Monospecific antibodies, pharmaceuticals, and complexes containing these monospecific antibodies.

Abstract

The invention relates to a specific monoantibody, a pharmaceutical composition, and a complex containing such a specific monoantibody. The antibody in the invention binds to von Willebrand factor in the blood plasma of the subject. Such antibodies are effective for therapeutic purposes to treat one or more blood disorders characterized by excessive bleeding.

Description

METHODS OF TREATING BLOOD DISORDERS WITH VWF-TARGETED MONOSPECIFIC ANTIBODIESCross-reference to Related Applications

[0001] The present application claims benefit of and priority to 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.Sequence Listing

[0002] The present specification makes reference to a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML file, created on August 5, 2024, is named HMT-005WO_SL.xml and is 678 kb in size.Summary of Certain Embodiments of the Disclosure

[0003] Disclosed herein, in certain embodiments, are compositions and methods for the treatment of blood disorders using monospecific antibodies targeted against von Willebrand factor (VWF).

[0004] Disclosed herein, in certain embodiments, are monospecific antibodies comprising an antigen-binding site that specifically binds to an epitope of a von Willebrand Factor (VWF) protein positioned at a cysteine knot (CK) domain and a fragment crystallizable (Fc) region, wherein binding of an antibody disclosed herein to the VWF protein results in accumulation of the VWF protein in blood plasma as compared to a blood plasma level of the VWF protein in the absence of the antibody.

[0005] In some embodiments, the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a variable light chain (VL) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with atleast 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 522 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 689 or 731, and a light chain (LC) region comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 690.

[0006] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least90% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 699, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 700.

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

[0008] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 575.In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 544, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 697, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 698.

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

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

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

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

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

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

[0015] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 595 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 703, and a LC comprising an amino acid sequence having at least 80% identity to SEQID NO: 463.

[0016] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 604 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ IDNO: 704, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

[0017] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 612 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 705, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

[0018] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 618 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In someembodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 706, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

[0019] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 624 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 624 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 624 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 624 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 624 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 625, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 624 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 625, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an aminoacid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 708, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

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

[0021] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 635 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 635 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 635 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 635 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 635 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 637, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 635 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 637, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to theamino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 711, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

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

[0023] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 644 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 644 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 644 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 644 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 644 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 645, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 646, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 644 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 645, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 646, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 714, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

[0024] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 649 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 649 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 649 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 649 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 651. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 649 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 651. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 650, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 652, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 649 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 650, anda CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 652, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 715, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 716.

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

[0026] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 498. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 498. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 499, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 500, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO:498 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 499, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 500, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

[0027] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 501. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 501. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 502, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 503, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 504. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 501 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 502, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 503, and a CDR L3 having an amino acid sequence100% identical to the amino acid sequence of SEQ ID NO: 504.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0042] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 567 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 567 and a VL having an amino acid sequence with at least90% identity to SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 567 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 572. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 572. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 568; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 573, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 568; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 573, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

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

[0044] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 585 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 585 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 585 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 585 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 585 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VHcomprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 586, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 587, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 585 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 586, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 587, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0045] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 590 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 590 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 590 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 590 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 593. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 590 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 593. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 591, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 592, and a CDR H3having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 594, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 590 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 591, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 592, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 594, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0046] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 599 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 599 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 599 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 599 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 599 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 601, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 599 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 601, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0047] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 608 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 608 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 608 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 608 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 608 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 609, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least80% identity to SEQ ID NO: 608 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 609, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0048] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 615 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 615 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 615 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 615 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 615 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 616, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 617, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 615 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 616, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 617, anda CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0049] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 621 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 621 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 621 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 621 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 621 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 622, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 623, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 621 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 622, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 623, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to theamino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

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

[0051] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 647 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 647 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 647 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 647 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 647 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 648, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 647 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 648, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0052] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 653 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibodycomprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 653 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 653 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 653 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 653 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 654, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 655, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 653 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 654, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 655, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0053] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 656 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 656 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with atleast 90% identity to SEQ ID NO: 656 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 656 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 656 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 657, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 656 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 657, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0054] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 658 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 658 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 658 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 658 and a VLhaving an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 658 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 659, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 660, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 661; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 658 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 659, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 660, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 661; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0055] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 662 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 662 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 662 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 662 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 663. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 662 and a VL having an amino acid sequence 100%identical to the amino acid sequence of SEQ ID NO: 663. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 664, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 662 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 664, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

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

[0057] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 668 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 668 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 668 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 668 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 668 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 669, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 670, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identicalto the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 668 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 669, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 670, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

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

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

[0060] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 679 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 679 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 679 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 679 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 682. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 679 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 682. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 680, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 681, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 642, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 679 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 680, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 681, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO:682 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 642, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0061] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 40 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 40 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 40 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 44. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 40 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 44. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDR L3 having an amino acid sequence 100% identical to the aminoacid sequence of SEQ ID NO: 46.

[0062] In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 12 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 12 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 12 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 12 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 12 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 12 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

[0063] In some embodiments, an antibody disclosed herein is a monovalent antibody. In some embodiments, the Fc region is a wild-type Fc region. In some embodiments, the Fcregion is a modified Fc region. In some embodiments, the modified Fc region comprises one or more mutations selected from the group consisting of a 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 / Q311 V / A378V mutation, T256D / H286D / T307R / Q311 V / 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 / P329G 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, F234 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 Fc region comprises an N-terminal truncation (e.g., a truncation by 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 N-terminal residues, or more). In some embodiments, the antibody is a humanIgG4 antibody comprising a first heavy chain and a second heavy chain. In some embodiments, the first heavy chain comprises a S228P / T366W / F234A / L235A / delta-K447 mutation and the second heavy chain comprises a S228P / T366S / L368A / Y407V / F234AZL235A / delta-K447 mutation. In some embodiments, the first heavy chain comprises a S228P / T366W / delta-K447 mutation and the second heavychain comprises a S228P / T366S / L368A / Y407V / delta-K447 mutation. In some embodiments, the first heavy chain and the second heavy chain further comprise a M252Y / S254T / T256E mutation.

[0064] Disclosed herein, in certain embodiments, is a complex comprising a 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 multimer has a molecular weight of at least 250 kDa (e.g., at least 250 kDa, 500 kDa, 750 kDa, 1000 kDa, 1,250 kDa, 1,500 kDa, 1,750 kDa, 2,000 kDa, 3,000 kDa, 4,000 kDa, 5,000 kDa, 6,000 kDa, 7,000 kDa, 8,000 kDa, 9,000 kDa, 10,000 kDa, 11,000 kDa, 12,000 kDa, 13,000 kDa, 14,000 kDa, 15,000 kDa, 16,000 kDa, 17,000 kDa, 18,000 kDa, 19,000 kDa, 20,000 kDa, 21,000 kDa, 22,000 kDa, 23,000 kDa, 24,000 kDa, 25,000 kDa, or more).

[0065] Disclosed herein, in certain embodiments, are 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 a stabilizer, buffer, surfactant, filler, solvent, tonicity or osmolarity adjusting agent, antioxidant, adjuvant, and antimicrobial agent.

[0066] Disclosed herein, in certain embodiments, are methods of treating a blood disorder characterized by excessive bleeding in a subject in need thereof, comprising administering to the subject a monospecific antibody or a 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, disorders of platelet function, and connective tissue disorders. In some embodiments, the VWD is congenital VWD (cVWD) or acquired VWD (aVWD). In some embodiments, the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3. In some embodiments, a composition disclosed herein treats one or more (e.g., 1, 2, 3, 4, 5, 6 ,7, 8, 9, 10, or more) symptoms of the blood disorder selected from the group consisting of epistaxis, cutaneous bleeding, bleeding from minor wounds, oral-cavity bleeding, angiodysplasia, gastrointestinal bleeding, bleeding from tooth extraction, postoperative bleeding, heavy menstrual bleeding, obstetric hemorrhage, hematuria, muscle hematoma, joint bleeding, visceral bleeding, and central nervous system (CNS) bleeding. In some embodiments, a composition or pharmaceutical composition disclosed herein promotes platelet adhesion, activation, and aggregation in thesubject.Disclosed herein, in certain embodiments, are methods of accumulating a VWF protein in blood plasma of a subject in need thereof, comprising administering to the subject a composition comprising a monospecific antibody of the foregoing aspects and embodiments.

[0067] Disclosed herein, in certain embodiments, are methods of accumulating a FVIII protein in blood plasma of a subject in need thereof, comprising administering to the subject a composition comprising a monospecific antibody of the foregoing aspects and embodiments.

[0068] Disclosed herein, in certain embodiments, are methods of increasing blood plasma half-life of a VWF protein in a subject in need thereof, comprising administering to the subject a composition comprising a monospecific antibody of the foregoing aspects and embodiments.

