WO2025037032A1 - Methods of treating blood disorders with vwf-targeted monospecific antibodies - Google Patents
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/36—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Definitions
- VWF von Willebrand factor
- VWF von Willebrand Factor
- CK cysteine knot
- Fc fragment crystallizable
- 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.
- 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.
- 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.
- 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 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.
- 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:
- 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:
- 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.
- HC first heavy chain
- LC light chain
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 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.
- 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.
- 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.
- 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.
- 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.
- 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, 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 sequence 100% identical to the amino acid sequence of SEQ ID NO: 504.
- 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.
- 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.
- 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.
- 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.
- 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. 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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 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: 525.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
- 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 least 90% identity to SEQ ID NO: 572.
- 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.
- 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.
- 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.
- 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.
- 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 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: 581.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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.
- 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.
- 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.
- 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.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% 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.
- 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.
- 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.
- 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.
- 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, 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.
- 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.
- 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.
- 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.
- 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 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.
- 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:
- 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.
- 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.
- 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.
- 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 antibody comprises 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.
- 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.
- 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.
- 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.
- 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 at least 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.
- 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.
- 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.
- 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 658 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: 658 and a VL having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 602.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 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.
- 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.
- 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.
- 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.
- 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.
- 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:
- CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17
- CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of 643
- CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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:
- 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.
- 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.
- 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.
- 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 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; 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 amino acid sequence of SEQ ID NO: 46.
- 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.
- 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.
- 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.
- 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.
- an antibody disclosed herein is a monovalent antibody.
- the Fc region is a wild-type Fc region.
- the Fc region is a modified Fc region.
- 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/H2
- 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,
- 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,
- the antibody is a human
- 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.
- the first heavy chain comprises a S228P/T366W/delta-K447 mutation and the second heavy chain comprises a S228P/T366S/L368A/Y407V/delta-K447 mutation.
- the first heavy chain and the second heavy chain further comprise a M252Y/S254T/T256E mutation.
- a complex comprising a VWF protein and a monospecific antibody of the foregoing aspects and embodiments.
- the complex comprises a VWF monomer.
- the complex comprises a VWF dimer.
- the complex comprises a VWF multimer.
- 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).
- kDa e.g.,
- compositions comprising a monospecific antibody of the foregoing aspects and embodiments and a pharmaceutically acceptable carrier, diluent, or excipient.
- 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.
- 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.
- VWD von Willebrand disease
- the VWD is congenital VWD (cVWD) or acquired VWD (aVWD).
- the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
- 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.
- 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.
- the blood disorder selected from the group consisting of epistaxis,
- a composition or pharmaceutical composition disclosed herein promotes platelet adhesion, activation, and aggregation in the subject.
- 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.
- 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.
- compositions comprising a monospecific antibody disclosed herein and a pharmaceutically acceptable carrier, diluent, or excipient.
- 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.
- 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.
- the one or more additional therapeutic modalities is one or more therapeutic agents.
- 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).
- DDAVP desmopressin
- TXA tranexamic acid
- thalidomide e.g., thalidomide
- tamoxifen e.g., thalidomide
- thalidomide e.g.
- 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.
- an antibody or composition of the disclosure is administered to a patient for whom 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.
- 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.
- 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.
- 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.
- 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.
- the VWD is cVWD or aVWD.
- the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
- 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.
- 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%.
- 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%.
- “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.
- “About” a number 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.
- a level e.g., concentration
- a particular protein such as, e.g., VWF or FVIII
- Various factors 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.
- accumulation of a target protein 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.
- 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.
- accumulation of a protein results directly from specific binding of an antibody of the disclosure to the protein.
- accumulation of a protein results indirectly from binding of the protein (e.g., FVIII) to another protein (e.g., VWF) bound by an antibody of the disclosure.
- 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.
- VH heavy chain variable domain
- VL light chain variable domain
- CDR complementarity-determining regions
- 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)).
- CDRs complementarity-determining regions
- hypervariable regions refer to the parts of the variable domains in antibodies that determine the 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.
- 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 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 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.
- 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.
- antibody fragment refers 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.
- one-arm antibodies comprising a single heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain.
- 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.
- function or expression of blood proteins that mediate or facilitate the production of insoluble cross-linked fibrin proteins during blood coagulation is impaired in a subject with the disorder.
- a blood disorder characterized by excessive bleeding include von Willebrand disease (VWD), hemophilia A, disorders of platelet function, and connective tissue disorders.
- VWD von Willebrand disease
- hemophilia A disorders of platelet function
- connective tissue disorders include von Willebrand disease (VWD), hemophilia A, disorders of platelet function, and connective tissue disorders.
- the VWD is congenital VWD (cVWD) or acquired VWD (aVWD).
- the aVWD includes Heydes syndrome.
- the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
- 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 are associated by any physical means, including covalent bonds, ionic bonds, hydrogen bonds, and van der Waal forces.
- a physical association between the two or more molecules is reversible.
- a physical association between the two or more molecules is irreversible.
- 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.
- 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).
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- computer programs are employed for such calculations. Exemplary programs that compare and align pairs of sequences, include ALIGN (Myers and Miller, Comput Appl Biosci.
- 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.
- 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
- 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.
- a polypeptide is an entire protein, or a fragment thereof.
- 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.
- 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.
- 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.
- the mammal is a human. None of the terms require the supervision of a medical professional.
- 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.
- terapéuticaally 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.
- 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 is not fixed per se.
- 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.
- therapeutically effective means that, after treatment, one or more signs or symptoms of the disease or disorder is ameliorated or eliminated.
- 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.
- a disease e.g., a blood disorder characterized by excessive bleeding
- 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.
- 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.
- 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.
- 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.
- treatment refers 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 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 primary disease; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression of the disease.
- a disease or disorder e.g., blood disorder characterized by excessive bleeding
- 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.
- 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.
- 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.
- 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.
- CK cysteine knot
- VWF von Willebrand Factor
- 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.
- Ka apparent equilibrium dissociation constant
- 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.
- 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).
- FIG. 4B VWF antigen (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
- FVIII antigen FVIII antigen
- 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).
- 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).
- 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 VWF ristocetin cofactor activity
- FVIILAg FVIILAg
- 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
- FVIIFAg FVIIFAg
- 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
- FVIILAg FIG. 9D
- 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
- FVIII antigen FVIII: Ag; FIG. 10D.
- FIGS. 11A-11D are plots showing pharmacokinetics and pharmacodynamics of monovalent (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
- FVIIFAg FVIIFAg
- 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
- FVIII antigen FVIII antigen
- VWF von Willebrand Factor
- pharmaceutical compositions containing the disclosed antibody and one or more pharmaceutically acceptable carriers, diluents or excipients are also disclosed herein.
- 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).
- an antibody of the disclosure or a composition containing the same e.g., a pharmaceutical composition
- 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.
- hemostasis Formation and degradation of blood clots are part of a process called hemostasis, which is regulated by a number 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.
- zymogens i.e., inactive protein precursors
- proteolytic cleavage 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 thrombin-activatable fibrinolysis inhibitor
- AT antithrombin
- serpin serine protease inhibitor
- 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 blood plasma 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.
- the VWF protein is a human VWF protein.
- the human VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1.
- the human VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1.
- the human VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1.
- the human VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 1.
- the human VWF protein has an amino acid sequence of SEQ ID NO: 1.
- the VWF protein is a VWF protein of a non-human primate (NHP; e.g.. Macaco fascicularis) .
- NHP VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2.
- the NHP VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2.
- the NHP VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2.
- the NHP VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 2.
- the NHP VWF protein has an amino acid sequence of SEQ ID NO: 2.
- the VWF protein is a VWF protein of a canine (e.g., Cams familiaris).
- the canine VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 3.
- the canine VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 3.
- the canine VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 3.
- the canine VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 3.
- the canine VWF protein has an amino acid sequence of SEQ ID NO: 3. [0121] MSPTRLVRVLLALALILPGKLCTKGTVGRSSMARCSLFGGDFINTFDESM
- the VWF protein is a VWF protein of a mouse (e.g., Mus musciihis).
- the murine VWF protein has an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 4.
- the murine VWF protein has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 4.
- the murine VWF protein has an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 4.
- the murine VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 4.
- the murine VWF protein has an amino acid sequence of SEQ ID NO: 4.
- 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.
- 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.
- 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.
- 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 acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 490.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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:
- 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:
- 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: 529.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 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.
- 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.
- 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.
- 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.
- 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.
- 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 amino acid sequence of SEQ ID NO: 527.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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% 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.
- 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.
- 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.
- 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.
- 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.
- 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 acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 579.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 595. 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: 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 SEQ ID 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.
- 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.
- 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.
- 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.
- 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.
- 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% 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at 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.
- 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.
- 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.
- 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.
- 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 ID NO: 602.
- 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.
- 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.
- 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.
- 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 80% identity to SEQ ID NO: 707.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 624. 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: 624. 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: 624. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 624. 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: 624. 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.
- the antibody comprises: (a) 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 624 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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.
- 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.
- 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; 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.
- 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: 708. 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: 708, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.
- the antibody comprises 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.
- 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 630. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 633.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 630. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 630. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633.
- the antibody comprises: (a) 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 (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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 630 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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: 709. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 710. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ
- I l l 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 635. 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: 635. 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: 635. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 635. 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: 635. 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.
- the antibody comprises: (a) 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 635 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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.
- 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.
- 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; 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.
- 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: 711. 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: 711, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 638. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 641.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 638. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 638. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 641.
- the antibody comprises: (a) 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 (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 638 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 641.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 641 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 641 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 712. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 713. 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 644. 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: 644. 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: 644. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 644. 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: 644. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 644 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588.
- 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.
- 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 SEQ ID NO: 588; 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.
- 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: 714. 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: 714, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 649. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 651.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 649. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 649. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 651.
- the antibody comprises: (a) a CDRH1 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 (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 649 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 651.
- the antibody comprises 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, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 715. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 716. 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 494. 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: 494. 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: 494.
- 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: 494. 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: 494.
- 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: 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.
- 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.
- 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 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: 494.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 494 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 494 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 498. 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: 498. 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: 498.
- 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: 498. 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: 498.
- 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: 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.
- 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.
- 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 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: 498.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 498 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 498 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 501. 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: 501. 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: 501.
- 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: 501. 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: 501.
- 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: 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.
- 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.
- 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 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: 501.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 501 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 501 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 508. 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: 508. 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: 508.
- 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: 508. 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: 508.
- 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: 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.
- 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. 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.
- 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 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: 508.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 508 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 508 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 514, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.
- 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: 512. 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: 512. 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: 512.
- 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: 512. 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: 512.
- 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: 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.
- 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.
- 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 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: 512.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 512 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 514, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.
- 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: 512 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 514, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 516. 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: 516. 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: 516.
- 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: 516. 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: 516.
- 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: 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.
- 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.
- 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: 516. 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: 516.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 516 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 516 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 526, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
- 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: 525. 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: 525. 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: 525.
- 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: 525. 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: 525.
- 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: 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.
- 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.
- 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 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: 525.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 525 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 526, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
- 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: 525 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 526, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 532. 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: 532. 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: 532.
- 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: 532. 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: 532.
- 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: 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.
- 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.
- 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 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: 532.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 532 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 532 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 535. 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: 535. 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: 535.
- 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: 535. 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: 535.
- 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: 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.
- 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.
- 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 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: 535.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 535 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 535 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 539. 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: 539. 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: 539.
- 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: 539. 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: 539.
- 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: 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.
- 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.
- 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 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: 539.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 539 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 539 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 545, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
- 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: 543. 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: 543. 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: 543.
- 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: 543. 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: 543.
- 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 545, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
- 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.
- 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 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: 543.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 543 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 545, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
- 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: 543 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 544, a CDRL2 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 546. 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: 546. 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: 546.
- 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: 546. 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: 546.
- 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: 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.
- 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.
- 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 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: 546.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 546 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 546 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 554. 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: 554. 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: 554.
- 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: 554. 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: 554.
- 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: 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.
- 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.
- 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 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: 554.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 554 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 554 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 558. 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: 558. 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: 558.
- 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: 558. 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: 558.
- 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: 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.
- 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.
- 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 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: 558.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 558 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 558 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 561. 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: 561. 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: 561.
- 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: 561. 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: 561.
- 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: 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.
- 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. 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.
- 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 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: 561.
- 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 489.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 561 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 561 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 568.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 569.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 567. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 567. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 569.
- 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: 568; and (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 569.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 569 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 569 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 568.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 572.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 567. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 567. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 572.
- 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: 568; and (b) a CDR LI having 100% sequence identity to an 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.
- 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 least 90% identity to SEQ ID NO: 572.
- 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 with the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 572.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 568; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- 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: 581. 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: 581. 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: 581.
- 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: 581. 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: 581.
- 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: 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.
- 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.
- 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 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: 581.
- 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 581 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 581 and comprising therein a CDR LI having 100% sequence identity to an 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 585. 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: 585. 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: 585. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 585. 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: 585. 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.
- the antibody comprises: (a) 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 585 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises 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 CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588.
- 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.
- 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 CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; 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.
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 590. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 593.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 590. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 590. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 593.
- the antibody comprises: (a) 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 (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 590 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 593.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593 and comprising therein a CDR LI having 100% sequence identity to an 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 599. 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: 599. 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: 599. 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:
- 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: 599. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 599 and 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 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:
- 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:
- 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; 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
- the antibody comprises 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.
- 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:
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 608. 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: 608. 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: 608. 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:
- 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: 608. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 608 and 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 VH having an amino acid sequence with at least 80% 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:
- 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.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% 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; 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.
- 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.
- 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.
- 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 SEQ ID 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.
- 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.
- 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.
- 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.
- 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.
- 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% 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.
- 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.
- 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.
- 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 615. 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: 615. 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: 615. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 615. 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: 615. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 615 and 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 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:
- 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.
- 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, 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: 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 621. 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: 621. 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: 621. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 621. 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: 621. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 621 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588.
- 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.
- 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; 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.
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 626. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 627.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 626. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 626. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 627.
- the antibody comprises: (a) 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 (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 626 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 627.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 627 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 627 and comprising therein a CDR LI having 100% sequence identity to an 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 647. 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: 647. 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: 647. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 647. 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: 647. 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.
- the antibody comprises: (a) 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 647 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611.
- 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.
- 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; 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 653. 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: 653. 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: 653. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 653. 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: 653. 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.
- the antibody comprises: (a) 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 (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.
- 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 antibody comprises 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.
- 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 with the amino acid sequence of SEQ ID NO: 653 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607.
- 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.
- 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; 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 656. 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: 656. 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: 656. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 656. 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: 656. 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.
- the antibody comprises: (a) 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 (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.
- 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 at least 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.
- 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 with the amino acid sequence of SEQ ID NO: 656 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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.
- 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:
- 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; 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
- the antibody comprises 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.
- 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:
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 658. 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: 658. 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: 658. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 658. 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: 658. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 658 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: 658 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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.
- 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:
- 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; 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
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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:
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 662. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 663.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 662. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 662. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 663.
- the antibody comprises: (a) a CDRH1 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 (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 662 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 663.
- the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO:
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663 and comprising therein a CDR LI having 100% sequence identity to an 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,
- the antibody comprises 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.
- 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 665. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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:
- the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 665. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633.
- the antibody comprises: (a) 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 (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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 665 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 668. 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: 668. 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: 668. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 602.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 668. 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: 668. 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.
- the antibody comprises: (a) a CDRH1 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 668 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 602.
- the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 607.
- 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.
- 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; 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.
- the antibody comprises 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.
- 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 643, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 671. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 674.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 671. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 671. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 674.
- the antibody comprises: (a) 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 (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 643, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 671 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 674.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 674 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 643, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 674 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 643, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 675. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 677.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 675. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 675. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 677.
- the antibody comprises: (a) 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 (b) a CDR LI having 100% sequence identity to an 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 675 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 677.
- the antibody comprises 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 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 677 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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 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 (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 677 and comprising therein a CDR LI having 100% sequence identity to an 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.
- the antibody comprises 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.
- the antibody comprises a CDR LI having 100% sequence identity to an 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 679. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 682.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 679. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 679. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 682.
- the antibody comprises: (a) 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 (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 642, 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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 679 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 682.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682 and comprising therein a CDR LI having 100% sequence identity to an 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.
- 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: 43.
- 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 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 44.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 40. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 40. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44.
- 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: 43; 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 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 40 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 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 507, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 and comprising therein a CDR LI having 100% sequence identity to an 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.
- the antibody comprises 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.
- 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.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 12. 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: 12. 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: 12. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 12. 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: 12. 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.
- the antibody comprises: (a) 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 (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.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 12 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises 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.
- 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.
- 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; 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.
- the antibody comprises 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.
- 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 KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 12. 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: 12. 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: 12. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 16.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 12. 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: 12. 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.
- the antibody comprises: (a) 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 (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 KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18
- 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.
- 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.
- the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 12 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises 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.
- 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 KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- 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; 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 CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 453. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. 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: 453, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 23.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 23.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 19 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 454. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 474. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 464. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 454, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 474, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 464.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 30.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 30.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 26 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 37.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and (b) a CDR LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 37.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 33 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 455. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 475. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 465. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 455, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 475, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 465.
- 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: 43.
- 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 GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 44.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 40. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 40. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44.
- 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: 43; 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 GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- 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.
- 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 with the amino acid sequence of SEQ ID NO: 40 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises 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.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 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 GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 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 GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 456. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 476. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 466. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 456, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 476, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 466.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 51.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 51.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 47 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 58.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 58.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 54 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 457. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 477. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 467. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 457, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 477, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 467.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 65.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 65.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 61 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 72.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 72.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 68 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 79.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 79.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 79.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 75 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 79.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 86.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 86.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 86.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 82 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 86.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 93.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 93.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 93.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 89 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 93.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 458. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 478. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 468. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 458, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 478, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 468.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 100.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 100.
- the antibody comprises: (a) a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 100.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 96 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 100.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99.
- the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- the antibody comprises a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106.
- the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109.
- the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 107.
- the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 107.
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Abstract
Provided herein are antibodies, compositions, and methods of use thereof. The disclosed antibodies bind to von Willebrand factor in blood plasma of a subject. Such antibodies are useful for methods of treatment, such methods of treating one or more blood disorders characterized by excessive bleeding.
Description
METHODS OF TREATING BLOOD DISORDERS WITH VWF-TARGETED MONOSPECIFIC ANTIBODIES
Cross-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 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 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 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 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 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 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 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 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 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. 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 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 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 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 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 acid
sequence 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 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 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 SEQ
ID 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 ID
NO: 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 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 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 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: 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 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: 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 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. 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, 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: 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 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: 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 sequence
100% 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 acid
sequence 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 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: 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 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: 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 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 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 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: 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 SEQ
ID 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 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. 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 least
90% 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 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: 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 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. 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 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. 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 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: 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 least
80% 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, 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.
[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 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.
[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 antibody
comprises 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 at
least 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 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: 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 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. 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% 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: 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 some
embodiments, 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 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; 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 amino
acid 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 Fc
region 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 human
IgG4 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 heavy
chain 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 the
subject.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 for
whom 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 techniques
of, 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. Various
factors 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 determine
the 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 is
not 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 primary
disease; (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) VWF
antigen (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 of
monovalent (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 a
number 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 blood
plasma 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 CQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGC
NTCVCQDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSN PGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVES GRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVE
EDPVDFGNSWKVS 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-human
primate (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 LRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLK
YTLFQIFGKIDRPEASRIALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHA NLKQIRLIEKQSPENKAFVLSGVDELEQQRDEIVSYLCDLAPEAPPPTLPPDMAQVTV
GSGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDG 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] MSPTRLVRVLLALALILPGKLCTKGTVGRSSMARCSLFGGDFINTFDESM
YSFAGDCSYLLAGDCQEHSVSLIGGFQNGKRVSLSVYLGEFFDIHLFVNGTMLQGTQ SISMPYASNGLYLEAEAGYYKLSSEAYGFVARIDGNGNFQVLLSDRYFNKTCGLCGN FNIFAEDDFRTQEGTLTSDPYDFANSWALSSGEQRCKRVSPPSSPCNVSSDEVQQVL WEQCQLLKSASVF ARCHPL VDPEPFVALCERTLCTCVQGMECPCAVLLEYARACAQ
QGIVLYGWTDHSVCRPACPAGMEYKECVSPCTRTCQSLHVKEVCQEQCVDGCSCPE GQLLDEGHCVGSAECSCVHAGQRYPPGASLLQDCHTCICRNSLWICSNEECPGECLV TGQSHFKSFDNRYFTFSGVCHYLLAQDCQDHTFSVVIETVQCADDLDAVCTRSVTV RLPGHHNSLVKLKHGGGVSMDGQDIQIPLLQGDLRIQHTVMASVRLSYGEDLQMD
WDGRGRLLVTLSPAYAGKTCGLCGNYNGNRGDDFVTPAGLAEPLVEDFGNAWKLL GACENLQKQHRDPCSLNPRQARFAEEACALLTSSKFEPCHRAVGPQPYVQNCRYDV CSCSDGRDCLCSAVANYAAACARRGVHIAWREPGFCALSCPQGQVYLQCGTPCNM TCRSLSYPEEDCNEVCLEGCFCPPGLYLDERGDCVPKAQCPCYYDGEIFQPEDIFSDH
HTMCYCEDGFMHCTTSGGLGSLLPNPVLSSPRSHRSKRSLSCRPPMVKLVCPADNPR AEGLECAKTCQNYDLQCMSTGCVSGCLCPQGMVRHENRCVALERCPCFHQGQEYA PGETVKIDCNTCVCRDRKWNCTDHVCDATCSAIGMAHYLTFDGLKYLFPGECQYVL VQDYCGSNPGTFRILVGNEGCSYPSVKCKKRVTILVEGGEIELFDGEVNVKKPMKDE THFEVVESGQYVILLLGKALSVVWDHRLSISVTLKRTYQEQVCGLCGNFDGIQNNDF TSSSLQIEEDPVDFGNSWKVNPQCADTKKVPLDSSPAVCHNNIMKQTMVDSSCRILT SDIFQDCNRLVDPEPFLDICIYDTCSCESIGDCTCFCDTIAAYAHVCAQHGKVVAWRT ATFCPQNCEERNLHENGYECEWRYNSCAPACPITCQHPEPLACPVQCVEGCHAHCPP
GKILDELLQTCIDPEDCPVCEVAGRRLAPGKKIILNPSDPEHCQICHCDGVNFTCQAC REPGSLVVPPTEGPIGSTTSYVEDTPEPPLHDFHCSRLLDLVFLLDGSSKLSEDEFEVL
KVFVVGMMEHLHISQKRIRVAVVEYHDGSHAYIELKDRKRPSELRRITSQVKYAGSE VASTSEVLKYTLFQIFGKIDRPEASRIALLLMASQEPSRLARNLVRYVQGLKKKKVIV IPVGIGPHASLKQIHLIEKQAPENKAFVFSGVDELEQRRDEIINYLCDLAPEAPAPTQH
PPMAQVTVGSELLGVSSPGPKRNSMVLDVVFVLEGSDKIGEANFNKSREFMEEVIQR MDVGQDRIHVT VLQYS YMVT VEYTF SEAQ SKGEVLQQ VRDIRYRGGNRTNTGLAL QYLSEHSFSVSQGDREQVPNLVYMVTGNPASDEIKRMPGDIQVVPIGVGPHANVQEL EKIGWPNAPILIHDFEMLPREAPDLVLQRCC SGEGLQIPTLSPTPDC SQPLDVVLLLDG SSSIPASYFDEMKSFTKAFISRANIGPRLTQVSVLQYGSITTIDVPWNVAYEKVHLLSL VDLMQQEGGP SQIGD ALSF AVRYVT SEVHGARPGASKAVVILVTD VS VD S VD AAAE AARSNRVTVFPIGIGDRYSEAQLSSLAGPKAGSNMVRLQRIEDLPTVATLGNSFFHKL CSGFDRVCVDEDGNEKRPGDVWTLPDQCHTVTCLPDGQTLLKSHRVNCDRGPRPSC
PNGQPPLRVEETCGCRWTCPCVCMGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDL EVILHNGACSPGAKETCMKSIEVKHDGLSVELHSDMQMTVNGRLVSIPYVGGDMEV NVYGTIMYEVRFNHLGHIFTFTPQNNEFQLQLSPRTFASKTYGLCGICDENGANDFIL RDGTVTTDWKALIQEWTVQQLGKTCQPVPEEQCPVSSSSHCQVLLSELFAECHKVL APATFYAMCQPDSCHPKKVCEAIALYAHLCRTKGVCVDWRRANFCAMSCPPSLVY NHCEHGCPRLCEGNTSSCGDQPSEGCFCPPNQVMLEGSCVPEEACTQCISEDGVRHQ FLETWVPAHQPCQICTCLSGRKVNCTLQPCPTARAPTCGPCEVARLRQNAEQCCPEY ECVCDLVSCDLPPVPPCEDGLQMTLTNPGECRPNFTCACRKDECRRESPPSCPPHRTL ALRKTQCCDEYECACNCVNSTVSCPLGYLASAVTNDCGCTTTTCFPDKVCVHRGTI YPVGQFWEEACDVCTCTDLEDSVMGLRVAQCSQKPCEDNCLSGFTYVLHEGECCG RCLP S ACEVVIGSPRGDAQ SHWKNVGSHWASPDNPCLINEC VRVKEEVF VQQRNVS
CPQLNVPTCPTGFQLSCKTSECCPTCHCEPLEACLLNGTIIGPGKSLMIDVCTTCRCTV 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 FDNRYFTFSGICQYLLARDCEDHTFSIVIETMQCADDPDAVCTRSVSVRLSALHNSLV
KLKHGGAVGIDGQDVQLPFLQGDLRIQHTVMASVRLSYAEDLQMDWDGRGRLLVK 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 DEDGNEKRPGDVWTLPDQCHTVTCLANGQTLLQSHRVNCDHGPRPSCANSQSPVR
VEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVIFQNKEQDLEVLLHNGA CSPGAKQACMKSIEIKHAGVSAELHSNMEMAVDGRLVLAPYVGENMEVSIYGAIMY EVRFTHLGHILTYTPQNNEFQLQLSPKTFASKMHGLCGICDENGANDFTLRDGTVTT DWKRLVQEWTVQQPGYTCQAVPEEQCPVSDSSHCQVLLSASFAECHKVIAPATFHTI CQQDSCHQERVCEVIASYAHLCRTSGVCVDWRTTDFCAMSCPPSLVYNHCERGCPR HCDGNTSFCGDHPSEGCFCPQHQVFLEGSCVPEEACTQCVGEDGVRHQFLETWVPD HQPCQICMCLSGRKINCTAQPCPTARAPTCGPCEVARLKQSTNLCCPEYECVCDLFN CNLPPVPPCEGGLQPTLTNPGECRPTFTCDCRKEECKRVSPPSCPPHRTPTLRKTQCC
DEYECACSCVNSTLSCPLGYLASATTNDCGCTTTTCLPDKVCVHRGTVYPVGQFWE 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 acid
sequence 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 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: 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 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: 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 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. 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 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: 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 SEQ
ID 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 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 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 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.
[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 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 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 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: 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 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: 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% 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 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 acid
sequence 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 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: 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 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 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 SEQ
ID 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% 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 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 with
at 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 ID
NO: 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 80% identity to SEQ ID NO: 707.
[0136] 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: 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. 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 with at least 80% identity to SEQ ID NO: 624. 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: 624. 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: 624. 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: 624. 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: 624. 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 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 (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: 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 with the amino acid sequence of SEQ ID NO: 624 and 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 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. 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: 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; 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: 708. 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: 708, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.
[0137] 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: 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. 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 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 630. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 630. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633. 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: 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 (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 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 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 with the amino acid sequence of SEQ ID NO: 630 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 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. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 709. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 710. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ
I l l
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.
[0138] 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: 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. 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 with at least 80% identity to SEQ ID NO: 635. 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: 635. 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: 635. 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: 635. 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: 635. 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 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 (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: 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 with the amino acid sequence of SEQ ID NO: 635 and 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 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. 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: 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; 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: 711. 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: 711, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.
[0139] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 638. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 638. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 641. 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: 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 (b) a CDR
LI having 100% sequence identity to an 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 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 with the amino acid sequence of SEQ ID NO: 638 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 641. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 641 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 641 and comprising therein a CDR LI having 100% sequence identity to an 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. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 712. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 713. 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.
[0140] 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: 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. 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 with at least 80% identity to SEQ ID NO: 644. 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: 644. 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: 644. 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: 644. 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: 644. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 644 and 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 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588. 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: 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 SEQ ID NO: 588; 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: 714. 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: 714, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 707.
[0141] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 649. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 649. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 651. 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: 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 (b) a CDR LI having 100% sequence identity to an 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 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 with the amino acid sequence of SEQ ID NO: 649 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 651. In some embodiments, the antibody comprises 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, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651 and comprising therein a CDR LI having 100% sequence identity to an 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) 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, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651 and comprising therein a CDR LI having 100% sequence identity to an 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. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 715. In some embodiments, the antibody comprises a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 716. 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.
[0142] 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: 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 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: 494. 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: 494. 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: 494. 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: 494. 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: 494. 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: 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. 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 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: 494. 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: 494 and comprising therein a CDR LI having 100% sequence identity to an 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 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: 494 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0143] 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: 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 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: 498. 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: 498. 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: 498. 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: 498. 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: 498. 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: 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 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 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: 498. 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: 498 and comprising therein a CDR LI having 100% sequence identity to an 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 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: 498 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0144] 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: 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 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: 501. 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: 501. 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: 501. 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: 501. 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: 501. 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: 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. 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 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: 501. 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: 501 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least
80% identity to SEQ ID NO: 501 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0145] 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: 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 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: 508. 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: 508. 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: 508. 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: 508. 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: 508. 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: 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. 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: 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 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: 508. 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: 508 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 508 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0146] 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: 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 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: 512. 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: 512. 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: 512. 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: 512. 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: 512. 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: 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. 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 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: 512. 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: 512 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 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 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: 512 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 514, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.
[0147] 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: 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 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: 516. 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: 516. 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: 516. 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: 516. 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: 516. 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: 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 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 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: 516. 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: 516. 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: 516 and comprising therein a CDR LI having 100% sequence identity to an 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 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: 516 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0148] 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 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 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: 525. 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: 525. 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: 525. 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: 525. 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: 525. 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: 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. 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 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: 525. 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: 525 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 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 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: 525 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 526, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[0149] 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: 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 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: 532. 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: 532. 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: 532. 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: 532. 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: 532. 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: 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. 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 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: 532. 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: 532 and comprising therein a CDR
LI having 100% sequence identity to an 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 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: 532 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0150] 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: 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 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: 535. 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: 535. 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: 535. 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: 535. 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: 535. 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: 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. 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 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: 535. 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: 535 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 535 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0151] 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: 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. 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: 539. 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: 539. 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: 539. 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: 539. 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: 539. 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: 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. 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 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: 539. 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: 539 and comprising therein a CDR LI having 100% sequence identity to an 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. 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: 539 and comprising therein a CDR LI having 100% sequence
identity to an 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.
