Antibody molecules to FIXA and FX and uses thereof

Abstract

Antibody molecules that bind to FIXa and / or FX are disclosed. The antibody molecules can be used to treat, prevent, and / or diagnose disorders, such as hemophilia A. Nucleic acid molecules encoding the antibody molecules, expression vectors, host cells, compositions, kits, containers, and methods for making the antibody molecules are also disclosed.

Description

[0001] ANTIBODY MOLECULES TO FIXA AND FX AND USES THEREOF

[0002] RELATED APPLICATIONS

[0003] This application claims priority to U.S. Serial No.: 63 / 680,892, filed on August 8, 2024, the contents of which are hereby incorporated by reference in its entirety.

[0004] SEQUENCE LISTING

[0005] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on August 1, 2025, is named ALTUS-002-WO-PCT_SL.xml and is 245,370 bytes in size.

[0006] BACKGROUND

[0007] The coagulation factor VIII (anti-hemophilic factor, AHF) is a vital blood-clotting protein. Factor VIII circulates in the bloodstream as an inactive protein, bound to a large multimeric glycoprotein called von Willebrand factor (VWF). In response to injury', coagulation factor VIII is activated to FVIIIa and separates from von Willebrand factor. FVIIIa then binds to the activated factor IX (FIXa) and proteolytically activates factor X (FX) to factor Xa (FXa).

[0008] Deficiency of FVIII (congenital or acquired deficiency) leads to Hemophilia A, a rare blood disorder which affects 1 out of every 5,000 male births. The disease is characterized by excessive bleeding events, including muscle and joint hemorrhages. Unfortunately, much of the affected population have little or no access to treatment. Standard treatment involves administration of exogenous human clotting factor VIII, which replaces the missing FVIII. However, the major drawbacks with FVIII therapy include the development of anti-factor VIII alloantibodies, low bioavailability, short half-life (~12 hours in adults) and frequent IV administration (thrice weekly).

[0009] As such, there exists an unmet need for developing new approaches, including improved agents, for treating, preventing, and diagnosing FVIIIa deficiency-associated disorders and other disorders that share similar disease mechanisms.

[0010] SUMMARY

[0011] This disclosure provides, at least in part, antibody molecules that bind to FIXa and / or FX, e.g.. human FIXa and / or FX (e.g.. human FIXa comprising the amino acid sequence of SEQ ID NO: 274 and / or human FX comprising the amino acid sequence of SEQ ID NO: 276), and that comprise one or more functional and structural properties disclosed herein. In an embodiment, the antibody molecule binds FIXa and / or FX, and mimics a biological function of FVIIIa (e.g., proteolytically activates FX to FXa). In an embodiment, the antibody molecule binds to and / or modulates (e.g., activates) one or more activities of FIXa and / or FX. In an embodiment, the antibody molecule comprises a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Tabic 4, or competes for binding to FIXa and / or FX with an antibody molecule comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule binds to the same or overlapping epitope as tire epitope recognized by an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises one or more VHs described in Table 2 or 4 and / or one or more VLs described in Table 1 or 4. In an embodiment, the antibody molecule comprises one or more heavy chain complementarity determining regions (HCDRs) described in Table 2 and / or one or more light chain complementarity determining regions (LCDRs) described in Table 1. In an embodiment, the antibody molecule comprises one or more heavy chains (HC) described in Table 4 and / or one or more light chains (LC) described in Table 4. In an embodiment, nucleic acid molecules encoding the antibody molecules, expression vectors, host cells, compositions (e.g.. pharmaceutical compositions), kits, containers, and methods for making the antibody molecules, are also provided. The antibody molecules disclosed herein are suitable for use in mimicking FVIIIa binding and activation of FX. The antibody molecules disclosed herein can be used (alone or in combination with other agents or therapeutic modalities) to treat, prevent and / or diagnose coagulation-associated disorders, e.g., FVIIIa-deficiency-associated disorders, e.g., hemophilia A.

[0012] Accordingly, in an aspect, this disclosure provides an antibody molecule, e.g., an antibody molecule described herein, having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9. 10, 11, 12, 13, 14. 15, 16, 17, 18, 19, 20, 21, 22, or all) of tire following properties: a) Binds to FIXa (e.g., human FIXa) with a desired affinity, e.g., with a dissociation constant (KD’) of about 100 pM or less, e.g., about 50 pM or less. 20 pM or less, 10 pM or less, 1 pM or less, 500 nM or less, 200 nM or less, 100 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 5 nM or less, 2 nM or less, 1 nM or less, 0.5 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, about 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, or 0.001 nM or less, e.g., between 0.005 nM and 50 pM, between 0.01 nM and 20 pM. between 0.02 nM and 10 pM, between 0.05 nM and 5 pM, between 0.1 nM and 2 pM, between 0.2 nM and 1 pM. between 0.005 nM and 20 pM, between 0.005 nM and 10 pM, between 0.005 nM and 5 pM. between 0.005 nM and 2 pM. between 0.005 nM and 1 pM, between 0.005 nM and 500 nM, between 0.005 nM and 200 nM. between 0.005 nM and 100 nM, between 0.005 nM and 50 nM, between 0.005 nM and 20 nM, between 0.005 nM and 10 nM, between 0.005 nM and 5 nM, between 0.005 nM and 2 nM. between 0.005 nM and 1 nM, between 0.005 nM and 0.5 nM. between 0.005 nM and 0.2 nM. between 0.005 nM and 0.1 nM, between 0.005 nM and 0.05 nM, between 0.005 nM and 0.02 nM. between 0.005 nM and 0.01 nM. between 0.01 nM and 50 gM, between 0.02 nM and 50 gM, between 0.05 nM and 50 gM, between 0.1 nM and 50 gM, between 0.2 nM and 50 gM, between 0.5 nM and 50 gM, betw een 1 nM and 50 gM, betw een 2 nM and 50 gM, between 5 nM and 50 gM, between 10 nM and 50 gM, between 20 nM and 50 gM, between 50 nM and 50 gM, between 100 nM and 50 gM, between 200 nM and 50 gM, between 500 nM and 50 gM, between 1 gM and 50 gM, between 2 gM and 50 gM, between 5 gM and 50 gM, between 10 gM and 50 gM. between 20 gM and 50 gM, between 0.005 nM and 0.01 nM, between 0.01 nM and 0.02 nM, between 0.02 nM and 0.05 nM, between 0.05 nM and 0.1 nM. between 0.1 nM and 0.2 nM, between 0.2 nM and 0.5 nM, between 0.5 nM and 1 nM, between 1 nM and 2 nM. between 2 nM and 5 nM, between 5 nM and 10 nM. between 10 nM and 20 nM, between 20 nM and 50 nM. between 50 nM and 100 nM. between 100 nM and 200 nM, between 200 nM and 500 nM, between 500 nM and 1 gM. between 1 gM and 2 gM. between 2 gM and 5 gM. between 5 gM and 10 gM. between 10 gM and 20 gM, or between 20 gM and 50 gM, e.g., as determined by a method described herein; b) Binds to FX (e.g.. human FX) with a desired affinity, e.g., with a dissociation constant (KD ) of about 100 gM or less, e.g.. about 50 gM or less. 20 gM or less. 10 gM or less, 1 gM or less. 500 run or less, 200 nM or less, 100 nM or less. 50 nM or less. 20 nM or less.

[0013] 10 nM or less, 5 nM or less. 2 nM or less, 1 nM or less. 0.5 nM or less, 0.2 nM or less, 0.1 nM or less. 0.05 nM or less. 0.02 nM or less, about 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, or 0.001 nM or less, e.g., between 0.005 nM and 50 gM, between 0.01 nM and 20 gM, between 0.02 nM and 10 gM, between 0.05 nM and 5 gM, between 0.1 nM and 2 gM, between 0.2 nM and 1 gM, between 0.005 nM and 20 gM, between 0.005 nM and 10 gM, between 0.005 nM and 5 gM, betw een 0.005 nM and 2 gM. between 0.005 nM and 1 gM, between 0.005 nM and 500 nM, between 0.005 nM and 200 nM, betw een 0.005 nM and 100 nM, between 0.005 nM and 50 nM, between 0.005 nM and 20 nM, between 0.005 nM and 10 nM, betw een 0.005 nM and 5 nM, between 0.005 nM and 2 nM, between 0.005 nM and 1 nM, between 0.005 nM and 0.5 nM, between 0.005 nM and 0.2 nM, between 0.005 nM and 0.1 nM, between 0.005 nM and 0.05 nM, between 0.005 nM and 0.02 nM, between 0.005 nM and 0.01 nM, between 0.01 nM and 50 gM, between 0.02 nM and 50 gM. between 0.05 nM and 50 gM, between 0.1 nM and 50 gM, between 0.2 nM and 50 gM, between 0.5 nM and 50 gM, between 1 nM and 50 gM. between 2 nM and 50 gM, between 5 nM and 50 gM, between 10 nM and 50 gM, between 20 nM and 50 gM, between 50 nM and 50 gM, between 100 nM and 50 gM, between 200 nM and 50 gM, between 500 nM and 50 gM, between 1 gM and 50 gM, between 2 gM and 50 gM, between 5 gM and 50 gM, between 10 gM and 50 gM, between 20 gM and 50 gM, between 0.005 nM and 0.01 nM. between 0.01 nM and 0.02 nM. between 0.02 nM and 0.05 nM, between 0.05 nM and 0.1 nM, between 0.1 nM and 0.2 nM, betw een 0.2 nM and 0.5 nM, betw een 0.5 nM and 1 nM, betw een 1 nM and 2 nM, between 2 nM and 5 nM, between 5 nM and 10 nM, between 10 nM and 20 nM, betw een 20 nM and 50 nM, between 50 nM and 100 nM, between 100 nM and 200 nM, between 200 nM and 500 nM, between 500 nM and 1 gM, between 1 gM and 2 gM. between 2 gM and 5 gM. between 5 gM and 10 gM. between 10 gM and 20 gM, or between 20 gM and 50 gM, e.g., as determined by a method described herein; c) Binds to FIXa (e.g., human FIXa) with a desired affinity, e.g., with a half maximal effective concentration (EC50) of about 50 gg / ml or less, e.g. 25 gg / ml or less, 10 gg / ml or less, 5 gg / ml or less. 2 gg / ml or less, 1 gg / ml or less, 0.5 gg / ml or less. 0.2 gg / ml or less. 0.1 gg / ml or less, 0.05 gg / ml or less, 0.02 gg / ml or less. 0.01 gg / ml or less, 0.005 gg / ml or less, e.g.. between 0.005 gg / ml and 50 gg / ml. between 0.01 gg / ml and 25 gg / ml, between 0.02 gg / ml and 20 gg / ml. between 0.05 gg / ml and 10 gg / ml, between 0.1 gg / ml and 5 gg / ml, between 0.2 gg / ml and 2 gg / ml. between 0.5 gg / ml and 1 gg / ml, between 0.01 gg / ml and 20 gg / ml, between 0.01 gg / ml and 10 gg / ml, between 0.01 gg / ml and 5 gg / ml. between 0.01 gg / ml and 2 gg / ml. between 0.01 gg / ml and 1 gg / ml. between 0.01 gg / ml and 0.5 gg / ml, between 0.01 gg / ml and 0.2 gg / ml, between 0.01 gg / ml and 0.1 gg / ml, between 0.01 gg / ml and 0.05 gg / ml, between 0.02 gg / ml and 50 gg / ml. between 0.05 gg / ml and 50 gg / ml, between 0.1 gg / ml and 50 gg / ml, between 0.2 gg / ml and 50 gg / ml, between 0.5 gg / ml and 50 gg / ml, between 1 gg / ml and 50 gg / ml, between 2 gg / ml and 50 gg / ml, between 5 gg / ml and 50 gg / ml, between 10 gg / ml and 50 gg / ml. between 20 gg / ml and 50 gg / ml, betw een 0.005 gg / ml and 0.01 gg / ml, between 0.01 gg / ml and 0.02 gg / ml, between 0.02 gg / ml and 0.05 gg / ml, between 0.05 gg / ml and 0.1 gg / ml, between 0.1 gg / ml and 0.2 gg / ml, between 0.2 gg / ml and 0.5 gg / ml, between 0.5 gg / ml and 1 gg / ml, between 1 gg / ml and 2 gg / ml, between 2 gg / ml and 5 gg / ml, betw een 5 gg / ml and 10 gg / ml, between 10 gg / ml and 50 gg / ml, or betw een 20 gg / ml and 50 gg / ml, e.g., between 0.01 gg / ml and 23.70 gg / ml, e.g., as determined by a method described herein; d) Binds to FX (e.g. , human FX) with a desired affinity, e.g., with a half maximal effective concentration (EC50) of about 10 gg / ml or less, e.g., 5 gg / ml or less, 2 gg / ml or less, 1 gg / ml or less, 0.5 gg / ml or less. 0.2 gg / ml or less, 0.1 gg / ml or less, 0.05 gg / ml or less, 0.02 gg / ml or less, 0.01 gg / ml or less. 0.005 gg / ml or less, e.g., between 0.005 gg / ml and 10 gg / ml, between 0.01 gg / ml and 5 gg / ml, between 0.02 gg / ml and 2 gg / ml, between 0.05 gg / ml and 1 gg / ml, between 0.1 gg / ml and 0.5 gg / ml. between 0.01 gg / ml and 10 gg / ml, between 0.01 gg / ml and 5 gg / ml, between 0.01 gg / ml and 2 gg / ml, between 0.01 gg / ml and 1 gg / ml, between 0.01 gg / ml and 0.5 gg / ml, between 0.01 gg / ml and 0.2 gg / ml, between 0.01 gg / ml and 0.1 gg / ml, between 0.01 gg / ml and 0.05 gg / ml, between 0.02 gg / ml and 10 gg / ml, between 0.05 gg / ml and 10 gg / ml. between 0.1 gg / ml and 10 gg / ml, between 0.2 gg / ml and 10 gg / ml, between 0.5 gg / ml and 10 gg / ml, between 1 gg / ml and 10 gg / ml, between 2 gg / ml and 10 gg / ml, between 5 gg / ml and 10 gg / ml, between 0.005 gg / ml and 0.01 gg / ml, between 0.01 gg / ml and 0.02 gg / ml, between 0.02 gg / ml and 0.05 gg / ml, betw een 0.05 gg / ml and 0.1 gg / ml, betw een 0.1 gg / ml and 0.2 gg / ml, between 0.2 gg / ml and 0.5 gg / ml, between 0.5 gg / ml and 1 gg / ml, between 1 gg / ml and 2 gg / ml, between 2 gg / ml and 5 gg / ml, or between 5 gg / ml and 10 gg / ml, e.g., between 0.01 gg / ml and 4.51 gg / ml, e.g., as determined by a method described herein; e) Binds specifically to an epitope on FIXa (e.g., human FIXa), e.g., the same, similar, or overlapping epitope as the epitope recognized by a bispecific antibody described herein (e.g., an antibody molecule (e.g, a bispecific antibody molecule) comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4);

[0014] 1) Binds specifically to an epitope on FX (e.g.. human FX). e.g., the same, similar, or overlapping epitope as the epitope recognized by a bispecific antibody described herein (e.g.. an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4); g) Modulates (e.g., activates) one or more biological activities of FIXa (e.g., human FIXa), in vitro, ex vivo, or in vivo; h) Modulates (e.g., activates) one or more biological activities of FX (e.g., human FX), in vitro, ex vivo, or in vivo; i) Modulates (e.g., activates) one or more biological activities of FIXa (e.g., human FIXa), e.g., at a half maximal effective concentration (ECso) of about 50 gg / ml or less, e.g., 25 gg / ml or less, 10 gg / ml or less, 5 gg / ml or less, 2 gg / ml or less. 1 gg / ml or less, 0.5 gg / ml or less, 0.2 gg / ml or less, 0.1 gg / ml or less, 0.05 gg / ml or less, 0.02 gg / ml or less, 0.01 gg / ml or less, 0.005 gg / ml or less, e.g., between 0.005 gg / ml and 50 gg / ml, between 0.01 gg / ml and 25 gg / ml, between 0.02 gg / ml and 20 gg / ml, between 0.05 gg / ml and 10 gg / ml, between 0.1 gg / ml and 5 gg / ml, between 0.2 gg / ml and 2 gg / ml, between 0.5 gg / ml and 1 gg / ml, between 0.01 gg / ml and 20 gg / ml, between 0.01 gg / ml and 10 gg / ml, between 0.01 gg / ml and 5 gg / ml, between 0.01 gg / ml and 2 gg / ml, between 0.01 gg / ml and 1 gg / ml. between 0.01 gg / ml and 0.5 gg / ml. between 0.01 gg / ml and 0.2 gg / ml. between 0.01 gg / ml and 0.1 gg / ml, between 0.01 gg / ml and 0.05 gg / ml, between 0.02 gg / ml and 50 gg / ml, between 0.05 gg / ml and 50 gg / ml, between 0.1 gg / ml and 50 gg / ml, between 0.2 gg / ml and 50 gg / ml, between 0.5 gg / ml and 50 gg / ml. between 1 gg / ml and 50 gg / ml, between 2 gg / ml and 50 gg / ml. between 5 gg / ml and 50 gg / ml. between 10 gg / ml and 50 gg / ml. between 20 gg / ml and 50 gg / ml, between 0.005 gg / ml and 0.01 gg / ml, between 0.01 gg / ml and 0.02 gg / ml. between 0.02 gg / ml and 0.05 gg / ml, between 0.05 gg / ml and 0.1 gg / ml, between 0.1 gg / ml and 0.2 gg / ml, betw een 0.2 gg / ml and 0.5 gg / ml, between 0.5 gg / ml and 1 gg / ml, between 1 gg / ml and 2 gg / ml, between 2 gg / ml and 5 gg / ml, between 5 gg / ml and 10 gg / ml, between 10 gg / ml and 50 gg / ml, or between 20 gg / ml and 50 gg / ml, e.g., as determined by a method described herein; j) Modulates (e.g., activates) one or more biological activities of FX (e.g., human FX), e.g., at a half maximal effective concentration (EC50) of about 10 gg / ml or less, e.g., 5 gg / ml or less, 2 gg / ml or less. 1 gg / ml or less, 0.5 gg / ml or less, 0.2 gg / ml or less, 0.1 gg / ml or less. 0.05 gg / ml or less, 0.02 gg / ml or less, 0.01 gg / ml or less, 0.005 gg / ml or less, e.g., between 0.005 gg / ml and 10 gg / ml. between 0.01 gg / ml and 5 gg / ml. between 0.02 gg / ml and 2 gg / ml, between 0.05 gg / ml and 1 gg / ml, between 0.1 gg / ml and 0.5 gg / ml, between 0.01 gg / ml and 10 gg / ml, between 0.01 gg / ml and 5 gg / ml, between 0.01 gg / ml and 2 gg / ml. between 0.01 gg / ml and 1 gg / ml, between 0.01 gg / ml and 0.5 gg / ml. between 0.01 gg / ml and 0.2 gg / ml. between 0.01 gg / ml and 0.1 gg / ml, between 0.01 gg / ml and 0.05 gg / ml, between 0.02 gg / ml and 10 gg / ml, between 0.05 gg / ml and 10 gg / ml. between 0.1 gg / ml and 10 gg / ml. between 0.2 gg / ml and 10 gg / ml. between 0.5 gg / ml and 10 gg / ml, between 1 gg / ml and 10 gg / ml, between 2 gg / ml and 10 gg / ml. between 5 gg / ml and 10 gg / ml, between 0.005 gg / ml and 0.01 gg / ml, between 0.01 gg / ml and 0.02 gg / ml, between 0.02 gg / ml and 0.05 gg / ml. between 0.05 gg / ml and 0.1 gg / ml. between 0.1 gg / ml and 0.2 gg / ml, between 0.2 gg / ml and 0.5 gg / ml, between 0.5 gg / ml and 1 gg / ml. betw een 1 gg / ml and 2 gg / ml, between 2 gg / ml and 5 gg / ml, or between 5 gg / ml and 10 gg / ml, e.g., as determined by a method described herein; k) Increases (e.g., activates) the level of FXa (e.g., FIXa-catalyzed FXa generation), e.g., at a half maximal effective concentration (ECso) of about 20 gg / ml or less, e.g., 10 gg / ml or less, 5 gg / ml or less, 2 gg / ml or less, 1 gg / ml or less, 0.5 gg / ml or less, 0.2 gg / ml or less, 0.1 gg / ml or less, 0.05 gg / ml or less, 0.02 gg / ml or less, 0.01 gg / ml or less, 0.005 gg / ml or less, e.g., between 0.005 gg / ml and 10 gg / ml, between 0.01 gg / ml and 5 gg / ml, between 0.02 gg / ml and 2 gg / ml, between 0.05 gg / ml and 1 gg / ml, between 0.1 gg / ml and 0.5 gg / ml, betw een 0.01 gg / ml and 10 gg / ml, betw een 0.01 gg / ml and 5 gg / ml, between 0.01 gg / ml and 2 gg / ml, between 0.01 gg / ml and 1 gg / ml, between 0.01 gg / ml and 0.5 gg / ml, between 0.01 gg / ml and 0.2 gg / ml, between 0.01 gg / ml and 0.1 gg / ml, between 0.01 gg / ml and 0.05 gg / ml, between 0.02 gg / ml and 10 gg / ml. between 0.05 gg / ml and 10 gg / ml, between 0.1 gg / ml and 10 gg / ml, between 0.2 gg / ml and 10 gg / ml. between 0.5 gg / ml and 10 gg / ml, between 1 gg / ml and 10 gg / ml. between 2 gg / ml and 10 gg / ml, between 5 gg / ml and 10 gg / ml, between 0.005 gg / ml and 0.01 gg / ml. between 0.01 gg / ml and 0.02 gg / ml. between 0.02 gg / ml and 0.05 gg / ml, between 0.05 gg / ml and 0.1 gg / ml. between 0.1 gg / ml and 0.2 gg / ml, between 0.2 gg / ml and 0.5 gg / ml, between 0.5 gg / ml and 1 gg / ml. between 1 gg / ml and 2 gg / ml, between 2 gg / ml and 5 gg / ml, betw een 5 pg / ml and 10 pg / ml, or between 10 pg / ml and 20 pg / ml, e.g., as determined by a method described herein; l) Shows the same or similar binding affinity or specificity, or both, as an antibody molecule (e g., a bispecific antibody) comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4; m) Shows the same or similar binding affinity or specificity, or both, as an antibody molecule (e.g., a bispecific antibody molecule) comprising a heavy chain variable region (VH) described in Table 2 or 4 and / or light chain variable region (VL) described in Table 1 or 4; n) Shows the same or similar binding affinity or specificity, or both, as an antibody molecule (e.g., a bispecific antibody molecule) comprising one or more (e.g.. two or three) heavy chain CDRs (HCDRs) described in Table 2 and / or one or more (e.g.. two or three) light chain CDRs (LCDRs) described in Table 1; o) Shows the same or similar binding affinity or specificity, or both, as an antibody molecule (e.g.. a bispecific antibody molecule) comprising an amino acid sequence shown in Tables 1, 2, or 4; p) Shows the same or similar binding affinity or specificity, or both, as an antibody molecule (e.g, a bispecific antibody molecule) comprising an amino acid sequence encoded by a nucleotide sequence described herein; q) Inhibits, e.g., competitively inhibits, the binding of a second antibody molecule to FIXa (e.g., human FIXa), wherein the second antibody molecule is an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4; r) Inhibits, e.g., competitively inhibits, the binding of a second antibody molecule to FX (e.g, human FX), wherein the second antibody molecule is an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a heavy drain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4; s) Competes for binding with a second antibody molecule to FIXa (e.g. , human FIXa), wherein the second antibody molecule is a bispecific antibody comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in or FIGs. 1A-1B, 2, or 3 or Table 4; t) Competes for binding with a second antibody molecule to FX (e.g.. human FX). wherein the second antibody molecule is a bispecific antibody comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4; u) Has one or more biological properties of a bispecific antibody comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4; v) Has one or more structural properties of a bispecific antibody comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4; or w) Has one or more pharmacokinetic properties of a bispecific antibody comprising a combination of a heavy chain variable region (VH) and a light chain variable region (VL) described in FIGs. 1A-1B, 2, or 3 or Table 4.