[0069] Disclosed herein, in certain embodiments, are pharmaceutical compositions comprising a monospecific antibody disclosed herein 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 a stabilizer, buffer, surfactant, filler, solvent, tonicity or osmolarity adjusting agent, antioxidant, adjuvant, and antimicrobial agent. In some embodiments, a pharmaceutical composition disclosed herein is administered in combination with one or more (e.g., 1, 2, 3, 4, 5, or more) additional therapeutic modalities. In some embodiments, the one or more additional therapeutic modalities is one or more therapeutic agents. In some embodiments, the one or more therapeutic agents is selected from the group consisting of desmopressin (DDAVP), tranexamic acid (TXA), thalidomide, tamoxifen, ocreotide, a concentrate of plasma-derived VWF protein, a concentrate of VWF protein in complex with FVIII (VWF :F VIII; e.g., Humate P and Wilate), a concentrate of recombinant VWF protein (e.g., Vonicog alfa), a concentrate of FVIII protein (e.g., Alphanate and Koate-HP), hormonal treatment (e.g., an oral contraceptive pill, e.g., an estrogen-containing contraceptive and an intrauterine device). In some embodiments, the one or more additional therapeutic modalities is surgery. In some embodiments, the one or more additional therapeutic modalities is blood transfusion. In some embodiments, the one or more additional therapeutic modalities is platelet transfusion. In some embodiments, the one or more additional therapeutic modalities is cauterization. In some embodiments, the one or more additional therapeutic modalities is gene therapy. In some embodiments, the gene therapy is FVIII gene therapy. For example, an antibody or composition of the disclosure may be administered in combination with a FVIII gene therapy to extend the half-life of FVIII and / or promote accumulation of FVIII in blood plasma of a subject. In some embodiments, an antibody or composition of the disclosure is administered to a patient forwhom FVIII gene therapy alone is insufficient to attain therapeutically effective levels of FVIII in blood plasma. In some embodiments, an antibody or composition of the disclosure achieves therapeutically effective levels of FVIII in blood plasma. In some embodiments, the one or more additional therapeutic modalities are administered to the subject prior to, concurrently with, or subsequent to administration of the composition or the pharmaceutical composition. In some embodiments, the one or more additional therapeutic modalities are administered to the subject prior to administration of the composition or the pharmaceutical composition. In some embodiments, the one or more additional therapeutic modalities are administered to the subject concurrently with the composition or the pharmaceutical composition. In some embodiments, the one or more additional therapeutic modalities are administered to the subject subsequent to administration of the composition or the pharmaceutical composition.

[0070] Disclosed herein, in certain embodiments, are kits comprising a monospecific antibody or a pharmaceutical composition of the foregoing aspects and embodiments, and a package insert instructing a user of the kit to perform a method of the foregoing aspects and embodiments.

[0071] Disclosed herein, in certain embodiments, are monospecific antibodies and pharmaceutical compositions of the foregoing embodiments for use as a medicament. In some embodiments, a monospecific antibody or the pharmaceutical composition of the foregoing embodiments is for use in the treatment of a blood disorder characterized by excessive bleeding.

[0072] Disclosed herein, in certain embodiments, are monospecific antibodies or pharmaceutical compositions of the foregoing embodiments for use in the treatment of a blood disorder characterized by excessive bleeding.

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

[0074] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. Generally, nomenclatures utilized in connection with, and techniquesof, immunology, oncology, cell and tissue culture, molecular biology, and protein and oligo- or polynucleotide chemistry and hybridization described herein are those well-known and commonly used in the art. It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0075] As used herein, singular forms “a,” “and,” and “the” include plural referents unless the context clearly indicates otherwise. Thus, e.g., reference to “an antibody” includes a plurality of antibodies and reference to “an antibody” in some embodiments includes multiple antibodies, and so forth.

[0076] As used herein, all numerical values or numerical ranges include whole integers within or encompassing such ranges and fractions of the values or the integers within or encompassing ranges unless the context clearly indicates otherwise. Thus, e.g., reference to a range of 90-100%, includes 91%, 92%, 93%, 94%, 95%, 95%, 97%, etc., as well as 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc., and so forth. In another example, reference to a range of 1-5,000 fold includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 fold, etc., as well as 1.1, 1.2, 1.3, 1.4, 1.5 fold, etc., 2.1, 2.2, 2.3, 2.4, 2.5 fold, etc., and so forth.

[0077] As used herein, the phrase “at least [X]% identity” refers to any percent identity value from (and including) X up to (and including) 100% identity, where X can be any integer from 1-99%. For example, the phrase “at least 80% identity” means any percent 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 embodiments, “at least 80% identity” in reference 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] “About” a number, as used herein, refers to range including the number and ranging from 10% below that number to 10% above that number. “About” a range refers to 10% below the lower limit of the range, spanning to 10% above the upper limit of the range.

[0079] As used herein, the term “accumulation” refers to an increase in a level (e.g., concentration) of a particular protein, such as, e.g., VWF or FVIII, in a blood compartment (e.g., blood plasma) of a subject following administration of an antibody of the disclosure or a composition (e.g., pharmaceutical composition) containing the same to the subject. Variousfactors may influence the rate of accumulation of a protein in a blood compartment of a subject, including but not limited to, the half-life of the target protein and / or the antibody in the blood compartment, the rate of sequestration of the protein by other tissues, clearance of the protein from the body, among others. According to the present disclosure, accumulation of a target protein (e.g., VWF or FVIII) may result in a blood plasma level of the protein that is at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11- fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold greater as compared to a blood plasma level of the protein in the absence of the antibody.Alternatively or additionally, accumulation of the target protein may results in a blood plasma level of the protein that is 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 greater as compared to a blood plasma level of the protein in the absence of the antibody. In some embodiments, accumulation of a protein (e.g., VWF) results directly from specific binding of an antibody of the disclosure to the protein. In some embodiments, accumulation of a protein (e.g., FVIII) results indirectly from binding of the protein (e.g., FVIII) to another protein (e.g., VWF) bound by an antibody of the disclosure.

[0080] As used herein “antibody” refers to a naturally-occurring or non-naturally- occurring protein that binds an antigen. An antibody often comprises a variable domain and a constant domain in each of a heavy chain and a light chain. Accordingly, most antibodies have a heavy chain variable domain (VH) and a light chain variable domain (VL) that together form the portion of the antibody that binds to the antigen, sometimes referred to as the “antigen receptor.” Within each variable domain are three complementarity-determining regions (CDR), which form loops in the VH and VL and contact the surface of the antigen. “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, mutated antibodies, grafted antibodies, antibody fragments, and in vitro-generated antibodies having the antigen-binding activity. The term also includes antibody conjugates having advantageous properties as compared to an unconjugated antibody (e.g., antibodies conjugated to a half-life extending moiety, e.g., a fatty acid)).

[0081] As used herein, “complementarity-determining regions,” “CDRs,” and “hypervariable regions” refer to the parts of the variable domains in antibodies that determinethe antibodies’ binding specificities to their specific antigen. A single variable region of an antibody polypeptide will typically comprise three CDRs, usually designated CDR1, CDR2, and CDR3. More particularly, a heavy chain variable region may contain CDRs designated Hl, H2, and H3; likewise, light chain variable region may contain CDRs LI, L2, and L3. Multiple methods may be used to define a CDR. The current art utilizes various numbering schemes with different definitions of CDR lengths and positions. For example, IMGT numbering scheme is a standardized numbering system based on alignments of sequences from a complete reference gene database including the whole immunoglobulin superfamily. The Kabat numbering scheme is based on sequence alignment and uses "variability parameter" of a given amino acid position (the number of different amino acids at a given position divided by the frequency of the most occurring amino acid at that position) to predict CDRs. The Chothia numbering scheme, on the other hand, is a structure-based numbering scheme where antibody crystal structures are aligned as define the loop structures as CDRs. The Martin numbering scheme focuses on the structure alignment of different framework regions of unconventional lengths. Honneger's numbering scheme (AHo's) is based on structural alignments of the 3D structure of the variable regions and uses structurally conserved Ca positions to deduce framework and CDR lengths. One of skill in the art will note that the definition of a CDR will vary based on the method used. Accordingly, CDR sequences of a given heavy or light chain variable region may vary depending on the numbering system used. Any method of defining a CDR is contemplated with the sequences disclosed herein. Unless stated otherwise, 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,” “antibody fragment” are used interchangeably herein to refer to one or more fragments of an antibody that retain the ability to specifically bind to the antigen. Non-limiting examples of antibody fragments included within such terms include, but are not limited to, e.g., a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CHI domains. Also included are “one-arm” antibodies comprising 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 disorders in a subject (e.g., a human) that confers a susceptibility to bleed to the subject (e.g., bleeding diathesis). Such a disorder is, in some embodiments, due to a condition associated with atypical and slow blood clotting. A “blood disorder characterized by excessive bleeding” may be genetic or acquired in origin. Platelet activation,adhesion, and / or aggregation (e.g., primary hemostasis) is, in some embodiments, impaired in a subject with said disorder. In some embodiments, function or expression of blood proteins that mediate or facilitate the production of insoluble cross-linked fibrin proteins during blood coagulation (e.g., secondary hemostasis) is impaired in a subject with the disorder. Nonlimiting examples of a blood disorder characterized by excessive bleeding include von Willebrand disease (VWD), hemophilia A, disorders of platelet function, and connective tissue disorders. In some embodiments, the VWD is congenital VWD (cVWD) or acquired VWD (aVWD). In some embodiments, the aVWD includes Heydes syndrome. In some embodiments, the 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, e.g., a VWF protein and an antibody described herein. The two or more molecules, in some embodiments, are associated by any physical means, including covalent bonds, ionic bonds, hydrogen bonds, and van der Waal forces. In some embodiments, a physical association between the two or more molecules is reversible. In some embodiments, a physical association between the two or more molecules is irreversible.

