Anti-CD30L antibodies, formulations and uses thereof

Abstract

Described herein are anti-CD30L antibodies and pharmaceutical compositions for the treatment of autoimmune diseases and disorders, such as inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC).

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 369,361, filed on July 25, 2022, and U.S. Provisional Patent Application No. 63 / 371,553, filed on August 16, 2022, both of which are incorporated herein by reference in their entireties.

[0003] References to sequence listings

[0004] This application contains a sequence listing submitted electronically in XML format, which is incorporated herein by reference in its entirety. This XML copy was created on June 26, 2023, is named 56884-409601.xml, and is 663,813 bytes in size. 1. Background Technology

[0005] Autoimmune diseases occur when the immune system breaks down its tolerance to autoreactive immune cells, leading to attacks on self-molecules. Many autoimmune diseases are closely linked to genetic, infectious, and / or environmental triggers, resulting in a wide range of symptoms and conditions, ranging from organ-specific to systemic dysfunction. Inflammatory bowel disease (IBD) refers to a range of intestinal disorders that cause inflammation of the gastrointestinal tract. The main types of IBD are ulcerative colitis (UC) and Crohn's disease (CD). These diseases are prevalent, with approximately 1.86 million people diagnosed with UC and 1.3 million with CD worldwide. Severe IBD may lead to or be characterized by intestinal fibrosis, the accumulation of scar tissue in the intestinal wall. The pathogenesis of IBD is believed to involve an uncontrolled immune response that may be triggered by certain environmental factors in genetically susceptible hosts. The heterogeneity in disease pathogenesis and clinical course, coupled with variable responses to treatment and associated side effects, suggests that targeted therapies are an ideal therapeutic strategy for treating these diseases. However, targeted therapies are rarely used in patients with IBD, particularly those who may not respond or have lost their response to existing IBD therapies. 2. Summary of the Invention

[0006] Provided herein are antibodies that bind to CD30 ligand (also referred to as CD30L, CD153, TNFSF8) and are useful for treating autoimmune diseases, such as IBD. Generally, in one aspect, the antibodies described herein effectively inhibit the interaction between CD30L and CD30, thereby effectively reducing, inhibiting, or preventing immune activation (e.g., an inflammatory response). Furthermore, the anti-CD30L antibodies described herein also possess properties useful for therapeutic applications, including, for example, reduced and / or low immunogenicity. The antibodies described herein also inhibit the expression / secretion of certain inflammatory cytokines (e.g., interleukin-6 and interleukin-8), which play a key role in inflammatory and autoimmune diseases (e.g., inflammatory bowel disease, Crohn's disease, and ulcerative colitis).

[0007] Thus, in one aspect, provided herein are antibodies or antigen-binding fragments thereof that bind to CD30L, wherein the antibodies or antigen-binding fragments thereof comprise: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751; (d) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759; and / or (e) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759. The amino acid sequence shown in any one of NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.

[0008] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 100-109, 628, 635, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 140-149, 642, 649, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 180-189, 656, 663, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 300-309, 670, 677, and 744-751; (e) a CDR-L2 comprising SEQ an amino acid sequence shown in any one of SEQ ID NOs: 340-349, 684, 691 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-389, 698, 705 and 760-765.

[0009] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 105-109, 628, 635, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 145-149, 642, 649, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 185-189, 656, 663, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 305-309, 670, 677, and 744-751; (e) a CDR-L2 comprising SEQ an amino acid sequence shown in any one of SEQ ID NOs: 345-349, 684, 691 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 385-389, 698, 705 and 760-765.

[0010] 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 selected from N165, K166, I168, K169, and D234 of CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid selected from N165, K166, I168, K169, and D234 of CD30L; (ii) any two amino acids selected from N165, K166, I168, K169, and D234 of CD30L; (iii) any three amino acids selected from N165, K166, I168, K169, and D234 of CD30L; (iv) any four amino acids selected from N165, K166, I168, K169, and D234 of CD30L; or (v) any five amino acids selected from N165, K166, I168, K169, and D234 of CD30L; wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO:33.

[0011] In one aspect, provided herein are antibodies or antigen-binding fragments thereof that bind to CD30L, wherein the antibodies or antigen-binding fragments thereof bind to an epitope comprising one or more amino acids selected from the group consisting of H167, S217, and D118 of CD30L, wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 33. In some embodiments, wherein the antibodies or antigen-binding fragments thereof bind to an epitope, wherein the epitope comprises: (i) any one amino acid selected from the group consisting of H167, S217, and D118 of CD30L; (ii) any two amino acids selected from the group consisting of H167, S217, and D118 of CD30L; or (iii) any three amino acids selected from the group consisting of H167, S217, and D118 of CD30L; wherein the amino acids are numbered according to the amino acid sequence of CD30L set forth in SEQ ID NO: 33.

[0012] 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 selected from D118, N165, K166, H167, I168, K169, S217, and D234 of CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234 in CD30L; (ii) any two amino acids selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234 in CD30L; (iii) any three amino acids selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234 in CD30L; (iv) any three amino acids selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234 in CD30L. (v) any five amino acids of CD30L selected from D118, N165, K166, H167, I168, K169, S217, and D234; (vi) any six amino acids of CD30L selected from D118, N165, K166, H167, I168, K169, S217, and D234; (vii) any seven amino acids of CD30L selected from D118, N165, K166, H167, I168, K169, S217, and D234; or (viii) any five amino acids of CD30L selected from D118, N165, K166, H167, I168, K169, S217, and D234; wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0013] In one aspect, provided herein are anti-CD30L antibodies or antigen-binding fragments thereof, wherein the antibodies or antigen-binding fragments thereof bind to an epitope in CD30L comprising K169, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0014] In some embodiments, the antibody or antigen-binding fragment thereof binds to an epitope in CD30L comprising D234, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the epitope further comprises N165 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the epitope further comprises I168 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the epitope further comprises K166 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the epitope further comprises H167 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the epitope further comprises S217 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the epitope further comprises D118 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:33.

[0015] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 110-119, 629, 636, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 150-159, 643, 650, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 190-199, 657, 664, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 310-319, 671, 678, and 744-751; (e) a CDR-L2 comprising SEQ an amino acid sequence shown in any one of SEQ ID NOs: 350-359, 685, 692, and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 390-399, 699, 706, and 760-765.

[0016] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 115-119, 629, 636, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 155-159, 643, 650, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 195-199, 657, 664, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 315-319, 671, 678, and 744-751; (e) a CDR-L2 comprising SEQ an amino acid sequence shown in any one of SEQ ID NOs: 355-359, 685, 692, and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 395-399, 699, 706, and 760-765.

[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: 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.

[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: 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.

[0019] 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: 130-139 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.

[0020] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 130-134; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 170-174; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 210-214; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 330-334; (e) a CDR-L2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 370-374; and / or (f) a CDR-L3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 410-414.

[0021] 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.

[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: 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.

[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 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.

[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: 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.

[0025] 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) 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) VL comprises an amino acid sequence having at least about 90, 95, 97, 98, 99 or 100% sequence identity to SEQ ID NO: 20.

[0026] 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.

[0027] 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) 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) VL comprises an amino acid sequence having at least about 90, 95, 97, 98, 99 or 100% sequence identity to SEQ ID NO:22.

[0028] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 465-469, 631, 638, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 490-494, 645, 652, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 528-532, 659, 666, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 553-557, 673, 680, and 744-751; (e) a CDR-L2 comprising SEQ an amino acid sequence shown in any one of SEQ ID NOs: 578-582, 687, 694 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 603-607, 701, 708 and 760-765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 470-474, 632, 639, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 495-499, 646, 653, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 533-537, 660, 667, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 558-562, 674, 681, and 744-751; (e) a CDR-L2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NO:583-587, 688, 695 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO:608-612, 702, 709 and 760-765.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 475-479, 633, 640, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 513-517, 647, 654, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 538-542, 661, 668, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 563-567, 675, 682, and 744-751; (e) a CDR-L2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NO:588-592, 689, 696 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO:613-617, 703, 710 and 760-765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 480-484, 630, 637, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 518-522, 644, 651, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 543-547, 658, 665, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 568-572, 672, 679, and 744-751; (e) a CDR-L2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NO:593-597, 686, 693 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO:618-622, 700, 707 and 760-765.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 485-489, 634, 641, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 523-527, 648, 655, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 548-552, 662, 669, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 573-577, 676, 683, and 744-751; (e) a CDR-L2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NO: 598-602, 690, 697 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO: 623-627, 704, 711 and 760-765.

[0029] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 712-723; (b) a CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 724-735; (c) a CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 736-743; (d) a CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 744-751; (e) a CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 760-765. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 712, 714, 716, 718, 720, and 722; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 724, 726, 728, 730, 732, and 734; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 736, 738, 740, and 742; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 744, 746, 748, and 750; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 752, 754, 756, and 758; and / or (f) a CDR-L3 comprising the amino acid sequence of 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) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 712; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 730; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises (v) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:713; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:731; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:737; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:745; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:753; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:761. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 712; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 724; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 713; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 725; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 761.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 714; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 726; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 760. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:715; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:727; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:737; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:745; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:753; and / or (f) CDR-L3 comprising the amino acid sequence shown 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 shown in SEQ ID NO: 716; (b) a CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 728; (c) a CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 736; (d) a CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 744; (e) a CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 752; and / or (f) a CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 761. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:717; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:729; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:737; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:745; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:753; and / or (f) CDR-L3 comprising the amino acid sequence shown 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 shown in SEQ ID NO: 718; (b) a CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 730; (c) a CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 738; (d) a CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 746; (e) a CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 754; and / or (f) a CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 762. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:719; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:731; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:739; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:747; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:755; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:763. In some embodiments, the antibody or antigen-binding fragment thereof comprises: a CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 720; (b) a CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 732; (c) a CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 740; (d) a CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 748; (e) a CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 756; and / or (f) a CDR-L3 comprising the amino acid sequence shown 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 shown in SEQ ID NO: 721; (b) a CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 733; (c) a CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 741; (d) a CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 749; (e) a CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 757; and / or (f) a CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 761.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 722; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 734; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 742; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 750; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 758; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 764. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:723; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:735; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:743; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:751; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:759; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:765.

[0030] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 635; (b) a CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 649; (c) a CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 663; (d) a CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 677; (e) a CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 691; and / or (f) a CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 705. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 107; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 147; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 187; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 307; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 347; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 387. In some embodiments, the antibody or antigen-binding fragment thereof comprises a CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 105; (b) a CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 145; (c) a CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 185; (d) a CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 305; (e) a CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 345; and / or (f) a CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 385. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 106; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 146; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 186; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 306; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 346; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 386.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 108; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 148; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 188; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 308; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 348; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 388. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 109; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 149; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 189; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 309; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 349; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 389. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 628; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 642; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 656; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 670; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 684; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 698.

[0031] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 636; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 650; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 664; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 678; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 692; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 706. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 117; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 157; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 197; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 317; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 357; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 397. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 115; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 155; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 195; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 315; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 355; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 395. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 116; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 156; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 196; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 316; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 356; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 396.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 118; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 158; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 198; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 318; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 358; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 398. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 119; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 159; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 199; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 319; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 359; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 399. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 629; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 643; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 657; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 671; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 685; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 699.

[0032] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 637; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 651; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 665; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 679; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 693; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 707. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 482; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 520; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 545; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 570; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 595; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 620. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 480; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 518; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 543; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 568; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 593; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 618. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 481; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 519; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 544; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 569; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 594; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 619.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 483; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 521; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 546; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 571; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 596; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 621. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 484; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 522; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 547; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 572; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 597; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 622. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 630; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 644; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 658; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 672; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 686; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 700.

[0033] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 638; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 652; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 666; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 680; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 694; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 708. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 467; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 492; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 530; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 555; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 580; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 605. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 465; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 490; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 528; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 553; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 578; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 603. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 466; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 491; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 529; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 554; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 579; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 604.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 468; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 493; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 531; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 556; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 581; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 606. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 469; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 494; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 532; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 557; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 582; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 607. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 631; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 645; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 659; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 673; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 687; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 701.

[0034] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 639; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 653; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 667; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 681; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 695; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 709. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 472; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 497; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 535; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 560; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 585; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 610. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 470; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 495; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 533; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 558; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 583; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 608. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 471; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 496; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 534; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 559; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 584; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 609.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 473; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 498; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 536; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 561; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 586; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 611. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 474; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 499; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 537; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 562; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 587; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 612. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 632; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 646; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 660; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 674; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 688; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 702.

[0035] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 640; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 654; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 668; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 682; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 696; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 710. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 477; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 515; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 540; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 565; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 590; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 615. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 475; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 513; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 538; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 563; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 588; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 613. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 476; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 514; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 539; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 564; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 589; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 614.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (v) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 478; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 516; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 541; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 566; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 591; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 616. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 479; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 517; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 542; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 567; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 592; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 617. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 633; ​​(b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 647; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 661; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 675; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 689; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 703.

[0036] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 641; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 655; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 669; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 683; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 697; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 711. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 487; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 525; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 550; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 575; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 600; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 625. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 485; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 523; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 548; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 573; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 598; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 623. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 486; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 524; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 549; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 574; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 599; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 624.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 488; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 526; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 551; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 576; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 601; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 626. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 489; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 527; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 552; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 577; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 602; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 627. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 634; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 648; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 662; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 676; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 690; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 704.

[0037] 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) 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 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; in some embodiments, the antibody or antigen-binding fragment thereof comprises: 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.

[0038] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of 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 of 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 VH comprising the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 3. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 2; and / or (b) a VL comprising the amino acid sequence of 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 (b) 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 (b) 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 (b) 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 (b) 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 of SEQ ID NO: 13; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 14; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 23; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 24.In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 25; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 26. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 27; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 28. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 29; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 30. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 31; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 32.

[0039] In some embodiments, the antibody or its antigen-binding fragment further comprises an IgG constant region. In some embodiments, the antibody or its antigen-binding fragment further comprises an IgG constant region, and the antibody or its antigen-binding fragment further comprises an IgG constant region, and the IgG constant region has a reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG and / or has a 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 with the amino acid sequence shown in any one of SEQ ID NOs: 500-512. In some embodiments, the constant region comprises an amino acid sequence shown in any one of SEQ ID NOs: 500-512.

[0040] In some embodiments, the antibody or antigen-binding fragment thereof comprises a constant region having an amino acid sequence variant corresponding to the following, 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 or 236V 6R, (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, 2 56K, 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, ) 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 382P, (nn) 385P, (oo) 424H, 424M or 424V, (pp) 434I, (qq) 438G, (rr) 439E, 439L 39H 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 P 329G, (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) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or any combination of (nnn)(a)-(mmm).

[0041] In some embodiments, the antibody or antigen-binding fragment thereof is an IgG antibody. In some embodiments, the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

[0042] In some embodiments, the antibody or antigen-binding fragment thereof is human, chimeric, or humanized.

[0043] In some embodiments, the antigen-binding fragment thereof is a Fab, F(ab')2, a single domain antibody, or a single chain variable fragment (scFv).

[0044] In some embodiments, the antibody or antigen-binding fragment thereof binds to one or more amino acid residues of CD30L that interact with CD30.

[0045] 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, the inhibition or blocking is determined in an ELISA assay, a cell binding assay with cells expressing CD30L, or a surface plasmon resonance (SPR) assay.

[0046] In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to CD30L.

[0047] In some embodiments, the antibody or antigen-binding fragment thereof (i) inhibits the secretion of interleukin-8 in a cell-based assay, (ii) inhibits the 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 the secretion of interleukin-8 in a cell-based assay, (ii) blocks the 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 of cells expressing CD30 and cells expressing CD30L.

[0048] 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.

[0049] In some embodiments, the antibody or antigen-binding fragment thereof binds to CD30L with a dissociation equilibrium constant (KD) of no more than 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. In some embodiments, the antibody or antigen-binding fragment thereof has a dissociation equilibrium constant (KD) of at least 0.1×10 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 1.55×10 6 M -1 S -1 The binding rate constant (k on ) binds to CD30L. In some embodiments, the antibody or antigen-binding fragment thereof binds to CD30L at a rate of no more than 1.4×10 -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 (koff) of β-catenin binds to CD30L.

[0050] In some embodiments, the antibody or antigen-binding fragment thereof is a recombinant antibody or antigen-binding fragment thereof.

[0051] In some embodiments, the antibody or antigen-binding fragment thereof is an isolated antibody or antigen-binding fragment thereof.

[0052] In one aspect, provided herein are recombinant antibodies and / or antigen-binding fragments thereof that bind to CD30L, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 100-139 or 220-234; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 140-179 or 235-249; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 180-219 or 250-264; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 300-339 or 420-434; (e) an immunoglobulin light chain CDR2 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 300-339 or 420-434; NO: 340-379 or 435-449 as shown in any one of the immunoglobulin light chain CDR2 (CDR-L2); and / or (f) comprising the amino acid sequence shown in any one of SEQ ID NO: 380-419 or 450-464 as shown in any one of the immunoglobulin light chain CDR3 (CDR-L3).

[0053] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 100-109; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 140-149; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 180-189; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 300-309; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 340-349; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 300-309. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 380-389.

[0054] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 100-104; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 140-144; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 180-184; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 300-304; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 340-344; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 300-304. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 380-384.

[0055] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 105-109; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 145-149; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 185-189; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 305-309; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 345-349; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 305-309. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 385-389.

[0056] In some embodiments, an 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.

[0057] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 110-119; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 150-159; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 190-199; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 310-319; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 350-359; and / or (e) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 310-319. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 390-399.

[0058] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 110-114; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 150-154; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 190-194; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 310-314; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 350-354; and / or (e) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 310-314. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 390-394.

[0059] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 115-119; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 155-159; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 195-199; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 315-319; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 355-359; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 315-319. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 395-399.

[0060] In some embodiments, an 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.

[0061] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 120-129; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 160-169; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 200-209; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 320-329; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 360-369; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 200-209. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 400-409.

[0062] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 120-124; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 160-164; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 200-204; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 320-324; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 360-364; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 200-204. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 400-404.

