Methods of treating blood disorders with monospecific antibodies targeting VWF

Abstract

Provided herein are antibodies, compositions, and methods of use thereof. The disclosed antibodies bind to a von Willebrand factor in the plasma of a subject. Such antibodies are useful in methods of treatment, such as methods of treating one or more blood conditions characterized by excessive bleeding.

Description

Cross-references to related applications

[0001] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 519,955, filed August 16, 2023, the entire contents of which are hereby incorporated by reference for all purposes.

[0002] sequence list This specification references a sequence list, which was submitted electronically in XML format and is hereby incorporated herein by reference in its entirety. The XML file was created on August 5, 2024, named HMT-005WO_SL.xml, and is 678kb in size. Summary of the Invention

[0003] In some embodiments, this document discloses compositions and methods for treating hematologic disorders using monospecific antibodies targeting von Willebrand factor (VWF).

[0004] In some embodiments, this document discloses a monospecific antibody comprising: an antigen-binding site that specifically binds to an epitope located in the cysteine ​​knot (CK) domain of a von Willebrand factor (VWF) protein; and a crystallizable fragment (Fc) region, wherein the binding of the antibody disclosed herein to the VWF protein results in the accumulation of VWF protein in plasma compared to plasma levels in the absence of the antibody.

[0005] In some embodiments, the antibody comprises a heavy chain variable (VH) region having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a light chain variable (VL) region having an amino acid sequence having at least 80% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH region having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL region having an amino acid sequence having at least 85% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH region having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL region having an amino acid sequence having at least 95% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH region having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL region having an amino acid sequence having at least 95% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 524, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 518.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 522, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 523, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises: a first heavy chain (HC) region containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC region containing an amino acid sequence having at least 80% identity with SEQ ID NO: 689 or 731, and a light chain (LC) region containing an amino acid sequence having at least 80% identity with SEQ ID NO: 690.

[0006] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 577, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 578.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 576, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 577, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 699, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 700.

[0007] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 507, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 493.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 505, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 506, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 507, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 685, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 686.

[0008] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises VH, which contains CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, which contains CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 544, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 524, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 575, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 544, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 527.In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 697, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 698.

[0009] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 491, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 492, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 493.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 490, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 491, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 492, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 683, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 684.

[0010] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 520, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 521, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 493.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 519, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 520, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 521, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 687, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 688.

[0011] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 528 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 529; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 531, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 46.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 528, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 529; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 530, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 513, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 531, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 691, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 692.

[0012] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 551, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 552, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 553.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 550, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 551, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 552, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 693, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 694.

[0013] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 564. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 564. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 564. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 564. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 564. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 565, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 566, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 527.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 564, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 565, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 566, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 695, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 696.

[0014] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 580, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 574, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 549.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 579, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 580, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 574, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 701, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 702.

[0015] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 595 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 595, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 596, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 597, and CDRH3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 598; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 703, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463.

[0016] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 604 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 604, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 605, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 606, and CDRH3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 704, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463.

[0017] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 612 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 612, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 613, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 614, and CDRH3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 705, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463.

[0018] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 618 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 618, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 619, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 620, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 706, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 707.

[0019] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 624 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 624 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 624 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 624 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 624 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 625, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 624, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 625, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 708, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 707.

[0020] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 630 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 630 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 630 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 630 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 630 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 631, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 632, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 634, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 630, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 631, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 632, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 633, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 634, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO:473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO:709, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO:710.

[0021] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 635 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 635 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 635 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 635 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 635 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 637, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 635, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 636, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 637, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 711, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 707.

[0022] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 638 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 641. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 638 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 641. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 638 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 641. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 638 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 641. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 638 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 641. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 639, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 640, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 642, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 643, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 638, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 639, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 640, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 598; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 641, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 642, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 643, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 712, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 713.

[0023] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 644 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 644 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 644 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 644 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 644 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 645, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 646, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 644, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 645, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 646, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 714, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 707.

[0024] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 649 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 649 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 649 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 649 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 649 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 650, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 652, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 649, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 636, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 650, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 651, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 652, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 715, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 716.

[0025] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 494. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 494. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 494. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 494. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 494. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 495, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 496, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 497.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 494, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 495, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 496, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 497.

[0026] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 499, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 400, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 46.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 498, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 499, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 400, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46.

[0027] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 502, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 503, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 504.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 501, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 502, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 503, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 504.

[0028] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 507, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 493.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 505, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 506, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 507, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493.

[0029] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 508. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 508. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 508. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 508. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 508. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 509, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 510, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 511.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 508, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 509, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 510, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 511.

[0030] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 512. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 512. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 512. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 512. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 512. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 514, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 515.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 512, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 513, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 514, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 515.

[0031] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 516. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 516. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 516. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 516. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 516. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 517, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 503, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 518.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 516, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 517, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 503, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 518.

[0032] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 525. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 525. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 525. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 525. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 525. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 526, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 527.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 525, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 526, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 527.

[0033] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 532. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 532. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 532. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 532. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 532. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 533, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 534, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 511.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 532, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 533, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 534, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 511.

[0034] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 535. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 535. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 535. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 535. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 535. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 536, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 537, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 538.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 535, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 536, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 537, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 538.

[0035] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 539. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 539. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 539. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 539. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 539. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 540, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 541, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 542.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 539, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 540, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of 541, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 542.

[0036] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 543. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 543. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 543. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 543. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 543. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 545, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 542.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 543, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 544, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 545, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 542.

[0037] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 546. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 546. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 546. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 546. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 546. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 547, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 548, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 549.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 546, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 547, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 548, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 549.

[0038] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 554. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 554. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 554. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 554. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 554. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 555, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 556, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 557.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 554, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 555, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 556, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 557.

[0039] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 558. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 558. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 558. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 558. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 558. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 559, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 560, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 46.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 558, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 559, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 560, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46.

[0040] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 561. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 561. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 561. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 561. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 561. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 562, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 563, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 511.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 561, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 562, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 563, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 511.

[0041] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 569. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 569. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 569. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 569. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 569. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 568; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 570, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 571, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 46.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 567, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 568; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 569, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 570, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 571, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46.

[0042] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 567 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 568; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 573, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 574, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 46.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 567, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 568; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 572, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 573, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 574, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46.

[0043] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 581. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 581. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 581. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 581. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 581. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 582, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 583, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 584.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 581, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 582, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 583, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 584.

[0044] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 585 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 585 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 585 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 585 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 585 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 586, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 587, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 585, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 586, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 587, and CDRH3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0045] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 590 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 590 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 590 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 590 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 590 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 591, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 592, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 594, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 590, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 591, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 592, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 593, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 594, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0046] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 599 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 599 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 599 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 599 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 599 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 601, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 599, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 600, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 601, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 598; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0047] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 608 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 608 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 608 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 608 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 608 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 609, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 611; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 608, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 609, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 610, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 611; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0048] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 615 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 615 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 615 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 615 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 615 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 616, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 617, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 615, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 616, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 617, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 598; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0049] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 621 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 621 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 621 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 621 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 621 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 622, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 623, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 621, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 622, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 623, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0050] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 626 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 627. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 626 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 627. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 626 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 627. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 626 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 627. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 626 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 627. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 591, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 592, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 628, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 629, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 626, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 591, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 592, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 598; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 627, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 628, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 629, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0051] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 647 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 647 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 647 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 647 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 647 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 648, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 611; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 647, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 648, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 28, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 611; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0052] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 653 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 653 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 653 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 653 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 653 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 654, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 655, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 653, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 654, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 655, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0053] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 656 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 656 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 656 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 656 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 656 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 657, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 656, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 657, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 610, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0054] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 658 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 658 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 658 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 658 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 658 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 659, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 660, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 661; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 658, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 659, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 660, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 661; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0055] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 662 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 662 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 662 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 662 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 662 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 664, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 662, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 600, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 21, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 663, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 664, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0056] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 665 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 665 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 665 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 665 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 665 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 633. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 666, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 667, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 634, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 665, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 666, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 667, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 633, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 634, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0057] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 668 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 668 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 668 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 668 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 668 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 669, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 670, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 668, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 669, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 670, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0058] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 671 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 674. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 671 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 674. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 671 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 674. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 671 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 674. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 671 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 674. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 672, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 673, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 643, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 671, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 672, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 673, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 674, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 643, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0059] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 675 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 677. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 675 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 677. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 675 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 677. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 675 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 677. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 675 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 677. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 676, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 587, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 664, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 678, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 675, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 676, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 587, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 677, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 664, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 678, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0060] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 679 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 679 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 679 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 679 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 679 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 680, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 681, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 642, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 679, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 680, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 681, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 588; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 682, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 642, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0061] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 40 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 40 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 40 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 40 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 40 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 43; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 407, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 46.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 40, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 43; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 44, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 407, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46.

