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 human hemophilia B subject in need thereof multiple doses of about 25 IU/kg to about 50 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 7 days between two doses, wherein the FcRn BP is human albumin.
2. The method of claim 1 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the human albumin.
3. The method of claim 2 , wherein the linker joins the FIX to the N-terminal end of the human albumin.
4. The method of claim 3 , wherein the dosing interval is 7 days.
5. The method of claim 4 , wherein each of the multiple doses is 25 IU/kg to 40 IU/kg.
6. The method of claim 1 , wherein the subject exhibits 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.
7. The method of claim 6 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the human albumin.
8. The method of claim 7 , wherein the linker joins the FIX to the N-terminal end of the human albumin.
9. The method of claim 8 , wherein the dosing interval is 7 days and each of the multiple doses is 25 IU/kg to 40 IU/kg.
10. A method of reducing the severity of a bleeding episode, comprising intravenously administering to a human hemophilia B subject in need thereof multiple doses of about 25 IU/kg to about 50 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 7 days between two doses, wherein the FcRn BP is human albumin.
11. The method of claim 10 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the human albumin.
12. The method of claim 11 , wherein linker joins the FIX to the N-terminal end of the human albumin.
13. The method of claim 12 , wherein the dosing interval is 7 days.
14. The method of claim 13 , wherein each of the multiple doses is 25 IU/kg to 40 IU/kg.
15. The method of claim 10 , wherein the subject exhibits 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.
16. The method of claim 15 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the human albumin.
17. The method of claim 16 , wherein the linker joins the FIX to the N-terminal end of the human albumin.
18. The method of claim 17 , wherein the dosing interval is 7 days and each of the multiple doses is 25 IU/kg to 40 IU/kg.