Tissue factor pathway inhibitor antibodies and uses thereof
AssigneePfizer Inc.
InventorsDebra Pittman, James R. Apgar, Zong Sean Juo, Macy Jin, Mark Stahl, Gregory J. Carven, Matthew Holsti, Susan Benard, Sunita R. Hett, Reema Jasuja
Life of this patent
Estimating the term…
Abstract
The invention relates to antibodies, and antigen-binding fragments thereof, that specifically bind TFPI and inhibit an activity thereof. Such antibodies and fragments are useful for treating bleeding disorders and shortening clotting time.
Claims15
1-18. (canceled)
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.
(canceled)
A method of shortening bleeding time in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of the 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.
(canceled)
(canceled)
Dependencies are inferred from the claim text.