[0062] In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 12 and a VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 12 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 12 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 12 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 12 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having a CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 15; and a VL having a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of 589, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 18.In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 12, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 13, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 14, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 15; VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18.

[0063] In some embodiments, the antibodies disclosed herein are monovalent antibodies. In some embodiments, the Fc region is a wild-type Fc region. In some embodiments, the Fc region is a modified Fc region. In some embodiments, the modified Fc region contains one or more mutations selected from the group consisting of: R435H mutation, N434A mutation, T252L / T253S / T254F mutation, E294delta / T307P / N434Y mutation, T256N / A378V / S383N / N434Y mutation, E294 delta mutation, M252Y / S254T / T256E mutation, M428L / N434S mutation, T307A / E380A / N434A mutation, T250Q / M428L mutation, T250Q / M428F mutation, T250E / M428F mutation, T250E / M428L mutation, T256D / Q311V / A378V mutation, T256D / H286D / T307R / Q311V / A378V mutation, H285N / T307Q / N315D mutation, T307Q / Q311V / A378V mutation, H285D / T307Q / A378V mutation, L234F / L235E / P331S mutation, L234F / L235Q / K322Q mutation, L234F / L235Q / P331G mutation, L234F / L235A / K322Q mutation, S228P / F234A / L235A / G237A / P238S mutation, L234A / L235E / G237A / A330S / P331S mutation, F243A / V264A mutation, S228P / L235E / P3 29G mutation, M252Y / M428L mutation, D259I / V308F mutation, T307Q / N434S mutation, M428L / V308F mutation, Q311V / N434S mutation, H433K / N434F mutation, E258F / V427T mutation, K288E / H435K mutation, F234A / L235A mutation, F234A / L235A / S228P mutation, L234A / L235A / P329G mutation, F234A / L235A / P329G mutation, P329G mutation, F 234 mutation, S228P mutation, delta-K447 mutation, L235A mutation, L235E mutation, V308P mutation, V308W mutation, V308Y mutation, V308F mutation, N434S mutation, T307 mutation, Q312A mutation, K322A mutation, P329A mutation, P331A mutation, P238A mutation, D265A mutation, D269A mutation, D270A mutation, N297A mutation, A327Q mutation, P329A mutation, S239A mutation, E294A mutation, Q295A mutation,V303A mutation, A330R mutation, T299A mutation, F234A mutation, T366W mutation, T366S mutation, L368A mutation, Y407V mutation, F405L mutation, K409R mutation, F405L / R409K mutation, and any combination thereof. In some embodiments, the modified Fc region includes N-terminal truncation (e.g., truncation of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50). (51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more N-terminal residues). In some embodiments, the antibody is a human IgG4 antibody comprising a first heavy chain and a second heavy chain. In some embodiments, the first heavy strand contains the S228P / T366W / F234A / L235A / delta-K447 mutation, and the second heavy strand contains the S228P / T366S / L368A / Y407V / F234A / L235A / delta-K447 mutation. In some embodiments, the first and second heavy strands also contain the M252Y / S254T / T256E mutation.

[0064] In some embodiments, this document discloses a complex comprising the VWF protein and a monospecific antibody of the foregoing aspects and embodiments. In some embodiments, the complex comprises a VWF monomer. In some embodiments, the complex comprises a VWF dimer. In some embodiments, the complex comprises a VWF multimer. In some embodiments, the polymer has a strength of at least 250 kDa (e.g., at least 250 kDa, 500 kDa, 750 kDa, 1000 kDa, 1250 kDa, 1500 kDa, 1750 kDa, 2000 kDa, 3000 kDa, 4000 kDa, 5000 kDa, 6000 kDa, 7000 kDa, 8000 kDa, 9000 kDa, 10000 kDa, 11000 kDa, 12000 kDa, 13000 kDa, 14000 kDa, 15000 kDa, 16000 kDa, 17000 kDa, 18000 kDa, 19000 kDa, 20000 kDa, 21000 kDa). Molecular weights of 22,000 kDa, 23,000 kDa, 24,000 kDa, 25,000 kDa or higher.

[0065] In some embodiments, this document discloses pharmaceutical compositions comprising a monospecific antibody of the foregoing aspects and embodiments, and a pharmaceutically acceptable carrier, diluent, or excipient. In some embodiments, the pharmaceutically acceptable carrier, diluent, or excipient is selected from the group consisting of stabilizers, buffers, surfactants, fillers, solvents, tonic or osmotic pressure regulators, antioxidants, adjuvants, and antimicrobial agents.

[0066] In some embodiments, this document discloses methods for treating a subject in need of a blood disorder characterized by excessive bleeding, comprising administering to the subject a monospecific antibody or pharmaceutical composition of the foregoing aspects and embodiments. In some embodiments, the blood disorder is selected from the group consisting of von Willebrand disease (VWD), Heydes syndrome, hemophilia A, platelet dysfunction, and connective tissue disorders. In some embodiments, VWD is congenital VWD (cVWD) or acquired VWD (aVWD). In some embodiments, VWD is type 1, 2A, 2B, 2M, 2N, or 3. In some embodiments, the compositions disclosed herein treat blood disorders of one or more symptoms selected from the group consisting of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more): epistaxis, skin bleeding, minor wound bleeding, oral bleeding, vascular dysplasia, gastrointestinal bleeding, tooth extraction bleeding, postoperative bleeding, severe menstrual bleeding, obstetric hemorrhage, hematuria, muscle hematoma, joint bleeding, visceral bleeding, and central nervous system (CNS) bleeding. In some embodiments, the compositions or pharmaceutical compositions disclosed herein promote platelet adhesion, activation, and aggregation in a subject. In some embodiments, a method for accumulating VWF protein in the plasma of a subject in need is disclosed herein, comprising administering to the subject a composition containing a monospecific antibody comprising the foregoing aspects and embodiments.

[0067] In some embodiments, this document discloses a method for accumulating FVIII protein in the plasma of a subject in need, which includes administering to the subject a composition comprising a monospecific antibody comprising the foregoing aspects and embodiments.

[0068] In some embodiments, this document discloses a method for increasing the plasma half-life of VWF protein in subjects in need, comprising administering to the subject a composition comprising a monospecific antibody comprising the foregoing aspects and embodiments.