[0063] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 125-129; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 165-169; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 205-209; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 325-329; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 365-369; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 205-209. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 405-409.

[0064] In some embodiments, an 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.

[0065] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 130-139; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 170-179; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 210-219; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 330-339; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 370-379; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 210-219. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 410-419.

[0066] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 130-134; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 170-174; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 210-214; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 330-334; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 370-374; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 210-214. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 410-414.

[0067] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 135-139; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 175-179; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 215-219; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 335-339; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 375-379; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 215-219. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 415-419.

[0068] In some embodiments, an 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.

[0069] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 220-224; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 235-239; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 250-254; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 420-424; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 435-439; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 250-254. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 450-454.

[0070] In some embodiments, an 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 NO: 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 NO: 15 and 18.

[0071] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 225-229; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 240-244; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 255-259; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 425-429; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 440-444; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 255-259. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 455-459.

[0072] In some embodiments, an 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 NO: 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 NO: 15 and 20.

[0073] In some embodiments, an antibody or antigen-binding fragment thereof according to any one of the preceding embodiments is provided, wherein the antibody or antigen-binding fragment thereof comprises: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 230-234; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 245-249; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 260-264; (d) an immunoglobulin light chain CDR1 (CDR-L1) comprising the amino acid sequence of any one of SEQ ID NOs: 430-434; (e) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 445-449; and / or (f) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 430-434. An immunoglobulin light chain CDR3 (CDR-L3) having the amino acid sequence shown in any one of NOs: 460-464.

[0074] In some embodiments, an 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 NO: 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 NO: 15 and 22.

[0075] In some embodiments, an antibody or antigen-binding fragment thereof according to any of the foregoing embodiments is provided, which comprises 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 according to any of the foregoing embodiments is provided, wherein the constant region comprises an amino acid sequence having 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs: 500-512. In some embodiments, an antibody or antigen-binding fragment thereof according to any of the foregoing embodiments is provided, wherein the constant region comprises an amino acid sequence shown in any one of SEQ ID NOs: 500-512.

[0076] In some embodiments, an antibody or antigen-binding fragment thereof of any of the foregoing embodiments is provided, comprising a constant region having an amino acid sequence variant corresponding to: (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, (j) 329A, 329G, 329Y, or 329R k) 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) 269N or 269Q, (w) 2 70A, 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 382P, (nn) 385P, (oo) 424H, 4 24M 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) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or any combination of (nnn)(a)-(mmm), according to EU numbering.

[0077] 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 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.

[0078] 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 Fab, F(ab')2, a single domain antibody or a single chain variable fragment (scFv). 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 a bispecific or multispecific antibody.

[0079] In some embodiments, the antibody or antigen-binding fragment thereof of any one of the preceding embodiments is provided, wherein the recombinant antibody or antigen-binding fragment thereof inhibits the binding interaction between CD30L and CD30.

[0080] In one aspect, a nucleic acid encoding a recombinant antibody or antigen-binding fragment thereof according to any of the foregoing embodiments is also provided. A cell comprising the recombinant antibody or antigen-binding fragment thereof according to any of the foregoing embodiments is also provided. In some embodiments, the cell is a eukaryotic cell. In some embodiments, the cell is a prokaryotic cell.

[0081] In one aspect, a recombinant antibody or antigen-binding fragment thereof according to any of the preceding embodiments is provided, for use in a method for inhibiting the binding of CD30L to CD30. Also provided is a recombinant antibody or antigen-binding fragment thereof according to any of the preceding embodiments, for use in a method for inhibiting the activation of CD30 signaling in a cell. Also provided is a recombinant antibody or antigen-binding fragment thereof according to any of the preceding embodiments, for use in a method for inhibiting the activation, expression, and / or secretion of a proinflammatory cytokine protein.

[0082] In one aspect, a recombinant antibody or antigen-binding fragment thereof according to any one of the foregoing 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 syndrome. In some embodiments, irritable bowel syndrome includes ulcerative colitis (UC) or Crohn's disease (CD).

[0083] 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 according to any of the preceding embodiments, thereby treating or ameliorating the autoimmune disease. Also provided is a method for inhibiting and / or reducing the binding of CD30L to CD30 in an individual suffering from an inflammatory or autoimmune disease, comprising administering to the individual suffering from an inflammatory or autoimmune disease a recombinant antibody or antigen-binding fragment thereof according to any of the preceding embodiments, thereby inhibiting and / or reducing the 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 according to any of the preceding embodiments, thereby reducing and / or inhibiting inflammation.

[0084] In some embodiments, the method of any of the preceding embodiments is provided, wherein the individual suffers from an autoimmune disease. In some embodiments, the method of any of the preceding embodiments is provided, wherein the autoimmune disease is irritable bowel syndrome. In some embodiments, the method of any of the preceding embodiments is provided, wherein irritable bowel syndrome comprises ulcerative colitis (UC) or Crohn's disease (CD).

[0085] In some embodiments, there is provided a method according to any one of the foregoing embodiments, wherein alleviating and / or suppressing inflammation includes reducing the amount of proinflammatory cytokine expression or secretion in the tissue of the individual or the individual. In some embodiments, there is provided a method according to any one of the foregoing embodiments, wherein proinflammatory cytokines include interleukin 8 and / or interleukin 6. In some embodiments, there is provided a method according to any one of the foregoing embodiments, wherein the individual suffers from an autoimmune disease. In some embodiments, there is provided a method according to any one of the foregoing embodiments, wherein the autoimmune disease is irritable bowel syndrome. In some embodiments, there is provided a method according to any one of the foregoing embodiments, wherein irritable bowel syndrome includes ulcerative colitis (UC) or Crohn's disease (CD).

[0086] Also provided herein are pharmaceutical compositions comprising antibodies that bind to CD30 ligand (also referred to as CD30L, CD153, TNFSF8), which can be used to treat autoimmune diseases, such as IBD. Generally, in one aspect, the pharmaceutical compositions provided herein comprise anti-CD30L, which effectively inhibits the interaction between CD30L and CD30, thereby effectively reducing, inhibiting, or preventing immune activation (e.g., an inflammatory response). In addition, the anti-CD30L in the pharmaceutical compositions provided herein also has properties useful for therapeutic applications, including, for example, reduced and / or low immunogenicity. Thus, the pharmaceutical compositions described herein comprising anti-CD30L can inhibit the expression / secretion of certain inflammatory cytokines (e.g., interleukin-6 and interleukin-8), which play a key role in inflammatory and autoimmune diseases (e.g., inflammatory bowel disease, Crohn's disease, and ulcerative colitis).

[0087] Thus, in one aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof comprises (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NOs: (d) a CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759; and / or (e) a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.

[0088] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof comprise (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 100-109, 628, 635, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 140-149, 642, 649, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 180-189, 656, 663, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 300-309, 670, 677, and 744-751; (e) a CDR-L2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: NO: 340-349, 684, 691 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO: 380-389, 698, 705 and 760-765.

[0089] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-104; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-144; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-184; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-304; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-344; and / or (f) a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-384.

[0090] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 105-109, 628, 635, and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 145-149, 642, 649, and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 185-189, 656, 663, and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 305-309, 670, 677, and 744-751; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NOs: NO: 345-349, 684, 691 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO: 385-389, 698, 705 and 760-765.

[0091] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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.

[0092] In one aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids in CD30L, wherein the one or more amino acids in CD30L are selected from N165, K166, I168, K169 and D234, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0093] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid in CD30L selected from the group consisting of N165, K166, I168, K169, and D234; (ii) any two amino acids in CD30L selected from the group consisting of N165, K166, I168, K169, and D234; (iii) any three amino acids in CD30L selected from the group consisting of N165, K166, I168, K169, and D234; (iv) any four amino acids in CD30L selected from the group consisting of N165, K166, I168, K169, and D234; or (v) any five amino acids in CD30L selected from the group consisting of N165, K166, I168, K169, and D234; wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0094] In another aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids in CD30L, wherein the one or more amino acids in CD30L are selected from H167, S217 and D118, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0095] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof binds to an epitope, wherein the epitope comprises: (i) any one amino acid in CD30L selected from H167, S217, and D118; (ii) any two amino acids in CD30L selected from H167, S217, and D118; or (iii) any three amino acids in CD30L selected from H167, S217, and D118; wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0096] In another aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids in CD30L, wherein the one or more amino acids in CD30L are selected from D118, N165, K166, H167, I168, K169, S217 and D234, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0097] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid in CD30L selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234; (ii) any two amino acids in CD30L selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234; (iii) any three amino acids in CD30L selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234; (iv) any four amino acids in CD30L selected from the group consisting of D118, N165, K166, H167, I168, K169, S217, and D234. 167, I168, K169, S217 and D234; (v) any five amino acids in CD30L selected from D118, N165, K166, H167, I168, K169, S217 and D234; (vi) any six amino acids in CD30L selected from D118, N165, K166, H167, I168, K169, S217 and D234; (vii) any seven amino acids in CD30L selected from D118, N165, K166, H167, I168, K169, S217 and D234; or (viii) any five amino acids in CD30L selected from D118, N165, K166, H167, I168, K169, S217 and D234; wherein the amino acids are according to SEQ ID NO: 1 The numbering is based on the CD30L amino acid sequence shown in ID NO: 33.

[0098] In another aspect, provided herein is a pharmaceutical composition comprising an anti-CD30L antibody or antigen-binding fragment thereof that binds to an epitope comprising K169 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0099] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof binds to an epitope in CD30L comprising D234, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0100] In one aspect, provided herein is a pharmaceutical composition comprising an anti-CD30L antibody or antigen-binding fragment thereof that binds to an epitope in CD30L comprising D234, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0101] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the epitope of the anti-CD30L antibody or antigen-binding fragment further comprises N165 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0102] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the epitope of the anti-CD30L antibody or antigen-binding fragment further comprises I168 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0103] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the epitope of the anti-CD30L antibody or antigen-binding fragment further comprises K166 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence set forth in SEQ ID NO: 33.

[0104] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the epitope of the anti-CD30L antibody or antigen-binding fragment further comprises H167 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0105] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the epitope of the anti-CD30L antibody or antigen-binding fragment further comprises S217 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0106] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the epitope of the anti-CD30L antibody or antigen-binding fragment further comprises D118 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO: 33.

[0107] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 110-119, 629, 636, and 712-723; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 150-159, 643, 650, and 724-735; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 190-199, 657, 664, and 736-743; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 310-319, 671, 678, and 744-751; (e) a CDR-L2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: NO: 350-359, 685, 692 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NO: 390-399, 699, 706 and 760-765.

[0108] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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: 110-114; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 150-154; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 190-194; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 310-314; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 350-354; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 390-394.

[0109] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof comprise: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 115-119, 629, 636, and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 155-159, 643, 650, and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 195-199, 657, 664, and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 315-319, 671, 678, and 744-751; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NOs: NOs: 355-359, 685, 692 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 395-399, 699, 706 and 760-765.

[0110] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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.

[0111] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 120-129 and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 160-169 and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 200-209 and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 320-329 and 744-751; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 360-369 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 400-409 and 760-765.

[0112] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 120-124; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 160-164; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 200-204; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 320-324; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 360-364; and / or (f) a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 400-404.

[0113] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises: (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 125-129 and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 165-169 and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 205-209 and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 325-329 and 744-751; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 365-369 and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 405-409 and 760-765.

[0114] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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.

[0115] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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: 130-139 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.

[0116] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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: 130-134; (b) a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 170-174; (c) a CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 210-214; (d) a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 330-334; (e) a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 370-374; and / or (f) a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 410-414.

[0117] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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.

[0118] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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.

[0119] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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.

[0120] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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 comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 18.

[0121] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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.

[0122] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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 immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 20.

[0123] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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.

[0124] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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 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 immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 22.

[0125] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0126] (i) (a) CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 465-469, 631, 638 and 712-723; (b) CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 490-494, 645, 652 and 724-735; (c) CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 528-532, 659, 666 and 736-743; (d) CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 553-557, 673, 680 and 744-751; (e) CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 578-582, 687, 694 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs: 603-607, 701, 708, and 760-765;

[0127] (ii) (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 470-474, 632, 639, and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 495-499, 646, 653, and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 533-537, 660, 667, and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 558-562, 674, 681, and 744-751; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 583-587, 688, 695, and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs: 608-612, 702, 709, and 760-765;

[0128] (iii) (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 475-479, 633, 640, and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 513-517, 647, 654, and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 538-542, 661, 668, and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 563-567, 675, 682, and 744-751; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 588-592, 689, 696, and 752-759; and / or (f) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 538-542, 661, 668, and 736-743. CDR-L3 of the amino acid sequence shown in any one of NOs: 613-617, 703, 710, and 760-765;

[0129] (iv) (a) CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 480-484, 630, 637 and 712-723; (b) CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 518-522, 644, 651 and 724-735; (c) CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 543-547, 658, 665 and 736-743; (d) CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 568-572, 672, 679 and 744-751; (e) CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 593-597, 686, 693 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs: 618-622, 700, 707, and 760-765; or

[0130] (v) (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 485-489, 634, 641, and 712-723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 523-527, 648, 655, and 724-735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 548-552, 662, 669, and 736-743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 573-577, 676, 683, and 744-751; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 598-602, 690, 697, and 752-759; and / or (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs: 623-627, 704, 711 and 760-765.

[0131] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0132] (i) (a) CDR-H1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 712-723; (b) CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 724-735; (c) CDR-H3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 736-743; (d) CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 744-751; (e) CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 752-759; and / or (f) CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 760-765;

[0133] (ii) (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 712, 714, 716, 718, 720, and 722; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 724, 726, 728, 730, 732, and 734; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 736, 738, 740, and 742; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 744, 746, 748, and 750; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 752, 754, 756, and 758; and / or (f) a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 760, 762, and 764;

[0134] (iii) (a) a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 713, 715, 717, 719, 721, and 723; (b) a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 725, 727, 729, 731, 733, and 735; (c) a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 737, 739, 741, and 743; (d) a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 745, 747, 749, and 751; (e) a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 753, 755, 757, and 759; and / or (f) a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 761, 763, and 765;

[0135] (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 712; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 730; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760;

[0136] (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 713; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 731; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761;

[0137] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 712; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 724; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760;

[0138] (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 713; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 725; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761;

[0139] (viii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 714; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 726; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760;

[0140] (ix) (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 715; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 727; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 761;

[0141] (x) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 716; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 728; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760;

[0142] (xi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 717; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 729; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761;

[0143] (xii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 718; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 730; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 738; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 746; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 754; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 762;

[0144] (xiii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 719; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 731; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 739; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 747; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 755; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 763;

[0145] (xiv) (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 720; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 732; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 740; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 748; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 756; and / or (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 760;

[0146] (xv) (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;

[0147] (xvi) (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; or

[0148] (xvii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 723; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 735; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 743; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 751; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 759; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 765.

[0149] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0150] (i) (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 635; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 649; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 663; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 677; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 691; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 705;

[0151] (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 107; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 147; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 187; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 307; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 347; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 387;

[0152] (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 105; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 145; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 185; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 305; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 345; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 385;

[0153] (iv) (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 106; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 186; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 306; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 346; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 386;

[0154] (v) (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 108; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 148; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 188; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 308; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 348; and / or (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 388;

[0155] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 109; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 149; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 189; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 309; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 349; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 389; or

[0156] (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 628; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 642; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 656; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 670; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 684; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 698.

[0157] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0158] (i) (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 636; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 650; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 664; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 678; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 692; and / or (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 706;

[0159] (ii) (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 117; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 157; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 197; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 317; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 357; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 397;

[0160] (iii) (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 115; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 155; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 195; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 315; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 355; and / or (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 395;

[0161] (iv) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 356; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 396;

[0162] (v) (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 158; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 198; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 318; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 358; and / or (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 398;

[0163] (vi) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 359; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 399; or

[0164] (vii) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 685; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 699.

[0165] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0166] (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 637; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 651; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 665; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 679; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 693; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 707;

[0167] (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 482; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 520; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 545; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 570; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 595; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 620;

[0168] (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 480; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 518; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 543; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 568; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 593; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 618;

[0169] (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 481; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 519; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 544; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 569; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 594; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 619;

[0170] (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 483; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 521; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 546; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 571; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 596; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 621;

[0171] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 484; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 522; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 547; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 572; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 597; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 622; or

[0172] (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 630; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 644; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 658; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 672; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 686; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 700.

[0173] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0174] (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 638; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 652; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 666; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 680; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 694; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 708;

[0175] (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 467; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 492; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 530; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 555; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 580; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 605;

[0176] (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 465; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 490; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 528; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 553; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 578; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 603;

[0177] (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 466; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 491; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 529; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 554; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 579; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 604;

[0178] (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 468; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 493; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 531; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 556; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 581; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 606;

[0179] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 469; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 494; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 532; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 557; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 582; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 607; or

[0180] (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 631; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 645; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 659; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 673; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 687; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 701.

[0181] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0182] (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 639; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 653; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 667; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 681; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 695; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 709;

[0183] (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 472; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 497; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 535; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 560; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 585; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 610;

[0184] (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 470; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 495; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 533; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 558; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 583; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 608;

[0185] (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 471; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 496; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 534; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 559; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 584; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 609;

[0186] (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 473; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 498; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 536; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 561; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 586; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 611;

[0187] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 474; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 499; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 537; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 562; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 587; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 612; or

[0188] (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 632; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 646; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 660; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 674; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 688; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 702.

[0189] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0190] (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 640; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 654; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 668; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 682; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 696; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 710;

[0191] (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 477; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 515; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 540; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 565; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 590; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 615;

[0192] (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 475; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 513; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 538; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 563; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 588; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 613;

[0193] (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 476; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 514; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 539; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 564; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 589; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 614;

[0194] (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 478; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 516; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 541; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 566; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 591; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 616;

[0195] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 479; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 517; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 542; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 567; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 592; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 617; or

[0196] (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 633; ​​(b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 647; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 661; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 675; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 689; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 703.

