduced complement-dependent cytotoxicity (CDC) compared to human IgG. In some embodiments, the constant region comprises an amino acid sequence having 80, 85, 90, 95, 97, 98, 99, or 100% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 500 to 512. In some embodiments, the constant region comprises the amino acid sequence set forth in any one of SEQ ID NOs: 500 to 512.

[0036] In some embodiments, the antibody or antigen-binding fragment thereof is selected from the group consisting of: (a) 297A, 297Q, 297G, or 297D, (b) 279F, 279K, or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R, or 235S, (e) 237A, 237E, 237K, 237N, or 237R, (f) 234A, 234V, or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R (k), according to EU numbering. 331S, (l) 236F or 236R, (m) 238A, 238E, 238G, 238H, 238I, 238V, 238W, or 238Y, (n) 248A, (o) 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, or 254V, (p) 255N, (q) 256H, 256K, 256R, or 256V, (r) 264S, (s) 265H, 265K, 265S, 265Y, or 265A, (t) 267G, 267H, 267I, or 267K, (u) 268K, (v) 26 9N or 269Q, (w) 270A, 270G, 270M, or 270N, (x) 271T, (y) 272N, (z) 292E, 292F, 292G, or 292I, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 311E, 311G, or 311S, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii) 343I or 343V, (jj) 373A, 373G, or 373S, (kk) 376E, 376W, or 376Y, (ll) 380 D, (mm) 382D or 382P, (nn) 385P, (oo) 424H, 424M, or 424V, (pp) 434I, (qq) 438G, (rr) 439E, 439H, or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T, or 440V, (tt) E233P, (uu) L235E, (vv) L234A and L235A, (ww) L234A, L235A, and G237A, (xx) L234A, L235A, and P329G, (yy) L234F, L235E, and P331S,(zz)L234A, L235E, and G237A, (aaa), L234A, L235E, G237A, and P331S (bbb)L234A, L235A, G237A, P238S, H268A, A330S, and P331S, (ccc)L234A, L235A, and P329A, (ddd)G236R and L328R, (eee)G237A, (fff (iii) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) any combination of (a) to (mmm).

[0037] In some embodiments, the antibody or antigen-binding fragment thereof is an IgG antibody. In some embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4.

[0038] In some embodiments, the antibody or antigen-binding fragment thereof is human, chimeric, or humanized.

[0039] In some embodiments, the antigen-binding fragment is a Fab, F(ab')2, a single domain antibody, or a single-chain variable fragment (scFv).

[0040] In some embodiments, the antibody or antigen-binding fragment thereof binds to one or more amino acid residues of CD30L that interact with CD30.

[0041] In some embodiments, the antibody or antigen-binding fragment thereof inhibits the binding interaction between CD30L and CD30. In some embodiments, the antibody or antigen-binding fragment thereof blocks the binding interaction between CD30L and CD30. In some embodiments, inhibition or blocking is determined in an ELISA assay, a cell binding assay using CD30L-expressing cells, or a surface plasmon resonance (SPR) assay.

[0042] In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to CD30L.

[0043] In some embodiments, the antibody or antigen-binding fragment thereof (i) inhibits secretion of interleukin-8 in a cell-based assay, (ii) inhibits secretion of interleukin-6 in a cell-based assay, or (iii) both (i) and (ii). In some embodiments, the antibody or antigen-binding fragment thereof (i) blocks secretion of interleukin-8 in a cell-based assay, (ii) blocks secretion of interleukin-6 in a cell-based assay, or (iii) both (i) and (ii). In some embodiments, the cell-based assay is a dual cell assay using cells expressing CD30 and cells expressing CD30L.

[0044] In some embodiments, the antibody or antigen-binding fragment thereof binds to (i) human CD30L, (ii) cynomolgus CD30L, or (iii) both human CD30L and cynomolgus CD30L.

[0045] In some embodiments, the antibody or antigen-binding fragment thereof has a dissociation equilibrium constant (K) of 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 pM or less. D In some embodiments, the antibody or antigen-binding fragment thereof binds to CD30L at a concentration of at least 0.1 x 10 6 , 0.2 × 10 6 , 0.3×10 6 , 0.4×10 6 , 0.5×10 6 , 0.6×10 6 , 0.7×10 6 , 0.8×10 6 , 0.9×10 6 , 1.0×10 6 , 1.1×10 6 , 1.2 × 10 6, 1.3 × 10 6 , 1.4×10 6 , 1.5×10 6 or 1.55 x 10 6 M -1 S -1 The binding rate constant (k on In some embodiments, the antibody or antigen-binding fragment thereof binds to CD30L at a concentration of 1.4 x 10 -4 , 1.41×10 -4 , 1.5×10 -4 , 1.6×10 -4 , 1.7×10 -4 , 1.8×10 -4 , 1.9×10 -4 , 2.0×10 -4 , 2.1×10 -4 , 2.2 × 10 -4 , 2.3 × 10 -4 , 2.4 × 10 -4 , 2.5×10 -4 , 2.6×10 -4 , 2.7 × 10 -4 , 2.8×10 -4 , 2.9 × 10 -4 , 3.0×10 -4 , 3.1 × 10 -4 , 3.2 × 10 -4 , 3.3 × 10 -4 , 3.4 × 10 -4 , or 3.5 × 10 -4 S -1 The dissociation rate constant (k off ) binds to CD30L.

[0046] In some embodiments, the antibody or antigen-binding fragment thereof is a recombinant antibody or antigen-binding fragment thereof.

[0047] In some embodiments, the antibody or antigen-binding fragment thereof is an isolated antibody or antigen-binding fragment thereof.

[0048] In one aspect, the present specification provides an antibody and / or antigen-binding fragment that binds to CD30L, the antibody or antigen-binding fragment comprising: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139 or 220 to 234; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179 or 235 to 249; (c) an immunoglobulin heavy chain CDR3 (CDR-H4) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219 or 250 to 264; (d) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339 or 420 to 434; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379 or 435 to 449; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419 or 450 to 464.

[0049] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100-109; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140-149; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180-189; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-309; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-349; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-389.

[0050] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100-104; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140-144; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180-184; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-304; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-344; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-384.

[0051] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 105-109; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 145-149; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 185-189; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 305-309; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 345-349; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 385-389.

[0052] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 1 and 2, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 3 and 4.

[0053] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 110-119; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 150-159; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 190-199; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 310-319; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 350-359; and / or (e) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 390-399.

[0054] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 110 to 114; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 150 to 154; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 190 to 194; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 310 to 314; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 350 to 354; and / or (e) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 390 to 394.

[0055] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 115-119; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 155-159; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 195-199; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 315-319; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 355-359; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 395-399.

[0056] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 5 and 6, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 7 and 8.

[0057] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 120 to 129; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 160 to 169; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 200 to 209; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 320 to 329; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 360 to 369; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 400 to 409.

[0058] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 120 to 124; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 160 to 164; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 200 to 204; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 320 to 324; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 360 to 364; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 400 to 404.

[0059] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 125-129; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 165-169; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 205-209; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 325-329; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 365-369; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 405-409.

[0060] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 9 and 10, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 11 and 12.

[0061] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 130 to 139; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 170 to 179; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 210 to 219; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 330 to 339; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 370 to 379; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 410 to 419.

[0062] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 130 to 134; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 170 to 174; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 210 to 214; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 330 to 334; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 370 to 374; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 410 to 414.

[0063] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 135-139; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 175-179; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 215-219; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 335-339; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 375-379; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 415-419.

[0064] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 13 and 14, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 15 and 16.

[0065] In some embodiments, there is provided an antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 220 to 224; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 235 to 239; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 250 to 254; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 420 to 424; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 435 to 439; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 450 to 454.

[0066] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 17, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 15 and 18.

[0067] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 225-229; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 240-244; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 255-259; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 425-429; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 440-444; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 455-459.

[0068] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 19, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 15 and 20.

[0069] In some embodiments, there is provided an antibody or antigen-binding fragment thereof of any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 230 to 234; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 245 to 249; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 260 to 264; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 430 to 434; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 445 to 449; and / or (f) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 460 to 464.

[0070] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising an immunoglobulin variable region heavy chain and an immunoglobulin variable region light chain, wherein: (a) the immunoglobulin variable region heavy chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 21, and / or (b) the immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 15 and 22.

[0071] In some embodiments, an antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising a constant region (e.g., a fragment crystallizable (Fc) region) that has reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG1 and / or reduced complement-dependent cytotoxicity (CDC) compared to human IgG1. In some embodiments, an antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the constant region comprises an amino acid sequence having 80, 85, 90, 95, 97, 98, 99, or 100% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 500-512. In some embodiments, an antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the constant region comprises the amino acid sequence set forth in any one of SEQ ID NOs: 500-512.

[0072] In some embodiments, according to EU numbering, (a) 297A, 297Q, 297G, or 297D, (b) 279F, 279K, or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R, or 235S, (e) 237A, 237E, 237K, 237N, or 237R, (f) 234A, 234V, or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R, (k) 331S, (l) 236F, if or 236R, (m) 238A, 238E, 238G, 238H, 238I, 238V, 238W, or 238Y, (n) 248A, (o) 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, or 254V, (p) 255N, (q) 256H, 256K, 256R, or 256V, (r) 264S, (s) 265H, 265K, 265S, 265Y, or 265A, (t) 267G, 267H, 267I, or 267K, (u) 268K, (v) 269N or 269Q, (w) 270A, 270G, 270M, or 270N, (x) 271T, (y) 272N, (z) 292E, 292F, 292G, or 292I, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 311E, 311G, or 311S, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii) 343I or 343V, (jj) 373A, 373G, or 373S, (kk) 376E, 376W, or 376Y, (ll) 380D, (mm) 382D, or 3 82P, (nn)385P, (oo)424H, 424M, or 424V, (pp)434I, (qq)438G, (rr)439E, 439H, or 439Q, (ss)440A, 440D, 440E, 440F, 440M, 440T, or 440V, (tt)E233P, (uu)L235E, (vv)L234A and L235A, (ww)L234A, L235A, and G237A, (xx)L234A, L235A, and P329G, (yy)L234F, L235E, and P331S, (zz)L234A, L235E,and G237A, (aaa), L234A, L235E, G237A, and P331S (bbb) L234A, L235A, G237A, P238S, H268A, A330S, and P331S, (ccc) L234A, L235A, and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh)

[0023] The antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, comprising a constant region having an amino acid sequence variant corresponding to: (i) D265A, (ii) D265A and N297A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) any combination of (a)-(mmm).

