Factor VIII chimeric and hybrid polypeptides, and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12186375-B2
Application number	US-202017112280-A
Country	US
Kind code	B2
Filing date	Dec 4, 2020
Priority date	Jul 8, 2011
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The present invention provides methods of administering Factor VIII (processed FVIII, single chain FVIII, or a combination thereof); methods of administering chimeric and hybrid polypeptides comprising Factor VIII; chimeric and hybrid polypeptides comprising Factor VIII; polynucleotides encoding such chimeric and hybrid polypeptides; cells comprising such polynucleotides; and methods of producing such chimeric and hybrid polypeptides using such cells.

First claim

What is claimed is:

1. A method for treating a subject in need of surgical prophylaxis, peri-operative management, or treatment for surgery, comprising administering to the subject a therapeutic dose of a chimeric polypeptide, the chimeric polypeptide comprising a Factor VIII portion and a second portion, wherein said Factor VIII portion comprises processed Factor VIII and single chain Factor VIII, wherein about 10% to about 40% of the Factor VIII portion is single chain Factor VIII; wherein the chimeric polypeptide is administered at a dosing interval of between about 12 hours and 24 hours; wherein the subject has hemophilia A.

2. The method of claim 1 , wherein the therapeutic dose is 10-100 IU/kg.

3. The method of claim 2 , wherein the therapeutic dose is 25-40 IU/kg.

4. The method of claim 2 , wherein the therapeutic dose is 40-60 IU/kg.

5. The method of claim 2 , wherein the therapeutic dose is 40-50 IU/kg.

6. The method of claim 1 , wherein the chimeric polypeptide is a FVIIIFc monomer dimer hybrid.

7. The method of claim 1 , wherein said Factor VIII portion has a full or partial deletion of the B domain.

8. The method of claim 1 , wherein about 10% of the Factor VIII portion is single chain Factor VIII, and wherein about 90% of the Factor VIII portion is processed Factor VIII.

9. The method of claim 1 , wherein about 15% of the Factor VIII portion is single chain Factor VIII, and wherein about 85% of the Factor VIII portion is processed Factor VIII.

10. The method of claim 1 , wherein about 20% of the Factor VIII portion is single chain Factor VIII, and wherein about 80% of the Factor VIII portion is processed Factor VIII.

11. The method of claim 1 , wherein about 25% of the Factor VIII portion is single chain Factor VIII, and wherein about 75% of the Factor VIII portion is processed Factor VIII.

12. The method of claim 1 , wherein about 30% of the Factor VIII portion is single chain Factor VIII, and wherein about 70% of the Factor VIII portion is processed Factor VIII.

13. The method of claim 1 , wherein about 35% of the Factor VIII portion is single chain Factor VIII, and wherein about 65% of the Factor VIII portion is processed Factor VIII.

14. The method of claim 1 , wherein about 40% of the Factor VIII portion is single chain Factor VIII, and wherein about 60% of the Factor VIII portion is processed Factor VIII.

15. The method of claim 1 , wherein about 40% of the Factor VIII portion is single chain Factor VIII, and wherein about 60% of the Factor VIII portion is processed Factor VIII.

16. The method of claim 1 , wherein the single chain Factor VIII comprises an amino acid sequence at least 95% identical to amino acids 20 to 1457 of SEQ ID NO: 2.

17. The method of claim 1 , wherein the single chain Factor VIII comprises an amino acid sequence identical to amino acids 20 to 1457 of SEQ ID NO: 2.

18. The method of claim 1 , wherein the second portion comprises an amino acid sequence at least 95% identical to amino acids 21 to 247 of SEQ ID NO: 4.

19. The method of claim 18 , wherein the second portion comprises an amino acid sequence identical to amino acids 21 to 246 of SEQ ID NO: 4.

Assignees

• Bioverativ Therapeutics Inc

Inventors

• Dumont Jennifer A
• Low Susan
• Bitonti Alan J
• Pierce Glenn
• Luk Alvin
• Jiang Haiyan
• Mckinney Byron
• Ottmer Matt
• Sommer Jurg
• Nugent Karen
• Li Lian
• Peters Robert T

Classifications

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title

• G01N33/86

  involving blood coagulating time {or factors, or their receptors} · CPC title

• C07K14/755

  Factors VIII {, e.g. factor VIII C (AHF), factor VIII Ag (VWF)} · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K47/68

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title