[0015] In an aspect, the disclosure features an isolated antibody molecule, comprising a first binding moiety capable of binding to FIXa. FX. or both, wherein the first binding moiety comprises: a first heavy chain variable region (VH) comprising an HCDR1 amino acid sequence of any of SEQ ID NOs: 214. 217, 220. 223, 226, 229. 232, 235, or 239; an HCDR2 amino acid sequence of any of SEQ ID NOs: 215, 218, 221. 224, 227, 230. 233, 236, 240. 242, 243, 244, 245, 246. or 260; and an HCDR3 amino acid sequence of any of SEQ ID NOs: 216, 219, 222. 225, 228, 231. 234, 237, 238. or 241; and a first light chain variable region (VL) comprising an LCDR1 amino acid sequence of any of SEQ ID NOs: 151. 154, 157, 160. 163, 166, 169, 172, 175, 181, 184, 251-253, or 258; an LCDR2 amino acid sequence of any of SEQ ID NOs: 152, 155, 158, 161, 164, 167, 170, 176, 249, 250. 254, or 255; and an LCDR3 amino acid sequence of any of SEQ ID NOs: 153, 156, 159, 162, 165, 168, 171, 174, 180, 183, 247, 248, 256, 257, 259, or 299.

[0016] In an embodiment, the first VH comprises:

[0017] (a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0018] (b) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0019] (c) the HCDR1 amino acid sequence of SEQ ID NO: 217, the HCDR2 amino acid sequence of SEQ ID NO: 218, and the HCDR3 amino acid sequence of SEQ ID NO: 222;

[0020] (d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221. and the HCDR3 amino acid sequence of SEQ ID NO: 225;

[0021] (e) the HCDR1 amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224. and the HCDR3 amino acid sequence of SEQ ID NO: 228;

[0022] (1) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227. and the HCDR3 amino acid sequence of SEQ ID NO: 231; (g) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0023] (li) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0024] (i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0025] (j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0026] (k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230. and the HCDR3 amino acid sequence of SEQ ID NO: 231;

[0027] (l) the HCDR1 amino acid sequence of SEQ ID NO: 232, the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;

[0028] (m) the HCDR1 amino acid sequence of SEQ ID NO: 235. the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;

[0029] (n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0030] (o) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0031] (p) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0032] (q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0033] (r) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0034] (s) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0035] (t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0036] (u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0037] (v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260. and the HCDR3 amino acid sequence of SEQ ID NO: 241; or

[0038] (w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260. and the HCDR3 amino acid sequence of SEQ ID NO: 219.

[0039] In an embodiment, the first VL comprises:

[0040] (a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 152. and the LCDR3 amino acid sequence of SEQ ID NO: 153; (b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0041] (c) the LCDR1 amino acid sequence of SEQ ID NO: 157, the LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;

[0042] (d) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0043] (e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0044] (1) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;

[0045] (g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;

[0046] (h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0047] (i) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0048] (j) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;

[0049] (k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0050] (l) the LCDR1 amino acid sequence of SEQ ID NO: 175. the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;

[0051] (m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0052] (n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;

[0053] (o) the LCDR1 amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;

[0054] (p) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0055] (q) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0056] (r) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;

[0057] (s) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156; (t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0058] (u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0059] (v) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0060] (w) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250. and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0061] (x) the LCDR1 amino acid sequence of SEQ ID NO: 253, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0062] (y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0063] (z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;

[0064] (aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;

[0065] (bb) the LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0066] (cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0067] (dd) tire LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0068] (ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;

[0069] (II) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0070] (gg) tire LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247; or

[0071] (hh) the LCDR1 ammo acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 247.

[0072] In an embodiment, the first VH comprises:

[0073] (a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215. and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0074] (b) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215. and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0075] (c) the HCDR1 amino acid sequence of SEQ ID NO: 217, the HCDR2 amino acid sequence of SEQ ID NO: 218. and the HCDR3 amino acid sequence of SEQ ID NO: 222; (d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221, and the HCDR3 amino acid sequence of SEQ ID NO: 225;

[0076] (e) the HCDR1 amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224, and the HCDR3 amino acid sequence of SEQ ID NO: 228;

[0077] (I) the HCDR1 amino acid sequence of SEQ ID NO: 229, tire HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231;

[0078] (g) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227. and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0079] (h) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230. and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0080] (i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0081] (j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0082] (k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 231 ;

[0083] (l) the HCDR1 amino acid sequence of SEQ ID NO: 232. the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;

[0084] (m) the HCDR1 amino acid sequence of SEQ ID NO: 235, the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;

[0085] (n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0086] (o) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0087] (p) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0088] (q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0089] (r) the HCDR1 amino acid sequence of SEQ ID NO: 239, tire HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0090] (s) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244. and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0091] (t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0092] (u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246. and the HCDR3 amino acid sequence of SEQ ID NO: 241; (v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 241; or

[0093] (w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 219; and the first VL comprises:

[0094] (a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0095] (b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0096] (c) the LCDR1 amino acid sequence of SEQ ID NO: 157, the LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;

[0097] (d) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152. and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0098] (e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0099] (1) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;

[0100] (g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;

[0101] (h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0102] (i) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0103] (j) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;

[0104] (k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0105] (l) the LCDR1 amino acid sequence of SEQ ID NO: 175, the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;

[0106] (m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0107] (n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;

[0108] (o) the LCDR1 amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;

[0109] (p) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249. and the LCDR3 amino acid sequence of SEQ ID NO: 247; (q) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0110] (r) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;

[0111] (s) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0112] (t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0113] (u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0114] (v) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0115] (w) the LCDR1 amino acid sequence of SEQ ID NO: 160. the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0116] (x) the LCDR1 amino acid sequence of SEQ ID NO: 253. the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0117] (y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0118] (z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;

[0119] (aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;

[0120] (bb) tire LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0121] (cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0122] (dd) tire LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0123] (ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;

[0124] (0) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250. and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0125] (gg) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 152. and the LCDR3 amino acid sequence of SEQ ID NO: 247; or

[0126] (hh) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 255. and the LCDR3 amino acid sequence of SEQ ID NO: 247. In an embodiment, the first VH comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 95-125 or 279-281. In an embodiment, the first VH comprises an amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281.

[0127] In an embodiment, the first VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69. 71-76, 78, 80, 82, 84, or 86-94. In an embodiment, the first VL comprises an amino acid sequence of any of SEQ ID NOs: 1-36. 48-51, 60-63, 65, 66, 68. 69, 71-76, 78. 80, 82, 84, or 86- 94.

[0128] In an embodiment, the first VH comprises an amino acid sequence at least 85%. 90%, 91%, 92%, 93%, 94%, 95%. 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 95-125 or 279-281; and the first VL comprises an amino acid sequence at least 85%. 90%, 91%, 92%. 93%. 94%, 95%, 96%. 97%, 98%, or 99% identical to any of SEQ ID NOs: 1-36, 48-51. 60-63, 65. 66. 68, 69, 71-76, 78, 80, 82, 84, or 86-94. In an embodiment, the first VH comprises an amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281; and the first VL comprises an amino acid sequence of any of SEQ ID NOs: 1-36, 48-51. 60-63, 65, 66. 68, 69, 71-76. 78, 80, 82, 84. or 86-94.

[0129] In an embodiment, the first binding moiety is capable of binding to FIXa and comprises:

[0130] (a) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;

[0131] (b) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 25;

[0132] (c) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:29;

[0133] (d) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 33;

[0134] (e) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:28;

[0135] (1) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 32;

[0136] (g) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 36;

[0137] (h) a first VH comprising the ammo acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 21;

[0138] (i) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 23;

[0139] (j) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 30; (k) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0140] (l) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;

[0141] (m) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0142] (n) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 34;

[0143] (o) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 35;

[0144] (p) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 62;

[0145] (q) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 63;

[0146] (r) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 75;

[0147] (s) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 73;

[0148] (t) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76;

[0149] (u) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90;

[0150] (v) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 91; or

[0151] (w) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 93.

[0152] In an embodiment, the first binding moiety is capable of binding to FX and comprises:

[0153] (a) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 17;

[0154] (b) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;

[0155] (c) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 25;

[0156] (d) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 29;

[0157] (e) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 33; (1) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 28;

[0158] (g) a first VH comprising tire amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 32;

[0159] (h) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 36;

[0160] (i) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 21;

[0161] (j) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 23;

[0162] (k) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 30;

[0163] (l) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0164] (m) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 34;

[0165] (n) a first VH comprising die amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 35;

[0166] (o) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 62;

[0167] (p) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 63;

[0168] (q) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 75;

[0169] (r) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 73;

[0170] (s) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 76;

[0171] (t) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 90;

[0172] (u) a first VH comprising the ammo acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 91;

[0173] (v) a first VH comprising the ammo acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 93;

[0174] (w) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 76; or (x) a first VH comprising die amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 90.

[0175] In an embodiment, the first binding moiety is capable of binding to bodi FIXa and FX. In an embodiment, the first binding moiety has a binding affinity to FIXa that is at least 0.5, 1, 2, 3, 4, 5, 6, 7. 8, 9, 10, 20, 50, or 100-fold higher than its binding affinity to FX. In an embodiment, the first binding moiety has a binding affinity to FX that is at least 0.5, 1, 2. 3, 4, 5, 6, 7, 8, 9, 10. 20, 50, or 100-fold higher than its binding affinity to FIXa. In an embodiment, the first binding moiety has a binding affinity to FIXa that is no more than 0.5, 1, 2, 3, 4. 5, 6, 7, 8, 9. or 10-fold higher than its binding affinity to FX. In an embodiment, the first binding moiety has a binding affinity to FX that is no more than 0.5, 1, 2. 3. 4, 5, 6, 7, 8. 9, or 10-fold higher than its binding affinity to FIXa.

[0176] In an embodiment, the antibody molecule further comprises a second binding moiety capable of binding to FIXa, FX, or both, wherein the second binding moiety comprises a second VH and a second VL.

[0177] In an embodiment, the second binding moiety comprises a second VH comprising an HCDR1 amino acid sequence of any of SEQ ID NOs: 214, 217. 220, 223, 226. 229, 232, 235. or 239; an HCDR2 amino acid sequence of any of SEQ ID NOs: 215, 218. 221, 224, 227, 230, 233. 236, 240, 242. 243, 244, 245. 246, or 260; and an HCDR3 amino acid sequence of any of SEQ ID NOs: 216, 219. 222, 225, 228. 231, 234, 237, 238, or 241; and a second VL comprising an LCDR1 amino acid sequence of any of SEQ ID NOs: 151, 154, 157. 160, 163, 166, 169, 172, 175, 181, 184. 251-253, or 258; an LCDR2 amino acid sequence of any of SEQ ID NOs: 152, 155, 158. 161, 164, 167. 170, 176, 249, 250, 254, or 255; and an LCDR3 amino acid sequence of any of SEQ ID NOs: 153, 156, 159, 162, 165, 168, 171, 174. 180, 183, 247, 248, 256, 257, 259, or 299.

[0178] In an embodiment, the second VH comprises:

[0179] (a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0180] (b) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0181] (c) tire HCDR1 amino acid sequence of SEQ ID NO: 217, the HCDR2 amino acid sequence of SEQ ID NO: 218, and the HCDR3 amino acid sequence of SEQ ID NO: 222;

[0182] (d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221. and the HCDR3 amino acid sequence of SEQ ID NO: 225;

[0183] (e) the HCDR1 amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224. and the HCDR3 amino acid sequence of SEQ ID NO: 228;

[0184] (1) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231; (g) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0185] (li) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0186] (i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0187] (j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0188] (k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230. and the HCDR3 amino acid sequence of SEQ ID NO: 231;

[0189] (l) the HCDR1 amino acid sequence of SEQ ID NO: 232, the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;

[0190] (m) the HCDR1 amino acid sequence of SEQ ID NO: 235. the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;

[0191] (n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241 ;

[0192] (o) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0193] (p) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0194] (q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0195] (r) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0196] (s) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0197] (t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0198] (u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0199] (v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260. and the HCDR3 amino acid sequence of SEQ ID NO: 241; or

[0200] (w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260. and the HCDR3 amino acid sequence of SEQ ID NO: 219.

[0201] In an embodiment, the second VL comprises:

[0202] (a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 152. and the LCDR3 amino acid sequence of SEQ ID NO: 153; (b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0203] (c) the LCDR1 amino acid sequence of SEQ ID NO: 157, the LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;

[0204] (d) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0205] (e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0206] (I) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;

[0207] (g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;

[0208] (h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0209] (i) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0210] (j) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;

[0211] (k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0212] (l) the LCDR1 amino acid sequence of SEQ ID NO: 175. the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;

[0213] (m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0214] (n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;

[0215] (o) the LCDR1 amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;

[0216] (p) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0217] (q) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0218] (r) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;

[0219] (s) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156; (t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0220] (u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0221] (v) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0222] (w) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250. and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0223] (x) the LCDR1 amino acid sequence of SEQ ID NO: 253, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0224] (y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0225] (z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;

[0226] (aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;

[0227] (bb) the LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0228] (cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0229] (dd) tire LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0230] (ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;

[0231] (II) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0232] (gg) tire LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247; or

[0233] (hh) the LCDR1 ammo acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 247.

[0234] In an embodiment, the second VH comprises:

[0235] (a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215. and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0236] (b) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215. and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0237] (c) the HCDR1 amino acid sequence of SEQ ID NO: 217, the HCDR2 amino acid sequence of SEQ ID NO: 218. and the HCDR3 amino acid sequence of SEQ ID NO: 222; (d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221, and the HCDR3 amino acid sequence of SEQ ID NO: 225;

[0238] (e) the HCDR1 amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224, and the HCDR3 amino acid sequence of SEQ ID NO: 228;

[0239] (I) the HCDR1 amino acid sequence of SEQ ID NO: 229, tire HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231;

[0240] (g) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227. and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0241] (h) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230. and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0242] (i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0243] (j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;

[0244] (k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 231 ;

[0245] (l) the HCDR1 amino acid sequence of SEQ ID NO: 232. the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;

[0246] (m) the HCDR1 amino acid sequence of SEQ ID NO: 235, the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;

[0247] (n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0248] (o) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;

[0249] (p) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0250] (q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;

[0251] (r) the HCDR1 amino acid sequence of SEQ ID NO: 239, tire HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0252] (s) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244. and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0253] (t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;

[0254] (u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246. and the HCDR3 amino acid sequence of SEQ ID NO: 241; (v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 241; or

[0255] (w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 219; and the second VL comprises:

[0256] (a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0257] (b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0258] (c) the LCDR1 amino acid sequence of SEQ ID NO: 157, the LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;

[0259] (d) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152. and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0260] (e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;

[0261] (1) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;

[0262] (g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;

[0263] (h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0264] (i) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;

[0265] (j) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;

[0266] (k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0267] (l) the LCDR1 amino acid sequence of SEQ ID NO: 175, the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;

[0268] (m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;

[0269] (n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;

[0270] (o) the LCDR1 amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;

[0271] (p) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249. and the LCDR3 amino acid sequence of SEQ ID NO: 247; (q) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0272] (r) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;

[0273] (s) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0274] (t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0275] (u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0276] (v) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0277] (w) the LCDR1 amino acid sequence of SEQ ID NO: 160. the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 156;

[0278] (x) the LCDR1 amino acid sequence of SEQ ID NO: 253. the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0279] (y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0280] (z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;

[0281] (aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;

[0282] (bb) tire LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0283] (cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0284] (dd) tire LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0285] (ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;

[0286] (If) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250. and the LCDR3 amino acid sequence of SEQ ID NO: 247;

[0287] (gg) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 152. and the LCDR3 amino acid sequence of SEQ ID NO: 247; or

[0288] (hh) the LCDR1 amino acid sequence of SEQ ID NO: 154. the LCDR2 amino acid sequence of SEQ ID NO: 255. and the LCDR3 amino acid sequence of SEQ ID NO: 247. In an embodiment, the second VH comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 95-125 or 279-281. In an embodiment, the second VH comprises an amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281.

[0289] In an embodiment, the second VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69. 71-76, 78, 80, 82, 84, or 86-94. In an embodiment, the second VL comprises an amino acid sequence of any of SEQ ID NOs: 1-36. 48-51, 60-63, 65, 66, 68. 69, 71-76, 78. 80, 82, 84, or 86- 94.

[0290] In an embodiment, the second VH comprises an amino acid sequence at least 85%, 90%. 91%, 92%, 93%, 94%. 95%, 96%, 97%, 98%. or 99% identical to any of SEQ ID NOs: 95-125 or 279-281; and the second VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%. 93%. 94%. 95%, 96%, 97%. 98%. or 99% identical to any of SEQ ID NOs: 1-36. 48-51, 60-63, 65, 66, 68. 69, 71-76, 78, 80, 82, 84, or 86-94. In an embodiment, the second VH comprises an amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281; and the second VL comprises an amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63. 65. 66, 68, 69, 71-76, 78, 80. 82. 84, or 86-94.

[0291] In an embodiment, the second binding moiety is capable of binding to FIXa and comprises:

[0292] (a) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;

[0293] (b) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 25;

[0294] (c) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO:29;

[0295] (d) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 33;

[0296] (e) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO:28;

[0297] (1) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 32;

[0298] (g) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 36;

[0299] (h) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 21;

[0300] (i) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 23;

[0301] (j) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 30; (k) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 31;

[0302] (l) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;

[0303] (m) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 31;

[0304] (n) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 34;

[0305] (o) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 35;

[0306] (p) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 62;

[0307] (q) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 63;

[0308] (r) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 75;

[0309] (s) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 73;

[0310] (t) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 76;

[0311] (u) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 90;

[0312] (v) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 91; or

[0313] (w) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 93.

[0314] In an embodiment, the second binding moiety is capable of binding to FX and comprises:

[0315] (a) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 17;

[0316] (b) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;

[0317] (c) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 25;

[0318] (d) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 29;

[0319] (e) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 33; (I) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 28;

[0320] (g) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 32;

[0321] (h) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 36;

[0322] (i) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 21;

[0323] (j) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 23;

[0324] (k) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 30;

[0325] (l) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 31 ;

[0326] (m) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 34;

[0327] (n) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 35;

[0328] (o) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 62;

[0329] (p) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 63;

[0330] (q) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 75;

[0331] (r) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 73;

[0332] (s) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 76;

[0333] (t) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 90;

[0334] (u) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 91;

[0335] (v) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 93;

[0336] (w) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 76; or (x) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 90.

[0337] In an embodiment, the second binding moiety is capable of binding to both FIXa and FX. In an embodiment, the first binding moiety is capable of binding to both FIXa and FX, and the second binding moiety is capable of binding to both FIXa and FX.