[0069] In some embodiments, pharmaceutical compositions disclosed herein comprise the monospecific antibody disclosed herein, along with a pharmaceutically acceptable carrier, diluent, or excipient. In some embodiments, the pharmaceutically acceptable carrier, diluent, or excipient is selected from the group consisting of stabilizers, buffers, surfactants, fillers, solvents, tonic or osmotic pressure regulators, antioxidants, adjuvants, and antimicrobial agents. In some embodiments, the pharmaceutical compositions disclosed herein are administered in combination with one or more (e.g., 1, 2, 3, 4, 5, or more) additional therapeutic forms. In some embodiments, one or more additional therapeutic forms are one or more therapeutic agents. In some embodiments, one or more therapeutic agents are selected from the group consisting of: desmopressin (DDAVP), tranexamic acid (TXA), thalidomide, tamoxifen, ocreotide, plasma-derived VWF protein concentrates, VWF protein concentrates complexed with FVIII protein (VWF:FVIII; e.g., Humate P and Wilate), recombinant VWF protein concentrates (e.g., Vonicog alfa), FVIII protein concentrates (e.g., Alphanate and Koate-HP), and hormone therapy (e.g., oral contraceptives, estrogen-containing contraceptives, and intrauterine devices). In some embodiments, one or more additional forms of treatment are surgery. In some embodiments, one or more additional forms of treatment are blood transfusions. In some embodiments, one or more additional forms of treatment are platelet transfusions. In some embodiments, one or more additional forms of treatment are cauterization. In some embodiments, one or more additional forms of treatment are gene therapy. In some embodiments, the gene therapy is FVIII gene therapy. For example, the antibodies or compositions of this disclosure may be administered in combination with FVIII gene therapy to prolong the half-life of FVIII and / or promote the accumulation of FVIII in the plasma of a subject. In some embodiments, the antibodies or compositions of this disclosure are administered to a patient to whom FVIII gene therapy alone is insufficient to achieve a therapeutically effective level of FVIII in plasma. In some embodiments, the antibodies or compositions of this disclosure achieve a therapeutically effective level of FVIII in plasma. In some embodiments, one or more additional forms of treatment are administered to the subject before, simultaneously with, or after administration of the composition or pharmaceutical composition. In some embodiments, one or more additional forms of treatment are administered to the subject before administration of the composition or pharmaceutical composition. In some embodiments, one or more additional forms of treatment are administered to the subject simultaneously with the composition or pharmaceutical composition. In some embodiments, one or more additional forms of treatment are administered to the subject after administration of the composition or pharmaceutical composition.

[0070] In some embodiments, this document discloses a kit comprising a monospecific antibody or pharmaceutical composition of the foregoing aspects and embodiments, and a pharmaceutical instruction manual instructing the user of the kit to perform the methods described in the foregoing aspects and embodiments.

[0071] In some embodiments, the monospecific antibody and pharmaceutical composition of the aforementioned embodiments are disclosed herein for use as a medicine. In some embodiments, the monospecific antibody or pharmaceutical composition of the aforementioned embodiments is used to treat blood disorders characterized by excessive bleeding.

[0072] In some embodiments, this document discloses monospecific antibody or pharmaceutical compositions of the aforementioned embodiments for the treatment of blood disorders characterized by excessive bleeding.

[0073] In some embodiments of the foregoing aspects, the blood disorder causing excessive bleeding is selected from the group consisting of VWD, Heydes syndrome, hemophilia A, platelet dysfunction, and connective tissue disorders. In some embodiments, VWD is cVWD or aVWD. In some embodiments, VWD is type 1, 2A, 2B, 2M, 2N, or 3.

[0074] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. Generally, the nomenclature and techniques used herein in conjunction with immunology, oncology, cell and tissue culture, molecular biology, and protein and oligonucleotide or polynucleotide chemistry and hybridization are well known and commonly used in the art. It should be understood that the above general description and the following detailed description are exemplary and explanatory only and do not limit any of the claimed subject matter. Section headings used herein are for organizational purposes only and should not be construed as limiting the described subject matter.

[0075] Unless the context clearly indicates otherwise, as used herein, the singular forms “a,” “an,” and “the” include multiple indicators. Thus, for example, reference to “an antibody” includes multiple antibodies, and in some embodiments, reference to “an antibody” includes multiple antibodies, and so on.

[0076] Unless the context explicitly indicates otherwise, as used herein, all numerical values ​​or ranges include all integers within or covering such ranges, as well as decimals of values ​​or integers within or covering such ranges. Thus, for example, references to a range of 90-100% include 91%, 92%, 93%, 94%, 95%, 95%, 97%, etc., and 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. In another example, the range of 1-5,000 times includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 times, as well as 1.1, 1.2, 1.3, 1.4, 1.5 times, 2.1, 2.2, 2.3, 2.4, 2.5 times, and so on.

[0077] As used herein, the phrase "at least [X]% identity" refers to any percentage of identity from (and including) X up to (and including) 100% identity, where X can be any integer from 1 to 99%. For example, the phrase "at least 80% identity" means any percentage of identity from (and including) 80% identity up to (and including) 100% identity, including 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and 100%. For example, in some implementations, "at least 80% identity" with respect to a particular sequence also includes at least 85% identity, at least 90% identity, at least 95% identity, at least 97% identity, at least 98% identity, at least 99% identity, and 100% identity.

[0078] As used in this article, “approximately” refers to a range that includes the value and is within the range of 10% lower to 10% higher than the value. “Approximately” also refers to a range that is 10% lower than the lower limit of the range and up to 10% higher than the upper limit of the range.

[0079] As used herein, the term "accumulation" refers to an increase in the level (e.g., concentration) of a specific protein, such as VWF or FVIII, in a subject's blood compartment (e.g., plasma) after administration of an antibody of this disclosure or a composition containing said antibody (e.g., a pharmaceutical composition). Various factors can affect the rate of protein accumulation in a subject's blood compartment, including but not limited to the half-life of the target protein and / or antibody in the blood compartment, the isolation rate of the protein by other tissues, the clearance of the protein from the body, and other factors. According to this disclosure, accumulation of the target protein (e.g., VWF or FVIII) can result in plasma protein levels that are at least 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 times higher than plasma protein levels in the absence of the antibody. Alternatively or additionally, the accumulation of the target protein may result in plasma protein levels that are at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, 10,000%, or higher than those in the absence of antibodies. In some embodiments, the accumulation of a protein (e.g., VWF) is directly caused by the specific binding of the antibody of this disclosure to the protein. In some embodiments, the accumulation of a protein (e.g., FVIII) is indirectly caused by the binding of the protein (e.g., FVIII) to another protein (e.g., VWF) that binds to the antibody of this disclosure.

[0080] As used herein, "antibody" refers to a naturally occurring or non-naturally occurring protein that binds to an antigen. Antibodies typically contain a variable domain and a constant domain in each of their heavy and light chains. Therefore, most antibodies possess a heavy chain variable domain (V... H ) and light chain variable structural domain (V L Together, these form the antibody portion that binds to the antigen, sometimes called the "antigen receptor." Within each variable domain are three complementarity-determining regions (CDRs), which are located at V... H and V LAn antibody forms a ring and contacts the antigen surface. "Antibody" includes, but is not limited to, monoclonal antibodies, monospecific antibodies, monovalent antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized antibodies, chimeric antibodies, synthetic antibodies, recombinant antibodies, hybrid antibodies, mutant antibodies, transplanted antibodies, antibody fragments, and antibodies produced in vitro with antigen-binding activity. The term also includes antibody conjugates (e.g., antibodies conjugated with a half-life extension, such as fatty acids) that have advantageous properties compared to unconjugated antibodies.

[0081] As used herein, “complementarity-determining region,” “CDR,” and “hypervariant region” refer to the portion of an antibody’s variable domain that determines the antibody’s binding specificity to its specific antigen. A single variable region of an antibody peptide will typically contain three CDRs, usually denoted as CDR1, CDR2, and CDR3. More specifically, the heavy chain variable region may contain CDRs denoted as H1, H2, and H3; similarly, the light chain variable region may contain CDRs L1, L2, and L3. Various methods can be used to define CDRs. Current techniques utilize multiple numbering schemes that define CDR length and position differently. For example, the IMGT numbering scheme is a standardized numbering system based on sequence alignment from a complete reference gene database, including the entire immunoglobulin superfamily. The Kabat numbering scheme is based on sequence alignment and predicts CDRs using a “variability parameter” (the number of times different amino acids appear at a given position divided by the frequency of the most frequently occurring amino acid at that position). On the other hand, the Chothia numbering scheme is a structure-based numbering scheme where the antibody crystal structure is aligned to define loop structures as CDRs. The Martin numbering scheme focuses on the structural alignment of different frame regions of unconventional lengths. The Honneger numbering scheme (AHo's) is based on the structural alignment of 3D structures of variable regions and derives frame and CDR lengths using structurally conservative Cα positions. Those skilled in the art should note that CDR definitions will vary depending on the method used. Therefore, the CDR sequence for a given heavy or light chain variable region may vary depending on the numbering system used. The sequences disclosed herein consider any method of defining CDRs. Unless otherwise stated, the CDRs disclosed herein are defined according to the IMGT numbering scheme.