[0152] 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 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 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: 543. 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: 543. 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: 543. 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: 543. 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: 543. 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 545, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542. 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 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: 543. 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: 543 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 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 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: 543 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 544, a CDRL2 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.
[0153] 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: 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 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: 546. 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: 546. 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: 546. 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: 546. 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: 546. 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: 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. 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 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: 546. 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: 546 and comprising therein a CDR LI having 100% sequence identity to an 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 SEQ ID NO: 489; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 546 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0154] 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: 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 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: 554. 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: 554. 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: 554. 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: 554. 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: 554. 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: 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. 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 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: 554. 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: 554 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 554 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0155] 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: 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 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: 558. 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: 558. 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: 558. 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: 558. 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: 558. 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: 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 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 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: 558. 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: 558 and comprising therein a CDR LI having 100% sequence identity to an 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 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: 558 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0156] 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: 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 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: 561. 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: 561. 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: 561. 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: 561. 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: 561. 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: 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 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. 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 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: 561. 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 CDRH3 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: 561 and comprising therein a CDR LI having 100% sequence identity to an 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 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: 561 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0157] 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: 568. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 567. In some embodiments, the antibody comprises a VL having an amino acid sequence 100%
identical with the amino acid sequence of SEQ ID NO: 569. 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: 568; and (b) a CDR LI having 100% sequence identity to an 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 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 with the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 569. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 569 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 569 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0158] 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: 568. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 567. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 572. 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: 568; and (b) a CDR LI
having 100% sequence identity to an 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 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 least 90% 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 with the amino acid sequence of SEQ ID NO: 567 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 572. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572 and comprising therein a CDR LI having 100% sequence identity to an 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 568; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0159] 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: 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 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: 581. 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: 581. 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: 581. 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: 581. 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: 581. 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: 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. 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 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: 581. 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: 581 and comprising therein a CDR LI having 100% sequence identity to an 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 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: 581 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0160] 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: 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. 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: 585. 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: 585. 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: 585. 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: 585. 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: 585. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 585 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: 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 CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588. 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: 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 CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; 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.
[0161] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 590. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 590. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 593. 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: 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 (b) a CDR LI having 100% sequence identity to an 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 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 with the amino acid sequence of SEQ ID NO: 590 and a VL having an amino acid sequence
100% identical with the amino acid sequence of SEQ ID NO: 593. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0162] 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: 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. 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 with at least 80% identity to SEQ ID NO: 599. 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: 599. 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: 599. 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:
599. 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: 599. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 599 and 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 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 CDRH3 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: 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: 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; 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.
[0163] 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: 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. 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 with at least 80% identity to SEQ ID NO: 608. 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: 608. 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: 608. 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:
608. 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: 608. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 608 and 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 VH having an amino acid sequence with at least 80% 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. 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: 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; 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.
[0164] 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 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. 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: 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% 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 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. [0165] 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: 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. 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 with at least 80% identity to SEQ ID NO: 615. 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: 615. 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: 615. 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:
615. 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: 615. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 615 and 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 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, 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: 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: 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, 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: 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.
[0166] 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: 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. 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 with at least 80% identity to SEQ ID NO: 621. 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: 621. 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: 621. 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: 621. 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: 621. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 621 and 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 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588. 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: 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; 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.
[0167] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 626. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 626. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 627. 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: 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 (b) a CDR LI having 100% sequence identity to an 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 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 with the amino acid sequence of SEQ ID NO: 626 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 627. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 627 and comprising therein a CDR LI having 100% sequence identity to an 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 627 and comprising therein a CDR LI having 100% sequence
identity to an 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.
[0168] 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: 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. 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 with at least 80% identity to SEQ ID NO: 647. 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: 647. 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: 647. 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: 647. 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: 647. 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 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 (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: 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 with the amino acid sequence of SEQ ID NO: 647 and 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 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 611. 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: 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; 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.
[0169] 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: 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. 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 with at least 80% identity to SEQ ID NO: 653. 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: 653. 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: 653. 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: 653. 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: 653. 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 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 (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: 653 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: 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 with the amino acid sequence of SEQ ID NO: 653 and 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 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 CDRH3 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: 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; 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.
[0170] 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: 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. 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 with at least 80% identity to SEQ ID NO: 656. 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: 656. 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: 656. 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: 656. 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: 656. 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 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 (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: 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 at least 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 with the amino acid sequence of SEQ ID NO: 656 and 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 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. 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: 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; 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.
[0171] 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: 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. 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 with
at least 80% identity to SEQ ID NO: 658. 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: 658. 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: 658. 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: 658. 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: 658. 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: 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 (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: 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 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: 658 and 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 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. 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: 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; 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.
[0172] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 662. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 662. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 663. 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: 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 (b) a CDR LI having 100% sequence identity to an 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. 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 with the amino acid sequence of SEQ ID NO: 662 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 663. In some embodiments, the antibody comprises 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 CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663 and comprising therein a CDR LI having 100% sequence identity to an 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. 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0173] 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: 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. 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 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 665. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 665. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633. 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: 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 (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 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 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 with the amino acid sequence of SEQ ID NO: 665 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 633. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 633 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 634, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0174] 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: 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. 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 with at least 80% identity to SEQ ID NO: 668. 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: 668. 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: 668. 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: 668. 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: 668. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 668 and 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 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 CDRH3 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: 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; 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.
[0175] 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: 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. 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 643, 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: 671. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 671. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 674. 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: 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 (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 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 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 with the amino acid sequence of SEQ ID NO: 671 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 674. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 674 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 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: 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 674 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 643, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0176] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 675. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 675. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 677. 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: 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 (b) a CDR LI having 100% sequence identity to an 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 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 with the amino acid sequence of SEQ ID NO: 675 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 677. In some embodiments, the antibody comprises 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 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 677 and comprising therein a CDR LI having 100% sequence identity to an 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 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 (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 677 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0177] 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: 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. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an 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. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 679. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 679. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 682. 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: 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 (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 642, 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. 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 with the amino acid sequence of SEQ ID NO: 679 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 682. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682 and comprising therein a CDR LI having 100% sequence identity to an 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. 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0178] 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: 43. 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 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 VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 40. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44. 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: 43; 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 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 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 with the amino acid sequence of SEQ ID NO: 40 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 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 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 and comprising therein a CDR LI having 100% sequence identity to an 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.
[0179] 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: 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. 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: 12. 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: 12. 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: 12. 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: 12. 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: 12. 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: 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 (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: 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 with the amino acid sequence of SEQ ID NO: 12 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: 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. 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: 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; 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.
[0180] 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: 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. 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 KAS, 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: 12. 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: 12. 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: 12. 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: 12. 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: 12. 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: 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 (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 KAS, 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: 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 with the amino acid sequence of SEQ ID NO: 12 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: 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. 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 KAS, 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; 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 CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, 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: 453. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473. 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: 453, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 473, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 463.
[0181] 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: 20, 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: 22. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ
ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 23. 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: 20, 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: 22; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 19 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 19 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 23. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 454. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 474. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 464. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 454, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 474, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 464.
[0182] 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: 27, 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: 29. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32. In some
embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 26. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 30. 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: 27, 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: 29; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 26 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 26 and a VL having an amino acid sequence 100% identical with
the amino acid sequence of SEQ ID NO: 30. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
[0183] 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: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid
sequence with at least 85% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 33. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 37. 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: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and (b) a CDR LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 33 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 33 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 37. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical
to the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 455. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 475. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 465. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 455, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 475, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 465.
[0184] 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: 43. 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 GSS, 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: 40. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises 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 with the amino acid sequence of SEQ ID NO: 40. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44. 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: 43; 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 GSS, 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: 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 with the amino acid sequence of SEQ ID NO: 40 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44. In some embodiments, the antibody comprises 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. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 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 GSS, 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; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 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 GSS, 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: 456. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 476. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 466. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 456, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 476, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 466.
[0185] 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: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid
sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 47. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 51. 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: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 47 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 51. In some embodiments, the
antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 47 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 51. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
[0186] 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: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58. In some embodiments, the
antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 54. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 58. 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: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 54 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 54 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 58. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino
acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 457. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 477. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 467. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 457, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 477, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 467. [0187] 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: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67. In some
embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 61. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 65. 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: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 61 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 61 and a VL having an amino acid sequence 100% identical with
the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
[0188] 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: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid
sequence with at least 85% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 72. 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: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 68 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 68 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid
sequence 100% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
[0189] 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: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 75. In some
embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 79. 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: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 75 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 75 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 79. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid
sequence 100% identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
[0190] 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: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 86. 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: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 82 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 82 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 86. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a
CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
[0191] 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: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 89. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 93. 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: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2
having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 89 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 89 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 93. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100%
identical to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 458. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 478. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 468. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 458, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 478, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 468.
[0192] 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: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99 In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 100. 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: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 96 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 96 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 100. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ
ID NO: 99; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
[0193] 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: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 103. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 107. 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: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid
sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 103 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 103 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 103 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 103 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 103 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 107. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 103 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 107 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 103 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 107 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
109.
[0194] 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: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 110. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 110. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 110. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 110. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 114. 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: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 110 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 114. In some
embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 110 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 110 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 110 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 110 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 110 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 114 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 110 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 114 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 459. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 479. In some embodiments, the antibody comprises a LC, comprising
an amino acid sequence having at least 80% identity to SEQ ID NO: 469. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 459, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 479, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 469.
[0195] 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: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 117. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 117. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 117. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 117. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 117. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 121. 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: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid
sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 117 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 117 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 117 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 117 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 117 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 121. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 117 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 121 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 117 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 121 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
123.
[0196] 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: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 124. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 124. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 124. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 124. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 128. 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: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 124 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 128. In some
embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 124 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 124 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 124 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 124 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 128. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 124 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 128 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 124 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 128 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130.
[0197] 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: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and
a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 131. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 131. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 131. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 131. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 131. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 135. 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: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 131 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 131 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 131 and a VL having an
amino acid sequence with at least 90% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 131 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 131 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 131 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 135 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 131 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 135 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137.
[0198] 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: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an
amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 138. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 138. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 138. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 138. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 138. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 142. 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: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 138 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 138 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 138 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 138 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid
sequence 100% identical with the amino acid sequence of SEQ ID NO: 138 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 142. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 138 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 142 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 138 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 142 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144.
[0199] 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: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 145. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 149. In some
embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 145. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 145. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 145. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 145. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 149. 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: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 145 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 145 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 145 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 145 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 145 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 149. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 145 and comprising therein a CDR Hl having an amino
acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 149 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 145 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 149 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151.
[0200] 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: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 152. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 152. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to
SEQ ID NO: 152. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 152. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 152. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 156. 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: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 152 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 152 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 152 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 152 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 152 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 156. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 152 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155. In some embodiments, the antibody comprises a VL having an
amino acid sequence with at least 80% identity to SEQ ID NO: 156 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 152 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 156 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
158.
[0201] 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: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 159. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 159. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 159. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
159. In some embodiments, the antibody comprises a VL having an amino acid sequence
with at least 95% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 159. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 163. 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: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 159 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 159 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 159 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 159 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 159 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 163. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 159 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 163 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of
SEQ ID NO: 165. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 159 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 163 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
165.
[0202] 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: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 166. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 166. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 166. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
166. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 166. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 170. 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: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 166 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 166 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 166 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 166 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 166 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 166 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 170 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 166 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid
sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 170 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
172.
[0203] 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: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 173. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 173. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 173. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
173. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 173. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 177. 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: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
176; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 173 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 173 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 173 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 173 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 173 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 177. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 173 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 177 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 173 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 177 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an
amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179.
[0204] 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: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 180. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 180. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 180. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 180. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 180. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 184. 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: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186. In some embodiments, the antibody comprises a VH
having an amino acid sequence with at least 80% identity to SEQ ID NO: 180 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 180 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 180 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 180 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 180 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 184. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 180 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 184 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 180 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 184 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186.
[0205] 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: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 187. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 187. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 187. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 187. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 187. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 191. 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: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 187 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 187 and a VL having an amino acid sequence with at least 85%
identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 187 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 187 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 187 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 191. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 187 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 191 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 187 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 191 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193.
[0206] 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: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197. In some embodiments, the antibody comprises a CDR LI having 100%
sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 194. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 194. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 194. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 194. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 198. 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: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 194 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 194 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 194 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to
SEQ ID NO: 194 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 194 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 198. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 194 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 198 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 194 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 198 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200.
[0207] 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: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207. In some embodiments, the antibody comprises a VH having an amino acid sequence with at
least 80% identity to SEQ ID NO: 201. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 201. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 201. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 201. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 201. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 205. 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: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 201 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 201 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 201 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 201 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 205. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 201 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 205. In
some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 201 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 205 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 201 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 205 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207.
[0208] 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: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 208. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 208. In some embodiments, the antibody comprises a VL having an
amino acid sequence with at least 85% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 208. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 208. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 208. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 212. 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: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 208 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 208 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 208 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 208 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 208 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 212. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 208 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 212 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 208 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 212 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214.
[0209] 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: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 215. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 215. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 215. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 219. In some embodiments, the antibody
comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 215. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 215. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 219. 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: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 215 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 215 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 215 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 215 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 215 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 219. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 215 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 219 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a
CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 215 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 219 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
221.
[0210] 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: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 222. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 222. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 222. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
222. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ
ID NO: 222. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 226. 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: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 222 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 222 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 222 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 222 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 222 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 226. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 222 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 226 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 222 and comprising therein a CDR
Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 226 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
228.
[0211] 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: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 229. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 229. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 229. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
229. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 229. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 233. 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: 230, a CDR H2 having an amino acid
sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 229 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 229 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 229 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 229 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 229 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 233. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 229 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 233 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 229 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; and (b) a VL having an amino acid sequence
with at least 80% identity to SEQ ID NO: 233 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
235.
[0212] 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: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 236. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 236. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 236. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
236. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 236. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 240. In some embodiments, the antibody comprises: (a) a complementarity determining SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100%
identical to the amino acid sequence of SEQ ID NO: 242. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 236 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 236 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 236 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 236 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 236 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 240. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 236 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 240 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 236 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 240 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242.
[0213] 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: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 243. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 243. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 243. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 243. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 243. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 247. 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: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 243 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85%
identity to SEQ ID NO: 243 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 243 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 243 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 243 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 247. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 243 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 247 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 243 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 247 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 460. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 480. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 470. In some
embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 460, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 480, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 470.
[0214] 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: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 255, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 256. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 250. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 250. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 250. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 250. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 250. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 254. 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: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 255, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the
amino acid sequence of SEQ ID NO: 256. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 250 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 250 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 250 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 250 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 250 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 254. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 250 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 254 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 255, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 256. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 250 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 254 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 255, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 256.
[0215] 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: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 262, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 263. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 257. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 257. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 257. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 257. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 257. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 261. 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: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 262, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 263. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 257 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85%
identity to SEQ ID NO: 257 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 257 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 257 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 257 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 261. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 257 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 261 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 262, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 263. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 257 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 261 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 262, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 263.
[0216] 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: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ
ID NO: 267. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 269, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAV, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 270. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 264. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 264. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 264. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 264. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 264. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 268. 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: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 267; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 269, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAV, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 270. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 264 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 264 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 264 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 268. In some embodiments,
the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 264 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 264 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 268. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 264 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 267. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 268 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 269, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAV, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 270. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 264 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 267; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 268 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 269, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAV, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 270.
[0217] 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: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 276, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 277. In
some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 271. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 271. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 271. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 271. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 271. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 275 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: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 276, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 277. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 271 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 271 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 271 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 271 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 271 and a VL having
an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 275. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 271 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 275 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 276, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 277. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 271 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 275 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 276, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 277.
[0218] 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: 279, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 283, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 284. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 278. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85%
identity to SEQ ID NO: 278. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 278. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 278. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 278. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 282. 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: 279, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 283, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 284. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 278 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 278 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 278 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 278 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 278 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 282. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 278 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 279, a CDR H2
having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 282 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 283, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 284. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 278 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 279, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 282 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 283, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 284.
[0219] 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: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 290, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 291. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 285. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 285. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 285. In some embodiments, the antibody comprises a VL having an amino acid
sequence with at least 90% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 285. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 285. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 289. 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: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 290, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 291. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 285 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 285 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 285 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 285 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 285 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 289. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 285 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 289 and comprising therein a
CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 290, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 291. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 285 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 289 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 290, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
291.
[0220] 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: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 297, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 298. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 292. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 292. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 292. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
292. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises
a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 292. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 296. 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: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 297, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 298. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 292 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 292 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 292 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 292 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 292 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 296. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 292 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 296 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 297, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 298. In some embodiments, the antibody comprises: (a) a VH having an amino
acid sequence with at least 80% identity to SEQ ID NO: 292 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 296 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 297, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
298.
[0221] 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: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 302. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 304, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 305. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 299. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 299. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 299. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
299. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 299. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 303. 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: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 302; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 304, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 305. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 299 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 299 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 299 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 299 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 299 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 303. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 299 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 302. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 303 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 304, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 305. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 299 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical
to the amino acid sequence of SEQ ID NO: 302; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 303 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 304, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
305.
[0222] 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: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 311, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 312. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 306. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 306. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 306. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
306. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 306. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 310. 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: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID
NO: 311, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 312. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 306 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 306 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 306 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 306 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 306 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 310. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 306 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 310 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 311, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 312. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 306 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 310 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 311, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3
having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
312. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 461. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 481. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 471. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 461, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 481, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 471.
[0223] 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: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 316. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 318, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 319. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 313. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 313. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 313. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
313. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 313. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 317. 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: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 316; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 318, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 319. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 313 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 313 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 313 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 313 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 313 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 317. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 313 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 316. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 317 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 318, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 319. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 313 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical
T15
to the amino acid sequence of SEQ ID NO: 316; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 317 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 318, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
319.
[0224] 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: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 323. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 325, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of STS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 326. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 320. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 320. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 320. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
320. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 320. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 324. 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: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 323; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID
NO: 325, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of STS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 326. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 320 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 320 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 320 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 320 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 320 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 324. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 320 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 323. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 324 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 325, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of STS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 326. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 320 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 323; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 324 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 325, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of STS, and a CDR L3
having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 326.
[0225] 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: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 332, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 333. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 327. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 327. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 327. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 327. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 327. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 331. 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: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 332, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 333. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 327 and a VL
having an amino acid sequence with at least 80% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 327 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 327 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 327 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 327 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 331. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 327 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 331 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 332, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 333. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 327 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 331 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 332, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 333.
[0226] 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: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and
a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 337. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 339, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 340. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 334. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 334. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 334. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 334. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 334. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 338. 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: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 337; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 339, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 340. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 334 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 334 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 334 and a VL having an
amino acid sequence with at least 90% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 334 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 334 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 338. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 334 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 337. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 338 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 339, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 340. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 334 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 337; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 338 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 339, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 340.
[0227] 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: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 346, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an
amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 347. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 341. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 341. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 341. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 341. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 341. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 345. 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: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 346, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 347. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 341 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 341 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 341 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 341 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid
sequence 100% identical with the amino acid sequence of SEQ ID NO: 341 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 345. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 341 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 345 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 346, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 347. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 341 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 345 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 346, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 347.
[0228] 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: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 353, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 354. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 348. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 352. In some
embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 348. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 348. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 348. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 348. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 352. 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: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 353, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 354. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 348 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 348 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 348 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 348 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 348 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 352. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 348 and comprising therein a CDR Hl having an amino
acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 352 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 353, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 354. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 348 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 352 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 353, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 354.
[0229] 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: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 360, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 361. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 355. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 355. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to
SEQ ID NO: 355. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 355. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 355. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 359. 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: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 360, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 361. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 355 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 355 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 355 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 355 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 355 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 359. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 355 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358. In some embodiments, the antibody comprises a VL having an
amino acid sequence with at least 80% identity to SEQ ID NO: 359 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 360, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 361. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 355 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 359 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 360, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
361.
[0230] 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: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 365. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 367, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 368. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 362. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 362. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 362. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
362. In some embodiments, the antibody comprises a VL having an amino acid sequence
with at least 95% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 362. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 366. 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: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 365; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 367, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 368. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 362 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 362 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 362 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 362 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 362 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 366. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 362 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 365. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 366 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 367, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of
SEQ ID NO: 368. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 362 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 365; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 366 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 367, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
368.
[0231] 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: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 374, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 369. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 369. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 369. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
369. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 369. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 373. 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: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 374, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 369 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 369 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 369 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 369 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 369 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 373. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 369 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 373 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 374, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 369 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid
sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 373 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 374, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
375.
[0232] 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: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 379. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 381, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ETS, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 382. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 376. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 376. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 376. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
376. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 376. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 380. 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: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
379; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 381, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ETS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 382. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 376 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 376 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 376 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 376 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 376 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 380. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 376 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 379. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 380 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 381, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ETS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 382. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 376 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 379; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 380 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 381, a CDR L2 having an
amino acid sequence 100% identical to the amino acid sequence of ETS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 382.
[0233] 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: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 388, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 389. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 383. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 383. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 383. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 383. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 383. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 387. 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: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 388, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 389. In some embodiments, the antibody comprises a VH
having an amino acid sequence with at least 80% identity to SEQ ID NO: 383 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 383 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 383 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 383 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 383 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 387. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 383 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 387 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 388, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 389. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 383 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 387 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 388, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 389.
[0234] 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: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 393. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 395, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 390. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 390. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 390. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 390. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 390. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 394. 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: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 393; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 395, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 390 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 390 and a VL having an amino acid sequence with at least 85%
identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 390 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 390 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 390 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 394. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 390 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 393. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 394 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 395, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 390 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 393; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 394 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 395, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 462. In some embodiments, the antibody comprises a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 482. In some embodiments, the antibody comprises a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 472. In some embodiments, the antibody comprises a first HC comprising an amino acid sequence having
at least 80% identity to SEQ ID NO: 462, a second HC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 482, and a LC, comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 472.
[0235] 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: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 402, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 403. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 397. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 397. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 397. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 397. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 397. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 401. 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: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 402, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 403. In some embodiments, the antibody comprises a VH
having an amino acid sequence with at least 80% identity to SEQ ID NO: 397 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 397 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 397 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 397 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 397 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 401. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 397 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 401 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 402, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 403. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 397 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 401 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 402, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 403.
[0236] 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: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 407. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 409, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 410. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 404. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 404. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 404. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 404. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 404. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 408. 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: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 407; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 409, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 410. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 404 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 404 and a VL having an amino acid sequence with at least 85%
identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 404 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 404 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 404 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 408. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 404 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 407. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 408 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 409, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 410. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 404 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 407; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 408 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 409, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 410.
[0237] 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: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414. In some embodiments, the antibody comprises a CDR LI having 100%
sequence identity to an amino acid sequence of SEQ ID NO: 416, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 417. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 411. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 411. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 411. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 411. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 411. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 415. 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: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 416, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 417. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 411 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 411 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 411 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to
SEQ ID NO: 411 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 411 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 415. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 411 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 415 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 416, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 417. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 411 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 415 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 416, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 417.
[0238] 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: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 421. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 423, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 424. In some embodiments, the antibody comprises a VH having an amino acid sequence with at
least 80% identity to SEQ ID NO: 418. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 418. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 418. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 418. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 418. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 422. 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: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 421; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 423, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 424. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 418 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 418 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 418 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 418 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 422. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 418 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 422. In
some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 418 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 421. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 422 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 423, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 424. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 418 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 421; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 422 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 423, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 424.
[0239] 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: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 430, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 431. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 425. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 425. In some embodiments, the antibody comprises a VL having an
amino acid sequence with at least 85% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 425. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 425. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 425. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 429. 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: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 430, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 431. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 425 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 425 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 425 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 425 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 425 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 429. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 425 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 429 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 430, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 431. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 425 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 429 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 430, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 431.
[0240] 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: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 437, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 438. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 432. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 432. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 432. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 436. In some embodiments, the antibody
comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 432. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 432. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 436. 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: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 437, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 438. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 432 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 432 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 432 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 432 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 432 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 436. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 432 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 436 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 437, a
CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 438. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 432 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 436 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 437, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
438.
[0241] 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: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 444, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 445. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 439. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 439. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 439. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO:
439. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ
ID NO: 439. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 443. 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: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 444, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 445. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 439 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 439 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 439 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 439 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 439 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 443. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 439 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 443 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 444, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 445. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 439 and comprising therein a CDR
Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDRH3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 443 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 444, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 445.
[0242] 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: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449. In some embodiments, the antibody comprises a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 451, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DNF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 452. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 446. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 446. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 446. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 446. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 446. In some embodiments, the antibody comprises a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 450. 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: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3
having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449; and (b) a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 451, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DNF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 452. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 446 and a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 85% identity to SEQ ID NO: 446 and a VL having an amino acid sequence with at least 85% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 90% identity to SEQ ID NO: 446 and a VL having an amino acid sequence with at least 90% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 446 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 446 and a VL having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 450. In some embodiments, the antibody comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 446 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449. In some embodiments, the antibody comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 450 and comprising therein a CDR LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 451, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DNF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 452. In some embodiments, the antibody comprises: (a) a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 446 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449; and (b) a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 450 and comprising therein a CDR LI having
100% sequence identity to an amino acid sequence of SEQ ID NO: 451, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DNF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 452.
[0243] In some embodiments, an antibody disclosed herein comprises a heavy chain (HC) region having an amino acid sequence with at least 80% identity to SEQ ID NO: 473 and a light chain (LC) region having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15.
[0244] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 683 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0245] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 685 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15.
[0246] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 687 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0247] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 689 or 731 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15.
[0248] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 691 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0249] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 693 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15.
[0250] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 695 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0251] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 697 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15.
[0252] In some embodiments, an antibody disclosed herein comprises a HC having an
amino acid sequence with at least 80% identity to SEQ ID NO: 699 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0253] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 701 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0254] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 703 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0255] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 704 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0256] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 705 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0257] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 706 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0258] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 708 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0259] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 709 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0260] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 711 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0261] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 712 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0262] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 714 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15 [0263] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 715 and a LC having at least
80% sequence identity to any one of the LC (“VL _LC”) regions listed in Table 4 or Table 15. [0264] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 453 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0265] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 454 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0266] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 455 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0267] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 456 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0268] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 457 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0269] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 458 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0270] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 459 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0271] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 460 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0272] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 461 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0273] In some embodiments, an antibody disclosed herein comprises a HC having an amino acid sequence with at least 80% identity to SEQ ID NO: 462 and a LC having at least 80% sequence identity to any one of the LC (“VL_LC”) regions listed in Table 4 or Table 15. [0274] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 684 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table
15.
[0275] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 686 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0276] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 688 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0277] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 690 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0278] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 692 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0279] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 694 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0280] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 696 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0281] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 698 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0282] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 700 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0283] In some embodiments, an antibody disclosed herein comprises a LC having an
amino acid sequence with at least 80% identity to SEQ ID NO: 702 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0284] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 463 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0285] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 707 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0286] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 710 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0287] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 713 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0288] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 716 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0289] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 463 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0290] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 464 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0291] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 465 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table
15.
[0292] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 466 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0293] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 467 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0294] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 468 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0295] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 469 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0296] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 470] and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0297] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 471 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0298] In some embodiments, an antibody disclosed herein comprises a LC having an amino acid sequence with at least 80% identity to SEQ ID NO: 472 and a HC having at least 80% sequence identity to any one of the HC (“VH_HC”) regions listed in Table 4 or Table 15.
[0299] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 488 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0300] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 528 and a VL having at least
80% sequence identity to any one of the VL regions listed in Table 1.
[0301] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 567 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0302] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 585 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0303] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 590 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0304] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 595 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0305] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 599 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0306] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 604 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0307] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 608 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0308] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 612 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0309] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 615 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0310] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 618 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0311] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 621 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0312] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 624 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0313] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 626 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0314] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 630 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0315] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 635 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0316] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 638 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0317] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 644 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0318] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 647 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0319] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 649 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0320] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 653 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0321] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 656 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0322] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 658 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0323] In some embodiments, an antibody disclosed herein comprises a VH having an
amino acid sequence with at least 80% identity to SEQ ID NO: 662 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0324] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 665 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0325] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 668 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0326] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 671 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0327] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 675 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0328] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 679 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0329] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0330] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 12 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0331] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 19 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0332] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 26 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0333] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 33 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0334] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 40 and a VL having at least
80% sequence identity to any one of the VL regions listed in Table 1.
[0335] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 47 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0336] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 54 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0337] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 61 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0338] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 68 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0339] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 75 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0340] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 82 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0341] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 89 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0342] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 96 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0343] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 103 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0344] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 110 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0345] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 117 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0346] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 124 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0347] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 131 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0348] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 138 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1
[0349] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 145 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0350] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 152 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0351] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 159 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0352] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 166 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0353] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 173 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0354] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 180 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table l.\
[0355] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 187 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0356] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 194 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0357] In some embodiments, an antibody disclosed herein comprises a VH having an
amino acid sequence with at least 80% identity to SEQ ID NO: 201 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0358] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 208 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0359] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 215 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0360] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 222 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0361] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 229 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0362] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 236 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0363] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 243 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0364] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 250 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0365] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 257 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0366] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 264 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0367] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 271 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0368] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 278 and a VL having at least
80% sequence identity to any one of the VL regions listed in Table 1.
[0369] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 285 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0370] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 292 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0371] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 299 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0372] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 306 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0373] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 313 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0374] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 320 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0375] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 327 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0376] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 334 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0377] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 341 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0378] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 348 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0379] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 355 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0380] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 362 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0381] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 369 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0382] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 376 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0383] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 383 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0384] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 390 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0385] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 397 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0386] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 404 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0387] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 411 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0388] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 418 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0389] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 425 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0390] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 432 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0391] In some embodiments, an antibody disclosed herein comprises a VH having an
amino acid sequence with at least 80% identity to SEQ ID NO: 439 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0392] In some embodiments, an antibody disclosed herein comprises a VH having an amino acid sequence with at least 80% identity to SEQ ID NO: 446 and a VL having at least 80% sequence identity to any one of the VL regions listed in Table 1.
[0393] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 490 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0394] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 494 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0395] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 498 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0396] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 501 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0397] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 505 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0398] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 508 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0399] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 512 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0400] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 516 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0401] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 519 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0402] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 522 and a VH having at least
80% sequence identity to any one of the VH regions listed in Table 1.
[0403] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 525 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0404] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 530 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0405] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 532 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0406] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 535 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0407] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 539 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0408] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 543 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0409] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 546 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0410] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 550 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0411] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 554 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0412] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 558 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0413] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 561 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0414] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 564 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0415] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 569 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0416] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 572 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0417] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 575 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0418] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 576 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0419] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 579 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0420] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 581 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0421] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 16 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0422] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 593 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0423] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 602 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0424] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 627 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0425] In some embodiments, an antibody disclosed herein comprises a VL having an
amino acid sequence with at least 80% identity to SEQ ID NO: 633 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0426] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 641 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0427] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 651 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0428] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 663 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0429] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 674 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0430] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 677 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0431] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 682 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0432] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0433] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 12 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0434] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 23 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0435] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 30 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0436] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 37 and a VH having at least
80% sequence identity to any one of the VH regions listed in Table 1.