[0197] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0198] (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 641; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 655; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 669; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 683; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 697; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 711;

[0199] (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 487; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 525; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 550; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 575; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 600; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 625;

[0200] (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 485; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 523; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 548; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 573; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 598; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 623;

[0201] (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 486; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 524; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 549; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 574; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 599; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 624;

[0202] (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 488; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 526; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 551; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 576; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 601; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 626;

[0203] (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 489; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 527; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 552; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 577; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 602; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 627; or

[0204] (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 634; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 648; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 662; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 676; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 690; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 704.

[0205] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0206] (i) (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;

[0207] (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: 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;

[0208] (iii) (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;

[0209] (iv) (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;

[0210] (v) (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;

[0211] (vi) (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;

[0212] (vii) (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;

[0213] (viii) (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;

[0214] (ix) (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;

[0215] (x) (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;

[0216] (xi) (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;

[0217] (xii) (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;

[0218] (xiii) (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; or

[0219] (xiv) (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.

[0220] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises:

[0221] (i) (a) a VH comprising the amino acid sequence of 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 of any one of SEQ ID NOs: 3, 4, 7, 8, 11, 12, 15, 16, 18, 20, 22, 24, 26, 28 and 30;

[0222] (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;

[0223] (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;

[0224] (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;

[0225] (v) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 6; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 8;

[0226] (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;

[0227] (vii) (a) a VH comprising the amino acid sequence of SEQ ID NO: 10; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 12;

[0228] (viii) (a) a VH comprising the amino acid sequence of SEQ ID NO: 13; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 15;

[0229] (ix) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 14; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 16;

[0230] (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;

[0231] (xi) (a) a VH comprising the amino acid sequence of SEQ ID NO: 25; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 26;

[0232] (xii) (a) a VH comprising the amino acid sequence of SEQ ID NO: 27; and / or (b) a VL comprising the amino acid sequence of SEQ ID NO: 28;

[0233] (xiii) (a) VH comprising the amino acid sequence of SEQ ID NO: 29; and / or (b) VL comprising the amino acid sequence of SEQ ID NO: 30; or

[0234] (xiv) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 31; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 32.

[0235] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof further comprises an IgG constant region.

[0236] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof further comprises an IgG constant region having reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG and / or reduced complement-dependent cytotoxicity (CDC) compared to human IgG.

[0237] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the constant region of the anti-CD30L antibody or antigen-binding fragment 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.

[0238] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the constant region of the anti-CD30L antibody or antigen-binding fragment comprises the amino acid sequence set forth in any one of SEQ ID NOs: 500-512.

[0239] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof comprises a constant region having an amino acid sequence variant corresponding to: (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, 329Q or 329L, 9Y or 329R, (k) 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) 269N or 269 Q, (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 382P, (nn) 385P, (oo) 424 H, 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) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or any combination of (nnn)(a)-(mmm), according to EU numbering.

[0240] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is an IgG antibody.

[0241] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the IgG antibody is IgG1, IgG2, IgG3, or IgG4.

[0242] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is human, chimeric, or humanized.

[0243] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is Fab, F(ab')2, a single domain antibody, or a single chain variable fragment (scFv).

[0244] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is a bispecific or multispecific antibody.

[0245] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof bind to one or more amino acid residues of CD30L that interact with CD30.

[0246] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof inhibit the binding interaction between CD30L and CD30.

[0247] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibodies or antigen-binding fragments thereof block the binding interaction between CD30L and CD30.

[0248] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, inhibition or blocking is determined in an ELISA assay, a cell binding assay with cells expressing CD30L, or a surface plasmon resonance (SPR) assay.

[0249] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof specifically binds to CD30L.

[0250] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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).

[0251] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, 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).

[0252] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the cell-based assay is a dual cell assay, wherein the cells express CD30 and the cells express CD30L.

[0253] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof binds to (i) human CD30L, (ii) cynomolgus monkey CD30L, or (iii) human CD30L and cynomolgus monkey CD30L.

[0254] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof has a dissociation equilibrium constant (K) of no more than 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. D ) binds to CD30L.

[0255] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is present in an amount of at least 0.1×10 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 1.55×10 6 M -1 S -1 The binding rate constant (k on ) binds to CD30L.

[0256] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is present at a concentration of no more than 1.4×10 -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 (koff) of β-catenin binds to CD30L.

[0257] In one aspect, provided herein is a pharmaceutical composition comprising an anti-CD30L antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof binds to isoform 1 of CD30L, and wherein the antibody or antigen-binding fragment thereof does not bind to isoform 2 of CD30L. In some embodiments, isoform 1 of CD30L comprises the amino acid sequence set forth in SEQ ID NO: 34, and wherein isoform 2 of CD30L comprises the amino acid sequence set forth in SEQ ID NO: 35.

[0258] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof binds to isoform 1 of CD30L, and wherein the antibody or antigen-binding fragment thereof does not bind to isoform 2 of CD30L. In some embodiments, isoform 1 of CD30L comprises the amino acid sequence set forth in SEQ ID NO: 34, and wherein isoform 2 of CD30L comprises the amino acid sequence set forth in SEQ ID NO: 35.

[0259] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is a recombinant antibody or antigen-binding fragment thereof.

[0260] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the antibody or antigen-binding fragment thereof is an isolated antibody or antigen-binding fragment thereof.

[0261] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the anti-CD30L antibodies or antigen-binding fragments are

[0262] (a) is a concentration of (i) about 50 mg / ml to about 275 mg / ml, (ii) about 50 mg / ml to about 250 mg / ml, (iii) about 50 mg / ml to about 225 mg / ml, (iv) about 50 mg / ml to about 200 mg / ml, (v) about 50 mg / ml to about 175 mg / ml, (vi) about 50 mg / ml to about 150 mg / ml, (vii) about 50 mg / ml to about 125 mg / ml, (viii) about 50 mg / ml to about 100 mg / ml, or (ix) about 50 mg / ml to about 75 mg / ml;

[0263] (b) is a concentration of (i) about 75 mg / ml to about 275 mg / ml, (ii) about 75 mg / ml to about 250 mg / ml, (iii) about 75 mg / ml to about 225 mg / ml, (iv) about 75 mg / ml to about 200 mg / ml, (v) about 75 mg / ml to about 175 mg / ml, (vi) about 75 mg / ml to about 150 mg / ml, (vii) about 75 mg / ml to about 125 mg / ml, or (viii) about 75 mg / ml to about 100 mg / ml;

[0264] (c) is a concentration of (i) about 100 mg / ml to about 275 mg / ml, (ii) about 100 mg / ml to about 250 mg / ml, (iii) about 100 mg / ml to about 225 mg / ml, (iv) about 100 mg / ml to about 200 mg / ml, (v) about 100 mg / ml to about 175 mg / ml, (vi) about 100 mg / ml to about 150 mg / ml, or (vii) about 100 mg / ml to about 125 mg / ml;

[0265] (d) is a concentration of (i) about 125 mg / ml to about 275 mg / ml, (ii) about 125 mg / ml to about 250 mg / ml, (iii) about 125 mg / ml to about 225 mg / ml, (iv) about 125 mg / ml to about 200 mg / ml, (v) about 125 mg / ml to about 175 mg / ml, or (vi) about 125 mg / ml to about 150 mg / ml;

[0266] (e) is a concentration of (i) about 150 mg / ml to about 275 mg / ml, (ii) about 150 mg / ml to about 250 mg / ml, (iii) about 150 mg / ml to about 225 mg / ml, (iv) about 150 mg / ml to about 200 mg / ml, or (v) about 150 mg / ml to about 175 mg / ml;

[0267] (f) a concentration of (i) about 175 mg / ml to about 275 mg / ml, (ii) about 175 mg / ml to about 250 mg / ml, (iii) about 175 mg / ml to about 225 mg / ml, or (iv) about 175 mg / ml to about 200 mg / ml;

[0268] (g) is at a concentration of (i) about 200 mg / ml to about 275 mg / ml, (ii) about 200 mg / ml to about 250 mg / ml, or (iii) about 200 mg / ml to about 225 mg / ml; or

[0269] (h) is a concentration of (i) at least about 50 mg / mL, (ii) at least about 75 mg / ml, (iii) at least about 100 mg / ml, (iv) at least about 125 mg / ml, (v) at least about 150 mg / ml, (vi) at least about 175 mg / ml, (vii) at least about 200 mg / ml, (viii) at least about 225 mg / ml or (ix) at least about 250 mg / ml.

[0270] In one aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment that binds to CD30L (anti-CD30L antibody or antigen-binding fragment) at a concentration of (i) at least about 50 mg / mL, (ii) at least about 75 mg / ml, (iii) at least about 100 mg / ml, (iv) at least about 125 mg / ml, (v) at least about 150 mg / ml, (vi) at least about 175 mg / ml, (vii) at least about 200 mg / ml, (viii) at least about 225 mg / ml, or (ix) at least about 250 mg / ml.

[0271] In another aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment that binds to CD30L (anti-CD30L antibody or antigen-binding fragment) at the following concentrations:

[0272] (a) a concentration of (i) about 50 mg / ml to about 275 mg / ml, (ii) about 50 mg / ml to about 250 mg / ml, (iii) about 50 mg / ml to about 225 mg / ml, (iv) about 50 mg / ml to about 200 mg / ml, (v) about 50 mg / ml to about 175 mg / ml, (vi) about 50 mg / ml to about 150 mg / ml, (vii) about 50 mg / ml to about 125 mg / ml, (viii) about 50 mg / ml to about 100 mg / ml, or (ix) about 50 mg / ml to about 75 mg / ml;

[0273] (b) a concentration of (i) about 75 mg / ml to about 275 mg / ml, (ii) about 75 mg / ml to about 250 mg / ml, (iii) about 75 mg / ml to about 225 mg / ml, (iv) about 75 mg / ml to about 200 mg / ml, (v) about 75 mg / ml to about 175 mg / ml, (vi) about 75 mg / ml to about 150 mg / ml, (vii) about 75 mg / ml to about 125 mg / ml, or (viii) about 75 mg / ml to about 100 mg / ml;

[0274] (c) a concentration of (i) about 100 mg / ml to about 275 mg / ml, (ii) about 100 mg / ml to about 250 mg / ml, (iii) about 100 mg / ml to about 225 mg / ml, (iv) about 100 mg / ml to about 200 mg / ml, (v) about 100 mg / ml to about 175 mg / ml, (vi) about 100 mg / ml to about 150 mg / ml, or (vii) about 100 mg / ml to about 125 mg / ml;

[0275] (d) a concentration of (i) about 125 mg / ml to about 275 mg / ml, (ii) about 125 mg / ml to about 250 mg / ml, (iii) about 125 mg / ml to about 225 mg / ml, (iv) about 125 mg / ml to about 200 mg / ml, (v) about 125 mg / ml to about 175 mg / ml, or (vi) about 125 mg / ml to about 150 mg / ml;

[0276] (e) a concentration of (i) about 150 mg / ml to about 275 mg / ml, (ii) about 150 mg / ml to about 250 mg / ml, (iii) about 150 mg / ml to about 225 mg / ml, (iv) about 150 mg / ml to about 200 mg / ml, or (v) about 150 mg / ml to about 175 mg / ml;

[0277] (f) a concentration of (i) about 175 mg / ml to about 275 mg / ml, (ii) about 175 mg / ml to about 250 mg / ml, (iii) about 175 mg / ml to about 225 mg / ml, or (iv) about 175 mg / ml to about 200 mg / ml; or

[0278] (g) a concentration of (i) about 200 mg / ml to about 275 mg / ml, (ii) about 200 mg / ml to about 250 mg / ml, or (iii) about 200 mg / ml to about 225 mg / ml.

[0279] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the pharmaceutical composition comprises a buffer. In some embodiments, the buffer is selected from acetate buffer, succinate buffer, histidine buffer, phosphate buffer, and citric acid buffer. In some embodiments, the buffer is a histidine buffer. In some embodiments, the concentration of the buffer is 0.1 mM to 1 M. In some embodiments, the concentration of the buffer is 1 mM to 100 mM. In some embodiments, the concentration of the buffer is 10 mM to 50 mM. In some embodiments, the concentration of the buffer is about 20 mM. In some embodiments, the pH of the buffer is 4 to 7. In some embodiments, the pH of the buffer is 5 to 6. In some embodiments, the pH of the buffer is about 5.5.

[0280] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the pharmaceutical compositions comprise a pharmaceutically acceptable excipient. In some embodiments, the excipient is arginine, arginine hydrochloride (arginine HCl), proline, a polyol, sodium chloride, glycine, lysine, lysine hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, calcium chloride, or a combination thereof. In some embodiments, the excipient is arginine HCl. In some embodiments, the concentration of arginine HCl is (i) 25 mM to 300 mM, (ii) 50 mM to 250 mM (iii) 50 mM to 200 mM, (iv) 75 mM to 150 mM, or (v) about 100 mM. In some embodiments, the polyol is selected from sugars, sugar alcohols, and sugar acids. In some embodiments, the sugar is sucrose. In some embodiments, sucrose is: (i) at a concentration of 5%-10% (weight to volume, w / v), (ii) at a concentration of about 5% (w / v), (iii) at a concentration of 150 mM to 300 mM, or (iv) at a concentration of about 150 mM.

[0281] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the pharmaceutical composition further comprises a surfactant. In some embodiments, the surfactant is a polysorbate. In some embodiments, the surfactant is polysorbate-80 (PS80). In some embodiments, the surfactant is poloxamer 188 (P188). In some embodiments, the surfactant is polysorbate-20 (PS20). In some embodiments, the concentration of the surfactant is (i) 0.001%-0.1% (w / v), (ii) 0.005-0.05% (w / v), (iii) 0.01-0.05% (w / v), (iv) 0.01-0.04% (w / v), (v) 0.01-0.03% (w / v), (vi) 0.01-0.02% (w / v), (vii) about 0.02% (w / v), (viii) about 0.03% (w / v), (ix) about 0.04% (w / v), or (x) about 0.05% (w / v).

[0282] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the pharmaceutical compositions comprise sodium chloride (NaCl). In some embodiments, the concentration of NaCl is (i) 25 mM to 150 mM, (ii) 25 mM to 100 mM, (iii) 50 mM to 100 mM, (iv) 75 mM to 100 mM, or (v) about 50 mM.

[0283] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the pharmaceutical composition comprises an antioxidant.

[0284] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the pharmaceutical compositions do not comprise an antioxidant.

[0285] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the viscosity of the composition is 1-50 cP at 25° C. In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the viscosity of the composition is 10-25 cP at 25° C. In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the viscosity of the composition is 1-50, 2-49, 3-48, 4-46, 5-45, 6-44, 7-43, 8-42, 9-41, 10-40, 10-35, 10-30, 11-29, 12-28, 13-27, 14-26, 15-25, 16-24, 17-23, 18-22, 18-21, 18-20, 18-19, 19-21, 1-10, 1-15, or 1-20 cP at 25°C. In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the viscosity of the composition is no more than 25 cP, no more than 24 cP, no more than 23 cP, no more than 22 cP, no more than 21 cP, no more than 20 cP, or no more than 19 cP at 25° C. In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the viscosity of the composition is about 15 cP, about 16 cP, about 17 cP, about 18 cP, about 19 cP, about 20 cP, about 21 cP, about 22 cP, about 23 cP, about 24 cP, or about 25 cP at 25° C.

[0286] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the composition is a stable composition. In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the composition is stable when: (i) stored at 25°C ± 5°C for at least 2, 4, 8, 12, 16, 20, or 24 weeks, (ii) stored at 40°C ± 5°C for at least 2, 4, or 8 weeks, or (iii) stored at 25°C ± 5°C for at least 2, 4, 8, 12, 16, 20, or 24 weeks. In some embodiments, the stability of the composition is determined by: (i) maintaining at least 98% of the main peak of the antibody in size exclusion chromatography, (ii) maintaining at least 65% of the main peak of the antibody in iCIEF, (iii) maintaining at least 98% purity, (iv) maintaining at least 99% antibody concentration, (v) maintaining no more than 500 particles / ml larger than 2 μm, no more than 10 particles / ml larger than 10 μm, and / or no more than 2 particles / ml larger than 25 μm, and / or any combination of (vi) (i)-(iv).

[0287] In some embodiments of the pharmaceutical compositions of the anti-CD30L antibodies or antigen-binding fragments provided herein, the composition comprises the anti-CD30L antibody or antigen-binding fragment at a concentration of 200 mg / mL, 20 mM histidine buffer, 100 mM arginine monohydrochloride, and 0.02% (w / v) PS20, at a pH of 5.5.

[0288] In one aspect, provided herein is a pharmaceutical composition comprising an anti-CD30L antibody or antigen-binding fragment at a concentration of 200 mg / mL, 20 mM histidine buffer, 100 mM arginine monohydrochloride, and 0.02% (w / v) PS20, at a pH of 5.5.

[0289] In some embodiments of the pharmaceutical compositions of anti-CD30L antibodies or antigen-binding fragments provided herein, the anti-CD30L blocks both soluble CD30L and transmembrane CD30L.

[0290] In another aspect, the present invention provides a method for preparing a pharmaceutical preparation described herein, comprising: culturing cells in a culture medium, wherein the cells comprise one or more polynucleotides comprising a nucleotide sequence encoding a heavy chain, a light chain, or both a heavy chain and a light chain of the antibody or its antigen-binding fragment. In some embodiments of the method for preparing a pharmaceutical preparation, the method further comprises expressing one or more polynucleotides in a cell. In some embodiments of the method for preparing a pharmaceutical preparation, the method further comprises purifying the antibody or its antigen-binding fragment. In some embodiments of the method for preparing a pharmaceutical preparation, the method further comprises a formulation step.

[0291] In some embodiments, provided herein are pharmaceutical compositions for use in a method of inhibiting binding of CD30L to CD30.

[0292] In some embodiments, provided herein are pharmaceutical compositions for use in a method of inhibiting CD30 signaling activation in a cell.