[0082] The terms “antigen-binding portion of an antibody,” “antigen-binding fragment,” “antigen-binding domain,” and “antibody fragment” are used interchangeably herein to refer to one or more fragments of an antibody that maintain the ability to specifically bind to an antigen. Non-limiting examples of antibody fragments included within such terms include, but are not limited to, for example, Fab fragments, which are formed by V… L V H C L and C H1Monovalent fragments composed of structural domains. Also included are "single-arm" antibodies containing a single heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain.

[0083] As used herein, the phrase "blood disorder characterized by excessive bleeding" refers to one or more conditions in a subject (e.g., a person) that confer a bleeding predisposition (e.g., bleeding diathesis). In some embodiments, such conditions are attributed to disorders associated with atypical and slow blood clotting. The origin of a "blood disorder characterized by excessive bleeding" can be hereditary or acquired. In some embodiments, platelet activation, adhesion, and / or aggregation (e.g., primary hemostasis) is impaired in subjects with said conditions. In some embodiments, the function or expression of blood proteins that mediate or promote the production of insoluble cross-linked fibrin (e.g., secondary hemostasis) is impaired in subjects with said conditions. Non-limiting examples of blood disorders characterized by excessive bleeding include von Willebrand disease (VWD), hemophilia A, platelet dysfunction, and connective tissue disorders. In some embodiments, VWD is congenital VWD (cVWD) or acquired VWD (aVWD). In some embodiments, aVWD includes Heydes syndrome. In some implementations, VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.

[0084] As used herein, the term "complex" refers to a molecular entity formed by two or more physically associated molecules (e.g., proteins), such as VWF protein and the antibody described herein. In some embodiments, the two or more molecules are associated by any physical means, including covalent bonds, ionic bonds, hydrogen bonds, and van der Waals forces. In some embodiments, the physical association between the two or more molecules is reversible. In some embodiments, the physical association between the two or more molecules is irreversible.

[0085] As used herein, the term "effective amount" refers to the amount of the antibody or its antigen-binding moiety described herein that is sufficient to induce the disclosed efficacy, such as achieving treatment (e.g., accumulation of VWF and / or FVIII proteins in plasma), prognosis, or diagnosis of the disease described herein (e.g., a blood disorder characterized by excessive bleeding), prognosis, or diagnosis. When used alone or in combination, the therapeutically effective amount of the antibodies provided herein will vary depending on the relative activity of the disclosed antibodies and combinations (e.g., in treating, alleviating, or improving the disease or condition described herein) and on the subject being treated and the disease condition, the subject's weight and age, the severity of the disease condition, the method of administration, and similar factors, and in some cases, it is readily determined by those skilled in the art.

[0086] As used herein, the term "monospecific" refers to an antibody that exhibits preferential affinity for a specific epitope (e.g., a VWF protein, such as an epitope contained in the CK domain of a human, NHP, mouse, or canine VWF protein).

[0087] As used herein, the term "monovalent" refers to the characteristic of an antibody or its antigen-binding fragment that the antibody has a single antigen-binding site targeting a specific protein epitope. For example, the monovalent antibodies of this disclosure utilize a single antigen-binding site to bind to an epitope of a VWF protein (e.g., an epitope in the CK domain). In some embodiments, within the context of this disclosure, the monovalent antibody is a single-arm antibody (e.g., having a heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain).

[0088] As used herein, the term "one-armed antibody" or "single-armed antibody" refers to a type of monovalent antibody fragment containing an antibody heavy chain, a truncated heavy chain lacking the Fab region, and a single light chain.

[0089] "Identity percentage" and "identity %" refer to the degree to which two sequences (nucleotides or amino acids) have identical residues at the same position when aligned. For example, "amino acid sequence is identical to SEQ ID NO: YX%" means that the amino acid sequence is % identical to SEQ ID NO: Y, and is detailed as X% of residues in the amino acid sequence being identical to residues in the sequence disclosed in SEQ ID NO: Y. Generally, such calculations are performed using computer programs. Exemplary programs for comparing and aligning sequence pairs include ALIGN (Myers and Miller, Comput Appl Biosci. March 1988; 4(1):11-7); FASTA (Pearson and Lipman, Proc Natl Acad Sci USA April 1988; 85(8):2444-8; Pearson, Methods: Enzymol. 1990; 183:63-98); Vacant BLAST (Altschul et al., Nucleic Acids Res. September 1, 1997; 25(17): 3389-40); BLASTP, BLASTN or GCG (Devereux et al., Nucleic Acids Res. January 11, 1984; 12(1 Pt 1):387-95).

[0090] The term "peptide" refers to a chain of amino acids (e.g., naturally occurring or non-naturally occurring amino acids). In some embodiments, a peptide comprises naturally occurring amino acids. In some embodiments, the polypeptide comprises non-naturally occurring amino acids (cystine, desmodium, isodesmodium, hydroxyproline, hydroxylysine, γ-carboxyglutamic acid, phosphoserine, phosphothreonine, phosphotyrosine, N-acetyllysine, methyllysine, inositol, L-homoalanine, L-2-aminobutyric acid, L-azidohomoalanine, β-phenylalanine, leucine, 3-fluorotyrosine, 4-fluorophenylalanine, L-3,4-dihydroxyphenylalanine, pNCSF, L-(7-hydroxycoumarin-4-yl)ethylglycine, 2,3-dihydroxypropylcysteine, arylglycine, PrDiAzK, (S)-N-(2-benzoylphenyl)-1-(2-fluorobenzylmethyl)-pyrrolidine-2-carboxamide, 4-phenanthrene-9-yl-1-phenylalanine, BN tryptophan analog, p-acetylphenylalanine, L-azidohomoalanine and other amino acids). A polypeptide is not limited to a product of a specific length (e.g., a polypeptide may contain at least two amino acids linked together by peptide bonds). The definition of polypeptide includes peptides, oligopeptides, and proteins, and these terms are used interchangeably herein unless otherwise specified. This term also covers peptide chains with naturally occurring and non-natural post-expression modifications (e.g., glycosylation, acetylation, phosphorylation, etc.) and other modifications known in the art. In some embodiments, a polypeptide is a whole protein or a fragment thereof.

[0091] The terms "preferential binding" or "specific binding" mean that the antibody or fragment thereof has a greater affinity for binding an epitope than for binding an unrelated amino acid sequence, and is non-toxic at the level formulated for human use if it cross-reacts with other peptides containing that epitope. In some embodiments, such affinity is at least 1.5 times, 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 58 times, at least 70 times, at least 80 times, at least 90 times, at least 94 times, or at least 1000 times the affinity of the antibody or fragment thereof for the unrelated amino acid sequence.

[0092] The terms “recipient,” “individual,” “subject,” “host,” and “patient” are used interchangeably herein and refer to any mammalian subject requiring diagnosis, treatment, or therapy, particularly a human. For therapeutic purposes, “mammal” means any animal classified as a mammal, including humans, domestic and agricultural animals, as well as laboratory, zoo, sporting, or pet animals such as dogs, horses, cats, cattle, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, monkeys, etc. In some implementations, the mammal is a human. These terms do not require the supervision of a medical professional.