[0437] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 44 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0438] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 51 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0439] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 58 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0440] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 65 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0441] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 72 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0442] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 79 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0443] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 86 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0444] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 93 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0445] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 100 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0446] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 107 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0447] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 114 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0448] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 121 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0449] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 128 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0450] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 135 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0451] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 142 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0452] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 149 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0453] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 156 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0454] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 163 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0455] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 170 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0456] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 177 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0457] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 184 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0458] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 191 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0459] In some embodiments, an antibody disclosed herein comprises a VL having an
amino acid sequence with at least 80% identity to SEQ ID NO: 198 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0460] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 205 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0461] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 212 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0462] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 219 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0463] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 226 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0464] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 233 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0465] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 240 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0466] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 247 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0467] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 254 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0468] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 261 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0469] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 268 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0470] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 275 and a VH having at least
80% sequence identity to any one of the VH regions listed in Table 1.
[0471] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 282 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0472] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 289 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0473] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 296 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0474] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 303 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0475] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 310 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0476] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 317 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0477] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 324 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0478] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 331 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0479] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 338 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0480] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 345 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0481] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 352 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0482] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 359 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0483] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 366 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0484] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 373 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0485] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 380 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0486] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 387 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0487] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 394 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0488] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 401 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0489] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 408 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0490] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 415 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0491] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 422 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0492] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 429 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0493] In some embodiments, an antibody disclosed herein comprises a VL having an
amino acid sequence with at least 80% identity to SEQ ID NO: 436 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0494] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 443 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0495] In some embodiments, an antibody disclosed herein comprises a VL having an amino acid sequence with at least 80% identity to SEQ ID NO: 450 and a VH having at least 80% sequence identity to any one of the VH regions listed in Table 1.
[0496] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[0497] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 497.
[0498] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0499] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 504.
[0500] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[0501] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.
[0502] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.
[0503] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518.
[0504] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence
identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[0505] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 of 524, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518.
[0506] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[0507] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[0508] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.
[0509] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 538.
[0510] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
[0511] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
[0512] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549.
[0513] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 553.
[0514] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 557.
[0515] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[0516] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino
acid sequence of SEQ ID NO: 511.
[0517] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[0518] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[0519] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[0520] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 524, and a CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[0521] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578.
[0522] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549.
[0523] In some embodiments, the antibody comprises a VH having at least 80% sequence
identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 584.
[0524] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0525] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0526] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0527] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0528] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0529] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0530] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0531] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 598; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0532] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0533] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0534] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0535] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0536] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0537] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0538] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence
identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0539] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 SEQ ID NO: 588; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0540] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0541] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 588; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0542] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0543] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0544] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0545] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0546] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0547] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0548] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0549] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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 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 having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0550] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0551] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[0552] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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.
[0553] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0554] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, 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: 22; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
[0555] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, 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: 29; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
[0556] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
[0557] In some embodiments, the antibody comprises a VH having at least 80% sequence
identity to any one of the VH amino acid sequences listed in Table 1 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; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 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 SEQ ID NO: GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[0558] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
[0559] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
[0560] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a
CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
[0561] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
[0562] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
[0563] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ
ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
[0564] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
[0565] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
[0566] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid
sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109.
[0567] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116.
[0568] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123.
[0569] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical
to the amino acid sequence of SEQ ID NO: 127; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130.
[0570] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137.
[0571] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144.
[0572] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; and a VL having at least 80% sequence
identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151.
[0573] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158.
[0574] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165.
[0575] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a
CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172.
[0576] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179.
[0577] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186.
[0578] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ
ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193.
[0579] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200.
[0580] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207.
[0581] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid
sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214.
[0582] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221.
[0583] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228.
[0584] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino
acid sequence of SEQ ID NO: 235.
[0585] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242.
[0586] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249.
[0587] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 255, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT:, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 256.
[0588] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 262, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 263.
[0589] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 267; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 269, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAV, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 270.
[0590] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 276, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 277.
[0591] In some embodiments, the antibody comprises a VH having at least 80% sequence
identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 279, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 283, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 284.
[0592] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 290, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 291.
[0593] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 297, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 298.
[0594] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a
CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 302; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 304, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 305.
[0595] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 311, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 312.
[0596] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 316; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 318, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 319.
[0597] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ
ID NO: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 323; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 325, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of STS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 326.
[0598] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 332, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 333.
[0599] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 337; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 339, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 340.
[0600] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid
sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 346, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 347.
[0601] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 353, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 354.
[0602] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 360, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 361.
[0603] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical
to the amino acid sequence of SEQ ID NO: 365; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 367, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 368.
[0604] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 374, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 375.
[0605] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 379; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 381, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ETS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 382.
[0606] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386; and a VL having at least 80% sequence
identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 388, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 389.
[0607] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 393; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 395, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 396.
[0608] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 402, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 403.
[0609] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 407; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a
CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 409, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 410.
[0610] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 416, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 417.
[0611] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 421; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 423, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 424.
[0612] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ
ID NO: 430, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 431.
[0613] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 437, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 438.
[0614] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 444, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 445.
[0615] In some embodiments, the antibody comprises a VH having at least 80% sequence identity to any one of the VH amino acid sequences listed in Table 1 and comprising therein a CDR Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449; and a VL having at least 80% sequence identity to any one of the VL amino acid sequences listed in Table 1 and comprising therein a CDR LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 451, a CDR L2 having an amino acid sequence 100% identical to the amino acid
sequence of DNF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 452.
[0616] In some embodiments, an antibody of the disclosure is antibody A06_Pl_A09 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_A09 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A06_Pl_A10 of Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_A11 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_A12 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_B12 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_B12 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody A06_Pl_C02 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_C04 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_C05 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_C11 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_C11 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody AO6_P1_C12 of Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_C12 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A06_PI_D04 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_D06 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_D06 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody A06_PI_D07 of Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_DI 1 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_E02 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_E04 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_E08 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_E10 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_E10 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody A06 P1 E11 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_F01 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_F08 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_F10 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06 P1 F10 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody A06_Pl_G03 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06_Pl_G08 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO6_P1_G12 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A06 P1 G12 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A06 P1 H01 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06 P1 H01 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A06 PI H06 of Table 1. In some embodiments, an antibody of the disclosure is antibody A06 P1 H06 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A06_Pl_H07 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_A08 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_A09 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09 P1 B01 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_B01 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A09_Pl_B05 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09 P1 B08 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_B08 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A09_Pl_B10 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_C05 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_C05 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody AO9_P1_C11 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_D01 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09 P1 D01 OA of
Table 15. In some embodiments, an antibody of the disclosure is antibody A09_Pl_D05 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_D07 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_D07 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A09_Pl_D08 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_D10 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09 P1 D10 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A09 P1 D11 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09 P1 D11 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody AO9_P1_D12 of Table 1. In some embodiments, an antibody of the disclosure is antibody AO9_P1_D12 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A09_Pl_E05 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_E05 OA of Table 15. In some embodiments, an antibody of the disclosure is antibody A09_Pl_E06 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_E07 of Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_E07 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09 Pl E08 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_E09 of
Table 1. In some embodiments, an antibody of the disclosure is antibody AO9_P1_E12 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_G01 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_G07 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_G08 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_H04 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_H08 of
Table 1. In some embodiments, an antibody of the disclosure is antibody A09_Pl_H09 of
Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A6* of
Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A9* of
Table 1. In some embodiments, an antibody of the disclosure is an antibody selected from
Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A9 of
Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A9 OA of
Table 4. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_G3 of
Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_G3 OA of
Table 4. In some embodiments, an antibody of the disclosure is antibody Libl_G3_A9 of
Table 1. In some embodiments, an antibody of the disclosure is antibody 1675_Lib 1 of Table 1. In some embodiments, an antibody of the disclosure is antibody 7046_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 7046_Lib8 OA of Table 4. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A6 of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A6 OA of Table 4. In some embodiments, an antibody of the disclosure is antibody 5802_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 1374_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 1374_Lib8 OA of Table 4. In some embodiments, an antibody of the disclosure is antibody 9301_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 9621_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 1405_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_H3 of Table 1. In some embodiments, an antibody of the disclosure is antibody 108 l_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 1081_Lib8 OA of Table 4. In some embodiments, an antibody of the disclosure is antibody 1081_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 108 l_Lib8 OA of Table 4. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_A5 of Table 1. In some
embodiments, an antibody of the disclosure is antibody Libi Pl DI of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_C6 of Table 1. In some embodiments, an antibody of the disclosure antibody Libl_Pl_C6 OA of Table 4. In some embodiments, an antibody of the disclosure is antibody 4142_Libl of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_E9 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib8_P4_D4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 4166_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_B4 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib8_P4_Cl l of Table 1. In some embodiments, an antibody of the disclosure is antibody 3964_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 3552_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 2738_Libl of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_Al of Table 1. In some embodiments, an antibody of the disclosure is antibody 189_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_Al of Table 1 In some embodiments, an antibody of the disclosure is antibody Lib6_P3_B9 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib6_P3_Al of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_A3 of Table 1. In some embodiments, an antibody of the disclosure is antibody 487_Libl of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib6_P3_E10 of Table 1. In some embodiments, an antibody of the disclosure is antibody 256_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 4035_Libl of Table 1. In some embodiments, an antibody of the disclosure antibody 4035_Libl OA of Table 4. In some embodiments, an antibody of the disclosure is antibody 96_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A2 of Table 1. In some embodiments, an antibody of the disclosure is antibody 2301_Lib4 of Table 1. In some embodiments, an antibody of the disclosure antibody Lib4_P2_Bl of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_A2 of Table 1. In some embodiments, an antibody of the disclosure is antibody 16_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 11485_Libl of Table 1. In some embodiments, an antibody of the disclosure is antibody 4956_Libl of Table 1. In some embodiments, an antibody of the disclosure is antibody 399_Libl of Table 1. In some embodiments, an antibody of the disclosure antibody 399_Libl OA of Table 4. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_A10 of Table 1. In some
embodiments, an antibody of the disclosure is antibody Lib6_P3_A8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 965_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 27_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 15244_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_Al l of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib8_P4_C10 of Table 1. In some embodiments, an antibody of the disclosure is antibody 8226_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 69_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 76_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 4675_Lib4 of Table 1. In some embodiments, an antibody of the disclosure is antibody 4029_Libl of Table 1. In some embodiments, an antibody of the disclosure is antibody 4029_Libl OA of Table 4. In some embodiments, an antibody of the disclosure is antibody 5662_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib6_P3_A4 of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl Pl FlO of Table 1. In some embodiments, an antibody of the disclosure is antibody Lib4_P2_Dl of Table 1. In some embodiments, an antibody of the disclosure is antibody Libl_Pl_A5 of Table 1. In some embodiments, an antibody of the disclosure is antibody 9312_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 4761_Lib8 of Table 1. In some embodiments, an antibody of the disclosure is antibody 17561_Lib6 of Table 1.
Table 1. Sequences of VH and VL regions of identified anti-VWF CK domain antibodies
[0617] In some embodiments, an antibody listed in Table l is a monovalent (one-arm; “OA”) human antibody in an IgG4 format. In some embodiments, one-arm antibodies of the disclosure include a first polypeptide chain comprising a first HC comprising, from N- terminus to C-terminus: a VH (e.g., any one of the VH regions listed in Table 1), a first heavy chain constant (CHI) region operably linked (e.g., via a peptide bond) to a first hinge domain at its C-terminus, a first CH2 region operably linked at its N-terminus (e.g., via a peptide bond) to the C-terminus of the first hinge domain, and a first CH3 region operably linked at its N-terminus (e.g., via a peptide bond) to the C-terminus of the first CH2 region. In some embodiments, the first HC region comprises a first CHl-hinge-CH2-CH3 polypeptide comprising an amino acid sequence of SEQ ID NO: 484 or a variant thereof having at least 80% sequence identity to SEQ ID NO: 484.
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ S SGLYSLSS VVTVPS S SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY TLPPSQEEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL VSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 484)
[0618] In some embodiments, the first polypeptide chain of the one-arm antibody is operably linked (e.g., via a disulfide bridge) to second polypeptide chain comprising a LC. In some embodiments, the light chain region is a polypeptide comprising, from N-terminus to C-terminus: a VL region (e.g., any one of the VL regions listed in Table 1) operably linked at its C-terminus to the N-terminus of a light chain constant (CL) region. In some embodiments, the CL region is a kappa chain. In some embodiments, the CL region comprises an amino acid sequence of SEQ ID NO: 485 or variant thereof having at least 80% sequence identity to SEQ ID NO: 485.
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQD SKD S TYSL S STLTL SK AD YEKHK VYACE VTHQGL S SP VTK SFNRGEC (SEQ ID NO: 485)
[0619] In some embodiments, the VH and VL regions together comprise an antigen binding site that specifically binds to the CK domain of a VWF protein.
[0620] In some embodiments, a one-arm antibody of the disclosure further comprises a third polypeptide chain comprising a second HC region, wherein the second HC region does not include a VH region. In some embodiments, the second HC region comprises a second CHI region operably linked (e.g., via a peptide bond) to a second hinge domain at its C- terminus, a second CH2 region operably linked at its N-terminus (e.g., via a peptide bond) to the C-terminus of the second hinge domain, and a second CH3 region operably linked at its N-terminus (e.g., via a peptide bond) to the C-terminus of the second CH2 region. In some embodiments, the second CHI region is truncated relative to a CHI region of the first HC domain (e.g., 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, or more amino acid residues). In some embodiments, the second HC region comprises an amino acid sequence of SEQ ID NO: 473 or is a variant thereof having at least 80% sequence identity to SEQ ID NO: 473.
ESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFN WYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSS IEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLS LG
(SEQ ID NO: 473)
[0621] In some embodiments, the CHI domain of the HC region is operably linked to the CL region via a disulfide bridge. In some embodiments, the first HC region and the second HC region are operably linked to one another by a disulfide bridge between the first hinge region and the second hinge region.
[0622] Accordingly, disclosed herein, in some embodiments, are antibodies comprising an antigen binding domain that specifically binds to the CK domain of a VWF protein, the antigen binding domain comprising: (1) a VH domain (e.g., any one of the VH domains listed in Table 1 or a variant thereof having at least 80% sequence identity thereto), the VH domain being operably linked (e.g., via a peptide bond) at its C-terminus to the N-terminus of a CH1- hinge-CH2-CH3 polypeptide of SEQ ID NO: 484 or a variant thereof having at least 80% sequence identity thereto; and (2) a VL domain (e.g., any one of the VL domains listed in Table 1 or a variant thereof having at least 80% sequence identity thereto) operably linked (e.g., via a peptide bond) at its C-terminus to the N-terminus of a CL region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 485 or a variant thereof having at least 80% sequence identity thereto; wherein the antibody further comprises a polypeptide of SEQ ID NO: 473 or a variant thereof having at least 80% sequence identity thereto operably linked (e.g., via a disulfide bridge) to the hinge region of the CHl-hinge- CH2-CH3 polypeptide.
[0623] In some embodiments, binding of an antibody disclosed herein to the VWF protein does not result in a change in function of the VWF protein. In some embodiments, binding of an antibody disclosed herein to VWF (e.g., to VWF CK domain) does not inhibit VWF protein binding to one or more binding partners. In some embodiments, the one or more binding partners are selected from the group consisting of Factor VIII (FVIII), collagen, glycoprotein lb (gplb), glycoprotein Hb/IIIa (gpIIb/IIIa), and ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 (ADAMTS13). In some embodiments, binding of an antibody disclosed herein does not inhibit binding of the VWF protein to platelet cells.
[0624] In some embodiments, an antibody disclosed herein binds specifically to a VWF homodimer comprising two VWF monomers linked tail-to-tail via CK-domain joining in a 1:1 stoichiometry. In some embodiments, an antibody disclosed herein binds specifically to a VWF homodimer comprising two VWF monomers linked tail-to-tail via CK domain joining in 2: 1 stoichiometry. In some embodiments, the antibody exhibits reduced cross-linking to VWF homodimers as compared to a bivalent antibody having the same VH and VL sequences as a monovalent antibody.
Binding Epitopes
[0625] Antibody epitopes are, in some embodiments, a linear peptide sequence (i.e., “continuous”) or is composed of noncontiguous amino acid sequences (i.e., “conformational” or “discontinuous”). In some embodiments, an antibody recognizes one or more amino acid sequences; therefore, an epitope defines more than one distinct amino acid sequence. Epitopes recognized by antibodies are determined, e.g., by peptide mapping and sequence analysis techniques well known to one of skill in the art. Binding interactions are manifested as intermolecular contacts with one or more amino acid residues of a CDR.
[0626] Disclosed herein are antibodies that specifically bind to an epitope of VWF (e.g., human or NHP VWF). In some embodiments, an antibody disclosed herein binds to an epitope comprising noncontiguous amino acid sequences. In some embodiments, a VWF- binding antibody described herein has one antigen-binding site for binding to VWF. In some embodiments, the VWF-binding antibody binds to an epitope in the CK domain of a human VWF protein having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 5 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 5. CNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTE PMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK
(SEQ ID NO: 5)
[0627] In some embodiments, the CK domain is positioned between amino acid positions 2,723 and 2,813 of SEQ ID NO: 1.
[0628] In some embodiments, the VWF-binding antibody binds to an epitope in the CK domain of a NHP VWF protein having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 6 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 6.
CSDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTE PMQ VPLHCTNGS WYHEVLNAMQCEC SPRKC SK
(SEQ ID NO: 6)
[0629] The disclosure provides, in certain embodiments, protein constructs containing the CK domain of VWF. In some embodiments, the protein construct contains a human, NHP, canine, or murine CK domain of VWF and, optionally, one or more sequences that facilitates the expression, isolation, purification, and/or detection of the protein construct in vitro, in vivo, or ex vivo. In some embodiments, the protein construct containing a human CK domain is a polypeptide having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 7 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 7.
MIPARFAGVLLALALILPGTLCAEHHHHHHGSGLNDIFEAOKIEWHEGSFFFZFOGP EPECNDITARLOYVKVGSCKSEVEVDIHYCOGKCASKAMYSIDINDVODOCSCC SPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK (SEQ ID NO: 7)
[0630] Sequence Key: single-underlined residues correspond to the N-terminal signal peptide sequence of VWF; bold residues correspond to a His6 tag (SEQ ID NO: 11); doubleunderlined residues correspond to a sequence for in vitro biotinylation; bold italic residues correspond to a HRV 3C sequence; and bold underlined residues correspond to the CK domain of human VWF protein as provided in SEQ ID NO: 5.
[0631] In some embodiments, the protein construct containing a human CK domain is a polypeptide having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 486 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 486.
MIPARFAGVLLALALILPGTLCAEHHHHHHGSSAWSHPOFEKGSFFFZF0GPEPEC NDITARLQYVKVGSCKSEVEVDIHYCOGKCASKAMYSIDINDVODQCSCCSPTR TEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSKGGGGSYPYDVPDYA (SEQ ID NO: 486)
[0632] Sequence Key: single-underlined residues correspond to the N-terminal signal peptide sequence of VWF; bold residues correspond to a His6 tag (SEQ ID NO: 11); doubleunderlined residues correspond to a sequence for in vitro biotinylation; bold italic residues correspond to a HRV 3C sequence; bold underlined residues correspond to the CK domain of human VWF protein as provided in SEQ ID NO: 5; and bold and double-underlined correspond to a C-terminal HA-tag.
[0633] In some embodiments, the protein construct containing a NHP CK domain is a polypeptide having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 8 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 8. MIPARFAGVLLALALILPGTLCAEHHHHHHGSGLNDIFEAOKIEWHEGSLFF7.FQGP EPECSDITARLQYVKVGSCKSEVEVDIHYCOGKCASKAMYSIDINDVODQCSCCS PTRTEPMQVPLHCTNGSVVYHEVLNAMQCECSPRKCSK
(SEQ ID NO: 8)
[0634] Sequence Key: single-underlined residues correspond to the N-terminal signal peptide sequence of VWF; bold residues correspond to a His6 tag (SEQ ID NO: 11); doubleunderlined residues correspond to a sequence for in vitro biotinylation; bold italic residues
correspond to a HRV 3C sequence; and bold underlined residues correspond to the CK domain of NHP VWF protein as provided in SEQ ID NO: 6.
[0635] In some embodiments, the protein construct containing a NHP CK domain is a polypeptide having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 487 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 487.
MIPARFAGVLLALALILPGTLCAEHHHHHHGSSAWSHPOFEKGSFEELFOGPEPECS DITARLQYVKVGSCKSEVEVDIHYCOGKCASKAMYSIDINDVODQCSCCSPTRT EPMQVPLHCTNGSVVYHEVLNAMQCECSPRKCSKGGGGSYPYDVPDYA (SEQ ID NO: 487)
[0636] Sequence Key: single-underlined residues correspond to the N-terminal signal peptide sequence of VWF; bold residues correspond to a His6 tag (SEQ ID NO: 11); doubleunderlined residues correspond to a sequence for in vitro biotinylation; bold italic residues correspond to a HRV 3C sequence; bold underlined residues correspond to the CK domain of a NHP VWF protein as provided in SEQ ID NO: 6; and bold and double-underlined correspond to a C-terminal HA-tag.
[0637] In some embodiments, the protein construct containing a canine CK domain is a polypeptide having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 9 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 9. MIPARFAGVLLALALILPGTLCAEHHHHHHGSGLNDIFEAOKIEWHEGSFFFZFOGP EPECKDIIAKLORVKVGDCKSEEEVDIHYCEGKCASKAVYSIHMEDVODQCSCC SPTQTEPMQVPLRCTNGSLIYHEILNAMQCRCSPRKCSK
(SEQ ID NO: 9)
[0638] Sequence Key: single-underlined residues correspond to the N-terminal signal peptide sequence of VWF; bold residues correspond to a His6 tag (SEQ ID NO: 11); doubleunderlined residues correspond to a sequence for in vitro biotinylation; bold italic residues correspond to a HRV 3C sequence; and bold underlined residues correspond to the CK domain of canine VWF protein.
[0639] In some embodiments, the protein construct containing a murine CK domain is a polypeptide having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 10 or a variant thereof having at least 85% sequence identity to SEQ ID NO: 10. MIPARFAGVLLALALILPGTLCAEHHHHHHGSGLNDIFEAOKIEWHEGSFEFZFDGP EPDCKDITAKVOYIKVGDCKSOEEVDIHYCOGKCASKAVYSIDIEDVOEQCSCCL PSRTEPMRVPLHCTNGSVVYHEVINAMQCRCSPRNCSK
(SEQ ID NO: 10)
[0640] Sequence Key: single-underlined residues correspond to the N-terminal signal peptide sequence of VWF; bold residues correspond to a His6 tag (SEQ ID NO: 11); doubleunderlined residues correspond to a sequence for in vitro biotinylation; bold italic residues correspond to a HRV 3C sequence; and bold underlined residues correspond to the CK domain of murine VWF protein.
[0641] In some embodiments, 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 of SEQ ID NO: 1. As used herein, unless otherwise noted, reference to residues within the VWF CK domain refer to numbering within the human VWF CK domain, c.g, with position numbering in reference to SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: D2726, R2730, D2746, and K2757 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744, and D2746 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, D2746, and K2757 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, D2746, and K2757 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, E2744, D2746, and D2763 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744, D2746, K2757, and D2763 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least amino acid residue K2735 of the VWF CK domain of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: D2726, K2735, and K2757 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735 and D2763 of SEQ ID NO: 1. In some embodiments, the antibody binds to at least one of (e.g., one of, two of, three of, four of, five of, six of, seven of, eight of, nine of, ten of, eleven of, twelve of, or all 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.
[0642] Also disclosed herein are additional antibodies that specifically bind to the epitope disclosed herein. These additional antibodies, or antigen-binding fragments thereof that specifically bind to the epitope disclosed herein are, in some embodiments, identified using
techniques known in the art. For example, a computational approach is used to design epitope-specific antibodies, as is known in the art. Another approach is used to identify antibodies that bind to specific epitopes from a library of antibodies that bind to the antigen, in some embodiments, such as the following: first incorporate noncanonical amino acids (ncAAs) /i-benzoyl-L-phenylalanine (pBpa) and p-azido-L-phenylalanine (pAzF) into the target epitope and then select the antibodies that cross-link with the ncAA incorporated epitope after UV irradiation. Because cross-linking only occurs when the distance between the antibody and the epitope is close enough, this method efficiently selects antibodies that specifically bind to the target epitope.
Modifications of Antibodies
[0643] Antibodies, or antigen-binding fragments thereof, are modified, in some cases, using techniques known in the art for various purposes.
[0644] In some embodiments, VWF-binding antibodies of the disclosure contain an Fc region. In some embodiments, the Fc region is a wild-type Fc region. In some embodiments, the Fc region is a modified Fc region. In some cases when an antigen-binding fragment does not contain an Fc region, an Fc region is added to (e.g., recombinantly) the fragment, e.g., to increase half-life of the antigen-binding fragment in circulation in blood when administered to a subject. Choice of an appropriate Fc region and methods of to incorporate such fragments are known in the art. Incorporating an Fc region of an IgG into a polypeptide of interest so as to increase its circulatory half-life, but so as not to lose its biological activity is accomplished, e.g., by using conventional techniques known in the art. In some embodiments, Fc regions of antibodies are further modified to increase half-life of the antigen-binding fragment in circulation in blood when administered to a subject. In some embodiments, an Fc region of an antibody disclosed herein is modified to reduce or silence effector functions of the antibody (e.g., antibody-dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), opsonization, phagocytosis, transcytosis, neutralization of infectivity, inflammation, mucosal immunity, and neonatal immunity). Modifications are, e.g., determined using conventional means in the art. 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).
[0645] In some embodiments, the first heavy chain (HC; e.g., any one of the “VH HC” sequences listed in Table 4 or Table 15) comprises a S228P/T366W/F234A/L235A/delta- K447 mutation and the second heavy chain (HC; e.g., any one of the “HC_trc” sequences listed in Table 4 or Table 15) comprises a S228P/T366S/L368A/Y407V/F234A/L235A/delta- K447 mutation. In some embodiments, the first heavy chain comprises a S228P/T366W/delta-K447 mutation and the second heavy chain 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.
[0646] In some embodiments, the modified Fc region increases the blood plasma half-life of the antibody as compared to a blood plasma half-life of an antibody lacking modifications in the Fc region. In some embodiments, the modified Fc region increases the blood plasma
half-life of an antibody disclosed herein by 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 half-life of an antibody lacking modifications in the Fc region. In some embodiments, the modified Fc region increases the blood plasma half-life of an antibody disclosed herein by 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 half-life of an antibody lacking modifications in the Fc region. In some embodiments, the modified Fc region reduces one or more effector functions of an antibody disclosed herein as compared to the effector functions of an antibody lacking modifications in the Fc region. In some embodiments, the one or more effector functions are selected from the group consisting of antibody-dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), opsonization, phagocytosis, transcytosis, neutralization of infectivity, inflammation, mucosal immunity, and neonatal immunity. In some embodiments, the modified Fc region reduces one or more effector functions of an antibody disclosed herein by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% as compared to the one or more effector functions of the antibody lacking modifications in the Fc region. In some embodiments, the modified Fc region reduces one or more effector functions of an antibody disclosed herein by 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 as compared to the one or more effector functions of the antibody lacking modifications in the Fc region.
[0647] In some embodiments, antibodies of the disclosure are modified, e.g., by addition of polyethylene glycol (PEG). In some embodiments, PEG modification (PEGylation) leads to one or more of improved circulation time, improved solubility, improved resistance to proteolysis, reduced antigenicity and immunogenicity, improved bioavailability, reduced toxicity, improved stability, and easier formulation.
[0648] Glycosylation of immunoglobulins has been shown to have significant effects on their effector functions, structural stability, and rate of secretion from antibody -producing cells. The carbohydrate groups responsible for these properties are generally attached to the constant (C) regions of the antibodies. For example, glycosylation of IgG at asparagine 297 in the CH2 domain is required for full capacity of IgG to activate the classical pathway of
complement-dependent cytolysis. Glycosylation of IgM at asparagine 402 in the CH3 domain is necessary for proper assembly and cytolytic activity of the antibody. Removal of glycosylation sites as positions 162 and 419 in the CHI and CH3 domains of an IgA antibody led to intracellular degradation and at least 90% inhibition of secretion.
[0649] Glycosylation of immunoglobulins in the variable (V) region has also been observed. About 20% of human antibodies are glycosylated in the V region. Glycosylation of the V domain is believed to arise from fortuitous occurrences of the N-linked glycosylation signal Asn-Xaa-Ser/Thr in the V region sequence and has not been recognized in the art as playing a role in immunoglobulin function.
[0650] Glycosylation at a variable domain framework residue, in some cases, alters the binding interaction of the antibody with antigen. The present disclosure includes criteria by which a limited number of amino acids in the framework or CDRs of a humanized immunoglobulin chain are chosen to be mutated (e.g., by substitution, deletion, or addition of residues) to increase the affinity of an antibody. In some embodiments, cysteine residue(s) are removed or introduced in the Fc region of an antibody or Fc-containing polypeptide, thereby eliminating or increasing interchain disulfide bond formation in this region.
[0651] It has been shown that sequences within the CDR cause an antibody to bind to MHC Class II and trigger an unwanted helper T-cell response in some cases. In some embodiments, a conservative substitution allows the antibody to retain binding activity yet reduce its ability to trigger an unwanted T-cell response. In one embodiment, one or more of the N-terminal 20 amino acids of the heavy or light chain is removed.
[0652] Covalent modifications of an antibody are also included herein. In some embodiments, they are made by chemical synthesis or by enzymatic or chemical cleavage of the antibody, if applicable. In some embodiments, other types of covalent modifications are introduced by reacting targeted amino acid residues with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C-terminal residues.
[0653] Cysteinyl residues are most commonly reacted with alpha-haloacetates (and corresponding amines), such as chloroacetic acid or chloroacetamide, to give carboxymethyl or carboxyamidomethyl derivatives. Cysteinyl residues also are derivatized by reaction with bromotrifluoroacetone, alpha-bromo-beta-(5-imidozoyl)propionic acid, chloroacetyl phosphate, N-alkylmaleimides, 3-nitro-2 -pyridyl disulfide, methyl 2-pyridyl disulfide, p- chloromercuribenzoate, 2-chloromercuri-4-nitrophenol, or chloro-7-nitrobenzo-2-oxa-l,3- diazole.
[0654] In some embodiments, histidyl residues are derivatized by reaction with diethylpyrocarbonate at pH 5.5-7.0 because this agent is relatively specific for the histidyl side chain. In some embodiments, para-bromophenacyl bromide also is useful; the reaction, in some embodiments, is performed in 0.1 M sodium cacodylate at pH 6.0.
[0655] In some embodiments, lysinyl and amino-terminal residues are reacted with succinic or other carboxylic acid anhydrides. Derivatization with these agents has the effect of reversing the charge of the lysinyl residues. Other suitable reagents for derivatizing alpha- amino-containing residues include imidoesters such as methyl picolinimidate, pyridoxal phosphate, pyridoxal, chloroborohydride, trinitrobenzenesulfonic acid, O-m ethylisourea, 2,4- pentanedione, and transaminase-catalyzed reaction with glyoxylate.
