Factor IX polypeptides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10898554-B1
Application number	US-202017032354-A
Country	US
Kind code	B1
Filing date	Sep 25, 2020
Priority date	Jul 9, 2010
Publication date	Jan 26, 2021
Grant date	Jan 26, 2021

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:

1. A method of reducing the frequency of spontaneous bleeding comprising intravenously administering to a hemophilia B human subject in need thereof multiple doses of about 50 IU/kg to about 100 IU/kg of a chimeric factor IX (“FIX”) polypeptide comprising human FIX having an amino acid sequence identical to amino acids 1 to 415 of SEQ ID NO:2 and an FcRn binding partner (“FcRn BP”) at a dosing interval of about 10 days to about 14 days between two doses, wherein the FcRn BP is human Fc or human albumin.

2. The method of claim 1 , wherein the dosing interval is 14 days and each of the multiple doses is 50 IU/kg.

3. The method of claim 1 , wherein the dosing interval is 14 days and each of the multiple doses is 60 IU/kg.

4. The method of claim 1 , wherein the dosing interval is 14 days and each of the multiple doses is 70 IU/kg.

5. The method of claim 1 , wherein the dosing interval is 14 days and each of the multiple doses is 80 IU/kg.

6. The method of claim 1 , wherein the dosing interval is 14 days and each of the multiple doses is 90 IU/kg.

7. The method of claim 1 , wherein the dosing interval is 14 days and each of the multiple doses is 100 IU/kg.

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

9. The method of claim 8 , wherein the human Fc comprises amino acids 1 to 227 of SEQ ID NO: 4.

10. The method of claim 9 , wherein the subject exhibits the plasma FIX activity above 1 IU/dL during the dosing interval as measured by a one stage clotting assay that determines activated partial thromboplastin time.

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

12. A method of reducing the severity of a bleeding episode comprising intravenously administering to a hemophilia B human subject in need thereof multiple doses of about 50 IU/kg to about 100 IU/kg of a chimeric factor IX (“FIX”) polypeptide comprising human FIX having an amino acid sequence identical to amino acids 1 to 415 of SEQ ID NO:2 and an FcRn binding partner (“FcRn BP”) at a dosing interval of about 10 days to about 14 days between two doses, wherein the FcRn BP is human Fc or human albumin.

13. The method of claim 12 , wherein the dosing interval is 14 days and each of the multiple doses is 50 IU/kg.

14. The method of claim 12 , wherein the dosing interval is 14 days and each of the multiple doses is 60 IU/kg.

15. The method of claim 12 , wherein the dosing interval is 14 days and each of the multiple doses is 70 IU/kg.

16. The method of claim 12 , wherein the dosing interval is 14 days and each of the multiple doses is 80 IU/kg.

17. The method of claim 12 , wherein the dosing interval is 14 days and each of the multiple doses is 90 IU/kg.

18. The method of claim 12 , wherein the dosing interval is 14 days and each of the multiple doses is 100 IU/kg.

19. The method of claim 12 , wherein the FcRn BP is human Fc.

20. The method of claim 19 , wherein the human Fc comprises amino acids 1 to 227 of SEQ ID NO: 4.

21. The method of claim 20 , wherein the subject exhibits the plasma FIX activity above 1 IU/dL during the dosing interval as measured by a one stage clotting assay that determines activated partial thromboplastin time.

22. The method of claim 12 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRN BP.

Assignees

• Bioverativ Therapeutics Inc

Inventors

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

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · 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

• C07K16/18

  against material from animals or humans · CPC title

• A61K47/68

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

• A61K47/643

  Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL] · CPC title