[0093] The term "specificity" refers to the preferential binding of an antibody to molecules other than those containing an epitope recognized by the antibody. This term also applies, for example, to cases where an antigen-binding domain is specific to a particular epitope carried by multiple antigens, in which case an antibody carrying the antigen-binding domain or its antigen-binding fragment will be able to bind to multiple antigens carrying epitopes.

[0094] The term "therapeuticly effective amount" generally refers to the amount of an antibody or drug disclosed herein that effectively "treats" a disease or condition in a subject or mammal. In some embodiments, the compositions described herein are administered to a subject in an amount that effectively produces a desired therapeutic effect by inhibiting the disease or condition described herein with a reasonable benefit / risk ratio suitable for any medical treatment. A therapeutically effective amount is the amount that at least partially achieves the desired therapeutic or preventative effect in an organ or tissue. The amount of antibody required to produce preventative and / or therapeutic treatment of a disease or condition is not fixed in itself. In some embodiments, the amount of antibody administered varies depending on the type of disease, the severity of the disease, and the size of the mammal suffering from the disease or condition. The term "therapeuticly effective," when used in conjunction with a treatment method involving the administration of a therapeutic agent after a subject has presented symptoms of a disease or condition, means that one or more signs or symptoms of the disease or condition are improved or eliminated after treatment.

[0095] In some embodiments, an effective response to this disclosure is achieved when a subject experiences partial or complete remission or reduction of the signs or symptoms of the disease, and in the case of treating a disease (e.g., a blood disorder characterized by excessive bleeding), specifically including, but not limited to, symptom improvement, slowed progression, cure, remission, prolonged survival, or other objective responses. In some embodiments, the expected progression-free survival is measured in months to years, depending on prognostic factors, including the number of relapses, disease stage, and other factors. Prolonged survival includes, but is not limited to, at least 1 month (mo.), about at least 2 months, about at least 3 months, about at least 4 months, about at least 6 months, about at least 1 year, about at least 2 years, about at least 3 years, etc. Total survival is also measured, for example, in months to years. Alternatively, in some embodiments, an effective response is a change in the subject's symptoms. Other indications for treatment of the indication are described in more detail below.

[0096] In some implementations, a therapeutic agent is administered through preventative methods before the undesirable symptoms of a disease or condition appear, thereby preventing the disease or condition from developing or alternatively delaying its progression. Therefore, when used in conjunction with preventative methods, the term "treatment-effective" means that, on average, a smaller number of subjects experienced an undesirable progression of disease or condition or symptom severity after treatment.

[0097] As used herein, the terms “treatment,” “treating,” etc., in some contexts refer to the administration of an agent or the performance of a procedure for the purpose of achieving an effect. An effect may be preventative in terms of the complete or partial prevention of a disease or its symptoms, and / or therapeutic in terms of achieving a partial or complete cure of the disease and / or its symptoms. As used herein, “treatment” includes treating diseases or conditions in mammals, particularly humans (e.g., blood disorders characterized by excessive bleeding), and includes: (a) preventing the onset of a disease or its symptoms in subjects susceptible to the disease but not yet diagnosed with it (e.g., diseases related to or caused by a primary disease); (b) suppressing the disease, i.e., halting its development; and (c) alleviating the disease, i.e., promoting its resolution. The term treatment includes any sign of success in treating or improving or preventing a disease or condition, including any objective or subjective parameter such as reduction; relief; lessening of symptoms or making the disease symptoms more tolerable for the patient; slowing the rate of deterioration or decline; or making the final point of deterioration less debilitating. Treatment or improvement of symptoms is based on one or more objective or subjective parameters, including the results of a physician’s examination. Therefore, the term "treatment" includes administering the agents of this disclosure to prevent or delay, alleviate, or inhibit or suppress the development of disease-related symptoms or conditions. The term "therapeutic effect" refers to the reduction, elimination, or prevention of a subject's disease, symptoms of the disease, or side effects of the disease. A subject's disease or condition is "treated" if, after receiving a therapeutic dose of the antibody of this disclosure, observable and / or measurable changes are observed in parameters or symptoms of the patient's disease or condition. Attached Figure Description

[0098] Figure 1 This flowchart shows a protocol for selecting antibodies that specifically bind to the cysteine ​​knot (CK) domain of the human von Willebrand factor (VWF) protein.

[0099] Figure 2 This displays the epistatic equilibrium dissociation constant (K0) used to measure the relationship between monovalent (single-arm; OA) anti-VWF CK domain antibody and the CK domain of VWF. d An overview of the experimental setup.

[0100] Figure 3 The chart shows the distribution of low molecular weight (LMW), medium molecular weight (IMW), and high molecular weight (HMW) VWF polymers after incubating normal human plasma overnight with 600 nM monovalent (single-arm) antibody and 1.5 mg / mL ristocetin. Two control conditions were included: plasma without antibody and ristocetin (untreated) and plasma treated with ristocetin only (control). Results are shown as mean ± standard deviation of plasma from three healthy human donors.

[0101] Figures 4A to 4E This is a graph showing the pharmacokinetics and pharmacodynamics of monovalent (single-arm) Lib1_P1_A6 (Lib_P1_A6OA) antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 3FG2 and 4FG2, respectively) on days 1 and 2. Plasma levels: ( Figure 4A ) Lib1_P1_A6 OA (Example 20), ( Figure 4B VWF antigen (VWF:Ag; Example 15), ( Figure 4C VWF ritomonas cofactor activity (VWF:RCo; Example 18), Figure 4D Distribution of low (LMW), medium (IMW), and high (HMW) molecular weight VWF polymers, and ( Figure 4E FVIII antigen (FVIII:Ag).

[0102] Figures 5A to 5E This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) Lib1_P1_A9 (Lib_P1_A9 OA) antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (1 MG1 and 2 FG1, respectively) on days 1 and 2. Plasma levels: ( Figure 5A ) Lib1_P1_A9 OA, ( Figure 5B VWF antigen (VWF:Ag), ( Figure 5C VWF ritomonas cofactor activity (VWF:RCo), Figure 5D Distribution of low (LMW), medium (IMW), and high (HMW) molecular weight VWF polymers, and ( Figure 5E FVIII antigen (FVIII:Ag).

[0103] Figure 6A and Figure 6B This refers to the interaction between human VWF CK domain dimer and monovalent or divalent anti-VWF CK domain antibody 1081_Lib8 ( Figure 6A ) and Lib1_P1_A6 ( Figure 6B Chromatogram of the complex formed between the two components by SEC-HPLC analysis.

[0104] Figures 7A to 7D This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) A06_P1_D11 OA antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 103M and 55F, respectively) on day 0. Plasma levels: A06_P1_D11 OA ( Figure 7A VWF antigen (VWF:Ag; Figure 7B VWF ritomonas cofactor activity (VWF:RCo); Figure 7C ), and FVIII antigen (FVIII:Ag; Figure 7D ).

[0105] Figures 8A to 8D This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) A09_P1_E07 OA antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 715M and 723F, respectively) on day 0. Plasma levels: A09_P1_E07 OA ( Figure 8A VWF antigen (VWF:Ag; Figure 8B VWF ritomonas cofactor activity (VWF:RCo); Figure 8C ), and FVIII antigen (FVIII:Ag; Figure 8D ).

[0106] Figures 9A to 9D This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) A06_P1_C12 OA antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 716M and 724F, respectively) on day 0. Plasma levels: A06_P1_C12 OA ( Figure 9A VWF antigen (VWF:Ag; Figure 9B VWF ritomonas cofactor activity (VWF:RCo); Figure 9C ), and FVIII antigen (FVIII:Ag; Figure 9D ).