[0293] In some embodiments, provided herein are pharmaceutical compositions for use in methods for inhibiting activation, expression, and / or secretion of proinflammatory cytokine proteins. In some embodiments, the proinflammatory cytokine proteins are interleukin-8 and / or interleukin-6. In some embodiments, interleukin-8 is expressed or released by T lymphocytes.

[0294] In some embodiments, provided herein is a pharmaceutical composition for treating an autoimmune disease in an individual in need thereof. In some embodiments, the autoimmune disease is irritable bowel syndrome. In some embodiments, irritable bowel syndrome includes ulcerative colitis (UC) or Crohn's disease (CD).

[0295] In one aspect, the present invention provides a method for treating or improving an autoimmune disease in an individual in need thereof, the method comprising administering a pharmaceutical composition as described herein to the individual, thereby treating or improving the autoimmune disease. In some embodiments, the autoimmune disease is irritable bowel syndrome. In some embodiments, irritable bowel syndrome includes ulcerative colitis (UC) or Crohn's disease (CD).

[0296] In another aspect, provided herein is a method for inhibiting and / or reducing the binding of CD30L to CD30 in an individual suffering from an inflammatory or autoimmune disease, the method comprising administering a pharmaceutical composition as described herein to an individual suffering from an inflammatory or autoimmune disease, thereby inhibiting and / or reducing the binding of CD30L to CD30. In some embodiments, the individual suffers from an autoimmune disease. In some embodiments, the autoimmune disease is irritable bowel syndrome. In some embodiments, irritable bowel syndrome includes ulcerative colitis (UC) or Crohn's disease (CD).

[0297] In another aspect, there is provided herein a method for reducing and / or suppressing inflammation in an individual, the method comprising administering a pharmaceutical composition as described herein to the individual, thereby reducing and / or suppressing inflammation. In some embodiments, reducing and / or suppressing inflammation comprises reducing the amount of proinflammatory cytokines expressed or secreted in the individual or the individual's tissue. In some embodiments, wherein reducing and / or suppressing inflammation comprises reducing the amount of proinflammatory cytokines expressed or secreted by T lymphocytes in the individual. In some embodiments, proinflammatory cytokines include interleukin-8. In some embodiments, the individual suffers from an autoimmune disease. In some embodiments, the autoimmune disease is irritable bowel syndrome. In some embodiments, irritable bowel syndrome includes ulcerative colitis (UC) or Crohn's disease (CD). 3. Description of the Figures

[0298] Figures 1A-1E Depicted are the dose-dependence curves of various anti-CD30L antibodies in the 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), ELISA assay for binding to rhCD30L (third column from the left), and ELISA assay for antibody-mediated blocking of CD30-Fc binding to huCD30L (fourth column from the left). ELISA units are OD 450 nm; cell binding assay units are mean fluorescence intensity (MFI). Figure 1A : Results of clone 2_germline, 62, 63, 64 and 65; Figure 1B : Results of clones 66, 67, 68, 69, 70, and 71; Figure 1C: Results of clones 72, 73, 74, 75, 76, and 77; Figure 1D : Results of clones 78, 79, 80, and 8; Figure 1E : Results of clones 82, 83, 84 and 85.

[0299] Figure 2 Overlapping patterns of peptides generated by trypsin, chymotrypsin, Asp-N, elastase, and / or thermolysin proteolysis are depicted, showing that the peptide signature covers 94.76% of the CD30L ECD sequence.

[0300] Figure 3 The epitope identified by cross-linking and mass spectrometry studies is depicted in the context of a portion of the CD30L ECD sequence (SEQ ID NO: 34).

[0301] Figure 4A Depicted are cell binding assays for determining anti-CD30L binding to CD30L-expressing cells and for determining anti-CD30L blocking / inhibition of CD30 binding to CD30L-expressing cells. Figure 4B and Figure 4C Depicts Figure 4A Representative binding curves of germline clone 2 in the cell binding assays shown in , where 4B shows binding to B16 cells expressing human CD30L, and 4C shows binding to HEK293 cells expressing cyno CD30L. Figure 4D and Figure 4E Depicts Figure 4A Representative blocking curves of germline clone 2 in the cell binding assay shown in , where 4D shows the blocking curve against B16 cells expressing human CD30L, and 4E shows the blocking curve against HEK293 cells expressing cyno CD30L. Figure 4F The ELISA setup for measuring anti-CD30L binding to purified CD30L is depicted, and Figure 4G Depicted is an ELISA setup for determining blocking / inhibition of CD30L binding to CD30 by anti-CD30L. Figure 4H Describes the use Figure 4F Representative binding curves of germline clone 2 as determined by ELISA are shown in FIG, and Figure 4I Describes the use Figure 4G Representative blocking curve of germline clone 2 assayed by ELISA is shown in . Figure 4J Depicted is a two-cell IL-8 release assay in which CD30-expressing cells release IL-8 following signaling via CD30-CD30L interactions to ligate cells expressing CD30L. Figure 4K and Figure 4L Depicts Figure 4JRepresentative IL-8 release curves of germline clone 2 from the dual cell assay shown in , where 4K shows the IL-8 release curve of B16 cells expressing human CD30L, and 4L shows the IL-8 release curve of HEK293 cells expressing cyno CD30L.

[0302] Figure 5A Depicted are the DSC curves for Formulations F1-F12 from the pH / buffer study described in Section 5.10.4. Figure 5B Depicted are the results of PEG precipitation testing in a pH / buffer study. Figures 5C-5D Depicted are the excipient comparison and surfactant comparison results of SE-UPLC in excipient and surfactant strength studies. Figures 5E-5F Depicted are excipient comparison and surfactant comparison results for iCIEF in excipient and surfactant strength studies. Figures 5G-5H Depicted are the excipient comparison and surfactant comparison results of Caliper-SDS-NR in the excipient and surfactant strength studies. Figures 5I-5J Depicted are the excipient comparison and surfactant comparison results for Caliper-SDS-R in the excipient and surfactant strength studies. Figure 5K Depicted are the DSC curves for formulations FeO1-FeO9 from the excipient and surfactant strength studies described in Section 5.10.5.

[0303] Figure 6A The major paratope residues of CD30L (upper panel) and germline clone 2 anti-CD30L Fab (lower panel) are shown as ribbons. Figure 6B The CD30L epitopes listed in Table 77 (left) and the germline clone 2 anti-CD30L Fab paratopes listed in Table 77 (right) are shown. Figure 6C An overview of the structure of the complex between CD30L and germline clone 2 Fab is shown. In the structure, two Fab molecules of germline clone 2, represented in light grey, are bound to two monomers of sCD30L, which form a CD30L dimer. Figure 6D and Figure 6E The cross-links between CD30L and germline clone 2 Fab identified by XL-MS were shown to be within the expected distance range for the periphery of the non-covalent interactions at the antibody-antigen interface found in the cryo-EM structure, thereby confirming the binding interface identified in the cryoEM structure. Figure 6F Shown is a close-up view of the contact site between E109 of CDR-H3 and N165 of CD30L in the CryoEM structure. Figure 6G Shown is a close-up view of the contact site between H32 of CDR-L1 and K169 of CD30L in the CryoEM structure. Figure 6HShown are close-up views of the contact sites between N31 of CDR-L1 and K166 and I168 of CD30L in the CryoEM structure. Figure 6I Close-up view of the contact site between R54 of CDR-H2 and D234 of CD30L in the cryoEM structure. Figure 6J Close-up view of the contact site between G28 of CDR-L1 and S217 of CD30L in the cryoEM structure. Figure 6K Close-up view of the contact site between Y91 of CDR-L3 and H167 of CD30L in the cryoEM structure.

[0304] Figure 7A Depicted are the percentage changes in body weight in a murine colitis model under various treatment conditions as indicated. CD30L blockade (prophylactic or therapeutic) by Clone_111 effectively prevented colitis-induced weight loss. Figure 7B Depicted are endoscopic scores in a murine colitis model under various treatment conditions, as indicated. Statistical significance was tested by one-way ANOVA followed by Dunnett's multiple comparison test using the PBS-treated group as a comparison. * indicates p < 0.05 and ** indicates p < 0.01. Clone_111 outperformed the anti-IL-12p40-treated positive control and effectively reduced macroscopic colonic pathology, with the majority of animals exhibiting normal colons at the macroscopic level. Figure 7C Depicted are the colon weight:length ratios in a murine colitis model under various treatment conditions, as indicated. Statistical significance was tested by one-way ANOVA followed by Dunnett's multiple comparison test using the PBS-treated group as a comparison. * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001. Anti-IL-12p40 treatment of the positive control significantly reduced the colon weight:length ratio, as did prophylactic and therapeutic CD30L blockade using Clone_111. Figure 7D Depicted are the total histopathological scores in the murine colitis model under the various treatment conditions shown. Statistical significance was also tested. * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001. Blockade of CD30L by Clone-111 prevented microscopic intestinal pathology to a similar extent as the anti-IL-12p40 positive control. This effect was observed not only with prophylactic CD30L blockade (anti-CD30L treatment before or at the beginning of T cell transfer) but also with therapeutic CD30L blockade (anti-CD30L treatment after colitis induction), indicating that the CD30-CD30L interaction plays a continuous role during the development of colitis. Figures 7E-7IRepresentative images of the proximal colon of untreated mice, isotype control, and Clone_111-treated mice are shown as indicated (untreated mouse on the left (7E), isotype control treatment in the middle two panels (7F and 7G), and Clone_111 treatment in the right two panels (7H and 7I)). Figures 7E-7I The images in the Figures demonstrate that CD30L blockade reduces and / or reverses intestinal pathology in colitis. Figure 7F and 7G In the figure, H indicates hyperplasia, E indicates edema, and M indicates affected mucosa. Figures 7J-7S Depicted are cytokine levels in a murine colitis model (IFNg in 7J, IL10 in 7K, IL1b in 7L, IL2 in 7M, IL4 in 7N, IL5 in 7O, IL6 in 7P, KC / Gro in 7Q, TNFα in 7R, IL12p70 in 7S) under various treatment conditions as indicated. Statistical significance was also tested. * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001. Positive control anti-IL-12p40 treatment significantly reduced all cytokines except IL-12p70, while increasing type 2 cytokines IL-4 and IL-5. Prophylactic or therapeutic CD30L blockade using Clone_111 significantly reduced IFNg, IL-2, IL-6, KC / Gro, and TNFα, but did not affect IL-4 or IL-5 levels. These data suggest that the observed anti-colitis effects of CD30L blockade may be due to the suppression of pathogenic immune responses, a mechanism distinct from that of IL-12p40 blockade.

[0305] Figure 8A Depicted are staining of untransfected cells (negative control), CD30L isoform 1 transfected cells, and CD30L isoform 2 transfected cells, stained with AF647-conjugated anti-CD30L antibody (germline clone 2). Also shown are fluorescence minus one ("FMO") controls, where AF647 FMO is stained only with the FITC Flag tag; and FITC FMO is stained only with anti-CD30L-AF647. In the full-panel staining, a clear, correlated FITC+ / AF647+ double-positive population is observed for CD30L isoform 1 transfected cells; whereas CD30L isoform 2 transfected cells are detected only with the FITC Flag tag, with little to no AF647 staining. Figure 8B Schematic diagram showing membrane-bound CD30L isoform 1 and isoform 2. Figure 8B Also described are: (1) the binding of the Flag tag to a FITC-conjugated anti-Flag antibody, and (2) the binding site of an anti-CD30L antibody (germline clone 2) on CD30L isoform 1 that is absent on CD30L isoform 2. 4. Specific Implementation Methods

[0306] Currently, there are a limited number of therapies available for the treatment of autoimmune diseases, such as IBD, and the development of new therapies presents a challenge for the treatment of autoimmune diseases, conditions, and their associated symptoms. A large number of anti-inflammatory therapies either fail to produce an effective therapeutic response or provide a durable response. Furthermore, while patients are receiving ineffective anti-inflammatory therapies, their condition can worsen. For these non-responsive patients, the only treatment option is surgery, typically involving strictureplasty (reshaping of the intestine) or resection (removal of the intestine). Surgical treatment of IBD is invasive, and an estimated one-third of patients undergoing surgery face postoperative risks such as anastomotic leaks, infection, and bleeding. Therefore, the heterogeneity in disease pathogenesis and clinical course, combined with variable and / or inconsistent responses to treatment, suggests that targeted therapies for the treatment of autoimmune diseases such as IBD are an ideal therapeutic strategy. However, very few targeted therapies have been discovered that are effective for patients with IBD, particularly those who may not respond to existing IBD anti-inflammatory therapies. Therefore, novel therapies that specifically target the pathogenesis of IBD are needed to treat autoimmune diseases such as IBD.

[0307] Described herein are antibodies that target and bind to CD30 ligand (CD30L), which in some cases provide effective targeted therapy for the treatment of autoimmune diseases (e.g., IBD). Generally, in one aspect, the antibodies described herein effectively inhibit the interaction between CD30L and CD30, thereby effectively reducing, inhibiting, or preventing immune activation (e.g., inflammatory response). CD30 ligand (also known 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 interacting with its receptor CD30, CD30L can induce signal transduction by regulating TNF receptor-associated factor 1 (TRAF1), TRAF2, 3, and 5. The interaction between CD30 and CD30L leads to triggering immune cell (e.g., T cell) activation (e.g., stimulating immune cell proliferation, releasing cytokines, etc.) and activation of inflammatory response. Therefore, the antibodies targeting CD30L described herein can be used to prevent, inhibit, or reduce CD30-CD30L-mediated immune cell activation and / or activation of an inflammatory response in an individual. In certain instances, preventing, inhibiting, or reducing CD30-CD30L-mediated immune cell activation and / or activation of an inflammatory response in an individual can be used to treat autoimmune diseases, such as IBD.

[0308] 4.1 Anti-CD30L Antibodies

[0309] Described herein are recombinant antibodies or antigen-binding fragments thereof that bind to CD30 ligand (CD30L). As used herein, CD30 ligand, CD30L, or human CD30L (also known as tumor necrosis factor ligand superfamily member 8, CD153; CD30L; CD30LG; TNLG3A) refers to any protein comprising the expressed and processed form of the Homo sapiens CD30L gene, which, in certain embodiments, is designated 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 variants, post-translational modification variants (e.g., as described in UniProtKB / Swiss-Prot P32971). CD30L can be an isoform of CD30L. This isoform of CD30L is the result of an alternative splice site in the coding region of the last exon. In some embodiments of the anti-CD30L antibodies or antigen-binding fragments thereof provided herein, including those described in Section 4.1, the CD30L that is the specific target of the antibody or antigen-binding fragment is isoform 1 of CD30L. In some embodiments of the anti-CD30L antibodies or antigen-binding fragments thereof provided herein, including those described in Section 4.1, the CD30L that is the specific target of the antibody or antigen-binding fragment is isoform 1 of CD30L, wherein isoform 1 comprises the amino acid sequence set forth in SEQ ID NO: 34. In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments thereof provided herein (including those described in Section 4.1), the CD30L that is the specific target of the antibody or antigen-binding fragment is isoform 2 of CD30L. In certain embodiments of the anti-CD30L antibodies or antigen-binding fragments thereof provided herein (including Section 4.1), the CD30L that is the specific target of the antibody or antigen-binding fragment is isoform 2 of CD30L, wherein isoform 2 comprises the amino acid sequence set forth in SEQ ID NO: 35. Isoform 1 of CD30L is described in more detail in NM_001244.4 (mRNA and protein sequences) and NP_001235.1 (protein sequence), which are incorporated herein by reference in their entireties. Isoform 2 of CD30L is described in more detail in NM_001252290.1 ​​(mRNA and protein sequences) and NP_001239219.1 (protein sequence), which are incorporated herein by reference in their entireties. These antibodies also block the interaction between CD30L and CD30 and inhibit the release of proinflammatory cytokines.

[0310] The term "and / or" used in a phrase with a list of members is intended to include all members individually and all combinations of all or part of the list of members. For example, a phrase herein such as "A and / or B" is intended to include A and B; A or B; A (alone); and B (alone). Similarly, the term "and / or" used in a phrase such as "A, B, and / or C" is intended to cover 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).

[0311] This disclosure provides that, in any case herein where an embodiment is provided using the term "comprising," similar embodiments described as "consisting of" and / or "consisting essentially of" are also provided, if similar embodiments are not explicitly provided. This disclosure further provides that, in any case herein where an embodiment is described using the phrase "consisting essentially of," similar embodiments described as "consisting of" are also provided. This disclosure further provides that, in any case herein where an embodiment is described using the phrase "consisting of," similar embodiments described as "consisting essentially of" are also provided.

[0312] All applications, publications, patents and other references, GenBank citations and ATCC citations cited herein are incorporated herein by reference in their entirety. In the event of a conflict, the specification, including definitions, will control.

[0313] As used herein, numerical values ​​are generally presented in range format throughout this document. Unless the context clearly indicates otherwise, the use of range format is merely for convenience and brevity and should not be interpreted as a rigid limitation on the scope of the invention. Therefore, unless the context clearly indicates otherwise, the use of ranges clearly includes all possible subranges, all individual values ​​within the range, and all values ​​or ranges of values, including integers within the range and fractions of values ​​or integers within the range. Regardless of how broad the range is, this interpretation applies in all contexts of this patent document. Thus, for example, a reference to a range of 90-100% includes 91-99%, 92-98%, 93-95%, 91-98%, 91-97%, 91-96%, 91-95%, 91-94%, 91-93%, etc. References to the 90-100% range 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., and so on.

[0314] In addition, 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, 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 25-250, 250-500, 500-1,000, 1,000-2,500, 2,500-5,000, 5,000-25,000, 25,000-50,000 includes any value or range therein or comprises these values, for example, 25, 26, 27, 28, 29...250, 251, 250, 251, 252, 253, 254...500, 501, 502, 503, 504...etc.