[0085] The term “effective amount” as used herein, refers to that amount of an antibody, or an antigen-binding portion thereof as described herein, that is sufficient to induce a disclosed effect, e.g., to effect treatment (e.g., accumulation of a VWF and / or FVin protein in blood plasma), prognosis, or diagnosis of a disease (e.g., a blood disorder characterized by excessive bleeding), as described herein, when administered to a subject. Therapeutically effective amounts of antibodies provided herein, when used alone or in combination, will vary depending upon the relative activity of the disclosed antibodies and combinations (e.g., in treating, reducing, or ameliorating a disease or disorder described herein) and depending upon the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration, and the like, which, in some cases, are readily determined by one of ordinary skill in the art.

[0086] As used herein, the term “monospecific” refers to an antibody that displays a preferential affinity for one particular epitope (e.g., an epitope contained in a CK domain of the VWF protein, such as, e.g., a human, NHP, murine, or canine VWF protein).

[0087] As used herein, the term “monovalent” refers to a property of an antibody or antigen-binding fragment thereof in which the antibody has one antigen-binding site to a target epitope of a particular protein. For example, an monovalent antibody of the disclosure binds to an epitope (e.g., an epitope in a CK domain) of a VWF protein with a single antigen-binding site. Within the context of the present disclosure, a monovalent antibody is, in some embodiments, a one-armed 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 terms “one-armed antibody” or “single-armed antibody” refer to a type of monovalent antibody fragment containing an antibody heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain.

[0089] “Percent identity” and “% identity” refers to the extent to which two sequences (nucleotide or amino acid) have the same residue at the same positions in an alignment. For example, “an amino acid sequence is X% identical to SEQ ID NO: Y” refers to % identity of the amino acid sequence to SEQ ID NO: Y and is elaborated as X% of residues in the amino acid sequence are identical to the residues of sequence disclosed in SEQ ID NO: Y. Generally, computer programs are employed for such calculations. Exemplary programs that compare and align pairs of sequences, include ALIGN (Myers and Miller, Comput Appl Biosci. 1988 Mar; 4(1): 11-7), FASTA (Pearson and Lipman, Proc Natl Acad Sci USA. 1988 Apr; 85(8) 2444-8; Pearson, Methods Enzymol . 1990; 183:63-98), gapped BLAST (Altschul et al., Nucleic Acids Res. 1997 Sep 1; 25(17): 3389-40), BLASTP, BLASTN, or GCG (Devereux et al., Nucleic Acids Res. 1984 Jan 11; 12(1 Pt l):387-95).

[0090] The term “polypeptide” refers to a chain of amino acids (e.g., naturally-occurring or non-naturally-occurring amino acids). In some embodiments, the polypeptide comprises amino acids that are naturally-occurring. In some embodiments, the polypeptide comprises amino acids that are non-naturally-occurring (cystine, desmosine, isodesmosine, hydroxyproline, hydroxylysine, gamma-carboxyglutamate, phosphoserine, phosphothreonine, phosphotyrosine, N-acetyl lysine, methyllysine, inositol, L-homoalanine, L-2-aminobutyric acid, L-azidohomoalanine, beta-phenylalanine, norleucine, 3-fluorotyrosine, 4- fluorophenylalanine, L-3,4-dyhydroxyphenylalanine, pNCSF, L-(7-hydroxycoumarin-4- yl)ethylglycine, 2,3 -dihydroxypropyl cysteine, arylglycine, PrDiAzK, (S)-N-(2- Benzoylphenyl)-l-(2-flurobenzyl)-pyrolidine-2-carboxamide, 4-Phenanthracen-9-yl-l- phenylalanine, BN tryptophan analog, p-acetylphenylalanine, L-azidohomoalanine, among others). The polypeptides are not limited to a specific length of the product (e.g., polypeptides can comprise at least 2 amino acids linked together by way of peptide bonds). Peptides, oligopeptides, and proteins are included within the definition of polypeptide, and such terms are used interchangeably herein unless specifically indicated otherwise. This term also encompasses chains of peptides with post-expression modifications, e.g., glycosylation, acetylation, phosphorylation, and the like, as well as other modifications known in the art,both naturally occurring and non-naturally occurring. In some embodiments, a polypeptide is an entire protein, or a fragment thereof.

[0091] The terms “preferentially binds” or “specifically binds” mean that the antibodies or fragments thereof bind to an epitope with greater affinity than it binds unrelated amino acid sequences, and, if cross-reactive to other polypeptides containing the epitope, are not toxic at the levels at which they are formulated for administration to human use. In some embodiments, such affinity is at least 1.5-fold greater, 2-fold greater, at least 3-fold greater, at least 4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7-fold greater, at least 8-fold greater, at least 9-fold greater, 10-fold greater, at least 20-fold greater, at least 30- fold greater, at least 40-fold greater, at least 50-fold greater, at least 58-fold greater, at least 70-fold greater, at least 80-fold greater, at least 90-fold greater, at least 94-fold greater, or at least 1000-fold greater than the affinity of the antibody or fragment thereof for unrelated amino acid sequences.

[0092] The terms “recipient,” “individual,” “subject,” “host,” and “patient,” are used interchangeably herein and refer to any mammalian subject for whom diagnosis, treatment, or therapy is desired, particularly humans. “Mammal” for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and laboratory, zoo, sports, or pet animals, such as dogs, horses, cats, cows, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, monkeys, etc. In some embodiments, the mammal is a human. None of the terms require the supervision of a medical professional.

[0093] The term “specific” refers to a situation in which an antibody will preferentially bind to molecules other than the antigen containing the epitope recognized by the antibody. The term is also applicable where e.g., an antigen-binding domain is specific for a particular epitope which is carried by a number of antigens, in which case the antibody or antigenbinding fragment thereof carrying the antigen-binding domain will be able to bind to the various antigens carrying the epitope.

[0094] The term “therapeutically effective amount” generally refers to an amount of a disclosed antibody or a drug effective to “treat” a disease or disorder in a subject or mammal. In some embodiments, a composition described herein is administered to a subject in an amount that is effective for producing some desired therapeutic effect by inhibiting a disease or disorder as described herein at a reasonable benefit / risk ratio applicable to any medical treatment. A therapeutically effective amount is an amount that achieves at least partially a desired therapeutic or prophylactic effect in an organ or tissue. The amount of an antibody necessary to bring about prevention and / or therapeutic treatment of a disease or disorder isnot fixed per se. In some embodiments, the amount of the antibody administered varies with the type of disease, extensiveness of the disease, and size of the mammal suffering from the disease or disorder. When used in conjunction with therapeutic methods involving administration of a therapeutic agent after the subject presents symptoms of a disease or disorder, the term “therapeutically effective” means that, after treatment, one or more signs or symptoms of the disease or disorder is ameliorated or eliminated.

[0095] In some embodiments, an effective response of the present disclosure is achieved when the subject experiences partial or total alleviation or reduction of signs or symptoms of illness and, in the case of the treatment of a disease (e.g., a blood disorder characterized by excessive bleeding), specifically includes, without limitation, amelioration of symptoms, prolongation of progression, cure, remission, prolongation of survival, or other objective responses. In some embodiments, the expected progression-free survival times are measured in months to years, depending on prognostic factors including the number of relapses, stage of disease, and other factors. Prolonging survival includes without limitation times of at least 1 month (mo ), about at least 2 mos., about at least 3 mos., about at least 4 mos., about at least 6 mos., about at least 1 year, about at least 2 years, about at least 3 years, etc. Overall survival is also measured, e.g., in months to years. Alternatively, an effective response, in some embodiments, is that a subject’s symptoms remain static. Further indications of treatment of indications are described in more detail below.

[0096] In some embodiments, administration of a therapeutic agent in a prophylactic method occurs prior to the manifestation of symptoms of an undesired disease or disorder, such that the disease or disorder is prevented or, alternatively, delayed in its progression. Thus, when used in conjunction with prophylactic methods, the term “therapeutically effective” means that, after treatment, a smaller number of subjects (on average) develop the undesired disease or disorder or progress in severity of symptoms.