[0656] In some embodiments, arginyl residues are modified by reaction with one or several conventional reagents, such as phenylglyoxal, 2, 3 -butanedione, 1,2- cyclohexanedione, and ninhydrin. Derivatization of arginine residues requires that the reaction be performed in alkaline conditions because of the high pKa of the guanidine functional group. Furthermore, these reagents, in some embodiments, react with the groups of lysine as well as the arginine epsilon-amino group.
[0657] In some embodiments, the specific modification of tyrosyl residues are made, with particular interest in introducing spectral labels into tyrosyl residues by reaction with aromatic diazonium compounds or tetranitromethane. Most commonly, N-acetylimidazole and tetranitromethane are used to form O-acetyl tyrosyl species and 3 -nitro derivatives, respectively, in some embodiments. Tyrosyl residues are iodinated using 125I or 131I to prepare labeled proteins for use in radioimmunoassay.
[0658] Carboxyl side groups (aspartyl or glutamyl) are specifically modified by reaction with carbodiimides (R-N=C=N-R’), where R and R’ are different alkyl groups, such as 1- cyclohexyl-3-(2-morpholinyl-4-ethyl) carbodiimide or l-ethyl-3-(4-azonia-4,4- dimethylpentyl)carbodiimide. Furthermore, aspartyl and glutamyl residues are converted to asparaginyl and glutaminyl residues by reaction with ammonium ions.
[0659] In some embodiments, glutaminyl and asparaginyl residues are deamidated to the corresponding glutamyl and aspartyl residues, respectively. These residues are deamidated under neutral or basic conditions.
[0660] Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains, acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.
[0661] Another type of covalent modification involves chemically or enzymatically coupling glycosides to the specific binding agent or antibody. These procedures do not require production of the polypeptide or antibody in a host cell that has glycosylation capabilities for N- or O-linked glycosylation. Depending on the coupling mode used, in some embodiments, the sugar(s) are attached to (a) arginine and histidine, (b) free carboxyl groups, (c) free sulfhydryl groups such as those of cysteine, (d) free hydroxyl groups such as those of serine, threonine, or hydroxyproline, (e) aromatic residues such as those of phenylalanine, tyrosine, or tryptophan, or (f) the amide group of glutamine.
[0662] Removal of any carbohydrate moieties present on the polypeptide or antibody are, in some embodiments, accomplished chemically or enzymatically. Chemical deglycosylation involves exposure of the antibody to the compound trifluoromethanesulfonic acid, or an equivalent compound. This treatment results in the cleavage of most or all sugars except the linking sugar (N-acetylglucosamine or N-acetylgalactosamine), while leaving the antibody intact. Enzymatic cleavage of carbohydrate moieties on an antibody is achieved by the use of a variety of endo- and exo-glycosidases in some embodiments.
[0663] Another type of covalent modification comprises linking an antibody to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, polyoxyethylated polyols, polyoxyethylated sorbitol, polyoxyethylated glucose, polyoxyethylated glycerol, polyoxyalkylenes, or polysaccharide polymers such as dextran. Such methods are known in the art.
[0664] Affinity for binding a pre-determined polypeptide antigen, generally, is modulated by introducing one or more mutations into the V region framework, typically in areas adjacent to one or more CDRs and/or in one or more framework regions. Typically, such mutations involve the introduction of conservative amino acid substitutions that either destroy or create the glycosylation site sequences but do not substantially affect the hydropathic structural properties of the polypeptide. Typically, mutations that introduce a proline residue are avoided.
[0665] In some embodiments, the antibody or antigen-binding fragment provided herein is conjugated or linked to a therapeutic moiety, an imaging or detectable moiety, or an affinity tag. Methods for conjugating or linking polypeptides are well known in the art. Associations (binding) between compounds and labels include any means known in the art including, but not limited to, covalent and non-covalent interactions, chemical conjugation, as well as recombinant techniques. An antibody or antigen-binding fragment thereof is conjugated to, or recombinantly engineered with, an affinity tag (e.g., a purification tag), in
some embodiments. Affinity tags such as, e.g., poly-histidine tags (e.g., His6 (SEQ ID NO: 11)) are conventional in the art.
[0666] In some embodiments, the antibody or antigen-binding fragment further comprises a detectable moiety. Detections accomplished, e.g., in vitro, in vivo or ex vivo. In vitro assays for the detection and/or determination (quantification, qualification, etc.) of, e.g., VWF protein levels using the antibodies or antigen-binding fragments thereof include but are not limited to, e.g., ELISAs, RIAs, and western blots. In some embodiments, in vitro detection, diagnosis, or monitoring of the antigen of the antibodies occurs by obtaining a sample (e.g., a blood sample) from a subject and testing the sample in, e.g., a standard ELISA assay.
Pharmaceutical Compositions
[0667] Disclosed herein, in certain embodiments, are pharmaceutical compositions comprising an antibody as disclosed herein and a pharmaceutically acceptable carrier, diluent, or excipient. Such compositions are useful for in vitro or in vivo analysis or, in the case of pharmaceutical compositions, for administration to a subject in vivo or ex vivo for treating a subject with the disclosed antibodies.
[0668] In some embodiments, the carrier, diluent, or excipient is a stabilizer, buffer, surfactant, filler, solvent, tonicity or osmolarity adjusting agent, antioxidant, adjuvant, and antimicrobial agent or other suitable materials known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material will depend on the route of administration.
[0669] Pharmaceutical formulations comprising an antibody or antigen-binding fragment, identified by the methods described herein are prepared for storage by mixing the protein having the desired degree of purity with optional physiologically acceptable carrier, diluent, or excipient (see, e.g., Remington ’s Pharmaceutical Sciences, 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions in some embodiments. Acceptable carrier, diluent, or excipient are those that are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin,
gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN®, PLURONICS® or polyethylene glycol (PEG). In certain embodiments, the pharmaceutical composition comprises the antibody at a concentration of between 5-200 mg/mL. In some embodiments, the pharmaceutical composition comprises the antibody at a concentration of 150 mg/mL. In some embodiments, the pharmaceutical composition is in a volume of no greater than 1.0 mL (e.g., 1.0 mb, 0.9 mL, 0.8 mb, 0.7 mL, 0.6 mL, 0.5 mL, 0.4 mL, 0.3 mL, 0.2 mL, 0.1 mL, or less). In some embodiments, the pharmaceutical composition is stable as a liquid solution at room temperature.
[0670] Acceptable carriers are physiologically acceptable to the administered subject and retain the therapeutic properties of the compounds with/in which it is administered.
Acceptable carriers and their formulations are and generally described in, e.g., Remington ’s Pharmaceutical Sciences, supra. One exemplary carrier is physiological saline. The phrase “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject compounds from the administration site of one organ, or portion of the body, to another organ, or portion of the body, or in an in vitro assay system. Each carrier is acceptable in the sense of being compatible with the other ingredients of the formulation and not injurious to a subject to whom it is administered. Nor should an acceptable carrier alter the specific activity of the subject compounds.
[0671] In another embodiment, a pharmaceutical composition disclosed herein further comprises an acceptable additive to improve the stability of the compounds in composition and/or to control the release rate of the composition. Acceptable additives do not alter the specific activity of the subject compounds. Exemplary acceptable additives include, but are not limited to, a sugar such as mannitol, sorbitol, glucose, xylitol, trehalose, sorbose, sucrose, galactose, dextran, dextrose, fructose, lactose, and mixtures thereof. Acceptable additives are combined with acceptable carriers and/or excipients such as dextrose, in some embodiments. Alternatively, exemplary acceptable additives include, but are not limited to, a surfactant such as polysorbate 20 or polysorbate 80 to increase stability of the peptide and decrease gelling of the solution. In some embodiments, the surfactant is added to the composition in an
amount of 0.01% to 5% of the solution. Addition of such acceptable additives increases the stability and half-life of the composition in storage.
[0672] In one embodiment, a pharmaceutical composition disclosed herein contains an isotonic buffer such as a phosphate, acetate, or TRIS buffer in combination with a tonicity agent such as a polyol, sorbitol, sucrose or sodium chloride, which tonicifies and stabilizes. In some embodiments, a tonicity agent is present in the composition in an amount of about 5%. [0673] In another embodiment, a pharmaceutical composition disclosed herein includes a surfactant such as to prevent aggregation and for stabilization at 0.01 to 0.02% w/v.
[0674] In another embodiment, the pH of a pharmaceutical composition disclosed herein ranges from 4.5-6.5 or 4.5-5.5.
[0675] In some embodiments, a pharmaceutical composition disclosed herein also contains more than one active compound as necessary for the indication being treated, such as those with complementary activities that do not adversely affect each other. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.
[0676] In some embodiments, active ingredients are entrapped in microcapsule prepared, e.g., by coacervation techniques or by interfacial polymerization, e.g., hydroxy methylcellulose or gelatin-microcapsule and poly-(methylmethacrylate) microcapsule, respectively, in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington ’s Pharmaceutical Sciences, supra.
[0677] Suspensions and crystal forms of antibodies are also contemplated herein; methods to make suspensions and crystal forms are known to one of skill in the art.
[0678] In some embodiments, a pharmaceutical composition disclosed herein is sterile. In some embodiments, a pharmaceutical composition disclosed herein is sterilized by conventional, well known sterilization techniques. For example, sterilization is readily accomplished by filtration through sterile filtration membranes. In some embodiments, the resulting solutions is packaged for use or filtered under aseptic conditions and lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration.
[0679] Freeze-drying is employed to stabilize polypeptides for long-term storage, such as when a polypeptide is relatively unstable in liquid compositions, in some embodiments.
[0680] In some embodiments, excipients such as, e.g., polyols (including mannitol, sorbitol, and glycerol), sugars (including glucose and sucrose), and amino acids (including alanine, glycine, and glutamic acid) act as stabilizers for freeze-dried products. Polyols and
sugars are also used to protect polypeptides from freezing and drying-induced damage and to enhance the stability during storage in the dried state in some embodiments. Sugars are, in some embodiments, effective in both the freeze-drying process and during storage. Other classes of molecules, including mono- and disaccharides and polymers, such as PVP, have also been reported as stabilizers of lyophilized products.
[0681] For injection, in some embodiments, a pharmaceutical composition disclosed herein is a powder suitable for reconstitution with an appropriate solution as described above. Examples of these include, but are not limited to, freeze dried, rotary dried, or spray dried powders, amorphous powders, granules, precipitates, or particulates. For injection, the compositions optionally contain stabilizers, pH modifiers, surfactants, bioavailability modifiers, and combinations of these.
[0682] Sustained-release preparations are prepared, in some embodiments. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsule. Examples of sustained-release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (see, e.g., U.S. Pat. No. 3,773,919), copolymers ofL-glutamic acid and y ethyl- L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the Lupron Depot. TM. (injectable microspheres composed of lactic acid- glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3 -hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. In some embodiments, while encapsulated antibodies remain in the body for a long time, they denature or aggregate as a result of exposure to moisture at 37 °C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies devised for stabilization are, in some cases, dependent on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S— bond formation through thiodisulfide interchange, stabilization is achieved, in some cases, by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.
[0683] In some embodiments, a pharmaceutical composition disclosed herein is designed to be short-acting, fast-releasing, long-acting, or sustained-releasing as described herein. In one embodiment, a pharmaceutical composition disclosed herein is formulated for controlled release or for slow release.
[0684] The pharmaceutical composition is administered, e.g., by injection, including, but not limited to, subcutaneous, intravitreal, intradermal, intravenous, intra-arterial, intraperitoneal, intracerebrospinal, or intramuscular injection. Excipients and carriers for use in formulation of compositions for each type of injection are contemplated herein. The following descriptions are by example only and are not meant to limit the scope of the compositions. Compositions for injection include, but are not limited to, aqueous solutions (where water soluble) or dispersions, as well as sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL.TM. (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In some embodiments, the carrier is a solvent or dispersion medium containing, e.g., water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. Fluidity is maintained, e.g., by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Antibacterial and antifungal agents include, e.g., parabens, chlorobutanol, phenol, ascorbic acid, and thimerosal. Isotonic agents, e.g., sugars, polyalcohols such as mannitol, sorbitol, and sodium chloride are included in the composition in some embodiments. In some embodiments, the resulting solutions are packaged for use as is, or lyophilized; the lyophilized preparation is later combined with a sterile solution prior to administration, in some embodiments. For intravenous injection or injection at the site of affliction, the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen- free and has suitable pH, isotonicity, and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, e.g., isotonic vehicles such as Sodium Chloride Injection, Ringer’s Injection, and Lactated Ringer’s Injection. Preservatives, stabilizers, buffers, antioxidants, and/or other additives are included as needed, in some embodiments. Sterile injectable solutions are prepared by incorporating an active ingredient in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization, in some embodiments. Generally, dispersions are prepared by incorporating the active ingredient into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.
[0685] Compositions are conventionally administered intravenously in some embodiments, such as by injection of a unit dose. For injection, in some embodiments, an active ingredient is in the form of a parenterally acceptable aqueous solution which is substantially pyrogen-free and has suitable pH, isotonicity, and stability. In some embodiments, one prepares suitable solutions using, e.g., isotonic vehicles such as Sodium Chloride Injection, Ringer’s Injection, Lactated Ringer’s Injection. Preservatives, stabilizers, buffers, antioxidants, and/or other additives are included, as required, in some embodiments. Additionally, compositions are administered via aerosolization in some embodiments.
[0686] For parenteral administration, the antibodies are formulated in a unit dosage injectable form (e.g., solution, suspension, or emulsion) in association with a pharmaceutically acceptable, parenteral vehicle. Examples of such vehicles are water, saline, Ringer’s solution, dextrose solution, and 5% human serum albumin. Nonaqueous vehicles such as fixed oils and ethyl oleate are also used. In some embodiments, liposomes are used as carriers. The vehicle contains minor amounts of additives such as substances that enhance isotonicity and chemical stability, e.g., buffers and preservatives. The antibodies are typically formulated in such vehicles at concentrations of about 1 mg/mL to 10 mg/mL.
[0687] In one embodiment, a pharmaceutical composition disclosed herein is lyophilized, e.g., to increase shelf-life in storage. When the compositions are considered for use in medicaments or any of the methods provided herein, in some embodiments, it is contemplated that the composition are substantially free of pyrogens such that the composition will not cause an inflammatory reaction or an unsafe allergic reaction when administered to a human subject. Testing compositions for pyrogens and preparing compositions substantially free of pyrogens are well understood to one or ordinary skill of the art and are accomplished using commercially available kits in some embodiments.
[0688] In some embodiments, acceptable carriers contain a compound that stabilizes, increases, or delays absorption or clearance. Such compounds include, e.g., carbohydrates, such as glucose, sucrose, or dextrans; low molecular weight proteins; compositions that reduce the clearance or hydrolysis of peptides; or excipients or other stabilizers and/or buffers. Agents that delay absorption include, e.g., aluminum monostearate and gelatin. In some embodiments, detergents also be used to stabilize or to increase or decrease the absorption of the pharmaceutical composition, including liposomal carriers. To protect from digestion the compound, in some embodiments, is complexed with a composition to render it resistant to acidic and enzymatic hydrolysis, or the compound is, in some embodiments,
complexed in an appropriately resistant carrier such as a liposome. Means of protecting compounds from digestion are known in the art.
Methods of Treatment
[0689] 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 an antibody or pharmaceutical composition containing the antibody disclosed herein. In some embodiments, the disclosure provides a use of an antibody as described herein for the manufacture of a medicament. In some embodiments, the disclosure provides a use of an antibody as described herein for the treatment of a blood disorder characterized by excessive bleeding.
[0690] Blood disorders characterized by excessive bleeding arise, in part, due to dysregulation of hemostasis, which can occur when proteins involved in the clotting signaling cascades are disrupted. For example, von Willebrand disease (VWD) is an inherited bleeding disorder that results from deficiency in VWF. Such deficiency can arise from low levels of VWF (i.e., quantitative effect) or from presence of dysfunctional VWF (i.e., qualitative effect). It is one of the most common inherited blood clotting disorders in humans. Hereditary forms of VWD include type 1, type 2, type 3, and platelet-type VWD. In addition to inherited pathology, VWD exists in acquired forms. Generally, VWD is characterized by tendency to bleed, easy bruising, nosebleeds, bleeding gums, heavy menstrual bleeding, and blood loss during childbirth. Recently, another diagnostic category of “low VWF” has emerged, corresponding to individuals with VWF levels that are below normal but insufficient to meet diagnostic criteria for VWD. VWF deficiency in VWD presents primarily in organs with small vessels, including skin, gastrointestinal tract, uterus, and colon.
[0691] As mentioned above, hereditary VWD occurs in multiple forms, including type 1, type 2, type 3, and platelet-type. Type 1 VWD is the predominant form (40-80% of all cases), which presents as VWF levels that are less than 50% of levels in healthy subjects. Type 1 VWD patients can be asymptomatic and lead a normal life without complications. Therefore, although VWD occurs in about 1% of the population, clinically significant cases are observed in about 1/10,000 cases. Type 2 VWD corresponds to 15-50% of all cases and generally presents as a bleeding tendency that varies between patients. Type 2 VWD can be further classified into subtypes based on the presence and behavior of VWF multimers, including Types 2A, 2B, 2M, and 2N. Type 2A is characterized by a defect in the ability to form large VWF multimers. Type 2B is characterized by a gain of function in which the binding
between VWF and platelet gplb receptor is strongly enhanced, resulting in abnormal platelet binding and rapid clearance of platelet- VWF multimer complexes. This leads to reduced or absent levels of large VWF multimers. Type 2M VWD results from reduced binding between VWF and gplb platelet receptor, resulting in reduced platelet adhesion and aggregation. Type 2N VWD corresponds to a deficiency in binding between VWF and FVIII, resulting in reduced blood plasma levels of FVIII similar to those seen in hemophilia A. Type 3 VWD is characterized by homozygosity for the defective VWF gene and features complete absence of VWF in plasma, resulting in the most severe form of VWD. Type 3 VWD is also associated with very low blood plasma levels of FVIII. Platelet-type VWD presents with qualitatively and quantitatively normal VWF protein, but features a defect in the platelet gplb receptor that results in increased affinity to VWF. This increased affinity to VWF produces abnormally large platelet aggregates that are cleared from circulation along with VWF multimers. The pathogenesis of acquired VWD is variable. It can be associated with the presence of autoantibodies to VWF, resulting in rapid clearance of VWF -autoantibody complexes from the circulation, or interference with its function. Acquired VWD can also occur with adsorption of VWF by tumor cells and non-immunologic mechanisms of destruction. Current treatments for VWD include use of desmopressin, tranexamic acid (TXA), and concentrates of plasma-derived VWF and/or FVIII or recombinant VWF. However, these therapies suffer from several shortcomings, including but not limited to short half-lives not suitable for bleeding prophylaxis, increased thrombotic and cardiovascular risk, gastrointestinal side effects, limited efficacy in major bleeds, high cost (e.g., VWF/FVIII supplementation), inconvenient intravenous administration (e.g., VWF and FVIII supplementation), and/or risk of blood-transmitted diseases. Therefore, there is an unmet need for the treatment of VWF deficiency that cannot be remedied by currently available therapies.
[0692] Hemophilia A is another disease characterized by disrupted hemostasis resulting from a genetic deficiency in functional FVIII. Such a deficiency can arise from low levels of normal FVIII protein and/or the presence of a dysfunctional variant of FVIII. Hemophilia A presents with internal or external bleeding episodes, with bleeding severity corresponding to the degree of FVIII deficiency. Patients with hemophilia A have an elevated risk for excessive bleeding from common injuries and often exhibit spontaneous bleeding without cause. Sites of bleeding may include skin, joints, muscles, digestive tract, and brain. Various mutations in FVIII can result in a positive diagnosis, with the severity of disease resulting from differences in amount of functional FVIII protein. Patients with less than 1% of normal
levels of active FVIII exhibit severe hemophilia, those with 1-5% exhibit moderate hemophilia, and those with 5-40% have mild hemophilia.
[0693] Heydes syndrome is a syndrome featuring abnormal hemostasis from acquired VWD and gastrointestinal bleeding from angiodysplasia, in the presence of aortic stenosis. Patients with aortic valve stenosis have a narrowed valve, resulting in increased sheer stress on blood passing through it. The increase in shear stress causes platelet and VWF activation, further resulting in the activation of ADAMTS13 and degradation of VWF. Accordingly, the reduced levels of VWF in the blood increase the propensity to bleed. Surgical correction of aortic stenosis results in resolution of the acquired VWD in most cases, but not all patients are suitable for surgery.
[0694] Abnormal uterine bleeding (AUB) is a disorder featuring vaginal bleeding from the uterus that is frequent, long-lasting, heavier than normal, and/or irregular, which may lead to anemia and reduced quality of life. AUB affects as many as 25% of women and may be associated with structural and non-structural causes. Examples of structural causes for AUB include leiomyoma (fibroids), adenomyosis (endometrial invasion of myometrium), polyps, and cancer. Non-structural causes for AUB may be medical (e.g., hypothyroidism) or may result from a disorder of hemostasis (accounting for about 10% of all AUB cases). Due to its heterogenous etiology, treatment of AUB is complicated, but generally involves use of hormonal therapies, non-steroidal anti-inflammatory drugs (NSAIDS), and TXA. A recent UK survey of AUB patients (Cox et al . , BMC Health Serv Res, 13 : 491 (2013)) has reported a low rate of satisfaction with treatment outcomes after one year, highlighting an unmet need for improved therapies to treat AUB.
[0695] Alpha-2-antiplasmin (A2AP/SERPINF2) deficiency is yet another blood disorder characterized by excessive bleeding. A2AP is a serine protease inhibitor that functions in inactivating plasmin and thereby inhibits fibrinolysis. A2AP deficiency is an especially rare disorder with a prevalence of less than 1 in 1,000,000 that occurs in a homozygous or heterozygous form. In the homozygous form, A2AP deficiency presents with severe bleeding characterized by spontaneous hemorrhage and hemarthrosis. The heterozygous form has variable presentation that can be associated with bleeding post-surgery/injury, and spontaneous musculoskeletal bleeds. No effective, long-lasting prophylactic treatments exist for the treatment of A2AP deficiency.
[0696] Disrupted hemostasis can also result from disorders of platelet function. As discussed above, platelet activation, adhesion, and aggregation are critical steps in clot formation and stabilization. Abnormal levels and/or functioning of platelets can result in
excessive bleeding (e.g., epistaxis, nosebleeds, gum bleeding, menorrhagia, and prolonged bleeding after cuts or surgery). Platelet disorders can be heritable or acquired. Examples of congenital disorders of platelet function include but are not limited to Glanzmann’s thrombasthenia, Bernard-Soulier syndrome, Chromosome 22ql 1.2 deletion syndromes, platelet-type VWF (PT-VWD), gray platelet syndrome, May-Hegglin anomaly, Epstein syndrome, Fechter syndrome, Sebastian syndrome, Wiskott-Aldrich syndrome, Chediak- Higashi syndrome, Hermansky-Pudlak syndrome, and storage pool/ secretion disorder. Nonlimiting examples of acquired disorders of platelet function include use of certain medications (e.g., aspirin, dipyridamole, clopidogrel, and ibuprofen), liver disease, uremia, and myeloproliferative disorders (e.g., essential thrombocythemia).
[0697] Abnormal bleeding can also be hallmarks of certain heritable connective tissue disorders, resulting from abnormal vasculature with increased vulnerability to injury and abnormal interactions with platelets and coagulation factors. Examples of such disorders include hereditary hemorrhagic telangiectasia (HHT)/Osler-Weber-Rendu (OWR) disease, which is characterized by formation of anteriovenous malformations (AVM) in internal organs, and telangiectasia on mucocutaneous surfaces including skin, gastrointestinal mucosa, and upper respiratory tract. HHT features an autosomal dominant pattern of inheritance and has a prevalence of 1/5000. The majority of HHT patients (80%) have an identifiable causative mutation in ENG, ACVRL1, or MADH4 genes, all of which are involved in TGF-p/BMP signaling pathway required for smooth muscle differentiation and vascular modeling. Mutations in each gene are distinctly associated with particular clinical subtypes of HHT. Specifically, HHT Type 1, accounting for about 60% of all HHT cases, is associated with mutations in ENG (chromosome 9q34.11) and presents with AVM in lungs and brain. HHT Type 2, accounting for about 38% of all HHT cases, is associated with mutations in ACVRL1 (chromosome 12ql 3.13) and presents with AVM in liver, lungs, and spine. The third subtype, HHT with juvenile polyposis coli, is associated with mutations in MADH4 (chromosome 18q21.2), presents with AVM and gastrointestinal polyps, and accounts for about 2% of all HHT cases. Among HHT patients, clinical presentation is highly variable and is associated with an increased risk for cerebral abscess, migraine, ischemic/embolic stroke, heart failure, colon cancer, and bleeding complications such as, e.g., epistaxis, gastrointestinal bleeding, hemorrhagic stroke secondary to CNS malformation, pulmonary hemorrhage, increased risk of mortality in pregnancy associated with pulmonary hemorrhage and CNS bleeds, and iron deficiency. Available treatment options for HHT include invasive techniques such as surgery cryotherapy, and ablation, treatment with TXA,
hormonal therapy (e.g., estrogen, tamoxifen, or danazol), or an anti -angiogenic therapy (e.g., thalidomide and bevacizumab).
[0698] Deficiency in anti -coagulation factors can also result in abnormal hemostasis. Loss of regulation of these factors results in an increased tendency to form a thrombus. For example, congenital deficiency in AT is an autosomal dominant disease state characterized by increased propensity for clotting, resulting in a 5-50 fold increase in the risk of thrombosis. Congenital AT deficiency is reported to occur with a prevalence of 1:500 to 1:5000. Two subtypes of AT have been identified, Type 1 (quantitative defect) and Type 2 (qualitative defect). Type 1 AT deficiency is associated with a decrease in AT activity and blood concentration and can be further divided into subgroup la, featuring normal affinity for heparin, and subgroup lb which features reduced affinity for heparin. Type 1 AT deficiency are predominately due to point mutations, deletions, or insertions within the AT gene. Type 2 AT deficiency is associated with normal AT levels, but reduced AT activity and is further divided into 3 subgroups, namely subgroup 2a, featuring decreased thrombin inactivation, FXa inactivation, and heparin affinity, subgroup 2b, featuring decreased thrombin inactivation and normal heparin affinity, and subgroup 2c, featuring normal thrombin inactivation and Xa inactivation and decreased heparin affinity. AT deficiency can also be acquired by one of three ways: (1) increased AT excretion, e.g., in renal failure associated with proteinuria nephrotic syndrome or in burns; (2) decreased AT production, e.g., as observed in liver dysfunction; or (3) accelerated consumption of AT, e.g., as a result of injury or invasive surgical procedures. Current therapies for congenital AT deficiency rely on anticoagulation therapies, however, these treatments are associated with an increased risk of spontaneous hemorrhage. Other therapies include use of low molecular weight heparin with addition of AT concentrate to overcome heparin resistance. However, AT concentrate is administered as an intravenous infusion, making it suitable only for short-term treatments (e.g., peri-operative bridging).
[0699] In some embodiments, a blood disorder characterized by excessive bleeding is selected from a von Willebrand disease (VWD), hemophilia A, disorders of platelet function, and connective tissue disorders. In some embodiments, a blood disorder characterized by excessive bleeding is VWD. In some embodiments, the VWD is congenital VWD (cVWD). In some embodiments, the VWD is acquired VWD (aVWD). In some embodiments, the aVWD includes Heydes syndrome. In some embodiments, the VWD is type 1 VWD. In some embodiments, the VWD is type 2A VWD. In some embodiments, the VWD is type 2B VWD. In some embodiments, the VWD is type 2M VWD. In some embodiments, the VWD
is type 2N VWD. In some embodiments, the VWD is type 3 VWD. In some embodiments, a blood disorder characterized by excessive bleeding is hemophilia A. In some embodiments, a blood disorder characterized by excessive bleeding is a disorder of platelet function. In some embodiments, a disorder of platelet function is Glanzmann’s thrombasthenia. In some embodiments, a disorder of platelet function is Bernard-Soulier syndrome. In some embodiments, a disorder of platelet function is a chromosome 22ql 1.2 deletion syndrome. In some embodiments, a disorder of platelet function is platelet type VWD. In some embodiments, a disorder of platelet function is gray platelet syndrome. In some embodiments, a disorder of platelet function is May-Hegglin anomaly. In some embodiments, a disorder of platelet function is Epstein syndrome. In some embodiments, a disorder of platelet function is Fechter syndrome. In some embodiments, a disorder of platelet function is Sebastian syndrome. In some embodiments, a disorder of platelet function is Wiskott-Aldrich syndrome. In some embodiments, a disorder of platelet function is Chediak-Higashi syndrome. In some embodiments, a disorder of platelet function is Hermansky-Pudlak syndrome. In some embodiments, a disorder of platelet function is a storage pool/secretion disorder. In some embodiments, a disorder of platelet function is an acquired disorder of platelet function resulting from use of certain medications (e.g., aspirin, dipyridamole, clopidogrel, and ibuprofen. In some embodiments, a disorder of platelet function is an acquired disorder of platelet function due to liver disease. In some embodiments, a disorder of platelet function is an acquired disorder of platelet function due to uremia. In some embodiments, a disorder of platelet function is an acquired disorder of platelet function due to a myeloproliferative disorder (e.g., essential thrombocythemia). In some embodiments, a disorder of platelet function is idiopathic, but evident in one or more assays used to assess platelet function. In some embodiments, a blood disorder characterized by excessive bleeding is a connective tissue disorder. In some embodiments, a connective tissue disorder is HHT. In some embodiments, the HHT is type 1 HHT. In some embodiments, the HHT is type 2 HHT. In some embodiments, the HHT is HHT with juvenile polyposis coli.
[0700] The antibody or the pharmaceutical composition disclosed herein are, in some embodiments, administered to the subject in need thereof in an amount and for a time sufficient to treat one or more symptoms 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.
[0701] Disclosed herein, in certain embodiments, are methods of accumulating VWF protein in blood plasma of a subject in need thereof, comprising administering to the subject a composition comprising an antibody or pharmaceutical composition disclosed herein. In some embodiments, the accumulation of the VWF protein results in a blood plasma level of the VWF protein that is at least 1.3-fold, 1.4-fold, 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 VWF protein in the absence of the antibody. In some embodiments, the accumulation of the VWF protein results in a blood plasma level of the VWF 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 VWF protein in the absence of the antibody. In some embodiments, the degree of accumulation of a VWF protein depends on the effective amount of an antibody or antigen-binding fragment thereof administered to a subject, as described herein.
[0702] Disclosed herein, in certain embodiments, are methods of accumulating Factor VIII protein in blood plasma of a subject in need thereof, comprising administering to the subject a composition comprising an antibody or pharmaceutical composition disclosed herein. In some embodiments, the accumulation of the Factor VIII protein results in a blood plasma level of the Factor VIII 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 Factor VIII protein in the absence of the antibody. In some embodiments, the accumulation of the Factor VIII protein results in a blood plasma level of the Factor VIII 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 the blood plasma level of a VWF protein in the absence of the antibody. In some embodiments, the degree of accumulation of a FVIII protein depends on the effective amount of an antibody or antigen-binding fragment thereof administered to a subject, as described herein.