[0073] In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the recombinant antibody or antigen-binding fragment thereof is an IgG antibody. In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4. In some embodiments, the antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the recombinant antibody or antigen-binding fragment thereof is human, chimeric, or humanized.

[0074] In some embodiments, an antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the recombinant antibody or antigen-binding fragment thereof is a Fab, F(ab)'2, single domain antibody, or single chain variable fragment (scFv). In some embodiments, an antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the recombinant antibody or antigen-binding fragment thereof is a bispecific antibody or a multispecific antibody.

[0075] In some embodiments, an antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided, wherein the recombinant antibody or antigen-binding fragment thereof inhibits the binding interaction between CD30L and CD30.

[0076] In certain aspects, further provided is a nucleic acid encoding the recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments. Also provided is a cell comprising the recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments. In some embodiments, the cell is a eukaryotic cell. In some embodiments, the cell is a prokaryotic cell.

[0077] In certain aspects, a recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided for use in a method of inhibiting binding of CD30L to CD30. Further, a recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided for use in a method of inhibiting activation of CD30 signaling in a cell. Also, a recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided for use in a method of inhibiting activation, expression, and / or secretion of a pro-inflammatory cytokine protein.

[0078] In some aspects, the recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments is provided for use in treating an autoimmune disease in an individual in need thereof. In some embodiments, the autoimmune disease is irritable bowel disease. In some embodiments, the irritable bowel disease comprises ulcerative colitis (UC) or Crohn's disease (CD).

[0079] In one aspect, a method for treating or ameliorating an autoimmune disease in an individual in need thereof is provided, comprising administering to the individual a recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments to treat or ameliorate the autoimmune disease. Also provided is a method for inhibiting and / or reducing binding of CD30L to CD30 in an individual with an inflammatory or autoimmune disorder, comprising administering to the individual a recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments to inhibit and / or reduce binding of CD30L to CD30. Also provided is a method for reducing and / or inhibiting inflammation in an individual, comprising administering to the individual a recombinant antibody or antigen-binding fragment thereof of any of the preceding embodiments to reduce and / or inhibit inflammation.

[0080] In some embodiments, the method of any of the preceding embodiments is provided wherein the individual has an autoimmune disease. In some embodiments, the method of any of the preceding embodiments is provided wherein the autoimmune disease is irritable bowel disease. In some embodiments, the method of any of the preceding embodiments is provided wherein the irritable bowel disease comprises ulcerative colitis (UC) or Crohn's disease (CD).

[0081] In some embodiments, the method of any of the preceding embodiments is provided wherein reducing and / or inhibiting inflammation comprises reducing the amount of expression or secretion of a pro-inflammatory cytokine in the individual or in a tissue of the individual. In some embodiments, the method of any of the preceding embodiments is provided wherein the pro-inflammatory cytokine comprises interleukin-8 and / or interleukin-6. In some embodiments, the method of any of the preceding embodiments is provided wherein the individual has an autoimmune disease. In some embodiments, the method of any of the preceding embodiments is provided wherein the autoimmune disease is irritable bowel disease. In some embodiments, the method of any of the preceding embodiments is provided wherein the irritable bowel disease comprises ulcerative colitis (UC) or Crohn's disease (CD). [Brief explanation of the drawings]

[0082] 3. Brief description of the drawings [Figure 1-1] Figures 1A-1E show the dose-response curves of various anti-CD30L antibodies in a B16-huCD30L cell binding assay (first column from the left), inhibition / blocking of IL-8 release in a dual cell assay (B16-huCD30L cells and K299 cells) (second column from the left), an ELISA assay for binding to rhCD30L (third column from the left), and an ELISA assay for antibody-mediated blocking of CD30-Fc binding to huCD30L (fourth column from the left). The ELISA unit is OD450nm. The cell binding assay unit is mean fluorescence intensity (MFI). Figure 1A: Results for clone 2_germlined 62, 63, 64, and 65. Figure 1B: Results for clones 66, 67, 68, 69, 70, and 71. Figure 1C: Results for clones 72, 73, 74, 75, 76, and 77. [Figure 1-2] Figure 1D: Results for clones 78, 79, 80 and 8. Figure 1E: Results for clones 82, 83, 84 and 85.

[0083] [Figure 2] Figure 2 shows overlapping mapping of peptides generated from trypsin, chymotrypsin, ASP-N, elastase, and / or thermolysin proteolysis, demonstrating that the peptide signatures cover 94.76% of the CD30L ECD sequence.

[0084] [Figure 3] FIG. 3 shows epitopes in a portion of the CD30L ECD sequence (SEQ ID NO: 34) determined from cross-linking studies and mass spectrometry studies.

[0085] [Figure 4]Figures 4A-4J show the three-dimensional structure of the identified epitope on CD30L. The CD30L PDB structure is shown in blue above the epitope site. The CD30L amino acids in dark gray correspond to 16-30 (KGGNCSEDLLCILKR) and 48-64 (KTKLSWNKDGILHGVRY) of SEQ ID NO: 34. Figures 4A-4E: Ribbon / surface representations of the front view (4A), back view (4B), side view 1 (4C), side view 2 (4D), and top view (4E). Figures 4F-4J: Ribbon representations of the front view (4F), back view (4G), side view 1 (4H), side view 2 (4I), and top view (4J).

[0086] [Figure 5-1] Figure 5A shows a cell binding assay to determine anti-CD30L binding to CD30L-expressing cells and to determine blocking / inhibition of CD30 binding to CD30L-expressing cells by anti-CD30L. Figures 5B and 5C show representative binding curves for germlined clone 2 obtained from the cell binding assay shown in Figure 5A. 5B shows binding to human CD30L-expressing B16 cells, and 5C shows binding to cynomolgus monkey CD30L-expressing HEK293 cells. Figures 5D and 5E show representative blocking curves for germlined clone 2 obtained from the cell binding assay shown in Figure 5A. 5D shows the blocking curve for human CD30L-expressing B16 cells, and 5E shows the blocking curve for cynomolgus monkey CD30L-expressing HEK293 cells. [Figure 5-2] Figure 5F shows the ELISA setup for determining binding of anti-CD30L to purified CD30L, and Figure 5G shows the ELISA setup for determining blocking / inhibition of CD30 and CD30L by anti-CD30L. Figure 5H shows a representative binding curve for germlined clone 2 using the ELISA assay shown in Figure 5F, and Figure 51 shows a representative blocking curve for germlined clone 2 using the ELISA assay shown in Figure 5G. [Figure 5-3]Figure 5J shows a dual-cell IL-8 release assay. In this assay, CD30-expressing cells release IL-8 upon signaling via ligation with CD30L-expressing cells via CD30-CD30L interactions. Figures 5K and 5L show representative IL-8 release curves for germline clone 2 obtained from the dual-cell assay shown in Figure 5J. Figure 5K shows the IL-8 release curve using human CD30L-expressing B16 cells, and Figure 5L shows the IL-8 release curve using cynomolgus monkey CD30L-expressing HEK293 cells.

[0087] [Figure 6] Figures 6A-6D show the effect of anti-CD30l on in vivo cynomolgus monkey T cell-dependent antibody responses. Figure 6A shows the time course of KLH-specific IgM levels in serum from animals receiving the various treatments indicated. Figure 6B shows the overall anti-KLH IgM levels (area under the curve) after various treatments based on the curve in Figure 6A. Figure 6C shows the time course of KLH-specific IgG levels in serum from animals receiving the various treatments indicated. Figure 6D shows the overall anti-KLH IgG levels (area under the curve) after various treatments based on the curve in Figure 6C. DETAILED DESCRIPTION OF THE INVENTION

[0088] 4. Form for carrying out the invention The number of available treatments for autoimmune disorders, such as IBD, is limited, making the development of new therapies challenging for the treatment of autoimmune diseases, disorders, and their associated symptoms. A significant number of anti-inflammatory therapies fail to produce an effective or sustained therapeutic response. Furthermore, the disease worsens while patients are treated with ineffective anti-inflammatory therapies. For such non-responsive patients, the only treatment is surgery, typically in the form of strictureplasty (reconstruction of the intestine) or resection (removal of the intestine). Surgical treatments for IBD are invasive and pose postoperative risks, such as anastomotic leakage, infection, and bleeding, in an estimated one-third of patients who undergo surgery. Therefore, the heterogeneity of disease etiology and clinical course, combined with variable and / or inconsistent responses to treatment, suggests that targeted therapeutic approaches are a desirable therapeutic strategy for treating autoimmune disorders, such as IBD. However, few effective targeted therapies have been identified for IBD patients, particularly those who may not respond to existing IBD anti-inflammatory therapies. Thus, there is a need for novel therapies for treating autoimmune diseases, such as IBD, that specifically target the pathogenesis of IBD.

[0089] Described herein are antibodies that target and bind to CD30 ligand (CD30L), which, in certain instances, provide an effective targeted therapeutic approach for the treatment of autoimmune disorders such as IBD. Generally, in certain embodiments, the antibodies described herein inhibit the interaction between CD30L and CD30, effectively reducing, inhibiting, or preventing immune activation (e.g., inflammatory responses). CD30 ligand (also referred to as CD30L, CD153, or TNFSF8) is a member of the tumor necrosis factor (TNF) family. CD30L is a transmembrane protein expressed on immune cells, including activated T cells and B cells. Generally, after interaction with its receptor, CD30, CD30L can induce signal transduction through regulation of TNF receptor-associated factor 1 (TRAF1), TRAF2, 3, and 5. Interaction between CD30-CD30L induces immune cell (e.g., T cell) activation (e.g., stimulation of immune cell proliferation, release of cytokines, etc.) and activation of an inflammatory response. Thus, the antibodies described herein that target CD30L are useful for preventing, inhibiting, or reducing CD30-CD30L-mediated immune cell activation and / or activation of an inflammatory response in an individual. In certain examples, preventing, inhibiting, or reducing CD30-CD30L-mediated immune cell activation and / or activation of an inflammatory response in an individual is useful for treating an autoimmune disorder, such as, for example, IBD.