[0097] As used herein, the terms “treatment,” “treating,” and the like, in some cases, refer to administering an agent, or carrying out a procedure, for the purposes of obtaining an effect. The effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and / or is therapeutic in terms of effecting a partial or complete cure for a disease and / or symptoms of the disease. “Treatment,” as used herein, includes treatment of a disease or disorder (e.g., blood disorder characterized by excessive bleeding) in a mammal, particularly in a human, and includes: (a) preventing the disease or a symptom of a disease from occurring in a subject which is predisposed to the disease but has not yet been diagnosed as having it (e.g., including diseases that is associated with or caused by a primarydisease; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression of the disease. The term treating includes to any indicia of success in the treatment or amelioration or prevention of a disease or disorder, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the disease condition more tolerable to the patient; slowing in the rate of degeneration or decline; or making the final point of degeneration less debilitating. The treatment or amelioration of symptoms is based on one or more objective or subjective parameters, including the results of an examination by a physician. Accordingly, the term “treating” includes the administration of the agents of the present disclosure to prevent or delay, to alleviate, or to arrest or inhibit development of the symptoms or conditions associated with diseases. The term “therapeutic effect” refers to the reduction, elimination, or prevention of the disease, symptoms of the disease, or side effects of the disease in the subject. A subject is “treated” for a disease or disorder if, after receiving a therapeutic amount of an antibody of the present disclosure, the patient shows observable and / or measurable change in a parameter or symptom of the disease or disorder.Brief Description of the Drawings

[0098] FIG. 1 shows a flowchart of the protocol used for selection of antibodies that specifically bind to the cysteine knot (CK) domain of human von Willebrand Factor (VWF) protein.

[0099] FIG. 2 shows an overview of the experimental setup used for measurement of the apparent equilibrium dissociation constant (Ka) between monovalent (one-arm; OA) anti- VWF CK domain antibody and CK domain of VWF.

[0100] FIG. 3 shows a bar graph illustrating the distribution of low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (BMW) VWF multimers following overnight incubation of normal human plasma with 600 nM of monovalent (one-arm) antibody and 1.5 mg / mL ristocetin. Two control conditions include plasma without antibody and ristocetin (Untreated) and plasma treated with ristocetin only (Control). Results are shown as mean ± standard deviation across plasma from three healthy human donors.

[0101] FIGS. 4A-4E are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) Libl_Pl_A6 (Lib_Pl_A6 OA) antibody administered subcutaneously at 4 mg / kg on day 1 and 2 to two cynomolgus monkeys (“cynos”; 3FG2 and 4FG2, respectively). Plasma levels of (FIG. 4A) Libl_Pl_A6 OA (Example 20), (FIG. 4B) VWFantigen (VWF:Ag; Example 15), (FIG. 4C) VWF ristocetin cofactor activity (VWF:RCo; Example 18), (FIG. 4D) distribution of low (LMW), intermediate (IMW) and high (HMW) molecular weight VWF multimers, and (FIG. 4E) FVIII antigen (FVIII: Ag).

[0102] FIGS. 5A-5E are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) Libl_Pl_A9 (Lib_Pl_A9 OA) antibody administered subcutaneously at 4 mg / kg on day 1 and 2 to two cynos (1MG1 and 2FG1, respectively). Plasma levels of (FIG. 5A) Libl_Pl_A9 OA, (FIG. 5B) VWF antigen (VWF:Ag), (FIG. 5C) VWF ristocetin cofactor activity (VWF:RCo), (FIG. 5D) distribution of low (LMW), intermediate (IMW) and high (HMW) molecular weight VWF multimers, and (FIG. 5E) FVIII antigen (FVIII :Ag).

[0103] FIGS. 6A and 6B are chromatograms from SEC-HPLC analysis of complexes formed between the human VWF CK domain dimer and monovalent or bivalent anti-VWF CK domain antibodies, 1081_Lib8 (FIG. 6A) and Libl_Pl_A6 (FIG. 6B).

[0104] FIGS. 7A-7D are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) AO6_P1_D11 OA antibody administered subcutaneously at 4 mg / kg on day 0 to two cynomolgus monkeys (“cynos”; 103M and 55F, respectively). Plasma levels of A06 P1 D11 OA (FIG. 7A), VWF antigen (VWF:Ag; FIG. 7B), VWF ristocetin cofactor activity (VWF:RCo; FIG. 7C), and FVIII antigen (FVIILAg; FIG. 7D).

[0105] FIGS. 8A-8D are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) A09_Pl_E07 OA antibody administered subcutaneously at 4 mg / kg on day 0 to two cynomolgus monkeys (“cynos”; 715M and 723F, respectively). Plasma levels of A09_Pl_E07 OA (FIG. 8A), VWF antigen (VWF:Ag; FIG. 8B), VWF ristocetin cofactor activity (VWF:RCo; FIG. 8C), and FVIII antigen (FVIIFAg; FIG. 8D).

[0106] FIGS. 9A-9D are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) AO6_P1_C12 OA antibody administered subcutaneously at 4 mg / kg on day 0 to two cynomolgus monkeys (“cynos”; 716M and 724F, respectively). Plasma levels of AO6_P1_C12 OA (FIG. 9A), VWF antigen (VWF:Ag; FIG. 9B), VWF ristocetin cofactor activity (VWF:RCo; FIG. 9C), and FVIII antigen (FVIILAg; FIG. 9D).

[0107] FIGS. 10A-10D are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) AO6_P1_B12 OA antibody administered subcutaneously at 4 mg / kg on day 0 to two cynomolgus monkeys (“cynos”; 717M and 727F, respectively). Plasma levels of A06 P1 B12 OA (FIG. 10A), VWF antigen (VWF:Ag; FIG. 10B), VWF ristocetin cofactor activity (VWF:RCo; FIG. 10C), and FVIII antigen (FVIII: Ag; FIG. 10D).

[0108] FIGS. 11A-11D are plots showing pharmacokinetics and pharmacodynamics ofmonovalent (one-arm) A06 P1 H01 OA antibody administered subcutaneously at 4 mg / kg on day 0 to two cynomolgus monkeys (“cynos”; 718M and 728F, respectively). Plasma levels of A06 P1 H01 OA (FIG. 11 A), VWF antigen (VWF:Ag; FIG. 11B), VWF ristocetin cofactor activity (VWF:RCo; FIG. 11C), and FVIII antigen (FVIIFAg; FIG. 11D).

[0109] FIGS. 12A-12D are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) AO6_P1_G12 OA antibody administered subcutaneously at 4 mg / kg on day 0 to two cynomolgus monkeys (“cynos”; 719M and 729F, respectively). Plasma levels of AO6_P1_G12 OA (FIG. 12A), VWF antigen (VWF:Ag; FIG. 12B), VWF ristocetin cofactor activity (VWF:RCo; FIG. 12C), and FVIII antigen (FVIII: Ag; FIG. 12D).Detailed Description

[0110] Disclosed herein, in certain embodiments, are antibodies that specifically bind to von Willebrand Factor (VWF). Also disclosed herein are pharmaceutical compositions containing the disclosed antibody and one or more pharmaceutically acceptable carriers, diluents or excipients. The disclosure also provides methods of using the disclosed antibodies or compositions containing the same for the treatment of a blood disorder characterized by excessive bleeding (e.g., von Willebrand disease (VWD), Heydes syndrome, hemophilia A, disorders of platelet function, and connective tissue disorders). A subject with a blood disorder characterized by excessive bleeding is treated in accord with the methods disclosed herein by administering an antibody of the disclosure or a composition containing the same (e.g., a pharmaceutical composition) to the subject by any acceptable route (e.g., subcutaneously).Regulation of Hemostasis[OHl] Blood circulation provides cells and tissues with necessary substances such as nutrients and oxygen and disposes of metabolic waste products from these cells. The blood vasculature establishes a physical barrier that ensures the containment of blood, regulation of its pressure throughout the organism, and tissue-directed delivery of nutrients and waste products. Disruption or damage to this barrier can result in potentially life-threatening blood loss. Blood plasma contains numerous soluble proteins that act in a concerted cascade of enzymatic reactions to produce a blood clot that can readily “plug” the damaged blood vessel and prevent or reduce further blood loss. This plug is stabilized by the proteolytic cleavage of fibrinogen into fibrin, which forms a mesh that ensheathes and reinforces the clot. Formation and degradation of blood clots are part of a process called hemostasis, which is regulated by anumber of soluble and membrane-tethered pro-coagulant and anti-coagulant proteins. A balance between coagulation and fibrinolysis (i.e., degradation of insoluble fibrin proteins) controls the stability of the blood clot.