[0338] In an embodiment, the second binding moiety has a binding affinity to FIXa that is at least 0.5, 1, 2, 3, 4, 5, 6. 7, 8, 9, 10, 20, 50, or 100-fold higher than its binding affinity to FX. In an embodiment, the second binding moiety' has a binding affinity to FX that is at least 0.5, 1, 2, 3. 4, 5, 6, 7. 8, 9, 10, 20. 50, or 100-fold higher than its binding affinity to FIXa. In an embodiment, the second binding moiety has a binding affinity to FIXa that is no more than 0.5, 1, 2. 3. 4, 5, 6, 7, 8. 9, or 10- fold higher than its binding affinity to FX. In an embodiment, the second binding moiety has a binding affinity to FX that is no more than 0.5, 1, 2. 3. 4, 5, 6, 7, 8. 9. or 10-fold higher than its binding affinity to FIXa.

[0339] In an embodiment, the first binding moiety is identical, or substantially identical, to the second binding moiety. In an embodiment, the first binding moiety' is different from the second binding moiety.

[0340] In an embodiment, the second VH is identical, or substantially identical, to the first VH, and the second VL is identical, or substantially identical, to the first VL. In an embodiment, the second VH is identical, or substantially identical, to the first VH, and the second VL is different from the first VL. In an embodiment, the second VH is different from the first VH. and the second VL is identical, or substantially identical, to the first VL. In an embodiment, the second VH is different from the first VH. and the second VL is different from the first VL.

[0341] In an embodiment, the second binding moiety' has a binding affinity to FIXa that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or 100-fold higher than the binding affinity of the first binding moiety' to FIXa. In an embodiment, the second binding moiety has a binding affinity' to FIXa that is no more than 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold higher than the binding affinity' of the first binding moiety' to FIXa. In an embodiment, the second binding moiety has a binding affinity' to FX that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9. 10, 20, 50, or 100-fold higher than the binding affinity of the first binding moiety to FX. In an embodiment, the second binding moiety has a binding affinity to FX that is no more than 0.5, 1, 2, 3, 4, 5, 6, 7, 8. 9, or 10-fold higher than the binding affinity' of the first binding moiety to FX.

[0342] In an embodiment, the first binding moiety comprises a Fab, the second binding moiety comprises a Fab, or both. In an embodiment, the first binding moiety and the second binding moiety are not covalently linked. In an embodiment, the antibody molecule is a tetramer comprising two VHs and two VLs.

[0343] In an embodiment, the first binding moiety comprises a single chain Fv (scFv), the second binding moiety comprises an scFv. or both. In an embodiment, the first binding moiety and the second binding moiety arc covalently linked. In an embodiment, the first binding moiety and the second binding moiety are covalently linked by a linker. In an embodiment, the linker comprises one or more glycine residues and one or more serine residues (“GS” linker).

[0344] In an embodiment, the first binding moiety' is capable of binding to FIXa and comprises:

[0345] (a) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;

[0346] (b) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 25;

[0347] (c) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:29;

[0348] (d) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 33;

[0349] (e) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:28;

[0350] (T) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 32;

[0351] (g) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 36;

[0352] (h) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 21;

[0353] (i) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 23;

[0354] (j) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 30;

[0355] (k) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0356] (l) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;

[0357] (m) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0358] (n) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 34;

[0359] (o) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 35;

[0360] (p) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 62; (q) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 63;

[0361] (r) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 75;

[0362] (s) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 73;

[0363] (t) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76;

[0364] (u) a first VH comprising the ammo acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90;

[0365] (v) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 91; or

[0366] (w) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 93; and the second binding moiety is capable of binding to FX and comprises:

[0367] (a) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 17;

[0368] (b) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;

[0369] (c) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 25;

[0370] (d) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 29;

[0371] (e) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 33;

[0372] (f) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 28;

[0373] (g) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 32;

[0374] (h) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 36;

[0375] (i) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 21;

[0376] (j) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 23;

[0377] (k) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 30; (l) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 31;

[0378] (m) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 34;

[0379] (n) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 35;

[0380] (o) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 62;

[0381] (p) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 63;

[0382] (q) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 75;

[0383] (r) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 73;

[0384] (s) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 76;

[0385] (t) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 90;

[0386] (u) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 91;

[0387] (v) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 93;

[0388] (w) a second VH comprising the ammo acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 76; or

[0389] (x) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 90.

[0390] In an embodiment, the first binding moiety comprises a first VH comprising an amino acid sequence described herein, e.g., as described in Table 2 or 4 and / or a first VL comprising an amino acid sequence described herein, e.g., as described in Table 1 or 4; and a second binding moiety comprising a second VH comprising an ammo acid sequence described herein, e.g., as described in Table 2 or 4 and / or a second VL comprising an amino acid sequence described herein, e.g., as described in Table 1 or 4, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0391] In an embodiment, the first binding moiety comprises any one of the following:

[0392] (a) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 20; (b) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 25;

[0393] (c) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 29;

[0394] (d) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 33;

[0395] (e) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 28;

[0396] (I) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 32;

[0397] (g) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 36;

[0398] (h) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 21;

[0399] (i) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 23;

[0400] (j) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 30;

[0401] (k) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0402] (l) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 20;

[0403] (m) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 31;

[0404] (n) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 34;

[0405] (o) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 35;

[0406] (p) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 62;

[0407] (q) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 63;

[0408] (r) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 75;

[0409] (s) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 73; (t) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 76;

[0410] (u) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 90;

[0411] (v) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 91; or

[0412] (w) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and / or a first VL comprising the amino acid sequence of SEQ ID NO: 93; and the second binding moiety comprises any one of the following:

[0413] (a) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 17;

[0414] (b) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 20;

[0415] (c) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 25;

[0416] (d) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 29;

[0417] (e) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 33;

[0418] (1) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 28;

[0419] (g) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 32;

[0420] (h) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 36;

[0421] (i) a second VH comprising Hie amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 21;

[0422] (j) a second VH comprising Hie amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 23;

[0423] (k) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 30;

[0424] (l) a second VH comprising tire amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 31;

[0425] (m) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 34;

[0426] (n) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 35; (o) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 62;

[0427] (p) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 63;

[0428] (q) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 75;

[0429] (r) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 73;

[0430] (s) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 76;

[0431] (t) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 90;

[0432] (u) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 91;

[0433] (v) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 93;

[0434] (w) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 76; or

[0435] (x) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and / or a second VL comprising the amino acid sequence of SEQ ID NO: 90.

[0436] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 20; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 20, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0437] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 62; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 62, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0438] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 63; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 63, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX. In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 75; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 75, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0439] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 73; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 73, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0440] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 76. wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0441] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 90, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0442] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 91; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 91, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0443] In an embodiment, the first binding moiety comprises a first VH comprising die amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 93; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 93, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX. In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 76, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0444] In an embodiment, the first binding moiety comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90; and the second moiety comprises a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 90, wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

[0445] In an embodiment, the antibody molecule is a multispecific antibody molecule. In an embodiment, the antibody molecule is a bispecific or dual specific antibody molecule. In an embodiment, the antibody molecule further comprises a third binding moiety. In an embodiment, the antibody molecule comprises an antigen-binding fragment. In an embodiment, the antigen-binding fragment comprises a Fab, F(ab')2, Fv, scFv. or sc(Fv)2. In an embodiment, the antibody molecule comprises a heavy chain constant region chosen from or derived from the heavy chain constant regions of IgGl, IgG2, IgG3, IgG4, or a chimera or combination thereof, and a light chain constant region chosen from or derived from the light chain constant regions of kappa or lambda. In an embodiment, the antibody molecule comprises a heavy chain constant region chosen from or derived from the heavy chain constant regions of IgGl, IgG2, IgG3, IgG4, or a chimera or combination thereof. In an embodiment, the antibody molecule comprises a light chain constant region chosen from or derived from the light chain constant regions of kappa or lambda. In an embodiment, the antibody molecule comprises an Fc region.

[0446] In an embodiment, the antibody molecule comprises a CHI comprising the amino acid sequence of SEQ ID NO: 262 or 282. In an embodiment, the first VH is linked to a CHI comprising the ammo acid sequence of SEQ ID NO: 262 or 282, directly or indirectly, and the second VH is linked to a CHI comprising the amino acid sequence of SEQ ID NO: 262 or 282, directly or indirectly. In an embodiment, the antibody molecule comprises a CL comprising the amino acid sequence of SEQ ID NO: 263 or 298. In an embodiment, the first VL is linked to a CL comprising the amino acid sequence of SEQ ID NO: 263 or 298, directly or indirectly, and the second VL is linked to a CL comprising the amino acid sequence of SEQ ID NO: 263 or 298, directly or indirectly. In an embodiment, the antibody molecule comprises a hinge region comprising the amino acid sequence of SEQ ID NO: 264. In an embodiment, the first VH is linked to a hinge region comprising the amino acid sequence of SEQ ID NO: 264. indirectly, and the second VH is linked to a hinge region comprising the amino acid sequence of SEQ ID NO: 264. indirectly. In an embodiment, the antibody molecule comprises a CH2 comprising the amino acid sequence of SEQ ID NO: 265. 261, or 283. In an embodiment, the antibody molecule the first VH is linked to a CH2 comprising the amino acid sequence of SEQ ID NO: 265, 261, or 283, indirectly, and the second VH is linked to a CH2 comprising the amino acid sequence of any of SEQ ID NO: 265, 261, or 283, indirectly. In an embodiment, the antibody molecule comprises a CH3 comprising the amino acid sequence of any of SEQ ID NO: 266, 271, 272, 284, 285, 296, or 297. In an embodiment, the antibody molecule the first VH is linked to a CH3 comprising the amino acid sequence of any of SEQ ID NOs: 266. 271, 272, 284, 285, 296, or 297, indirectly, and the second VH is linked to a CH3 comprising the amino acid sequence of any of SEQ ID NOs: 266, 271, 272. 284, 285, 296, or 297, indirectly.

[0447] In some embodiments, an antibody molecule described herein comprises a CH3 comprising a M428L substitution. In some embodiments, an antibody molecule described herein comprises a CH3 comprising aN434S substitution. In some embodiments, an antibody molecule described herein comprises a CH3 comprising M428L and N434S substitutions.

[0448] In an embodiment, said antibody molecule is an isolated antibody molecule. In an embodiment, said antibody molecule is a humanized antibody molecule. In an embodiment, said antibody molecule is a monoclonal antibody molecule. In an embodiment, said antibody molecule is a synthetic antibody molecule.

[0449] In an embodiment, the FIXa is a human FIXa. In an embodiment, the FX is a human FX.

[0450] In an aspect, the disclosure features an antibody molecule that competes for binding to FIXa, FX, or both, with an antibody molecule described herein.

[0451] In an aspect, the disclosure features an antibody molecule that binds to the same or overlapping epitope on FIXa, FX. or both, as the epitope recognized by an antibody molecule described herein.

[0452] In an aspect, the disclosure features a pharmaceutical composition comprising the isolated antibody molecule described herein and a pharmaceutically acceptable carrier, excipient or stabilizer.

[0453] In an aspect, the disclosure features an isolated nucleic acid encoding the first VH, first VL, or both, of an antibody molecule described herein. In an aspect, the disclosure features an isolated nucleic acid encoding the second VH, second VL, or both, of an antibody molecule described herein.

[0454] In an aspect, the disclosure features an expression vector comprising an isolated nucleic acid encoding the first VH, first VL, or both, of an antibody molecule described herein. In an aspect, the disclosure features an expression vector comprising an isolated nucleic acid encoding the second VH, second VL, or both, of an antibody molecule described herein. In an aspect, the disclosure features an expression vector comprising an isolated nucleic acid encoding the first VH, first VL, or both, of an antibody molecule described herein, and an isolated nucleic acid encoding the second VH. second VL, or both, of an antibody molecule described herein.

[0455] In an aspect, the disclosure features a host cell comprising a nucleic acid described herein or a vector described herein. In an aspect, the disclosure features a method of producing an antibody molecule, comprising culturing the host cell described herein under conditions suitable for gene expression.

[0456] In an aspect, the disclosure features a method of increasing die level of FXa, comprising contacting a cell deficient of FVIII with an antibody molecule described herein, or a pharmaceutical composition described herein.

[0457] In an embodiment, the contacting step occurs in vitro, ex vivo, or in vivo.

[0458] In an aspect, the disclosure features a method of treating a disorder associated with a coagulation pathway, comprising administering to a subject in need thereof an antibody molecule described herein, or a pharmaceutical composition described herein, in an amount effective to treat the disorder.

[0459] In an embodiment, the disorder is a hemophilia. In an embodiment, the hemophilia is hemophilia A.

[0460] In an embodiment, the antibody molecule is administered to the subject at a dose between 0.1 mg / kg and 50 mg / kg. In an embodiment, the antibody molecule is administered to the subject at a dose between 10 mg and 2500 mg.

[0461] In an embodiment, the method further comprises administering a second therapeutic agent or modality. In an embodiment, the second therapeutic agent or modality is administered before, during, or after the antibody molecule is administered.

[0462] In an aspect, the disclosure features a method of detecting FIXa, FX, or both, comprising (i) contacting a sample or a subject with an antibody molecule described herein under conditions that allow interaction of the antibody molecule and FIXa, FX, or both, to occur, and (ii) detecting formation of a complex between the antibody molecule and FIXa, FX, or both, in the sample or subject.

[0463] In an embodiment, the method further comprises (i) contacting a reference sample or subject with an antibody molecule described herein under conditions that allow interaction of the antibody molecule and FIXa, FX, or both, to occur, and (ii) detecting formation of a complex between the antibody molecule and FIXa, FX, or both, in the sample or subject.

[0464] In an aspect, the disclosure features an antibody molecule described herein, or a pharmaceutical composition described herein, for use in treating a disorder associated with a coagulation pathway in a subject.

[0465] In an embodiment, the disorder is a hemophilia. In an embodiment, the hemophilia is hemophilia A.

[0466] In an aspect, the disclosure features a use of an antibody molecule described herein, or a pharmaceutical composition described herein, in the manufacture of a medicament for treating a disorder associated with a coagulation pathway in a subject.

[0467] In an embodiment, the disorder is a hemophilia. In an embodiment, the hemophilia is hemophilia A. BRIEF DESCRIPTION OF THE DRAWINGS

[0468] FIGs. 1A-1B are plots showing ELISA binding of factors FIXa and FX by exemplary monospecific antibodies to each factor. The dotted line indicated with “Threshold Signal” corresponds to a reference antibody comprising SEQ ID NOs: 293-295. The VH-VL combination (SEQ ID NOs) employed in the exemplary monospecific antibodies are mentioned in the x-axis.

[0469] FIG. 2 depicts a panel of LC-MS characterization and purity assessment of a representative FIXa and FX bispecific antibody. SEQ ID NOs of VHs and VLs that form each of the arms are indicated above the MS spectra.

[0470] FIG. 3 depicts activity of exemplary bispecific antibodies (200 nM) in FVIII deficient plasma. Peak thrombin generation is represented relative to the value obtained for a reference antibody comprising the amino acid sequences of SEQ ID NOs. 293-295. PNP and F8d refer to pooled normal plasma (positive control) and Factor VIII -deficient plasma (negative control), respectively. SEQ ID NOs of VHs and VLs of the exemplary’ bispecific antibodies are provided in the table.

[0471] FIG. 4 is a graph depicting thrombin peak profile and FVIII-equivalence. Thrombin peak height (nM) is plotted against increasing concentrations of two bispecific antibodies (BsAbl and a reference antibody) in FVIII-deficient plasma (left panel), and against recombinant human FVIII (rhFVIII) concentrations in lU / dL (right panel). BsAbl (squares) and the reference antibody (open triangles) both dose-dependently enhance thrombin generation, with BsAbl showing superior potency. The horizontal dashed line denotes thrombin levels consistent with near-normal FVIII activity (~40 lU / dL). rhFVIII (circles, right panel) exhibits a dose-response, serving as a benchmark for physiological FVIII equivalence. FVIII-deficient plasma alone (black triangle) shows no or minimal thrombin generation.

[0472] FIG. 5 is a graph depicting in vitro FVIII coagulant (FVIIIc) activity of exemplar}' bispecific antibodies compared to Reference Antibody. The rate of FXa generation (OD / As) was measured in the presence of 400 nM of bispecific antibodies using a chromogenic assay. Each bar represents the mean ± standard deviation from replicate measurements for the indicated antibody clone. Several antibodies demonstrated comparable or superior to the Reference Antibody under these assay conditions, with BsAbl and BsAb2 demonstrating the highest rates of FXa generation.

[0473] DETAILED DESCRIPTION

[0474] Disclosed herein are antibody molecules that bind to FIXa and / or FX. e.g., human FIXa and / or FX, with desired affinity and specificity. Advantageously, several of the antibody molecules describe herein can mimic a biological function of FVIlla (e.g., FIX-catalyzed FXa generation), e.g.. by modulating (e.g.. activating) one or more biological activities of FIXa and FX. Without wishing to be bound by theory, it is believed that in some embodiments, the antibody molecules described herein can be used to overcome, at least in part, the drawbacks of treating hemophilia A with FVIII.

[0475] Nucleic acid molecules encoding the antibody molecules, expression vectors, host cells, compositions (e.g. , pharmaceutical compositions), kits, and methods for making the antibody molecules, are also provided. The antibody molecules and pharmaceutical compositions disclosed herein can be used (alone or in combination with other agents or therapeutic modalities) to treat, prevent, and / or diagnose disorders and conditions, e.g., disorders and conditions associated with deficiency of FVIIIa, e.g., hemophilia A.

[0476] Without wishing to be bound by theory, it is believed that in some embodiments, bispecific antibodies that mimic the function of FVIII can exhibit FVIII cofactor function substitution activity and restore hemostasis. For example, these antibodies may bind to FIXa and FX, bringing them close together to replicate FVIII’s cofactor role. In some embodiments, the efficacy of these antibodies can be increased by fine-tuning the binding affinity and orientation for FIXa and FX. Emicizumab is a bispecific antibody that binds FIXa and FX and has been tested in patients with hemophilia A. In some embodiments, the antibody molecules described herein can enhance maximum thrombin production (peak height) in in vitro thrombin generation tests using FVIII -deficient plasma (e.g., less than 80-100 U / dL) more effectively than emicizumab. Thrombin generation tests, e.g.. with hemophilia A plasma, may correlate with FVIII activity, indicate overall blood clotting ability, and correlate with clinical symptoms (Verhagen MJA et al., J Thromb Haemost. 2022). Furthermore, the limited potency of emicizumab can result in breakthrough bleeding (Levy-Mendelovich S et al., J Clin Med. 2021, PMID: 34640320). In some embodiments, the antibody molecules described herein have higher maximum thrombin generation activity and / or effective FVIII function at lower doses. Without wishing to be bound by theory’, it is believed that in some embodiments the antibody molecules described herein can enhance treatment efficacy and / or reduce breakthrough bleeding. In some embodiments, the antibody molecules described herein have improved activities and are suitable for use at a reduced dosage to benefit hemophilia patients.

[0477] Definitions

[0478] As used herein, the articles “a” and “an” refer to one or to more than one (e.g., to at least one) of the grammatical object of the article.

[0479] The term “or” is used herein to mean, and is used interchangeably with, the term “and / or”, unless context clearly indicates otherwise.

[0480] “About” and “approximately” shall generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary’ degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% (e.g., within 4%, 3%, 2%, or 1%) of a given value or range of values. The compositions and methods disclosed herein encompass polypeptides and nucleic acids having the sequences specified, or sequences substantially identical or similar thereto, e.g., sequences at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical or higher to the sequence specified.

[0481] In the context of an amino acid sequence, the term “substantially identical” is used herein to refer to a first amino acid that contains a sufficient or minimum number of amino acid residues that are a) identical to, or b) conservative substitutions of aligned amino acid residues in a second amino acid sequence such that the first and second amino acid sequences can have a common structural domain and / or common functional activity. For example, amino acid sequences that contain a common structural domain having at least about 80%, 85%, 90%, 91%. 92%, 93%, 94%, 95%. 96%. 97%, 98% or 99% identity to a reference sequence, e.g., a sequence provided herein.

[0482] In the context of nucleotide sequence, the term “substantially identical” is used herein to refer to a first nucleic acid sequence that contains a sufficient or minimum number of nucleotides that are identical to aligned nucleotides in a second nucleic acid sequence such that the first and second nucleotide sequences encode a polypeptide having common functional activity or encode a common structural polypeptide domain or a common functional polypeptide activity. For example, nucleotide sequences having at least about 80%, 85%, 90%. 91%, 92%, 93%, 94%. 95%, 96%, 97%, 98%. or 99% identity to a reference sequence, e.g., a sequence provided herein.

[0483] The term “functional variant” refers to polypeptides that have a substantially identical amino acid sequence to the naturally occurring sequence, or are encoded by a substantially identical nucleotide sequence, and can have one or more activities of the naturally occurring sequence.

[0484] Calculations of homology or sequence identity between sequences (the terms are used interchangeably herein) are performed as follows.

[0485] To determine the percent identity of two amino acid sequences, or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). In a typical embodiment, the length of a reference sequence aligned for comparison purposes is at least 30%, e.g., at least 40%, 50%, 60%, 70%, 80%, 90%, or 100% of the length of the reference sequence. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position.

[0486] The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In an embodiment, the percent identify between tw o amino acid or nucleotide sequences is determined using Clustal Omega (Sievers et al. Mol Syst Biol. 2011; 7:539). In an embodiment, the percent identify betw een two amino acid or nucleotide sequences is determined using Kalign2 (Lassmann et al. Nucleic Acids Res. 2009; 37(3):858-65; Lassmann and Sonnhammer BMC Bioinformatics. 2005; 6:298). In an embodiment, the percent identify between two amino acid or nucleotide sequences is determined using MAFFT (Katoh and Standley Mol Biol Evol. 2013; 30(4): 772-80). In an embodiment, the percent identify between two amino acid or nucleotide sequences is determined using MUSCLE (Edgar Nucleic Acids Res. 2004; 32(5): 1792-7: Edgar BMC Bioinformatics. 2004; 5: 113). In an embodiment, the percent identify between two amino acid or nucleotide sequences is determined using MView (Brown et al. Bioinjormatics . 1998; 14(4): 380-1). Other methods for determining the percent identify between two sequences are also described, e.g., in Li et al. Nucleic Acids Res. 2015; 43(Wl):W580-4; McWilliam et al. Nucleic Acids Res. 2013; 41(Web Server issue):W597-600.