[0703] Also disclosed herein, in certain embodiments, are methods of increasing bloodplasma half-life of a VWF protein in a subject in need thereof, comprising administering to the subject a composition comprising an antibody or pharmaceutical composition disclosed herein. In some embodiments, the antibody increases the blood plasma half-life of the VWF protein by 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 as compared to the blood plasma half-life of the VWF protein in the absence of the antibody. In some embodiments, the antibody increases the blood plasma half-life of the VWF protein by 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%, or 10,000% as compared to the blood plasma half-life of the VWF protein in the absence of the antibody.
[0704] Any of the methods disclosed herein, in some instances, further include administering to the subject an additional therapeutic modality. Non-limiting examples of additional therapeutic modalities include therapeutic agents other than the antibody of the disclosure (e.g, compounds, peptides, nucleic acids, gene therapy, cell therapy etc.). In some embodiments, other antibodies, small molecule therapeutics, and/or other agents are combined in separate compositions for simultaneous or sequential administration. In one embodiment, simultaneous administration comprises one or more compositions that are administered at the same time, or within 30 minutes of each other. In some embodiments, administration occurs at the same or different sites.
Route of Administration
[0705] Antibodies or antigen-binding fragments thereof are formulated for any suitable route of administration to a subject including, but not limited to injection (e.g., intravenous injection), in some embodiments. Injection includes, e.g., subcutaneous, peritoneal, intravenous injection, intramuscular injection, or spinal injection into the cerebrospinal fluid (CSF). In some embodiments, the antibodies of the disclosure are formulated for subcutaneous administration. In some embodiments, the antibodies of the disclosure are formulated for peritoneal administration. In some embodiments, the antibodies of the disclosure are formulated for intravenous administration (e.g., intravenous injection or infusion). In some embodiments, the antibodies of the disclosure are formulated for
intramuscular administration. In some embodiments, the antibodies of the disclosure are formulated for spinal injection into the cerebrospinal fluid (CSF) administration. In some embodiments, administration is in one, two, three, four, five, six, seven, or more injection sites. In some embodiments, administration is in one injection site. In some embodiments, administration is in two injection sites. In some embodiments, administration is in three injection sites. In some embodiments, administration is in four injection sites. In some embodiments, administration is in five injection sites. In some embodiments, administration is in six injection sites.
[0706] For in vivo applications, contacting occurs, e.g., via administration of a composition (e.g, a composition described herein) to a subject by any suitable means. An antibody described herein, in some embodiments, is administered, e.g., either systemically or locally, including via parenteral, subcutaneous, intraperitoneal, intracerebrospinal, intrapulmonary, and intranasal administration, and, if desired for local treatment, intralesional administration. Parenteral routes include, e.g., intravenous, intraarterial, intraperitoneal, epidural, intramuscular, and intrathecal administration. Such administration, in some embodiments, is as a bolus, continuous infusion, or pulse infusion. In some embodiments, compositions are administered by injection depending in part on whether the administration is brief or chronic. Other modes of administration methods are contemplated, including topical, particularly transdermal, transmucosal, rectal, oral, or local administration e.g., through a catheter placed close to the desired site.
Diagnostic Products and Methods
[0707] Disclosed herein, in certain embodiments, are methods of detection of a VWF protein in a sample or a subject to assess a treatment state of a patient or diagnose a disease or disorder described herein.
[0708] In the in vivo detection, diagnosis or monitoring of soluble VWF protein, or expression of a VWF protein by cells or tissues, a subject is administered an antibody or antigen-binding fragment as described herein, which antibody or antigen-binding fragment is bound to a detectable moiety. The detectable moiety is visualized, in some embodiments, using art-recognized methods such as, but not limited to, magnetic resonance imaging (MRI), fluorescence, radioimaging, light sources supplied by endoscopes, laparoscopes, or intravascular catheter (i.e., via detection of photoactive agents), photoscanning, positron emission tomography (PET) scanning, whole body nuclear magnetic resonance (NMR), radioscintigraphy, single photon emission computed tomography (SPECT), targeted near infrared region (NIR) scanning, X-ray, ultrasound. Labels for detecting compounds using
such methods are also known in the art. Visualization of the detectable moiety allows, in some embodiments, for detection, diagnosis, and/or monitoring of a disease or disorder in the subject. Additional diagnostic assays that utilize antibodies specific to the desired target protein are known in the art and are also contemplated herein.
[0709] For in vitro detection methods, samples to be obtained from a subject include, but are not limited to, blood, tissue biopsy samples, and fluid therefrom.
[0710] Thus, the disclosure provides antibodies and antigen-binding fragments thereof that are useful for detecting or diagnosing VWF level or activity associated with one or more of the disorders described herein, potentially indicating need for therapeutic treatment. In some embodiments, the antibody further comprises a second agent. Such an agent, in some embodiments, is a molecule or moiety such as, e.g., a reporter molecule or a detectable label. Detectable labels/moieties for such detection methods are known in the art and are described in more detail below. Reporter molecules are any moiety which are detected using an assay. Non-limiting examples of reporter molecules which have been conjugated to polypeptides include enzymes, radiolabels, haptens, fluorescent labels, phosphorescent molecules, chemiluminescent molecules, chromophores, luminescent molecules, photoaffinity molecules, and colored particles or ligands, such as biotin. In some embodiments, detectable labels include compounds and/or elements that are detected due to their specific functional properties, and/or chemical characteristics, the use of which allows the polypeptide to which they are attached to be detected, and/or further quantified if desired. Many appropriate detectable (imaging) agents are known in the art, as are methods for their attachment to polypeptides.
[0711] Polypeptides are conjugated to a wide variety of fluorescent dyes, quenchers, and haptens such as fluorescein, R-phycoerythrin, and biotin in some embodiments. In some embodiments, conjugation occurs either during polypeptide synthesis or after the polypeptide has been synthesized and purified.
[0712] Alternatively, an antibody, antigen-binding fragment or binding protein is conjugated with a fluorescent moiety in some embodiments. Conjugating polypeptides with fluorescent moieties (e.g., R-Phycoerythrin, fluorescein isothiocyanate (FITC), etc.) is, e.g., accomplished using art-recognized techniques. Numerous commercially available fluorescent dyes and dye-conjugation kits are commercially available for particular applications, such as fluorescence microscopy, flow cytometry, fluorescence-activated cell sorting (FACS), etc. [0713] In one non-limiting embodiment, an antibody antigen-binding fragment is associated with (conjugated to) a detectable label, such as a radionuclide, a dye, an imaging
agent, or a fluorescent agent for immunodetection of binding to antigen which is used to visualize binding of the antibodies to soluble or bound VWF protein in vitro and/or in vivo. [0714] Non-limiting examples of radiolabels include, e.g, 32P, 33P, 43K, 52Fe, 57Co, 64Cu, 67Ga, 67Cu, 68Ga, 71Ge, 75Br, 76Br, 77Br, 77As, 77Br, 81Rb/81mKr, 87mSr, 90Y, 97Ru, "Tc, "mTc, 100Pd, 101Rh, 103Pb, 105Rh, 109Pd, mAg, mIn, 113In, 119Sb, 121Sn, 123I, 125I, 127Cs, 128Ba, 129Cs, 131I, 131Cs, 143Pr, 153Sm, 161Tb, 166Ho, 169Eu, 177Lu, 186Re, 188Re, 189Re, 191Os, 193Pt, 194Ir, 197Hg, 199 Au, 203Pb, 211At, 212Pb, 212Bi, and 213Bi. In some embodiments, radiolabels are attached to compounds using conventional chemistry known in the art of antibody imaging. Radiolabeled compounds are useful in in vitro diagnostics techniques and in in vivo radioimaging techniques and in radioimmunotherapy.
[0715] Compositions of antibodies and antigen-binding fragments described herein are also used as non-therapeutic agents (e.g., as affinity purification agents) in some embodiments.
Combination Therapy
[0716] The antibodies and compositions described herein are administered in combination with one or more (e.g, 1, 2, 3, 4, 5 or more) additional therapeutic agents or modalities for treatment of a disease or disorder described herein (e.g., a blood disorder characterized by excessive bleeding), in some embodiments.
[0717] In some embodiments, the one or more additional therapeutic agents is 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), or a concentrate of recombinant VWF protein (e.g., Vonicog alfa), or a concentrate of FVIII protein (e.g., Alphanate and Koate- HP). In cases where the blood disorder is heavy menstrual bleeding, the one or more additional therapeutic agents is a hormonal treatment, such as, e.g, an oral contraceptive pill (e.g, an estrogen-containing contraceptive) or an intrauterine device, in some embodiments. 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 for whom 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.
[0718] In some embodiments, the one or more additional therapeutic modalities include blood transfusion, platelet transfusion, surgery, or cauterization. In some embodiments, the one or more additional therapeutic modalities include blood transfusion. In some embodiments, the one or more additional therapeutic modalities include platelet transfusion. In some embodiments, the one or more additional therapeutic modalities include surgery. In some embodiments, the one or more additional therapeutic modalities include cauterization. [0719] In some embodiments, a composition (an antibody or an antigen-binding fragment described herein) is administered alone or in combination with a second composition either simultaneously or sequentially dependent upon the condition to be treated.
Antibody Technology
[0720] As will be understood by the skilled artisan, general description of antibodies herein and methods of preparing and using the same also apply to individual antibody polypeptide constituents and antibody fragments.
[0721] The antibodies of the present disclosure are monoclonal or polyclonal antibodies. In some embodiments, the antibodies of the disclosure are monoclonal. In some embodiments, the antibodies of the disclosure are polyclonal. In particular embodiments, antibodies of the present disclosure are human antibodies. Methods of producing polyclonal and monoclonal antibodies are known in the art (see, e.g., Azevedo Reis Teixeira et al. mAbs 13:1 (2021). Antibodies, antigen-binding fragments, and other proteins that bind VWF are generated using such methods are tested for one or more of their binding affinity, avidity, and modulating capabilities in some embodiments.
[0722] In some embodiments, the antibodies of the present disclosure are one-armed antibodies (e.g., comprising a single heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain). In some embodiments, the antibodies of the present disclosure are intact immunoglobulin molecules, such as, e.g., a human antibody, as well as those portions of a humanized Ig molecule that contain the antigen-binding site (i.e., paratope) or a single heavy chain and a single light chain, including those portions known in the art as Fab, Fab’, F(ab)’, F(ab’)2, Fd, scFv, a variable heavy domain, a variable light domain, a variable NAR domain, a single chain binding polypeptide, a dAb fragment, a nanobody, a VHH, and others also referred to as antigen-binding fragments. When constructing an immunoglobulin molecule or fragments thereof, variable regions or portions thereof are, in some embodiments, fused to, connected to, or otherwise joined to one or more constant regions or portions thereof to produce any of the antibodies or fragments thereof
described herein. Thus, in some embodiments, the antigen-binding fragment of any one of the antibodies described above is a Fab, Fab’, F(ab)’, F(ab’)2, Fd, scFv, a variable heavy domain, a variable light domain, a variable NAR domain, a dAb fragment, a nanobody, a VHH, a single chain binding polypeptide (e.g., a scFv with Fc portion) or any other functional fragment thereof as described herein.
[0723] In some embodiments, antibodies of the present disclosure are of any immunoglobulin class, and, therefore, in some embodiments, have a gamma, mu, alpha, delta, or epsilon heavy chain. In some embodiments, the gamma chain is gamma 1, gamma 2, gamma 3, or gamma 4. In some embodiments, the alpha chain is alpha 1 or alpha 2.
[0724] In some embodiments, an antibody of the present disclosure is an IgA immunoglobulin. In some embodiments, antibodies of the present disclosure are of any IgA subclass. In some embodiments, the antibody is IgAl. In some embodiments, the antibody is IgA2. In some embodiments, an antibody of the present disclosure is an IgD immunoglobulin. In some embodiments, an antibody of the present disclosure is an IgE immunoglobulin In some embodiments, an antibody of the present disclosure is an IgG immunoglobulin. In some embodiments, antibodies of the present disclosure are of any IgG subclass. In some embodiments, the antibody is IgGl. In some embodiments, the antibody is IgG2. In some embodiments, the antibody is IgG3. In some embodiments, the antibody is IgG4. In some embodiments, an antibody of the present disclosure is an IgM immunoglobulin.
[0725] In some embodiments, antibodies of the present disclosure comprise a variable light chain that is either kappa or lambda. In some embodiments, the lambda chain is of any subtype, including, e.g., lambda 1, lambda 2, lambda 3, and lambda 4. In some embodiments, the light chain is kappa.
[0726] In some embodiments, an antibody of the present disclosure has one binding site for the VWF protein (e.g., a binding site to a single epitope of the VWF protein). In some embodiments, an antibody of the present disclosure is monospecific. Exemplary monospecific antibodies bind one epitope of a single antigen. In some embodiments, the monospecific antibody is a monovalent antibody (e.g., having a single Fab domain and a single Fc domain; a one-armed antibody).
[0727] In some embodiments, an antibody of the present disclosure is a SMIP or binding domain immunoglobulin fusion protein specific for the target protein. These constructs are single-chain polypeptides comprising antigen-binding domains fused to immunoglobulin domains necessary to carry out antibody effector functions.
[0728] In some embodiments, an antibody of the present disclosure comprises a single chain binding polypeptide having a heavy chain variable region, and/or a light chain variable region which binds an epitope disclosed herein and has, optionally, an immunoglobulin Fc region. Such a molecule is a single chain variable fragment (scFv) optionally having effector function or increased half-life through the presence of the immunoglobulin Fc region.
[0729] In some embodiments, VWF -binding antibodies include at least one heavy chain and at least one light chain. In some embodiments, VWF -binding antibodies include one heavy chain and one light chain. In some embodiments, VWF -binding antibodies include at least one heavy chain comprising a heavy chain variable domain (VH) and at least one light chain comprising a light chain variable domain (VL). In some embodiments, the VWF- binding antibodies of the disclosure include a single full-length heavy chain, a single truncated heavy chain lacking VH and CHI domains, and a single light chain. In some embodiments, VWF antibodies include one heavy chain comprising a VH and one light chain comprising a VL.
[0730] In some embodiments, the antibody disclosed herein is a monoclonal antibody In some embodiments, an antibody disclosed herein is a monospecific and monovalent antibody containing a single arm of an immunoglobulin molecule (e.g., a one-armed antibody that includes a single full-length heavy chain, a single truncated heavy chain lacking VH and CHI domains, and a single light chain). In some embodiments, an antibody disclosed herein is selected from a half-immunoglobulin (e.g., a one-armed antibody) or whole immunoglobulin. In some embodiments, an antibody disclosed herein is a one-armed antibody. In some embodiments, an antibody disclosed herein is an antigen binding fragment. In some embodiments, an antibody disclosed herein is human. In some embodiments, an antibody disclosed herein is humanized. In some embodiments, an antibody disclosed herein is chimeric.
Packages, Kits, and Pre-Filled Containers
[0731] Also provided herein are kits containing one or more compounds described above. The kit comprises, in some embodiments, an antibody or antigen-binding fragment thereof as described herein in suitable container means.
[0732] In some embodiments, there is provided is a container means comprising a composition described herein. In some embodiments, the container means is any suitable container which houses, e.g., a liquid or lyophilized composition including, but not limited to, a vial, syringe, bottle, and an intravenous (IV) bag or ampoule. A syringe holds any volume
of liquid suitable for injection into a subject, including, but not limited to, 0.5 cc, 1 cc, 2 cc, 5 cc, 10 cc, or more.
[0733] Provided herein are kits comprising a composition or compositions described herein. In some embodiments, provided herein is a kit for treating a subject having a blood disorder characterized by excessive bleeding comprising an antibody as described herein and, optionally, an additional therapeutic agent.
[0734] In some embodiments, provided herein is a kit for treating a blood disorder characterized by excessive bleeding comprising an antibody as described herein and a label attached to or packaged with the container, the label describing use of the antibody, optionally, in combination with an additional therapeutic agent.
[0735] In some embodiments, the container means of the kits will generally include at least one vial, test tube, flask, bottle, ampoule, syringe, an intravenous (IV) bag, and/or other container means, into which at least one antibody of the disclosure is placed, and/or preferably, suitably aliquoted. Provided herein is a container means comprising a composition described herein.
[0736] The kits, in some embodiments, include a means for containing at least one fusion protein, detectable moiety, reporter molecule, and/or any other reagent containers in close confinement for commercial sale. In some embodiments, such containers include injection and/or blow-molded plastic containers into which the desired vials are retained. In some embodiments, kits also include printed material for use of the materials in the kit.
[0737] Packages and kits additionally include a buffering agent, a preservative, and/or a stabilizing agent in a pharmaceutical formulation, in some embodiments. In some embodiments, each component of the kit is enclosed within an individual container and all of the various containers are within a single package. In some embodiments, disclosure kits are designed for cold storage or room temperature storage.
[0738] Additionally, in some embodiments, the preparations contain stabilizers to increase the shelf-life of the kits and include, e.g., bovine serum albumin (BSA). Where the compositions are lyophilized, the kit contains, in some embodiments, further preparations of solutions to reconstitute the lyophilized preparations. Acceptable reconstitution solutions are well known in the art and include, e.g. , pharmaceutically acceptable phosphate buffered saline (PBS)In some embodiments, packages and kits further include one or more components for an assay, such as, e.g., an ELISA assay. Samples to be tested in this application include, e.g., blood, plasma, serum, tissue sections and secretions, urine, lymph,
and products thereof. In some embodiments, packages and kits further include one or more components for collection of a sample (e.g., a syringe, a cup, a swab, etc.).
[0739] In some embodiments, packages and kits further include a label specifying information required by US FDA or similar regulatory authority, e.g., a product description, amount and mode of administration, and/or indication of treatment. In some embodiments, packages provided herein include any of the compositions as described herein.
[0740] The term “packaging material” refers to a physical structure housing the components of the kit. In some embodiments, the packaging material maintains the components sterile and is made of material commonly used for such purposes (e.g., paper, corrugated fiber, glass, plastic, foil, ampules, etc.). In some embodiments, the label or packaging insert includes appropriate written instructions (e.g., instructing the user of the kit to perform one or more methods disclosed herein). Kits, in some embodiments, additionally include labels or instructions for using the kit components in any method of the disclosure. In some embodiments, a kit includes a compound in a pack or dispenser together with instructions for administering the compound in a method described herein.
[0741] In still further embodiments, a kit further comprises a container means for one or more additional therapeutics for a blood disorder characterized by excessive bleedingin some embodiments, instructions include instructions for practicing any of the methods described herein including treatment methods. In some embodiments, instructions additionally include indications of a satisfactory clinical endpoint or any adverse symptoms that occur, or additional information required by regulatory agencies such as the Food and Drug Administration for use on a human subject.
[0742] The instructions are, in some embodiments, on “printed matter,” e.g., on paper or cardboard within or affixed to the kit, or on a label affixed to the kit or packaging material, or attached to a vial or tube containing a component of the kit. Instructions are additionally included on a computer readable medium, such as, e.g., CD-ROMs, DVDs, flash memory devices, solid state memory, magnetic disks and disk devices, magnetic tapes, cloud computing systems and services, and the like, in some embodiments. In some cases, the program and instructions are permanently, substantially permanently, semi-permanently, or non-transitorily encoded on the media.
[0743] Provided herein is a container means comprising a composition described herein. In some embodiments, the container means is any suitable container which houses a liquid or lyophilized composition including, but not limited to a vial, syringe, bottle, intravenous (IV)
bag, or ampoule. A syringe, in some embodiments, holds any volume of liquid suitable for injection into a subject, including but not limited to 0.5 cc, 1 cc, 2 cc, 5 cc, 10 cc or more. [0744] Provided herein are kits comprising a composition described herein. In some embodiments, provided herein is a kit for treating a blood disorder characterized by excessive bleeding, comprising an antibody as described herein, optionally, in combination with one or more additional therapeutic agents.
[0745] In some embodiments, provided herein is a kit for treating a blood disorder characterized by excessive bleeding, comprising an antibody as described herein, and a label attached to or packaged with the container, the label describing use of the antibody or an antigen-binding fragment thereof as described herein, optionally, with an additional therapy. In some embodiments, the blood disorder characterized by excessive bleeding is VWD, hemophilia A, disorders of platelet function, and connective tissue disorders. In some embodiments, the VWD is cVWD or 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.
Examples
[0746] The following examples are put forth to provide those of ordinary skill in the art with a description of how the compositions and methods described herein may be used, made, and evaluated, and are intended to be purely exemplary of the disclosure and are not intended to limit the scope of what the inventors regard as their invention.
Example 1: Recombinant expression and purification of von Willebrand factor cysteine knot domain constructs
[0747] Protein constructs for the expression of the human and cynomolgus monkey (“cyno”) VWF cysteine knot (CK) domains were designed according to Zhou et al. Blood 123: 1785-93 (2014) with the sequences provided in SEQ ID NO: 5 and SEQ ID NO: 6, respectively. In addition to the CK domain sequence, the constructs were equipped with an N-terminal signal peptide derived from VWF followed by a hexa-histidine tag (SEQ ID NO: 11), in vitro biotinylation tag, HRV-3C protease cleavage site, and 3 residues from VWF immediately prior to the CK domain. Expression, purification, and in vitro biotinylation were performed using HEK293 EBNA cells and a BirA biotin-protein ligase kit. Consistent with the CK domain carrying one N-glycan and forming disulfide-linked homodimers, the two protein constructs were found to migrate with apparent molecular weights of 35-kDa and 16- kDa under non-reducing and reducing conditions, respectively.
Example 2. Generation of anti-VWF CK domain antibodies using phage and yeast display
[0748] Human monoclonal antibodies to the human biotinylated VWF cysteine knot (CK)-domain were identified. Methods for antibody library design and antibody selections by phage and yeast display are well-known. During antibody selections, the biotinylated human VWF CK domain was used as a primary antigen. From the pool of apparent high-affinity antibody binders, antibodies cross-reacting with the biotinylated cyno VWF CK domain were selected. An overview of the selection protocol is provided in FIG. 1.
[0749] In a first round of screening, a total of 63 antibodies in single-chain variable fragment (scFv) format were identified from the phage/yeast selection campaign. Amino acid sequences of the variable heavy chain (VH) and VLs of each antibody are provided in Table 1 along with sequences of the associated complementarity determining region 1 (CDR1), CDR2, and CDR3 loops. CDR loop sequences were extracted from each VH and VL using ANARCI and the IMGT scheme
Example 3: Production of anti-VWF antibodies using hybridoma technology
[0750] Protein constructs containing a CK domain of VWF (e.g., SEQ ID NO: 5 and/or SEQ ID NO: 6) are injected (e.g, intravenously) into a mouse host by one or more (e.g, 1, 2, 3, 4, 5, 6, or more) injections over the course of several weeks. B cells clones are harvested from the mouse. The harvested B cells are fused with immortal myeloma cells using, e.g., electrofusion or polyethylene glycol (PEG) induction to produce hybridoma cells expressing antibodies specific to the CK domain of VWF (e.g., SEQ ID NO: 5 and/or SEQ ID NO: 6). Prior to fusion, myeloma cells are selected for ability to grow in culture and to ensure they do not intrinsically produce antibodies and lack expression of the HGPRT gene. Fused cells are cultured in HAT (hypoxanthine-aminoptern-thymidine) medium for about 10-14 days.
Unfused myeloma cells are removed from culture. The incubated medium is diluted into multi-well plates, such that each well contains one hybridoma cell.
[0751] Following incubation, hybridomas are screened and selected for antibodies having desirable specificity to the CK domain of VWF. Screening is performed using standard techniques, such as, e.g., ELISA, western blot, immunocytochemistry, or immunoprecipitation-mass spectrometry. Selected hybridomas are transferred to tissue culture flasks and cultured to establish a colony of hybridoma cells that produce the anti- VWF antibody. Antibodies are isolated and purified using routine and conventional methods.
Example 4: Production of anti-VWF antibodies using transgenic animals
[0752] A transgenic animal host (e.g., mouse) is produced by genetically modifying the host germ line to replace endogenous loci encoding immunoglobulin (Ig) genes with a transgene(s) encoding human or non-human primate (e.g. , Macaca fascicularis) Ig in the host genome. For example, the murine endogenous locus encoding variable, diversityjoining, and constant region gene segments is substituted with corresponding human gene segments as described in Jakobovits et al., Proc Natl Acad Sci USA, 90:2551 (1993); Jakobovits et al., Nature 362:255-58 (1993); Bruggemann et al., Year in Immunol., 7:33 (1993); U.S. Pat. Nos. 5,545,806, 5,569,825, 5,591,669; U.S. Pat. No. 5,545,807; and WO 97/17852. The transgenic host is subsequently inoculated with an antigen encoding the human (SEQ ID NO: 5) or non- human primate (SEQ ID NO: 6) CK domain of VWF protein to stimulate production of human or non-human primate antibodies against the CK domain. Optionally, B cells are isolated from the host and hybridoma cells are produced according to the methods described in Example 3. Antibodies targeting the CK domain of VWF are isolated and purified according to routine and conventional methods.
Example 5: High-throughput screening of identified antibodies for binding to human and non-human primate VWF CK domain.
[0753] The 63 identified antibody sequences from the phage/yeast selection campaign (FIG. 1; Examples 1 and 2) were cloned into a yeast expression vector (pFLYS6) and expressed in Saccharomyces cerevisiae as soluble scFvs equipped with C-terminal 3xFLAG and SV5 tags. The scFv constructs had a VH-linker-VL configuration with the linker consisting of the amino acid sequence SGGSTITSYNVYYTKLSSSGT (SEQ ID NO: 483). [0754] To initially characterize the ability of the scFv constructs to bind biotinylated human and cyno VWF CK domain constructs, Surface Plasmon Resonance (SPR) experiments were conducted. Briefly, a sensor chip was activated and coupled with an anti- SV5 mouse monoclonal antibody using amine coupling. The soluble scFvs in crude yeast supernatants were printed on the anti-SV5 lawn. Binding to the biotinylated human VWF CK domain was measured at room temperature and pH 7.4 (in 10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% Tween 20, pH 7.4 and 0.5 mg/mL BSA) or pH 5.5 (in 20 mM MES, 150 mM NaCl, pH 5.5, and 0.5 mg/mL BSA) by injection of a concentration range of CK domain from 0.3 to 500 nM. Similarly, binding to the biotinylated cyno VWF CK domain was measured at room temperature and pH 7.4. From the measured association (kon) and
dissociation (koff) rate constants, an apparent equilibrium dissociation constant (Ka = koff/kon) was estimated. Due to the dimeric state of the CK construct and consequent possibility for simultaneous binding of captured scFv to both monomers in the CK dimer, the SPR setup was expected to overestimate the binding affinity. Nevertheless, high-throughput binding study demonstrated that all 63 scFv candidates were capable of binding the human VWF CK domain construct at pH 7.4 with apparent Ka values ranging from about 50 pM to 10 nM. Several scFv candidates retained binding to human VWF CK at pH 5.5 and cyno VWF CK at pH 7.4. Results are summarized in Table 2.
Table 2. Overview of binding properties of scFv anti- VWF CK domain antibodies
[0755] Binding to human VWF CK domain was measured at pH 7.4 and 5.5 and to cyno VWF CK domain at pH 7.4. Apparent Ka values estimated from the binding kinetics are listed. ND, not determined.
Example 6: Recombinant expression and purification of anti-VWF CK domain for binding studies
[0756] For in vitro characterization studies, human and cyno VWF CK domains were modified with an N-terminal signal peptide derived from VWF followed by a hexa-histidine tag (SEQ ID NO: 11), StrepTagll, HRV-3C protease cleavage site, and three residues from VWF immediately N-terminal to the CK domain. In addition, a HA-tag was added to the C- terminus. Amino acid sequences are provided in Table 3.
Table 3. VWF CK domain constructs
[0757] The corresponding DNA sequences were synthesized and inserted between the Xbal and Agel restriction sites of the pcDNA3.4 vector. Expression was performed using Gibco CHO cells and a transient expression system essentially. Cells were maintained at 37°C in a humidified atmosphere of 8% CO2 with orbital shaking and sub-cultivated every 3-4 days in a cell medium prior to transfection.
[0758] Cells were transfected at a cell density of about 6 million cells/mL using a suitable reagent. For each 100 mL of cells, transfection was performed by diluting a total of 80 pL (1 mg/mL) DNA into 4 mL serum-free medium and combining this with 320 pL transfection reagent mixed with 3.7 mL serum-free medium. The mixture was then transferred to the cell culture. One day post-transfection, 600 pL transfection enhancer was added together with 24 mL culture feed. Cell culture supernatants were harvested 7-8 days post-transfection by centrifugation and followed by filtration.
[0759] Purification of expressed VWF CK domain was conducted by affinity chromatography utilizing the His-tag and standard purification methods. Briefly, clarified culture medium was loaded onto a HisTrap Excel column equilibrated in 20 mM HEPES, 100 mM NaCl, pH 7.4 (Buffer A). Following washing with 6% (v/v) Buffer B (20 mM HEPES, 100 mM NaCl, 500 mM Imidazole, pH 7.4) in Buffer A, bound protein was eluted with a linear gradient of 0-100% Buffer B. Purified protein was up-concentrated using a spin concentrator and subsequently dialyzed into 20 mM HEPES, 100 mM NaCl, pH 7.3.
Example 7: Reformatting, expression, and purification of anti- VWF CK domain antibodies
[0760] Using the VH and VL sequences of antibodies produced in the first round of screening (see Table 1), antibodies were converted into desired formats for subsequent expression and purification. Table 4 lists the sequences of a selected set of antibodies configured to a monovalent (one-arm) human IgG4 format, also termed “OA” antibodies.
Table 4. Sequences of anti-VWF CK domain antibodies in monovalent (one-arm; OA) human IgG4 format
[0761] Abbreviations: HC trc, truncated heavy chain; VH HC, heavy chain containing VH; VL LC, light chain containing VL. All CDR sequences in Table 4 were defined using the IMGT scheme.
[0762] Here, the full-length HC contains S228P, F234A/L235A, T366S/L368A/Y407V, and delta-K447 mutations. The truncated HC (HC_trc) starts at residue 216 (EU numbering) and contains S228P, F234A/L235A, T366W, and delta-K447 mutations. The LC is human kappa. The T366W and T366S/L368A/Y407V mutations are the so-called knob/hole mutations that facilitate hetero-dimer assembly, i.e., pairing of HC and HC trc, and the F234A/L235A mutations are effector silencing mutations. As will be appreciated by a person of skill in the art, the knob/hole mutations can be interchanged between the HC and HC_trc, and mutations can be omitted or combined as needed.
[0763] Each of the three antibody chains (HC, HC_trc, and LC) were synthesized as DNA and cloned into the pcDNA3.1 vector. The expression of antibodies was performed using the CHO cells. Cells were expanded from a working cell bank and passaged in serum- free, protein-free, animal origin-free medium. Cells were cultured for 14 days, and the harvest was performed by filtration using 0.22 pm filtration units and DE as filter aid, after which antibodies were purified using standard affinity chromatographic methods.