[0112] There are two central pathways that trigger blood clotting, namely the tissue factor (or extrinsic) pathway and the contact (or intrinsic) pathway. These clotting cascades proceed by sequential activation of zymogens (i.e., inactive protein precursors) by proteolytic cleavage. Each zymogen, when activated, acts as a serine protease that activates downstream zymogens to drive clot formation. Protein cofactors also act in the blood clotting cascade, generally circulating as inactive pro-cofactors in blood plasma until activated by limited proteolysis.

[0113] The extrinsic pathway is initiated when a cell-surface complex of an integral membrane protein, tissue factor (TF), and Factor Vila (TF :VIIa) activates Factor IX (FIX) and Factor X (FX) by limited proteolysis, thereby producing activated FIX (FIXa) and activated FX (FXa). The contact pathway initiates when Factor Xlla (FXII), prekallikrein (PK), and kininogen (HK) assemble on a surface or polymer. Assembly results in reciprocal activation of FXII to FXIIa by kallikrein (KK), and PK to KK by FXIIa. FXIIa then activates Factor XI (FXI) to FXIa, which then enzymatically converts FIX to FIXa. Activated FVIII (FVIIIa) combines with FIXa to form an Xase (FVIIIa:FIXa) complex responsible for the generation of FXa together with the initiating TF:FVIIa complex. Extrinsic and intrinsic pathways ultimately converge on the production of FXa, which leads to the activation of thrombin from prothrombin, thrombin-mediated cleavage of fibrinogen to fibrin, and activation, adhesion, and aggregation of platelets at the site of the clot.

[0114] VWF plays a critical role in platelet adhesion, activation, and aggregation during blood coagulation. Increased local shear stress near sites of vascular injury results in VWF binding to collagen in the sub -endothelial membrane, which in turn induces platelets to attach to tethered VWF by way of surface glycoprotein to initiate formation of the platelet plug. Under normal physiological conditions, the interaction between VWF and platelets occurs strictly in the context of vascular damage, since VWF does not interact with circulating platelets in the absence of injury. The Al and C4 domains of VWF are essential for binding with platelet glycoproteins, such as, e.g., the platelet gplb and gpllbllla receptors, respectively. Because VWF and FVIII circulate as a complex in plasma under physiological conditions, accumulation of VWF at the site of vascular injury may increase the local concentration of FVIII. Similarly, reduced levels of VWF, as occurs, e.g., in VWD, may lead to reduced levels of FVIII.

[0115] Regulation of hemostasis is also critical in preventing excessive blood clotting, which can lead to the formation of thrombi that can dislodge from their site of formation and cause a potentially life-threatening embolism. Endothelial cells of intact blood vessels regulate clotting by way of thrombomodulin, an integral membrane protein, which reduces clotting by converting thrombin to an anti -coagulant form of the enzyme. At the same time, the thrombomodulin-thrombin complex can enzymatically activate the thrombin-activatable fibrinolysis inhibitor (TAFI) protein, a carboxypeptidase enzyme that reduces fibrinolysis by removing C-terminal lysine residues exposed on fibrin that are critical for the conversion of plasminogen to plasmin. TAFI’s ability to attenuate fibrinolysis is highly dependent on its concentration, rate of activation, and blood plasma half-life.

[0116] Another factor important for the control of hemostasis is antithrombin (AT or AT3), a serine protease inhibitor (also known as serpin) that serves to regulate coagulation by inhibiting multiple proteases in the coagulation cascade, including FIXa, FXa, and thrombin. Its ability to inhibit coagulation factors is generally strongly enhanced by binding to heparin. By inhibiting proteins in the coagulation cascade, AT regulates the blood clotting process to prevent excessive clotting and thrombosis. In humans, AT deficiency is associated with an increased risk for thrombotic disease and pulmonary embolism.Anti-von Willebrand Factor Antibodies

[0117] The mature VWF polypeptide is a large (2,050 amino acid residues) blood glycoprotein that functions in hemostasis and platelet adhesion. VWF is generally localized to the blood plasma, vascular endothelium, megakaryocytes, and subendothelial connective tissue, and exists in multimers of various sizes ranging from about 500 to 20,000 kDa. VWF multimer size typically scales with its role in hemostasis, i.e., larger VWF multimers are more effective at promoting clotting. Different domains of VWF are involved different functions. VWF contains the following domains, from N-terminus to C-terminus: D1-D2-D - D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK. The Dl-D2 domains, corresponding to the VWF propeptide, are proteolytically cleaved during processing of VWF into mature VWF. The D’-D3 domain mediates multimerization of VWF dimers and also binds to Factor VIII. The Al domain binds to platelet gplb receptor, heparin, and collagen. The A2 domain is cleaved by AD AMTS 13, resulting in generation of smaller VWF multimers. The A3 domain binds to collagen. The C4 domain binds to platelet to gpIIa / IIIb. The CK domain is important for tail-to-tail homodimerization of VWF monomers. Binding of VWF to other proteins, such as, e.g., FVIII, results in the stabilization of the binding partner and increases its bloodplasma half-life. For example, in the absence of VWF, FVIII has a half-life of about 1-2 hours, but extends to 8-12 hours when bound by VWF. In addition to acting as a carrier of FVIII, VWF promotes clotting by facilitating platelet adhesion, activation, and aggregation. Deficiency or dysfunction of VWF is associated with a tendency to bleed and occurs in a number of blood disorders characterized by excessive bleeding, including, e.g., VWD and Heydes syndrome.

[0118] Provided herein, in certain embodiments, are antibodies that specifically bind to VWF proteins. In some embodiments, the VWF protein is a human VWF protein. In some embodiments, the human VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence of SEQ ID NO: 1.MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCS YLLAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYAS KGLYLETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDD FMTQEGTLTSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLL KSTSVF ARCHPL VDPEPFVALCEKTLCECAGGLECACP ALLEY ARTCAQEGMVLYG WTDHSACSPVCPAGMEYRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEG LCVESTECPCVHSGKRYPPGTSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKS FDNRYFTFSGICQYLLARDCQDHSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLV KLKHGAGVAMDGQDVQLPLLKGDLRIQHTVTASVRLSYGEDLQMDWDGRGRLLV KLSPVYAGKTCGLCGNYNGNQGDDFLTPSGLAEPRVEDFGNAWKLHGDCQDLQKQ HSDPCALNPRMTRF SEEACAVLT SPTFEACHRAVSPLP YLRNCRYD VC SC SDGRECL CGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQCGTPCNLTCRSLSYPDE ECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDG FMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNLRAEGLECTKT CQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGCNTCVCQDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSN PGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVES GRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFGNSWKVS SQCADTRKVPLD S SP ATCHNNIMKQTMVD S SCRILT SD VFQDC NKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCP QSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKIL DELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEP GGLWPPTDAPVSPTTLYVEDISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAF VVDMMERLRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQV ASTSEVLKYTLFQIFSKIDRPEASRITLLLMASQEPQRMSRNFVRYVQGLKKKKVIVIP VGIGPHANLKQIRLIEKQAPENKAFVLSSVDELEQQRDEIVSYLCDLAPEAPPPTLPPD MAQVTVGPGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRM DVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGDILQRVREIRYQGGNRTNTGLALRYL SDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERI GWPNAPILIQDFETLPREAPDL VLQRCC SGEGLQIPTL SPAPDC SQPLDVILLLDGS S SF PASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITTIDVPWNVVPEKAHLLSLVDV MQREGGP S QIGD ALGF A VR YLT SEMHGARPGASK A V VIL VTD V S VD S VD A A AD AA RSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTMVTLGNSFLHKLCS GFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCDRGLRPSCPN SQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDLEV ILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEVN VYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFML RDGT VTTDWKTLVQEWT VQRPGQTCQPILEEQCLVPD S SHCQ VLLLPLF AECHKVL APATFYAICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYN HCEHGCPRHCDGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQ FLEAWVPDHQPCQICTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPE YECVCDPVSCDLPPVPHCERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRL PTLRKTQCCDEYECACNCVNSTVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTI YPVGQFWEEGCDVCTCTDMEDAVMGLRVAQCSQKPCEDSCRSGFTYVLHEGECCG RCLPSACEVVTGSPRGDSQSSWKSVGSQWASPENPCLINECVRVKEEVFIQQRNVSC PQLEVPVCPSGFQLSCKTSACCPSCRCERMEACMLNGTVIGPGKTVMIDVCTTCRCM VQVGVISGFKLECRKTTCNPCPLGYKEENNTGECCGRCLPTACTIQLRGGQIMTLKR DETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHKCLAEGGKIMKIPGTCCDTC EEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSP TRTEPMQ VALHCTNGS VVYHEVLNAMECKC SPRKC SK (SEQ ID NO: 1; UniProt No. P04275-1)

