Targeted coagulation factors and method of using the same

Patent metadata

Field	Value
Publication number	US-9422362-B2
Application number	US-201414252823-A
Country	US
Kind code	B2
Filing date	Apr 15, 2014
Priority date	May 16, 2008
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

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 the platelet specific molecule is fused to the B-domain or a portion of the B-domain of Factor VIII.

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 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

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• 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

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title