[0090] 4.1 Anti-CD30L antibody Described herein are recombinant antibodies or antigen-binding fragments thereof that bind to CD30 ligand (CD30L). As used herein, CD30 ligand or CD30L or human CD30L (also known and referred to as tumor necrosis factor ligand superfamily member 8, CD153, CD30L, CD30LG, TNLG3A) refers to any protein, including the expressed and processed form of the human (Homo sapiens) CD30L gene, which in certain embodiments is designated as UniProtKB / Swiss-Prot P32971 (NCBI Reference Sequence: NM_001244.4→NP_001235.1 or NM_001252290.1→NP_001239219.1). As used herein, the term "CD30L" includes the wild-type protein and all naturally occurring variants and / or isoforms thereof, as well as all transcriptional, post-translationally modified variants (e.g., as described as part of the record in UniProtKB / Swiss-Prot P32971). The antibody further blocks the interaction between CD30L and CD30 and inhibits the release of pro-inflammatory cytokines.

[0091] When used in a phrase with a list of members, the term "and / or" is intended to include all members individually and all combinations of the complete or partial list of members. For example, the phrase "A and / or B" herein is intended to include both A and B, A or B, A alone and B alone. Similarly, when used in a phrase such as "A, B, and / or C," the term "and / or" is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B, or C; A and C; A and B; B and C; A alone; B alone; and C alone.

[0092] The present disclosure provides that when an embodiment including the term "comprising" is provided herein, similar embodiments described as "consisting of" and / or "consisting essentially of" are also provided, even if such similar embodiments are not expressly provided. The present disclosure further provides that when an embodiment including the phrase "consisting essentially of" is described herein, similar embodiments described as "consisting of" are also provided. The present disclosure also provides that when an embodiment including the phrase "consisting of" is described herein, similar embodiments described as "consisting essentially of" are also provided.

[0093] All applications, publications, patents and other references, GenBank citations, and ATCC citations cited herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control.

[0094] As used herein, numerical values ​​are often presented in range format throughout the document. The use of the range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention unless the context clearly indicates otherwise. Thus, the use of a range explicitly includes all possible subranges, all individual numerical values ​​within that range, and integers within such ranges, or all numerical ranges, including fractions of values ​​or integers within a range, unless the context clearly indicates otherwise. This configuration applies regardless of the breadth of the range and in all contexts throughout this patent document. Thus, for example, reference to a range of 90 to 100% includes 91 to 99%, 92 to 98%, 93 to 95%, 91 to 98%, 91 to 97%, 91 to 96%, 91 to 95%, 91 to 94%, 91 to 93%, etc. References to the range of 90-100% also include 91%, 92%, 93%, 94%, 95%, 95%, 97%, etc., as well as 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc.

[0095] Furthermore, references to ranges of 1-3, 3-5, 5-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-170, 170-180, 180-190, 190-200, 200-225, and 225-250 include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc. In a further example, reference to ranges of 25 to 250, 250 to 500, 500 to 1,000, 1,000 to 2,500, 2,500 to 5,000, 5,000 to 25,000, and 25,000 to 50,000 includes any number or range between or including the values, e.g., 25, 26, 27, 28, 29, 250, 251, 252, 253, 254, 500, 501, 502, 503, 504, etc.

[0096] Also, as used herein, a series of ranges is disclosed throughout the specification. The use of a series of ranges includes combining upper and lower ranges to provide a separate range. This configuration applies regardless of the breadth of the ranges and in all contexts throughout this patent document. Thus, for example, reference to a series of ranges such as 5 to 10, 10 to 20, 20 to 30, 30 to 40, 40 to 50, 50 to 75, 75 to 100, 100 to 150 includes, for example, ranges such as 5 to 20, 5 to 30, 5 to 40, 5 to 50, 5 to 75, 5 to 100, 5 to 150, and 10 to 30, 10 to 40, 10 to 50, 10 to 75, 10 to 100, 10 to 150, and 20 to 40, 20 to 50, 20 to 75, 20 to 100, 20 to 150, etc.

[0097] In some embodiments, the term "about" refers to an average within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of a given value, amount, or range. For example, an antibody variable region with about 90% identity to a reference variable region may have 82% to 98% identity to the reference variable region.

[0098] When used in the context of one molecule binding to another, the terms "specifically binds to," "specific binding," and similar terms refer to one molecule binding to another molecule with an affinity significantly higher than any cross-reactive antigens or non-target antigens (collectively, non-target antigens), as determined using experimental techniques such as, for example, surface plasmon resonance (SPR), fluorescence-activated cell sorting (FACS) analysis, equilibrium exclusion assay (KinExA), isothermal titration calorimetry (ITC), radioimmunoassay (RIA), and enzyme-linked immunosorbent assay (ELISA). A specific or selective response typically has a non-target signal or noise that is at least two times higher than the non-target signal or noise, and may be more than ten times higher than the non-target signal or noise. For discussions of antibody specificity, see, for example, Fundamental Immunology332-36 (Paul ed., 2d ed. 1989). An antibody or antigen-binding fragment thereof that binds to a target of interest (e.g., targeting CD30L) is one that binds to the target with sufficient affinity so that the antibody or antigen-binding fragment thereof is useful as a therapeutic agent in targeting cells or tissues that express the target, and does not significantly cross-react with other proteins. In such embodiments, the extent of binding of the antibody or antigen-binding fragment to a "non-target" protein is less than about 10% of the binding of the antibody or antigen-binding fragment thereof to its particular target protein, as determined, for example, by FACS analysis, SPR, KinExA, ITC, ELISA, or RIA. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule. A control molecule is typically a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule similar to the target, such as an excess of unlabeled target. In this case, specific binding is indicated when the binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target. Thus, the terms "specific binding," "specifically binds to," "specifically inhibits," "specifically blocks," or "is specific for" a particular target, as used herein, refer to binding, blocking, or inhibition when a molecule binds to, blocks, or inhibits a particular target without substantially binding to or inhibiting non-targets. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments thereof provided herein specifically bind to CD30L. In some embodiments, an anti-CD30L antibody or antigen-binding fragment thereof that specifically binds to CD30L indicates that the antibody reacts with or associates with CD30L more frequently, more rapidly, for a longer period of time, with higher affinity, or some combination of the foregoing, than with another substance, including an unrelated protein.

[0099] As used herein, the terms "inhibit," "inhibiting," or "inhibition," when used in reference to CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions, are intended to mean decreasing, attenuating, reducing, diminishing, or completely eliminating CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions (e.g., CD30L-mediated IL-8 release in CD30-expressing cells). For example, the inhibition of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function may be a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% reduction in CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function. In another example, the inhibition of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function may be a complete abolition of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function. In one embodiment, the anti-CD30L antibody or antigen-binding fragment provided herein inhibited CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function by at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%.In another embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein inhibited CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions by about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99%. In yet another embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein completely abolished CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions.

[0100] As used herein, the term "block" or "blocking," when used in reference to CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions, is intended to mean decreasing, attenuating, reducing, diminishing, or completely eliminating CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions (e.g., CD30L-mediated IL-8 release in CD30-expressing cells) to the extent that the remaining CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function is no longer biologically significant. For example, the blockade of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function may be a 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% reduction in CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function. In another example, the blockade of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function may be a complete abolition of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function.In one embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein block CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function by reducing CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function by at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%, such that any remaining CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function is no longer biologically significant. In another embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein block up to about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99% of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function, such that any remaining CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function is no longer biologically significant. In yet another embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein block, e.g., completely abolish, CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions.

[0101] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a type of cytotoxicity in which secreted immunoglobulins bound to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages) enable these cytotoxic effector cells to specifically bind to antigen-bearing target cells and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are therefore absolutely necessary for such killing. NK cells, the primary cells mediating ADCC, express only FcγRIII, whereas monocytes express FcγRI, FcγRII, and FcγRIII. Expression of FcRs on hematopoietic cells is also known (see, e.g., Ravetch and Kinet, 1991, Annu. Rev. Immunol. 9:457-92). To assess the ADCC activity of a molecule of interest, an in vitro ADCC assay (e.g., U.S. Patent Nos. 5,500,362 and 5,821,337) can be performed. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells. Alternatively, or additionally, the ADCC activity of a molecule of interest can be assessed in vivo, for example, in an animal model (see, e.g., Clynes et al., 1998, Proc. Natl. Acad. Sci. USA 95:652-56). Antibodies with little or no ADCC activity can be selected for use.

[0102] "Antibody-dependent cellular phagocytosis" or "ADCP" refers to the destruction of target cells via monocyte- or macrophage-mediated phagocytosis when immunoglobulins bound to Fc receptors (FcRs) present on certain phagocytes (e.g., neutrophils, monocytes, and macrophages) can specifically bind to antigen-bearing target cells and subsequently kill them. To assess the ADCP activity of a molecule of interest, an in vitro ADCP assay (see, e.g., Bracher et al., 2007, J. Immunol. Methods 323:160-71) can be performed. Phagocytic cells useful for such assays include peripheral blood mononuclear cells (PBMCs), monocytes purified from PBMCs, or U937 cells differentiated into mononuclear forms. Alternatively, or additionally, the ADCP activity of the molecule of interest may be assessed in vivo, for example, in an animal model (see, e.g., Wallace et al., 2001, J. Immunol. Methods 248:167-82). Antibodies with little or no ADCP activity may be selected for use.

[0103] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to antibodies (of the appropriate subclass) bound to their cognate antigen. To assess complement activation, a CDC assay (see, e.g., Gazzano-Santoro et al., 1996, J. Immunol. Methods 202:163) may be performed. Polypeptide variants with altered Fc region amino acid sequences (polypeptides with variant Fc regions) that have increased or decreased C1q binding ability have been reported (see, e.g., U.S. Patent No. 6,194,551; WO 1999 / 51642; Idusogie et al., 2000, J. Immunol. 164:4178-84). Antibodies with little or no CDC activity may be selected for use.

[0104] As provided herein, the term "antibody" is used in its broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments thereof, including fragment antigen-binding (Fab) fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments, including single-chain variable fragments (sFv or scFv), and single-domain antibody (e.g., sdAb, sdFv, nanobody) fragments. The term also encompasses genetically engineered and / or otherwise modified types of immunoglobulins, including intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific antibodies, e.g., bispecifics, diabodies, triabodies, and tetrabodies, tandem di-scFvs, and tandem tri-scFvs. Unless otherwise specified, the term "antibody" should be understood to encompass functional antibody fragments thereof. The term also encompasses intact or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses, IgM, IgE, IgA, and IgD. The antibody may comprise a human IgG1 constant region. The antibody may comprise a human IgG4 constant region.