[0119] In some embodiments, the VWF protein is a VWF protein of a non-humanprimate (NHP; e.g.. Macaco fascicularis) . In some embodiments, the NHP VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence of SEQ ID NO: 2.MIPARLAGVLLALALVLPGTLCAEGTRGRSSMARCSLFGSDFINTFDGSMYSFAGYC SYLLAGDCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVIQGDKSVSMPYAS KGLYLETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDD FMTQEGT VT SDP YDF ANS WAL S SGEQWCERASPP S S SCNIS SGEVQKGLWEQCQLLK STSVF ARCHPL VDPEPFVALCEKTSCECAGGLECTCPAFLEYTRTCAQEGMVLYGWT DHSACSPVCPAGMEYKQCVSPCARTCQSLHINEVCQERCVDGCSCPEGQLLDEGLC VESTECPCMHSGKRYPPGASLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFD NRYFTFSGICQYLLARDCQDHSFSIVIETVQCADDPDAVCTRSVTVRLPGLHNSLVKL KHGGGVAMDGQDVQLPLLKGDLRIQHSVTASVRLSYGEDLQMDWDGRGRLLVKL SPVYAGKTCGLCGNYNGNQGDDFLTPSGLAEPRVEDFGNAWKLHADCQDLQKQHS DPCALNPRMTRFSEEACAVLTSPTFEACHRAVSPLPYLRNCRYDVCSCSDGRECLCG ALASYAACAGGVVAWEPGRCELKCPKGQVYLQCGTPCNLTCRALSYPDEECSEACL EGCFCPPGLYMDEMGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDGFMHCTM SGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNPRAEGLECAKTCQNYDL ECMSMGCVSGCLCPPGMVRHENRCVALERCPCLHQGKEYAPGEAVKIDCNTCVCR DRKWNCTDHVCDATCSMIGMAHYLTFDGLKYMFPGECQYVLVQDYCGGNPGTFRI LVGNEGCSHPSVKCKKHVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRYIILL LGKAISWWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFG NSWKVSSQCADTRKVPLDSSPATCHNNLMKQTMVDSSCRILTSDVFQDCNKLVDPE PFLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNL RENGYECEWRYNSCAPACRVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCV SPEDCPVCEAAGRRFASGKKVTLNPSDPEHCQICHCDGVNLTCEACEEPGGLVVPPT D APVSPTTPYVEDISEPPLHDF YC SRLLDL VFLLDGS SRL SEAEFEVLKAF VVDMMER LRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFGKIDRPEASRIALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHA NLKQIRLIEKQSPENKAFVLSGVDELEQQRDEIVSYLCDLAPEAPPPTLPPDMAQVTVGSGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDG IHVTVLQYSYTVAVEYPFSEAQSKGDILQRVREIRYQGGNRTNTGLALQYLSDHSFL VSQGDREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPHANVQELERIGWPNAP ILIQDFETLPREAPDLVLQSCCSGEGLKIPTLSPAPDCSQPLDVILLLDGSSSFPAAYFD EMI<SFAI<AFISI<ANIGPHLTQVSVLQYGSITTIDVPWNVAPEI<AHLLSLVDVMQREG GPSQIGGALGFAVRYLTSEMHGARPGASKAVVILVMDVSVDAVDAAADAARSNRV AVFPIGIGDRYDAAQLRILAGPAGNSNVVKLQRIEDLPTMVTLGNSFLHKLCSGFVRI CMDEDGNERRPGDIWTLPDQCHTVTCQPDGQTLLESHRVNCDRGLRPSCPNSQSPV KVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDLEVILHNG ACSPAARQGCMKSIEVKHAALSVELHSDMEVTVNGRLVSVPYVGGNMEVNVYGAI MHEIRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRDGTV TTDWKTLVQEWTVQRPGQTCQPILEEQCLVPNSSQCQVLLSALFAECHKVLAPATFY AICQQD SCHREQ VCEVIAS YAHLCRTNGVC VDWRTPDFC AMSCPP SLVYNPCERGC PRHCNGNVSSCGDHPSEGCFCPPNKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWV PDHQPCQICTCLSGRKANCTMQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCD PESCDLPPVPHCEGGLQPTLTNPGECRPNFTCACRKEECKRVSLPSCPPHRLPTLRKT QCCDEYECACNCVNSTVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQF WEEGCDVCTCTDMEDAVMGLRVVQCSQKPCEDSCRSGFTYVPREGECCGRCLPSA CEVVTGSPRGDSQSSWKSVGSHWASPENPCLINECVRVKEEVFVQQRNVSCPQLEVP VCPSGFQLSCKTSACCPSCRCEPVEACMLNGTMIGPGKSVMIDACTTCRCIVQVGSIS GFKLECRKTICNPCPLGYKEEKNTGECCGRCLPTVCTIRLRGGQIMTLKRDETLQDG CDTHFCKVNERGEYFWEKRVTGCPPFDEHKCLAEGGKIKKIPGTCCDTCEEPECSDIT ARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTEPMQV PLHCTNGS VVYHEVLNAMQCEC SPRKC SK (SEQ ID NO: 2; UniProtNo. A0A2K5X4G5)

[0120] In some embodiments, the VWF protein is a VWF protein of a canine (e.g., Cams familiaris). In some embodiments, the canine VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence of SEQ ID NO: 3.

[0121] MSPTRLVRVLLALALILPGKLCTKGTVGRSSMARCSLFGGDFINTFDESMYSFAGDCSYLLAGDCQEHSVSLIGGFQNGKRVSLSVYLGEFFDIHLFVNGTMLQGTQ SISMPYASNGLYLEAEAGYYKLSSEAYGFVARIDGNGNFQVLLSDRYFNKTCGLCGN FNIFAEDDFRTQEGTLTSDPYDFANSWALSSGEQRCKRVSPPSSPCNVSSDEVQQVL WEQCQLLKSASVF ARCHPL VDPEPFVALCERTLCTCVQGMECPCAVLLEYARACAQQGIVLYGWTDHSVCRPACPAGMEYKECVSPCTRTCQSLHVKEVCQEQCVDGCSCPE GQLLDEGHCVGSAECSCVHAGQRYPPGASLLQDCHTCICRNSLWICSNEECPGECLV TGQSHFKSFDNRYFTFSGVCHYLLAQDCQDHTFSVVIETVQCADDLDAVCTRSVTV RLPGHHNSLVKLKHGGGVSMDGQDIQIPLLQGDLRIQHTVMASVRLSYGEDLQMDWDGRGRLLVTLSPAYAGKTCGLCGNYNGNRGDDFVTPAGLAEPLVEDFGNAWKLL GACENLQKQHRDPCSLNPRQARFAEEACALLTSSKFEPCHRAVGPQPYVQNCRYDV CSCSDGRDCLCSAVANYAAACARRGVHIAWREPGFCALSCPQGQVYLQCGTPCNM TCRSLSYPEEDCNEVCLEGCFCPPGLYLDERGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDGFMHCTTSGGLGSLLPNPVLSSPRSHRSKRSLSCRPPMVKLVCPADNPR AEGLECAKTCQNYDLQCMSTGCVSGCLCPQGMVRHENRCVALERCPCFHQGQEYA PGETVKIDCNTCVCRDRKWNCTDHVCDATCSAIGMAHYLTFDGLKYLFPGECQYVL VQDYCGSNPGTFRILVGNEGCSYPSVKCKKRVTILVEGGEIELFDGEVNVKKPMKDE THFEVVESGQYVILLLGKALSVVWDHRLSISVTLKRTYQEQVCGLCGNFDGIQNNDF TSSSLQIEEDPVDFGNSWKVNPQCADTKKVPLDSSPAVCHNNIMKQTMVDSSCRILT SDIFQDCNRLVDPEPFLDICIYDTCSCESIGDCTCFCDTIAAYAHVCAQHGKVVAWRT ATFCPQNCEERNLHENGYECEWRYNSCAPACPITCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCIDPEDCPVCEVAGRRLAPGKKIILNPSDPEHCQICHCDGVNFTCQAC REPGSLVVPPTEGPIGSTTSYVEDTPEPPLHDFHCSRLLDLVFLLDGSSKLSEDEFEVLKVFVVGMMEHLHISQKRIRVAVVEYHDGSHAYIELKDRKRPSELRRITSQVKYAGSE VASTSEVLKYTLFQIFGKIDRPEASRIALLLMASQEPSRLARNLVRYVQGLKKKKVIV IPVGIGPHASLKQIHLIEKQAPENKAFVFSGVDELEQRRDEIINYLCDLAPEAPAPTQHPPMAQVTVGSELLGVSSPGPKRNSMVLDVVFVLEGSDKIGEANFNKSREFMEEVIQR MDVGQDRIHVT VLQYS YMVT VEYTF SEAQ SKGEVLQQ VRDIRYRGGNRTNTGLAL QYLSEHSFSVSQGDREQVPNLVYMVTGNPASDEIKRMPGDIQVVPIGVGPHANVQEL EKIGWPNAPILIHDFEMLPREAPDLVLQRCC SGEGLQIPTLSPTPDC SQPLDVVLLLDG SSSIPASYFDEMKSFTKAFISRANIGPRLTQVSVLQYGSITTIDVPWNVAYEKVHLLSL VDLMQQEGGP SQIGD ALSF AVRYVT SEVHGARPGASKAVVILVTD VS VD S VD AAAE AARSNRVTVFPIGIGDRYSEAQLSSLAGPKAGSNMVRLQRIEDLPTVATLGNSFFHKL CSGFDRVCVDEDGNEKRPGDVWTLPDQCHTVTCLPDGQTLLKSHRVNCDRGPRPSCPNGQPPLRVEETCGCRWTCPCVCMGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDL EVILHNGACSPGAKETCMKSIEVKHDGLSVELHSDMQMTVNGRLVSIPYVGGDMEV NVYGTIMYEVRFNHLGHIFTFTPQNNEFQLQLSPRTFASKTYGLCGICDENGANDFIL RDGTVTTDWKALIQEWTVQQLGKTCQPVPEEQCPVSSSSHCQVLLSELFAECHKVL APATFYAMCQPDSCHPKKVCEAIALYAHLCRTKGVCVDWRRANFCAMSCPPSLVY NHCEHGCPRLCEGNTSSCGDQPSEGCFCPPNQVMLEGSCVPEEACTQCISEDGVRHQ FLETWVPAHQPCQICTCLSGRKVNCTLQPCPTARAPTCGPCEVARLRQNAEQCCPEY ECVCDLVSCDLPPVPPCEDGLQMTLTNPGECRPNFTCACRKDECRRESPPSCPPHRTL ALRKTQCCDEYECACNCVNSTVSCPLGYLASAVTNDCGCTTTTCFPDKVCVHRGTI YPVGQFWEEACDVCTCTDLEDSVMGLRVAQCSQKPCEDNCLSGFTYVLHEGECCG RCLP S ACEVVIGSPRGDAQ SHWKNVGSHWASPDNPCLINEC VRVKEEVF VQQRNVSCPQLNVPTCPTGFQLSCKTSECCPTCHCEPLEACLLNGTIIGPGKSLMIDVCTTCRCTV QVGVISGFKLECRKTTCEACPLGYKEEKNQGECCGRCLPIACTIQLRGGQIMTLKRDE TIQDGCDSHFCKVNERGEYIWEKRVTGCPPFDEHKCLAEGGKIMKIPGTCCDTCEEP ECKDIIAKLQRVKVGDCKSEEEVDIHYCEGKCASKAVYSIHMEDVQDQCSCCSPTQT EPMQVPLRCTNGSLIYHEILNAMQCRCSPRKCSK(SEQ ID NO: 3; UniProt ID No. Q28295-1)