[0315] As used herein, a range of ranges is also disclosed throughout this document. The use of a range of ranges includes the combination of upper and lower ranges to provide another range. No matter how wide the range is and in all contexts of this patent document, this construction is applicable. Thus, for example, reference to a range of ranges, such as 5-10, 10-20, 20-30, 30-40, 40-50, 50-75, 75-100, 100-150, includes, for example, 5-20, 5-30, 5-40, 5-50, 5-75, 5-100, 5-150 and 10-30, 10-40, 10-50, 10-75, 10-100, 10-150 and 20-40, 20-50, 20-75, 20-100, 20-150, etc.

[0316] In some embodiments, the term "about" refers to within 10%, within 9%, within 8%, within 7%, within 6%, within 5%, within 4%, within 3%, within 2%, within 1%, or less of a given value, amount, or range. For example, an antibody variable region having about 90% identity to a reference variable region can include an antibody variable region having 82% to 98% identity to the reference variable region.

[0317] The terms "specifically binds to," "specifically binds," and similar terms, when used in the context of one molecule binding to another, refer to one molecule binding to another with an affinity that is significantly greater than any cross-reactive antigen or off-target antigen (collectively referred to as non-target antigens) as determined using experimental techniques such as surface plasmon resonance (SPR), fluorescence activated cell sorting (FACS) analysis, kinetic exclusion assay (KinExA), isothermal titration calorimetry (ITC), radioimmunoassay (RIA), and enzyme-linked immunosorbent assay (ELISA). Typically, the specific or selective response is at least two times greater than the noise of the non-target signal or non-target binding, and may exceed 10 times the non-target binding. See, e.g., Fundamental Immunology 332-36 (Paul ed., 2d ed. 1989) regarding antibody specificity. An antibody or antigen-binding fragment thereof that binds to a target of interest (e.g., target CD30L) is one that binds to the target with sufficient affinity to allow it to be used as a therapeutic agent targeting cells or tissues expressing the target, and does not significantly cross-react with other proteins. In these embodiments, the extent of binding of the antibody or antigen-binding fragment to a "non-target" protein is less than about 10% of the extent of binding of the antibody or antigen-binding fragment to its specific target protein (as determined, for example, by FACS analysis, SPR, KinExA, ITC, ELISA, or RIA). Specific binding can be measured, for example, by measuring the binding of a molecule compared to the binding of a control molecule, which is typically a molecule with a similar structure but no binding activity. For example, specific binding can be determined by competition with a control molecule similar to the target (e.g., an excess of unlabeled target). In this case, specific binding is indicated if binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target. Thus, as used herein, the terms "specifically bind," "specifically binds to," "specifically inhibits," "specifically blocks," or "is specific for" a particular target refer to binding, blocking, or inhibition wherein a molecule binds to, blocks, or inhibits a particular target while not substantially binding to or inhibiting non-targets. In certain embodiments, the anti-CD30L antibodies or antigen-binding fragments provided herein specifically bind to CD30L. In some embodiments, an anti-CD30L antibody or antigen-binding fragment that specifically binds to CD30L indicates that the antibody reacts or binds to CD30L more frequently, more rapidly, for a longer duration, with greater affinity, or a combination thereof, than it reacts or binds to an alternative substance, including an unrelated protein.

[0318] 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 reducing, attenuating, decreasing, diminishing, or completely abolishing 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, such inhibition of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function can 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 other examples, such inhibition of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function can be a complete ablation 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 inhibit 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 inhibit CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function 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 another embodiment, the anti-CD30L antibodies or antigen-binding fragments provided herein completely abrogate CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function.

[0319] As used herein, the terms "blocking" or "blocking" when applied to CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions, means reducing, attenuating, decreasing, 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), such that the remaining CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions are no longer biologically significant. For example, such blocking of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function can reduce CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function by 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%. In other examples, such blocking of CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function can completely eliminate 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 the 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 CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological function by 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 the 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 completely block, e.g., completely abrogate, CD30-CD30L binding or interaction, CD30L-mediated CD30 signaling, or other CD30L biochemical or biological functions.

[0320] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which secreted immunoglobulins bind to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages), enabling these cytotoxic effector cells to specifically bind to antigenic target cells and subsequently kill the target cells with cytotoxins. Antibodies "arm" the cytotoxic cells and are absolutely necessary for this killing. NK cells are the primary cells that mediate ADCC and express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. FcR expression is known on hematopoietic cells (see, e.g., Ravetch and Kinet, 1991, Annu. Rev. Immunol. 9:457-92). In order to assess the ADCC activity of a target molecule, an in vitro ADCC assay (see, 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 (PBMC) and natural killer (NK) cells. Alternatively or additionally, ADCC activity of the target molecule can be assessed in vivo, for example in an animal model (see, for example, Clynes et al., 1998, Proc. Natl. Acad. Sci. USA 95: 652-56). Antibodies with little or no ADCC activity can be selected.

[0321] "Antibody-dependent cellular phagocytosis" or "ADCP" refers to the binding of immunoglobulins to Fc receptors (FcRs) present on certain phagocytes (e.g., neutrophils, monocytes, and macrophages), enabling these cytotoxic effector cells to specifically bind to antigenic target cells and subsequently kill the target cells. In order to assess the ADCP activity of a target molecule, an in vitro ADCP assay can be performed (see Bracher et al., 2007, J. Immunol. Methods 323: 160-71). Useful phagocytes for such assays include peripheral blood mononuclear cells (PBMCs), purified monocytes from PBMCs, or U937 cells differentiated into a mononuclear type. Alternatively or additionally, the ADCP activity of a target molecule can 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 can be selected for use.

[0322] "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 binding of the first component of the complement system (Clq) to an antibody (of the appropriate subclass) that binds to its cognate antigen. To assess complement activation, a CDC assay can be performed (e.g., see Gazzano-Santoro et al., 1996, J. Immunol. Methods 202:163). Polypeptide variants with altered Fc region amino acid sequences (polypeptides with variant Fc regions) and increased or decreased Clq binding capacity have been described (e.g., see 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 can be selected for use.

[0323] As described herein, the term "antibody" is used in the broadest sense, including polyclonal and monoclonal antibodies, including complete 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 antibodies (e.g., sdAb, sdFv, nanobody) fragments. The term covers genetically engineered and / or otherwise modified immunoglobulin forms, such as intracellular antibodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies and heterologous conjugate antibodies, multispecifics (e.g., bispecific antibodies, double antibodies, three antibodies and four antibodies), tandem double scFv, tandem three scFv. Unless otherwise indicated, the term "antibody" should be understood to cover its functional antibody fragments. The term also covers complete 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.

[0324] The antibodies provided can be used as multispecific antibodies (e.g., bispecific antibodies and multireactive antibodies) and antibody fragments (e.g., scFv forms) in monoclonal antibodies and polyclonal antibody compositions. Antibodies provided herein also include antibody conjugates and molecules comprising antibodies, such as chimeric molecules. Therefore, antibodies include but are not limited to full-length and natural antibodies, as well as fragments and portions retaining their binding specificity, such as any specific binding portion thereof, including those with 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')2, Fv, and scFv (single chain or related entities). Monoclonal antibodies are typically one of substantially homogeneous antibody compositions; therefore, any single antibody included in a monoclonal antibody composition is identical, except for a small amount of naturally occurring mutations that may be present. Polyclonal antibodies are a preparation comprising different antibodies of different sequences, which are typically directed against two or more different determinants (epitopes). Monoclonal antibodies can include human IgG1 constant regions. The monoclonal antibody may comprise a human IgG4 constant region.The term "anti-CD30L" is used as an abbreviation for an anti-CD30L antibody or antigen-binding fragment thereof.

[0325] The terms "complementarity determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art to refer to discontinuous amino acid sequences within an antibody variable region that confer antigen specificity and / or binding affinity. Typically, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3). "Framework region" and "FR" are known in the art to refer to the non-CDR portions of the heavy and light chain variable regions. Typically, 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 well-known schemes, including 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 Plückthun 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 modelling antibodies on the WEB," Protein Eng. 2000 Dec; 13 (12): 819-24 ("AbM" numbering scheme). The CDRs of the antibodies described herein can be defined by the Kabat, IMGT, Chothia, AbM, Aho, Contact numbering schemes, or any combination thereof.

[0326] The boundaries of a given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignments, while the Chothia scheme is based on structural information. The numbering of both the Kabat and Chothia schemes is based on the most common antibody region sequence lengths, with insertions accommodated by inserting letters, such as "30a", while deletions occur 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 analysis of complex crystal structures and is similar to the Chothia numbering scheme in many respects. Table 26 below summarizes the various numbering schemes and the CDR boundaries according to each numbering scheme.

[0327] Table 26: CDR boundaries according to various numbering schemes

[0328] <![CDATA[ IMGT ]]> <![CDATA[ Kabat ]]> <![CDATA[ AbM ]]> <![CDATA[ Chothia ]]> <![CDATA[ Contact ]]> <![CDATA[ Aho ]]> CDR-H1 (VHCDR1) 27-38 31-35 26-35 26-32 30-35 25-40 CDR-H2 (VHCDR2) 56-65 50-65 50-58 52-56 47-58 58-77 CDR-H3 (VHCDR3) 105-117 95-102 95-102 96-101 93-101 109-137 CDR-L1(VLCDR1) 27-38 24-34 24-34 26-32 30-36 25-40 CDR-L2(VLCDR2) 56-65 50-56 50-56 50-52 46-55 58-77 CDR-L3(VLCDR3) 105-117 89-97 89-97 91-96 89-96 109-137

[0329] Thus, the terms "variable region residue numbering as in Kabat" or "amino acid position numbering as in Kabat" and variations thereof refer to the numbering system used in Kabat et al., supra for the compilation of heavy or light chain variable regions of antibodies. 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, the heavy chain variable domain may include 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, etc.). The Kabat numbering of the residues for a given antibody can be determined by aligning the antibody sequence with the "standard" Kabat numbering sequence at the homologous region of the antibody sequence. When referring to the residues in the variable domain (approximately residues 1-107 for the light chain and residues 1-113 for the heavy chain), the Kabat numbering system (e.g., Kabat et al., supra) is generally used. When referring to the residues of the immunoglobulin heavy chain constant region, the "EU numbering system" or "EU index" is generally used (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 been described by AbM, Chothia, Contact, IMGT, and AHon.

[0330] The term "variable region" or "variable domain" refers to the domain of an antibody heavy chain or light chain that is involved in binding an antibody to an antigen. The variable domains of the heavy and light chains of natural antibodies (VH and VL, respectively) generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs (see, for example, Kindt et al. Kuby Immunology, 6th ed., WH Freeman and Co., page 91 (2007)). A single VH or VL domain may be sufficient to confer antigen binding specificity. In addition, VH or VL domains from antibodies that bind to a specific antigen can be used to screen libraries of complementary VL or VH domains, respectively, to isolate antibodies that bind to that antigen (see, for example, Portolano et al., J. Immunol. 150: 880-887 (1993); Clarkson et al., Nature 352: 624-628 (1991)).

[0331] When used to refer to antibodies, the term "heavy chain" refers to a polypeptide chain of about 50-70 kDa, wherein the amino-terminal portion includes a variable region of about 120-130 or more amino acids, and the carboxyl-terminal portion includes a constant region. Based on the amino acid sequence of the heavy chain constant region, the constant region can be one of five different types (e.g., isotypes) called alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ). Different heavy chains are of different sizes: α, δ, and γ contain about 450 amino acids, while μ and ε contain about 550 amino acids. When combined with a light chain, these different types of heavy chains produce the five well-known antibody classes, IgA, IgD, IgE, IgG, and IgM, respectively, including the four subclasses of IgG, IgG1, IgG2, IgG3, and IgG4. The heavy chain can be a human heavy chain.

[0332] When used in reference to antibodies, the term "light chain" refers to a polypeptide chain of about 25 kDa, wherein the amino terminal portion includes a variable region of about 100 to about 110 or more amino acids, and the carboxyl terminal portion includes a constant region. The approximate length of a light chain is 211 to 217 amino acids. Based on the amino acid sequence of the constant domain, there are two different types, referred to as kappa (κ) or lambda (λ). Light chain amino acid sequences are well known in the art. The light chain can be a human light chain.

[0333] The antibodies provided include antibody fragments. "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 include a portion of an intact antibody that binds to the antigen to which the intact antibody binds. Examples of antibody 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 a specific embodiment, the antibody is a single-chain antibody fragment, such as scFv, comprising a variable heavy chain region and / or a variable light chain region. Typically, an antibody fragment or antigen-binding fragment will contain one or more CDRs from a parent antibody sufficient to confer binding specificity.

[0334] When referring to an antibody binding to a particular target or binding to a particular target, the term "contacting" or "in contact with..." as used herein means that the amino acid residues of the variable region or CDR are within 5, 4, 3 or less angstroms of the contact residue. Contacts include hydrogen bonds, van der Waals interactions, and salt bridge formation between the amino acid residues of the antibody variable region or CDR and the residue.

[0335] An "epitope" is a site on the surface of an antigen molecule that binds to a single antibody molecule, such as a localized region on the surface of an antigen (e.g., a CD30L polypeptide, a CD30L polypeptide fragment) that is capable of binding to one or more antigen-binding regions of an antibody and having antigenic or immunogenic activity capable of eliciting an immune response in an animal (e.g., a mammal). An epitope with immunogenic activity is a portion of a polypeptide that elicits an antibody response in an animal. An epitope with antigenic activity is a portion of a polypeptide, as determined by any method well known in the art (including, for example, by immunoassay). An antigenic epitope is not necessarily immunogenic. An epitope is typically composed of chemically active surface groups of a molecule (e.g., amino acids or sugar side chains) and has specific three-dimensional structural characteristics as well as specific charge characteristics. Antibody epitopes can be linear or conformational. Linear epitopes are formed by contiguous amino acid sequences in a protein. Conformational epitopes are formed by discontinuous amino acids in a protein sequence that aggregate when the protein folds into its three-dimensional structure. Induced epitopes are formed when the three-dimensional structure of a protein is in an altered conformation, such as upon activation or binding by another protein or ligand. In certain embodiments, a CD30L epitope is a three-dimensional surface feature of a CD30L polypeptide. In other embodiments, a CD30L epitope is a linear feature of a CD30L polypeptide. Typically, an antigen has several or more different epitopes and can react with many different antibodies.

[0336] When two antibodies recognize the same, overlapping, or adjacent epitopes in three-dimensional space, the antibodies bind to the "epitope," "substantially the same epitope," or "the same epitope" as a reference antibody. The most widespread and rapid method for determining whether two antibodies bind to the same, overlapping, or adjacent epitopes in three-dimensional space is a competition assay, which can be configured in a variety of different formats, for example, using labeled antigens or labeled antibodies. In some assays, the antigen is immobilized on a 96-well plate or expressed on the surface of cells, and a radioactive, fluorescent, or enzymatic label is used to measure the ability of the unlabeled antibody to block the binding of the labeled antibody.

[0337] "Epitope mapping" is the process of identifying the binding site, or epitope, of an antibody on its target antigen. "Epitope classification" is the process of classifying antibodies based on the epitope they recognize. More specifically, epitope classification includes methods and systems for distinguishing the epitope recognition properties of different antibodies, clustering antibodies based on their epitope recognition properties using competition assays combined with computational processes, and identifying antibodies with different binding specificities.

[0338] Antibody fragments can be made by various techniques, including but not limited to proteolytic digestion of intact antibodies and production of recombinant host cells. In some embodiments, the antibody is a fragment produced by recombinant production, such as a fragment comprising a non-naturally occurring arrangement, such as two or more antibody regions or chains connected by a synthetic linker (e.g., 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 a scFv.

[0339] Generally, humanized antibodies are antibodies in which all or substantially all CDR amino acid residues are derived from non-human CDRs and all or substantially all FR amino acid residues are derived from human FRs. Humanized antibodies may optionally include 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, typically to reduce immunogenicity to humans while retaining the specificity and affinity of the parent non-human antibody. In some embodiments, some FR residues in the humanized antibody are replaced with corresponding residues of a non-human antibody (e.g., an antibody derived from CDR residues), for example, to restore or improve antibody specificity or affinity. In some embodiments, a humanized antibody refers to a non-human (e.g., mouse) or non-fully humanized antibody having a specific immunoglobulin chain, chimeric immunoglobulin, or its fragment, comprising minimal non-human (e.g., mouse) sequences. In non-limiting examples, a humanized antibody comprises less than about 40% non-human sequences in the variable region. In some embodiments, the humanized antibody comprises less than about 20% non-human sequences in the full-length antibody sequence. In another non-limiting example, the humanized antibody comprises less than about 20% non-human sequences in the framework region of the heavy chain and light chain variable regions. For example, the humanized antibody comprises 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 region of the heavy chain and light chain variable regions. As another example, the humanized antibody comprises about or less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 non-human sequences in the framework region of the heavy chain and light chain variable regions. In some embodiments, humanized antibodies are human immunoglobulins in which the residues of the complementary determining regions (CDRs) are replaced by CDR residues of non-human species (e.g., mouse, rat, rabbit, hamster) with the desired specificity, affinity, and ability. These humanized antibodies may contain one or more non-human species mutations, for example, the heavy chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework region, and the light chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework region. The humanized heavy chain variable domain may comprise an IGHV3-9, IGHV4-59, or IGHV3-33 framework having no or less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 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 an IGKV1-16, IGKV1-6 or IGKV2-28 framework with no or fewer than about 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid mutations.

[0340] The antibodies provided include human antibodies. "Human antibody" refers to an antibody having an amino acid sequence corresponding to an antibody produced by a human or human cell or an antibody produced from a non-human source using a human antibody library or other human antibody coding sequences (including a human antibody library). The term does not include humanized forms of non-human antibodies that contain non-human antigen binding regions, such as antibodies in which all or substantially all of the CDRs are non-human.

[0341] Human antibodies can be prepared by administering immunogens to transgenic animals, which have been modified to produce complete human antibodies or complete antibodies with human variable regions in response to antigenic attacks. This type of animal generally contains all or part of human immunoglobulin loci, which replace endogenous immunoglobulin loci, or are present in extrachromosomal or randomly integrated into the chromosome of the animal. In this type of transgenic animal, endogenous immunoglobulin loci are generally inactivated. Human antibodies can also be obtained or selected from human antibody libraries (including phage display and cell-free libraries), comprising antibody coding sequences derived from the human library. In certain embodiments, human antibodies can be selected to eliminate sequence disadvantages or increase their affinity by continuous rounds of selections such as phage display.

