CPC C07K 16/38 (2013.01) [A61K 38/4846 (2013.01); A61K 39/0011 (2013.01); A61K 39/3955 (2013.01); C12Y 304/21021 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5158 (2013.01); A61K 2039/55522 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] | 11 Claims |
1. A method of reducing the activity of Tissue Factor Pathway Inhibitor (TFPI) in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to an epitope in Kunitz Domain 2 (K2) of Tissue Pathway Factor Inhibitor (TFPI), wherein the antibody comprises:
(a) a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR-H1) comprising the amino acid sequence of SEQ ID NO:48, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:49, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:50, and a light chain variable region (VL) comprising a VL complementarity determining region one (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 43, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:44, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:45;
(b) a VH comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 51, and SEQ ID NO: 79 and a VL comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 46, SEQ ID NO: 71, SEQ ID NO: 73, SEQ ID NO: 75 and SEQ ID NO: 77;
(c) a VH comprising the amino acid sequence of SEQ ID NO:51 and a VL comprising the amino acid sequence of SEQ ID NO:46;
(d) a heavy chain consisting of the amino acid sequence of SEQ ID NO:52 and a light chain consisting of the amino acid sequence of SEQ ID NO:47;
(e) a VH comprising the amino acid sequence of SEQ ID NO:67 and a VL comprising the amino acid sequence of SEQ ID NO: 77; or
(f) a heavy chain consisting of the amino acid sequence of SEQ ID NO: 68 and a light chain consisting of the amino acid sequence of SEQ ID NO: 78.
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