[0122] In some embodiments, the VWF protein is a VWF protein of a mouse (e.g., Mus musciihis). In some embodiments, the murine VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence of SEQ ID NO: 4.MNPFRYEICLL VL ALTWPGTLCTEKPRDRP ST ARC SLFGDDFINTFDETMYSF AGGC S YLLAGDCQKRSFSILGNFQDGKRMSLSVYLGEFFDIHLFANGTVMQGDQSISMPYAS QGLYLELEAGYYKLSSETFGFAARIDGNGNFQVLMSDRHFNKTCGLCGDFNIFAEDD FRTQEGTLTSDPYDFANSWALSSEEQRCKRASPPSRNCESSSGDMHQAMWEQCQLL KTASVF ARCHPL VDPESFVALCEKILCTCATGPECACPVLLEYARTCAQEGMVLYG WTDHSACRPACPAGMEYKECVSPCPRTCQSLSINEVCQQQCVDGCSCPEGELLDED RCVQSSDCPCVHAGKRYPPGTSLSQDCNTCICRNSLWICSNEECPGECLVTGQSHFKS FDNRYFTFSGICQYLLARDCEDHTFSIVIETMQCADDPDAVCTRSVSVRLSALHNSLVKLKHGGAVGIDGQDVQLPFLQGDLRIQHTVMASVRLSYAEDLQMDWDGRGRLLVK LSPVYSGKTCGLCGNYNGNKGDDFLTPAGLVEPLVVDFGNAWKLQGDCSDLRRQH SDPCSLNPRLTRFAEEACALLTSSKFEACHHAVSPLPYLQNCRYDVCSCSDSRDCLCN AVANYAAECARKGVHIGWREPGFCALGCPQGQVYLQCGNSCNLTCRSLSLPDEECS EVCLEGCYCPPGLYQDERGDCVPKAQCPCYYDGELFQPADIFSDHHTMCYCEDGFM HCTTSGTLGSLLPDTVLSSPLSHRSKRSLSCRPPMVKLVCPADNPRAQGLECAKTCQ NYDLERMSLGCVSGCLCPPGMVRHENKCVALERCPCFHQGAEYAPGDTVKIGCNTC VCRERKWNCTNHVCDATRSAIGMAHYLTFDGLKYLFPGECQYVLVYDYCGSNPGT FQILVGNEGCSYPSVKCRKRVTILVDGGELELFDGEVNVKRPLRDESHFEVVESGRY VILLLGQALSVVWDHHLSISVVLKHTYQEQVCGLCGNFDGIQNNDSTTSSLQVEEDP VNFGNSWKVS SQC ADTRKL SLDVSP ATCHNNIMKQTMVD S ACRILT SD VFQGCNRL VDPEPYLDICIYDTCSCESIGDCACFCDTIAAYAHVCAQHGQVVAWRTPTLCPQSCEE KNVRENGYECEWRYNSCAPACPVTCQHPEPLACPVQCVEGCHAHCPPGRILDELLQ TCVDPQDCPVCEVAGRRLAPGKKITLSPDDPAHCQNCHCDGVNLTCEACQEPGGLV APPTDAP VS STTP YVEDTPEPPLHNF YC SKLLDLVFLLDGS SML SEAEFEVLKAF VVG MMERLHISQKRIRVAVVEYHDGSRAYLELKARKRPSELRRITSQIKYTGSQVASTSEV LKYTLFQIFGKIDRPEASHITLLLTASQEPPRMARNLVRYVQGLKKKKVIVIPVGIGPH ASLKQIRLIEKQAPENKAFLLSGVDELEQRRDEIVSYLCDLAPEAPAPTQPPQVAHVT VSPGIAGISSPGPKRKSMVLDVVFVLEGSDEVGEANFNKSKEFVEEVIQRMDVSPDA TRIS VLQ YS YTVTMEYAFNGAQ S K EE VLRH VRE IR YQGGNRTNTGQ ALQ YL SEHSF S PSQGDRVEAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPHANMQELERISRPIAPIF IRDFETLPREAPDLVLQTCCSKEGLQLPTLPPLPDCSQPLDVVLLLDGSSSLPESSFDK MKSFAKAFISKANIGPHLTQVSVIQYGSINTIDVPWNVVQEKAHLQSLVDLMQQEGG PSQIGDALAFAVRYVTSQIHGARPGASKAVVIIIMDTSLDPVDTAADAARSNRVAVFP VGVGDRYDEAQLRILAGPGASSNWKLQQVEDLSTMATLGNSFFHKLCSGFSGVCV DEDGNEKRPGDVWTLPDQCHTVTCLANGQTLLQSHRVNCDHGPRPSCANSQSPVRVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVIFQNKEQDLEVLLHNGA CSPGAKQACMKSIEIKHAGVSAELHSNMEMAVDGRLVLAPYVGENMEVSIYGAIMY EVRFTHLGHILTYTPQNNEFQLQLSPKTFASKMHGLCGICDENGANDFTLRDGTVTT DWKRLVQEWTVQQPGYTCQAVPEEQCPVSDSSHCQVLLSASFAECHKVIAPATFHTI CQQDSCHQERVCEVIASYAHLCRTSGVCVDWRTTDFCAMSCPPSLVYNHCERGCPR HCDGNTSFCGDHPSEGCFCPQHQVFLEGSCVPEEACTQCVGEDGVRHQFLETWVPD HQPCQICMCLSGRKINCTAQPCPTARAPTCGPCEVARLKQSTNLCCPEYECVCDLFN CNLPPVPPCEGGLQPTLTNPGECRPTFTCDCRKEECKRVSPPSCPPHRTPTLRKTQCCDEYECACSCVNSTLSCPLGYLASATTNDCGCTTTTCLPDKVCVHRGTVYPVGQFWE EGCDTCTCTDMEDTVVGLRVVQCSQRPCEDSCQPGFSYVLHEGECCGRCLPSACKV VAGSLRGDSHSSWKSVGSRWAVPENPCLVNECVRVEDAVFVQQRNISCPQLAVPTC PTGFQLNCETSECCPSCHCEPVEACLLNGTIIGPGKSVMVDLCTTCRCIVQTDAISRFK LECRKTTCEACPMGYREEKSQGECCGRCLPTACTIQLRGGRIMTLKQDETFQDGCDS HLCRVNERGEYIWEKRVTGCPPFDEHKCLAEGGKIVKIPGTCCDTCEEPDCKDITAK VQYIKVGDCKSQEEVDIHYCQGKCASKAVYSIDIEDVQEQCSCCLPSRTEPMRVPLH CTNGSVVYHEVINAMQCRCSPRNCSK(SEQ ID NO: 4; UniProt ID No. Q8CIZ8-1)Antibody Sequences

[0123] In some embodiments, the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 491, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 492, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acidsequence 100% identical with the amino acid sequence of SEQ ID NO: 490. In some embodiments, the antibody comprises: (a) a CDRH1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 491, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 492, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 490. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 490 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 491, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 492, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 490 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 491, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 492, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 683. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 684. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 683, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 684.

