Stable aqueous anti-TFPI antibody formulation

1 . A stable pharmaceutical formulation consisting of: about 100 mg/mL to about 150 mg/mL of an antibody that specifically binds to an epitope in Kunitz Domain 2 (K2) of Tissue Factor Pathway Inhibitor (TFPI), about 20 mM histidine buffer, about 85 mg/mL sucrose, about 0.2 mg/mL polysorbate 80 and about 0.05 mg/mL disodium edetate dihydrate (EDTA), wherein the formulation has a pH at about 5.8, wherein the histidine buffer comprises L-histidine, L-histidine monohydrochloride or a mixture thereof, and wherein the antibody comprises:

(i) a heavy chain variable region (VH) comprising: (a) a VH complementarity determining region one (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 13; (b) a VH complementarity determining region two (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 14; and (c) a VH complementarity determining region three (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 15, and

(ii) a light chain variable region (VL) comprising: (a) a VL complementarity determining region one (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 8; (b) a VL complementarity determining region two (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 9; and (c) a VL complementarity determining region three (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 10.

2 . The stable pharmaceutical formulation of claim 1 , wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 18, and a VL comprising the amino acid sequence of SEQ ID NO: 11.

3 . The stable pharmaceutical formulation of claim 1 , wherein the antibody comprises a VH sequence encoded by the insert present in the plasmid deposited under ATCC Accession No. PTA-122329, and a VL sequence encoded by the insert present in the plasmid deposited under ATCC Accession No. PTA-122328.

4 . The stable pharmaceutical formulation of claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 19, and a light chain comprising the amino acid sequence of SEQ ID NO: 12.

5 . The stable pharmaceutical formulation of claim 1 , wherein the concentration of the antibody is about 100 mg/mL, about 115 mg/mL or about 150 mg/mL.

6 . A stable pharmaceutical formulation consisting of: 150 mg/mL of an antibody that specifically binds to an epitope in Kunitz Domain 2 (K2) of Tissue Factor Pathway Inhibitor (TFPI), 20 mM histidine buffer, 85 mg/mL sucrose, 0.2 mg/mL polysorbate 80, and 0.05 mg/mL disodium edetate dihydrate, wherein the histidine buffer comprises L-histidine, L-histidine monohydrochloride or a mixture thereof, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 18, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11, and wherein the formulation has a pH of 5.8.

7 . A stable pharmaceutical formulation consisting of: 150 mg/mL of an antibody that specifically binds to an epitope in Kunitz Domain 2 (K2) of Tissue Factor Pathway Inhibitor (TFPI), 20 mM histidine buffer, 85 mg/mL sucrose, 0.2 mg/mL polysorbate 80, and 0.05 mg/mL disodium edetate dihydrate, wherein the histidine buffer comprises L-histidine, L-histidine monohydrochloride or a mixture thereof, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 19, and a light chain comprising the amino acid sequence of SEQ ID NO: 12, and wherein the formulation has a pH of 5.8.

8 . A stable pharmaceutical formulation consisting of: 150 mg/mL of an antibody that specifically binds to an epitope in Kunitz Domain 2 (K2) of Tissue Factor Pathway Inhibitor (TFPI), 20 mM histidine buffer, 85 mg/mL sucrose, 0.2 mg/mL polysorbate 80, and 0.05 mg/mL disodium edetate dihydrate, wherein the histidine buffer comprises L-histidine, L-histidine monohydrochloride or a mixture thereof, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 17, and a light chain comprising the amino acid sequence of SEQ ID NO: 12, and wherein the formulation has a pH of 5.8.

9 . The stable pharmaceutical formulation of claim 1 , wherein the formulation has a shelf life of at least about 24 months at 5±3° C.

10 . The stable pharmaceutical formulation of claim 1 , wherein the formulation has less than about 7% high molecular mass species (HMMS) at 40° C./75% relative humidity (RH) for up to 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, optionally as measured by size exclusion high performance liquid chromatography (SE-HPLC).

11 . The stable pharmaceutical formulation of claim 1 , wherein the formulation has less than about 3% HMMS at 40° C. for up to 1 month, 2 months, or 3 months, optionally as measured by SE-HPLC.

12 . The stable pharmaceutical formulation of claim 1 , wherein the formulation has less than about 2% HMMS at 40° C. for up to 1 month, optionally as measured by SE-HPLC.

13 . A method of shortening bleeding time, comprising administering to a subject in need thereof a therapeutically effective amount of the stable pharmaceutical formulation of claim 1 .

14 . A method of treating a deficiency in blood coagulation or a bleeding disorder, comprising administering to a subject in need thereof a therapeutically effective amount of the stable pharmaceutical formulation of claim 1 .

15 . A method of treating hemophilia A, B or C, comprising administering to a subject in need thereof a therapeutically effective amount of the stable pharmaceutical formulation of claim 1 .

16 . A method of treating von Willebrand Disease (vWD), comprising administering to a subject in need thereof a therapeutically effective amount of the stable pharmaceutical formulation of claim 1 .

17 . A method for reducing the activity of TFPI, comprising administering to a subject in need thereof a therapeutically effective amount of the stable pharmaceutical formulation of claim 1 .

18 . The method of claim 13 , wherein the stable pharmaceutical formulation is administered to the subject subcutaneously or intravenously.