[0342] The terms "polypeptide" and "protein" are used interchangeably to refer to polymers of amino acid residues and are not limited to a minimum length. Polypeptides (including the antibodies and antibody chains provided and other peptides, such as linkers and binding peptides) can include amino acid residues, including natural and / or non-natural amino acid residues. These terms also include post-expression modifications of the polypeptide, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. In some aspects, a polypeptide may contain modifications relative to the native or natural sequence, as long as the protein maintains the desired activity. These modifications can be intentional, such as by site-directed mutagenesis, or accidental, such as by mutations in the host producing the protein or errors due to PCR amplification.

[0343] After the sequences are aligned and gaps are introduced (if necessary) to achieve maximum percent sequence identity, without considering any conservative substitutions as part of sequence identity, the percent (%) sequence identity relative to a reference polypeptide sequence refers to the percentage of amino acid residues in the candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence. Alignment for the purpose of determining percent amino acid sequence identity can be achieved 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 can be determined, including algorithms for achieving maximum alignment over the full length of the compared sequences. However, for the purposes of this article, the sequence comparison computer program ALIGN-2 is used to generate % amino acid sequence identity values. The ALIGN-2 sequence comparison computer program was written by Genentech, Inc., and its source code has been submitted to the U.S. Copyright Office (Washington, D.C., 20559) as a user document, and it is registered with U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc. in South San Francisco, California, or can be assembled from source code. The ALIGN-2 program should be assembled 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 change.

[0344] In cases where ALIGN-2 is used for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (alternatively referred to as a given amino acid sequence A having or comprising a particular % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be understood that when the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B is not equal to the % amino acid sequence identity of B to A. Unless expressly stated otherwise, all % amino acid sequence identity values ​​used herein were obtained using the ALIGN-2 computer program as described in the preceding paragraph.

[0345] In some embodiments, amino acid sequence variants of the antibodies provided herein are contemplated. Variants typically differ from the polypeptides specifically disclosed herein in terms of one or more substitutions, deletions, additions, and / or insertions. Such variants may be naturally occurring or synthetically produced, for example, by modifying one or more of the above-mentioned polypeptide sequences of the present invention and evaluating one or more biological activities of the polypeptides described herein and / or using any of a number of known techniques. For example, it may be necessary to improve the binding affinity and / or other biological properties of the antibody, and amino acid sequence variants of the antibody may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions and / or insertions and / or substitutions of residues in the amino acid sequence of the antibody. Any combination of deletions, insertions, and substitutions may be performed to obtain the final construct, provided that the final construct has the desired properties, such as antigen binding.

[0346] In some embodiments, antibody variants with one or more amino acid substitutions are provided. The target sites for mutagenesis by substitution include CDRs and FRs. Amino acid substituents can be introduced into the target antibody, and the product can be screened to obtain the desired activity, such as retaining / improving antigen binding, reducing immunogenicity (such as reducing ADCC or CDC). In some embodiments, substitutions, insertions or deletions can occur in one or more CDRs, wherein the substitutions, insertions or deletions do not significantly reduce the binding of the antibody to the antigen. For example, conservative substitutions that do not significantly reduce binding affinity can be made in the CDRs. Such changes can be outside the CDR "hot spots". In some embodiments of variant VH and VL sequences, each CDR is unchanged.

[0347] In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. In some embodiments, the CDR residues involved in the antigen binding are modified. Alternatively, or additionally, a crystal structure of an antigen-antibody complex can identify contact points between the antibody and the antigen. Such contact residues and adjacent residues can be targeted or eliminated as replacement candidates. Variants can be screened to determine whether they contain the desired properties.

[0348] Amino acid sequence insertions and deletions include amino and / or carboxyl terminal fusions of a length from one residue to a polypeptide containing one hundred or more residues, and insertions and deletions within the sequence of a single or multiple amino acid residues. Examples of terminal insertions include antibodies with an N-terminal methionyl residue. Other insertion variants of antibody molecules include fusing the N-terminus or C-terminus of the antibody to an enzyme (e.g., for ADEPT) or a polypeptide that increases the serum half-life of the antibody. Examples of insertion variants within the sequence of antibody molecules include inserting 3 amino acids in the light chain. Examples of terminal deletions include antibodies with 7 or fewer amino acids missing at the light chain termini.

[0349] In some embodiments, the antibody is changed to increase or decrease its glycosylation (e.g., by changing the amino acid sequence, thereby creating or removing one or more glycosylation sites). The carbohydrate attached to the Fc region of the antibody can be changed. Natural antibodies from mammalian cells typically contain a branched biantennary oligosaccharide attached to Asn297 of the CH2 domain of the Fc region via an N bond (see, e.g., Wright et al. TIBTECH 15: 26-32 (1997)). Oligosaccharides can be various carbohydrates, e.g., mannose, N-acetylglucosamine (GlcNAc), galactose, sialic acid, fucose attached to the GlcNAc in the biantennary oligosaccharide structure stem. The oligosaccharides in the antibody can be modified, e.g., to produce antibody variants with certain improved properties. Antibody glycosylation variants can change ADCC and / or CDC function. Cell lines (e.g., knockout cell lines) and methods of using the same can be used to produce defucosylated antibodies, such as Lec13 CHO cells 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).

[0350] In some embodiments, one or more amino acid modifications can be introduced into the Fc region of the antibody provided herein, thereby producing Fc region variants. The Fc region herein is the C-terminal region of the immunoglobulin heavy chain comprising at least a portion of the constant region. The Fc region includes a native sequence Fc region and a variant Fc region. The Fc region variant may include a human Fc region sequence (e.g., human IgG1, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g., substitution) at one or more amino acid positions.

[0351] In some embodiments, the antibodies of the present disclosure are variants with some but not all effector functions, making them ideal candidates for applications where the half-life of the antibody in vivo is important but certain effector functions (e.g., complement and ADCC) are unnecessary or deleterious. In vitro and / or in vivo cytotoxicity assays can be performed to confirm the reduction / depletion of CDC and / or ADCC activity. For example, Fc receptor (FcR) binding assays can be performed to ensure that the antibody lacks FcγR binding (and therefore may lack ADCC activity). Non-limiting examples of in vitro assays for evaluating ADCC activity of a target molecule are described in U.S. Patent Nos. 5,500,362 and 5,821,337. Alternatively, non-radioactive assays (e.g., ACTI TM and CytoTox Non-radioactive cytotoxicity assays). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMCs), monocytes, macrophages, and natural killer (NK) cells.

[0352] The antibodies may have increased half-life and improved binding to the neonatal Fc receptor (FcRn) (see, e.g., US 2005 / 0014934). Such antibodies may comprise an Fc region having one or more substitutions that improve binding of the Fc region to FcRn, and include antibodies having 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. Pat. No. 7,371,826). Other examples of Fc region variants are also contemplated (see, eg, Winter, Nature 322:738-40 (1988); US Patent Nos. 5,648,260 and 5,624,821; and WO 94 / 29351).

[0353] Reactive groups can be positioned at sites for binding to other moieties (e.g., drug moieties or linked drug moieties) to produce immunoconjugates. In certain embodiments, the recombinant anti-CD30L antibodies provided herein can also be modified to include other known and available non-proteinaceous moieties. Suitable moieties for antibody derivatization 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, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, ethylene / maleic anhydride copolymers, polyamino acids (homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone) polyethylene glycol, polypropylene-ethylene glycol homopolymers, polypropylene oxide / ethylene oxide copolymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in preparation due to its stability in water. 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.

[0354] The antibodies described herein can be encoded by nucleic acids. Nucleic acid is a polynucleotide comprising two or more nucleotide bases. In certain embodiments, nucleic acids are components of vectors that can be used to transfer polynucleotides encoding polypeptides into cells. The term "vector" as used herein refers to a nucleic acid molecule capable of transporting another nucleic acid to which it is attached. Another type of vector is a genomic integration vector or "integration vector," which can be integrated into the chromosomal DNA of a host cell. Another type of vector is an "episomal" vector, for example, a nucleic acid capable of extrachromosomal replication. Vectors capable of directing the expression of genes operably linked thereto 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, regulatory elements (e.g., promoters, enhancers, polyadenylation signals) for controlling transcription can be derived from mammalian, microbial, viral, or insect genes. Selection genes that enhance the ability to replicate in the host (usually conferred by an origin of replication) and promote transformant recognition can also be integrated. Vectors from viruses (e.g., lentiviruses, retroviruses, adenoviruses, adeno-associated viruses, etc.) can be used. Plasmid vectors can be linearized for integration into a chromosomal location. The vector may comprise sequences that direct site-specific integration into a defined location or a restricted set of sites in the genome (eg, AttP-AttB recombination). Additionally, the vector may comprise sequences from a transposable element.

[0355] As used herein, the terms "homology," "homology," or "percent homology" when used to describe an amino acid sequence or nucleic acid sequence relative to a reference sequence can be determined using the formula described by Karlin and Altschul (Proc. Natl. Acad. Sci. USA 87:2264-2268, 1990, modified as in Proc. Natl. Acad. Sci. USA 90:5873-5877, 1993). This formula is incorporated into the Basic Local Alignment Search Tool (BLAST) program of Altschul et al. (J. Mol. Biol. 215:403-410, 1990). The most recent version of BLAST available as of the filing date of this application can be used to determine percent homology of a sequence.

[0356] Nucleic acids encoding the antibodies described herein can be used to infect, transfect, transform, or otherwise genetically modify cells suitable for the nucleic acids, thereby enabling the production of antibodies for commercial or therapeutic use. Standard cell lines and methods for producing antibodies from large-scale cell cultures 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 cells are eukaryotic cells. In certain embodiments, the eukaryotic cells are mammalian cells. In certain embodiments, the mammalian cells are Chinese hamster ovary (CHO) cells, NSO mouse myeloma cells, HEK293 (human embryonic kidney 293) cells, or PER. In certain embodiments, the nucleic acid encoding the antibody is integrated into a genomic site of a cell that can be used to produce the antibody. In certain embodiments, a method of preparing an antibody is described herein, comprising culturing a cell comprising a nucleic acid encoding the antibody under in vitro conditions sufficient to allow production and secretion of the antibody.

[0357] 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 genomic location; 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 nucleic acids encoding an antibody having (i) a heavy chain variable region amino acid sequence having an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 1, 2, 5, 6, 9, 10, 13, 14, 17, 19, 21, 23, 25, 27, 29, or 31; and (ii) a light chain variable region amino acid sequence having an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 3, 4, 7, 8, 11, 12, 15, 16, 18, 20, 22, 24, 26, 28, 30, or 32, integrated at a genomic location; and (b) a cryoprotectant. 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 capable of withstanding liquid nitrogen freezing.

[0358] Also described herein are methods for preparing antibodies described herein. Such methods include incubating cells or cell lines comprising nucleic acids encoding antibodies in a cell culture medium under conditions sufficient to allow expression and secretion of the antibody, and also harvesting the antibody from the cell culture medium. Harvesting may also include one or more purification steps to remove living cells, cell debris, non-antibody proteins or polypeptides, unwanted salts, buffers, and culture medium components. In certain embodiments, additional purification steps include centrifugation, ultracentrifugation, dialysis, desalination, protein A, protein G, protein A / G, or protein L purification and / or ion exchange chromatography.

[0359] The recombinant antibodies or antibody fragments disclosed herein specifically bind to CD30L and are characterized by high affinity for CD30L. Therefore, the antibodies disclosed herein can be used to target (i.e., bind) CD30L. In some embodiments, provided anti-CD30L antibodies include a heavy chain and a light chain, wherein the heavy chain includes four heavy chain framework regions (HCFRs) and three heavy chain complementarity determining regions (HCDRs): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3, and HCFR4; and the light chain includes four light chain framework regions (LCFRs) and three light chain complementarity determining regions (LCDRs): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3, and LCFR4.

[0360] In one aspect, provided herein are antibodies or antigen-binding fragments thereof that bind to CD30L, wherein the antibodies or antigen-binding fragments thereof comprise: (a) an immunoglobulin heavy chain CDR1 (CDR-H1) comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723; (b) an immunoglobulin heavy chain CDR2 (CDR-H2) comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; (c) an immunoglobulin heavy chain CDR3 (CDR-H3) comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743; (d) an immunoglobulin heavy chain CDR4 (CDR-5) comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 250-264, 528-552, 656-669, and 736-743; (d) an immunoglobulin light chain CDR2 (CDR-L2) comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759; and / or (e) an immunoglobulin light chain CDR3 (CDR-L3) comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.

[0361] Consistent with the above aspects, in one embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of 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 of 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 of 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 of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. In another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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: 100-139, 220-234, 465-489, 628-641 and 712-723 and 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 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: 100-139, 220-234, 465-489, 628-641, and 712-723, and 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 certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723 and a CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723 and a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759. 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: 100-139, 220-234, 465-489, 628-641, and 712-723, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, and 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 one 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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751.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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. 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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. In other 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, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751. In other 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, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, 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: 180-219, 250-264, 528-552, 656-669, and 736-743, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765.In one embodiment, 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: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. In another embodiment, 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: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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: 340-379, 435-449, 578-602, 684-697, and 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, and a CDR-H3 comprising the amino acid sequence of 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-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, 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, and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, and a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.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: 100-139, 220-234, 465-489, 628-641, and 712-723; 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; and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751. 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: 100-139, 220-234, 465-489, 628-641, and 712-723; 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; and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723; a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743; and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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: 100-139, 220-234, 465-489, 628-641, and 712-723; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; 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; and a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751. 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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; 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; and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759.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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; 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; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751; and a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. 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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765.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: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759; and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. In other 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, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. In other 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, a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. 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, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765.In some 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: 300-339, 420-434, 553-577, 670-683, and 744-751, a CDR-L2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759, and a CDR-L3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, and a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 200-211, 213-224, 227-235, 238-240, 241-252, 253-254, 261-262 and 270-271. CDR-L1 of the amino acid sequence shown in any one of NOs: 300-339, 420-434, 553-577, 670-683 and 744-751. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, and a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 200-211, 213-224, 227-235, 238-240, 241-252, 253-254, 261-262 and 263-276. CDR-L2 of the amino acid sequence shown in any one of NOs: 340-379, 435-449, 578-602, 684-697 and 752-759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, and a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 250-264, 528-552, 656-669, and 736-743. CDR-L3 of the amino acid sequence shown in any one of NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751. CDR-L2 of the amino acid sequence shown in any one of NOs: 340-379, 435-449, 578-602, 684-697 and 752-759. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723; a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735; a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751; and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759, and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. CDR-L3 of the amino acid sequence shown in any one of NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, and a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759, and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In yet another embodiment, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759, and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751. CDR-L2 of the amino acid sequence shown in any one of NOs: 340-379, 435-449, 578-602, 684-697 and 752-759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, and a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743. CDR-L3 of the amino acid sequence shown in any one of NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In other embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759, and a CDR-L4 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759. CDR-L3 of the amino acid sequence shown in any one of NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759, and a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, CDR-L3 of the amino acid sequence shown in any one of NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743; a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751; a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697, and 752-759; and a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711, and 760-765. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 250-264, 528-552, 656-669 and 736-743, a CDR-H5 comprising the amino acid sequence of any one of SEQ ID NOs: 182-191, 250-264, 528-552, 656-669 and 736-743, a CDR-H6 comprising the amino acid sequence of any one of SEQ ID NOs: 183-192, 250-264, 528-552, 656-669 and 736-743, a CDR-H7 comprising the amino acid sequence of any one of SEQ ID NOs: 184-193, 250-264, 528-552, 656-669 and 736-743, a CDR-H8 comprising the amino acid sequence of any one of SEQ ID NOs: 1 A CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, and a CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 250-264, 528-552, 656-669, and 736-743, a CDR-H5 comprising the amino acid sequence of any one of SEQ ID NOs: 182-191, 250-264, 528-552, 656-669, and 736-743, a CDR-H6 comprising the amino acid sequence of any one of SEQ ID NOs: 183-192, 250-264, 528-552, 656-669, and 736-743, a CDR-H7 comprising the amino acid sequence of any one of SEQ ID NOs: 184-193, 250-264, 528-552, A CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, and a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641, and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 181-190, 250-264, 528-552, 656-669, and 736-743, a CDR-H5 comprising the amino acid sequence of any one of SEQ ID NOs: 182-191, 250-264, 528-552, 656-669, and 736-743, a CDR-H6 comprising the amino acid sequence of any one of SEQ ID NOs: 183-192, 250-264, 528-552, 656-669, and 736-743, a CDR-H7 comprising the amino acid sequence of any one of SEQ ID NOs: 184-193, 250-264, 528-552, 656-669, and 736-743, a CDR-H8 comprising the amino acid sequence of any one of A CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759, and a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-L4 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-L5 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, A CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759, and a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765. In certain embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-H4 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-L5 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751, a CDR-H6 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, A CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759, and a CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.In some embodiments, the antibody or antigen-binding fragment thereof comprises or consists of a CDR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655, and 724-735, a CDR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669, and 736-743, a CDR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, a CDR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, a CDR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683, and 744-751, a CDR-L4 comprising the amino acid sequence of any one of SEQ ID NOs: 300-339, 420-434, A CDR-L2 compri...

Claims

1. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 100-139, 220-234, 465-489, 628-641 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 140-179, 235-249, 490-499, 513-527, 642-655 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180-219, 250-264, 528-552, 656-669 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-339, 420-434, 553-577, 670-683 and 744-751; (d) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-379, 435-449, 578-602, 684-697 and 752-759; and / or (e) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-419, 450-464, 603-627, 698-711 and 760-765.

2. The pharmaceutical composition according to claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 100-109, 628, 635 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 140-149, 642, 649 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180-189, 656, 663 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-309, 670, 677 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-349, 684, 691 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-389, 698, 705 and 760-765.