[0487] In an embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch (J Mol Biol. 1970; 48(3):443-53) algorithm which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com). using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10. 8. 6, or 4 and a length weight of 1. 2. 3, 4, 5, or 6. In an embodiment, the percent identity betw een two nucleotide sequences is determined using the GAP program in the GCG softw are package (available at www. gcg.com), using an NWSgapdna. CMP matrix and a gap weight of 40, 50, 60. 70, or 80 and a length weight of 1. 2, 3, 4, 5, or 6. One suitable set of parameters (and the one that should be used unless otherwise specified) are a Blossum 62 scoring matrix w ith a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.

[0488] The percent identity betw een tw o amino acid or nucleotide sequences can be determined using the algorithm of Mey ers and Miller (Comput Appl Biosci. 1988; 4(1) : 11-7) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty’ of 4.

[0489] The nucleic acid and protein sequences described herein can be used as a ’‘query sequence" to perfonn a search against public databases, for example, to identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. 1990; J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to a nucleic acid as described herein. BLAST protein searches can be performed with the XBLAST program, score = 50. w ordlength = 3 to obtain amino acid sequences homologous to protein molecules described herein. To obtain gapped alignments for comparison pinposes. Gapped BLAST can be utilized as described in Altschul et al.. Nucleic Acids Res. 1997; 25:3389-3402. When utilizing BLAST and gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST andNBLAST) can be used. See www.ncbi.nlm.nih.gov.

[0490] As used herein, the term “hybridizes under low stringency, medium stringency, high stringency , or very high stringency conditions” describes conditions for hybridization and washing. Guidance for performing hybridization reactions can be found in Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. which is incorporated by reference. Aqueous and nonaqueous methods are described in that reference and either can be used. Specific hybridization conditions referred to herein are as follows: 1) low stringency hybridization conditions in 6X sodium chloride / sodium citrate (SSC) at about 45°C, followed by two washes in 0.2X SSC, 0.1% SDS at least at 50°C (the temperature of the washes can be increased to 55°C for low stringency conditions); 2) medium stringency hybridization conditions in 6X SSC at about 45°C, followed by one or more washes in 0.2X SSC. 0.1% SDS at 60°C; 3) high stringency hybridization conditions in 6X SSC at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 65°C; and preferably 4) very high stringency hybridization conditions are 0.5M sodium phosphate, 7% SDS at 65°C. followed by one or more washes at 0.2X SSC, 1% SDS at 65°C. Very high stringency conditions 4) are suitable conditions and the ones that should be used unless otherwise specified.

[0491] It is understood that the molecules described herein may have additional conservative or non- essential amino acid substitutions, which do not have a substantial effect on their functions.

[0492] The term “amino acid” is intended to embrace all molecules, whether natural or synthetic, which include both an amino functionality and an acid functionality and capable of being included in a polymer of naturally occurring amino acids. Exemplary amino acids include naturally occurring amino acids; analogs, derivatives and congeners thereof; amino acid analogs having variant side chains; and all stereoisomers of any of any of the foregoing. As used herein the term “amino acid” includes both the D- or L- optical isomers and peptidomimetics.

[0493] A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., gly cine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, try ptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., ty rosine, phenylalanine, try ptophan, histidine).

[0494] The terms “polypeptide," “peptide” and “protein” (if single chain) are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified, for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. The polypeptide can be isolated from natural sources, can be a produced by recombinant techniques from a eukaryotic or prokaryotic host, or can be a product of synthetic procedures.

[0495] The terms “nucleic acid,” “nucleic acid sequence," “nucleotide sequence," or “polynucleotide sequence," and “polynucleotide" are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. The polynucleotide may be either single-stranded or double-stranded, and if single-stranded may be the coding strand or non-coding (antisense) strand. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. The nucleic acid may be a recombinant polynucleotide, or a polynucleotide of genomic. cDNA. semisynthetic, or synthetic origin which either does not occur in nature or is linked to another polynucleotide in a non-natural arrangement.

[0496] The term “isolated.” as used herein, refers to material that is removed from its original or native environment (e.g., the natural environment if it is naturally occurring). For example, a naturally occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated by human intervention from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotides could be part of a vector and / or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of the environment in which it is found in nature.

[0497] As used herein, the term “treat," e.g., a FVIIIa deficiency-associated disorder, means that a subject (e.g., a human) who has a disorder, e.g., a FVIIIa deficiency -associated disorder, and / or experiences a sy mptom of a disorder, e.g., a FVIIIa deficiency-associated disorder, will, in an embodiment, suffer less a severe symptom and / or recover faster when an antibody molecule is administered than if the antibody molecule were never administered. In an embodiment, when a FVIIIa deficiency-associated disorder, is treated, the level of FXa may be increased in a treated subject compared to a comparable untreated subject. For example, a diagnostic method using enzyme-linked immunosorbent assay (ELISA) will detect FXa in a biological sample of a subject after administration of an antibody molecule described herein for the effective treatment of the coagulation disorder. Other assays, e.g., fluorometric enzyme assays, can also be used to monitor treatment in a patient, or to detect the presence, e.g., decreased presence (or absence), of a symptom of the disorder, e.g., the FVIIIa deficiency -associated disorder, after treatment of the disorder in the subject. Treatment can, e.g., partially or completely, alleviate, ameliorate, relieve, inhibit, or reduce the severity of, and / or reduce incidence, and optionally, delay onset of. one or more manifestations of the effects or symptoms, features, and / or causes of a disorder, e.g., a FVIIIa deficiency -associated disorder. In an embodiment, treatment is of a subject who docs not exhibit certain signs of a disorder, e.g., a FVIIIa deficiency -associated disorder, and / or of a subject who exhibits only early signs of a disorder, e.g., a FVIIIa deficiency -associated disorder. In an embodiment, treatment is of a subject who exhibits one or more established signs of a disorder, e.g., a FVIIIa deficiency -associated disorder. In an embodiment, treatment is of a subject diagnosed as suffering from a disorder, e.g., a FVIIIa deficiency -associated disorder. In an embodiment, the disorder is a FVIIIa deficiency -associated disorder described herein.

[0498] As used herein, the term “prevent,” a disorder, e.g., a FVIIIa deficiency -associated disorder, means that a subject (e.g., a human) is less likely to have the disorder, e.g., a FVIIIa-associated disorder, if the subject receives the antibody molecule. In an embodiment, the subject is at risk of developing the disorder, e.g., a FVIIIa deficiency -associated disorder. In an embodiment, the disorder is a FVIIIa deficiency -associated disorder described herein.

[0499] Various aspects of the compositions and methods herein are described in further detail below. Additional definitions are set out throughout the specification.

[0500] FVIII

[0501] Coagulation factor VIII (anti-hemophilic factor, AHF) is an important component of a family of proteins involved in the blood clot formation pathway. FVIII is mainly produced and secreted by liver cells into the bloodstream where its inactive form binds to the large multimeric glycoprotein von

[0502] Willenbrand factor (VWF). Upon injury, FVIII dissociates from VWF as an active FVIIIa. The active form then binds to the activated factor IX (FIXa), which proteolytically activates FX to FXa.

[0503] Deficiency of FVIIIa is associated with the blood clotting disorder Hemophilia A.

[0504] The amino acid and nucleotide sequences of human FVIII are known in the art. An exemplary' amino acid sequence of human FVIII is provided as follows.

[0505] MQIELSTCFFLCLLRFCFSATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSWYKKTLF VEFTVHLFNIAKPRPPWMGLLGPTIQAEVYDTWITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQR EKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQT LHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMG TTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPE EPQLRMKNNEEAEDYDDDLTDSEMDWRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLA PDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLI IFKNQASR

[0506] PYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMER DLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQAS NIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMS MENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNSRHPST RQKQFNATTIPENDIEKTDPWF7XHRTPMPKIQNVSSSDLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPS PGAIDSNNSLSEMTHFRPQLHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSSTSNNLISTIPS

[0507] DNLAAGTDNTSSLGPPSMPVHYDSQLDTTLFGKKSSPLTESGGPLSLSEENNDSKLLESGLMNSQESSWG KNVSSTESGRLFKGKR7XHGPALLTKDNALFKVSISLLKTNKTSNNSATNRKTHIDGPSLLIENSPSVWQN ILESDTEFKKVTPLIHDRMLMDKNATALRLNHMSNKTTSSKNMEMVQQKKEGPIPPDAQNPDMSFFKMLF LPESARWIQRTHGKNSLNSGQGPSPKQLVSLGPEKSVEGQNFLSEKNKVWGKGEFTKDVGLKEMVFPSS RNLFLTNLDNLHENNTHNQEKKIQEEIEKKETLIQENWLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYE GAYAPVLQDFRSLNDSTNRTKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNTSQQNFVTQRS KRALKQFRLPLEETELEKRIIVDDTSTQWSKNMKHLTPSTLTQIDYNEKEKGAITQSPLSDCLTRSHSIP QANRSPLPIAKVSSFPSIRPIYLTRVLFQDNSSHLPTtASYRKKDSGVQESSHFLQGAKKNNLSLAILTLE MTGDQREVGSLGTSATNSVTYKKVENTVLPKPDLPKTSGKVELLPKVHIYQKDLFPTETSNGSPGHLDLV EGSLLQGTEGAIKWNEANRPGKVPFLRVATESSAKTPSKLLDPLAWDNHYGTQIPKEEWKSQEKSPEKTA FKKKDTILSLNACESNHAI7XAINEGQNKPEIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEE IDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFK KWFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGAE PRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQV TVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIR WYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHAGMS TLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMII HGIKTQGARQKFSSLYISQFI IMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRL HPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRP QVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFT PWNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY (SEQ ID NO : 273 )

[0508] FIX

[0509] Coagulation factor IX (FIX) is a serine protease, belonging to the peptidase family SI, important for the blot clotting cascade pathway. Initially produced as an inactive protein, FIX is activated (FIXa) by the action of factor Xia and factor Vila resulting in a two-chain form where the chains are linked by a disulfide bridge. FIXa proteolytically activates factor X (FX) to FXa by hydrolyzing one arginine-isoleucine bond in FX in the presence of calcium, membrane phospholipids and FVIIIa. FIX deficiency has been linked to Hemophilia B.

[0510] The amino acid and nucleotide sequences of human FIXa are known in the art. An exemplary amino acid sequence of human FIXa is provided as follows.

[0511] TCNIKNGRCKQFCKNTADNKWCSCTEGYRLAENQKSCEPAVPFPCGRVSVSQTSTLTRAETVFPDVE YVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPWQWLNGKVDAFCGGSIVNEKWWTAAHC VETDAKITWAGEHNIEETEHTEQKRNVIRI IPHHNYNATINKYNHDIALLELDEPLVLNSYVTPICI ADKEYTNIFLKFGSGYVSGWGRVFNKGRSASVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGR DSCQGDSGGPHVTEVEGTSFLTGI ISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT ( SEQ ID NO : 274 )

[0512] The amino acid and nucleotide sequences of human FIX are known in the art. An exemplary amino acid sequence of human FIX is provided as follows. MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERECMEEK CNFEEAREVFENTEKTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCPFGFEGKNCELDVTCNI KNGRCKQFCKNTADNKWCSCTEGYRLAENQKSCEPAVPFPCGRVSVSQTSTLTRAETVFPDVEYVNS TEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPWQWLNGKVDAFCGGS IVNEKWWTAAHCVETD AKITWAGEHNIEETEHTEQKRNVIRI IPHHNYNATINKYNHDIALLELDEPLVLNSYVTPICIADKE YTNIFLKFGSGYVSGWGRVFNKGRSASVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQ GDSGGPHVTEVEGTSFLTGI ISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT (SEQ ID NO : 275 )

[0513] In an embodiment, when an antibody molecule binds, or substantially binds, to FIXa. it binds, or substantially binds, to one or more isoforms of FIXa, e.g., one or more isoforms of human FIXa described herein. In an embodiment, the antibody molecule binds or substantially binds to FIXa having the amino acid sequence of SEQ ID NO: 274. FX

[0514] Coagulation factor X (FX) is a serine endopeptidase that in humans is encoded by the coagulation factor X gene. FX is a key component of the blood coagulation cascade as, once activated by proteolytic cleavage by FIXa, the activated FX (FXa) is responsible for the conversion of prothrombin to thrombin in the presence of factor Va, calcium, and membrane phospholipids. Mutations of this gene product result in FX deficiency, a severe hemorrhagic condition.

[0515] The amino acid and nucleotide sequences of human FX are known in the art. An exemplary amino acid sequence of human FX is provided as follows.

[0516] MGRPLHLVLLSAFLASLLLPGESLFIRREQANNVLARVRRSNSFLEEMKKGNLERECMEETCSYEEAR EVFEDSDKTNEFWNKYKDGDQCETSPCQNEGKCRDGLGEYTCTCLEGFEGKNCELFTRKLCSLDNGEC DQFCHEEQNSWCSCARGYTLADNGKACI PTGPYPCGKQTLERRKRSAAQATNSSGEAPDNI IWKPDD AADLDATENPFDLLDFNQTQPERGDNNLIRIVGGRECENGECPWQALLINEENEGFCGGTILSEFYIL TAAHCLYQAKRFKVRVGDRDMEQEEGGEAVHEVEVI IKHNRFTKETYDFDIAVLRLKSPITFRMNVAP ACLPERDWAESTLMTQKTGIVSGFGRTHEKGRQSTRLKMLEVPYVDRNSCKLSSSFI ITQNMFCAGYH AKQEDACQGDSGGPHVTRFKDTYFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTRGLPKAES RAPE ( SEQ ID NO : 276 )

[0517] In an embodiment, when an antibody molecule binds, or substantially binds, to FX, it binds, or substantially binds, to one or more isofonns of FX, e.g., one or more isofonns of human FX described herein. In an embodiment, the antibody molecule binds or substantially binds to FX having the amino acid sequence of SEQ ID NO: 276.

[0518] Antibody Molecules

[0519] Disclosed herein are antibody molecules that bind to FIXa and / or FX, e.g., a multispecific (e.g., bispecific) antibody molecule described herein.

[0520] As used herein, the term “antibody molecule” refers to a protein, e.g., an immunoglobulin chain or a fragment thereof, comprising at least one immunoglobulin variable domain sequence. The term “antibody molecule” includes, for example, a full-length antibody and an antigen-binding fragment of an antibody. In an embodiment, the antibody molecule comprises, or is derived from, two or more monospecific antibody moieties, e.g., two or more monospecific antibody molecules described herein. In an embodiment, an antibody molecule is multispecific (e.g., bispecific). The term “multispecific antibody molecule,” as used herein, refers to an antibody molecule capable of selectively binding two or more epitopes (e.g. , two or more epitopes on different target molecules or tw o or more epitopes on the same target molecule). In an embodiment, the multispccific antibody molecule is a bispecific antibody molecule. Bispecific antibody molecules may, in an embodiment, comprise two different heavy / light chain pairs, each of which specifically binds a different epitope, either on two different molecules (e.g., antigens) or on the same molecule (e.g., on the same antigen). Bispecific antibody molecules may, in an embodiment, comprise two identical or substantially identical heavy / light chain pairs, both of which specifically bind the same two epitopes, either on two different molecules (e.g.. antigens) or on the same molecule (e.g., on the same antigen).

[0521] The antibody molecules (e.g., multispecific antibody molecules) described herein can have different format. In an embodiment, the antibody molecule is a dual specific antibody molecule with specificities for FIXa and FX (e.g., human FIXa and FX). In an embodiment, the antibody molecule is a bispecific antibody where one arm preferentially targets FIXa (e.g.. human FIXa) and the other arm preferentially targets FX (e.g., human FX). In yet another embodiment, the antibody molecule is a single polypeptide comprising two scFvs covalently linked by a linker (e.g.. a flexible GS linker), wherein one scFv preferentially targets FIXa (e.g.. human FIXa) and the other scFv preferentially targets FX (e.g.. human FX). An antibody molecule that is capable of binding to FIXa and FX can bind to FIXa and FX at the same time or sequentially.

[0522] For example, an antibody molecule can include a heavy (H) chain variable domain sequence (abbreviated herein as VH), and a light (L) chain variable domain sequence (abbreviated herein as VL). In another example, an antibody molecule includes two heavy (H) chain variable domain sequences and two light (L) chain variable domain sequence, thereby forming two antigen binding sites, such as Fab, Fab’. F(ab’)2, Fc. Fd. Fd’. Fv. single chain antibodies (scFv or sc(Fv)2, for example), single variable domain antibodies, diabodies (Dab) (bivalent and bispecific). and chimeric (e.g., humanized) antibodies, which may be produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA technologies. These functional antibody fragments retain the ability to selectively bind with their respective antigen or receptor. Antibodies and antibody fragments can be from any class of antibodies including, but not limited to. IgG, IgA, IgM, IgD, and IgE, and from any subclass (e.g., IgGl, IgG2, IgG3, and IgG4) of antibodies. The antibody molecules can be monoclonal or polyclonal. In embodiments, the antibody molecule is a whole IgG antibody. The antibody molecule can also be a human, humanized, CDR-grafted, or in vitro generated antibody. The antibody molecule can have a heavy chain constant region chosen from, e.g., IgGl, IgG2, IgG3, IgG4, or a chimera of two or more isotypes. The antibody molecule can also have a light chain chosen from, e.g., kappa or lambda. The term “immunoglobulin'’ (Ig) is used interchangeably with the term “antibody’’ herein. In embodiments, the antibody molecule is a multispecific antibody molecule (e.g., a bispecific antibody molecule).

[0523] Examples of antigen-binding fragments include: (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CHI domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a diabody (dAb) fragment, which consists of a VH domain; (vi) a camelid or camelized variable domain; (vii) a single chain Fv (scFv). see e.g.. Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883): or (viii) a single domain antibody. These antibody fragments may be obtained using any suitable method, including several conventional techniques known to those with skill in the art, and tire fragments can be screened for utility in die same manner as are intact antibodies.

[0524] The term “antibody” includes intact molecules as well as functional fragments thereof. Constant regions of the antibodies can be altered, e.g., mutated, to modify die properties of the antibody (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function).

[0525] In an embodiment, the antibody molecule is a single chain antibody. A single-chain antibody (scFv) may be engineered (see. for example, Colcher, D. et al. (1999) Ann N Y Acad Sci 880:263-80; and Reiter, Y. (1996) Clin Cancer Res 2:245-52). The single chain antibody can be dimerized or multimerized to generate multivalent antibodies having specificities for different epitopes of the same target protein.

[0526] In an embodiment, the antibody molecule is a single domain antibody. Single domain antibodies can include antibodies whose complementarity determining regions are part of a single domain polypeptide. Examples include, but are not limited to, heavy chain antibodies, antibodies naturally devoid of light chains, single domain antibodies derived from conventional 4-chain antibodies, engineered antibodies and single domain scaffolds other than those derived from antibodies. Single domain antibodies may be any of the art, or any future single domain antibodies. Single domain antibodies may be derived from any species including, but not limited to mouse, human, camel, llama, fish, shark, goat, rabbit, and bovine. In an embodiment, a single domain antibody is a naturally occurring single domain antibody known as heavy chain antibody devoid of light chains. Such single domain antibodies are disclosed in WO 94 / 04678, for example. For clarify reasons, this variable domain derived from a heavy chain antibody naturally devoid of light chain is known herein as a VHH or nanobody to distinguish it from the conventional VH of four chain immunoglobulins. Such a VHH molecule can be derived from antibodies raised in Camelidae species, for example in camel, llama, dromedary, alpaca and guanaco. Other species besides Camelidae may produce heavy chain antibodies naturally devoid of light chain; such VHHs are also within the scope of the invention.

[0527] The VH and VL regions can be subdivided into regions of hypervariability, termed “complementarity determining regions” (CDR), interspersed with regions that are more conserved, termed “framework regions” (FR or FW). The tenns “complementarity determining region,” and “CDR,” as used herein refer to the sequences of amino acids within antibody variable regions which confer antigen specificity and binding affinity. In general, there are three CDRs in each heavy chain variable region (HCDR1, HCDR2, HCDR3) and three CDRs in each light chain variable region (LCDR1, LCDR2. LCDR3). As used herein, the terms "framework,” “FW” and "FR” are used interchangeably.

[0528] The extent of the framework region and CDRs has been precisely defined by a number of methods (see. Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest. Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242 ("Kabat" numbering scheme); Chothia, C. et al. (1987) J. Mol. Biol. 196:901-917 (“Chothia” numbering scheme); and the AbM definition used by Oxford Molecular's AbM antibody modeling software. See, generally, e.g., Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Antibody Engineering Lab Manual (Ed.: Duebel, S. and Kontermann, R., Springer-Verlag, Heidelberg). As used herein, the CDRs defined according the “Chothia” number scheme are also sometimes referred to as “hypervariable loops.” Under all definitions, each VH and VL typically includes three CDRs and four FRs, arranged from amino -terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3. CDR3, FR4.