Example 8: Binding of anti-VWF CK domain antibodies to recombinant human and cynomolgus monkey VWF CK domain
[0764] To determine the affinity of monovalent anti-VWF CK domain antibodies for the recombinant human and cyno CK domains and human plasma-derived VWF (e.g, free of FVIII), a solution-phase binding assay was performed. In this assay, a concentration range of antibody (0-140 nM) was allowed to bind to a fixed concentration (10 or 20 nM) of the CK domain or plasma-derived VWF in pH 7.4 (20 mM HEPES, 150 mM NaCl, 5 mM CaCh, 1% (w/w) BSA, pH 7.4) or pH 5.5 (20 mM MES, 150 mM NaCl, 5 mM CaCl2, 1% (w/w) BSA, pH 5.5) buffer. Following incubation for 30 min at room temperature to establish equilibrium, unbound antibody was quantified by ELISA using the immobilized human CK domain for capture and HRP -conjugated goat anti -human IgG Fc antibody for detection. By relating the measured ELISA signal to a standard curve prepared with defined concentrations of the same antibody in absence of CK or VWF, the concentration of unbound antibody in the equilibrium mixtures was determined. Incubation times in the ELISA were optimized to ensure minimal perturbation of the equilibrium between antibody and CK or VWF. See FIG. 2 for an outline of the assay.
[0765] The ELISA was prepared by coating a 96-well plate with 100 pL 2 pg/mL human VWF CK domain in TBS (10 mM Tris-HCl, 150 mM NaCl, pH 7.5) overnight at 5°C. Following a single wash of the plate with 200 pL of wash buffer (TBS containing 0.05%
(v/v) Tween-20 and 5 mM CaCh), the plate was blocked by incubation with 200 pL blocking buffer (TBS containing 5 mM CaCh and 1% (w/w) BSA) for 1 hour at room temperature. Before transfer of 100 pL of free antibody or antib ody/CK/VWF equilibrium mixture to the plate, it was washed with 200 pL wash buffer. Incubation lasted 3 min and was followed by 5-min incubation with 100 pL HRP-conjugated goat anti-human IgG Fc antibody for detection (1 mg/mL stock diluted 1:20,000 in blocking buffer). Before and after addition of a detection antibody, the plate was washed 5 times with 200 pL wash buffer. A chromogenic horseradish peroxidase (HRP) substrate (100 pL) was then added and following color development for 3 min, 100 pL ELISA stop solution were added to quench the reaction. Absorbance was measured at 450 nm with subtraction of the absorbance at 620 nm.
[0766] The standard curve prepared with free antibody was fitted to a Sigmoidal four- parameter logistic (4PL) model. Using the standard curve, the ELISA readouts for the equilibrium mixtures were converted to concentrations of unbound antibody. For this conversion, only equilibrium mixtures yielding ELISA readouts mapping onto the mid-to- lower part of the standard curve were selected. From the concentration of unbound antibody an apparent equilibrium dissociation constant (Kd) could be calculated using Eq. 1:
[0767] Here, OAtotai is the total molar concentration of antibody, OAfree is the concentration of unbound antibody determined by ELISA, VWFCKtotai is the concentration of antibody binding sites on the CK domain or VWF. For the CK domain, the number of binding sites is twice the molar concentration of the CK dimer, while the number of binding sites on VWF equals its monomer concentration.
[0768] Apparent Kd-values for a subset of monovalent antibodies are listed in Table 5.
Table 5. Apparent Ka-values for the binding of one-arm (OA) anti- VWF CK antibodies to recombinant human or cyno CK domain or plasma-derived VWF (pd-VWF)
Results are shown as mean ± standard deviation (n = 2). Abbreviations: ND, not determined; Cyno, Cynomolgus monkey
[0769] For all antibodies, binding to the recombinant human CK domain and human plasma-derived VWF at pH 7.4 was similar, indicating that epitopes are fully accessible when the CK domain is embedded in VWF. Binding to the cyno CK domain was retained for all antibodies with less than 2-fold change in Ka value as compared to the human counterpart.
Example 9: Mapping of hot spot residues for antibody binding on the human CK domain
[0770] Amino acid residues in the VWF CK domain important for antibody binding (so- called hot spot residues) were identified by alanine-scanning mutagenesis. A panel of alanine substitution variants of the human recombinant CK domain were produced. Positions selected for alanine substitution were all surface exposed and selected based on inspection of the crystal structure of the CK domain.
[0771] Binding was assessed using a direct ELISA system. The ELISA was prepared by coating of a 96-well plate with 100 pL (2 pg/mL) of each of human VWF CK domain alanine variants in TBS (10 mM Tris-HCl, 150 mM NaCl, pH 7.5) overnight at 5°C. Following a single wash of the plate with 200 pL of wash buffer (TBS containing 0.05% (v/v) Tween-20 and 5 mM CaCh), the plate was blocked by incubation with 200 pL blocking buffer (TBS containing 5 mM CaCh and 1% BSA) for 1 hour at room temperature. Before transfer of 100 pL of monovalent (one-arm) antibody at 20 nM, 5 nM, or 0.5 nM in 20 mM HEPES, 150 mM NaCl, 5 mM CaCh, 1% (w/w) BSA, pH 7.4 buffer, the plate was washed with 200 pL wash buffer. Incubation with the antibody lasted 45 min and was followed by a 5-min incubation with 100 pL HRP -conjugated goat anti -human IgG Fc antibody for detection (1 mg/mL stock diluted 1 :20,000 in blocking buffer). Before and after addition of detection antibody, the plate was washed 5 times with 200 pL wash buffer. An HRP -based chromogenic substrate (100 pL) was then added and, following color development for 3 min, 100 pL ELISA stop solution were added to quench the reaction. Absorbance was measured at 450 nm with subtraction of the absorbance at 620 nm. Amino acid positions important for binding of a given antibody were defined as those in which the measured absorbance was <33% of the absorbance measured for the binding of the same antibody to the wild-type
human VWF CK domain. Results are shown in Table 6.
Table 6. Monovalent (one-arm) antibody binding to alanine substitution variant of the human VWF CK domain
Substitutions resulting in <33% binding compared to the wild-type CK domain at 0.5, 5 or 20 nM monovalent (OA) antibody are marked by an ‘X’ and define a hot spot.
Example 10: Effect of anti- VWF CK domain antibodies on the VWF:FVIII interaction [0772] VWF is a carrier of coagulation Factor VIII (FVIII) in circulation and is critical for maintaining its half-life and concentration in plasma. To investigate the effect of antibody binding on the VWF FVIII interaction, the capacity of VWF to bind FVIII in the presence of monovalent (one-arm) anti-VWF CK domain antibody was determined. To this end, the VWF antigen level in plasma from 5 healthy human donors was determined using a VWF:Ag immuno-turbidimetric assay. Plasma samples (stabilized in 3.2% sodium citrate) were then incubated for 17 hours at 37°C in the presence of 0 nM (“untreated”), 200 nM, or 600 nM antibody concentrations followed by dilution of plasma to 0.1 lU/mL (10%) VWF and measurement of the FVIII binding capacity of VWF using a quantitative VWF:FVIIIB enzyme immunoassay. In this assay, VWF from plasma was captured using a rabbit anti
human VWF F(ab’)2 fragment followed by detection of bound FVIII using a peroxidase- conjugated mouse anti-human FVIII monoclonal antibody for detection.
[0773] Results are shown in Table 7. For all antibodies, the mean level of VWF:FVIII was greater than 80% of the level in untreated donor-matched plasma. The results demonstrate that the tested antibodies minimally affected the capacity of VWF to bind FVIII.
Table 7. VWF binding to FVIII following incubation of plasma with one-arm anti- VWF CK domain antibodies
[0774] Measured binding levels were normalized to untreated plasma from the same donor. Results are shown as mean ± standard deviation for plasma from 5 healthy human donors.
Example 11: Effect of anti- VWF CK domain antibodies on the VWF:platelet gplb interaction
[0775] Glycoprotein lb (gplb) is a key receptor for VWF on the platelet. The interaction with gplb is dependent upon the exposure of a binding site in the Al domain of VWF. Under physiological conditions, the gplb binding site becomes accessible when VWF is subjected to shear stress at sites of vascular injury. Under static conditions, such as those prevailing in vitro, the effect of shear stress can be recapitulated by addition of the peptide antibiotic ristocetin, which enhances the binding of VWF to gplb receptors on platelets.
[0776] To evaluate the effect of monovalent (one-arm) anti -VWF CK domain antibodies on the ability of VWF to engage the gplb receptor on platelets, plasma from three healthy human donors (stabilized in 3.2% sodium citrate) was incubated with 0 nM (“untreated”), 200 nM, 600 nM, or 1000 nM of antibody for 10-30 mins followed by quantitative
determination of the ristocetin cofactor activity of VWF using the STA-VWF:RCo assay. This assay is based on the change in turbidity of a platelet suspension, as measured by photometry. A suspension of reconstituted lyophilized platelets is added to the test plasma followed by the addition of ristocetin to induce VWF- and gplb-dependent platelet aggregation. Aggregation induces a decrease in turbidity and, consequently, a decrease in absorbance, which can be measured photometrically. The decrease in absorbance is a function of the VWF activity in the plasma sample.
[0777] For each combination of donor plasma, antibody, and antibody concentration, the ristocetin cofactor activity of VWF was measured and normalized to that of a donor-matched control plasma without antibody. As shown in Table 8, VWF retains the ability to bind platelet gplb in the presence of Libl_Pl_A9 and Libl_Pl_A6 monovalent antibodies.
Table 8. Ristocetin cofactor activity of VWF (VWF:Rco) following incubation of plasma with one-arm anti- VWF CK antibodies
[0778] Measured activity levels were normalized to the activity of untreated plasma from the same donor. Results are shown as mean ± standard deviation for plasma from 3 healthy human donors.
Example 12: Effect of anti- VWF CK domain antibodies on the cleavage of VWF by ADAMTS13
[0779] The plasma protease ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 (ADAMTS13) is responsible for processing of VWF into shorter multimers. The cleavage site for ADAMTS13 within the VWF A2 domain is cryptic under static conditions and is exposed when VWF is subjected to shear stress. Under static conditions, shear stress is
mimicked by ristocetin, which in turn triggers a reduction in VWF multimer size upon addition to human plasma.
[0780] To evaluate the effect of monovalent (one-arm) anti -VWF CK domain antibodies on the ability of ADAMTS13 to process VWF, human plasma from three healthy donors (stabilized in 3.2% sodium citrate) was incubated overnight at 37°C in a 10 mM HEPES and 6.5 mM BaC12 buffer (pH 7.4) with or without 1.5 mg/mL ristocetin and 0 nM or 600 nM of antibody.
[0781] The VWF multimers were analyzed via SDS gel electrophoresis. The electrophoretic separation of multimers was performed after dilution of plasma at 1/6 or 1/20 in a dilution buffer supplied by the kit. The plasma samples were electrophoresed on a gel containing a high concentration of agarose (2%) allowing for the separation of VWF multimers in the size range of 449-20000 kDa. VWF multimers were immunofixated with a polyclonal anti-VWF IgG antibody for 1 h followed by a second immunofixation with peroxi dase-conjugated anti-IgG antibody for 30 min. The gels were subsequently stained with a peroxidase and chromogenic substrate and prepared for interpretation. Gels were scanned and densitometrically evaluated and quantified relative to the control with peaks 1-3 classified as low molecular weight (LMW) VWF, peaks 4-8 as intermediate molecular weight (IMW) VWF, and all other peaks being high molecular weight (HMW) VWF.
[0782] The fractional content of LMW, IMW, and HMW VWF in plasma for the different conditions tested is shown in FIG. 3. Upon treatment of plasma with ristocetin a marked decrease in HMW and corresponding increase in LMW was observed. The same shift in VWF multimer pattern was observed when plasma was treated with ristocetin in the presence of 600 nM antibody including Libl_Pl_A9 and Libl_Pl_A6. These results indicate that the processing of VWF by ADAMTS13 is retained when anti-VWF CK antibodies are bound to the VWF CK domain.
Example 13: Effect of anti-VWF CK domain antibodies on the binding of VWF to collagen
[0783] Multimeric VWF binds to collagen in the perivascular connective tissue and in the subendothelial matrix. The A3 domain contains the major binding site for collagen type III). The effect of monovalent (one-arm) anti-VWF CK domain antibodies on the ability of VWF to bind collagen type III was explored by incubating plasma (stabilized in 3.2% sodium citrate) from five healthy human donors for 17 hrs at 37°C in the presence of 0 nM (“untreated”) or 600 nM antibody. Following incubation, collagen binding was determined
relative to untreated plasma. In this assay, VWF in plasma was captured by collagen type III from human placenta coated in the ELISA plate. Next, bound VWF was quantified using a secondary peroxidase-conjugated rabbit anti-VWF antibody.
[0784] Relative levels of VWF binding to collagen in presence of antibody are provided in Table 9 and demonstrate that VWF retained the ability to bind collagen in presence of all tested antibodies.
Table 9. Binding of VWF in plasma to collagen type III in the presence one-arm anti- VWF CK domain antibodies
[0785] Measured binding levels were normalized to that of untreated plasma from the same donor. Results are shown as mean ± standard deviation.
Example 14: Effect of anti-VWF CK domain antibodies on the VWF:platelet interaction [0786] The effect of monovalent (one-arm) anti-VWF CK domain antibodies on binding of VWF to platelets was assessed by incubating platelet rich plasma (PRP) with antibody and ristocetin to facilitate gplb binding followed by FACS-based detection of VWF binding to platelets.
[0787] Blood from healthy donors was collected aseptically into vacuum tubes via an antecubital puncture (1 volume trisodium citrate 0.105 M to 9 volumes blood). PRP was prepared by centrifuging the blood at 250 g for 15 min. PRP from two healthy human donors was diluted 1/4 in HBS buffer (10 mM HEPES, 150 mM NaCl, 1 mM MgSO4, 5 mM KC1, pH 7.4) and 5 pL was added to a 20-pl reaction mixture consisting of FITC-conjugated anti- VWF antibody (final concentration 8 pg/mL), 0.5 mg/ml ristocetin, and 0 or 600 nM monovalent (one-arm) anti-VWF CK domain antibody in HBS-buffer. Samples were incubated for exactly 20 min before quenching by addition of 200 pL of fixation solution (137 mM NaCl, 2.7 mM KCl, 1.12 mM NaH2PO4, 1.15 mM KH2PO4, 10.2 mM Na2HPO4, 4 mM EDTA, 0.5% formaldehyde). Sample analysis was performed on a flow cytometer.
Using forward (FSC) and sideward (SSC) scatter pattern, a gate was placed on the platelets. The fluorescent intensity in the FITC gate was selected to determine the binding of VWF to platelets.
[0788] The fraction of platelet bound VWF in presence of antibody relative to the same plasma without antibody is listed for each antibody in Table 10. The results show that vWF retain ability to bind platelets in presence of the tested antibodies.
Table 10. Binding of VWF in platelet rich plasma to platelets in the presence of one-arm anti- VWF CK domain antibodies and ristocetin
[0789] Measured binding levels were normalized to that of untreated plasma from the same donor. Results are shown as mean ± standard deviation.
Example 15: Quantification of VWF antigen in cynomolgus monkey plasma samples [0790] An assay based on the change in turbidity of a microparticle suspension, as measured by photometry, was used to quantify VWF antigen (VWF:Ag) in plasma samples from cynos. A suspension of latex microparticles, coated with antibody specific for VWF, is mixed with the test plasma to be quantified. An antigen-antibody reaction takes place, leading to an agglutination of the latex microparticles which induces an increase in turbidity of the reaction medium. This increase in turbidity is reflected by an increase in absorbance, the
latter being measured photometrically. The increase in absorbance is a function of the VWF antigen level present in the test sample.
[0791] Plasma levels of VWF were measured in cyno plasma stabilized with 3.2% sodium citrate and diluted 4-fold in 10 mM HEPES, 150 mM NaCl, ImM MgSCU, 5 mM KC1, pH 7.4 buffer.
Example 16: Quantification of VWF ristocetin cofactor activity (VWF:RCo) in cynomolgus monkey plasma samples
[0792] An assay based on the change in turbidity of a platelet suspension, as measured by photometry, was performed to quantify VWF in plasma samples from cynos. A suspension of reconstituted lyophilized platelets was added to the test plasma followed by the addition of ristocetin to induce VWF- and gplb-dependent platelet aggregation. Aggregation induces a decrease in turbidity and consequently a decrease in absorbance, which can be measured photometrically. The decrease in absorbance is a function of the VWF activity in the plasma sample.
[0793] Plasma activity levels of VWF were measured in cyno plasma stabilized with 3.2% sodium citrate and diluted 4-fold in 10 mM HEPES, 150 mM NaCl, 1 mM MgSCU, 5 mM KC1, pH 7.4 buffer.
Example 17: Measurement of VWF multimer distribution in cynomolgus monkey plasma samples
[0794] The multimer pattern of VWF in plasma samples from cynos was analyzed as described for human plasma in Example 12. Before analysis, plasma samples were diluted 1:6 or 1:20.
Example 18: Quantification of FVIII antigen (FVIIEAg) in cynomolgus monkey plasma samples
[0795] FVIII antigen (FVIIEAg) was quantified in plasma samples from cynos. In this assay, FVIII in plasma samples is captured by mouse monoclonal anti-human FVIIEAg antibody coated on the internal walls of a plastic microplate well. Next, mouse anti-human FVIII antibodies coupled with peroxidase bind to the remaining free antigenic determinants of the bound factor VIII. The bound enzyme peroxidase is revealed by its action on the TMB
substrate. After stopping the reaction with a strong acid, the intensity of the color is proportional to the concentration of factor VIII initially present in the sample.
Example 19: Quantification of anti-VWF CK antibody
[0796] Quantification of anti-VWF CK domain antibody in plasma samples is done by immunoaffinity capture followed by tryptic digest and quantification using LC-MS/MS. [0797] Using biotinylated goat-anti-human IgG antibody coupled to streptavidin-coated high-capacity magnetic beads, anti-VWF CK domain antibody is selectively captured from cyno plasma samples and combined with an antibody standard. Following rounds of washing of the beads to remove non-specific plasma constituents, bound antibody is subjected to tryptic digest and then quantified by LC-MS/MS. For the quantification, the isotope labelled tryptic peptide VVSVLTVLHQDWLNGK (SEQ ID NO: 723) is used. This peptide is derived from the antibody heavy chain and is conserved across IgGl-4 including the antibodies tested in Example 20.
Example 20: Pharmacokinetics and pharmacodynamics of anti-VWF CK antibodies in cynomolgus monkey
[0798] The pharmacokinetics of the monovalent (one-arm) Libl_Pl_A9 and Libl_Pl_A6 antibodies and their ability to accumulate VWF and FVIII in circulation was assessed in cynos (n = 2 per antibody). Antibodies were administered subcutaneously at day 1 and 8 at 4 mg/kg in a volume of 0.17 ml/kg.
[0799] Blood samples were collected at day 1 (pre-dose), 2, 3, 4, 6, 8 (pre-dose), 9, 11, 13, 15 and 22 into polypropylene test tubes with 3.2% sodium citrate as anticoagulant. Platelet poor plasma was prepared by two rounds of centrifugation (2840 g for 10 min) followed by aliquoting into fresh polypropylene tubes and immediate freezing on dry ice. Samples were stored at -80°C until measurement of VWF:Ag, VWF:RCo, VWF multimer distribution, FVIILAg, and antibody levels according to the methods described in Examples 15, 16, 17, 18, and 19, respectively.
[0800] Results for Libl_Pl_A6 OA and Libl_Pl_A9 OA are shown in FIG. 4 and FIG. 5, respectively, and summarized in Table 11. Using the assays with human plasma calibrators, the pre-dose levels of VWF and FVIII were found to be elevated in cynos as compared to humans with mean values of 258% (VWF:Ag), 295% (VWF:RCo), and 187% (FVIILAg). From the time-dependent change in VWF and FVIII following dosing of antibody, it can be concluded that both were capable of accumulating VWF. The relative
VWF accumulation according to the VWF :RCo assay was comparable to that measured using the VWF : Ag assay, indicating that VWF retains activity upon accumulation and that VWF maintains activity upon anti -VWF CK domain antibody binding, which is in agreement with the functional studies. Consistent with retained FVIII binding by VWF in presence of antibody, accumulation of VWF was further accompanied by a corresponding increase in plasma levels of FVIII. VWF accumulation was most pronounced for the Libl_Pl_A6 OA antibody for which the CmaX/Cpre-dose ratio was about 2 and maintained until study end at day 22 in animal 4FG2. In animal 3FG2, levels of Libl_Pl_A6 OA, VWF, and FVIII declined from around day 10. This timing is consistent with anti-drug antibody (ADA) development, which was not addressed in the present study. Analysis of VWF multimers demonstrated a steady distribution of low (LMW), intermediate (IMW) and high (HMW) molecular weight VWF throughout the study comparable to the pre-dose distribution.
[0801] Table 11. Summary of results from PK/PD study of Libl_Pl_A6 OA and Lib_Pl_A9 OA in cynomolgus monkeys
[0802] Measured plasma levels (in % of assay standard) of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo) and FVIII antigen (FVIIFAg) before first
dosing (Cpre-dose), at maximum (Cmax), and at day 22 (Cday22). The fold accumulation at Cmax relative to Cpre-dose is given in square brackets.
Example 21: Administration of an anti-VWF antibody to a subject having a blood disorder characterized by excessive bleeding
[0803] Antibodies targeting a CK domain of a human (SEQ ID NO: 5) or a non-human primate (NHP; SEQ ID NO: 6) VWF protein are administered to a subject (e.g., a human) having a blood disorder characterized by excessive bleeding, such as, e.g., von Willebrand disease (VWD). The VWD is congenital VWD. Prior to administration, the subject is, assessed for the presence and/or severity of one or more symptoms selected from 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 the subject using routine and conventional methods. The therapeutic efficacy of the pharmaceutical composition in treating the blood disorder is ascertained by measuring VWF activity in blood using bioanalytical assays known to one of skill in the art. Subsequent doses are administered as needed.
Example 22: Affinity maturation of anti-VWF CK domain antibodies using phage and yeast display
[0804] In a second round of screening, the antibodies Libl_Pl_A6 and Libl_Pl_A9 (Table 1) were subjected to affinity maturation using conventional phage and yeast display methods. During antibody selections, the biotinylated human VWF CK domain was used as a primary antigen. To enrich for high-affinity binders, the concentration of primary antigen was progressively lowered. Diversity was introduced in the two parental antibodies using defined collections of natural complementarity determining regions (CDRs). These CDRs were inserted into the parental antibodies while maintaining the heavy chain CDR3 and framework regions unchanged to retain the same epitope binding as the parental antibody. In the heavy chain CDR3, single site saturation mutagenesis was explored. From the pool of apparent high-affinity binders, antibodies maintaining cross-reactivity with the biotinylated cyno VWF CK domain were selected.
[0805] A total of 55 antibodies in single-chain variable fragment (scFv) format were identified from the affinity maturation campaign. Amino acid sequences of the variable heavy chain (VH) and VLs of each antibody are provided in Table 1 (designated within the table
under the heading “Affinity -matured antibodies”) along with sequences of the associated CDR1, CDR2, and CDR3 loops. CDR loop sequences were extracted from each VH and VL using the IMGT scheme, except for the CDR L2 which was determined using the Kabat scheme. Sequence alignments of the CDRs of each antibody relative to its parental antibody are provided for the Libl_Pl_A6* and Libl_Pl_A9* families in Table 12A and Table 13A, respectively. Sequence identity to the parental antibody is indicated by a dot while a missing residue is indicated by a hyphen. The prefix L or H is added to CDR label in each column title to indicate the light chain or heavy chain, respectively. The corresponding SEQ ID NOs: for the CDRs of each antibody shown in Tables 12A and 13A are shown in Tables 12B and 13B, respectively.
Table 12A. Alignment of CDR loops of anti-VWF CK domain antibodies relative to the parental Libl_Pl_A6* antibody
Table 12B. SEQ ID NOs corresponding to sequences of CDR loops of anti-VWF CK domain antibodies shown in Table 12A
Table 13A. Alignment of CDR loops of anti-VWF CK domain antibodies relative to the parental Libl_Pl_A9* antibody
Table 13B. SEQ ID NOs corresponding to sequences of CDR loops of anti-VWF CK domain antibodies shown in Table 13A
Example 23: High-throughput screening of identified antibodies for binding to the human VWF CK domain
[0806] The identified antibody sequences from the affinity maturation campaign (Example 23) were produced as monovalent (one-arm) scFv-IgGl antibody fusions. The scFv constructs had a VH-linker-VL configuration with the linker consisting of the amino acid sequence SGGSTITSYNVYYTKLSSSGT (SEQ ID NO: 483). They were subsequently cloned into the pcDNA3.4 vector as N-terminal fusions to a truncated des(VH-CHl) IgGl HC (SEQ ID NO: 717) carrying the knob/hole mutation T366W. Co-transfection with a second pcDNA3.4 plasmid encoding a truncated IgGl HC with knob/hole mutations T366S/L368A/Y407V (SEQ ID NO: 718) in expiCHO cells (see Example 24) allowed for efficient production of monovalent scFv-IgGl antibodies, which were purified using standard methods.
GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK
(SEQ ID NO: 717) Truncated IgGl HC (T366W) used for N-terminal fusion of scFv constructs.
[0807] DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWES NGQPENNYKTTPP VLD SDGSFFLVSKLTVDK SRWQQGNVF SC S VMHEALHNHYTQ KSLSLSPGK
(SEQ ID NO: 718) Truncated IgGl HC (T366S/L368A/Y407V) used for co-expression. [0808] To initially characterize the ability of the monovalent scFv-IgGl antibodies to bind the human VWF CK domain, Surface Plasmon Resonance (SPR) experiments were conducted. Briefly, a sensor chip was activated and coupled with neutravidin using amine coupling followed by capture of biotinylated human VWF CK domain (Example 1). Binding to purified monovalent scFv-IgGl antibody was measured at room temperature and pH 7.4 (in 10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% Tween 20, pH 7.4) by inj ection of a single concentration of scFv-IgGl . From the estimated association (kon) and dissociation (kOff) rate constants, an apparent equilibrium dissociation constant (Ka = kOff/kOn) was calculated.
Comparison to the parental Libi Pl A6 and Libi Pl A9 antibodies produced in the same scFv-IgGl format demonstrated that most candidates exhibited improved affinity to the human VWF CK domain. Results are summarized in Table 14.
[0809] Table 14. SPR analysis of the binding properties of scFv-IgGl antibodies to the human VWF CK domain at pH 7.4 and room temperature
Example 24: Recombinant expression and purification of anti-VWF CK domain for binding studies
[0810] For in vitro characterization studies, human and cyno VWF CK domains were equipped with an N-terminal signal peptide derived from VWF followed by a hexa-histidine tag, StrepTagll, HRV-3C protease cleavage site, and three residues from VWF immediately N-terminal to the CK domain. In addition, a HA-tag was added to the C-terminus. Amino acid sequences are provided in Table 3, above.
[0811] The corresponding DNA sequences were synthesized and inserted between the Xbal and Agel restriction sites of the pcDNA3.4 vector. Expression was performed using Gibco expiCHO cells and a transient expression system. Cells were maintained at 37°C in a humidified atmosphere of 8% CO2 with orbital shaking and sub-cultivated every 3-4 days in a cell medium prior to transfection.
[0812] Cells were transfected at a cell density of about 6 million cells/mL using a suitable reagent. For each 100 mL of cells, transfection was performed by diluting a total of 80 pL (1 mg/mL) DNA into 4 mL serum-free medium and combining this with 320 pL transfection reagent mixed with 3.7 mL serum-free medium. The mixture was then transferred to the cell culture. One day post-transfection, 600 pL transfection enhancer was added together with 24 mL culture feed. Cell culture supernatants were harvested 7-8 days post-transfection by centrifugation and followed by filtration.
[0813] Purification of expressed VWF CK domain was conducted by affinity chromatography utilizing the His-tag and standard purification methods. Briefly, clarified culture medium was loaded onto a HisTrap Excel column equilibrated in 20 mM HEPES, 100 mM NaCl, pH 7.4 (Buffer A). Following washing with 6% (v/v) Buffer B (20 mM HEPES, 100 mM NaCl, 500 mM Imidazole, pH 7.4) in Buffer A, bound protein was eluted with a linear gradient of 0-100% Buffer B. Purified protein was up-concentrated using a spin concentrator and subsequently dialyzed into 20 mM HEPES, 100 mM NaCl, pH 7.3.
Example 25: Reformatting, expression, and purification of anti-VWF CK domain
antibodies
[0814] Using the VH and VL sequences of affinity-matured antibodies from Table 1, antibodies were converted into the desired format for subsequent expression and purification. Table 15 lists the sequences of the antibodies configured to a monovalent (one-arm) human IgG4 format, also termed OA antibodies.
Table 15. Sequences of the affinity-matured antibodies in monovalent OA and bivalent mAb format
Example 26: Binding of anti-vWF CK domain antibodies to recombinant human and cynomolgus monkey VWF CK domain
[0815] SPR was employed to measure the affinity of monovalent anti-VWF CK domain antibodies for the recombinant human and cyno CK domains. Briefly, a sensor chip was activated and couple with anti-mouse IgG capture antibody. This was followed by the sequential non-covalent capture of mouse anti-Strep-Tag antibody (STREP-TAG IMMO) and human or cyno VWF CK domain carrying an N-terminal StrepTagll epitope tag (Example 25). Binding was measured for 360 s by injection of 0.5-4 nM monovalent anti-VWF CK domain antibody (Example 25) or 10-80 nM in case of the parental antibodies Libl_Pl_A6 and Libl_Pl_A9 OA for 360 s. This was immediately followed by a dissociation phase of 3600 s. From the estimated association (kon) and dissociation (kOff) rate constants, apparent equilibrium dissociation constants (Ka = koff/kon) were calculated.
[0816] To mimic binding in the vascular compartment (pH 7.4) and under endosomal conditions (pH 5.5), binding experiments were conducted at 37°C in 10 mM HEPES, 150 mM NaCl, 0.05% Tween 20, pH 7.4 buffer containing 1 mg/ml BSA and at 25°C in 20 mM MES, 150 mM NaCl, pH 5.5 buffer containing 1 mg/ml BSA. Results are provide in Table 16 and Table 17, respectively.
