Targeted coagulation factors and method of using the same

Patent metadata

Field	Value
Publication number	US-10035840-B2
Application number	US-201615222001-A
Country	US
Kind code	B2
Filing date	Jul 28, 2016
Priority date	May 16, 2008
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

Targeted coagulation factors comprising a coagulation factor linked with at least one domain that specifically binds to a membrane protein on a blood cell is provided. The disclosed targeted coagulation factors increase the efficiency of coagulation factors and prolong their duration of action and thus, are an improvement for the treatment of hematological diseases such as hemophilia A.

First claim

The invention claimed is:

1. A Factor VIII molecule comprising an amino acid sequence that is at least 95% identical to the mature portion of an amino acid sequence selected from the group consisting of SEQ. ID NO: 1, and SEQ ID NO: 2, which molecule is covalently attached to a platelet specific molecule, wherein said platelet specific molecule is a single chain GPIIb/IIIa antibody fragment.

2. A Factor VIII molecule as recited in claim 1 , wherein the platelet specific molecule is fused to the Factor VIII molecule.

3. A Factor VIII molecule as recited in claim 1 , wherein Factor VIII molecule further comprises a B-domain or portion of the B-domain and the platelet specific molecule is fused to the B-domain or portion of the B-domain.

4. A Factor VIII molecule as recited in claim 1 , wherein the Factor VIII molecule further comprises a C-terminus and the platelet specific molecule is fused to the C-terminus of the Factor VIII molecule.

5. A Factor VIII molecule as recited in claim 1 , wherein said molecule has reduced von Willebrand factor binding capacity.

6. A Factor VIII molecule as recited in claim 1 , wherein said molecule has increased binding affinity to a platelet in the absence of von Willebrand factor.

7. A Factor VIII molecule as recited in claim 1 , wherein said single chain GPIIb/IIIa antibody fragment is covalently attached to Factor VIII via a cysteine residue.

8. A Factor VIII molecule as recited in claim 7 , wherein said cysteine residue is located in a B-domain of a B domain truncated Factor VIII molecule.

9. A Factor VIII molecule according to claim 1 , wherein the Factor VIII further comprises an a3 domain and the a3 domain of the Factor VIII molecule is replaced with the single chain GPIIb/IIIa antibody fragment.

10. A nucleic acid encoding a Factor VIII molecule according to claim 1 .

11. A host cell comprising a nucleic acid according to claim 10 .

12. A method of producing a Factor VIII molecule said method comprising expressing the nucleic acid according to claim 10 in a host cell.

13. A method of producing a Factor VIII molecule according to claim 1 , wherein said method comprises conjugation of the FVIII molecule with the single chain GPIIb/IIIa antibody fragment.

14. A pharmaceutical composition comprising a Factor VIII molecule according to claim 1 .

15. A Factor VIII molecule according to claim 1 for use in a method for the treatment of hemophilia A or von Willebrand Disease.

Assignees

• Bayer Healthcare Llc

Inventors

• Feldman Richard
• Kim Ji-Yun
• Jiang Haiyan
• Mclean Kirk
• Pan Junliang
• Pierce Glenn
• Wu James
• Zhao Xiao-Yan

Classifications

• A61K38/4846

  Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38) · CPC title

• A61K38/37 Primary

  Factors VIII · CPC title

• A61P7/04

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

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• C07K16/2848

  against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61 · CPC title