[0529] For example, under Kabat, the CDR amino acid residues in the heavy chain variable domain (VH) can be numbered 31-35 (HCDR1), 50-65 (HCDR2), and 95-102 (HCDR3); and the CDR amino acid residues in the light chain variable domain (VL) are numbered 24-34 (LCDR1), 50-56 (LCDR2), and 89-97 (LCDR3). Under Chothia the CDR amino acids in the VH can be numbered 26-32 (HCDR1). 52-56 (HCDR2), and 95-102 (HCDR3); and the CDR amino acid residues in the VL can be numbered 26-32 (LCDR1), 50-52 (LCDR2), and 91-96 (LCDR3). By combining the CDR definitions of both Kabat and Chothia. the CDRs can consist of amino acid residues 26-35 (HCDR1). 50-65 (HCDR2). and 95-102 (HCDR3) in human VH and amino acid residues 24-34 (LCDR1), 50-56 (LCDR2), and 89-97 (LCDR3) in human VL.

[0530] Generally, unless specifically indicated, the antibody molecules described herein can include any combination of one or more Kabat CDRs (e.g., described in Table 1 or Table 2) and / or Chothia hypervariable loops.

[0531] As used herein, an “immunoglobulin variable domain sequence” refers to an amino acid sequence which can form the structure of an immunoglobulin variable domain. For example, the sequence may include all or part of the amino acid sequence of a naturally occurring variable domain. For example, the sequence may or may not include one, two, or more N- or C-tenninal amino acids, or may include other alterations that are compatible with formation of the protein structure.

[0532] The term “antigen-binding region” refers to the part of an antibody molecule that comprises determinants that form an interface that binds to an antigen, e.g., FIXa and / or FX, e.g., human FIXa and / or FX, or an epitope thereof. With respect to proteins (or protein mimetics), the antigen-binding region typically includes one or more loops (of at least, e.g., four amino acids or amino acid mimics) that form an interface that binds to the antigen, e.g., FIXa and / or FX , e.g., human FIXa and / or FX . Typically, the antigen-binding region of an antibody molecule includes at least one or two CDRs and / or hypervariable loops, or more typically at least three, four, five or six CDRs and / or hypervariable loops.

[0533] The terms “compete” or “cross-compete” are used interchangeably herein to refer to the ability of an antibody molecule to interfere with binding of an antibody molecule, e.g., an antibody molecule provided herein, to a target, e.g., FIXa and / or FX, e.g., human FIXa and / or FX. The interference with binding can be direct or indirect (e.g., through an allosteric modulation of the antibody molecule or the target). The extent to which an antibody molecule is able to interfere with the binding of another antibody molecule to the target, and therefore whether it can be said to compete, can be determined using a competition binding assay, for example, a FACS assay, an ELISA, or a BIACORE assay. In an embodiment, a competition binding assay is a quantitative competition assay. In an embodiment, a first antibody molecule is said to compete for binding to the target with a second antibody molecule when the binding of the first antibody molecule to the target is reduced by 10% or more, e.g., 20% or more, 30% or more. 40% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more. 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more in a competition binding assay (e.g., a competition assay described herein).

[0534] The terms “monoclonal antibody” or “monoclonal antibody composition” as used herein refer to a preparation of antibody molecules of single molecular composition. A monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope. A monoclonal antibody can be made by hybridoma technology or by methods that do not use hybridoma technology (e.g., recombinant methods).

[0535] An “effectively human” protein is a protein that does not evoke a neutralizing antibody response, e.g., the human anti-murine antibody (HAMA) response. HAMA can be problematic in a number of circumstances, e.g., if the antibody molecule is administered repeatedly, e.g., in treatment of a chronic or recurrent disease condition. A HAMA response can make repeated antibody administration potentially ineffective because of an increased antibody clearance from the serum and potential allergic reactions (see, e.g., Saleh et al., Cancer Immunol. Immunother. , 32:180-190 (1990); LoBuglio et al., Hybridoma, 5:5117-5123 (1986)).

[0536] The antibody molecule can be a polyclonal or a monoclonal antibody. In an embodiment, the antibody can be recombinantly produced, e.g., produced by any suitable phage display or combinatorial methods.

[0537] Various phage display and combinatorial methods for generating antibodies are known in the art (as described in, e.g., Ladner et al. U.S. Patent No. 5,223,409; Kang et al. International Publication No. WO 92 / 18619; Dower et al. International Publication No. WO 91 / 17271; Winter et al. International Publication WO 92 / 20791; Markland et al. International Publication No. WO 92 / 15679; Breitling et al. International Publication WO 93 / 01288; McCafferty et al. International Publication No. WO 92 / 01047; Garrard et al. International Publication No. WO 92 / 09690; Ladner et al. International Publication No. WO 90 / 02809; Fuchs et al. (1991) Bio / Technology 9:1370-1372; Hay et al. (1992) Hum Antibod Hybridomas 3:81-85; Huse et al. (1989) Science 246:1275-1281; Griffths et al. (1993) EMBO J 12:725-734; Hawkins et al. (1992) J Mol Biol 226:889-896; Clackson et al. (1991) Nature 352:624-628; Gram et al. (1992) PNAS 89:3576-3580; Garrad et al. (1991) Bio Technology 9:1373-1377; Hoogcnboom et al. (1991) Nuc Acid Res 19:4133-4137; and Barbas et al. (1991) PNAS 88:7978-7982, the contents of all of which are incorporated by reference herein).

[0538] In an embodiment, the antibody molecule is a fully human antibody (e.g., an antibody made in a mouse which has been genetically engineered to produce an antibody from a human immunoglobulin sequence), or a non-human antibody, e.g., a rodent (e.g., mouse or rat), goat, primate (e.g., monkey), camel antibody. In an embodiment, the non-human antibody is a rodent (e.g., mouse or rat antibody). Methods of producing rodent antibodies are known in the art.

[0539] Human monoclonal antibodies can be generated using transgenic mice carrying the human immunoglobulin genes rather than the mouse system. Splenocytes from these transgenic mice immunized with the antigen of interest are used to produce hybridomas that secrete human mAbs with specific affinities for epitopes from a human protein (see e.g., Wood et al. International Application WO 91 / 00906, Kucherlapati et al. PCT publication WO 91 / 10741; Lonberg et al. International Application WO 92 / 03918; Kay et al. International Application 92 / 03917; Lonberg. N. et al. 1994 Nature 368:856-859; Green, L.L. et al. 1994 / Vafwre Genet. 1'. 13-21; Morrison, S.L. et al. 1994 Proc. Natl. Acad. Set. USA 81:6851-6855; Bruggeman et al. 1993 Year Immunol 7:33-40; Tuaillon et al. 1993 PAAS’ 90:3720-3724; Bruggeman et al. 1991 Eur J Immunol 21:1323-1326).

[0540] An antibody can be one in which the variable region, or a portion thereof, e.g.. the CDRs, are generated in a non-human organism, e.g., a rat or mouse. Chimeric, CDR-grafted. and humanized antibodies are within the invention. Antibodies generated in a non-human organism, e.g., a rat or mouse, and then modified, e.g. , in the variable framework or constant region, to decrease antigenicity in a human are within the invention.

[0541] Chimeric antibodies can be produced by any suitable recombinant DNA technique. Several are known in the art (see Robinson et al., International Patent Application Publication No. WO1987 / 002671; Akira, et al., European Patent Application Publication No. 184,187; Taniguchi, M., European Patent Application Publication No. 171,496; Morrison et al., European Patent Application Publication No. 173,494; Neuberger et al., International Patent Application Publication No. WO 86 / 01533; Cabilly et al. U.S. Patent No. 4,816,567; Cabilly et al., European Patent Application Publication No. 125,023; Better et al. (1988 Science 240:1041-1043); Liu et al. (1987) PNAS 84:3439-3443; Liu et a / .. 1987, J. Immunol. 139:3521-3526; Sun et a / . (1987) PNAS 84:214-218; Nishimura et al., 1987, Cane. Res. 47:999-1005; Wood et al. (1985) Nature 314:446-449; and Shaw et al., 1988, J. Natl Cancer Inst. 80:1553-1559).

[0542] A humanized or CDR-grafted antibody will have at least one or two but generally all three recipient CDRs (of heavy and or light immunoglobulin chains) replaced with a donor CDR. The antibody may be replaced with at least a portion of a non-human CDR or only some of the CDRs may be replaced with non-human CDRs. It is only necessary to replace the number of CDRs required for binding of the humanized antibody to lipopolysaccharide. In an embodiment, the donor will be a rodent antibody, e.g., a rat or mouse antibody, and the recipient will be a human framework or a human consensus framework. Typically, the immunoglobulin providing the CDRs is called the “donor’’ and tire immunoglobulin providing the framework is called the “acceptor.” In an embodiment, the donor immunoglobulin is a non-human (e.g., rodent). The acceptor framework is typically a naturally -occurring (e.g., a human) framework or a consensus framework, or a sequence about 85% or higher, e.g., 90%, 95%, 99% or higher identical thereto.

[0543] As used herein, die term “consensus sequence” refers to the sequence formed from the most frequently occurring amino acids (or nucleotides) in a family of related sequences (See e.g., Wiimaker, From Genes to Clones (Verlagsgesellschaft, Weinheim, Germany 1987). In a family of proteins, each position in the consensus sequence is occupied by the amino acid occurring most frequently at that position in the family. If two amino acids occur equally frequently, either can be included in the consensus sequence. A “consensus framework” refers to the framework region in the consensus immunoglobulin sequence.

[0544] An antibody can be humanized by any suitable method, and several such methods known in the art (see e.g., Morrison, S. L.. 1985. Science 229: 1202-1207, by Oi et al., 1986, BioTechniques 4:214. and by Queen et al. US 5,585,089, US 5,693,761 and US 5,693,762, the contents of all of which are hereby incorporated by reference).

[0545] Humanized or CDR-grafted antibodies can be produced by CDR-grafting or CDR substitution, wherein one, two, or all CDRs of an immunoglobulin chain can be replaced. See e.g., U.S. Patent 5,225,539; Jones et al. 1986 Nature 321 : 552-525; Verhoeyan et al. 1988 Science 239: 1534; Beidler et al. 1988 J. Immunol. 141 :4053-4060; Winter US 5,225,539, the contents of all of which are hereby expressly incorporated by reference. Winter describes a CDR-grafting method which may be used to prepare humanized antibodies (UK Patent Application GB 2188638A, filed on March 26, 1987; Winter US 5,225,539). the contents of which is expressly incorporated by reference.

[0546] Also provided are humanized antibodies in which specific amino acids have been substituted, deleted or added. Criteria for selecting amino acids from the donor are described in, e.g., US 5,585,089, e.g., columns 12-16 of US 5,585,089, the contents of which are hereby incorporated by reference. Other techniques for humanizing antibodies are described in Padlan et al. EP 519596 Al, published on December 23, 1992.

[0547] In an embodiment, the antibody molecule has a heavy chain constant region chosen from, e.g., the heavy chain constant regions of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgD, and IgE; particularly, chosen from, e.g, the (e.g., human) heavy chain constant regions of IgGl, IgG2, IgG3, and IgG4. In another embodiment, the antibody molecule has a light chain constant region chosen from, e.g., the (e.g., human) light chain constant regions of kappa or lambda. The constant region can be altered, e.g., mutated, to modify the properties of the antibody molecule (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, and / or complement function). In an embodiment, the antibody molecule has effector function and can fix complement. In another embodiment, the antibody molecule does not recruit effector cells or fix complement. In an embodiment, the antibody molecule has reduced or no ability to bind an Fc receptor. For example, it may be an isotype or subtype, fragment or other mutant, which does not support binding to an Fc receptor, e.g., it has a mutated or deleted Fc receptor binding region.

[0548] In an embodiment, a constant region of the antibody molecule is altered. Methods for altering an antibody constant region are known in the art. Antibody molecules with altered function, e.g. altered affinity for an effector ligand, such as FcR on a cell, or the Cl component of complement can be produced by replacing at least one amino acid residue in the constant portion of the antibody with a different residue (see, e.g., EP 388,151 Al, U.S. Pat. No. 5,624,821 and U.S. Pat. No. 5.648.260. the contents of all of which are hereby incorporated by reference). Amino acid mutations which stabilize antibody structure, such as S228P (EU nomenclature, S241P in Kabat nomenclature) in human IgG4 are also contemplated. Similar type of alterations could be described which if applied to the murine, or other species immunoglobulin would reduce or eliminate these functions.

[0549] In an embodiment, the only amino acids in the antibody molecule are canonical amino acids. In an embodiment, the antibody molecule comprises naturally -occurring amino acids; analogs, derivatives and congeners thereof; amino acid analogs having variant side chains; and / or all stereoisomers of any of the foregoing. The antibody molecule may comprise the D- or L- optical isomers of amino acids and peptidomimetics.

[0550] In an embodiment, the antibody molecule comprises a monoclonal antibody (e.g., a full- length antibody which has an immunoglobulin Fc region). In an embodiment, the antibody molecule comprises a full length antibody or full length immunoglobulin chain. In an embodiment, the antibody molecule comprises an antigen binding or functional fragment of a full-length antibody or full length immunoglobulin chain.

[0551] In an embodiment, the antibody molecule is a monospecific antibody molecule, e.g., it binds a single epitope. For example, a monospecific antibody molecule can have a plurality of immunoglobulin variable region sequences, each of which binds the same epitope.

[0552] In an embodiment, the antibody molecule is a multispecific antibody molecule, e.g., it comprises a plurality of immunoglobulin variable region sequences, wherein a first immunoglobulin variable region sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable region sequence of the plurality has binding specificity for a second epitope. In an embodiment, the first and second epitopes are on the same antigen, e.g. , the same protein (or subunit of a multimeric protein). In an embodiment, the first and second epitopes overlap. In an embodiment, the first and second epitopes do not overlap. In an embodiment, the first and second epitopes are on different antigens, e.g., different proteins (or different subunits of a multimeric protein). In an embodiment, a multispecific antibody molecule comprises a third, fourth or fifth immunoglobulin variable domain. In an embodiment, a multispecific antibody molecule is a bispecific antibody molecule, a trispecific antibody molecule, or tetraspecific antibody molecule. In an embodiment, a multispccific antibody molecule is a bispccific antibody molecule. A bispecific antibody lias specificity for no more than two antigens. A bispecific antibody molecule is typically characterized by a first immuno globulin variable domain sequence which has binding preference for a first epitope and a second immuno globulin variable domain sequence that has binding preference for a second epitope. In an embodiment, the first and second epitopes are on the same antigen, e.g., the same protein (or subunit of a multimeric protein). In an embodiment, the first and second epitopes overlap. In an embodiment, the first and second epitopes do not overlap. In an embodiment, the first and second epitopes are on different antigens, e.g., different proteins (or different subunits of a multimeric protein). In an embodiment, a bispecific antibody molecule comprises a heavy chain variable region sequence and a light chain variable region sequence which have binding specificity for a first epitope, and a heavy chain variable region sequence and a light chain variable region sequence which have binding specificity for a second epitope. In an embodiment, a bispecific antibody molecule comprises a half antibody having binding specificity for a first epitope and a half antibody having binding specificity for a second epitope. In an embodiment, a bispecific antibody molecule comprises a half antibody, or a fragment thereof, having binding specificity' for a first epitope, and a half antibody, or fragment thereof, having binding specificity for a second epitope. In an embodiment a bispecific antibody molecule comprises an scFv, or a fragment thereof, having binding specificity for a first epitope, and an scFv, or a fragment thereof, having binding specificity' for a second epitope.

[0553] Protocols for generating bispecific or heterodimeric antibody molecules are known in the art; including but not limited to, for example, the “knob in a hole” approach described in, e.g., US5731168; the electrostatic steering Fc pairing as described in, e.g., WO 09 / 089004, WO 06 / 106905 and WO 2010 / 129304; Strand Exchange Engineered Domains (SEED) heterodimer formation as described in, e.g., WO 07 / 110205; Fab arm exchange as described in, e.g., WO 08 / 119353, WO 2011 / 131746, and WO 2013 / 060867; double antibody conjugate, e.g., by antibody cross-linking to generate a bi-specific structure using a heterobifunctional reagent having an amine -re active group and a sulfhydryl reactive group as described in, e.g., US4433059; bispecific antibody determinants generated by recombining half antibodies (heavy-light chain pairs or Fabs) from different antibodies through cycle of reduction and oxidation of disulfide bonds between the two heavy chains, as described in, e.g., US 4444878; trifunctional antibodies, e.g.. three Fab' fragments cross-linked through sulfhdryl reactive groups, as described in, e.g., US5273743; biosynthetic binding proteins, e.g., pair of scFvs cross-linked through C-terminal tails preferably through disulfide or amine-reactive chemical cross-linking, as described in, e.g., US5534254; bifunctional antibodies, e.g., Fab fragments with different binding specificities dimerized through leucine zippers (e.g., c-fos and c-jun) that have replaced the constant domain, as described in. e.g., US5582996; bispecific and oligospecific mono- and oligovalent receptors, e.g.. VH-CH1 regions of two antibodies (two Fab fragments) linked through a polypeptide spacer between the CHI region of one antibody and the VH region of the other antibody ty pically with associated light chains, as described in, e.g., US5591828; bispccific DNA- antibody conjugates, e.g., crosslinking of antibodies or Fab fragments through a double stranded piece of DNA, as described in, e.g., US5635602; bispecific fusion proteins, e.g., an expression construct containing two scFvs with a hydrophilic helical peptide linker between them and a full constant region, as described in, e.g., US5637481; multivalent and multispecific binding proteins, e.g., dimer of polypeptides having first domain with binding region of Ig heavy chain variable region, and second domain with binding region of Ig light chain variable region, generally termed diabodies (higher order structures are also disclosed creating bispecific, trispecific, or tetraspecific molecules, as described in, e.g., US5837242; minibody constructs with linked VL and VH chains further connected with peptide spacers to an antibody hinge region and CH3 region, which can be dimerized to form bispecific / multivalent molecules, as described in, e.g.. US5837821; VH and VL domains linked with a short peptide linker (e.g.. 5 or 10 amino acids) or no linker at all in either orientation, which can form dimers to form bispecific diabodies; trimers and tetramers, as described in, e.g., US5844094; String of VH domains (or VL domains in family members) connected by peptide linkages with crosslinkable groups at the C-terminus further associated with VL domains to form a series of FVs (or scFvs), as described in. e.g., US5864019; and single chain binding polypeptides with both a VH and a VL domain linked through a peptide linker are combined into multivalent structures through non- covalent or chemical crosslinking to form, e.g., homobivalent, heterobivalent, trivalent, and tetravalent structures using both scFV or diabody type format, as described in. e.g., US5869620. The contents of the above-referenced applications are incorporated herein by reference in their entirety.

[0554] Additional methods of making multispecific or bispecific antibody molecules can be found, for example, in US5910573, US5932448, US5959083, US5989830, US6005079, US6239259, US6294353. US6333396, US6476198, US6511663, US6670453, US6743896, US6809185, US6833441. US7129330, US7183076, US7521056, US7527787, US7534866, US7612181, US2002 / 004587, US2002 / 076406, US2002 / 103345, US2003 / 207346, US2003 / 211078, US2004 / 219643, US2004 / 220388, US2004 / 242847, US2005 / 003403, US2005 / 004352, US2005 / 069552, US2005 / 079170, US2005 / 100543, US2005 / 136049, US2005 / 136051, US2005 / 163782, US2005 / 266425, US2006 / 083747, US2006 / 120960, US2006 / 204493, US2006 / 263367, US2007 / 004909, US2007 / 087381, US2007 / 128150, US2007 / 141049, US2007 / 154901, US2007 / 274985, US2008 / 050370, US2008 / 069820, US2008 / 152645, US2008 / 171855, US2008 / 241884, US2008 / 254512, US2008 / 260738, US2009 / 130106, US2009 / 148905, US2009 / 155275, US2009 / 162359. US2009 / 162360, US2009 / 175851, US2009 / 175867, US2009 / 232811, US2009 / 234105. US2009 / 263392, US2009 / 274649, EP346087, WO00 / 06605. WO02 / 072635, W004 / 081051, W006 / 020258, W02007 / 044887, W02007 / 095338A2, W02007 / 137760A2, W02008 / 119353, W02009 / 021754. W02009 / 068630. WO91 / 03493. WO93 / 23537. WO94 / 09131. WO94 / 12625. WO95 / 09917. WO96 / 37621. WO99 / 64460. The contents of the above-referenced applications arc incorporated herein by reference in their entirety.

[0555] A polypeptide of an antibody molecule described herein may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The antibody molecule may also be modified; for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. The polypeptide can be isolated from natural sources, can be a produced by recombinant techniques from a eukaryotic or prokaryotic host, or can be a product of synthetic procedures.

[0556] An antibody molecule described herein can be used alone in unconjugated form, or can be bound to a substance, e.g., a toxin or moiety (e.g, a therapeutic drug; a compound emitting radiation; molecules of plant, fungal, or bacterial origin; or a biological protein (e.g., a protein toxin) or particle (e.g., a recombinant viral particle, e.g., via a viral coat protein)). For example, the antibody molecule can be coupled to a radioactive isotope such as an a-, 0-. or y-cm liter, or a 0-and y-cm liter.

[0557] An antibody molecule can be derivatized or linked to another functional molecule (e.g., another peptide or protein). As used herein, a “derivatized” antibody molecule is one that has been modified. Methods of derivatization include but are not limited to the addition of a fluorescent moiety, a radionucleotide, a toxin, an enzyme or an affinity ligand such as biotin. Accordingly, the antibody molecules are intended to include derivatized and otherwise modified forms of the antibodies described herein, including immunoadhesion molecules. For example, an antibody molecule can be functionally linked (by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody (e.g., a bispecific antibody or a diabody), a detectable agent, a toxin, a pharmaceutical agent, and / or a protein or peptide that can mediate association of the antibody or antibody portion with another molecule (such as a streptavidin core region or a poly histidine tag).

