US 12,168,698 B2
Tissue factor pathway inhibitor antibodies and uses thereof
Debra Pittman, Windham, NH (US); James R. Apgar, Newton, MA (US); Zong Sean Juo, Cambridge, MA (US); Macy Jin, Lexington, MA (US); Mark Stahl, Lexington, MA (US); Gregory J. Carven, Maynard, MA (US); Matthew Holsti, Boston, MA (US); Susan Benard, Melrose, MA (US); Sunita R. Hett, Arlington, MA (US); and Reema Jasuja, Cambridge, MA (US)
Assigned to Pfizer Inc., New York, NY (US)
Filed by Pfizer Inc., New York, NY (US)
Filed on Mar. 13, 2023, as Appl. No. 18/182,619.
Application 18/182,619 is a division of application No. 17/102,883, filed on Nov. 24, 2020, granted, now 11,634,504.
Application 17/102,883 is a division of application No. 16/716,790, filed on Dec. 17, 2019, granted, now 10,875,929, issued on Dec. 29, 2020.
Application 16/716,790 is a division of application No. 15/239,556, filed on Aug. 17, 2016, granted, now 10,550,200, issued on Feb. 4, 2020.
Claims priority of provisional application 62/360,205, filed on Jul. 8, 2016.
Claims priority of provisional application 62/207,229, filed on Aug. 19, 2015.
Prior Publication US 2023/0416405 A1, Dec. 28, 2023
Int. Cl. C07K 16/38 (2006.01); A61K 38/48 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01)
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.