Factor IX polypeptides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9675676-B2
Application number	US-201615043445-A
Country	US
Kind code	B2
Filing date	Feb 12, 2016
Priority date	Jul 9, 2010
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The present invention provides methods of administering Factor IX; methods of administering chimeric and hybrid polypeptides comprising Factor IX; 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 treating hemophilia B in a human subject in need thereof, comprising intravenously administering to the subject multiple doses of about 100 IU/kg to about 150 IU/kg of a chimeric Factor IX (“FIX”) polypeptide at a dosing interval of about 19 days to about 40 days between two doses, wherein the chimeric FIX polypeptide comprises FIX and an FcRn binding partner (FcRn BP), which comprises Fe or albumin, and wherein the administration maintains the plasma FIX activity of the subject above 1 IU/dL between the dosing interval.

2. The method of claim 1 , wherein each of the multiple doses is 100 IU/kg.

3. The method of claim 1 , wherein the dosing interval is 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, or 40 days.

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

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

6. The method of claim 1 , wherein the FIX is at least 95% identical to amino acids 1 to 415 of SEQ ID NO:2.

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

8. The method of claim 2 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRn BP.

9. The method of claim 3 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRn BP.

10. The method of claim 4 , wherein chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRn BP.

11. The method of claim 1 , wherein the plasma level of the FIX polypeptide reaches a trough of at least 5 IU/dl after six days after each administration.

12. The method of claim 2 , wherein the plasma level of the FIX polypeptide reaches a trough of at least 5 IU/dl after six days after each administration.

13. The method of claim 1 , wherein the plasma level of the FIX polypeptide reaches a trough of at least 3 IU/dl after six days after each administration.

14. The method of claim 2 , wherein the plasma level of the FIX polypeptide reaches a trough of at least 3 IU/dl after six days after each administration.

15. The method of claim 1 , wherein each of the multiple doses is about 110 IU/kg.

16. The method of claim 1 , wherein each of the multiple doses is about 120 IU/kg.

17. The method of claim 1 , wherein each of the multiple doses is about 130 IU/kg.

18. The method of claim 1 , wherein each of the multiple doses is about 140 IU/kg.

19. The method of claim 1 , wherein each of the multiple doses is about 150 IU/kg.

20. The method of claim 1 , wherein the dosing interval is about 19 days.

21. The method of claim 1 , wherein the dosing interval is about 20 days.

22. The method of claim 1 , wherein the dosing interval is about 21 days.

23. The method of claim 1 , wherein the dosing interval is about 22 days.

24. The method of claim 1 , wherein the dosing interval is about 23 days.

25. The method of claim 1 , wherein the dosing interval is about 24 days.

26. The method of claim 1 , wherein the dosing interval is about 25 days.

27. The method of claim 1 , wherein the dosing interval is about 26 days.

28. The method of claim 1 , wherein the dosing interval is about 27 days.

29. The method of claim 1 , wherein the dosing interval is about 28 days.

30. The method of claim 1 , wherein the dosing interval is about 29 days.

Assignees

• Bioverativ Therapeutics Inc

Inventors

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

Classifications

• C07K2317/90

  characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin · CPC title

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2319/31

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