[0558] Some types of derivatized antibody molecule are produced by crosslinking two or more antibodies (of the same type or of different types, e.g., to create bispecific antibodies). Suitable crosslinkers include those that are heterobifunctional, having two distinctly reactive groups separated by an appropriate spacer (e.g., m-maleimidobenzoyl-N-hydroxysuccinimide ester) or homobifunctional (e.g., disuccinimidyl suberate). Such linkers are available from Pierce Chemical Company. Rockford, Ill.

[0559] Useful detectable agents with which an antibody molecule described herein may be derivatized (or labeled) to include fluorescent compounds, various enzymes, prosthetic groups, luminescent materials, bioluminescent materials, fluorescent emitting metal atoms, e.g., europium (Eu), and other anthanides. and radioactive materials (described below). Exemplary fluorescent detectable agents include fluorescein, fluorescein isothiocyanate, rhodamine, 5dimethylamine-l- napthalenesulfonyl chloride, phycoerythrin and the like. An antibody may also be derivatized with detectable enzymes, such as alkaline phosphatase, horseradish peroxidase, 0-galaclosidasc. acetylcholinesterase, glucose oxidase and the like. When an antibody is dcrivatizcd with a detectable enzy me, it is detected by adding additional reagents that the enzyme uses to produce a detectable reaction product. For example, when the detectable agent horseradish peroxidase is present, the addition of hydrogen peroxide and diaminobenzidine leads to a colored reaction product, which is detectable. An antibody molecule may also be derivatized with a prosthetic group (e.g., streptavidin / biotin and avidin / biotin). For example, an antibody may be derivatized with biotin, and detected through indirect measurement of avidin or streptavidin binding. Examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; and examples of bioluminescent materials include luciferase, luciferin, and aequorin.

[0560] Labeled antibody molecules can be used, for example, diagnostically and / or experimentally in a number of contexts, including (i) to isolate a predetermined antigen by standard techniques, such as affinity chromatography or immunoprecipitation; (ii) to detect a predetermined antigen (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the protein; or (iii) to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to determine the efficacy of a given treatment regimen.

[0561] An antibody7molecule described herein can be conjugated to another molecular entity, typically a label or a therapeutic (e.g., antimicrobial (e.g., antibacterial or bactericidal), immunomodulatory, immunostimularoty, cytotoxic, or cytostatic) agent or moiety. Radioactive isotopes can be used in diagnostic or therapeutic applications. Radioactive isotopes that can be coupled to the antibody molecules include, but are not limited to a-, 0-, or y-emitters, or 0-and y- emitters. Such radioactive isotopes include, but are not limited to iodine (131I or125I), yttrium (90Y), lutetium (177Lu), actinium (223Ac), praseody mium, astatine (211At), rhenium (186Re), bismuth (212Bi or213Bi), indium (n lIn), technetium ("mTc), phosphorus (32P), rhodium (188Rh), sulfur (35S) , carbon (14C), tritium (3H), chromium (51Cr), chlorine (36C1), cobalt (57Co or58Co), iron (59Fe), selenium (75Se), or gallium (67Ga). Radioisotopes useful as therapeutic agents include yttrium (90Y), lutetium t' Lu). actinium (225Ac), praseodymium, astatine (2I1At), rhenium (186Re), bismuth (212Bi or213Bi). and rhodium (188Rh). Radioisotopes useful as labels, e.g., for use in diagnostics, include iodine (131I or125I), indium (U 1ln), technetium (y9mTc), phosphorus (32P), carbon (14C), and tritium (3H), or one or more of the therapeutic isotopes listed above.

[0562] The present disclosure provides radiolabeled antibody molecules and methods of labeling the same. In an embodiment, a method of labeling an antibody molecule is disclosed. The method includes contacting an antibody molecule, with a chelating agent, to thereby produce a conjugated antibody. The conjugated antibody is radiolabeled with a radioisotope, e.g.,U 1lndium, "Yttrium and1' Lutetium, to thereby produce a labeled antibody molecule. In an embodiment, the antibody molecule is conjugated to a therapeutic agent. Therapeutically active radioisotopes are disclosed herein. Examples of other therapeutic agents include, but are not limited to, taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, maytansinoids, e.g., maytansinol (see e.g., U.S. Pat. No. 5,208,020), CC-1065 (see e.g., U.S. Pat. Nos. 5.475,092, 5.585,499, 5,846, 545) and analogs or homologs thereof. Therapeutic agents include, but are not limited to. antimetabolites (e.g., methotrexate. 6-mercaptopurine. 6-thioguanine, cytarabine, 5- fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thioepa chlorambucil. CC-1065, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide. busulfan, dibromomannitol, streptozotocin. mitomycin C. and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclinies (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and anti-mitotic agents (e.g., vincristine, vinblastine, taxol and maytansinoids).

[0563] In an embodiment, the antibody molecule is covalently linked, e.g., fused, to another partner e.g.. a protein, e.g.. as a fusion molecule (e.g., a fusion protein).

[0564] As used herein, a “fusion protein” and “fusion polypeptide” refer to a polypeptide having at least two portions covalently linked together, where each of the portions is a polypeptide. In an embodiment, each of the portions is a polypeptide that has a different property. The property can be a biological property, such as activity in vitro or in vivo. The property can also be simple chemical or physical property, such as binding to a target molecule, catalysis of a reaction, etc. The two portions can be linked directly by a single peptide bond or through a linker (e.g., peptide linker), but are in reading frame with each other.

[0565] In one aspect, the invention features a method of providing a target binding agent that specifically binds to FIXa and / or FX (e.g., human FIXa and / or FX). For example, the target binding molecule is an antibody molecule. The method includes: providing a target protein that comprises at least a portion of non-human protein, the portion being homologous to (e.g., at least 70, 75, 80, 85, 87, 90, 92, 94, 95, 96, 97, 98% identical to) a corresponding portion of a human target protein, but differing by at least one amino acid (e.g., at least one, two, three, four, five, six, seven, eight, or nine amino acids); obtaining a binding agent (e.g., an antibody molecule) that specifically binds to the target protein; and evaluating efficacy of the binding agent in modulating an activity of the target protein. The method can further include administering the binding agent (e.g., antibody molecule) or a derivative (e.g., a humanized antibody molecule) to a subject (e.g, a human subject).

[0566] In another aspect, this disclosure provides a method of making an antibody molecule disclosed herein. The method includes: providing an antigen, e.g., FIXa and / or FX (e.g., human FIXa and / or FX ) or a fragment thereof; obtaining an antibody molecule that specifically binds to the antigen; evaluating efficacy of the antibody molecule in modulating activity of the antigen and / or organism expressing the antigen, e.g., FIXa and / or FX , e.g., human FIXa and / or FX. The method can further include administering the antibody molecule, including a derivative thereof (e.g., a humanized antibody molecule) to a subject, e.g., a human. This disclosure provides an isolated nucleic acid molecule encoding the above antibody molecule, vectors and host cells thereof. The nucleic acid molecule includes, but is not limited to, RNA. genomic DNA and cDNA.

[0567] Amino acid sequences of exemplary' antibody molecules are described in Tables 1-4.

[0568] Table 1: Exemplary light chain variable sequences of FIXa and FX Fabs. The CDR loops are defined according to Kabat classification scheme.

[0569] 1601181767.1

[0570]

[0571] 1601181767.1

[0572]

[0573] 1601181767.1

[0574]

[0575] 1601181767.1

[0576]

[0577] 1601181767.1

[0578]

[0579] 1601181767.1

[0580]

[0581] 1601181767.1

[0582]

[0583] 1601181767.1

[0584] Table 2: Exemplary heavy chain variable sequences of FIXa and FX Fabs. The CDR loops are defined according to Kabat classification scheme.

[0585] 1601181767.1

[0586]

[0587] 1601181767.1

[0588]

[0589] 1601181767.1

[0590]

[0591] 1601181767.1

[0592]

[0593] 1601181767.1

[0594] Table 3: Exemplary constant regions of heavy or light chains

[0595] 1601181767.1

[0596] p y q p y

[0597] 1601181767.1

[0598]

[0599] 1601181767.1

[0600]

[0601] 1601181767.1

[0602]

[0603] 1601181767.1

[0604]

[0605] 1601181767.1

[0606]

[0607] 1601181767.1

[0608]

[0609] 1601181767.1

[0610]

[0611] 1601181767.1

[0612]

[0613] 1601181767.1

[0614]

[0615] 1601181767.1

[0616]

[0617] 1601181767.1

[0618]

[0619] 1601181767.1

[0620]

[0621] 1601181767.1

[0622]

[0623] 1601181767.1

[0624]

[0625] 1601181767.1

[0626] In an embodiment, an antibody molecule described herein comprises a first binding moiety capable of binding to FIXa and a second binding moiety capable of binding to FX. In an embodiment, an antibody molecule described herein comprises a first binding moiety capable of binding to FX and a second binding moiety capable of binding to FIXa. In an embodiment, an antibody molecule described herein comprises a first binding moiety capable of binding to FIXa and a second binding moiety capable of binding to FIXa. In an embodiment, an antibody molecule described herein comprises a first binding moiety capable of binding to FX and a second binding moiety capable of binding to FX.

[0627] In an embodiment, the antibody molecule comprises one, two, or three CDRs of the VH region of an antibody molecule described herein, e.g., an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4 using the Kabat or Chothia definitions of CDRs. In an embodiment, the antibody molecule comprises one, two, or three CDRs of the VL region of an antibody molecule described herein, e.g., an antibody molecule (e.g. , a bispecific antibody molecule) comprising a combination (e.g., abispecific antibody molecule) of VH and VL described in FIGs. 1A-1B, 2, or 3 or Table 4, using the Kabat or Chothia definitions of CDRs. In an embodiment, the antibody molecule comprises one or more (e.g., two or three) CDRs of the VH region and / or one or more (e.g. , two or three) CDRs of the VL region of an antibody molecule described herein, e.g., an antibody molecule (e.g.. a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4, respectively, e.g., using the Kabat definitions of CDRs.

[0628] In an embodiment, the antibody molecule comprises one, two, or three VH CDRs described in Table 2. In an embodiment, the antibody molecule comprises one, two, or three VL CDRs described in Table 1. In an embodiment, the antibody molecule comprises one or more (e g., two orthree) VH CDRs described in Table 2 and / or one or more (e.g.. two or three) VL CDRs described in Table 1.

[0629] In an embodiment, the antibody molecule comprises one, two, three, or four frameworks of the VH region of an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises one, two, three, or four frameworks of the VL region of an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises one or more (e.g., two, three, or four) frameworks of the VH region and / or one or more (e.g., two. three, or four) frameworks of the VL region of an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4.

[0630] In an embodiment, the antibody molecule comprises a heavy chain variable region of an antibodymolecule described herein, e.g., an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises a light chain variable region of an antibody molecule described herein, e.g., an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises a heavy chain variable region and a light chain variable region of an antibody molecule described herein, e.g., an antibody molecule (e.g.. a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises a heavy chain and a light chain of an antibody molecule described herein, e.g., an antibody molecule (e.g., a bispecific antibody molecule) described in Table 4.

[0631] In an embodiment, the antibody molecule comprises a heavy chain variable region having an amino acid sequence described in Table 2, or an amino acid sequence substantially identical thereof. In an embodiment, the antibody molecule comprises a light chain variable region having an amino acid sequence described in Table 1, or an amino acid sequence substantially identical thereof. In an embodiment, the antibody molecule comprises a heavy chain variable region having an amino acid sequence described in Table 2 (or an amino acid sequence substantially identical thereof) and a light chain variable region having an amino acid sequence described in Table 1 (or an amino acid sequence substantially identical thereof). Any of the VHs described in Table 2 can be combined with any of the VLs described in Table 1.

[0632] Exemplary VH and VL amino acid sequences are also described in Tables 2 and 1, respectively. Exemplary CDR amino acid sequences are also described in Tables 2 and 1, respectively.

[0633] In an embodiment, the antibody molecule comprises a heavy chain variable region encoded by a nucleotide sequence. In an embodiment, the antibody molecule comprises a light chain variable region encoded by a nucleotide sequence. In an embodiment, the antibody molecule comprises a heavy chain variable region encoded by a nucleotide sequence and a light chain variable region encoded by a nucleotide sequence.

[0634] In an embodiment, the antibody molecule further comprises a heavy chain constant region. In an embodiment, the heavy chain constant region is an IgGl constant region or a functional portion thereof. In another embodiment, the heavy chain constant region is an IgG2 constant region or a functional portion thereof. In an embodiment, the antibody molecule further comprises a light chain constant region. In an embodiment, the antibody molecule further comprises a heavy chain constant region. In an embodiment, the heavy chain constant region is an IgG3 constant region or a functional portion thereof. In an embodiment, the antibody molecule further comprises a heavy chain constant region. In an embodiment, the heavy chain constant region is an IgG4 constant region or a functional portion thereof. In an embodiment, the antibody molecule has a chimeric constant region comprising of IgG2, IgG3 and / or IgG4 isotypes. In an embodiment, the antibody molecule further comprises a heavy chain constant region and a light chain constant region. In an embodiment, the antibody molecule comprises a heavy chain constant region, a light chain constant region, and heavy and light chain variable regions of an antibody molecule (e.g. , a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4. In an embodiment, the antibody molecule comprises a heavy chain constant region, a light chain constant region, and variable regions that comprise one, two, three, four, five, or six CDRs of an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL described in FIGs. 1A-1B, 2, or 3 or Table 4.

[0635] Exemplary heavy and light chain constant regions are described in Tables 3-4.

[0636] In an embodiment, the antibody molecule comprises one or more (e.g., 2, 3, 4, 5, or all) of the CDRs of an antibody molecule (e.g., a bispecific antibody molecule) comprising a combination of a VH and a VL of FIGs. 1A-1B, 2, or 3 or Table 4; and a human IgGl constant region as described herein. In an embodiment, the antibody molecule comprises one or more (e.g., 2, 3, 4, 5, or all) of the CDRs of an antibody molecule (e.g. , a bispecific antibody molecule) comprising a combination of a VH and a VL of FIGs. 1A-1B, 2, or 3 or Table 4; and one or more (e.g.. 2, 3, 4, 5, or 6) of a CHI (e.g., one or both of CHI (WT) or CH1.1), a CL (e.g., one or both of CL (WT) or CL’), a hinge region (e.g., Hinge (WT))_ a CH2 (e.g.. one, two. or all of CH2 (WT), CH2. 1, or CH2.2). or a CH3 (e.g.. one, two, three, four, five, six, or all of CH3 (WT), CH3. 1, CH3.2, CH3.3, CH3.4, CH3.5, or CH3.6), e.g., as desenbed herein (e.g., in Table 3).

[0637] In some embodiments, the antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL). wherein the VH comprises three heavy chain complementarity determining regions (HCDR1. HCDR2, and HCDR3). wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the VH comprises one, two, or all of the following:

[0638] (i) an HCDR1 comprising the amino acid sequence:

[0639] XiX2X3X4X5, wherein: Xi is D, Y, or F;

[0640] X2is N, Y, or F; X3is N, T, or D; X4is M, I, or V; and X5is D, N or Q;

[0641] (ii) an HCDR2 comprising the amino acid sequence: X, X2X3X4X5X6X7XSX9X10YXl 1 X!2Xl 3X14X15X1... wherein: Xi is D or S;

[0642] X2is I or V;

[0643] X3 is N or S;

[0644] X4 is T or P;

[0645] X5 is R, S, or T;

[0646] Xs is S or G;

[0647] X7is G or Q;

[0648] Xsis G or S;

[0649] X9is S or T;

[0650] X10 is I. Y, or F;

[0651] Xn is N, R. or K;

[0652] Xi2is D, E, G, Q or R;

[0653] X13 is E, K, T, or S;

[0654] Xi4is F, Y, or V;

[0655] X15 is E, Q or K; and

[0656] Xis is D or G;

[0657] (iii) an HCDR3 comprising the amino acid sequence:

[0658] (a) RXIX2YGX3YX4DX5(SEQ ID NO: 288) wherein: Xi is K or R;

[0659] X2is S, T, or G;

[0660] X3is Y orW;

[0661] X4 is L. V, or F; and

[0662] X5 is E. Y, or V; or

[0663] (b) RTGREYX1X2GWYFX3X4(SEQ ID NO: 289) wherein: Xi is G or S;

[0664] X2is G or S;

[0665] X3is D or A; and

[0666] X4is Y or V; and / or wherein the VL comprises one, two. or all of the following:

[0667] (iv) an LCDR1 comprising the amino acid sequence:

[0668] XiASXjXsX^XsXyXsA. wherein: Xi is K or R;

[0669] X2is K, Q or R; X3is N or S;

[0670] X4 IS L, l or V;

[0671] X5is E, D, or S;

[0672] Xe is R or S;

[0673] X7 is Q, S, Y. N or H; and

[0674] Xs is L or V;

[0675] (v) an LCDR2 comprising the amino acid sequence:

[0676] X1X2SX3X4X5X6, wherein: Xi is Q, D, R, or N;

[0677] X2is A, S, or V;

[0678] X3is R, N, or K;

[0679] X4is L. N, R. or K;

[0680] X5 is E, D, A, I; and

[0681] X6is S or T; and

[0682] (vi) an LCDR3 comprising the amino acid sequence:

[0683] X1QX2X3X4X5X6PX7X8, wherein: Xi is Q or H;

[0684] X2is F. Y or H;

[0685] X3is S, N, or G;

[0686] X4is D, E, or S;

[0687] X5is W, or absent;

[0688] X6is P, H, S, T, or Y;

[0689] X7is L. F, I, or V; and

[0690] Xs is T or D.

[0691] In some embodiments, the antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3). wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the VH comprises one. two, or all of the following:

[0692] (i) an HCDR1 comprising the amino acid sequence:

[0693] DX1X.X3X4, wherein: Xi is N or Y;

[0694] X2is N or T; X3 is M or I; and

[0695] X4is N or D;

[0696] (ii) an HCDR2 comprising the amino acid sequence:

[0697] DX1NX2RSGGX3IYNX4X5X6X7X8wherein: Xi is V or I;

[0698] X2is T or P;

[0699] X3is S or T;

[0700] X4is G, E, Q, or D;

[0701] X5is K, E, T, or S;

[0702] X6is F or Y;

[0703] X7is K, Q, or E; and X8is G or D;

[0704] (SEQ ID NO: 301);

[0705] (iii) an HCDR3 comprising the amino acid sequence:

[0706] RX1X2YGX3YX4DX5 wherein: Xi is K or R;

[0707] X2is S. T, or G;

[0708] X3is Y or W;

[0709] X4 is L, V, or F; and

[0710] X5is E, Y, or V

[0711] (SEQ ID NO: 288); and / or wherein the VL comprises one, two, or all of the following:

[0712] (iv) an LCDR1 comprising the amino acid sequence:

[0713] X1ASX2X3X4X5X6X7X8A wherein: Xi is K or R;

[0714] X2is K, Q or R;

[0715] X3is N or S;

[0716] X4is L. I or V;

[0717] X5is E. D, or S;

[0718] X6is R or S;

[0719] X7is Q, S, Y, N or H; and X8is L or V;

[0720] (v) an LCDR2 comprising the amino acid sequence:

[0721] X1X2SX3X4X5X6, wherein: Xi is Q, D, R, or N;

[0722] X2is A, S, or V;

[0723] X3is R, N, or K;

[0724] X4is L, N, R, or K;

[0725] X5 is E. D, A, I; and

[0726] Xe is S or T; and

[0727] (vi) an LCDR3 comprising the amino acid sequence:

[0728] X! QX2X3X4X5X6PX7Xg wherein: Xi is Q or H;

[0729] X2is F, Y or H;

[0730] X3is S. N, or G;

[0731] X4is D, E, or S;

[0732] Xs is W, or absent;

[0733] X6is P, H, S, T, or Y;

[0734] X7is L, F, I, or V; and

[0735] X8is T or D.

[0736] In some embodiments, the antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the VH comprises one, two, or all of the following:

[0737] (i) an HCDR1 comprising the amino acid sequence:

[0738] XIX2DX3X4, wherein: Xi is Y or F;

[0739] X2is Y or F;

[0740] X3is V or I; and

[0741] X4is Q or N;

[0742] (ii) an HCDR2 comprising tire amino acid sequence:

[0743] SlSPXiGQSX2X3YX4REXsKG, wherein: Xi is S or T;

[0744] X2is S or T;

[0745] X3is Y or F;

[0746] X4is R or K; and X5is V or F;

[0747] (SEQ ID NO: 303);

[0748] (iii) an HCDR3 comprising the amino acid sequence:

[0749] RTGREYX1X2GWYFX3X4 wherein: Xi is G or S;

[0750] X2 is G or S;

[0751] X3 is D or A; and

[0752] X4is Y or V;

[0753] (SEQ ID NO: 289); and / or wherein the VL comprises one, two. or all of the following:

[0754] (iv) an LCDR1 comprising the amino acid sequence:

[0755] X1ASX2X3X4X5X6X7X8A, wherein: Xi is K or R;

[0756] X2is K, Q or R;

[0757] X3is N or S;

[0758] X4is L. I or V;

[0759] X5 is E. D, or S;

[0760] Xe is R or S;

[0761] X7is Q, S, Y, N or H; and X8is L or V;

[0762] (v) an LCDR2 comprising the amino acid sequence:

[0763] X1X2SX3X4X5X6, wherein: Xi is Q, D, R, or N;

[0764] X2 is A, S, or V;

[0765] X3is R, N, or K;

[0766] X4is L, N, R, or K;

[0767] X5is E, D, A, I; and

[0768] X6is S or T; and

[0769] (vi) an LCDR3 comprising the amino acid sequence:

[0770] X1QX2X3X4X5X6PX7X8. wherein: Xi is Q or H;

[0771] X2is F, Y or H;

[0772] X3is S, N, or G;

[0773] X4is D, E, or S; Xs is W, or absent:

[0774] X6is P, H, S, T, or Y;

[0775] X7is L, F, I, or V; and

[0776] Xs is T or D.