[0107] Figures 10A to 10D This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) A06_P1_B12 OA antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 717M and 727F, respectively) on day 0. Plasma levels: A06_P1_B12 OA ( Figure 10A VWF antigen (VWF:Ag; Figure 10B VWF ritomonas cofactor activity (VWF:RCo); Figure 10C ), and FVIII antigen (FVIII:Ag; Figure 10D ).

[0108] Figures 11A to 11D This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) A06_P1_H01 OA antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 718M and 728F, respectively) on day 0. Plasma levels: A06_P1_H01 OA ( Figure 11AVWF antigen (VWF:Ag; Figure 11B VWF ritomonas cofactor activity (VWF:RCo); Figure 11C ), and FVIII antigen (FVIII:Ag; Figure 11D ).

[0109] Figures 12A to 12D This is a graph showing the pharmacokinetics and pharmacodynamics of a monovalent (single-arm) A06_P1_G12 OA antibody administered subcutaneously at 4 mg / kg to two cynomolgus monkeys (“cyno”; 719M and 729F, respectively) on day 0. Plasma levels: A06_P1_G12 OA ( Figure 12A VWF antigen (VWF:Ag; Figure 12B VWF ritomonas cofactor activity (VWF:RCo); Figure 12C ), and FVIII antigen (FVIII:Ag; Figure 12D ). Detailed Implementation

[0110] In some embodiments, antibodies that specifically bind to von Willebrand factor (VWF) are disclosed herein. Pharmaceutical compositions comprising the disclosed antibodies and one or more pharmaceutically acceptable carriers, diluents, or excipients are also disclosed herein. This disclosure further provides methods for treating blood disorders characterized by excessive bleeding (e.g., von Willebrand disease (VWD), Heydes syndrome, hemophilia A, platelet dysfunction, and connective tissue disorders) using the disclosed antibodies or compositions containing said antibodies. A subject suffering from a blood disorder characterized by excessive bleeding is treated by administering the disclosed antibodies or compositions containing said antibodies (e.g., pharmaceutical compositions) to the subject via any acceptable route (e.g., subcutaneously) according to the methods disclosed herein.

[0111] Regulation of hemostasis Blood circulation provides cells and tissues with essential substances such as nutrients and oxygen, and removes metabolic waste products from these cells. The vascular system forms a physical barrier, ensuring the containment of blood, regulating its pressure throughout the organism, and directing the delivery of nutrients and waste products to tissues. Damage to or disruption of this barrier can lead to life-threatening blood loss. Plasma contains many soluble proteins that play a role in a coordinated cascade of enzymatic reactions to form a blood clot, which readily “plugs” damaged blood vessels and prevents or reduces further blood loss. This plugging is stabilized by the hydrolysis of fibrinogen into fibrin, which forms a network that coats and reinforces the clot. The formation and degradation of blood clots are part of a process known as hemostasis, regulated by a variety of soluble and membrane-anchored procoagulant and anticoagulant proteins. The balance between coagulation and fibrinolysis (i.e., the degradation of insoluble fibrin) controls the stability of the blood clot.

[0112] There are two central pathways that trigger blood clotting: the tissue factor (or exogenous) pathway and the contact (or endogenous) pathway. These clotting cascades proceed through the sequential activation of zymogens (i.e., inactive protein precursors) via proteolysis. Upon activation, each zymogen acts as a serine protease, activating downstream zymogens to drive clot formation. Protein cofactors also play a role in the blood clotting cascade, typically circulating in plasma as inactive pro-cofactors until activated by limited proteolysis.

[0113] The extrinsic pathway is initiated when the cell surface complex (TF:VIIa) of integrated membrane proteins, tissue factor (TF), and factor VIIa activates factors IX (FIX) and X (FX) via limited proteolysis, thereby producing activated FIX (FIXa) and activated FX (FXa). The contact pathway is initiated when factor XIIa (FXII), prokallikrein (PK), and kininogen (HK) assemble on a surface or polymer. Assembly induces cross-activation, where kallikrein (KK) activates FXII to FXIIa, and FXIIa in turn activates PK to KK. FXIIa then activates factor XI (FXI) to FXIa, which subsequently enzymatically converts FIX to FIXa. Activated FVIII (FVIIIa) combines with FIXa to form the X enzyme (FVIIIa:FIXa) complex, which is responsible for producing FXa together with the initiating TF:FVIIa complex. Exogenous and endogenous pathways ultimately converge to produce FXa, which leads to thrombin activation from prothrombin, thrombin-mediated fibrinogen cleavage into fibrin, and platelet activation, adhesion, and aggregation at the clot site.

[0114] VWF plays a crucial role in platelet adhesion, activation, and aggregation during blood coagulation. Increased local shear stress near the site of vascular injury causes VWF to bind to collagen in the subendothelial membrane, subsequently inducing platelets to attach to the anchored VWF via surface glycoproteins, thus initiating platelet plug formation. Under normal physiological conditions, the interaction between VWF and platelets occurs strictly in the presence of vascular injury, as VWF does not interact with circulating platelets in the absence of injury. The A1 and C4 domains of VWF are essential for binding to platelet glycoproteins, such as the platelet gp1b and gpIIbIIIa receptors, respectively. Because VWF and FVIII circulate in plasma as a complex under physiological conditions, accumulation of VWF at the site of vascular injury can increase local FVIII concentrations. Similarly, a decrease in VWF levels, for example, occurring in VWD, can lead to a decrease in FVIII levels.

[0115] Regulation of hemostasis is also crucial for preventing excessive blood clotting, which can lead to thrombus formation. Thrombi can detach from their formation site and potentially cause life-threatening embolisms. Endothelial cells of intact blood vessels regulate coagulation with the help of thrombomodulin, an integrated membrane protein that reduces clotting by converting thrombin into an anticoagulant form. Simultaneously, the thrombomodulin-thrombin complex can enzymatically activate thrombin, which in turn activates thrombin-activatable fibrinolysis inhibitor (TAFI) proteins. TAFI is a carboxypeptidase that reduces fibrinolysis by removing C-terminal lysine residues exposed on fibrin, which are essential for the conversion of plasminogen to plasmin. The fibrinolytic ability of TAFI is highly dependent on its concentration, activation rate, and plasma half-life.

[0116] Another crucial factor for controlling hemostasis is antithrombin (AT or AT3), a serine protease inhibitor (also known as serine protease inhibitor (serpin)) that regulates coagulation by inhibiting multiple proteases in the coagulation cascade, including FIXa, FXa, and thrombin. Its ability to inhibit coagulation factors is typically enhanced by binding to heparin. By inhibiting proteins in the coagulation cascade, AT regulates the blood clotting process, thereby preventing excessive clotting and thrombus formation. In humans, AT deficiency is associated with an increased risk of thrombotic diseases and pulmonary embolism.

[0117] Anti-von Willebrand factor antibody Mature VWF polypeptide is a large (2,050 amino acid residues) blood glycoprotein that plays a role in hemostasis and platelet adhesion. VWF is generally located in plasma, vascular endothelium, megakaryocytes, and subendothelial connective tissue, and exists as multimers of various sizes ranging from approximately 500 to 20,000 kDa. The size of VWF multimers is typically proportional to their hemostatic effect; larger VWF multimers are more effective in promoting coagulation. Different domains of VWF are involved in different functions. VWF contains the following domains from the N-terminus to the C-terminus: D1-D2-D'-D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK. During VWF processing into mature VWF, the D1-D2 domain corresponding to the VWF propeptide is cleaved by proteolytic hydrolysis. The D'-D3 domain mediates VWF dimerization and binding to factor VIII. The A1 domain binds to platelet gp1b receptors, heparin, and collagen. The A2 domain is cleaved by ADAMTS13, resulting in smaller VWF multimers. The A3 domain binds to collagen. The C4 domain binds to platelet gpIIa / IIIb. The CK domain is crucial for tail-to-tail isodimerization of VWF monomers. Binding of VWF to other proteins, such as FVIII, leads to stabilization of the binding pair and increases its plasma half-life. For example, in the absence of VWF, FVIII has a half-life of approximately 1–2 hours, but this is extended to 8–12 hours when bound to VWF. In addition to acting as a carrier of FVIII, VWF also promotes coagulation by facilitating platelet adhesion, activation, and aggregation. VWF deficiency or dysfunction is associated with bleeding tendency and occurs in many hematologic disorders characterized by excessive bleeding, including, for example, VWD and Heydes syndrome.