3. The pharmaceutical composition according to claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 100-104; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 140-144; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 180-184; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 300-304; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 340-344; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 380-384.

4. The pharmaceutical composition according to claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 105-109, 628, 635 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 145-149, 642, 649 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 185-189, 656, 663 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 305-309, 670, 677 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 345-349, 684, 691 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 385-389, 698, 705 and 760-765.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein 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 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.

6. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids selected from N165, K166, I168, K169 and D234 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

7. The pharmaceutical composition of claim 6, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid selected from N165, K166, I168, K169 and D234 in CD30L; (ii) any two amino acids selected from N165, K166, I168, K169 and D234 in CD30L; (iii) any three amino acids selected from N165, K166, I168, K169 and D234 in CD30L; (iv) any four amino acids selected from N165, K166, I168, K169 and D234 in CD30L; or (v) any five amino acids selected from N165, K166, I168, K169 and D234 in CD30L; The amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

8. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids selected from H167, S217 and D118 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

9. The pharmaceutical composition according to claim 6 or 7, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid selected from H167, S217 and D118 in CD30L; (ii) any two amino acids selected from H167, S217 and D118 in CD30L; or (iii) any three amino acids selected from H167, S217 and D118 in CD30L; The amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

10. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD30L (anti-CD30L antibody or antigen-binding fragment), wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising one or more amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

11. The pharmaceutical composition of claim 10, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising: (i) any one amino acid selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; (ii) any two amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; (iii) any three amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; (iv) any four amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; (v) any five amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; (vi) any six amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; (vii) any seven amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; or (viii) any five amino acids selected from D118, N165, K166, H167, I168, K169, S217 and D234 in CD30L; The amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

12. A pharmaceutical composition comprising an anti-CD30L antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising K169 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

13. The pharmaceutical composition of claim 12, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising D234 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

14. A pharmaceutical composition comprising an anti-CD30L antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising D234 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

15. The pharmaceutical composition according to claims 12-14, wherein the epitope further comprises N165 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

16. The pharmaceutical composition according to any one of claims 12-15, wherein the epitope further comprises I168 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

17. The pharmaceutical composition according to any one of claims 12-16, wherein the epitope further comprises K166 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

18. The pharmaceutical composition according to any one of claims 12-17, wherein the epitope further comprises H167 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

19. The pharmaceutical composition according to any one of claims 12-18, wherein the epitope further comprises S217 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

20. The pharmaceutical composition according to any one of claims 12-19, wherein the epitope further comprises D118 in CD30L, wherein the amino acids are numbered according to the CD30L amino acid sequence shown in SEQ ID NO:

33.

21. The pharmaceutical composition according to any one of claims 1 and 6-20, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 110-119, 629, 636 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 150-159, 643, 650 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190-199, 657, 664 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 310-319, 671, 678 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 350-359, 685, 692 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 390-399, 699, 706 and 760-765.

22. The pharmaceutical composition according to any one of claims 1 and 6-20, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 110-114; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 150-154; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 190-194; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 310-314; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 350-354; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 390-394.

23. The pharmaceutical composition according to any one of claims 1 and 6-20, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 115-119, 629, 636 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 155-159, 643, 650 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 195-199, 657, 664 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 315-319, 671, 678 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 355-359, 685, 692 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 395-399, 699, 706 and 760-765.

24. The pharmaceutical composition according to any one of claims 1, 6-20 and 21-23, wherein 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 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.

25. The pharmaceutical composition of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 120-129 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 160-169 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 200-209 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 320-329 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 360-369 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 400-409 and 760-765.

26. The pharmaceutical composition according to claim 1 or 25, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 120-124; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 160-164; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 200-204; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 320-324; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 360-364; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 400-404.

27. The pharmaceutical composition of claim 1 or 25, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 125-129 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 165-169 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 205-209 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 325-329 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 365-369 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 405-409 and 760-765.

28. The pharmaceutical composition according to any one of claims 1 and 25-27, wherein 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 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.

29. The pharmaceutical composition of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 130-139 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 170-179 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 210-219 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 330-339 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 370-379 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 410-419 and 760-765.

30. The pharmaceutical composition of claim 1 or 29, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 130-134; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 170-174; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 210-214; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 330-334; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 370-374; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 410-414.

31. The pharmaceutical composition of claim 1 or 29, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 135-139 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 175-179 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 215-219 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 335-339 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 375-379 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 415-419 and 760-765.

32. The pharmaceutical composition of any one of claims 1 and 29-31, wherein 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 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.

33. The pharmaceutical composition of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 220-224 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 235-239 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 250-254 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 420-424 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 435-439 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 450-454 and 760-765.

34. The pharmaceutical composition of claim 1 or 33, wherein 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 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 comprises an amino acid sequence having at least about 90, 95, 97, 98, 99 or 100% sequence identity to SEQ ID NO:

18.

35. The pharmaceutical composition of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 225-229 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 240-244 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 255-259 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 425-429 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 440-444 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 455-459 and 760-765.

36. The pharmaceutical composition of claim 1 or 35, wherein 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 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 immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99 or 100% sequence identity to SEQ ID NO:

20.

37. The pharmaceutical composition of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 230-234 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 245-249 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 260-264 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 430-434 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 445-449 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 460-464 and 760-765.

38. The pharmaceutical composition of claim 1 or 37, wherein 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 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 immunoglobulin variable region light chain comprises an amino acid sequence having at least about 90, 95, 97, 98, 99 or 100% sequence identity to SEQ ID NO:

22.

39. The pharmaceutical composition of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 465-469, 631, 638 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 490-494, 645, 652 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 528-532, 659, 666 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 553-557, 673, 680 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 578-582, 687, 694 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: The amino acid sequence shown in any one of NO:603-607, 701, 708 and 760-765; (ii) (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 470-474, 632, 639 and 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 495-499, 646, 653 and 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 533-537, 660, 667 and 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 558-562, 674, 681 and 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 583-587, 688, 695 and 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: The amino acid sequence shown in any one of NO:608-612, 702, 709 and 760-765; (iii) (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 475-479, 633, 640 and 712-723; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 513-517, 647, 654 and 724-735; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 538-542, 661, 668 and 736-743; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 563-567, 675, 682 and 744-751; (e) a CDR-L2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 588-592, 689, 696 and 752-759; and / or (f) a CDR-L3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: The amino acid sequence shown in any one of NO:613-617, 703, 710 and 760-765; (iv) (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 480-484, 630, 637 and 712-723; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 518-522, 644, 651 and 724-735; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 543-547, 658, 665 and 736-743; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 568-572, 672, 679 and 744-751; (e) a CDR-L2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 593-597, 686, 693 and 752-759; and / or (f) a CDR-L3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: The amino acid sequence shown in any one of NO:618-622, 700, 707 and 760-765; or (v) (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 485-489, 634, 641 and 712-723; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 523-527, 648, 655 and 724-735; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 548-552, 662, 669 and 736-743; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 573-577, 676, 683 and 744-751; (e) a CDR-L2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 598-602, 690, 697 and 752-759; and / or (f) a CDR-L3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: The amino acid sequence shown in any one of NOs: 623-627, 704, 711 and 760-765.

40. The pharmaceutical composition of any one of claims 1 and 6-20, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 712-723; (b) CDR-H2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 724-735; (c) CDR-H3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 736-743; (d) CDR-L1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 744-751; (e) CDR-L2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 752-759; and / or (f) CDR-L3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 760-765; (ii) (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 712, 714, 716, 718, 720 and 722; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 724, 726, 728, 730, 732 and 734; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 736, 738, 740 and 742; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 744, 746, 748 and 750; (e) a CDR-L2 comprising an amino acid sequence as 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 as set forth in any one of SEQ ID NOs: 760, 762 and 764; (iii) (a) a CDR-H1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 713, 715, 717, 719, 721 and 723; (b) a CDR-H2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 725, 727, 729, 731, 733 and 735; (c) a CDR-H3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 737, 739, 741 and 743; (d) a CDR-L1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 745, 747, 749 and 751; (e) a CDR-L2 comprising an amino acid sequence as 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 as set forth in any one of SEQ ID NOs: 761, 763 and 765; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 712; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 730; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 713; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 731; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761; (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 712; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 724; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760; (vii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 713; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 725; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761; (viii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 714; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 726; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760; (ix) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 715; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 727; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761; (x) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 716; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 728; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 736; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 744; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 752; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 760; (xi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 717; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 729; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 737; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 745; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 753; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761; (xii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 718; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 730; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 738; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 746; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 754; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 762; (xiii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 719; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 731; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 739; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 747; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 755; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 763; (xiv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:720; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:732; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:740; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:748; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:756; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:760; (xv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 721; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 733; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 741; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 749; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 757; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 761; (xvi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 722; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 734; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 742; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 750; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 758; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 764; or (xvii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:723; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:735; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:743; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:751; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:759; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

765.

41. The pharmaceutical composition according to any one of claims 1-4 and 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 635; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 649; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 663; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 677; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 691; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 705; (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 107; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 147; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 187; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 307; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 347; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 387; (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 105; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 145; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 185; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 305; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 345; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 385; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 106; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 146; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 186; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 306; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 346; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 386; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 108; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 148; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 188; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 308; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 348; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 388; (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 109; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 149; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 189; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 309; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 349; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 389; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:628; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:642; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:656; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:670; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:684; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

698.

42. The pharmaceutical composition of any one of claims 1, 6-23 and 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 636; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 650; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 664; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 678; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 692; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 706; (ii) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 357; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 397; (iii) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 355; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 395; (iv) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 356; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 396; (v) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 358; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 398; (vi) (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) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 359; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 399; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:629; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:643; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:657; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:671; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:685; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

699.

43. The pharmaceutical composition of claim 1 or 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 637; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 651; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 665; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 679; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 693; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 707; (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 482; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 520; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 545; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 570; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 595; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 620; (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 480; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 518; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 543; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 568; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 593; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 618; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:481; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:519; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:544; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:569; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:594; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:619; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 483; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 521; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 546; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 571; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 596; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 621; (vi) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 484; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 522; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 547; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 572; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 597; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 622; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:630; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:644; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:658; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:672; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:686; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

700.

44. The pharmaceutical composition of claim 1 or 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 638; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 652; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 666; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 680; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 694; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 708; (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:467; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:492; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:530; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:555; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:580; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:605; (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:465; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:490; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:528; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:553; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:578; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:603; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:466; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:491; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:529; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:554; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:579; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:604; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:468; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:493; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:531; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:556; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:581; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:606; (vi) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:469; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:494; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:532; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:557; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:582; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:607; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:631; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:645; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:659; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:673; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:687; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

701.

45. The pharmaceutical composition of claim 1 or 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 639; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 653; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 667; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 681; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 695; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 709; (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:472; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:497; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:535; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:560; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:585; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:610; (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 470; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 495; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 533; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 558; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 583; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 608; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:471; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:496; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:534; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:559; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:584; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:609; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 473; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 498; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 536; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 561; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 586; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 611; (vi) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 474; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 499; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 537; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 562; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 587; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 612; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:632; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:646; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:660; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:674; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:688; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

702.

46. ​​The pharmaceutical composition of claim 1 or 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 640; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 654; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 668; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 682; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 696; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 710; (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:477; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:515; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:540; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:565; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:590; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:615; (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:475; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:513; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:538; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:563; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:588; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:613; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:476; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:514; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:539; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:564; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:589; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:614; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:478; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:516; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:541; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:566; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:591; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:616; (vi) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:479; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:517; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:542; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:567; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:592; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:617; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:633; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:647; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:661; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:675; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:689; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

703.

47. The pharmaceutical composition of claim 1 or 40, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 641; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 655; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 669; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 683; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 697; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 711; (ii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:487; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:525; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:550; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:575; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:600; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:625; (iii) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:485; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:523; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:548; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:573; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:598; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:623; (iv) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:486; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:524; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:549; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:574; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:599; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:624; (v) (a) CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:488; (b) CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:526; (c) CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:551; (d) CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:576; (e) CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:601; and / or (f) CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:626; (vi) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO: 489; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO: 527; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO: 552; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO: 577; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO: 602; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO: 627; or (vii) (a) CDR-H1 comprising the amino acid sequence shown in SEQ ID NO:634; (b) CDR-H2 comprising the amino acid sequence shown in SEQ ID NO:648; (c) CDR-H3 comprising the amino acid sequence shown in SEQ ID NO:662; (d) CDR-L1 comprising the amino acid sequence shown in SEQ ID NO:676; (e) CDR-L2 comprising the amino acid sequence shown in SEQ ID NO:690; and / or (f) CDR-L3 comprising the amino acid sequence shown in SEQ ID NO:

704.

48. The pharmaceutical composition of any one of claims 1-47, wherein the antibody or antigen-binding fragment thereof comprises: (i) (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; (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: 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; (iii) (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; (iv) (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; (v) (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; (vi) (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; (vii) (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; (viii) (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; (ix) (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; (x) (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; (xi) (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; (xii) (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; (xiii) (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; or (xiv) (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.

49. The pharmaceutical composition of any one of claims 1, 40 and 48, wherein the antibody or antigen-binding fragment thereof comprises: (i) (a) a VH comprising an amino acid sequence as shown 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 an amino acid sequence as shown 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) VH comprising the amino acid sequence shown in SEQ ID NO: 1; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 3; (iii) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 2; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 4; (iv) (a) VH comprising the amino acid sequence shown in SEQ ID NO:5; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO:7; (v) (a) VH comprising the amino acid sequence shown in SEQ ID NO:6; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO:8; (vi) (a) VH comprising the amino acid sequence shown in SEQ ID NO:9; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO:11; (vii) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 10; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 12; (viii) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 13; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 15; (ix) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 14; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 16; (x) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 23; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 24; (xi) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 25; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 26; (xii) (a) VH comprising the amino acid sequence set forth in SEQ ID NO:27; and / or (b) VL comprising the amino acid sequence set forth in SEQ ID NO:28; (xiii) (a) VH comprising the amino acid sequence shown in SEQ ID NO: 29; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO: 30; or (xiv) (a) VH comprising the amino acid sequence shown in SEQ ID NO:31; and / or (b) VL comprising the amino acid sequence shown in SEQ ID NO:

32.

50. The pharmaceutical composition of any one of claims 1-49, wherein the antibody or antigen-binding fragment thereof further comprises an IgG constant region.

51. A pharmaceutical composition according to any one of claims 1-50, wherein the antibody or antigen-binding fragment thereof further comprises an IgG constant region having reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG and / or reduced complement-dependent cytotoxicity (CDC) compared to human IgG.

52. A pharmaceutical composition according to claim 50 or 51, wherein the constant region comprises an amino acid sequence having 80, 85, 90, 95, 97, 98, 99 or 100% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs: 500-512.

53. A pharmaceutical composition according to any one of claims 50-52, wherein the constant region comprises the amino acid sequence shown in any one of SEQ ID NOs: 500-512.

54. A pharmaceutical composition according to any one of claims 1-53, wherein the antibody or antigen-binding fragment thereof comprises a constant region having an amino acid sequence variant corresponding to the following 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, 329Q, 329R or 329S. 9Y or 329R, (k) 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) 269N or 269 Q, (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 382P, (nn) 385P, (oo) 42 4H, 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) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or any combination of (nnn)(a)-(mmm). , 55. The pharmaceutical composition of any one of claims 1-54, wherein the antibody or antigen-binding fragment thereof is an IgG antibody.

56. The pharmaceutical composition of claim 55, wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

57. The pharmaceutical composition of any one of claims 1-56, wherein the antibody or antigen-binding fragment thereof is human, chimeric or humanized.

58. The pharmaceutical composition of any one of claims 1-57, wherein the antibody or antigen-binding fragment thereof is a Fab, F(ab')2, a single domain antibody, or a single chain variable fragment (scFv).

59. The pharmaceutical composition of any one of claims 1-58, wherein the antibody or antigen-binding fragment thereof is a bispecific or multispecific antibody.

60. The pharmaceutical composition of any one of claims 1-59, wherein the antibody or antigen-binding fragment thereof binds to one or more amino acid residues of CD30L that interact with CD30.

61. The pharmaceutical composition of any one of claims 1-60, wherein the antibody or antigen-binding fragment thereof inhibits the binding interaction between CD30L and CD30.

62. The pharmaceutical composition of any one of claims 1-60, wherein the antibody or antigen-binding fragment thereof blocks the binding interaction between CD30L and CD30.

63. The pharmaceutical composition of claim 61 or 62, wherein the inhibition or blocking is determined in an ELISA assay, a cell binding assay using cells expressing CD30L, or a surface plasmon resonance (SPR) assay.

64. The pharmaceutical composition of any one of claims 1-63, wherein the antibody or antigen-binding fragment thereof specifically binds to CD30L.

65. A pharmaceutical composition according to any one of claims 1-64, wherein the antibody or antigen-binding fragment thereof (i) inhibits the secretion of interleukin-8 in a cell-based assay, (ii) inhibits the secretion of interleukin-6 in a cell-based assay, or (iii) both (i) and (ii).

66. A pharmaceutical composition according to any one of claims 1-64, wherein 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).

67. The pharmaceutical composition of claim 65 or 66, wherein the cell-based assay is a dual cell assay using cells expressing CD30 and cells expressing CD30L.

68. The pharmaceutical composition of any one of claims 1-67, wherein the antibody or antigen-binding fragment thereof binds to (i) human CD30L, (ii) cynomolgus monkey CD30L, or (iii) both human CD30L and cynomolgus monkey CD30L.

69. The pharmaceutical composition of any one of claims 1-68, wherein the antibody or antigen-binding fragment thereof has a dissociation equilibrium constant (K) of no more than 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. D ) binds to CD30L.

70. The pharmaceutical composition according to any one of claims 1-69, wherein the antibody or antigen-binding fragment thereof is present in an amount of at least 0.1×10 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 × 10 6 M -1 S -1 The binding rate constant (k on ) binds to CD30L.