[0777] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in T able 2 for VH- 1. In an embodiment, the VH comprises one, two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1. 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 215; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 216.

[0778] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-2. In an embodiment, the VH comprises one, two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1. 2, or 3 amino acid residues from, or has at least 85. 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 215; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 216.

[0779] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one. two, or all of the CDR sequences listed in Table 2 for VH-3. In an embodiment, the VH comprises one, two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 215; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 216.

[0780] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-4. In an embodiment, the VH comprises one, two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 215; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0781] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one. two, or all of the CDR sequences listed in Table 2 for VH-5. In an embodiment, the VH comprises one, two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology w ith, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 215; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0782] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one. two, or all of the CDR sequences listed in Table 2 for VH-6. In an embodiment, the VH comprises one, two. or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 215; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0783] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one. two, or all of the CDR sequences listed in Table 2 for VH-7. In an embodiment, the VH comprises one, two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 217; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 218; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 222.

[0784] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one. two, or all of the CDR sequences listed in Table 2 for VH-8. In an embodiment, the VH comprises one, two. or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 220; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 221; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 225.

[0785] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-9. In an embodiment, the VH comprises one, two. or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 223; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 224; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 228.

[0786] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-10. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 227; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 231.

[0787] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-11. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 226; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 227; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0788] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-12. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 226; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 227; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0789] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-13. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 226; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 227; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0790] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-14. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 230; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0791] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-15. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 230; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0792] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-16. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 226; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 230; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0793] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-17. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 227; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0794] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-18. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 230; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 231.

[0795] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-19. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 232; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 233; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 237.

[0796] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-20. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 235; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 236; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 238.

[0797] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-21. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 230; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0798] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-22. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 240; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0799] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-23. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 242; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 216.

[0800] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-24. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 214; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 242; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0801] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-25. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 242; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0802] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-26. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 243; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0803] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-27. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 244; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0804] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-28. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 245; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0805] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-29. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 246; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0806] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-30. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 260; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 241.

[0807] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-31. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 260; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0808] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-32. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 229; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 230; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 234.

[0809] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-33. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85. 90. 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 260; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0810] In an embodiment, the antibody molecule comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the CDR sequences listed in Table 2 for VH-34. In an embodiment, the VH comprises one. two, or all of the following: an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 239; an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, tire amino acid sequence of SEQ ID NO: 260; or an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 219.

[0811] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-1. In an embodiment, the VL comprises one, two. or all of tire following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 151; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 153.

[0812] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-2. In an embodiment, the VL comprises one, two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 156.

[0813] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-3. In an embodiment, the VL comprises one, two. or all of tire following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 156.

[0814] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-4. In an embodiment, the VL comprises one, two. or all of tire following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 156.

[0815] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-5. In an embodiment, the VL comprises one, two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 157; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 155; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 159.

[0816] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-6. In an embodiment, the VL comprises one, two. or all of tire following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 299.

[0817] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-7. In an embodiment, the VL comprises one, two. or all of tire following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 163; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 299.

[0818] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-8. In an embodiment, the VL comprises one, two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 158; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 162.

[0819] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-9. In an embodiment, the VL comprises one, two. or all of tire following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 166; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 161; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 165.

[0820] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-10. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 169; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 153.

[0821] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-11. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 153.

[0822] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-12. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 164; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 168.

[0823] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-13. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 172; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 167; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 171.

[0824] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-14. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 175; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 170; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 174.

[0825] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-15. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 151; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 176; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 171.

[0826] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-16. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 181; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 180.

[0827] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-17. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 184; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 158; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 183.

[0828] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-18. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 184; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 158; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 183.

[0829] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-19. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 184; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 158; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 183.

[0830] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-20. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0831] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-21. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0832] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-22. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 248.

[0833] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-23. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0834] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-24. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0835] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-25. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0836] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-26. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0837] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-27. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 156.

[0838] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-28. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 254; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0839] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-29. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 252; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0840] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-30. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0841] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-31. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 156.

[0842] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-32. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 253; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0843] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-33. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 152; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0844] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-34. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 255; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0845] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-35. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 154; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 255; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 256.

[0846] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-36. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 257.

[0847] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-48. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 258; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0848] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-49. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0849] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-50. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0850] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-51. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 259.

[0851] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-60. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0852] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-61. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0853] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-62. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0854] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-63. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0855] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-65. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0856] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-66. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0857] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-68. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0858] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-69. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0859] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-71. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0860] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-72. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0861] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-73. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0862] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-74. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0863] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-75. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0864] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-76. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0865] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-78. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0866] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-80. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0867] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-82. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0868] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-84. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0869] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-86. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0870] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-87. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0871] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-88. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0872] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-89. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0873] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-90. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 251; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0874] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-91. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 249; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0875] In an embodiment, the antibody molecule comprises a light chain variable region (VL), w'herein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-92. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0876] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2. and LCDR3), wherein the light chain variable region comprises one, two, or all of the CDR sequences listed in Table 1 for VL-93. In an embodiment, the VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0877] In an embodiment, the antibody molecule comprises a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), w herein the light chain variable region comprises one, tw o, or all of the CDR sequences listed in Table 1 for VL-94. In an embodiment, tire VL comprises one. two, or all of the following: an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2. or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 160; an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 250; or an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90. 95. 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 247.

[0878] In an embodiment, the antibody molecule comprises a VH comprising an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to, or differing by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, any of SEQ ID NOs: 95-125 or 279-281. In embodiments, the antibody molecule comprises a VH comprising the amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281.

[0879] In an embodiment, the antibody molecule comprises a VL comprising an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to, or differing by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94. In embodiments, the antibody molecule comprises a VL comprising the amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94.

[0880] In an embodiment, the antibody molecule comprises a VH comprising an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to, or differing by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. 11, 12, 13, 14, or 15 amino acid residues from, any of SEQ ID NOs: 95-125 or 279-281 and a VL comprising an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to, or differing by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94. In embodiments, the antibody molecule comprises a VH comprising the amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281 and a VL comprising the amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69. 71-76, 78, 80, 82, 84, or 86-94.

[0881] In an embodiment, the antibody molecule, e.g, the multispecific (e.g., bispecific) antibody molecule capable of binding to FIXa comprises a VH comprising an amino acid sequence of SEQ ID NO: 105 and / or a VL comprising an amino acid sequence of SEQ ID NO: 20. In an embodiment, the antibody molecule, e.g., the multispecific (e.g, bispecific) antibody molecule capable of binding to FIXa comprises a VH comprising an amino acid sequence...

Claims

CLAIMSWhat is claimed is:

1. An isolated antibody molecule, comprising a first binding moiety capable of binding to FIXa, FX, or both, wherein the first binding moiety comprises: a first heavy chain variable region (VH) comprising an HCDR1 amino acid sequence of any of SEQ ID NOs: 214, 217, 220, 223, 226, 229, 232, 235, or 239; an HCDR2 amino acid sequence of any of SEQ ID NOs: 215, 218, 221, 224, 227, 230, 233, 236, 240, 242, 243, 244, 245, 246. or 260; and an HCDR3 amino acid sequence of any of SEQ ID NOs: 216, 219. 222, 225. 228, 231. 234, 237. 238, or 241 ; and a first light chain variable region (VL) comprising an LCDR1 amino acid sequence of any of SEQ ID NOs: 151, 154, 157, 160, 163, 166, 169, 172, 175, 181, 184, 251-253, or 258; an LCDR2 amino acid sequence of any of SEQ ID NOs:

152. 155, 158. 161, 164. 167, 170, 176, 249, 250, 254, or 255; and an LCDR3 amino acid sequence of any of SEQ ID NOs: 153, 156, 159, 162, 165, 168, 171, 174, 180, 183, 247. 248, 256. 257, 259. or 299.

2. Tire antibody molecule of claim 1, wherein the first VH comprises:(a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(b) the HCDR1 amino acid sequence of SEQ ID NO:

214. the HCDR2 amino acid sequence of SEQ ID NO:

215. and the HCDR3 amino acid sequence of SEQ ID NO: 219;(c) the HCDR1 amino acid sequence of SEQ ID NO: 217, the HCDR2 amino acid sequence of SEQ ID NO: 218, and the HCDR3 amino acid sequence of SEQ ID NO: 222;(d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221, and the HCDR3 amino acid sequence of SEQ ID NO: 225;(e) tire HCDR1 amino acid sequence of SEQ ID NO:

223. the HCDR2 amino acid sequence of SEQ ID NO: 224, and the HCDR3 amino acid sequence of SEQ ID NO: 228;(f) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(g) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(h) the HCDR1 amino acid sequence of SEQ ID NO:

229. the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(l) the HCDR1 amino acid sequence of SEQ ID NO: 232, the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;(m) the HCDR1 amino acid sequence of SEQ ID NO: 235, the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;(n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(o) the HCDR1 amino acid sequence of SEQ ID NO:

239. the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(p) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(r) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(s) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(u) the HCDR1 amino acid sequence of SEQ ID NO:

239. the HCDR2 amino acid sequence of SEQ ID NO:

246. and the HCDR3 amino acid sequence of SEQ ID NO: 241;(v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 241; or(w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 219.

3. The antibody molecule of claim 1 or 2, wherein the first VE comprises:(a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(c) the LCDR1 amino acid sequence of SEQ ID NO: 157, the LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;(d) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(f) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;(g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;(h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(i) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(j) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;(k) the LCDRl amino acid sequence of SEQ ID NO:

172. the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(l) the LCDRl amino acid sequence of SEQ ID NO: 175, the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;(m) the LCDRl amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(n) the LCDRl amino acid sequence of SEQ ID NO:

181. the LCDR2 amino acid sequence of SEQ ID NO:

152. and the LCDR3 amino acid sequence of SEQ ID NO: 180;(o) the LCDRl amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;(p) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(q) the LCDRl amino acid sequence of SEQ ID NO:

160. the LCDR2 amino acid sequence of SEQ ID NO:

250. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(r) the LCDRl amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;(s) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(v) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(w) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(x) the LCDR1 amino acid sequence of SEQ ID NO: 253, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;(aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;(bb) the LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO:

249. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(dd) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO:

249. and the LCDR3 amino acid sequence of SEQ ID NO: 259;(ff) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(gg) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247; or(hh) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO:

255. and the LCDR3 amino acid sequence of SEQ ID NO: 247.

4. Tire antibody molecule of any of claims 1-3, wherein the first VH comprises:(a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(b) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(c) the HCDR1 amino acid sequence of SEQ ID NO:

217. the HCDR2 amino acid sequence of SEQ ID NO: 218, and the HCDR3 amino acid sequence of SEQ ID NO: 222;(d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221, and the HCDR3 amino acid sequence of SEQ ID NO: 225;(e) the HCDR1 amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224, and the HCDR3 amino acid sequence of SEQ ID NO: 228;(f) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(g) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(h) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(l) the HCDR1 amino acid sequence of SEQ ID NO: 232, the HCDR2 amino acid sequence of SEQ ID NO:

233. and the HCDR3 amino acid sequence of SEQ ID NO: 237;(m) the HCDR1 amino acid sequence of SEQ ID NO: 235, the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;(n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(o) the HCDR1 amino acid sequence of SEQ ID NO:

239. the HCDR2 amino acid sequence of SEQ ID NO:

242. and the HCDR3 amino acid sequence of SEQ ID NO: 216;(p) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(r) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(s) the EICDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 241; or(w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 219; and wherein the first VL comprises:(a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(c) the LCDR1 amino acid sequence of SEQ ID NO:

157. the LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;(d) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(e) tire LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(f) the LCDR1 amino acid sequence of SEQ ID NO:

154. the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;(g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;(h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(i) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(j) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;(k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(l) the LCDR1 amino acid sequence of SEQ ID NO: 175, the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;(m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;(o) the LCDR1 amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;(p) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(q) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(r) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;(s) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO:

152. and the LCDR3 amino acid sequence of SEQ ID NO: 156;(t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(v) the LCDRl amino acid sequence of SEQ ID NO:

160. the LCDR2 amino acid sequence of SEQ ID NO:

250. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(w) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(x) the LCDRl amino acid sequence of SEQ ID NO: 253, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(y) the LCDRl amino acid sequence of SEQ ID NO:

251. the LCDR2 amino acid sequence of SEQ ID NO:

152. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(z) the LCDRl amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;(aa) the LCDRl amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;(bb) the LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(dd) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;(ff) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(gg) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247; or(hh) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 247.

5. The antibody molecule of any of claims 1-4, wherein the first VH comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%. 98%. or 99% identical to any of SEQ ID NOs: 95-125 or 279-281.

6. Tire antibody molecule of any of claims 1-5, wherein the first VH comprises the amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281.

7. The antibody molecule of any of claims 1-6, wherein the first VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%. 98%. or 99% identical to any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94.

8. Tire antibody molecule of any of claims 1-7, wherein the first VL comprises the amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76. 78, 80, 82, 84, or 86-94.

9. The antibody molecule of any of claims 1-5 or 7, wherein the first VH comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 95-125 or 279-281; and wherein the first VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69. 71-76, 78, 80, 82, 84, or 86-94.

10. The antibody molecule of any of claims 1-9, wherein the first VH comprises the amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281; and wherein the first VL comprises the amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76. 78, 80, 82, 84, or 86-94.

11. The antibody molecule of any of claims 1-10. wherein the first binding moiety is capable of binding to FIXa and comprises:(a) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;(b) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 25;(c) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:29;(d) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 33;(e) a first VH comprising tire amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:28;(f) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 32:(g) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 36;(h) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 21;(i) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 23:(j) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 30;(k) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;(l) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;(m) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;(n) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 34;(o) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 35;(p) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 62;(q) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 63;(r) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 75;(s) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 73;(t) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76;(u) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90;(v) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 91; or(w) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 93.

12. The antibody molecule of any of claims 1-10, wherein the first binding moiety is capable of binding to FX and comprises:(a) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 17;(b) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;(c) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 25;(d) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 29;(e) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 33;(f) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 28;(g) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 32;(h) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 36;(i) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 21;(j) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 23;(k) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 30;(l) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;(m) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 34;(n) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 35;(o) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 62;(p) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 63;(q) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 75;(r) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 73;(s) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 76;(t) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 90;(u) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 91;(v) a first VH comprising the amino acid sequence of SEQ ID NO: 125 and a first VL comprising the amino acid sequence of SEQ ID NO: 93;(w) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 76; or(x) a first VH comprising the amino acid sequence of SEQ ID NO: 95 and a first VL comprising the amino acid sequence of SEQ ID NO: 90.

13. The antibody molecule of any of claims 1-12. wherein the first binding moiety is capable of binding to both FIXa and FX.

14. Tire antibody molecule of any of claims 1-13, wherein the first binding moiety has a binding affinity to FIXa that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or 100-fold higher than its binding affinity to FX.

15. The antibody molecule of any of claims 1-13, wherein the first binding moiety has a binding affinity to FX that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or 100-fold higher than its binding affinity to FIXa.

16. The antibody molecule of any of claims 1-13. wherein the first binding moiety has a binding affinity to FIXa that is no more than 0.5, 1, 2.

3. 4, 5, 6.

7. 8, 9, or 10-fold higher than its binding affinity to FX.

17. Tire antibody molecule of any of claims 1-13, wherein the first binding moiety has a binding affinity to FX that is no more than 0.5, 1, 2, 3. 4, 5, 6, 7, 8, 9, or 10-fold higher than its binding affinity to FIXa.

18. The antibody molecule of any of claims 1-16, further comprising a second binding moiety capable of binding to FIXa, FX, or both, wherein the second binding moiety comprises a second VH and a second VL.

19. The antibody molecule of claim 18. wherein tire second binding moiety comprises a second VH comprising an HCDR1 amino acid sequence of any of SEQ ID NOs:

214. 217, 220. 223, 226.229, 232, 235, or 239; an HCDR2 amino acid sequence of any of SEQ ID NOs: 215, 218, 221, 224, 227,230, 233, 236, 240, 242, 243, 244, 245, 246, or 260; and an HCDR3 amino acid sequence of any of SEQ ID NOs: 216, 219, 222, 225, 228, 231, 234, 237, 238, or 241; anda second VL comprising an LCDR1 amino acid sequence of any of SEQ ID NOs: 151, 154, 157, 160, 163, 166, 169, 172, 175, 181, 184, 251-253, or 258; an LCDR2 amino acid sequence of any of SEQ ID NOs: 152, 155, 158, 161, 164, 167, 170, 176, 249, 250, 254, or 255; and an LCDR3 amino acid sequence of any of SEQ ID NOs: 153, 156, 159, 162, 165. 168, 171, 174, 180, 183, 247, 248, 256, 257, 259, or 299.

20. The antibody molecule of claim 18 or 19, wherein the second VH comprises:(a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(b) the HCDRl amino acid sequence of SEQ ID NO:

214. tire HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(c) the HCDRl amino acid sequence of SEQ ID NO:

217. the HCDR2 amino acid sequence of SEQ ID NO: 218, and the HCDR3 amino acid sequence of SEQ ID NO: 222;(d) the HCDRl amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221, and the HCDR3 amino acid sequence of SEQ ID NO: 225;(e) the HCDRl amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224, and the HCDR3 amino acid sequence of SEQ ID NO: 228;(f) the HCDRl amino acid sequence of SEQ ID NO:

229. the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(g) the HCDRl amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(h) the HCDRl amino acid sequence of SEQ ID NO:

229. the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(i) the HCDRl amino acid sequence of SEQ ID NO:

226. the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(j) the HCDRl amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(k) the HCDRl amino acid sequence of SEQ ID NO:

229. the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(l) the HCDRl amino acid sequence of SEQ ID NO:

232. the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;(m) the HCDRl amino acid sequence of SEQ ID NO: 235, the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;(n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(o) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(p) the HCDR1 amino acid sequence of SEQ ID NO:

214. the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(r) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(s) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 244, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(v) the HCDR1 amino acid sequence of SEQ ID NO:

239. the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 241; or(w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 219.

21. The antibody molecule of any of claims 18-20, wherein the second VL comprises:(a) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO:

152. and the LCDR3 amino acid sequence of SEQ ID NO: 153;(b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(c) the LCDR1 amino acid sequence of SEQ ID NO: 157, tire LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;(d) the LCDR1 amino acid sequence of SEQ ID NO:

160. the LCDR2 amino acid sequence of SEQ ID NO:

152. and the LCDR3 amino acid sequence of SEQ ID NO: 299;(e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(f) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;(g) the LCDR1 amino acid sequence of SEQ ID NO: 166, the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;(h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(i) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(j) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;(k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(l) the LCDR1 amino acid sequence of SEQ ID NO: 175, the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;(m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;(o) the LCDRl amino acid sequence of SEQ ID NO:

184. the LCDR2 amino acid sequence of SEQ ID NO:

158. and the LCDR3 amino acid sequence of SEQ ID NO: 183;(p) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(q) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(r) the LCDRl amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO:

250. and the LCDR3 amino acid sequence of SEQ ID NO: 248;(s) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(t) the LCDRl amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(u) the LCDRl amino acid sequence of SEQ ID NO:

252. the LCDR2 amino acid sequence of SEQ ID NO:

249. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(v) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(w) the LCDRl amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(x) the LCDR1 amino acid sequence of SEQ ID NO: 253, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 256;(aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;(bb) the LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247(cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247(dd) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(ee) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;(ff) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO:

250. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(gg) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247; or(hh) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 247.

