Factor IX polypeptides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9867873-B2
Application number	US-201514982934-A
Country	US
Kind code	B2
Filing date	Dec 29, 2015
Priority date	Jul 9, 2010
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

The present invention provides methods of administering Factor IX; methods of administering chimeric and hybrid polypeptides comprising Factor IX; 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 of controlling a bleeding episode in a human subject having hemophilia B, comprising intravenously administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of about 7 days between two doses, wherein the FcRn BP comprises Fc or albumin and wherein the subject exhibits a trough level of the plasma FIX activity of at least 3 IU/dL after six days each administration.

2. A method of prophylactic treatment of hemophilia B in a human subject in need thereof, comprising administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of about 7 days between two doses, wherein the FcRn BP comprises Fc or albumin and wherein the subject exhibits a trough level of the plasma FIX activity of at least 3 IU/dL after six days each administration.

3. The method of claim 1 , wherein the dosing interval is 7 days.

4. The method of claim 1 , wherein each of the multiple doses is 25 IU/kg to 40 IU/kg.

5. The method of claim 3 , wherein each of the multiple doses is about 25 IU/kg, about 30 IU/kg, about 35 IU/kg, about 40 IU/kg, about 45 IU/kg, or about 50 IU/kg.

6. The method of claim 1 , wherein the Factor IX is at least 90% identical to amino acids 1 to 415 of SEQ ID NO:2.

7. The method of claim 1 , wherein the chimeric polypeptide is a hybrid and comprises a second polypeptide in association with the chimeric polypeptide, wherein the second polypeptide comprises a second FcRn BP.

8. The method of claim 1 , wherein the FcRn BP comprises Fc.

9. The method of claim 1 , wherein the FcRn BP comprises albumin.

10. The method of claim 5 , wherein each of the multiple doses is about 25 IU/kg.

11. The method of claim 5 , wherein each of the multiple doses is about 30 IU/kg.

12. The method of claim 5 , wherein each of the multiple doses is about 35 IU/kg.

13. The method of claim 5 , wherein each of the multiple doses is about 40 IU/kg.

14. The method of claim 5 , wherein each of the multiple doses is about 45 IU/kg.

15. The method of claim 5 , wherein each of the multiple doses is about 50 IU/kg.

16. The method of claim 1 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 5 IU/dL after six days each administration.

17. The method of claim 4 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 5 IU/dL after six days each administration.

18. The method of claim 1 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 4 IU/dL after six days each administration.

19. The method of claim 4 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 4 IU/dL after six days each administration.

20. The method of claim 4 , wherein the FcRn BP comprises Fc.

21. The method of claim 4 , wherein the FcRn BP comprises albumin.

22. The method of claim 1 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.

23. The method of claim 9 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.

24. The method of claim 21 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.

25. The method of claim 4 , wherein the dosing interval is 7 days.

Assignees

• Bioverativ Therapeutics Inc

Inventors

• Pierce Glenn
• Truex Samantha
• Peters Robert T
• Jiang Haiyan

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P7/04

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

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K38/4846 Primary

  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

• A61K38/38

  Albumins · CPC title