Table 16. SPR analysis of the binding properties of monovalent anti-vWF CK domain
OA antibodies to the human and cyno CK domains at pH 7.4 and 37°C
Table 17. SPR analysis of the binding properties of monovalent anti-vWF CK domain
OA antibodies to the human and cyno CK domains at pH 5.5 and 25°C
Example 27: Effect of anti-VWF CK domain antibodies on the VWF:platelet gplb interaction
[0817] To evaluate the effect of monovalent (one-arm) anti-VWF CK domain antibodies on the ability of VWF to engage the gplb receptor on platelets, plasma from three healthy human donors (stabilized in 3.2% sodium citrate) was incubated with 0 nM (“untreated”), 300 nM, or 600 nM of antibody for 10-30 mins followed by quantitative determination of the ristocetin cofactor activity of VWF using the STA-VWF:RCo assay. This assay is based on the change in turbidity of a platelet suspension, as measured by photometry. A suspension of reconstituted lyophilized platelets is added to the test plasma followed by the addition of ristocetin to induce VWF- and gplb-dependent platelet aggregation. Aggregation induces a decrease in turbidity and, consequently, a decrease in absorbance, which can be measured photometrically. The decrease in absorbance is a function of the VWF activity in the plasma sample.
[0818] For each combination of donor plasma, antibody, and antibody concentration, the ristocetin cofactor activity of VWF was measured and normalized to that of a donor-matched control plasma without antibody. As shown in Table 18, VWF retains the ability to bind platelet gplb in the presence of Libl_Pl_A9 and Libl_Pl_A6 monovalent antibodies. Results are shown as mean ± standard deviation for plasma from 3 healthy human donors.
Table 18. Ristocetin cofactor activity of VWF (VWF:Rco) following incubation of plasma with monovalent anti- VWF CK domain OA antibodies
Example 28: Effect of monovalent versus bivalent anti- VWF CK domain antibody on CK domain aggregation
[0819] Since VWF exists as multimeric species in the human circulation each VWF is expected to contain multiple (>2) binding sites for a given anti-VWF antibody. With a standard anti-VWF mAb the combination of two binding sites on the mAb and multiple epitopes on VWF may results in cross-linking with potential detrimental effects on VWF activity and aggregation as a result. This is avoided with a monovalent (one-arm) antibody format containing only one binding site on each antibody. To explore these aspects, the Libl_Pl_A6 and 1081_Lib8 anti-VWF CK domain antibodies were produced in OA and mAb formats using the expiCHO expression system described in Example 24. Sequences of each antibody are listed in Table 19.
Table 19. Sequences of the Libl_Pl_A6 and 1081_Lib8 antibodies in monovalent OA and bivalent mAb format
Abbreviations: HC_trc, truncated heavy chain; VH_HC, heavy chain containing VH;
VL LC, light chain containing VL.
[0820] Antibody and a human CK domain dimer (Example 24) were incubated a equimolar concentrations of 3 |iM in 20 mM HEPES, 100 mM NaCl, pH 7.3 buffer at 37°C for 15 min before analysis of aliquot by size exclusion chromatography (SEC)-HPLC with a mobile phase consisting of 0.2 M potassium phosphate, 0.2 M KC1, and pH 6.8. Elution was monitored by UV detection at 280 nm. SEC-HPLC runs of the individual components were included for comparison. Chromatograms are shown for 1081_Lib8 and Libl_Pl_A6 runs in
FIG. 6A and FIG. 6B, respectively. By relating elution times to a standard curve prepared with protein standards spanning a relevant range of molecular weights, it was found that incubation of each OA antibody with the human VWF CK domain resulted in the formation of well-defined complexes comprising two OA antibodies bound to a single CK domain dimer, i.e., no cross-linking of VWF CK was observed in accordance with the monovalency of the OA antibody. In contrast, incubation of each mAb antibody with the human VWF CK domain resulted in the formation of higher order soluble aggregates that appeared to comprise 3-7 VWF CK domain dimers linked by the bivalent mAbs.
Example 29: Measurement of VWF multimer distribution in cynomolgus monkey plasma samples
[0821] The VWF multimer distribution in plasma obtained from cynomolgus monkey was analyzed as described in Example 12.
Example 30: Pharmacokinetics and pharmacodynamics of anti- VWF CK antibodies in cynomolgus monkeys
[0822] The pharmacokinetics of the monovalent (one-armed) antibodies AO9_P1_D11 OA, A09_Pl_E07 OA, AO6_P1_C12 OA, AO6_P1_B12 OA, A06_Pl_H01 OA and AO6_P1_G12 OA (see Table 15), including their ability to accumulate VWF and FVIII in circulation was assessed in cynomolgus monkey (1 male + 1 female per antibody).
Antibodies were administered the antibody (IV) on day 1 at a dose of 4 mg/kg in a volume of 0.15-0.16 mL/kg.
[0823] Plasma sampling was performed at day 0 (pre-dose) and after administration at 20 min, 4-, 8-, 12-hours, and daily until the end of the study. Blood was collected into polypropylene test tubes with 3.2% sodium citrate as anticoagulant. Platelet poor plasma was prepared by two rounds of centrifugation (2840 g for 10 min) followed by aliquoting into fresh polypropylene tubes and immediate freezing on dry ice. Samples were stored at -80°C until measurement of VWF:Ag, VWF:RCo, FVIII: Ag, and antibody levels according to the methods described in Examples 15, 16, 18, and 19, respectively.
[0824] Results for each of the antibodies are shown in FIGS. 7A-7D (AO9_P1_D11 OA), FIGS. 8A-8D (A09_Pl_E07 OA), FIGS. 9A-9D (AO6_P1_C12 OA), FIGS. 10A-10D (A06 P1 B12 OA), FIGS. 11A-11D (A06_Pl_H01 OA), and FIGS. 12A-12D (AO6_P1_G12 OA) and are summarized in Table 20, which shows measured plasma levels (in % of assay standard) of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity
(VWF:RCo), and FVIII antigen (FVIII:Ag) before first dosing (Cpre-dose) and at maximum (Cmax). The ratio of Cmax and Cpre-dose gives the maximum relative accumulation. Using the assays with human plasma calibrators, the pre-dose levels of VWF and FVIII were found to be elevated in cynomolgus monkey compared to humans with mean values of 276% (VWF:Ag), 294% (VWF:RCo), and 191% (FVIII Ag).
[0825] It can be concluded from the time-dependent change in VWF and FVIII following dosing of antibody that all of the tested antibodies are capable of accumulating VWF. The relative VWF accumulation according to the VWF:RCo assay is comparable to that measured using the VWF:Ag assay, indicating that VWF retains activity upon accumulation, and that VWF maintains activity upon anti-VWF CK domain antibody binding, in agreement with the functional studies.
[0826] Consistent with retained FVIII binding by VWF in the presence of an anti-VWF antibody, accumulation of VWF was furthermore accompanied by a corresponding increase in plasma levels of FVIII. VWF accumulation was most pronounced for A06 P1 C12 OA, for which the Cmax/Cpre-dose ratio was about 2 5 (animal 724F).
Table 20. Summary of results from study of monovalent (one-arm) anti-VWF CK domain antibodies in cynomolgus monkey
Example 31: Effect of anti-VWF CK domain antibodies on the VWF:collagen III interaction
[0827] The effect of monovalent (one-arm) anti-VWF CK domain antibodies on the binding of VWF to collagen III was evaluated using an ELISA with collagen III coated to the plate surface and incubation with a fixed concentration of plasma-derived VWF (2 nM) preincubated with 0 or 300 nM monovalent antibody. VWF binding was detected using a HRP- conjugated anti-VWF antibody. By relating the readout in the presence of monovalent antibody with that in the absence, the effect of monovalent antibody on collagen binding was determined.
[0828] Human placenta collagen III was dissolved in 0.05 M acetic acid to a concentration of 1 mg/mL followed by extensive dialysis against TBS (10 mM Tris-HCl, 150 mM NaCl, pH 7.5). The ELISA assay was prepared by coating a 96-well plate with 100 pL of 50 pg/mL collagen III in coating buffer (TBS containing 5 mM CaCh) overnight at 5°C. Following a single wash of the plate with 200 pL of wash buffer (TBS containing 0.05% (v/v) Tween-20 and 5 mM CaCh), the plate was blocked by incubation with 200 pL blocking buffer (TBS containing 5 mM CaCh and 1% (w/w) BSA) for 1 hour at room temperature. After wash with 200 pL wash buffer, the plate was incubated with 100 pL of plasma-derived VWF (2 nM) pre-incubated for 30-min with 0 or 300 nM monovalent antibody. Incubation lasted 60 min and was followed by consecutive 5-min incubations with 100 pL of monoclonal rabbit anti-VWF antibody (1 mg/mL diluted 1 : 1000) and 100 pL of HRP-
conjugated goat anti-rabbit IgG antibody (1 mg/mL diluted 1:2000). Before and after addition of a primary and secondary antibody, the plate was washed 5 times with 200 pL wash buffer. A chromogenic horseradish peroxidase (HRP) substrate (100 pL) was then added and, following color development for 8 min, ELISA stop solution (100 pL) was added to quench the reaction. Absorbance was measured at 450 nm with subtraction of the absorbance at 620 nm.
[0829] Relative levels of VWF binding to collagen in presence of antibody are provided in Table 21, demonstrating that VWF retained the ability to bind collagen in presence of all tested monovalent antibodies.
Table 21. Binding of VWF to collagen III following incubation of VWF with monovalent anti- VWF CK domain OA antibodies
VWF binding (mean ± SD; n = 2) at 300 nM monovalent antibody is provided relative to the measured binding of VWF in the absence of the antibody.
Example 32: Expression and purification of cynomolgus monkey VWF CK domain [0830] The cynomolgus monkey (Macaca fascicularis) VWF CK domain construct used for expression was obtained from UniProt (uniprot.org) entry A0A2K5X4G5. To facilitate purification, the CK domain was equipped with an N-terminal hexa-histidine tag (His-tag) (SEQ ID NO: 11) followed by an HRV-3C sequence. The amino acid sequence is provided in Table 22. Expression was performed using the pcDNA3.4 vector (Genscript, Rijswijk, Netherlands), Gibco ExpiCHO-S™ cells, and the Gibco ExpiCHO™ Transient Expression System essentially according to manufacturer’s recommendations (Gibco Thermo Fischer Scientific). Purification was conducted by affinity chromatography utilizing the His-tag and standard purification methods. Briefly, clarified culture medium was loaded onto a HisTrap Excel column (Cytiva) equilibrated in 20 mM HEPES, 100 mM NaCl, pH 7.4 (Buffer A). Following washing with 6% (v/v) Buffer B (20 mM HEPES, 100 mM NaCl, 500 mM
Imidazole, pH 7.4) in Buffer A, bound protein was eluted with a linear gradient of 0-100% Buffer B. Purified cynomolgus monkey VWF CK domain was up-concentrated to 15.2 mg/mL using a spin concentrator and subsequently dialyzed into 20 mM HEPES, 100 mM NaCl, pH 7.3. Subsequent SDS-PAGE analysis under reducing and non-reducing conditions demonstrated that the purified cynomolgus CK domain is a disulfide-linked homodimer as described for the human VWF CK domain (Zhou and Springer, Blood, 123(12): 1785-1793 (2014)).
Table 22. Amino acid sequence of the cynomolgus monkey VWF CK domain construct
[0831] Sequence key: residues in italics correspond to an N-terminal extension comprising a His-tag and HRV-3C sequence. Bold and underlined residues correspond to the cynomolgus monkey VWF CK domain as provided in SEQ ID NO: 6.
Example 33: Expression and purification of A06 P1 C12 Fab
[0832] The Fab of AO6_P1_C12 was produced by transient co-expression of pcDNA3.4 DNA constructs encoding heavy and light chains as described for the cynomolgus CK domain (Example 32). The heavy and light chain sequences of the AO6_P1_C12 Fab are provided in Table 23. Following transient expression in the ExpiCHO™ Transient Expression System, purification was performed by affinity chromatography. Briefly, clarified culture medium was loaded onto a HisTrap KappaSelect column (Cytiva) equilibrated in 20 mM HEPES, 150 mM NaCl, pH 7.2. Following washing with 6% (v/v) Buffer B (100 mM sodium citrate, pH 3.0) in Buffer A, bound protein was eluted with a linear gradient of 0- 100% Buffer B. Collected fractions were neutralized by addition of TRIS-HC1, pH 9.0. Purified AO6_P1_C12 Fab was dialyzed into 20 mM HEPES, 100 mM NaCl, pH 7.3 and subsequently up-concentrated to 13.3 mg/mL using a spin concentrator.
Table 23. Amino acid sequence of the A06 P1 C12 Fab
[0833] The heavy chain (HC) comprises variable heavy (VH) and first constant heavy (CHI) domains. The light chain (LC) is human kappa
Example 34: Epitope and Paratope mapping of the A06 P1 C12 Fab:VWF CK domain complex by X-ray crystallography
[0834] The epitope on the cynomolgus monkey VWF CK domain (CK domain) recognized by the A06 P1 C12 Fab (Fab) and the corresponding paratope on the AO6_P1_C12 Fab were determined by X-ray crystallography.
Crystallisation:
[0835] The two proteins, CK domain and Fab, were mixed and incubated for an hour on ice using the molar ratio of 1:1.2 (CK domaimFab) and injected on a size exclusion chromatography (SEC) Superdex 200 Increase 10/300 GL column (Cytiva) equilibrated in buffer consisting of 20 mM HEPES, 100 mM NaCl, pH 7.3. The eluted peaks were analysed using SDS-PAGE analysis and the peak corresponding to the CK domaimFab complex was up-concentrated to 15 mg/mL and immediately used to perform crystallization screens. Initial crystals of the complex appeared in 0.1 M HEPES, pH 7.5 containing 70% MPD (2-Methyl- 2,4-pentanediol). These crystals were used to perform microseed matrix screening (MMS) experiments and subsequent optimization of initial crystal conditions. The drops were setup at 6 mg/mL using 30 nL of seed, 100 nL of sample and 120 nL of the well solution. The MMS strategy yielded crystals in several conditions. The crystal used for structure determination grew under the conditions of 0.1 M Bis-TRIS, pH 5.5 and 2 M ammonium sulfate.
Diffraction Data Collection:
[0836] The best diffracting crystal was flash-frozen in liquid N2 after soaking in reservoir solution supplemented with 25 % glycerol as a cryoprotectant. Diffraction data were collected at the BioMAX beamline (MAX IV, Lund, Sweden) at 100 K and X = 0.9762 A. A total of 3600 images were collected with an oscillation range of 0.1° per image using a Dectris EIGER 16M detector. Data were processed using the autoPROC pipeline (Vonrhein et al., Acta Crystallogr. D Biol. Crystallogr., 67: 293-302 (2011)), which includes the software programs XDS (Kabsch, Acta Crystallogr. D Biol. Crystallogr. , 66: 125-132 (2010)) and Aimless (Evans and Murshudov, Acta Crystalllogr. D Biol. Crystallogr. , 69: 1204-1214 (2013)). Diffraction data statistics are summarised in Table 24.
Structure Determination and Refinement:
[0837] The starting model for the Fab was constructed using Molrep (Vagin and Teplyakov, J. Appl. Cryst., 30: 1022-1025 (1997)) and a heavy chain (HC) from the protein data bank (PDB) entry 4HCR and a light chain (LC) from the PDB entry 4DKF.
Subsequently, complementarity determining region (CDR) loops were removed and the CK domain was fitted using the PDB entry 4NT5 and the program Phaser (Kovalevskiy, et al., Acta Crystallogr. D Biol. Crystallogr., 74: 492-505 (2018)). The structure was refined using the software programs Refmac5 (Kovalevskiy, et al., Acta Crystallogr. D Biol. Crystallogr. , 74: 492-505 (2018)) and Buster (Bricogne, et al., (2017). BUSTER. Cambridge, United Kingdom: Global Phasing Ltd.). Model building was carried out using the software program Coot (Emsley et al., Acta Crystallogr. D Biol. Crystallogr. , 66: 486-501 (2010)). One molecule of the Fab and one monomer subunit of the CK domain dimer were found in the asymmetric unit. The CK domain homodimer, bound to two Fab molecules, is observed when the symmetry-related molecules are generated. Refinement statistics are summarised in Table 24.
Table 24. Data collection and refinement statistics from X-ray structure determination of the complex between the cynomolgus monkey VWF CK domain and the A06 P1 C12 Fab. Statistics for the highest-resolution shell are shown in parentheses
[0838] HC and LC refer to the heavy and light chains of the AO6_P1_C12 Fab, respectively, and chain A to the monomer subunit of the VWF CK domain homodimer. Ramachandran plot quality was calculated using MolProbity server (Chen et al., Acta Crystallogr. D Biol. Crystallogr. , 66: 12-21 (2010))
Paratope Mapping:
[0839] Residues in the AO6_P1_C12 Fab within 4.0 A of the VWF CK domain in the
crystal structure were defined as constituting the paratope. The paratope was found to be comprised of residues belonging to the LC and HC of the AO6_P1_C12 Fab. Paratope residues are listed in Table 25.
Table 25. Paratope residues in A06 P1 C12 as determined by X-ray crystallography
[0840] LC and HC refer to the light and heavy chains of the A06 P1 C12 Fab, respectively. Positions constituting the paratope are numbered consecutively according to the sequences provided in Table 23 and according to Kabat and IMGT numbering schemes as indicated.
Epitope Mapping:
[0841] Residues in the VWF CK domain within 4 A of either the heavy- or light chain of the AO6_P1_C12 Fab in the crystal structure were defined as constituting the epitope. Within the VWF CK domain symmetry-related homodimer, the two epitopes (epitope 1 and 2) bound by a AO6_P1_C12 Fab, were found to comprise residues from each of the two monomer subunits (subunits A and B) in the CK domain. Epitope residues are listed in Table 26. The epitope was confirmed by mapping of key residues involved in A06 P1 C12 binding using
alanine-scanning mutagenesis of the human VWF CK domain.
Table 26. Epitope residues in the cynomolgus VWF CK domain as determined by X- ray crystallography
[0842] The VWF CK domain homodimer is comprised of two identical subunits denoted
A and B. Positions constituting the two epitopes (1 and 2) in the homodimer are numbered according to SEQ ID NO: 6 and according to the sequence of full-length VWF (SEQ ID NO: 2, entry A0A2K5X4G5 in Uniprot) as indicated. The corresponding positions in the human VWF CK domain (SEQ ID NO: 1; entry P04275 in UniProt) are included. The cynomolgus monkey and human VWF CK domains share 100% sequence identity at positions constituting the epitope.
Other Embodiments
[0843] Various modifications and variations of the described disclosure will be apparent to those skilled in the art without departing from the scope and spirit of the disclosure.
Although the disclosure has been described in connection with specific embodiments, it
should be understood that the disclosure as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the disclosure that are obvious to those skilled in the art are intended to be within the scope of the disclosure. Certain embodiments are in the claims.
Numbered Embodiments
[0844] EMBODIMENT 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.
[0845] EMBODIMENT 2: The monospecific antibody of embodiment 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.
[0846] EMBODIMENT 3: The monospecific antibody of embodiment I, wherein 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.
[0847] EMBODIMENT 4: The monospecific antibody of embodiment 1, wherein 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.
[0848] EMBODIMENT 5: The monospecific antibody of embodiment 1, wherein 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.
[0849] EMBODIMENT 6: The monospecific antibody of embodiment 1, wherein 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.
[0850] EMBODIMENT 7: The monospecific antibody of embodiment 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.
[0851] EMBODIMENT 8: The monospecific antibody of embodiment 1, wherein 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 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: 518.
[0852] EMBODIMENT 9: The monospecific antibody of embodiment 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, and a LC comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 690.
[0853] EMBODIMENT 10: The monospecific antibody of embodiment 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: 576.
[0854] EMBODIMENT 11 : The monospecific antibody of embodiment 1, wherein 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.
[0855] EMBODIMENT 12: The monospecific antibody of embodiment 1, wherein 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.
[0856] EMBODIMENT 13: The monospecific antibody of embodiment 1, wherein 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.
[0857] EMBODIMENT 14: The monospecific antibody of embodiment 1, wherein 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.
[0858] EMBODIMENT 15: The monospecific antibody of embodiment 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 577, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 578.
[0859] EMBODIMENT 16: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0860] EMBODIMENT 17: The monospecific antibody of embodiment 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.
[0861] EMBODIMENT 18: The monospecific antibody of embodiment 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.
[0862] EMBODIMENT 19: The monospecific antibody of embodiment 1, wherein 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.
[0863] EMBODIMENT 20: The monospecific antibody of embodiment 1, wherein 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.
[0864] EMBODIMENT 21 : The monospecific antibody of embodiment 1, wherein 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.
[0865] EMBODIMENT 22: The monospecific antibody of embodiment 1, wherein 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.
[0866] EMBODIMENT 23: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[0867] EMBODIMENT 24: The monospecific antibody of embodiment 1, wherein 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 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: 493.
[0868] EMBODIMENT 25: The monospecific antibody of embodiment 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.
[0869] EMBODIMENT 26: The monospecific antibody of embodiment 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.
[0870] EMBODIMENT 27: The monospecific antibody of embodiment 1, wherein 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.
[0871] EMBODIMENT 28: The monospecific antibody of embodiment 1, wherein 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.
[0872] EMBODIMENT 29: The monospecific antibody of embodiment 1, wherein 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.
[0873] EMBODIMENT 30: The monospecific antibody of embodiment 1, wherein 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.
[0874] EMBODIMENT 31 : The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[0875] EMBODIMENT 32: The monospecific antibody of embodiment 1, wherein 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.
[0876] EMBODIMENT 33: The monospecific antibody of embodiment 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.
[0877] EMBODIMENT 34: The monospecific antibody of embodiment 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.
[0878] EMBODIMENT 35: The monospecific antibody of embodiment 1, wherein 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.
[0879] EMBODIMENT 36: The monospecific antibody of embodiment 1, wherein 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.
[0880] EMBODIMENT 37: The monospecific antibody of embodiment 1, wherein 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.
[0881] EMBODIMENT 38: The monospecific antibody of embodiment 1, wherein 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.
[0882] EMBODIMENT 39: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[0883] EMBODIMENT 40: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0884] EMBODIMENT 41 : The monospecific antibody of embodiment 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.
[0885] EMBODIMENT 42: The monospecific antibody of embodiment 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.
[0886] EMBODIMENT 43: The monospecific antibody of embodiment 1, wherein 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.
[0887] EMBODIMENT 44: The monospecific antibody of embodiment 1, wherein 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.
[0888] EMBODIMENT 45: The monospecific antibody of embodiment 1, wherein 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.
[0889] EMBODIMENT 46: The monospecific antibody of embodiment 1, wherein 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.
[0890] EMBODIMENT 47: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[0891] EMBODIMENT 48: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0892] EMBODIMENT 49: The monospecific antibody of embodiment 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.
[0893] EMBODIMENT 50: The monospecific antibody of embodiment 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.
[0894] EMBODIMENT 51 : The monospecific antibody of embodiment 1, wherein 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.
[0895] EMBODIMENT 52: The monospecific antibody of embodiment 1, wherein 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.
[0896] EMBODIMENT 53: The monospecific antibody of embodiment 1, wherein 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.
[0897] EMBODIMENT 54: The monospecific antibody of embodiment 1, wherein 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.
[0898] EMBODIMENT 55: The monospecific antibody of embodiment 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 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.
[0899] EMBODIMENT 56: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0900] EMBODIMENT 57: The monospecific antibody of embodiment 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.
[0901] EMBODIMENT 58: The monospecific antibody of embodiment 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.
[0902] EMBODIMENT 59: The monospecific antibody of embodiment 1, wherein 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.
[0903] EMBODIMENT 60: The monospecific antibody of embodiment 1, wherein 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.
[0904] EMBODIMENT 61 : The monospecific antibody of embodiment 1, wherein 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.
[0905] EMBODIMENT 62: The monospecific antibody of embodiment 1, wherein 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.
[0906] EMBODIMENT 63: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 553.
[0907] EMBODIMENT 64: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0908] EMBODIMENT 65: The monospecific antibody of embodiment 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.
[0909] EMBODIMENT 66: The monospecific antibody of embodiment 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.
[0910] EMBODIMENT 67: The monospecific antibody of embodiment 1, wherein 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.
[0911] EMBODIMENT 68: The monospecific antibody of embodiment 1, wherein 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.
[0912] EMBODIMENT 69: The monospecific antibody of embodiment 1, wherein 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.
[0913] EMBODIMENT 70: The monospecific antibody of embodiment 1, wherein 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.
[0914] EMBODIMENT 71 : The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[0915] EMBODIMENT 72: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0916] EMBODIMENT 73: The monospecific antibody of embodiment 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: 696.
[0917] EMBODIMENT 74: The monospecific antibody of embodiment 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.
[0918] EMBODIMENT 75: The monospecific antibody of embodiment 1, wherein 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.
[0919] EMBODIMENT 76: The monospecific antibody of embodiment 1, wherein 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.
[0920] EMBODIMENT 77: The monospecific antibody of embodiment 1, wherein 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.
[0921] EMBODIMENT 78: The monospecific antibody of embodiment 1, wherein 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.
[0922] EMBODIMENT 79: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549.
[0923] EMBODIMENT 80: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0924] EMBODIMENT 81 : The monospecific antibody of embodiment 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.
[0925] EMBODIMENT 82: The monospecific antibody of embodiment 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.
[0926] EMBODIMENT 83: The monospecific antibody of embodiment 1, wherein 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.
[0927] EMBODIMENT 84: The monospecific antibody of embodiment 1, wherein 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.
[0928] EMBODIMENT 85: The monospecific antibody of embodiment 1, wherein 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.
[0929] EMBODIMENT 86: The monospecific antibody of embodiment 1, wherein 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.
[0930] EMBODIMENT 87: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0931] EMBODIMENT 88: The monospecific antibody of claim 1, wherein 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; 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 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.
[0932] EMBODIMENT 89: The monospecific antibody of embodiment 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.
[0933] EMBODIMENT 90: The monospecific antibody of embodiment 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.
[0934] EMBODIMENT 91 : The monospecific antibody of embodiment 1, wherein 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.
[0935] EMBODIMENT 92: The monospecific antibody of embodiment 1, wherein 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.
[0936] EMBODIMENT 93: The monospecific antibody of embodiment 1, wherein 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.
[0937] EMBODIMENT 94: The monospecific antibody of embodiment 1, wherein 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.
[0938] EMBODIMENT 95: The monospecific antibody of embodiment 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 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.
[0939] EMBODIMENT 96: The monospecific antibody of embodiment 1, wherein 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; 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 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.
[0940] EMBODIMENT 97: The monospecific antibody of embodiment 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.
[0941] EMBODIMENT 98: The monospecific antibody of embodiment 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.
[0942] EMBODIMENT 99: The monospecific antibody of embodiment 1, wherein 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.
[0943] EMBODIMENT 100: The monospecific antibody of embodiment 1, wherein 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.
[0944] EMBODIMENT 101 : The monospecific antibody of embodiment 1, wherein 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.
[0945] EMBODIMENT 102: The monospecific antibody of embodiment 1, wherein 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.
[0946] EMBODIMENT 103: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0947] EMBODIMENT 104: The monospecific antibody of embodiment 1, wherein 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; 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 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.
[0948] EMBODIMENT 105: The monospecific antibody of embodiment 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.
[0949] EMBODIMENT 106: The monospecific antibody of embodiment 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.
[0950] EMBODIMENT 107: The monospecific antibody of embodiment 1, wherein 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.
[0951] EMBODIMENT 108: The monospecific antibody of embodiment 1, wherein 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.
[0952] EMBODIMENT 109: The monospecific antibody of embodiment 1, wherein 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.
[0953] EMBODIMENT 110: The monospecific antibody of embodiment 1, wherein 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.
[0954] EMBODIMENT 111 : The monospecific antibody of embodiment 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: 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.
[0955] EMBODIMENT 112: The monospecific antibody of embodiment 1, wherein 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 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.
[0956] EMBODIMENT 113: The monospecific antibody of embodiment 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.
[0957] EMBODIMENT 114: The monospecific antibody of embodiment 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.
[0958] EMBODIMENT 115: The monospecific antibody of embodiment 1, wherein 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.
[0959] EMBODIMENT 116: The monospecific antibody of embodiment 1, wherein 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.
[0960] EMBODIMENT 117: The monospecific antibody of embodiment 1, wherein 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.
[0961] EMBODIMENT 118: The monospecific antibody of embodiment 1, wherein 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.
[0962] EMBODIMENT 119: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0963] EMBODIMENT 120: The monospecific antibody of embodiment 1, wherein 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 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.
[0964] EMBODIMENT 121 : The monospecific antibody of embodiment 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.
[0965] EMBODIMENT 122: The monospecific antibody of embodiment 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.
[0966] EMBODIMENT 123: The monospecific antibody of embodiment 1, wherein 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
[0967] EMBODIMENT 124: The monospecific antibody of embodiment 1, wherein 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.
[0968] EMBODIMENT 125: The monospecific antibody of embodiment 1, wherein 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.
[0969] EMBODIMENT 126: The monospecific antibody of embodiment 1, wherein 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.
[0970] EMBODIMENT 127: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0971] EMBODIMENT 128: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0972] EMBODIMENT 129: The monospecific antibody of embodiment 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.
[0973] EMBODIMENT 130: The monospecific antibody of embodiment 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.
[0974] EMBODIMENT 131 : The monospecific antibody of embodiment 1, wherein 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.
[0975] EMBODIMENT 132: The monospecific antibody of embodiment 1, wherein 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.
[0976] EMBODIMENT 133: The monospecific antibody of embodiment 1, wherein 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.
[0977] EMBODIMENT 134: The monospecific antibody of embodiment 1, wherein 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.
[0978] EMBODIMENT 135: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0979] EMBODIMENT 136: The monospecific antibody of embodiment 1, wherein 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 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.
[0980] EMBODIMENT 137: The monospecific antibody of embodiment 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.
[0981] EMBODIMENT 138: The monospecific antibody of embodiment 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.
[0982] EMBODIMENT 139: The monospecific antibody of embodiment 1, wherein 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.
[0983] EMBODIMENT 140: The monospecific antibody of embodiment 1, wherein 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.
[0984] EMBODIMENT 141 : The monospecific antibody of embodiment 1, wherein 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.
[0985] EMBODIMENT 142: The monospecific antibody of embodiment 1, wherein 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.
[0986] EMBODIMENT 143: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0987] EMBODIMENT 144: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[0988] EMBODIMENT 145: The monospecific antibody of embodiment 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.
[0989] EMBODIMENT 146: The monospecific antibody of embodiment 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.
[0990] EMBODIMENT 147: The monospecific antibody of embodiment 1, wherein 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.
[0991] EMBODIMENT 148: The monospecific antibody of embodiment 1, wherein 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.
[0992] EMBODIMENT 149: The monospecific antibody of embodiment 1, wherein 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.
[0993] EMBODIMENT 150: The monospecific antibody of embodiment 1, wherein 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.
[0994] EMBODIMENT 151 : The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[0995] EMBODIMENT 152: The monospecific antibody of embodiment 1, wherein 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 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 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.
[0996] EMBODIMENT 153: The monospecific antibody of embodiment 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.
[0997] EMBODIMENT 154: The monospecific antibody of embodiment 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.
[0998] EMBODIMENT 155: The monospecific antibody of embodiment 1, wherein 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.
[0999] EMBODIMENT 156: The monospecific antibody of embodiment 1, wherein 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.
[1000] EMBODIMENT 157: The monospecific antibody of embodiment 1, wherein 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.
