Monoclonal antibodies against antithrombin beta

Patent metadata

Field	Value
Publication number	US-10144784-B2
Application number	US-201815908705-A
Country	US
Kind code	B2
Filing date	Feb 28, 2018
Priority date	Mar 14, 2013
Publication date	Dec 4, 2018
Grant date	Dec 4, 2018

Abstract

This patent document relates to antibodies, antigen-binding antibody fragments (Fabs), and other protein scaffolds, directed against human antithrombin β complexed with heparin and/or heparin-like structure (ATβH). These ATβH binding proteins can block the anti-coagulant activity of ATβ to induce coagulation. Therapeutic uses of these antibodies and binders are described herein as are methods of panning and screening specific antibodies.

First claim

We claim:

1. A method for treating coagulopathy comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody capable of binding the antithrombin (β) heparin complex (ATβH), wherein:
the heavy chain of said antibody comprises: a CDR1 sequence of amino acids 31 to 35 (AYRMG) of SEQ ID NO: 2, a CDR2 sequence of amino acids 50 to 66 (RIYSSGGRTRYADSVKG) of SEQ ID NO: 2, and a CDR3 sequence of amino acids 97 to 114 (AREKASDLSGSFSEALDY) of SEQ ID NO: 2; and
the light chain of said antibody comprises: a CDR1 sequence of amino acids 24 to 34 (QGDSLRSYYAS) of SEQ ID NO: 1, a CDR2 sequence of amino acids 50 to 56 (GKNNRPS) of SEQ ID NO: 1; and a CDR3 sequence of amino acids 89 to 99 (NSRDSSGNHLV) of SEQ ID NO: 1.

2. The method of claim 1 , wherein the coagulopathy is hemophilia A, hemophilia B, or hemophilia C.

3. The method of claim 1 , wherein the coagulopathy is trauma-induced coagulopathy or severe bleeding.

4. The method of claim 1 , further comprising administering a clotting factor.

5. The method of claim 4 , wherein the clotting factor is selected from the group consisting of Factor VIIa, Factor VIII, and Factor IX.

6. The method of claim 1 , wherein the monoclonal antibody is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, an IgG4 antibody, an IgM antibody, an IgA1 antibody, an IgA2 antibody, a secretory IgA antibody, an IgD antibody, an IgE antibody, or an antibody fragment.

7. A method for treating coagulopathy comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody capable of binding the antithrombin (β) heparin complex (ATβH), wherein:
the heavy chain of said antibody comprises: a CDR1 sequence of amino acids 31 to 35 (KYKMD) of SEQ ID NO: 4, a CDR2 sequence of amino acids 50 to 66 (RIGPSGGKTM YADSVKG) of SEQ ID NO: 4, and a CDR3 sequence of amino acids 97 to 114 (AREKASDLSG TYSEALDY) of SEQ ID NO: 4; and
the light chain of said antibody comprises: a CDR1 sequence of amino acids 26 to 37 (RASQSVSSSYLA) of SEQ ID NO: 3, a CDR2 sequence of amino acids 53 to 59 (GASSRAT) of SEQ ID NO: 3, and a CDR3 sequence of amino acids 92 to 99 (QQYGSSRT) of SEQ ID NO: 3.

8. The method of claim 7 , wherein the coagulopathy is hemophilia A, hemophilia B, or hemophilia C.

9. The method of claim 7 , wherein the coagulopathy is trauma-induced coagulopathy or severe bleeding.

10. The method of claim 7 , further comprising administering a clotting factor.

11. The method of claim 10 , wherein the clotting factor is selected from the group consisting of Factor VIIa, Factor VIII, and Factor IX.

12. The method of claim 7 , wherein the monoclonal antibody is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, an IgG4 antibody, an IgM antibody, an IgA1 antibody, an IgA2 antibody, a secretory IgA antibody, an IgD antibody, an IgE antibody, or an antibody fragment.

13. A method for treating coagulopathy comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody capable of binding the antithrombin 03) heparin complex (ATβH), wherein:
the heavy chain of said antibody comprises: a CDR1 sequence of amino acids 31 to 35 (KYRMD) of SEQ ID NO: 6, a CDR2 sequence of amino acids 50 to 66 (RIGPSGGKTT YADSVKG) of SEQ ID NO: 6, and a CDR3 sequence of amino acids 97 to 114 (AREKTSDLSG SYSEALDY) of SEQ ID NO: 6; and
the light chain of said antibody comprises: a CDR1 sequence of amino acids 26 to 36 (RASQNINRNLA) of SEQ ID NO: 5, a CDR2 sequence of amino acids 52 to 58 (TASTRAP) of SEQ ID NO: 5, and a CDR3 sequence of amino acids 91 to 99 (QQYASPPRT) of SEQ ID NO: 6.

14. The method of claim 13 , wherein the coagulopathy is hemophilia A, hemophilia B, or hemophilia C.

15. The method of claim 13 , wherein the coagulopathy is trauma-induced coagulopathy or severe bleeding.

16. The method of claim 13 , further comprising administering a clotting factor.

17. The method of claim 16 , wherein the clotting factor is selected from the group consisting of Factor VIIa, Factor VIII, and Factor IX.

18. The method of claim 16 , wherein the monoclonal antibody is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, an IgG4 antibody, an IgM antibody, an IgA1 antibody, an IgA2 antibody, a secretory IgA antibody, an IgD antibody, an IgE antibody, or an antibody fragment.

Assignees

• Bayer Healthcare Llc

Inventors

• Jin Ye
• Murphy John E
• Hermiston Terry
• Myles Timothy
• Dittmer Frank
• Strerath Michael
• Gritzan Uwe

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K16/38

  against protease inhibitors of peptide structure · CPC title