[0105] The provided antibodies are useful as monoclonal antibodies, in polyclonal antibody compositions, as multispecific antibodies (e.g., bispecific and polyreactive antibodies), and as antibody fragments (e.g., in the scFv format). The antibodies provided herein also include antibody conjugates and antibody-comprising molecules such as, for example, chimeric molecules. Thus, antibodies include, but are not limited to, full-length and native antibodies, as well as fragments and portions thereof that retain their binding specificity, including any specific binding portion thereof, including those having any number of immunoglobulin classes and / or isotypes (e.g., IgG1, IgG2, IgG3, IgG4, IgA, IgD, IgE, and IgM); and biologically relevant (antigen-binding) fragments or specific binding portions thereof, including, but not limited to, Fab, F(ab'), Fv, and scFv (single chain or related entities). Monoclonal antibodies generally have a substantially homogeneous antibody composition, and therefore, any individual antibody contained within a monoclonal antibody composition is identical except for naturally occurring variants that may be present in minor amounts. Polyclonal antibodies are preparations containing different antibodies of various sequences, generally directed against two or more different determinants (epitopes). Monoclonal antibodies may contain a human IgG1 constant region. Monoclonal antibodies may contain a human IgG4 constant region.

[0106] The terms "complementarity-determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art to refer to non-contiguous sequences of amino acids in an antibody variable region that confer antigen specificity and / or binding affinity. Generally, there are three CDRs (CDR-H1, CDR-H2, CDR-H3) in each heavy chain variable region and three CDRs (CDR-L1, CDR-L2, CDR-L3) in each light chain variable region. The terms "framework region" and "FR" are known in the art to refer to the non-CDR portions of the heavy and light chain variable regions. Generally, there are four FRs (FR-H1, FR-H2, FR-H3, and FR-H4) in each full-length heavy chain variable region and four FRs (FR-L1, FR-L2, FR-L3, and FR-L4) in each full-length light chain variable region.The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of known schemes, including those described by Kabat et al. (1991), "Sequences of Proteins of Immunological Interest," 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD ("Kabat" numbering scheme); Al-Lazikani et al., (1997) JMB 273, 927-948 ("Chothia" numbering scheme); MacCallum et al., J. Mol. Biol. 262:732-745 (1996), "Antibody-antigen interactions: Contact analysis and binding site topography," J. Mol. Biol. 262, 732-745 ("Contact" numbering scheme); Lefranc MP et al., "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol,2003 Jan;27(1):55-77 ("IMGT" numbering scheme); Honegger A and Pluckthun A, "Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool," J Mol Biol,2001 Jun 8;309(3):657-70, ("Aho" numbering scheme); and Whitelegg NR and Rees AR, "WAM: an improved algorithm for modeling antibodies on the WEB," Protein Eng.2000 Dec;13(12):819-24 ("AbM" numbering scheme).The CDRs of the antibodies described herein may be defined according to the Kabat, IMGT, Chothia, AbM, Aho, Contact numbering schemes, or any combination thereof.

[0107] The boundaries of a given CDR or FR may vary depending on the scheme used to identify it. For example, the Kabat scheme is based on structural alignment, while the Chothia scheme is based on structural information. The numbering in both the Kabat and Chothia schemes is based on the sequence length of the most common antibody regions, with insertions indicated by an insertion letter, e.g., "30a," and deletions found in some antibodies. The two schemes place certain insertions and deletions (indels) in different positions, resulting in different numbering. The Contact scheme is based on the analysis of complex crystal structures and is similar in many ways to the Chothia numbering scheme. Various numbering schemes and their CDR associations are summarized in Table 26 below.

[0108] [Table 1]

[0109] Thus, "Kabat variable region residue numbering" or "Kabat amino acid position numbering," and variations thereof, refer to the numbering system used for the heavy or light chain variable regions of the antibody compilations in Kabat et al., supra. Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to shortening or insertion of FRs or CDRs of the variable domain. For example, a heavy chain variable domain may contain a single amino acid insertion after residue 52 (residue 52a according to Kabat) and three inserted residues after residue 82 (e.g., residues 82a, 82b, and 82c according to Kabat). The Kabat numbering of residues can be determined for a given antibody by alignment with regions of homologous antibody sequences using the "standard" Kabat numbering sequence. The Kabat numbering system is generally used when referring to residues in the variable domain (approximately residues 1-107 in the light chain and residues 1-113 in the heavy chain) (e.g., Kabat et al., supra). The "EU numbering system" or "EU index" is commonly used when referring to residues in immunoglobulin heavy chain constant regions (e.g., the EU index reported in Kabat et al., supra). The "EU index as in Kabat" refers to the residue numbering of the human IgG1 EU antibody. Other numbering systems have also been reported, such as the AbM, Chothia, Contact, IMGT, and AHo numbering systems.

[0110] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to an antigen. The variable domains of the heavy and light chains (VH and VL, respectively) of natural antibodies generally have similar structures, with each domain comprising four conserved framework regions (FR) and three CDRs (see, e.g., Kindt et al., Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind to a specific antigen may be isolated by screening a library of complementary VL or VH domains using the VH or VL domain of an antigen-binding antibody, respectively (see, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991)).

[0111] The term "heavy chain" when used in reference to an antibody refers to a polypeptide chain of approximately 50 to 70 kDa, the amino-terminal portion of which contains a variable region of approximately 120 to 130 amino acids or more, and the carboxy-terminal portion of which contains a constant region. The constant region may be one of five different types (e.g., isotypes) designated alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ) based on the amino acid sequence of the heavy chain constant region. Different heavy chains vary in size: α, δ, and γ contain approximately 450 amino acids, while μ and ε contain approximately 550 amino acids. When combined with light chains, these different types of heavy chains form the five well-known antibody classes, IgA, IgD, IgE, IgG, and IgM, with four subclasses, namely, IgG1, IgG2, IgG3, and IgG4. The heavy chain may be a human heavy chain.

[0112] The term "light chain" when used in reference to an antibody refers to a polypeptide chain of approximately 25 kDa, the amino-terminal portion of which contains a variable region of approximately 100-110 amino acids or more, and the carboxy-terminal portion of which contains a constant region. The approximate length of a light chain is 211-217 amino acids. There are two different types, called kappa (κ) or lambda (λ), based on the amino acid sequence of the constant domain. The amino acid sequences of light chains are known in the art. The light chain may be a human light chain.

[0113] The provided antibodies include antibody fragments. The terms "antibody fragment," "antigen-binding fragment," "antigen-binding domain," "antigen-binding region," "antigen-binding fragment," "antigen-binding domain," "antigen-binding region," and similar terms refer to molecules other than intact antibodies that contain a portion of an intact antibody that binds to the antigen to which the intact antibody binds. Examples of antigen fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv or sFv); and multispecific antibodies formed from antibody fragments. In certain embodiments, the antibody is a single-chain antibody fragment, such as an scFv, that contains a variable heavy chain region and / or a variable light chain region. Generally, an antibody fragment or antigen-binding fragment comprises one or more CDRs from the parent antibody sufficient to confer binding specificity.

[0114] As used herein, the term "contact" with respect to antibody binding, or binding to a specific target, refers to amino acid residues in the variable regions or CDRs that are within 5, 4, 3, or fewer of the listed contact residues. Contacts include hydrogen bonds, van der Waals interactions, and salt bridge formation between amino acid residues in the variable regions or CDRs of the antibody and the listed residues.

[0115] Antibody fragments can be produced by a variety of techniques, including, but not limited to, proteolytic digestion of intact antibodies and production by recombinant host cells. In some embodiments, the antibody is a recombinantly produced fragment, e.g., a fragment containing a configuration not found in nature, e.g., two or more antibody regions or chains joined by a synthetic linker, such as a polypeptide linker, and / or a fragment not produced by enzymatic digestion of a naturally occurring intact antibody. In some aspects, the antibody fragment is an scFv.

[0116] Generally, a humanized antibody is an antibody in which all or substantially all of the amino acid residues in the CDRs are derived from non-human CDRs and all or substantially all of the amino acid residues in the FRs are derived from human FRs. A humanized antibody may optionally contain at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of a non-human antibody refers to a variant of a non-human antibody that has undergone humanization and is typically less immunogenic to humans, while retaining the specificity and affinity of the parent non-human antibody. In some embodiments, some FR residues in a humanized antibody are substituted with corresponding residues from the non-human antibody (e.g., the antibody from which the CDR residues were derived) to, for example, restore or improve the specificity or affinity of the antibody. In some embodiments, a humanized antibody refers to a non-human (e.g., murine) antibody or a form of an antibody that is not fully humanized, having a particular immunoglobulin chain, chimeric immunoglobulin, or fragment thereof, that contains minimal non-human (e.g., murine) sequence. In a non-limiting example, a humanized antibody contains less than about 40% non-human sequence in the variable regions. In some embodiments, a humanized antibody contains less than about 20% non-human sequences in the full-length antibody sequence. In a further non-limiting example, a humanized antibody contains less than about 20% non-human sequences in the framework regions of each of the heavy and light chain variable regions. For example, a humanized antibody contains less than about 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% non-human sequences in the framework regions of each of the heavy and light chain variable regions. In another example, a humanized antibody contains less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequence in the framework regions of each of the heavy and light chain variable regions. In some embodiments, humanized antibodies are human immunoglobulins in which residues from a complementarity-determining region (CDR) are replaced by residues from a CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) having the desired specificity, affinity, and capacity.These humanized antibodies may contain one or more non-human species mutations, for example, the heavy chain may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework regions, and the light chain may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework regions. The humanized heavy chain variable domain may comprise an IGHV3-9, IGHV4-59, or IGHV3-33 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutation, or no amino acid mutations. In some embodiments, the heavy chain variable domain comprises an IGHV3-9 framework. In some embodiments, the heavy chain variable domain comprises an IGHV4-59 framework. In some embodiments, the heavy chain variable domain comprises an IGHV3-33 framework. The humanized light chain variable domain may comprise the framework of IGKV1-16, IGKV1-6 or IGKV2-28 with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutation, or with no amino acid mutations.

[0117] The provided antibodies include human antibodies. A "human antibody" is an antibody having an amino acid sequence corresponding to that of an antibody produced by a human or human cell, or produced by a non-human source that utilizes a human antibody repertoire or other human antibody coding sequence, including a human antibody library. The term excludes humanized forms of non-human antibodies that contain non-human antigen-binding regions, e.g., those in which all or substantially all CDRs are non-human.