22. The antibody molecule of any of claims 18-21, wherein the second VH comprises:(a) the HCDR1 amino acid sequence of SEQ ID NO: 214, the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(b) the HCDR1 amino acid sequence of SEQ ID NO:

214. the HCDR2 amino acid sequence of SEQ ID NO: 215, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(c) the HCDR1 amino acid sequence of SEQ ID NO:

217. the HCDR2 amino acid sequence of SEQ ID NO: 218, and the HCDR3 amino acid sequence of SEQ ID NO: 222;(d) the HCDR1 amino acid sequence of SEQ ID NO: 220, the HCDR2 amino acid sequence of SEQ ID NO: 221, and the HCDR3 amino acid sequence of SEQ ID NO: 225;(e) the HCDR1 amino acid sequence of SEQ ID NO: 223, the HCDR2 amino acid sequence of SEQ ID NO: 224, and the HCDR3 amino acid sequence of SEQ ID NO: 228;(f) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(g) the HCDR1 amino acid sequence of SEQ ID NO:

226. the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(h) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(i) the HCDR1 amino acid sequence of SEQ ID NO: 226, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(j) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 227, and the HCDR3 amino acid sequence of SEQ ID NO: 234;(k) the HCDR1 amino acid sequence of SEQ ID NO: 229, the HCDR2 amino acid sequence of SEQ ID NO: 230, and the HCDR3 amino acid sequence of SEQ ID NO: 231;(l) the HCDR1 amino acid sequence of SEQ ID NO: 232, the HCDR2 amino acid sequence of SEQ ID NO: 233, and the HCDR3 amino acid sequence of SEQ ID NO: 237;(m) the HCDR1 amino acid sequence of SEQ ID NO: 235, the HCDR2 amino acid sequence of SEQ ID NO: 236, and the HCDR3 amino acid sequence of SEQ ID NO: 238;(n) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 240, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(o) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 216;(p) the HCDR1 amino acid sequence of SEQ ID NO:

214. the HCDR2 amino acid sequence of SEQ ID NO:

242. and the HCDR3 amino acid sequence of SEQ ID NO: 241;(q) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 242, and the HCDR3 amino acid sequence of SEQ ID NO: 219;(r) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 243, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(s) the HCDR1 amino acid sequence of SEQ ID NO:

239. the HCDR2 amino acid sequence of SEQ ID NO:

244. and the HCDR3 amino acid sequence of SEQ ID NO: 241;(t) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 245, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(u) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 246, and the HCDR3 amino acid sequence of SEQ ID NO: 241;(v) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 241; or(w) the HCDR1 amino acid sequence of SEQ ID NO: 239, the HCDR2 amino acid sequence of SEQ ID NO: 260, and the HCDR3 amino acid sequence of SEQ ID NO: 219; and wherein the second VL comprises:(a) the LCDR1 amino acid sequence of SEQ ID NO:

151. the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(b) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(c) the LCDR1 amino acid sequence of SEQ ID NO: 157, tire LCDR2 amino acid sequence of SEQ ID NO: 155, and the LCDR3 amino acid sequence of SEQ ID NO: 159;(d) the LCDR1 amino acid sequence of SEQ ID NO:

160. the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(e) the LCDR1 amino acid sequence of SEQ ID NO: 163, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 299;(f) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 162;(g) the LCDR1 amino acid sequence of SEQ ID NO:

166. the LCDR2 amino acid sequence of SEQ ID NO: 161, and the LCDR3 amino acid sequence of SEQ ID NO: 165;(h) the LCDR1 amino acid sequence of SEQ ID NO: 169, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(i) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 153;(j) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 164, and the LCDR3 amino acid sequence of SEQ ID NO: 168;(k) the LCDR1 amino acid sequence of SEQ ID NO: 172, the LCDR2 amino acid sequence of SEQ ID NO: 167, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(l) the LCDR1 amino acid sequence of SEQ ID NO: 175, the LCDR2 amino acid sequence of SEQ ID NO: 170, and the LCDR3 amino acid sequence of SEQ ID NO: 174;(m) the LCDR1 amino acid sequence of SEQ ID NO: 151, the LCDR2 amino acid sequence of SEQ ID NO: 176, and the LCDR3 amino acid sequence of SEQ ID NO: 171;(n) the LCDR1 amino acid sequence of SEQ ID NO: 181, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 180;(o) the LCDR1 amino acid sequence of SEQ ID NO: 184, the LCDR2 amino acid sequence of SEQ ID NO: 158, and the LCDR3 amino acid sequence of SEQ ID NO: 183;(p) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(q) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(r) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 248;(s) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 156;(t) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 254, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(u) the LCDR1 amino acid sequence of SEQ ID NO: 252, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(v) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(w) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO:

250. and the LCDR3 amino acid sequence of SEQ ID NO: 156;(x) the LCDR1 amino acid sequence of SEQ ID NO: 253, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(y) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(z) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO:

255. and the LCDR3 amino acid sequence of SEQ ID NO: 256;(aa) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 257;(bb) the LCDR1 amino acid sequence of SEQ ID NO: 258, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(cc) the LCDR1 amino acid sequence of SEQ ID NO: 160, the LCDR2 amino acid sequence of SEQ ID NO:

249. and the LCDR3 amino acid sequence of SEQ ID NO: 247;(dd) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(cc) the LCDR1 amino acid sequence of SEQ ID NO: 251, the LCDR2 amino acid sequence of SEQ ID NO: 249, and the LCDR3 amino acid sequence of SEQ ID NO: 259;(ff) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 250, and the LCDR3 amino acid sequence of SEQ ID NO: 247;(gg) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 152, and the LCDR3 amino acid sequence of SEQ ID NO: 247; or(hh) the LCDR1 amino acid sequence of SEQ ID NO: 154, the LCDR2 amino acid sequence of SEQ ID NO: 255, and the LCDR3 amino acid sequence of SEQ ID NO: 247.

23. Tire antibody molecule of any of claims 18-22, wherein the second VH comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 95-125 or 279-281.

24. The antibody molecule of any of claims 18-23, wherein the second VH comprises the amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281.

25. Tire antibody molecule of any of claims 18-24, wherein the second VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 1-36, 48-51. 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94.

26. The antibody molecule of any of claims 18-25, wherein the second VL comprises the amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94.

27. The antibody molecule of any of claims 18-23 or 25, wherein the second VH comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%. 96%. 97%. 98%. or 99% identical to any of SEQ ID NOs: 95-125 or 279-281; and wherein the second VL comprises an amino acid sequence at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94.

28. The antibody molecule of any of claims 18-27, wherein the second VH comprises the amino acid sequence of any of SEQ ID NOs: 95-125 or 279-281; and wherein the second VL comprises the amino acid sequence of any of SEQ ID NOs: 1-36, 48-51, 60-63, 65, 66, 68, 69, 71-76, 78, 80, 82, 84, or 86-94.

29. The antibody molecule of any of claims 18-28, wherein the second binding moiety is capable of binding to FIXa and comprises:(a) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;(b) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 25;(c) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO:29;(d) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 33;(e) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO:28;(f) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 32;(g) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising tire amino acid sequence of SEQ ID NO: 36;(h) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 21;(i) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 23;(j) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising tire amino acid sequence of SEQ ID NO: 30;(k) a second VH comprising the amino acid sequence of SEQ ID NO: 105 and a second VL comprising the amino acid sequence of SEQ ID NO: 31;(l) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;(m) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising tire amino acid sequence of SEQ ID NO: 31;(n) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 34;(o) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 35;(p) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising tire amino acid sequence of SEQ ID NO: 62;(q) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 63;(r) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 75;(s) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 73;(t) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 76;(u) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 90;(v) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 91; or(w) a second VH comprising the amino acid sequence of SEQ ID NO: 115 and a second VL comprising the amino acid sequence of SEQ ID NO: 93.

30. The antibody molecule of any of claims 18-29, wherein the second binding moiety is capable of binding to FX and comprises:(a) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 17;(b) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;(c) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 25;(d) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 29;(e) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 33;(f) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 28;(g) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 32;(h) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 36;(i) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 21;(j) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 23;(k) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 30;(l) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 31 ;(m) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 34;(n) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 35;(o) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 62;(p) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 63;(q) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 75;(r) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 73;(s) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 76;(t) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 90;(u) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 91;(v) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 93;(w) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 76; or(x) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 90.

31. The antibody molecule of any of claims 18-30, wherein the second binding moiety is capable of binding to both FIXa and FX.

32. The antibody molecule of any of claims 18-31, wherein the first binding moiety is capable of binding to both FIXa and FX, and wherein the second binding moiety is capable of binding to both FIXa and FX.

33. Tire antibody molecule of any of claims 18-32, wherein the second binding moiety has a binding affinity to FIXa that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or 100-fold higher than its binding affinity to FX.

34. The antibody molecule of any of claims 18-32, wherein the second binding moiety has a binding affinity to FX that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or 100-fold higher than its binding affinity to FIXa.

35. The antibody molecule of any of claims 18-32, wherein the second binding moiety has a binding affinity to FIXa that is no more than 0.5, 1, 2, 3. 4, 5, 6, 7. 8, 9, or 10-fold higher than its binding affinity to FX.

36. Tire antibody molecule of any of claims 18-32, wherein the second binding moiety has a binding affinity to FX that is no more than 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold higher than its binding affinity to FIXa.

37. The antibody molecule of any of claims 18-32, wherein the first binding moiety is identical, or substantially identical, to the second binding moiety.

38. Tire antibody molecule of any of claims 18-36, wherein the first binding moiety is different from the second binding moiety.

39. The antibody molecule of any of claims 18-32 or 37, wherein the second VH is identical, or substantially identical, to the first VH, and wherein the second VL is identical, or substantially identical, to the first VL.

40. The antibody molecule of any of claims 18-32 or 38, wherein the second VH is identical, or substantially identical, to the first VH, and wherein the second VL is different from the first VL.

41. Tire antibody molecule of any of claims 18-32 or 38, wherein tire second VH is different from tire first VH, and wherein the second VL is identical, or substantially identical, to the first VL.

42. The antibody molecule of any of claims 18-32 or 38, wherein the second VH is different from the first VH, and wherein the second VL is different from the first VL.

43. Tire antibody molecule of any of claims 18-36, wherein the second binding moiety has a binding affinity to FIXa that is at least 0.5, 1, 2, 3, 4, 5, 6, 7. 8, 9, 10, 20, 50, or 100-fold higher than the binding affinity of the first binding moiety to FIXa.

44. Tire antibody molecule of any of claims 18-36, wherein the second binding moiety has a binding affinity to FIXa that is no more than 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold higher than tire binding affinity of the first binding moiety to FIXa.

45. The antibody molecule of any of claims 18-36 or 43-44, wherein the second binding moiety has a binding affinity to FX that is at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or 100-fold higher than the binding affinity of the first binding moiety to FX.

46. The antibody molecule of any of claims 18-36 or 43-44, wherein the second binding moiety has a binding affinity to FX that is no more than 0.

5. 1, 2, 3, 4. 5, 6, 7, 8. 9, or 10-fold higher than the binding affinity of the first binding moiety to FX.

47. Tire antibody molecule of any of claims 18-46, wherein the first binding moiety comprises a Fab, the second binding moiety comprises a Fab, or both.

48. The antibody molecule of any of claims 18-47, wherein the first binding moiety and the second binding moiety are not covalently linked.

49. Tire antibody molecule of any of claims 1-48, which is a tetramer comprising two VHs and two VLs.

50. The antibody molecule of any of claims 18-46, wherein the first binding moiety comprises a single chain Fv (scFv), the second binding moiety comprises an scFv, or both.

51. Tire antibody molecule of any of claims 18-47 or 49-50, wherein the first binding moiety and the second binding moiety are covalently linked.

52. The antibody molecule of claim 51, wherein the first binding moiety and the second binding moiety are covalently linked by a linker.

53. Tire antibody molecule of claim 52, wherein the linker comprises one or more glycine residues and one or more serine residues f‘GS” linker).

54. The antibody molecule of any of claims 1-53, wherein the first binding moiety is capable of binding to FIXa and comprises:(a) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;(b) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 25;(c) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 29;(d) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 33;(e) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO:28;(f) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 32;(g) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 36;(h) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 21;(i) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 23;(j) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 30;(k) a first VH comprising the amino acid sequence of SEQ ID NO: 105 and a first VL comprising the amino acid sequence of SEQ ID NO: 31 ;(l) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 20;(m) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 31;(n) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 34;(o) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 35;(p) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 62;(q) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 63;(r) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 75;(s) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 73;(t) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76;(u) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90;(v) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 91; or(w) a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 93; and wherein the second binding moiety is capable of binding to FX and comprises:(a) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 17;(b) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 20;(c) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 25;(d) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 29;(e) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 33;(f) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 28;(g) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 32;(h) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 36;(i) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 21;(j) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 23;(k) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 30;(l) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 31;(m) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 34;(n) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 35;(o) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 62;(p) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 63;(q) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 75;(r) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 73;(s) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 76;(t) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 90;(u) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 91;(v) a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 93;(w) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 76; or(x) a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 90.

55. Tire antibody molecule of any of claims 1-54, wherein:(a) the first binding moiety comprises a VH comprising an amino acid sequence as described in Table 2 or 4 and / or a VL comprising an amino acid sequence as described in Table 1 or 4: and(b) the second binding moiety comprises a VH comprising an amino acid sequence as described in Table 2 or 4 and / or a VL comprising an amino acid sequence as described in Table 1 or 4; wherein the first binding moiety is capable of binding to FIXa and the second binding moiety is capable of binding to FX.

56. The antibody molecule of any of claims 1-55. wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 20; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 20.

57. The antibody molecule of any of claims 1-55. wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 62; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 62.

58. The antibody molecule of any of claims 1-55. wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 63; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 63.

59. The antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 75; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 75.

60. Tire antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 73; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 73.

61. Tire antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76; and wherein the second moiety’ is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 76.

62. Tire antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90; and wherein the second moiety’ is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 90.

63. The antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 91; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 91.

64. Tire antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 93; and wherein the second moiety iscapable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 125 and a second VL comprising the amino acid sequence of SEQ ID NO: 93.

65. The antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 76; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 76.

66. Tire antibody molecule of any of claims 1-55, wherein the first binding moiety is capable of binding to FIXa and comprises a first VH comprising the amino acid sequence of SEQ ID NO: 115 and a first VL comprising the amino acid sequence of SEQ ID NO: 90; and wherein the second moiety is capable of binding to FX and comprises a second VH comprising the amino acid sequence of SEQ ID NO: 95 and a second VL comprising the amino acid sequence of SEQ ID NO: 90.

67. The antibody molecule of any of claims 1-66, which is a multispecific antibody molecule.

68. The antibody molecule of any of claims 1-67. which is a bispecific or dual specific antibody molecule.

69. Tire antibody molecule of any of claims 1-68, further comprising a third binding moiety.

70. The antibody molecule of any of claims 1-69. which comprises an antigen-binding fragment.

71. Tire antibody molecule of claim 70, wherein the antigen-binding fragment comprises a Fab, F(ab')2, Fv, scFv, or sc(Fv)2.

72. The antibody molecule of any of claims 1-71. which comprises a heavy chain constant region chosen from the heavy chain constant regions of IgGl. IgG2. lgG3, lgG4, or a chimera or combination thereof, and a light chain constant region chosen from the light chain constant regions of kappa or lambda.

73. The antibody molecule of any of claims 1-72, which comprises a light chain constant region chosen from the light chain constant regions of kappa or lambda.

74. Tire antibody molecule of any of claims 1-73, which comprises an Fc region.

75. The antibody molecule of any of claims 1-74. which comprises a CHI comprising the amino acid sequence of SEQ ID NO: 262 or 282.

76. Tire antibody molecule of any of claims 18-75, wherein the first VH is linked to a CHI comprising the amino acid sequence of SEQ ID NO: 262 or 282, directly or indirectly, and wherein the second VH is linked to a CHI comprising the amino acid sequence of SEQ ID NO: 262 or 282, directly or indirectly.

77. Tire antibody molecule of any of claims 1-76, which comprises a CH2 comprising the amino acid sequence of any of SEQ ID NOs: 265, 261, or 283.

78. The antibody molecule of any of claims 18-77, wherein the first VH is linked to a CH2 comprising the amino acid sequence of any of SEQ ID NOs: 265, 261 , or 283, indirectly, and wherein the second VH is linked to a CH2 comprising the amino acid sequence of any of SEQ ID NOs: 265, 261, or 283, indirectly.

79. The antibody molecule of any of claims 1-78. wherein the antibody molecule comprises a CL comprising the amino acid sequence of SEQ ID NO: 263 or 298.

80. Tire antibody molecule of any of claims 18-79, wherein the first VL is linked to a CL comprising the amino acid sequence of SEQ ID NO: 263 or 298, directly or indirectly, and the second VL is linked to a CL comprising the amino acid sequence of SEQ ID NO: 263 or 298, directly or indirectly.

81. The antibody molecule of any of claims 1-80, which comprises a hinge region comprising the amino acid sequence of SEQ ID NO: 264.

82. Tire antibody molecule of any of claims 18-81, wherein the first VH is linked to a hinge region comprising the amino acid sequence of SEQ ID NO: 264, indirectly, and wherein the second VH is linked to a hinge region comprising the amino acid sequence of SEQ ID NO:

264. indirectly.

83. The antibody molecule of any of claims 1-82, which comprises a CH3 comprising the amino acid sequence of any of SEQ ID NOs: 266, 271, 272, 284, 285, 296, or 297.

84. The antibody molecule of any of claims 18-83, wherein the first VH is linked to a CH3 comprising the amino acid sequence of any of SEQ ID NOs: 266, 271, 272, 284, 285, 296, or 297, indirectly, and wherein the second VH is linked to a CH3 comprising the amino acid sequence of any of SEQ ID NOs: 266, 271, 272, 284, 285, 296, or 297, indirectly.

85. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 311.

86. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 314, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 315, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 311.

87. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 316.

88. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 317.

89. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 318.

90. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise tire amino acid sequence of SEQ ID NO: 319.

91. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise tire amino acid sequence of SEQ ID NO: 320.

92. The antibody molecule of any of claims 1-84. which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 321.

93. The antibody molecule of any of claims 1-84. which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 310, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 322.

94. The antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 323, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 319.

95. Tire antibody molecule of any of claims 1-84, which comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 309, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 323, and a first light chain and second light chain, wherein each of the first and second light chains comprise the amino acid sequence of SEQ ID NO: 320.

96. Tire antibody molecule of any of the preceding claims, wherein said antibody molecule is an isolated antibody molecule.

97. The antibody molecule of any of the preceding claims, wherein said antibody molecule is a humanized antibody molecule.

98. Tire antibody molecule of any of the preceding claims, wherein said antibody molecule is a monoclonal antibody molecule.

99. The antibody molecule of any of the preceding claims, wherein said antibody molecule is a synthetic antibody molecule.

100. Tire antibody molecule of any of the preceding claims, wherein the FIXa is a human FIXa.101 . The antibody molecule of any of the preceding claims, wherein the FX is a human FX.

102. Tire antibody molecule of any of the preceding claims, which, when contacted to a cell, tissue, or subject, increases the level of thrombin in the cell, tissue, or subject relative to a control cell, tissue, or subject that was not administered the antibody molecule.

103. The antibody molecule of any of the preceding claims, which, when contacted to a cell, tissue, or subject, the level of thrombin in the cell, tissue, or subject is higher (e.g., at least 2-fold, at least 3 -fold, at least 4-fold, at least 5 -fold, or at least 6-fold higher) relative to a cell, tissue, or subject that was administered an antibody molecule comprising the amino acid sequences of SEQ ID NOs. 293-295.

104. An antibody molecule that competes for binding to FIXa. FX. or both, with an antibodymolecule of any of the preceding claims.

105. An antibody molecule that binds to the same or overlapping epitope on FIXa, FX, or both, as the epitope recognized by an antibody molecule of any of the preceding claims.

106. A pharmaceutical composition comprising the isolated antibody molecule of any of the preceding claims and a pharmaceutically acceptable carrier, excipient or stabilizer.

107. An isolated nucleic acid encoding the first VH, first VL, or both, of the antibody molecule of any of claims 1-105.

108. An isolated nucleic acid encoding the second VH, second VL, or both, of the antibody molecule of any of claims 18-105.

109. An expression vector comprising the nucleic acid of claim 107, 108, or both.

110. A host cell comprising the nucleic acid of claim 107 or 108 or the expression vector of claim 109.

111. A method of producing an antibody molecule, comprising culturing the host cell of claim 110 under conditions suitable for gene expression.

112. A method of increasing the level of FXa, comprising contacting a cell deficient of F VIII with an antibody molecule of any of claims 1-105, or a pharmaceutical composition of claim 106.

113. The method of claim 112, wherein the contacting step occurs in vitro, ex vivo, or in vivo.

114. A method of treating a disorder associated with a coagulation pathway, comprising administering to a subject in need thereof an antibody molecule of any of claims 1-105, or a pharmaceutical composition of claim 106, in an amount effective to treat the disorder.

115. The method of claim 114, wherein tire disorder is a hemophilia.

116. The method of claim 115. wherein the hemophilia is hemophilia A.

117. Tire method of any of claims 114-116, wherein the antibody molecule is administered to the subject at a dose between 0. 1 mg / kg and 50 mg / kg.

118. The method of any of claims 114-117, wherein the antibody molecule is administered to the subject at a dose between 10 mg and 2500 mg.

119. Tire method of any of claims 114-118, further comprising administering a second therapeutic agent or modality.

120. The method of claim 119, wherein the second therapeutic agent or modality is administered before, during, or after the antibody molecule is administered.

121. A method of detecting FIXa, FX, or both, comprising (i) contacting a sample or a subject with an antibody molecule of any of claims 1-105 under conditions that allow interaction of the antibody molecule and FIXa, FX. or both, to occur, and (ii) detecting formation of a complex between the antibody molecule and FIXa, FX, or both, in the sample or subject.

122. Tire method of claim 121, further comprising contacting a reference sample or subject with an antibody molecule of any of claims 1-105 under conditions that allow interaction of the antibody molecule and FIXa, FX, or both, to occur, and (ii) detecting formation of a complex between the antibody molecule and FIXa, FX. or both, in the sample or subject.

123. An antibody molecule of any of claims 1-105, or a pharmaceutical composition of claim 106, for use in treating a disorder associated with a coagulation pathway in a subject.

124. The antibody molecule, or pharmaceutical composition, for use of claim 123, wherein tire disorder is a hemophilia.

125. Tire antibody molecule, or pharmaceutical composition, for use of claim 124, wherein the hemophilia is hemophilia A.

126. Use of an antibody molecule of any of claims 1-105, or a pharmaceutical composition of claim 106. in the manufacture of a medicament for treating a disorder associated with a coagulation pathway in a subject.

127. Tire use of claim 126, wherein the disorder is a hemophilia.

128. The use of claim 127, wherein the hemophilia is hemophilia A.

129. Use of an antibody molecule of any of claims 1-105, or a pharmaceutical composition of claim 106, in treating a disorder associated with a coagulation pathway in a subject.

130. The use of claim 129, wherein the disorder is a hemophilia.

131. The use of claim 130, wherein the hemophilia is hemophilia A.

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