[0118] In some embodiments, this document provides antibodies that specifically bind to the VWF protein. In some embodiments, the VWF protein is the human VWF protein. In some embodiments, the human VWF protein has an amino acid sequence having at least 85% sequence identity with SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 1. In some embodiments, the human VWF protein has the amino acid sequence of SEQ ID NO: 1.

[0119] (SEQ ID NO: 1; UniProt No. P04275-1) In some embodiments, the VWF protein is a VWF protein from a non-human primate (NHP; e.g., a cynomolgus monkey). In some embodiments, the NHP VWF protein has an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has the amino acid sequence of SEQ ID NO: 2.

[0120] (SEQ ID NO: 2; UniProt No. A0A2K5X4G5) In some embodiments, the VWF protein is a VWF protein of a canine animal (e.g., a domestic dog). In some embodiments, the canine VWF protein has an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has the amino acid sequence of SEQ ID NO: 3.

[0121] (SEQ ID NO: 3; UniProt ID No. Q28295-1) In some embodiments, the VWF protein is a mouse (e.g., a house mouse) VWF protein. In some embodiments, the mouse VWF protein has an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 4. In some embodiments, the mouse VWF protein has an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 4. In some embodiments, the mouse VWF protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 4. In some embodiments, the mouse VWF protein has an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 4. In some embodiments, the mouse VWF protein has the amino acid sequence of SEQ ID NO: 4.

[0122] (SEQ ID NO: 4;UniProt ID No. Q8CIZ8-1) antibody sequence In some embodiments, the antibody comprises a complementarity-determining region (CDR) H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDRL1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 491, a CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 492, and a CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a heavy chain variable (VH) region having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a light chain variable (VL) region having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 490.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 491, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 492, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 490. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 490, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 491, a CDR L2 having 100% identity with the amino acid sequence of SEQ ID NO: 492, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDRH3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 490, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 491, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 492, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 683. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 684. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 683, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 684.

[0123] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 506, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 507, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 505.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 506, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 507, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 505, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 506, a CDRL2 having 100% identity with the amino acid sequence of SEQ ID NO: 507, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 505, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 506, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 507, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 685. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 686. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 685, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 686.

[0124] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 520, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 521, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 519.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 520, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 521, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 519, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 520, CDRL2 having 100% identity with the amino acid sequence of 521, and CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 519, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 520, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 521, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 687. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 688. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 687, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 688.

[0125] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 523, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 524, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 522.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 523, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 522, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 523, a CDRL2 having 100% identity with the amino acid sequence of SEQ ID NO: 524, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 522, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 523, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 689. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 731. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 690. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 689 or 731, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 690.

[0126] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 529. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 513, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 531, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 528. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 530.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 529; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 513, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 531, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 528 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 528 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 528 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 530. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 528, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 529.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 530, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 513, a CDR L2 having 100% identity with the amino acid sequence of 531, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 528, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 529; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 530, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 513, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 531, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 691. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 692. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 691, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 692.

[0127] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 551, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 552, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 550.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 551, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 552, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 550. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 550, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 551, a CDRL2 having 100% identity with the amino acid sequence of SEQ ID NO: 552, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 550, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 551, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 552, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 693. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 694. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 693, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 694.

[0128] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 544, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 524, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 575.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 544, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 575, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 544, CDRL2 having 100% identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 575, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 544, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 524, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 697. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 698. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 697, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 698.

[0129] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 45, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 577, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 576.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 45, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 577, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 576, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 45, a CDRL2 having 100% identity with the amino acid sequence of SEQ ID NO: 577, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises: (a) VH, the VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, the VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 576, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 577, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 699. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 700. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 699, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 700.

[0130] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 580, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 574, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 579.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 580, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 574, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 488 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 579. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 489.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 579, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 580, a CDRL2 having 100% identity with the amino acid sequence of SEQ ID NO: 574, and a CDR L3 having 100% identity with the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises: (a) VH, the VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 489; and (b) VL, the VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 579, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 580, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 574, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 701. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 702. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 701, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 702.

[0131] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 596, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 597, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 595. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 16.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 595 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 595 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 595 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 595, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 596, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 597, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 598.In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 16, and comprising CDRL1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity with the amino acid sequence of 589, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 595, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 596, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 597, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 598; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 703. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 703, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463.

[0132] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 605, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 604. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 16.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 604 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 604 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 604 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 604, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 605, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 606, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 607.In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 16, and comprising CDRL1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity with the amino acid sequence of 589, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) VH, said VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 604, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 605, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; and (b) VL, said VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 704. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 704, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463.

[0133] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 613, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 614, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 612. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 16.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 612 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 612 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 612 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 612, and comprising CDR H1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 613, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 614, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 607.In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 16, and comprising CDRL1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity with the amino acid sequence of 589, and CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) VH, the VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 612, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 613, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 614, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; and (b) VL, the VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 16, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 705. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 705, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 463.

[0134] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 619, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 620, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 618. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 618 and VL having an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 618 and a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 618 and a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 618, and comprising CDRH1 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 619, CDR H2 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 620, and CDR H3 having an amino acid sequence that is 100% identical to that of SEQ ID NO: 607.In some embodiments, the antibody comprises a VL having an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 602, and comprising a CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, a CDR L2 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) VH, the VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 618, and comprising CDR H1 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 619, CDR H2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 620, and CDR H3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 607; and (b) VL, the VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602, and comprising CDR L1 having 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence having 100% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 706. In some embodiments, the antibody comprises an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 707. In some embodiments, the antibody comprises: a first HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 706, and an LC containing an amino acid sequence having at least 80% identity with SEQ ID NO: 707.

[0135] In some embodiments, the antibody comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 625, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises CDR L1 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 17, CDR L2 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having 100% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises VH having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the antibody comprises VL having an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 85% identity with SEQ ID NO: 624. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 85% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 90% identity with SEQ ID NO: 624. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 90% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence having at least 95% identity with SEQ ID NO: 624. In some embodiments, the antibody comprises a VL having an amino acid sequence having at least 95% identity with SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the antibody comprises a VL having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 602.In some embodiments, the antibody comprises: (a) CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 625, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence 100% identical to the am...

Claims

1. A monospecific antibody comprising: an antigen-binding site that specifically binds to an epitope located in the cysteine ​​knot (CK) domain of a von Willebrand factor (VWF) protein; and a crystallizable fragment (Fc) region, wherein the binding of the antibody to the VWF protein in plasma leads to the accumulation of the VWF protein in plasma compared to plasma levels in the absence of the antibody.

2. The monospecific antibody of claim 1, wherein the antibody comprises a heavy chain variable (VH) region having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and a light chain variable (VL) region having an amino acid sequence having at least 80% identity with SEQ ID NO:

522.

3. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH contains a complementarity determination region (CDR) H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL contains a CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 524, and a CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

518.

4. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 689 or 731, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

690.

5. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 577, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

578.

6. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 699, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

700.

7. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

505.

8. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 506, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 507, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

493.

9. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 685, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

686.

10. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

575.

11. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 544, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 524, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

527.

12. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 697, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

698.

13. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

490.

14. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 491, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 492, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

493.

15. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 683, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

684.

16. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

519.

17. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 520, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of 521, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

493.

18. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 687, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

688.

19. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 528 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

530.

20. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 529; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 513, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 531, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

46.

21. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 691, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

692.

22. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

550.

23. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 551, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 552, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

553.

24. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 693, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

694.

25. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

564.

26. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 565, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 566, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

527.

27. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 695, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

696.

28. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

579.

29. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 580, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 574, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

549.

30. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 701, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

702.

31. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 595 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

16.

32. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

33. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 703, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

463.

34. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 604 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

16.

35. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 605, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

36. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 704, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

463.

37. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 612 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

16.

38. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

39. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 705, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

463.

40. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 618 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

41. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 619, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 620, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

42. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 706, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

707.

43. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 624 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

44. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 625, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 606, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

45. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 708, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

707.

46. ​​The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 630 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

633.

47. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 631, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 632, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 634, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

48. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 709, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

710.

49. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 635 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO: 602; The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 637, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

50. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 711, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

707.

51. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 638 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

641.

52. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 639, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 640, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 642, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 643, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

53. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 712, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

713.

54. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 644 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

55. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 645, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 646, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

56. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 714, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

707.

57. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 649 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

651.

58. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 636, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 650, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 652, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

59. The monospecific antibody of claim 1, wherein the antibody comprises: a first HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 715, and an LC comprising an amino acid sequence having at least 80% identity with SEQ ID NO:

716.

60. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

494.

61. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 495, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 496, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

497.

62. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

498.

63. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 499, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 500, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

46.

64. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

501.

65. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 502, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 503, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

504.

66. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

505.

67. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 506, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 507, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

493.

68. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

508.

69. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 509, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 510, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

511.

70. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

512.

71. An acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

512.

72. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 513, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 514, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

515.

73. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

516.

74. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 517, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 503, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

518.

75. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

525.

76. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 526, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

527.

77. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

532.

78. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 533, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 534, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

511.

79. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

535.

80. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 536, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 537, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

538.

81. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

539.

82. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 540, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of 541, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

542.

83. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

543.

84. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 544, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 545, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

542.

85. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

546.

86. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 547, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 548, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

549.

87. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

554.

88. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 555, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 556, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

557.

89. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

558.

90. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 559, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 560, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

46.

91. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

561.

92. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 562, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 563, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

511.

93. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 567 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

569.

94. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 568; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 570, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of 571, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

46.

95. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 567 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

572.

96. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 568; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 573, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 574, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

46.

97. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 488 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

581.

98. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 489; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 582, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 583, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

584.

99. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 585 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

16.

100. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 586, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 587, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

101. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 590 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

593.

102. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 591, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 592, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 594, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 589, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

103. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 599 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

104. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 600, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 601, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

105. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 608 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

106. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 609, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 610, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 611; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

107. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 615 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

108. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 616, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 617, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

109. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 621 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

110. An amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

602.

111. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 622, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 623, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

112. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 626 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

627.

113. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 591, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 592, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 598; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 628, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 629, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

114. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 647 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

115. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 648, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

116. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 653 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

117. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 654, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 655, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

118. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 656 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

119. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 657, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 610, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

120. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 658 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

121. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 659, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 660, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 661; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

122. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 662 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

663.

123. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 664, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

124. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 665 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

633.

125. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 666, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 667, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 634, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

126. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 668 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

602.

127. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 669, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 670, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 607; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

128. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 671 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

674.

129. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 672, CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 673, and CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 643, and CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:

18.

130. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 675 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

677.

131. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 676, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 587, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 664, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 678, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

132. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 679 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

682.

133. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 680, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 681, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 588; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 642, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 603, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

134. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 40 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

44.

135. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 41, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 42, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 43; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 45, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 407, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

46.

136. The monospecific antibody of claim 1, wherein the antibody comprises VH having an amino acid sequence having at least 80% identity with SEQ ID NO: 12 and VL having an amino acid sequence having at least 80% identity with SEQ ID NO:

16.

137. The monospecific antibody of claim 1, wherein the antibody comprises VH, wherein the VH comprises CDR H1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 13, CDR H2 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 14, and CDR H3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 15; and VL, wherein the VL comprises CDR L1 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 17, CDR L2 having an amino acid sequence that is 100% identical to the amino acid sequence of 589, and CDR L3 having an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:

18.

138. The antibody according to any one of claims 1 to 137, wherein the antibody is a monovalent antibody.

139. The monospecific antibody according to any one of claims 1 to 138, wherein the Fc region is a wild-type Fc region.

140. The monospecific antibody according to any one of claims 1 to 138, wherein the Fc region is a modified Fc region.

141. The monospecific antibody according to any one of claims 1 to 140, wherein the antibody is a human IgG4 antibody comprising a first heavy chain and a second heavy chain.

142. The monospecific antibody of claim 141, wherein the first heavy chain comprises the S228P / T366W / F234A / L235A / delta-K447 mutation, and the second heavy chain comprises the S228P / T366S / L368A / Y407V / F234A / L235A / delta-K447 mutation.

143. The monospecific antibody according to any one of claims 1 to 142, wherein the antibody binds to one or more amino acid residues selected from D2726, R2730, K2735, E2744, D2746, K2757, D2763 and T2789 of the VWF CK domain.

144. The monospecific antibody according to any one of claims 1 to 142, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744 and D2746.

145. The monospecific antibody according to any one of claims 1 to 142, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, D2746, and K2757.

146. The monospecific antibody according to any one of claims 1 to 142, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, D2746, and K2757.

147. The monospecific antibody according to any one of claims 1 to 142, wherein the antibody binds to at least amino acid residue K2735 of the VWF CK domain.

148. The monospecific antibody according to any one of claims 1 to 142, wherein the antibody binds to at least one of the following amino acid residues of the VWF CK domain: T2728, R2730, L2731, Q2732, Y2733, V2734, K2735, E2744, D2746, K2757, M2759, Y2760 and I2762 of SEQ ID NO:

1.

149. A complex comprising VWF protein and a monospecific antibody according to any one of claims 1 to 148.

150. A pharmaceutical composition comprising the monospecific antibody as described in any one of claims 1 to 148 and a pharmaceutically acceptable carrier, diluent, or excipient.

151. A method of treating a subject in need, characterized by a blood disorder of excessive bleeding, comprising administering to the subject a monospecific antibody as described in any one of claims 1 to 148 or a pharmaceutical composition as described in claim 150.

152. The method of claim 151, wherein the hematologic disorder is selected from the group consisting of von Willebrand disease (VWD), Heydes syndrome, hemophilia A, platelet dysfunction, and connective tissue disorders.

153. The method of claim 151 or 152, wherein the composition treats one or more symptoms of the blood disorder selected from the group consisting of: nosebleeds, skin bleeding, minor wound bleeding, oral bleeding, vascular dysplasia, gastrointestinal bleeding, tooth extraction bleeding, postoperative bleeding, severe menstrual bleeding, obstetric hemorrhage, hematuria, muscle hematoma, joint bleeding, visceral bleeding, and central nervous system (CNS) bleeding.

154. A method for accumulating VWF protein in plasma, accumulating FVIII protein in plasma, and / or increasing the plasma half-life of VWF protein in a subject in need, comprising administering to the subject a composition comprising the monospecific antibody of any one of claims 1 to 148 or a pharmaceutical composition of claim 151.

155. The method of any one of claims 151 to 154, wherein the subject is a human being.

156. The monospecific antibody as described in any one of claims 1 to 148 or the pharmaceutical composition as described in claim 150, used as a medicament.

157. The monospecific antibody or pharmaceutical composition of claim 156, for treating blood disorders characterized by excessive bleeding.

158. The monospecific antibody as described in any one of claims 1 to 148 or the pharmaceutical composition as described in claim 150, for the treatment of blood disorders characterized by excessive bleeding.

159. The monospecific antibody or pharmaceutical composition for use according to claim 157 or 158, wherein the characteristic is that the excessive bleeding hematologic disorder is selected from the group consisting of VWD, Heydes syndrome, hemophilia A, platelet dysfunction, and connective tissue disorders.

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