Factor IX polypeptides and methods of use thereof
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.
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.