[0118] Human antibodies may be prepared by administering an immunogen to a transgenic animal that has been engineered to produce intact human antibodies or intact antibodies containing human variable regions in response to antigenic challenge. Such animals typically contain all or part of human immunoglobulin loci, which replace endogenous immunoglobulin loci or which are extrachromosomally present or randomly integrated into the animal's chromosomes. In such transgenic animals, endogenous immunoglobulin loci are generally inactivated. Human antibodies may also be derived from or selected from human antibody libraries, including phage display and cell-free libraries, containing antibody coding sequences derived from the human repertoire. In certain embodiments, human antibodies may be subjected to successive rounds of selection, e.g., by phage display, to remove sequence defects or increase their affinity.

[0119] The terms "polypeptide" and "protein" are used interchangeably and refer to polymers of amino acid residues and are not limited to a minimum length. Polypeptides, including the provided antibodies and antibody chains, as well as other peptides, such as linkers and connecting peptides, can contain amino acid residues, including naturally occurring amino acid residues and / or unnatural amino acid residues. The term also includes post-expression modifications of the polypeptide, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. In some embodiments, a polypeptide can contain modifications to the native or naturally occurring sequence, so long as the protein maintains the desired activity. These modifications can be deliberate, such as through site-directed mutagenesis, or can be accidental, such as through mutations of hosts producing the protein or through errors due to PCR amplification.

[0120] The percent sequence identity (%) with respect to a reference polypeptide sequence is the percent of amino acid residues in a candidate sequence that are identical to those in the reference polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity; any conservative substitutions are not considered part of the sequence identity. Alignment for the purpose of determining percent amino acid sequence identity can be performed in a variety of known ways, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences, including the algorithm required to achieve maximum alignment across the entire length of the sequences being compared, can be determined. However, for purposes of this specification, the percent amino acid sequence identity values ​​are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and the source code has been submitted, along with user documentation, to the U.S. Copyright Office, Washington, DC 20559, and is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or may be compiled from the source code. The ALIGN-2 program must be compiled for use on UNIX operating systems, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

[0121] When ALIGN-2 is employed to compare amino acid sequences, the percent amino acid sequence identity of a given amino acid sequence A with or relative to a given amino acid sequence B (alternatively, a given amino acid sequence A can be expressed as having or comprising a particular percent amino acid sequence identity with or relative to a given amino acid sequence B) is calculated as follows: multiply the fraction X / Y by 100, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in its alignment of A and B, and Y is the total number of amino acid residues in B. It will be understood that the length of amino acid sequence A is not the same as the length of amino acid sequence B, and the percent amino acid sequence identity between A and B is not the same as the percent amino acid sequence identity between B and A. Unless specifically stated otherwise, all percent amino acid sequence identity values ​​used herein are obtained using the ALIGN-2 computer program as described in the immediately preceding paragraph.

[0122] In some embodiments, amino acid sequence variants of the antibodies provided herein are contemplated. Variants typically differ from the polypeptides specifically disclosed herein by one or more substitutions, deletions, additions, and / or insertions. Such variants may be natural or may be synthetically produced by modifying one or more of the above-described polypeptides of the invention and assessing one or more biological activities described herein, and / or using numerous known techniques. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody. Amino acid sequence variants of antibodies may be produced by introducing appropriate modifications into the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions, insertions, and / or substitutions of residues within the amino acid sequence of the antibody. Any combination of deletions, insertions, and substitutions can be made to produce the final construct, provided that the final construct retains the desired characteristics, e.g., antigen binding.

[0123] In some embodiments, antibody variants with one or more amino acid substitutions are provided. Target sites for substitutional mutagenesis include CDRs and FRs. Amino acid substitutions may be introduced into a subject antibody, and the products may be screened for a desired activity, e.g., retention / improvement of antigen binding, or reduction in immunogenicity, such as reduced ADCC or CDC. In some embodiments, substitutions, insertions, or deletions may be made within one or more CDRs, provided that the substitutions, insertions, or deletions do not substantially reduce antibody binding to the antigen. For example, conservative substitutions that do not substantially reduce binding affinity may be made in a CDR. Such changes may be outside the "hot spots" of the CDRs. In some embodiments of the VH and VL sequences of the variants, each CDR is unchanged.

[0124] Alterations (e.g., substitutions) may be made to CDRs to improve antibody affinity. Such alterations may be made in CDRs encoding codons with high mutation rates during somatic maturation (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008)), and the resulting variants can be tested for binding affinity. Affinity maturation (e.g., using error-prone PCR, chain shuffling, CDR randomization, or oligonucleotide-directed mutagenesis) can be used to improve antibody affinity (see, e.g., Hoogenboom et al. in Methods in Molecular Biology 178:1-37 (2001)). CDR residues involved in antigen binding can be specifically identified, for example, using alanine scanning mutagenesis or modeling (see, e.g., Cunningham and Wells Science, 244:1081-1085 (1989)). CDR-H3 and CDR-L3 are often particularly targeted. Alternatively, or additionally, a crystal structure of the antigen-antibody complex can be used to identify contact points between the antibody and antigen. Such contact residues and neighboring residues can be targeted or excluded as candidates for substitution. Variants can be screened to determine whether they have the desired properties.

[0125] Amino acid sequence insertions and deletions include amino- and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing 100 or more residues, as well as intrasequence insertions and deletions of single or multiple amino acid residues. An example of a terminal insertion is an antibody with an N-terminal methionyl residue. Other insertional variants of antibody molecules include fusing the N- or C-terminus of the antibody to an enzyme (e.g., ADEPT) or a polypeptide that increases the serum half-life of the antibody. An example of an intrasequence insertional variant of an antibody molecule is an insertion of three amino acids into the light chain. An example of a terminal deletion is an antibody with seven or fewer amino acids deleted at the end of the light chain.

[0126] In some embodiments, antibodies are altered to increase or decrease glycosylation (e.g., by altering the amino acid sequence to create or remove one or more glycosylation sites). The carbohydrate attached to the Fc region of an antibody may also be altered. Natural antibodies derived from mammalian cells typically contain branched, biantennary oligosaccharides attached via an N-linkage to Asn297 in the CH2 domain of the Fc region (see, e.g., Wright et al., TIBTECH 15:26-32 (1997)). The oligosaccharides may be various carbohydrates, such as mannose, N-acetylglucosamine (GlcNAc), galactose, sialic acid, or fucose, and are attached to the GlcNAc at the stem of the biantennary oligosaccharide structure. For example, modifications of the oligosaccharides in an antibody may be performed to generate antibody variants with improved specific performance. Antibody glycosylation variants can alter ADCC and / or CDC function. Cell lines, such as knockout cell lines and methods for using them, can be used to produce defucosylated antibodies, such as Lec13 CHO cells, which are deficient in protein fucosylation, and alpha-1,6-fucosyltransferase gene (FUT8) knockout CHO cells (see, e.g., Ripka et al., Arch. Biochem. Biophys. 249:533-545 (1986); Yamane-Ohnuki et al., Biotech. Bioeng. 87:614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006)). Other antibody glycosylation variants are also included (see, e.g., U.S. Patent No. 6,602,684).

[0127] In some embodiments, one or more amino acid modifications are made to the Fc region of an antibody provided herein, thereby creating an Fc region variant. As used herein, an Fc region is the C-terminal region of an immunoglobulin heavy chain, containing at least a portion of the constant region. Fc regions include native-sequence Fc regions and variant Fc regions. An Fc region variant may comprise a human Fc region sequence (e.g., a human IgG1, IgG2, IgG3, or IgG4 Fc region) containing an amino acid modification (e.g., substitution) at one or more amino acid positions.

[0128] In some embodiments, the antibodies of the present disclosure are variants that retain some, but not all, effector functions. This makes them promising candidates for applications in which the in vivo half-life of the antibody is important, but certain effector functions (e.g., complement and ADCC) are unnecessary or harmful. In vitro and / or in vivo cytotoxicity assays can be performed to confirm reduced / loss of CDC and / or ADCC activity. For example, Fc receptor (FcR) binding assays can be performed to confirm that the antibody lacks FcγR binding (and therefore likely lacks ADCC activity). Non-limiting examples of in vitro assays for assessing ADCC activity of a molecule of interest are described in U.S. Patent Nos. 5,500,362 and 5,821,337. Alternatively, non-radioactive assays can be employed (e.g., ACTI™ and CytoTox 96® non-radioactive cytotoxicity assays). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC), monocytes, macrophages, and natural killer (NK) cells.

[0129] The antibodies can have increased half-life and improved binding to fetal Fc receptors (FcRn) (see, e.g., US 2005 / 0014934). Such antibodies can comprise an Fc region with one or more substitutions that improve binding of the Fc region to FcRn. Such antibodies include those with substitutions at one or more of the following Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, ​​413, 424, or 434 according to the EU numbering system (see, e.g., U.S. Patent No. 7,371,826). Other examples of Fc region variants are anticipated (e.g., contemplated) (see, e.g., Duncan & Winter, Nature 322:738-40 (1988); U.S. Patent Nos. 5,648,260 and 5,624,821; and WO 94 / 29351).

[0130] Reactive groups may be positioned at sites for conjugation to other moieties, such as drug moieties or linker drug moieties, to create immunoconjugates. In certain embodiments, the recombinant anti-CD30L antibodies provided herein may be further modified to contain additional, known and available nonproteinaceous moieties. Suitable moieties for derivatization of antibodies include, but are not limited to, water-soluble polymers. Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), ethylene glycol / propylene glycol copolymers, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, ethylene / maleic anhydride copolymers, polyamino acids (either homopolymers or random copolymers), and dextran, or poly(n-vinylpyrrolidone), polyethylene glycol, polypropylene glycol homopolymer, polypropylene oxide / ethylene oxide copolymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde, due to its stability, may be advantageous for preparation in aqueous solution. The polymer may be of any molecular weight and may be branched or unbranched. The number of polymers attached to the antibody may vary, and if two or more polymers are attached, they may be the same or different molecules.

[0131] The antibodies described herein may be encoded by nucleic acids. A nucleic acid is a type of polynucleotide containing two or more nucleotide bases. In certain embodiments, a nucleic acid is a component of a vector, which can be used to transport a polynucleotide encoding a polypeptide into a cell. As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it is linked. Some vectors are genome-integrating vectors, or "integrating vectors," and can be integrated into the chromosomal DNA of a host cell. Another type of vector is an "episomal" vector, such as a nucleic acid capable of extrachromosomal replication. Vectors capable of inducing the expression of an operably linked gene are referred to herein as "expression vectors." Suitable vectors include plasmids, bacterial artificial chromosomes, yeast artificial chromosomes, viral vectors, and the like. In expression vectors, control elements, such as promoters, enhancers, and polyadenylation signals used to control transcription, may be derived from mammalian, microbial, viral, or insect genes. The ability to replicate in a host cell is usually conferred by an origin of replication, and a selection gene may be incorporated to facilitate recognition of transformants. Vectors derived from viruses such as lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses may be employed. Plasmid vectors may be linearized for integration into specific chromosomal locations. Vectors may contain sequences that direct site-specific integration into defined locations or a limited set of sites in the genome (e.g., AttP-AttB recombination). Additionally, vectors may contain sequences derived from transposable elements.