[0124] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises: (a) a CDRH1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 505. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and aCDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 685. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 686. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 685, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 686.

[0125] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 520, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 521, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 519. In some embodiments,the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises: (a) a CDRH1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 520, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 521, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequenceof SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 519 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 520, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 521, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 519 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 520, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 521, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 687. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 688. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 687, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 688.

[0126] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VLhaving an amino acid sequence with at least 80% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises: (a) a CDRH1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 522. In some embodiments, the antibody comprises a VH having an amino acid sequence with atleast 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 522 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 522 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:689. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 731. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 690. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 689 or 731, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:690.

[0127] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQID NO: 529. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 531, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 528. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 530. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 529; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 531, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 528 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 528 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 528 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VHhaving an amino acid sequence with at least 95% identity to SEQ ID NO: 528 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 528 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 530. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 528 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 529. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 530 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 531, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 528 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 529; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 530 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 531, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 691. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 692. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 691, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 692.

[0128] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 551, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 552, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 550. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 551, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 552, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85%identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 550. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 550 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 551, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 552, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 550 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 551, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 552, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 553. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 693. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 694. In some embodiments, the antibodycomprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 693, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 694.

[0129] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDRL3 having an amino acid sequence 100% identical to the aminoacid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 575. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence havingat least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 697. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 698. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 697, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 698.

[0130] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576 and comprising therein a CDR LI having 100% sequenceidentity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 699. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 700. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 699, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 700.

[0131] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 580, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antibody comprises a VL having an amino acidsequence 100% identical with the amino acid sequence of SEQ ID NO: 579. In some embodiments, the antibody comprises: (a) a CDRH1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 580, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 488 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 579. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 579 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 580, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 579 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 580, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 701. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 702. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 701, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 702.

[0132] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 595. In someembodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 595. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 595 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDR L3 having an amino acidsequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 703. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 703, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

[0133] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO:604. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 604. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 604 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80%identity to SEQ ID NO: 16 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 704. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 704, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

[0134] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 612. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 612 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identicalto the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 705. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 705, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

[0135] In some embodiments, the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a VH having an amino acid sequence withat least 80% identity to SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 618. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antibody comprises: (a) a CDRH1 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 618 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ IDNO: 602. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 706. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 706, and a LC comprising an amino acid sequence having at least 8...

Claims

ClaimsWhat is claimed is:

1. A monospecific antibody comprising an antigen-binding site that specifically binds to an epitope of a von Willebrand Factor (VWF) protein positioned at a cysteine knot (CK) domain and a fragment crystallizable (Fc) region, wherein binding of the antibody to the VWF protein in blood plasma results in accumulation of the VWF protein in blood plasma as compared to a blood plasma level of the VWF protein in the absence of the antibody.

2. The monospecific antibody of claim 1, wherein the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a variable light chain (VL) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 522.

3. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 523, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDR L3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 689 or 731, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 690.

5. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein aCDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 577, and a CDR L3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 699, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 700.

7. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505.

8. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 685, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 686.

10. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575.

11. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 524, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 697, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 698.

13. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 490.

14. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 491, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 492, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:683, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 684.

16. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 519.

17. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 520, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 521, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 687, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 688.

19. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 528 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 530.

20. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 529; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence 100% identical to the amino acidsequence of 531, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 691, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 692.

22. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 550.

23. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 551, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 552, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 693, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 694.

25. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 564.

26. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 565, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 566, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 695, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 69628. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 579.

29. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 580, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:701, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 702.

31. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16.

32. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 596, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 597, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDRL3 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 703, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

34. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16.

35. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 605, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acidsequence of 589, and a CDRL3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:704, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

37. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16.

38. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 613, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 614, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDRL3 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:705, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.

40. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

41. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequenceof SEQ ID NO: 619, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 620, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 706, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

43. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 624 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

44. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 625, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 606, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 708, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

46. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 630 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633.

47. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 631, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 632, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 634, and a CDRL3 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 709, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 710.

49. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 635 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 637, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:711, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

51. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 638 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 641.

52. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 639, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 640, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 642, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 643, and a CDRL3 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:712, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 713.

54. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 644 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

55. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 645, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 646, and a CDR H3 having an amino acid sequence 100%identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:714, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.

57. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 649 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651.

58. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 636, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 650, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 652, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 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 to SEQ ID NO: 473, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO:715, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 716.

60. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 494.

61. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 495, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 496, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 497.

62. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 498.

63. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 499, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 500, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

64. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 501.

65. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 502, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 503, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 504.

66. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505.

67. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 506, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.

68. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 508.

69. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQID NO: 509, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 510, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.

70. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 512.

71. acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 512.

72. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 513, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 514, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.

73. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 516.

74. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 517, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 503, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518.

75. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 525.

76. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 526, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.

77. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 532.

78. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 533, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 534, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.

79. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 535.

80. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 536, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 537, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 538.

81. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 539.

82. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 540, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 541, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.

83. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 543.

84. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQID NO: 544, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 545, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.

85. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 546.

86. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 547, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 548, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549.

87. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 554.

88. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 555, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 556, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 557.

89. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 558.

90. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 559, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 560, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

91. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 561.

92. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 562, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 563, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.

93. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 569.

94. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 568; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 570, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 571, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

95. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572.

96. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 568; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 573, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 574, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

97. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 581.

98. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQID NO: 582, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 583, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 584.

99. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 585 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16.

100. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 586, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 587, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

101. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 590 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593.

102. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 591, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 592, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 594, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 599 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

104. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 601, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

105. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 608 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

106. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 609, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

107. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 615 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

108. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the aminoacid sequence of SEQ ID NO: 616, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 617, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

109. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 621 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

110. an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602.

111. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 622, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 623, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

112. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 626 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 627.

113. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 591, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 592, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VLcomprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 628, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 629, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

114. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 647 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

115. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 648, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 653 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

117. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 654, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 655, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 656 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

119. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 657, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 610, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

120. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 658 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

121. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 659, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 660, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 661; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 662 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663.

123. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 600, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 664, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 665 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633.

125. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 666, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 667, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

126. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 668 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602.

127. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 669, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 670, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the aminoacid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

128. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 671 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 674.

129. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 672, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 673, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 643, and a 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 a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 675 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 677.

131. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 676, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 587, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 664, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 678, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

132. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 679 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682.

133. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 680, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 681, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 642, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 603, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

134. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44.

135. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.

136. The monospecific antibody of claim 1, wherein the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 12 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16.

137. The monospecific antibody of claim 1, wherein the antibody comprises a VH comprising therein a CDR Hl having an amino acid sequence 100% identical to the aminoacid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; and a VL comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence 100% identical to the amino acid sequence of 589, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.

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

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

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

141. The monospecific antibody of any one of claims 1-140, 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 a S228P / T366W / F234A / L235A / delta-K447 mutation and the second heavy chain comprises a S228P / T366S / L368A / Y407V / F234A / L235A / delta-K447 mutation.

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

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

148. The monospecific antibody of any one of claims 1-142, wherein the antibody binds to at least one of the following amino acid residues of VWF CK domain: T2728, R2730, L2731, Q2732, Y2733, V2734, K2735, E2744, D2746, K2757, M2759, Y2760, and 12762 of SEQ ID NO: 1.

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

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

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

152. The method of claim 151, wherein the blood disorder is selected from the group consisting of von Willebrand disease (VWD), Hey des syndrome, hemophilia A, disorders of platelet function, 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 epistaxis, cutaneous bleeding, bleeding from minor wounds, oral-cavity bleeding, angiodysplasia, gastrointestinal bleeding, bleeding from tooth extraction, postoperative bleeding, heavy menstrual bleeding,obstetric hemorrhage, hematuria, muscle hematoma, joint bleeding, visceral bleeding, and central nervous system (CNS) bleeding.

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

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

156. A monospecific antibody of any one of claims 1-148 or the pharmaceutical composition of claim 150 for use as a medicament.

157. The monospecific antibody or the pharmaceutical composition of claim 156 for use in the treatment of a blood disorder characterized by excessive bleeding.

158. A monospecific antibody of any one of claims 1-148 or the pharmaceutical composition of claim 150 for use in the treatment of a blood disorder characterized by excessive bleeding.

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

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