[1001] EMBODIMENT 158: The monospecific antibody of embodiment 1, wherein 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.
[1002] EMBODIMENT 159: The monospecific antibody of embodiment 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.
[1003] EMBODIMENT 160: The monospecific antibody of embodiment 1, wherein 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, 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: 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.
[1004] EMBODIMENT 161 : The monospecific antibody of embodiment 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.
[1005] EMBODIMENT 162: The monospecific antibody of embodiment 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.
[1006] EMBODIMENT 163: The monospecific antibody of embodiment 1, wherein 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.
[1007] EMBODIMENT 164: The monospecific antibody of embodiment 1, wherein 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.
[1008] EMBODIMENT 165: The monospecific antibody of embodiment 1, wherein 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.
[1009] EMBODIMENT 166: The monospecific antibody of embodiment 1, wherein 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.
[1010] EMBODIMENT 167: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 497.
[ion] EMBODIMENT 168: The monospecific antibody of embodiment 1, wherein 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: 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 CDRL2 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.
[1012] EMBODIMENT 169: The monospecific antibody of embodiment 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.
[1013] EMBODIMENT 170: The monospecific antibody of embodiment 1, wherein 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.
[1014] EMBODIMENT 171 : The monospecific antibody of embodiment 1, wherein 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.
[1015] EMBODIMENT 172: The monospecific antibody of embodiment 1, wherein 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.
[1016] EMBODIMENT 173: The monospecific antibody of embodiment 1, wherein 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.
[1017] EMBODIMENT 174: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[1018] EMBODIMENT 175: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1019] EMBODIMENT 176: The monospecific antibody of embodiment 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.
[1020] EMBODIMENT 177: The monospecific antibody of embodiment 1, wherein 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.
[1021] EMBODIMENT 178: The monospecific antibody of embodiment 1, wherein 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.
[1022] EMBODIMENT 179: The monospecific antibody of embodiment 1, wherein 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.
[1023] EMBODIMENT 180: The monospecific antibody of embodiment 1, wherein 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.
[1024] EMBODIMENT 181 : The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 504.
[1025] EMBODIMENT 182: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1026] EMBODIMENT 183: The monospecific antibody of embodiment 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.
[1027] EMBODIMENT 184: The monospecific antibody of embodiment 1, wherein 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.
[1028] EMBODIMENT 185: The monospecific antibody of embodiment 1, wherein 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.
[1029] EMBODIMENT 186: The monospecific antibody of embodiment 1, wherein 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.
[1030] EMBODIMENT 187: The monospecific antibody of embodiment 1, wherein 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.
[1031] EMBODIMENT 188: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 493.
[1032] EMBODIMENT 189: The monospecific antibody of embodiment 1, wherein 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 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: 493.
[1033] EMBODIMENT 190: The monospecific antibody of embodiment 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.
[1034] EMBODIMENT 191 : The monospecific antibody of embodiment 1, wherein 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.
[1035] EMBODIMENT 192: The monospecific antibody of embodiment 1, wherein 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
[1036] EMBODIMENT 193: The monospecific antibody of embodiment 1, wherein 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.
[1037] EMBODIMENT 194: The monospecific antibody of embodiment 1, wherein 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.
[1038] EMBODIMENT 195: The monospecific antibody of embodiment 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: 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.
[1039] EMBODIMENT 196: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1040] EMBODIMENT 197: The monospecific antibody of embodiment 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.
[1041] EMBODIMENT 198: The monospecific antibody of embodiment 1, wherein 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.
[1042] EMBODIMENT 199: The monospecific antibody of embodiment 1, wherein 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.
[1043] EMBODIMENT 200: The monospecific antibody of embodiment 1, wherein 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.
[1044] EMBODIMENT 201 : The monospecific antibody of embodiment 1, wherein 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.
[1045] EMBODIMENT 202: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 515.
[1046] EMBODIMENT 203: The monospecific antibody of embodiment 1, wherein 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: 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 CDRL2 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.
[1047] EMBODIMENT 204: The monospecific antibody of embodiment 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.
[1048] EMBODIMENT 205: The monospecific antibody of embodiment 1, wherein 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.
[1049] EMBODIMENT 206: The monospecific antibody of embodiment 1, wherein 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.
[1050] EMBODIMENT 207: The monospecific antibody of embodiment 1, wherein 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: 516.
[1051] EMBODIMENT 208: The monospecific antibody of embodiment 1, wherein 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.
[1052] EMBODIMENT 209: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 518.
[1053] EMBODIMENT 210: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1054] EMBODIMENT 211 : The monospecific antibody of embodiment 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.
[1055] EMBODIMENT 212: The monospecific antibody of embodiment 1, wherein 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.
[1056] EMBODIMENT 213: The monospecific antibody of embodiment 1, wherein 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.
[1057] EMBODIMENT 214: The monospecific antibody of embodiment 1, wherein 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.
[1058] EMBODIMENT 215: The monospecific antibody of embodiment 1, wherein 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: 525.
[1059] EMBODIMENT 216: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 527.
[1060] EMBODIMENT 217: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1061] EMBODIMENT 218: The monospecific antibody of embodiment 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.
[1062] EMBODIMENT 219: The monospecific antibody of embodiment 1, wherein 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.
[1063] EMBODIMENT 220: The monospecific antibody of embodim/ent 1, wherein 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.
[1064] EMBODIMENT 221 : The monospecific antibody of embodiment 1, wherein 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.
[1065] EMBODIMENT 222: The monospecific antibody of embodiment 1, wherein 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.
[1066] EMBODIMENT 223: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.
[1067] EMBODIMENT 224: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1068] EMBODIMENT 225: The monospecific antibody of embodiment 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.
[1069] EMBODIMENT 226: The monospecific antibody of embodiment 1, wherein 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
[1070] EMBODIMENT 227: The monospecific antibody of embodiment 1, wherein 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.
[1071] EMBODIMENT 228: The monospecific antibody of embodiment 1, wherein 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.
[1072] EMBODIMENT 229: The monospecific antibody of embodiment 1, wherein 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.
[1073] EMBODIMENT 230: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 538.
[1074] EMBODIMENT 231 : The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1075] EMBODIMENT 232: The monospecific antibody of embodiment 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.
[1076] EMBODIMENT 233: The monospecific antibody of embodiment 1, wherein 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.
[1077] EMBODIMENT 234: The monospecific antibody of embodiment 1, wherein 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.
[1078] EMBODIMENT 235: The monospecific antibody of embodiment 1, wherein 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.
[1079] EMBODIMENT 236: The monospecific antibody of embodiment 1, wherein 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.
[1080] EMBODIMENT 237: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
[1081] EMBODIMENT 238: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1082] EMBODIMENT 239: The monospecific antibody of embodiment 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.
[1083] EMBODIMENT 240: The monospecific antibody of embodiment 1, wherein 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.
[1084] EMBODIMENT 241 : The monospecific antibody of embodiment 1, wherein 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.
[1085] EMBODIMENT 242: The monospecific antibody of embodiment 1, wherein 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.
[1086] EMBODIMENT 243: The monospecific antibody of embodiment 1, wherein 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.
[1087] EMBODIMENT 244: The monospecific antibody of embodiment 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 545, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 542.
[1088] EMBODIMENT 245: The monospecific antibody of embodiment 1, wherein 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: 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 CDRL2 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.
[1089] EMBODIMENT 246: The monospecific antibody of embodiment 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.
[1090] EMBODIMENT 247: The monospecific antibody of embodiment 1, wherein 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.
[1091] EMBODIMENT 248: The monospecific antibody of embodiment 1, wherein 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.
[1092] EMBODIMENT 249: The monospecific antibody of embodiment 1, wherein 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.
[1093] EMBODIMENT 250: The monospecific antibody of embodiment 1, wherein 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.
[1094] EMBODIMENT 251 : The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 549.
[1095] EMBODIMENT 252: The monospecific antibody of embodiment 1, wherein 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: 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 CDRL2 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.
[1096] EMBODIMENT 253: The monospecific antibody of embodiment 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.
[1097] EMBODIMENT 254: The monospecific antibody of embodiment 1, wherein 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.
[1098] EMBODIMENT 255: The monospecific antibody of embodiment 1, wherein 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.
[1099] EMBODIMENT 256: The monospecific antibody of embodiment 1, wherein 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.
[1100] EMBODIMENT 257: The monospecific antibody of embodiment 1, wherein 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.
[HOI] EMBODIMENT 258: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 557.
[1102] EMBODIMENT 259: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1103] EMBODIMENT 260: The monospecific antibody of embodiment 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
[1104] EMBODIMENT 261 : The monospecific antibody of embodiment 1, wherein 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
[1105] EMBODIMENT 262: The monospecific antibody of embodiment 1, wherein 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
[1106] EMBODIMENT 263: The monospecific antibody of embodiment 1, wherein 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
[1107] EMBODIMENT 264: The monospecific antibody of embodiment 1, wherein 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.
[1108] EMBODIMENT 265: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[1109] EMBODIMENT 266: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1110] EMBODIMENT 267: The monospecific antibody of embodiment 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.
[HU] EMBODIMENT 268: The monospecific antibody of embodiment 1, wherein 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.
[1112] EMBODIMENT 269: The monospecific antibody of embodiment 1, wherein 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.
[1H3] EMBODIMENT 270: The monospecific antibody of embodiment 1, wherein 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.
[1H4] EMBODIMENT 271 : The monospecific antibody of embodiment 1, wherein 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.
[1115] EMBODIMENT 272: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 511.
[1116] EMBODIMENT 273: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1H7] EMBODIMENT 274: The monospecific antibody of embodiment 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.
[1H8] EMBODIMENT 275: The monospecific antibody of embodiment 1, wherein 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.
[1119] EMBODIMENT 276: The monospecific antibody of embodiment 1, wherein 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.
[1120] EMBODIMENT 277: The monospecific antibody of embodiment 1, wherein 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.
[H21] EMBODIMENT 278: The monospecific antibody of embodiment 1, wherein 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.
[1122] EMBODIMENT 279: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[1123] EMBODIMENT 280: The monospecific antibody of embodiment 1, wherein 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.
[H24] EMBODIMENT 281 : The monospecific antibody of embodiment 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.
[H25] EMBODIMENT 282: The monospecific antibody of embodiment 1, wherein 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.
[1126] EMBODIMENT 283: The monospecific antibody of embodiment 1, wherein 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: 572.
[1127] EMBODIMENT 284: The monospecific antibody of embodiment 1, wherein 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.
[1128] EMBODIMENT 285: The monospecific antibody of embodiment 1, wherein 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.
[1129] EMBODIMENT 286: The monospecific antibody of embodiment 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 CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
[1130] EMBODIMENT 287: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[H31] EMBODIMENT 288: The monospecific antibody of embodiment 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.
[1132] EMBODIMENT 289: The monospecific antibody of embodiment 1, wherein 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.
[1133] EMBODIMENT 290: The monospecific antibody of embodiment 1, wherein 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.
[1134] EMBODIMENT 291 : The monospecific antibody of embodiment 1, wherein 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.
[1135] EMBODIMENT 292: The monospecific antibody of embodiment 1, wherein 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.
[1136] EMBODIMENT 293: The monospecific antibody of embodiment 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: 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.
[1137] EMBODIMENT 294: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1138] EMBODIMENT 295: The monospecific antibody of embodiment 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.
[1139] EMBODIMENT 296: The monospecific antibody of embodiment 1, wherein 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.
[1140] EMBODIMENT 297: The monospecific antibody of embodiment 1, wherein 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.
[1141] EMBODIMENT 298: The monospecific antibody of embodiment 1, wherein 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.
[1142] EMBODIMENT 299: The monospecific antibody of embodiment 1, wherein 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.
[H43] EMBODIMENT 300: The monospecific antibody of embodiment 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 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.
[1144] EMBODIMENT 301 : The monospecific antibody of embodiment 1, wherein 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 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: 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 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.
[1145] EMBODIMENT 302: The monospecific antibody of embodiment 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.
[1146] EMBODIMENT 303: The monospecific antibody of embodiment 1, wherein 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.
[H47] EMBODIMENT 304: The monospecific antibody of embodiment 1, wherein 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.
[1148] EMBODIMENT 305: The monospecific antibody of embodiment 1, wherein 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.
[1149] EMBODIMENT 306: The monospecific antibody of embodiment 1, wherein 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.
[1150] EMBODIMENT 307: The monospecific antibody of embodiment 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.
[H51] EMBODIMENT 308: The monospecific antibody of embodiment 1, wherein 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 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.
[1152] EMBODIMENT 309: The monospecific antibody of embodiment 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.
[1153] EMBODIMENT 310: The monospecific antibody of embodiment 1, wherein 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
[1154] EMBODIMENT 311 : The monospecific antibody of embodiment 1, wherein 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.
[1155] EMBODIMENT 312: The monospecific antibody of embodiment 1, wherein 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.
[1156] EMBODIMENT 313: The monospecific antibody of embodiment 1, wherein 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.
[H57] EMBODIMENT 314: The monospecific antibody of embodiment 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.
[1158] EMBODIMENT 315: The monospecific antibody of embodiment 1, wherein 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 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.
[1159] EMBODIMENT 316: The monospecific antibody of embodiment 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.
[1160] EMBODIMENT 317: The monospecific antibody of embodiment I, wherein 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.
[H61] EMBODIMENT 318: The monospecific antibody of embodiment 1, wherein 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.
[1162] EMBODIMENT 319: The monospecific antibody of embodiment 1, wherein 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.
[1163] EMBODIMENT 320: The monospecific antibody of embodiment 1, wherein 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.
[1164] EMBODIMENT 321 : The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1165] EMBODIMENT 322: The monospecific antibody of embodiment 1, wherein the antibody comprises: (a) a VH having an amino acid sequence with at least 80% 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 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.
[1166] EMBODIMENT 323: The monospecific antibody of embodiment 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.
[H67] EMBODIMENT 324: The monospecific antibody of embodiment 1, wherein 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.
[1168] EMBODIMENT 325: The monospecific antibody of embodiment 1, wherein 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.
[1169] EMBODIMENT 326: The monospecific antibody of embodiment 1, wherein 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.
[1170] EMBODIMENT 327: The monospecific antibody of embodiment 1, wherein 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.
[1171] EMBODIMENT 328: The monospecific antibody of embodiment 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: 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.
[1172] EMBODIMENT 329: The monospecific antibody of embodiment 1, wherein 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, 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 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.
[1173] EMBODIMENT 330: The monospecific antibody of embodiment 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.
[1174] EMBODIMENT 331 : The monospecific antibody of embodiment 1, wherein 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.
[1175] EMBODIMENT 332: The monospecific antibody of embodiment 1, wherein 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.
[1176] EMBODIMENT 333: The monospecific antibody of embodiment 1, wherein 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.
[1177] EMBODIMENT 334: The monospecific antibody of embodiment 1, wherein 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.
[1178] EMBODIMENT 335: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1179] EMBODIMENT 336: The monospecific antibody of embodiment 1, wherein 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 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.
[1180] EMBODIMENT 337: The monospecific antibody of embodiment 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.
[1181] EMBODIMENT 338: The monospecific antibody of embodiment 1, wherein 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.
[1182] EMBODIMENT 339: The monospecific antibody of embodiment 1, wherein 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.
[1183] EMBODIMENT 340: The monospecific antibody of embodiment 1, wherein 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.
[1184] EMBODIMENT 341 : The monospecific antibody of embodiment 1, wherein 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.
[1185] EMBODIMENT 342: The monospecific antibody of embodiment 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 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.
[1186] EMBODIMENT 343: The monospecific antibody of embodiment 1, wherein 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 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.
[1187] EMBODIMENT 344: The monospecific antibody of embodiment 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.
[1188] EMBODIMENT 345: The monospecific antibody of embodiment 1, wherein 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.
[1189] EMBODIMENT 346: The monospecific antibody of embodiment 1, wherein 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.
[1190] EMBODIMENT 347: The monospecific antibody of embodiment 1, wherein 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.
[H91] EMBODIMENT 348: The monospecific antibody of embodiment 1, wherein 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.
[1192] EMBODIMENT 349: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1193] EMBODIMENT 350: The monospecific antibody of embodiment 1, wherein 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 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.
[1194] EMBODIMENT 351 : The monospecific antibody of embodiment 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.
[H95] EMBODIMENT 352: The monospecific antibody of embodiment 1, wherein the antibody comprises 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.
[1196] EMBODIMENT 353: The monospecific antibody of embodiment 1, wherein 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.
[1197] EMBODIMENT 354: The monospecific antibody of embodiment I, wherein 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.
[1198] EMBODIMENT 355: The monospecific antibody of embodiment 1, wherein 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.
[1199] EMBODIMENT 356: The monospecific antibody of embodiment 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.
[1200] EMBODIMENT 357: The monospecific antibody of embodiment 1, wherein 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 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.
[1201] EMBODIMENT 358: The monospecific antibody of embodiment I, 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.
[1202] EMBODIMENT 359: The monospecific antibody of embodiment 1, wherein 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.
[1203] EMBODIMENT 360: The monospecific antibody of embodiment 1, wherein the antibody comprises a VH having an amino acid sequence with at least 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.
[1204] EMBODIMENT 361 : The monospecific antibody of embodiment 1, wherein 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.
[1205] EMBODIMENT 362: The monospecific antibody of embodiment 1, wherein 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.
[1206] EMBODIMENT 363: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1207] EMBODIMENT 364: The monospecific antibody of embodiment 1, wherein 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 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.
[1208] EMBODIMENT 365: The monospecific antibody of embodiment 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.
[1209] EMBODIMENT 366: The monospecific antibody of embodiment 1, wherein 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.
[1210] EMBODIMENT 367: The monospecific antibody of embodiment 1, wherein 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.
[1211] EMBODIMENT 368: The monospecific antibody of embodiment 1, wherein the antibody comprises a VH having an amino acid sequence with at least 95% identity to SEQ ID NO: 658 and a VL having an amino acid sequence with at least 95% identity to SEQ ID NO: 602.
[1212] EMBODIMENT 369: The monospecific antibody of embodiment 1, wherein 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.
[1213] EMBODIMENT 370: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1214] EMBODIMENT 371 : The monospecific antibody of embodiment 1, wherein 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 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.
[1215] EMBODIMENT 372: The monospecific antibody of embodiment 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.
[1216] EMBODIMENT 373: The monospecific antibody of embodiment 1, wherein 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.
[1217] EMBODIMENT 374: The monospecific antibody of embodiment 1, wherein 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.
[1218] EMBODIMENT 375: The monospecific antibody of embodiment 1, wherein 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.
[1219] EMBODIMENT 376: The monospecific antibody of embodiment 1, wherein 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.
[1220] EMBODIMENT 377: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1221] EMBODIMENT 378: The monospecific antibody of embodiment 1, wherein 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 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.
[1222] EMBODIMENT 379: The monospecific antibody of embodiment 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.
[1223] EMBODIMENT 380: The monospecific antibody of embodiment 1, wherein 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.
[1224] EMBODIMENT 381 : The monospecific antibody of embodiment 1, wherein 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.
[1225] EMBODIMENT 382: The monospecific antibody of embodiment 1, wherein 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.
[1226] EMBODIMENT 383: The monospecific antibody of embodiment 1, wherein 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.
[1227] EMBODIMENT 384: The monospecific antibody of embodiment 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.
[1228] EMBODIMENT 385: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1229] EMBODIMENT 386: The monospecific antibody of embodiment 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.
[1230] EMBODIMENT 387: The monospecific antibody of embodiment 1, wherein 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.
[1231] EMBODIMENT 388: The monospecific antibody of embodiment 1, wherein 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.
[1232] EMBODIMENT 389: The monospecific antibody of embodiment 1, wherein 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.
[1233] EMBODIMENT 390: The monospecific antibody of embodiment 1, wherein 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.
[1234] EMBODIMENT 391 : The monospecific antibody of embodiment 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 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.
[1235] EMBODIMENT 392: The monospecific antibody of embodiment 1, wherein 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 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.
[1236] EMBODIMENT 393: The monospecific antibody of embodiment 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.
[1237] EMBODIMENT 394: The monospecific antibody of embodiment 1, wherein 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.
[1238] EMBODIMENT 395: The monospecific antibody of embodiment 1, wherein 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.
[1239] EMBODIMENT 396: The monospecific antibody of embodiment 1, wherein 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.
[1240] EMBODIMENT 397: The monospecific antibody of embodiment 1, wherein 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.
[1241] EMBODIMENT 398: The monospecific antibody of embodiment 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.
[1242] EMBODIMENT 399: The monospecific antibody of embodiment 1, wherein 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 CDRL2 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.
[1243] EMBODIMENT 400: The monospecific antibody of embodiment 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.
[1244] EMBODIMENT 401 : The monospecific antibody of embodiment 1, wherein 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.
[1245] EMBODIMENT 402: The monospecific antibody of embodiment 1, wherein 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.
[1246] EMBODIMENT 403: The monospecific antibody of embodiment 1, wherein 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.
[1247] EMBODIMENT 404: The monospecific antibody of embodiment 1, wherein 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.
[1248] EMBODIMENT 405: The monospecific antibody of embodiment 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.
[1249] EMBODIMENT 406: The monospecific antibody of embodiment 1, wherein 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 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; 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 CDRL2 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.
[1250] EMBODIMENT 407: The monospecific antibody of embodiment 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
[1251] EMBODIMENT 408: The monospecific antibody of embodiment 1, wherein 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.
[1252] EMBODIMENT 409: The monospecific antibody of embodiment 1, wherein 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.
[1253] EMBODIMENT 410: The monospecific antibody of embodiment 1, wherein 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.
[1254] EMBODIMENT 411 : The monospecific antibody of embodiment 1, wherein 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.
[1255] EMBODIMENT 412: The monospecific antibody of embodiment 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 CDRL3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
[1256] EMBODIMENT 413: The monospecific antibody of embodiment 1, wherein 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.
[1257] EMBODIMENT 414: The monospecific antibody of embodiment 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.
[1258] EMBODIMENT 415: The monospecific antibody of embodiment 1, wherein 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.
[1259] EMBODIMENT 416: The monospecific antibody of embodiment 1, wherein 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.
[1260] EMBODIMENT 417: The monospecific antibody of embodiment 1, wherein 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.
[1261] EMBODIMENT 418: The monospecific antibody of embodiment 1, wherein 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.
[1262] EMBODIMENT 419: The monospecific antibody of embodiment 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: 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.
[1263] EMBODIMENT 420: The monospecific antibody of embodiment 1, wherein 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 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.
[1264] EMBODIMENT 421 : The monospecific antibody of embodiment 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.
[1265] EMBODIMENT 422: The monospecific antibody of embodiment 1, wherein 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.
[1266] EMBODIMENT 423: The monospecific antibody of embodiment 1, wherein 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.
[1267] EMBODIMENT 424: The monospecific antibody of embodiment 1, wherein 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.
[1268] EMBODIMENT 425: The monospecific antibody of embodiment 1, wherein 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.
[1269] EMBODIMENT 426: The monospecific antibody of embodiment 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: 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 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.
[1270] EMBODIMENT 427: The monospecific antibody of embodiment 1, wherein 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 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.
[1271] EMBODIMENT 428: The antibody of any one of embodiments 1-427, wherein the antibody is a monovalent antibody.
[1272] EMBODIMENT 429: The monospecific antibody of any one of embodiments 1- 428, wherein the Fc region is a wild-type Fc region.
[1273] EMBODIMENT 430: The monospecific antibody of any one of embodiments 1- 428, wherein the Fc region is a modified Fc region.
[1274] EMBODIMENT 431 : The monospecific antibody of embodiment 430, wherein 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/Q311V/A378V mutation, T256D/H286D/T307R/Q311V/A378V mutation, H285N/T307Q/N315D mutation, T307Q/Q311V/A378V mutation, H285D/T307Q/A378V mutation, L234F/L235E/P331S mutation, L234F/L235Q/K322Q mutation, L234F/L235Q/P331G mutation, L234F/L235A/K322Q mutation, S228P/F234A/L235A/G237A/P238S mutation, L234A/L235E/G237A/A330S/P331S mutation, F243A/V264A mutation, S228P/L235E/P329G mutation, M252Y/M428L mutation, D2591/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.
[1275] EMBODIMENT 432: The monospecific antibody of embodiment 430 or 431, wherein the modified Fc region is N-terminally truncated.
[1276] EMBODIMENT 433: The monospecific antibody of embodiment 432, wherein the modified Fc region is N-terminally truncated 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, or more amino acid residues.
[1277] EMBODIMENT 434: The monospecific antibody of any one of embodiments 1- 433, wherein the antibody is a human IgG4 antibody comprising a first heavy chain and a second heavy chain.
[1278] EMBODIMENT 435: The monospecific antibody of embodiment 434, 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.
[1279] EMBODIMENT 436: The monospecific antibody of embodiment 434, wherein the first heavy chain comprises a S228P/T366W/delta-K447 mutation and the second heavy chain comprises a S228P/T366S/L368A/Y407V/delta-K447 mutation.
[1280] EMBODIMENT 437: The monospecific antibody of any one of embodiments 434-436, wherein the first heavy chain and the second heavy chain further comprise a M252Y/S254T/T256E mutation.
[1281] EMBODIMENT 438: The monospecific antibody of any one of embodiments 1- 437, 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.
[1282] EMBODIMENT 439: The monospecific antibody of any one of embodiments 1-
437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: D2726, R2730, D2746, and K2757.
[1283] EMBODIMENT 440: The monospecific antibody of any one of embodiments 1-
437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744, and D2746.
[1284] EMBODIMENT 441 : The monospecific antibody of any one of embodiments 1-
437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, D2746, and K2757.
[1285] EMBODIMENT 442: The monospecific antibody of any one of embodiments 1-
437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, D2746, and K2757.
[1286] EMBODIMENT 443: The monospecific antibody of any one of embodiments 1-
437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, E2744, D2746, and D2763.
[1287] EMBODIMENT 444: The monospecific antibody of any one of embodiments 1- 437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744, D2746, K2757, and D2763.
[1288] EMBODIMENT 445: The monospecific antibody of any one of embodiments 1- 437, wherein the antibody binds to at least amino acid residue K2735 of the VWF CK domain.
[1289] EMBODIMENT 446: The monospecific antibody of any one of embodiments 1- 437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: D2726, K2735, and K2757.
[1290] EMBODIMENT 447: The monospecific antibody of any one of embodiments 1- 437, wherein the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735 and D2763.
[1291] EMBODIMENT 448: A complex comprising a VWF protein and a monospecific antibody of any one of embodiments 1-447.
[1292] EMBODIMENT 449: A pharmaceutical composition comprising the monospecific antibody of any one of embodiments 1-447 and a pharmaceutically acceptable carrier, diluent, or excipient.
[1293] EMBODIMENT 450: The pharmaceutical composition of embodiment 449, wherein 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.
[1294] EMBODIMENT 451 : 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 embodiments 1-447 or the pharmaceutical composition of embodiment 449 or 450.
[1295] EMBODIMENT 452: The method of embodiment 451, wherein 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.
[1296] EMBODIMENT 453 : The method of embodiment 452, wherein the VWD is congenital VWD (cVWD) or acquired VWD (aVWD).
[1297] EMBODIMENT 454: The method of embodiment 452 or 453, wherein the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
[1298] EMBODIMENT 455: The method of any one of embodiments 451-454, 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.
[1299] EMBODIMENT 456: The method of any one of embodiments 451-455, wherein the composition or pharmaceutical composition promotes platelet adhesion and/or aggregation in the subject.
[1300] EMBODIMENT 457: A method of accumulating a VWF protein in blood plasma of a subject in need thereof, comprising administering to the subject a composition comprising the monospecific antibody of any one of embodiments 1-447 or the pharmaceutical composition of embodiment 449 or 450.
[1301] EMBODIMENT 458: A method of accumulating a FVIII protein in blood plasma of a subject in need thereof, comprising administering to the subject a composition comprising the monospecific antibody of any one of embodiments 1-447 or the pharmaceutical composition of embodiment 449 or 450.
[1302] EMBODIMENT 459: A method 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 any one of embodiments 1-447 or the pharmaceutical composition of embodiment 449 or 450.
[1303] EMBODIMENT 460: The method of any one of embodiments 451-459, wherein the composition is a pharmaceutical composition comprising the monospecific antibody and a pharmaceutically acceptable carrier, diluent, or excipient.
[1304] EMBODIMENT 461 : The method of embodiment 460, wherein 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.
[1305] EMBODIMENT 462: The method of any one of embodiments 451-461, wherein the composition or the pharmaceutical composition is administered in combination with one or more additional therapeutic modalities.
[1306] EMBODIMENT 463 : The method of embodiment 462, wherein the one or more additional therapeutic modalities are 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 protein, a concentrate of recombinant VWF protein, a concentrate of FVIII protein, hormonal treatment, gene therapy, blood transfusion, platelet transfusion, surgery, and cauterization.
[1307] EMBODIMENT 464: The method of embodiment 463, wherein the gene therapy is FVIII gene therapy.
[1308] EMBODIMENT 465: The method of any one of embodiments 462-464, wherein 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.
[1309] EMBODIMENT 466: The method of any one of embodiments 451-465, wherein the subject is a human.
[1310] EMBODIMENT 467: A monospecific antibody of any one of embodiments 1-447 or the pharmaceutical composition of embodiment 449 or 450 for use as a medicament.
[1311] EMBODIMENT 468: The monospecific antibody or the pharmaceutical composition of embodiment 467 for use in the treatment of a blood disorder characterized by excessive bleeding.
[1312] EMBODIMENT 469: A monospecific antibody of any one of embodiments 1-447 or the pharmaceutical composition of embodiment 449 or 450 for use in the treatment of a blood disorder characterized by excessive bleeding.
[1313] EMBODIMENT 470: The monospecific antibody or the pharmaceutical composition for use according to embodiment 468 or 469, 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.
[1314] EMBODIMENT 471 : The monospecific antibody or the pharmaceutical composition for use according to embodiment 470, wherein the VWD is cVWD or aVWD.
[1315] EMBODIMENT 472: The monospecific antibody or the pharmaceutical composition for use according to embodiment 470 or 471, wherein the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
Claims
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 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.
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 acid
sequence 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: 696
28. 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 acid
sequence 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 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 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 SEQ
ID 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 SEQ
ID 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 SEQ
ID 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 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 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 VL
comprising 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 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.
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 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.
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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| US202363519955P | 2023-08-16 | 2023-08-16 | |
| US63/519,955 | 2023-08-16 |
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| WO2025037032A1 true WO2025037032A1 (en) | 2025-02-20 |
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| PCT/EP2024/073157 WO2025037032A1 (en) | 2023-08-16 | 2024-08-16 | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
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| WO (1) | WO2025037032A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018203086A1 (en) * | 2017-05-04 | 2018-11-08 | Imperial Innovations Limited | Truncated vwf |
| WO2023156409A1 (en) * | 2022-02-15 | 2023-08-24 | Hemab Aps | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
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2024
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018203086A1 (en) * | 2017-05-04 | 2018-11-08 | Imperial Innovations Limited | Truncated vwf |
| WO2023156409A1 (en) * | 2022-02-15 | 2023-08-24 | Hemab Aps | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
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