[0132] As used herein, the terms "homologous," "homology," or "percent homology" when used herein to describe an amino acid sequence or a nucleic acid sequence compared to a reference sequence can be determined using the formula set forth in Karlin and Altschul (Proc. Natl. Acad. Sci. USA 87:2264-2268, 1990, modified as in Proc. Natl. Acad. Sci. USA 90:5873-5877, 1993). Such formula is incorporated into the basic local alignment search tool (BLAST) program of Altschul et al. (J. Mol. Biol. 215:403-410, 1990). Percent sequence homology can be determined using the most recent version of BLAST available as of the filing date of this application.

[0133] Nucleic acids encoding the antibodies described herein may be used to infect, transfect, transform, or otherwise render suitable cells transgenic for the nucleic acid, thereby enabling the production of antibodies for commercial or therapeutic use. Standard cell lines and methods for large-scale antibody production from cell culture are known in the art. See, for example, Li et al., "Cell culture processes for monoclonal antibody production." Mabs. 2010 Sep-Oct;2(5):466-477. In certain embodiments, the cell is a eukaryotic cell. In certain embodiments, the eukaryotic cell is a mammalian cell. In certain embodiments, the mammalian cell is a Chinese hamster ovary (CHO) cell, an NS0 mouse myeloma cell, an HEK293 (human embryonic kidney 293) cell, or a PER.C6® cell. In certain embodiments, the nucleic acid encoding the antibody is integrated into a genomic locus of a cell useful for antibody production. In certain embodiments, methods of producing an antibody are described herein, the methods comprising culturing cells containing nucleic acid encoding the antibody under in vitro conditions sufficient to allow the production and secretion of the antibody.

[0134] In certain embodiments, described herein is a master cell bank comprising: (a) a mammalian cell line comprising one or more nucleic acids encoding an antibody described herein integrated at a designated location in its genome; and (b) a cryoprotectant. In certain embodiments, the cryoprotectant comprises glycerol, DMSO, or a combination thereof. In certain embodiments, the master cell bank comprises: (a) a CHO cell line comprising a nucleic acid encoding an antibody having (i) a heavy chain variable region amino acid sequence at least 90% identical to the sequence set forth in SEQ ID NO: 1, 2, 5, 6, 9, 10, 13, 14, 17, 19, 21, 23, 25, 27, 29, or 31, integrated at a designated location in its genome, and (ii) a light chain amino acid sequence at least 90% identical to the sequence set forth in SEQ ID NO: 3, 4, 7, 8, 11, 12, 15, 16, 18, 20, 22, 24, 26, 28, 30, or 32, and (b) a cryopreservation agent. In certain embodiments, the cryoprotectant comprises glycerol, DMSO, or a combination thereof. In certain embodiments, the master cell bank is contained in a suitable vial or container that can withstand freezing with liquid nitrogen.

[0135] Also described herein are methods of producing the antibodies described herein. Such methods include incubating cells or cell lines containing nucleic acid encoding the antibody in cell culture medium under conditions sufficient to allow expression and secretion of the antibody, and recovering the antibody from the cell culture medium. Recovery may further include one or more purification steps to remove viable cells, cellular debris, non-antibody proteins or polypeptides, undesired salts, buffers, and medium components. In certain embodiments, additional purification steps include centrifugation, ultracentrifugation, dialysis, desalting, Protein A purification, Protein G purification, Protein A / G purification, or Protein L purification, and / or ion exchange chromatography.

[0136] The recombinant antibodies or antibody fragments thereof disclosed herein specifically bind to CD30L and are characterized by high affinity for CD30L. Thus, the antibodies disclosed herein are useful for targeting (i.e., binding to) CD30L. In some embodiments, the provided anti-CD30L antibodies comprise a heavy chain comprising the following four heavy chain framework regions (HCFRs) and three heavy chain complementarity-determining regions (HCDRs): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3, and HCFR4; and a light chain comprising the following four light chain framework regions (LCFRs) and three light chain complementarity-determining regions (LCDRs): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3, and LCFR4.

[0137] In one aspect, the present specification provides an antibody or antigen-binding fragment that binds to CD30L, the antibody or antigen-binding fragment comprising: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; or (c) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743. (d) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; (d) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and / or (e) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.

[0138] Consistent with the above aspect, in one embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In still other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In one embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, and a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, and a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, and a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In a further embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, and a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743.In one embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, and a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743, and a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In yet another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743, and a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752-759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In one embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751, and a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751, and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; and a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743. In still other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In a further embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In certain embodiments, the antibody or antigen-binding fragment thereof comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723, SEQ ID NOs: 180 to 219, 250. The present invention comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759, and a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In yet another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In yet another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof comprises, or consists of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In yet another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743, a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759, and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751.In a further embodiment, the antibody or antigen-binding fragment thereof comprises or consists of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, SEQ ID NOs: 140-179. , 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759, or consisting of these. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In still other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In a further embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In a further embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. In certain embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 65 The CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and the CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759, or consists of these.In some embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 65 The CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; and the CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or consists of these. In some embodiments, the antibody or antigen-binding fragment thereof comprises CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; and CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 550 to 560. The CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 28 to 552, 656 to 669, and 736 to 743; a CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or consists of these. In certain embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 67 The CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 0 to 683, and 744 to 751; a CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or consists of these.In certain embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-H4 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 68 3, and 744 to 751; CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or consisting of these. In certain embodiments, the antibody or antigen-binding fragment thereof includes a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; a CDR-H4 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 67 The CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 0 to 683, and 744 to 751; a CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or consists of these.In some embodiments, the antibody or antigen-binding fragment thereof comprises: CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; or CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743. a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or alternatively consisting of these.In some embodiments, the antibody or antigen-binding fragment thereof comprises CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; 3. It comprises or consists of any one of: CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-H4 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30 to 320; The CDR-L1 may comprise any two of the amino acid sequences set forth in any one of SEQ ID NOs: 0 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; the CDR-L2 may comprise any one of the amino acid sequences set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and the CDR-L3 may comprise any one of the amino acid sequences set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-H4 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30 to 320; The CDR-L1 may comprise any one of the amino acid sequences set forth in SEQ ID NOs: 0 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; the CDR-L2 may comprise any one of the amino acid sequences set forth in SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and the CDR-L3 may comprise any one of the amino acid sequences set forth in SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-H4 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30 to 320; The CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 0 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. The CDR-L1 comprises any four of the amino acid sequences set forth in any one of SEQ ID NOs: 0 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765.In some embodiments, the antibody or antigen-binding fragment thereof includes CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; CDR-H4 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 30 to 320; The CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 0 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; a CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and a CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765. The CDR-L1 comprises any five of the amino acid sequences set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759.In some embodiments, the antibody or antigen-binding fragment thereof comprises CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100 to 139, 220 to 234, 465 to 489, 628 to 641, and 712 to 723; CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140 to 179, 235 to 249, 490 to 499, 513 to 527, 642 to 655, and 724 to 735; CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180 to 219, 250 to 264, 528 to 552, 656 to 669, and 736 to 743; the CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300 to 339, 420 to 434, 553 to 577, 670 to 683, and 744 to 751; the CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340 to 379, 435 to 449, 578 to 602, 684 to 697, and 752 to 759; and the CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, 698 to 711, and 760 to 765, or all six of these. Or it will be.

[0139] In some embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100-109, 628, 635, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140-149, 642, 649, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180-189, 656, 663, and 712-723; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 309, 670, 677, and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 349, 684, 691, and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 389, 698, 705, and 760 to 765.

[0140] In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 100-109, 628, 635, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 140-149, 642, 649, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 180-189, 656, 663, and 712-723; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300 to 309, 670, 677, and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 340 to 349, 684, 691, and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 389, 698, 705, and 760 to 765.

[0141] In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 105-109, 628, 635, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 145-149, 642, 649, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 185-189, 656, 663, and 712-723; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 305 to 309, 670, 677 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 345 to 349, 684, 691 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 385 to 389, 698, 705 and 760 to 765.

[0142] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to CD30L, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO:34.

[0143] The anti-CD30L antibodies provided herein can bind to epitopes of various combinations of amino acids in CD30L as described herein. Thus, in one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment binds to an epitope comprising any one amino acid in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment binds to an epitope comprising any two amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64. In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments bind to an epitope that includes any three amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments bind to an epitope that includes any four amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64. In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments bind to an epitope comprising any five amino acids in CD30L selected from the group consisting of K16, S21, R30, K48, R63, and Y64. In one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments bind to an epitope comprising K16, S21, R30, K48, R63, and Y64.The amino acid positions in this paragraph are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO:34.