71. The pharmaceutical composition according to any one of claims 1-70, wherein the antibody or antigen-binding fragment thereof is present at a concentration of no more than 1.4×10 -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.

72. A pharmaceutical composition comprising an anti-CD30L antibody or an antigen-binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof binds to subtype 1 of CD30L, and wherein the antibody or the antigen-binding fragment thereof does not bind to subtype 2 of CD30L.

73. The pharmaceutical composition of any one of claims 1-71, wherein the antibody or antigen-binding fragment thereof binds to subtype 1 of CD30L, and wherein the antibody or antigen-binding fragment thereof does not bind to subtype 2 of CD30L.

74. The pharmaceutical composition according to claim 72 or 73, wherein the subtype 1 of CD30L comprises the amino acid sequence shown in SEQ ID NO: 34, and wherein the subtype 2 of CD30L comprises the amino acid sequence shown in SEQ ID NO:

35.

75. The pharmaceutical composition of any one of claims 1-71, wherein the antibody or antigen-binding fragment thereof is a recombinant antibody or antigen-binding fragment thereof.

76. The pharmaceutical composition of any one of claims 1-75, wherein the antibody or antigen-binding fragment thereof is an isolated antibody or antigen-binding fragment thereof.

77. The pharmaceutical composition of any one of claims 1-76, wherein the anti-CD30L antibody or antigen-binding fragment (a) is a concentration of (i) about 50 mg / ml to about 275 mg / ml, (ii) about 50 mg / ml to about 250 mg / ml, (iii) about 50 mg / ml to about 225 mg / ml, (iv) about 50 mg / ml to about 200 mg / ml, (v) about 50 mg / ml to about 175 mg / ml, (vi) about 50 mg / ml to about 150 mg / ml, (vii) about 50 mg / ml to about 125 mg / ml, (viii) about 50 mg / ml to about 100 mg / ml, or (ix) about 50 mg / ml to about 75 mg / ml; (b) is a concentration of (i) about 75 mg / ml to about 275 mg / ml, (ii) about 75 mg / ml to about 250 mg / ml, (iii) about 75 mg / ml to about 225 mg / ml, (iv) about 75 mg / ml to about 200 mg / ml, (v) about 75 mg / ml to about 175 mg / ml, (vi) about 75 mg / ml to about 150 mg / ml, (vii) about 75 mg / ml to about 125 mg / ml, or (viii) about 75 mg / ml to about 100 mg / ml; (c) is a concentration of (i) about 100 mg / ml to about 275 mg / ml, (ii) about 100 mg / ml to about 250 mg / ml, (iii) about 100 mg / ml to about 225 mg / ml, (iv) about 100 mg / ml to about 200 mg / ml, (v) about 100 mg / ml to about 175 mg / ml, (vi) about 100 mg / ml to about 150 mg / ml, or (vii) about 100 mg / ml to about 125 mg / ml; (d) is a concentration of (i) about 125 mg / ml to about 275 mg / ml, (ii) about 125 mg / ml to about 250 mg / ml, (iii) about 125 mg / ml to about 225 mg / ml, (iv) about 125 mg / ml to about 200 mg / ml, (v) about 125 mg / ml to about 175 mg / ml, or (vi) about 125 mg / ml to about 150 mg / ml; (e) is a concentration of (i) about 150 mg / ml to about 275 mg / ml, (ii) about 150 mg / ml to about 250 mg / ml, (iii) about 150 mg / ml to about 225 mg / ml, (iv) about 150 mg / ml to about 200 mg / ml, or (v) about 150 mg / ml to about 175 mg / ml; (f) a concentration of (i) about 175 mg / ml to about 275 mg / ml, (ii) about 175 mg / ml to about 250 mg / ml, (iii) about 175 mg / ml to about 225 mg / ml, or (iv) about 175 mg / ml to about 200 mg / ml; (g) is at a concentration of (i) about 200 mg / ml to about 275 mg / ml, (ii) about 200 mg / ml to about 250 mg / ml, or (iii) about 200 mg / ml to about 225 mg / ml; or (h) is a concentration of (i) at least about 50 mg / mL, (ii) at least about 75 mg / ml, (iii) at least about 100 mg / ml, (iv) at least about 125 mg / ml, (v) at least about 150 mg / ml, (vi) at least about 175 mg / ml, (vii) at least about 200 mg / ml, (viii) at least about 225 mg / ml or (ix) at least about 250 mg / ml.

78. A pharmaceutical composition comprising an antibody or antigen-binding fragment that binds to CD30L (anti-CD30L antibody or antigen-binding fragment) at a concentration of (i) at least about 50 mg / mL, (ii) at least about 75 mg / ml, (iii) at least about 100 mg / ml, (iv) at least about 125 mg / ml, (v) at least about 150 mg / ml, (vi) at least about 175 mg / ml, (vii) at least about 200 mg / ml, (viii) at least about 225 mg / ml, or (ix) at least about 250 mg / ml.

79. A pharmaceutical composition comprising an antibody or antigen-binding fragment that binds to CD30L (anti-CD30L antibody or antigen-binding fragment) at the following concentrations: (a) a concentration of (i) about 50 mg / ml to about 275 mg / ml, (ii) about 50 mg / ml to about 250 mg / ml, (iii) about 50 mg / ml to about 225 mg / ml, (iv) about 50 mg / ml to about 200 mg / ml, (v) about 50 mg / ml to about 175 mg / ml, (vi) about 50 mg / ml to about 150 mg / ml, (vii) about 50 mg / ml to about 125 mg / ml, (viii) about 50 mg / ml to about 100 mg / ml, or (ix) about 50 mg / ml to about 75 mg / ml; (b) a concentration of (i) about 75 mg / ml to about 275 mg / ml, (ii) about 75 mg / ml to about 250 mg / ml, (iii) about 75 mg / ml to about 225 mg / ml, (iv) about 75 mg / ml to about 200 mg / ml, (v) about 75 mg / ml to about 175 mg / ml, (vi) about 75 mg / ml to about 150 mg / ml, (vii) about 75 mg / ml to about 125 mg / ml, or (viii) about 75 mg / ml to about 100 mg / ml; (c) a concentration of (i) about 100 mg / ml to about 275 mg / ml, (ii) about 100 mg / ml to about 250 mg / ml, (iii) about 100 mg / ml to about 225 mg / ml, (iv) about 100 mg / ml to about 200 mg / ml, (v) about 100 mg / ml to about 175 mg / ml, (vi) about 100 mg / ml to about 150 mg / ml, or (vii) about 100 mg / ml to about 125 mg / ml; (d) a concentration of (i) about 125 mg / ml to about 275 mg / ml, (ii) about 125 mg / ml to about 250 mg / ml, (iii) about 125 mg / ml to about 225 mg / ml, (iv) about 125 mg / ml to about 200 mg / ml, (v) about 125 mg / ml to about 175 mg / ml, or (vi) about 125 mg / ml to about 150 mg / ml; (e) a concentration of (i) about 150 mg / ml to about 275 mg / ml, (ii) about 150 mg / ml to about 250 mg / ml, (iii) about 150 mg / ml to about 225 mg / ml, (iv) about 150 mg / ml to about 200 mg / ml, or (v) about 150 mg / ml to about 175 mg / ml; (f) a concentration of (i) about 175 mg / ml to about 275 mg / ml, (ii) about 175 mg / ml to about 250 mg / ml, (iii) about 175 mg / ml to about 225 mg / ml, or (iv) about 175 mg / ml to about 200 mg / ml; or (g) a concentration of (i) about 200 mg / ml to about 275 mg / ml, (ii) about 200 mg / ml to about 250 mg / ml, or (iii) about 200 mg / ml to about 225 mg / ml.

80. The pharmaceutical composition of any one of claims 1-79, further comprising a buffer.

81. The pharmaceutical composition of claim 80, wherein the buffer is selected from the group consisting of acetate buffer, succinate buffer, histidine buffer, phosphate buffer, and citrate buffer.

82. The pharmaceutical composition of claim 80 or 81, wherein the buffer is a histidine buffer.

83. The pharmaceutical composition of any one of claims 80-82, wherein the concentration of the buffer is 0.1 mM to 1 M.

84. The pharmaceutical composition of any one of claims 80-83, wherein the concentration of the buffer is 1 mM to 100 mM.

85. The pharmaceutical composition of any one of claims 80-84, wherein the concentration of the buffer is 10 mM to 50 mM.

86. The pharmaceutical composition of any one of claims 80-85, wherein the concentration of the buffer is about 20 mM.

87. A pharmaceutical composition according to any one of claims 80-86, wherein the pH of the buffer is 4-7.

88. A pharmaceutical composition according to any one of claims 80-87, wherein the pH of the buffer is 5-6.

89. The pharmaceutical composition of any one of claims 80-88, wherein the pH of the buffer is about 5.

5.

90. The pharmaceutical composition of any one of claims 1-89, further comprising a pharmaceutically acceptable excipient.

91. The pharmaceutical composition of claim 90, wherein the excipient is arginine, arginine hydrochloride (arginine HCl), proline, a polyol, sodium chloride, glycine, lysine, lysine HCl, arginine glutamate, potassium chloride, magnesium chloride, calcium chloride, or a combination thereof.

92. The pharmaceutical composition of claim 90 or 91, wherein the excipient is arginine HCl.

93. according to the pharmaceutical composition described in claim 91 or 92, wherein the concentration of said arginine HCl is (i) 25 mM to 300 mM, (ii) 50mM to 250mM (iii) 50 mM to 200 mM, (iv) 75 mM to 150 mM, or (v) about 100 mM.

94. A pharmaceutical composition according to any one of claims 91-93, wherein the polyol is selected from sugars, sugar alcohols and sugar acids.

95. The pharmaceutical composition of claim 94, wherein the sugar is sucrose.

96. The pharmaceutical composition of claim 95, wherein the concentration of sucrose is: (i) 5%-10% (weight / volume, w / v), (ii) about 5% (w / v), (iii) 150 mM to 300 mM, or (iv) about 150 mM.

97. A pharmaceutical composition according to any one of claims 1-96, further comprising a surfactant.

98. The pharmaceutical composition of claim 97, wherein the surfactant is a polysorbate.

99. The pharmaceutical composition of claim 97 or 98, wherein the surfactant is polysorbate-80 (PS80).

100. The pharmaceutical composition of claim 97 or 98, wherein the surfactant is poloxamer 188 (P188).

101. The pharmaceutical composition of claim 97 or 98, wherein the surfactant is polysorbate-20 (PS20).

102. A pharmaceutical composition according to any one of claims 97-101, wherein the concentration of the surfactant is: (i) 0.001%-0.1% (w / v), (ii) 0.005-0.05% (w / v), (iii) 0.01-0.05% (w / v), (iv) 0.01-0.04% (w / v), (v) 0.01-0.03% (w / v), (vi) 0.01-0.02% (w / v), (vii) about 0.02% (w / v), (viii) about 0.03% (w / v), (ix) about 0.04% (w / v), or (x) about 0.05% (w / v).

103. The pharmaceutical composition of any one of claims 1-102, comprising sodium chloride (NaCl).

104. The pharmaceutical composition according to claim 103, wherein the concentration of NaCl is (i) 25 mM to 150 mM, (ii) 25 mM to 100 mM, (iii) 50 mM to 100 mM, (iv) 75 mM to 100 mM, or (v) about 50 mM.

105. The pharmaceutical composition of any one of claims 1-104, wherein the pharmaceutical composition comprises an antioxidant.

106. The pharmaceutical composition of any one of claims 1-104, wherein the pharmaceutical composition does not comprise an antioxidant.

107. The pharmaceutical composition of any one of claims 1-106, wherein the viscosity of the composition is 1-50 cP at 25°C.

108. The pharmaceutical composition of any one of claims 1-107, wherein the viscosity of the composition is 10-25 cP at 25°C.

109. The pharmaceutical composition of any one of claims 1-107, wherein the viscosity of the composition is 1-50, 2-49, 3-48, 4-46, 5-45, 6-44, 7-43, 8-42, 9-41, 10-40, 10-35, 10-30, 11-29, 12-28, 13-27, 14-26, 15-25, 16-24, 17-23, 18-22, 18-21, 18-20, 18-19, 19-21, 1-10, 1-15 or 1-20 cP at 25°C.

110. The pharmaceutical composition of any one of claims 1-109, wherein the viscosity of the composition at 25°C is no more than 25 cP, no more than 24 cP, no more than 23 cP, no more than 22 cP, no more than 21 cP, no more than 20 cP, or no more than 19 cP.

111. The pharmaceutical composition of any one of claims 1-110, wherein the viscosity of the composition at 25°C is about 15 cP, about 16 cP, about 17 cP, about 18 cP, about 19 cP, about 20 cP, about 21 cP, about 22 cP, about 23 cP, about 24 cP, or about 25 cP.

112. The pharmaceutical composition of any one of claims 1-111, wherein the composition is a stable composition.

113. The pharmaceutical composition of any one of claims 1-112, wherein the composition is stable under the following conditions: (i) stored at 25°C ± 5°C for at least 2, 4, 8, 12, 16, 20 or 24 weeks, (ii) stored at 40°C ± 5°C for at least 2, 4 or 8 weeks, or (iii) stored at 25°C ± 5°C for at least 2, 4, 8, 12, 16, 20 or 24 weeks.

114. The pharmaceutical composition of claim 112 or 113, wherein the stability of the composition is determined by: (i) maintaining at least 98% of the antibody main peak in size exclusion chromatography, (ii) maintaining at least 65% of the main antibody peak in iCIEF, (iii) maintain a purity of at least 98%, (iv) maintaining at least 99% antibody concentration, (v) maintaining no more than 500 particles / ml of particles larger than 2 μm, no more than 10 particles / ml of particles larger than 10 μm, and / or no more than 2 particles / ml of particles larger than 25 μm, and / or (vi) Any combination of (i) to (iv).

115. The pharmaceutical composition of any one of claims 1-114, wherein the composition comprises the anti-CD30L antibody or antigen-binding fragment at a concentration of 200 mg / mL, 20 mM histidine buffer, 100 mM arginine monohydrochloride and 0.02% (w / v) PS20, at a pH of 5.

5.

116. A pharmaceutical composition comprising an anti-CD30L antibody or antigen-binding fragment at a concentration of 200 mg / mL, 20 mM histidine buffer, 100 mM arginine monohydrochloride and 0.02% (w / v) PS20, with a pH of 5.

5.

117. The pharmaceutical composition of any one of claims 1-116, wherein the anti-CD30L blocks both soluble CD30L and transmembrane CD30L.

118. A method for preparing a pharmaceutical formulation according to any one of claims 1 to 117, comprising: The cells are cultured in a culture medium, wherein the cells contain one or more polynucleotides comprising a nucleotide sequence encoding a heavy chain, a light chain, or both a heavy chain and a light chain of the antibody or antigen-binding fragment thereof.

119. The method of claim 118, further comprising expressing the one or more polynucleotides in the cell.

120. The method of claim 118 or 119, further comprising purifying the antibody or antigen-binding fragment thereof.

121. The method of any one of claims 118-120, further comprising a formulation step.

122. The pharmaceutical composition according to any one of claims 1-117, for use in a method of inhibiting the binding of CD30L to CD30.

123. The pharmaceutical composition according to any one of claims 1-117, for use in a method of inhibiting CD30 signaling activation in a cell.

124. A pharmaceutical composition according to any one of claims 1-117, for use in a method of inhibiting the activation, expression and / or secretion of a pro-inflammatory cytokine protein.

125. The pharmaceutical composition of claim 124, wherein the pro-inflammatory cytokine protein is interleukin-8 and / or interleukin-6.

126. A pharmaceutical composition for use according to claim 124, wherein interleukin-8 is expressed or released by T lymphocytes.

127. A pharmaceutical composition according to any one of claims 1-117 for use in treating an autoimmune disease in a subject in need thereof.

128. The pharmaceutical composition of claim 127, wherein the autoimmune disease is irritable bowel syndrome.

129. The pharmaceutical composition of claim 127, wherein the irritable bowel syndrome comprises ulcerative colitis (UC) or Crohn's disease (CD).

130. A method for treating or improving an autoimmune disease in an individual in need thereof, the method comprising administering to the individual a pharmaceutical composition according to any one of claims 1-117, thereby treating or improving the autoimmune disease.

131. The method of claim 130, wherein the autoimmune disease is irritable bowel syndrome.

132. The method of claim 131, wherein the irritable bowel syndrome comprises ulcerative colitis (UC) or Crohn's disease (CD).

133. A method for inhibiting and / or reducing the binding of CD30L to CD30 in an individual suffering from an inflammatory or autoimmune disease, the method comprising administering to the individual suffering from the inflammatory or autoimmune disease a pharmaceutical composition according to any one of claims 1-117, thereby inhibiting and / or reducing the binding of CD30L to CD30.

134. The method of claim 133, wherein the individual suffers from an autoimmune disease.

135. The method of claim 133, wherein the autoimmune disease is irritable bowel syndrome.

136. The method of claim 135, wherein the irritable bowel syndrome comprises ulcerative colitis (UC) or Crohn's disease (CD).

137. A method of reducing and / or inhibiting inflammation in an individual, the method comprising administering to the individual a pharmaceutical composition according to any one of claims 1-117, thereby reducing and / or inhibiting inflammation.

138. The method of claim 137, wherein reducing and / or inhibiting inflammation comprises reducing the amount of pro-inflammatory cytokine expression or secretion in the individual or a tissue of the individual.

139. The method of claim 137 or 138, wherein reducing and / or inhibiting inflammation comprises reducing the amount of pro-inflammatory cytokines expressed or secreted by T lymphocytes in the individual.

140. The method of claim 137, 138 or 139, wherein the proinflammatory cytokine comprises interleukin-8.

141. The method of any one of claims 137-140, wherein the individual has an autoimmune disease.

142. The method of claim 141, wherein the autoimmune disease is irritable bowel syndrome.

143. The method of claim 142, wherein the irritable bowel syndrome comprises ulcerative colitis (UC) or Crohn's disease (CD).

Images