[0144] Additionally, the anti-CD30L antibodies provided herein, including those in Section 2 and this section (Section 4.1), can bind to certain epitopes of specific amino acid combinations of CD30L described herein, which epitopes are further provided in this paragraph. Thus, in one embodiment, the epitope of an anti-CD30L provided herein comprises or consists of K16. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21. In specific embodiments, the epitope of an anti-CD30L provided herein comprises or consists of R30. In other embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K48. In yet other embodiments, the epitope of an anti-CD30L provided herein comprises or consists of R63. In another embodiment, the epitope of an anti-CD30L provided herein comprises or consists of Y64. In one embodiment, the epitope of the anti-CD30L provided herein comprises or consists of K16 and S21. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16 and R30. In a specific embodiment, the epitope of the anti-CD30L provided herein comprises or consists of K16 and K48. In other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16 and R63. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16 and Y64. In a further embodiment, the epitope of the anti-CD30L provided herein comprises or consists of S21 and R30. In one embodiment, the epitope of the anti-CD30L provided herein comprises or consists of S21 and K48. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21 and R63. In certain embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21 and Y64.In other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of R30 and K48. In still other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of R30 and R63. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of R30 and Y64. In one embodiment, the epitope of the anti-CD30L provided herein comprises or consists of K48 and R63. In another embodiment, the epitope of the anti-CD30L provided herein comprises or consists of K48 and Y64. In another embodiment, the epitope of the anti-CD30L provided herein comprises or consists of R63 and Y64. In other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, S21, and R30. In still other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, S21, and K48. In further embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, S21, and R63. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, S21, and Y64. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, R30, and K48. In specific embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, R30, and R63. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, R30, and Y64. In still other embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, K48, and R63. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, K48, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, R63, and Y64.In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, and K48. In specific embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, and R63. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, and Y64. In other embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, K48, and R63. In still other embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, K48, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R63, and Y64. In still other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of R30, K48, and R63. In other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of R30, K48, and Y64. In specific embodiments, the epitope of the anti-CD30L provided herein comprises or consists of R30, R63, and Y64. In some embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K48, R63, and Y64. In other embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, S21, R30, and K48. In further embodiments, the epitope of the anti-CD30L provided herein comprises or consists of K16, S21, R30, and R63. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, R30, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, K48, and R63. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, K48, and Y64.In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, R63, and Y64. In specific embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, R30, K48, and R63. In specific embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, R30, K48, and Y64. In specific embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, R30, R63, and Y64. In yet other embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, K48, R63, and Y64. In further embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, K48, and R63. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, K48, and Y64. In further embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, R63, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, K48, R63, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of R30, K48, R63, and Y64. In a specific embodiment, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, R30, K48, and R63. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, R30, K48, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, R30, R63, and Y64. In specific embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, K48, R63, and Y64.In certain embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, R30, K48, R63, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of S21, R30, K48, R63, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of K16, S21, R30, K48, R63, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of any one of K16, S21, R30, K48, R63, and Y64. In some embodiments, the epitope of an anti-CD30L provided herein comprises or consists of any two of any combination or permutation of K16, S21, R30, K48, R63, and Y64. In some embodiments, the epitopes of anti-CD30L provided herein comprise or consist of any three of K16, S21, R30, K48, R63, and Y64 in any combination or permutation. In some embodiments, the epitopes of anti-CD30L provided herein comprise or consist of any four of K16, S21, R30, K48, R63, and Y64 in any combination or permutation. In some embodiments, the epitopes of anti-CD30L provided herein comprise or consist of any five of K16, S21, R30, K48, R63, and Y64 in any combination or permutation. In some embodiments, the epitopes of anti-CD30L provided herein comprise or consist of all six of K16, S21, R30, K48, R63, and Y64. The amino acid positions in this paragraph are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO:34.

[0145] In some embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 110-119, 629, 636, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 150-159, 643, 650, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 190-199, 657, 664, and 724-735; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 310 to 319, 671, 678 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 350 to 359, 685, 692 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 390 to 399, 699, 706 and 760 to 765.

[0146] In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 110-114, 629, 636, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 150-154, 643, 650, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 190-194, 657, 664, and 724-735; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 310 to 314, 671, 678 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 350 to 354, 685, 692 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 390 to 394, 699, 706 and 760 to 765.

[0147] In other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 115-119, 629, 636, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 155-159, 643, 650, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 195-199, 657, 664, and 73 (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 315 to 319, 671, 678, and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 355 to 359, 685, 692, and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 395 to 399, 699, 706, and 760 to 765.

[0148] In some embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 120-129 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 160-169 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 200-209 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 320-329 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 360-369 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 400-409 and 760-765.

[0149] In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 120-124 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 160-164 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 200-204 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 320-324 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 360-364 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 400-404 and 760-765.

[0150] In other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 125-129 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 165-169 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 205-209 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 325-329 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 365-369 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 405-409 and 760-765.

[0151] In some embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 130-139 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 170-179 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 210-219 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 330-339 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 370-379 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 410-419 and 760-765.

[0152] In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 130-134 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 170-174 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 210-214 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 330-334 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 370-374 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 410-414 and 760-765.

[0153] In other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 135-139 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 175-179 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 215-219 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 335-339 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 375-379 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 415-419 and 760-765.

[0154] In some embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 220-224 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 235-239 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 250-254 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 420-424 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 435-439 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 450-454 and 760-765.

[0155] In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 225-229 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 240-244 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 255-259 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 425-429 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 440-444 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 455-459 and 760-765.

[0156] In other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 230-234 and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 245-249 and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 260-264 and 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 430-434 and 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 445-449 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 460-464 and 760-765.

[0157] In one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 465-469, 631, 638, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 490-494, 645, 652, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 528-532, 659, 666, and 728-732; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 553 to 557, 673, 680 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 578 to 582, 687, 694 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 603 to 607, 701, 708 and 760 to 765.

[0158] In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 470-474, 632, 639, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 495-499, 646, 653, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 533-537, 660, 667, and 733-735; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 558 to 562, 674, 681 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 583 to 587, 688, 695 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 608 to 612, 702, 709, and 760 to 765.

[0159] In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 475-479, 633, 640, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 513-517, 647, 654, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 538-542, 661, 668, and 724-735; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 563 to 567, 675, 682 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 588 to 592, 689, 696 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 613 to 617, 703, 710, and 760 to 765.

[0160] In still other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 480-484, 630, 637, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 518-522, 644, 651, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 543-547, 658, 665, and 766; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 568 to 572, 672, 679, and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 593 to 597, 686, 693, and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 618 to 622, 700, 707, and 760 to 765.

[0161] In one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 485-489, 634, 641, and 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 523-527, 648, 655, and 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 548-552, 662, 669, and 772-773; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 573 to 577, 676, 683 and 744 to 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 598 to 602, 690, 697 and 752 to 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 623 to 627, 704, 711 and 760 to 765.

[0162] The present disclosure further provides sequence and structural features in the CDR sequences common to antibodies that confer binding affinity, specificity, and the ability to functionally block CD30-CD30L interaction, CD30L-mediated CD30 signaling, and IL-8 release to anti-CD30L antibodies. Accordingly, also provided herein are anti-CD30L antibodies having consensus CDR sequences that confer binding affinity, specificity, and the ability to functionally block CD30-CD30L interaction, CD30L-mediated CD30 signaling, and IL-8 release to anti-CD30L antibodies. In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765.In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712, 714, 716, 718, 720, and 722; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724, 726, 728, 730, 732, and 734; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 73 (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 744, 746, 748, and 750; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 752, 754, 756, and 758; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 760, 762, and 764. In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 713, 715, 717, 719, 721, and 723; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 725, 727, 729, 731, 733, and 735; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 726, 727, 729, 731, 733, and 735; (d) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 745, 747, 749, and 751; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 753, 755, 757, and 759; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 761, 763, and 765.In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:712, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:730, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:760. In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:713, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:731, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:761. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:712, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:724, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:760.In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:713, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:725, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:761. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:714, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:726, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:760. In one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:715, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:727, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:761.In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:716, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:728, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:736, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:744, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:752, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:760. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:717, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:729, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:737, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:745, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:753, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:761. In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:718, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:730, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:738, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:746, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:754, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:762.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:719, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:731, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:739, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:747, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:755, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:763. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:720, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:732, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:740, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:748, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:756, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:760. In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:721, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:733, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:741, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:749, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:757, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:761.In further embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:722; (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:734; (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:742; (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:750; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 758, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 764. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 723, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 735, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 743, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 751, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 759, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 765. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-H1 comprises an amino acid set forth in any one of SEQ ID NOs: 105-109, 628, 635, 115-119, 629, 636, 480-484, 630, 637, 465-469, 631, 638, 470-474, 632, 639, 475-479, 633, 640, 485-489, 634, and 641. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-H2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 145-149, 642, 649, 155-159, 643, 650, 518-522, 644, 651, 490-494, 645, 652, 495-499, 646, 653, 513-517, 647, 654, 523-527, 648, and 655. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), the CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 185-189, 656, 663, 195-199, 657, 664, 543-547, 658, 665, 528-532, 659, 666, 533-537, 660, 667, 538-542, 661, 668, 548-552, 662, and 669.In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 305-309, 670, 677, 315-319, 671, 678, 568-572, 672, 679, 553-557, 673, 680, 558-562, 674, 681, 563-567, 675, 682, 573-577, 676, and 683. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 345-349, 684, 691, 355-359, 685, 692, 593-597, 686, 693, 578-582, 687, 694, 583-587, 688, 695, 588-592, 689, 696, 598-602, 690, and 697. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 385-389, 698, 705, 395-399, 699, 706, 618-622, 700, 707, 603-607, 701, 708, 608-612, 702, 709, 613-617, 703, 710, 623-627, 704, and 711. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-H1 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 105-109, 628, 635, 115-119, 629, 636, 480-484, 630, and 637. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-H2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 145-149, 642, 649, 155-159, 643, 650, 518-522, 644, and 651.In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as those in this paragraph), CDR-H3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 185-189, 656, 663, 195-199, 657, 664, 543-547, 658, and 665. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as those in this paragraph), CDR-L1 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 305-309, 670, 677, 315-319, 671, 678, 568-572, 672, and 679. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-L2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 345-349, 684, 691, 355-359, 685, 692, 593-597, 686, and 693. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-L3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 385-389, 698, 705, 395-399, 699, 706, 618-622, 700, and 707.

[0163] Further with respect to the anti-CD30L antibodies (e.g., those described in the preceding paragraphs) provided herein, including in Section 2 and this Section 4.1, in one embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735. In specific embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In still other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In another embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In one embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723 and a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723 and a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743.In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In further embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765.In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743.In still other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In further embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In still other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In other embodiments, the anti-CD30L antibody or antigen-binding fragment provided herein comprises, or consists of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In still other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In still other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751. In further embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In specific embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759.In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765. In still other embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In further embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In further embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765.In certain embodiments, the anti-CD30L antibody or antigen-binding fragment provided herein comprises, or consists of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723. and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765. In certain embodiments, the anti-CD30L antibody or antigen-binding fragment provided herein comprises or consists of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759; ... In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, a CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735, a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of any one of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, any two of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765, in any combination or permutation.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, any three of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765, in any combination or permutation. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, any four of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765, in any combination or permutation. In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise, or consist of, any five of the following in any combination or permutation: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765.In some embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein comprise or consist of all six of: CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724 to 735; CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759; and CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-H1 comprises an amino acid set forth in any one of SEQ ID NOs: 105-109, 628, 635, 115-119, 629, 636, 480-484, 630, 637, 465-469, 631, 638, 470-474, 632, 639, 475-479, 633, 640, 485-489, 634, and 641. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-H2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 145-149, 642, 649, 155-159, 643, 650, 518-522, 644, 651, 490-494, 645, 652, 495-499, 646, 653, 513-517, 647, 654, 523-527, 648, and 655. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), the CDR-H3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 185-189, 656, 663, 195-199, 657, 664, 543-547, 658, 665, 528-532, 659, 666, 533-537, 660, 667, 538-542, 661, 668, 548-552, 662, and 669.In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-L1 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 305-309, 670, 677, 315-319, 671, 678, 568-572, 672, 679, 553-557, 673, 680, 558-562, 674, 681, 563-567, 675, 682, 573-577, 676, and 683. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-L2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 345-349, 684, 691, 355-359, 685, 692, 593-597, 686, 693, 578-582, 687, 694, 583-587, 688, 695, 588-592, 689, 696, 598-602, 690, and 697. In some embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., those in this paragraph), CDR-L3 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 385-389, 698, 705, 395-399, 699, 706, 618-622, 700, 707, 603-607, 701, 708, 608-612, 702, 709, 613-617, 703, 710, 623-627, 704, and 711. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-H1 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 105-109, 628, 635, 115-119, 629, 636, 480-484, 630, and 637. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-H2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 145-149, 642, 649, 155-159, 643, 650, 518-522, 644, and 651.In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as those in this paragraph), CDR-H3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 185-189, 656, 663, 195-199, 657, 664, 543-547, 658, and 665. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as those in this paragraph), CDR-L1 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 305-309, 670, 677, 315-319, 671, 678, 568-572, 672, and 679. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-L2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 345-349, 684, 691, 355-359, 685, 692, 593-597, 686, and 693. In certain embodiments of anti-CD30L provided herein, including in Section 2 and this Section 4.1 (e.g., such as in this paragraph), CDR-L3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 385-389, 698, 705, 395-399, 699, 706, 618-622, 700, and 707.

[0164] Additionally, the anti-CD30L antibodies provided herein, including in Section 2 and this section (Section 4.1), can comprise a specific combination of CDRs from each anti-CD30L clone listed in Tables 10 through 16. Accordingly, in one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:635, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:649, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:663, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:677, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:691, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:705. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 107, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 147, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 187, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 307, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 347, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 387. In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 105, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 145, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 185, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 305, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 345, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 385.In one embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 106, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 146, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 186, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 306, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 346, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 386. In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 108, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 148, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 188, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 308, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 348, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 388. In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 109, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 149, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 189, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 309, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 349, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 389.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 628, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 642, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 656, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 670, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 684, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 698.

[0165] Similarly, in one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 636, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 650, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 664, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 678, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 692, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 706. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 117, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 157, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 197, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 317, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 357, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 397. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 115, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 155, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 195, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 315, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 355, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 395.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 116, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 156, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 196, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 316, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 356, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 396. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 118, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 158, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 198, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 318, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 358, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 398. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 159, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 199, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 319, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 359, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 399.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 629, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 643, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 657, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 671, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 685, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 699.

[0166] Similarly, in one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 637, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 651, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 665, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 679, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 693, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 707. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:482, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:520, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:545, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:570, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:595, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:620. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:480, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:518, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:543, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:568, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:593, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:618.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:481, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:519, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:544, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:569, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:594, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:619. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:483, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:521, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:546, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:571, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:596, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:621. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:484, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:522, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:547, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:572, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:597, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:622.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 630, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 644, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 658, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 672, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 686, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 700.

[0167] Thus, in one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (i) (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 638, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 652, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 666, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 680, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 694, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 708. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:467, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:492, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:530, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:555, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:580, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:605. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:465, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:490, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:528, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:553, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:578, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:603.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:466, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:491, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:529, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:554, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:579, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:604. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:468, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:493, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:531, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:556, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:581, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:606. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:469, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:494, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:532, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:557, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:582, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:607.In one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 631; (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 645; (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 659; (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 673; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 687; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 701.

[0168] Similarly, in one embodiment of the anti-CD30L antibody or antigen-binding fragment provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 639, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 653, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 667, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 681, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 695, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 709. In another embodiment of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:472, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:497, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:535, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:560, (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:585, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:610. In yet other embodiments of the anti-CD30L antibodies or antigen-binding fragments provided herein, including in Section 2 and this section (Section 4.1), the antibody or antigen-binding fragment comprises: (a) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:470, (b) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:495, (c) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:533, (d) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:5...

Claims

1. An antibody or antigen-binding fragment thereof that binds to CD30L, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 712 to 723; (b) CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 724 to 735; (c) CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 736 to 743; (d) CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 744 to 751; (d) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 752 to 759, and / or (e) an antibody or antigen-binding fragment thereof, comprising a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 760 to 765.

2. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 100-139, 220-234, 465-489, and 628-641; (b) CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, and 642-655; (c) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 180-219, 250-264, 528-552, and 656-669; (d) CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, and 670-683; (e) SEQ ID NOs: 340-379, 435-449, 578-602, and 684-6 and / or (f) the antibody or antigen-binding fragment thereof according to claim 1, comprising a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 380 to 419, 450 to 464, 603 to 627, and 698 to 711.

3. The antibody or antigen-binding fragment thereof, (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 720 and 721; (b) CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 732 and 733; (c) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 740 and 741; (d) CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 748 and 749; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 756 and 757; and / or (f) a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 760 and 761; or

4. The antibody or antigen-binding fragment thereof, (a) a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 115 to 119 and 629; (b) CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 155 to 159 and 643; (c) a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 195, 198-199, and 657; (d) CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 315, 318-319, and 671; (e) a CDR-L2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 355, 358-359, and 685; and / or (f) the antibody or antigen-binding fragment thereof according to claim 1, comprising a CDR-L3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 395, 398, and 699.

5. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 117; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 157; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 197; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 317; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 357, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 397; or an antigen-binding fragment thereof, comprising the antibody or antigen-binding fragment of claim 1 .

6. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 115; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 155; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 195; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 315; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 355, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:

395.

7. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 116; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 156; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 196; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 316; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 356, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 396; or an antigen-binding fragment thereof, comprising the antibody or antigen-binding fragment of claim 1 .

8. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 118; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 158; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 198; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 318; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 358, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:

398.

9. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 159; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 199; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 319; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 359, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:

399.

10. The antibody or antigen-binding fragment thereof, (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 629; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 643; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 657; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 671; (e) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 685, and / or (f) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:699; or an antigen-binding fragment thereof, comprising the antibody or antigen-binding fragment of claim 1 .

11. The antibody or antigen-binding fragment thereof, (i) (a) the immunoglobulin variable region heavy chain (VH) comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 1, 2, 5, and 6, and / or (b) the immunoglobulin variable region light chain (VL) comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to any one of SEQ ID NOs: 3, 4, 7, and 8, or (ii) (a) a VH comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO:6, and / or (b) a VL comprising an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO:8; The antibody or antigen-binding fragment thereof of claim 1 or 2.

12. The antibody or antigen-binding fragment thereof, (i) (a) an immunoglobulin variable region heavy chain (VH) comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 2, 5, 6, 9, 10, 13, 14, 17, 19, 21, 23, 25, 27, 29, and 31; and / or (b) an immunoglobulin variable region light chain (VL) comprising an amino acid sequence set forth in any one of SEQ ID NOs: 3, 4, 7, 8, 11, 12, 15, 16, 18, 20, 22, 24, 26, 28, and 30; (ii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 1, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 3; (iii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 2, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 4; (iv) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:5, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO:7; (v) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:6, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO:8; (vi) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:9, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO:11; (vii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 10, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 12; (viii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 13, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 15; (ix) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 14, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 16; (x) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 23, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 24; (xi) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 25, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 26; (xii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 27, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 28; (xiii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 29, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 30, or (xiv) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 31, and / or (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 32; The antibody or antigen-binding fragment thereof of claim 1 or 2.

13. Comprising VH and VL, (a) a VH comprising an amino acid sequence having at least about 90% sequence identity to SEQ ID NO:6; and (b) a VL comprising an amino acid sequence having at least about 90% sequence identity to SEQ ID NO:8; The antibody or antigen-binding fragment thereof of claim 1 or 2.

14. The antibody or antigen-binding fragment thereof, (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:6; and (b) a VL comprising the amino acid sequence set forth in SEQ ID NO:8; The antibody or antigen-binding fragment thereof of claim 1 or 2.

15. The antibody or antigen-binding fragment thereof, (a) a VH comprising the amino acid sequence set forth in SEQ ID NO:5; and (b) a VL comprising the amino acid sequence set forth in SEQ ID NO: 7; The antibody or antigen-binding fragment thereof of claim 1 or 2.

16. Further comprising an IgG constant region, optionally wherein the IgG constant region has reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG, and / or reduced complement-dependent cytotoxicity (CDC) function compared to human IgG; The antibody or antigen-binding fragment thereof according to any one of claims 1 to 15, having the following structure:

17. (i) the IgG constant region comprises an amino acid sequence having 80, 85, 90, 95, 97, 98, 99 or 100% sequence identity to an amino acid sequence set forth in any one of SEQ ID NOs:500 to 512; or (ii) The antibody or antigen-binding fragment thereof according to claim 16, wherein the IgG constant region comprises an amino acid sequence set forth in any one of SEQ ID NOs: 500 to 512.

18. The antibody or antigen-binding fragment thereof described in claim 17, wherein the IgG constant region comprises an amino acid sequence set forth in SEQ ID NO:

504. (i) the antibody or antigen-binding fragment thereof is an antibody, the antibody being an IgG antibody; (ii) the antibody or antigen-binding fragment thereof is human, chimeric or humanized; or (iii) the antibody or antigen-binding fragment thereof is a Fab, F(ab')2, a single domain antibody, or a single chain variable fragment (scFv); An antibody or antigen-binding fragment thereof according to any one of claims 1 to 18.

20. The antibody or antigen-binding fragment thereof described in claim 19, wherein the IgG antibody is IgG1, IgG2, IgG3, or IgG4.

21. A nucleic acid encoding an antibody or antigen-binding fragment thereof described in any one of claims 1 to 20.

22. A cell comprising an antibody or antigen-binding fragment thereof described in any one of claims 1 to 20, or a nucleic acid described in claim 21.

23. The cell described in claim 22, wherein the cell is a eukaryotic cell or a prokaryotic cell.

24. An antibody or antigen-binding fragment thereof described in any one of claims 1 to 20 for use in treating an autoimmune disease in an individual in need thereof.

25. The antibody or antigen-binding fragment thereof for use according to claim 24, wherein the autoimmune disease is irritable bowel disease.

26. The antibody or antigen-binding fragment thereof for use according to claim 25, wherein the irritable bowel disease comprises ulcerative colitis (UC) or Crohn's disease (CD).

Images