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; 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 treating hemophilia B in a human subject in need thereof comprising intravenously administering to the subject multiple doses of about 50 IU/kg to about 100 IU/kg of a chimeric factor IX (“FIX”) polypeptide comprising FIX 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 comprises Fc or albumin, wherein the administration maintains the plasma FIX activity of the subject above 1 IU/dL between the dosing interval, and wherein the administration treats the human subject by reducing the frequency of spontaneous bleeding.
2. The method of claim 1 , wherein each of the multiple doses is 50 IU/kg to 60 IU/kg, 70 IU/kg to 80 IU/kg, or 90 IU/kg to 100 IU/kg.
3. The method of claim 1 , wherein each of the multiple doses is 50 IU/kg to 60 IU/kg.
4. The method of claim 1 , wherein each of the multiple doses is 70 IU/kg to 80 IU/kg.
5. The method of claim 1 , wherein each of the multiple doses is 90 IU/kg to 100 IU/kg.
6. The method of claim 1 , wherein the dosing interval is 10 days to 13 days.
7. The method of claim 1 , wherein the dosing interval is 10 days.
8. The method of claim 1 , wherein the dosing interval is 11 days.
9. The method of claim 1 , wherein the dosing interval is 12 days.
10. The method of claim 1 , wherein the dosing interval is 13 days.
11. The method of claim 1 , wherein the dosing interval is 14 days.
12. The method of claim 1 , wherein each of the multiple doses is 50 IU/kg.
13. The method of claim 1 , wherein each of the multiple doses is 60 IU/kg.
14. The method of claim 1 , wherein each of the multiple doses is 75 IU/kg.
15. The method of claim 1 , wherein each of the multiple doses is 90 IU/kg.
16. The method of claim 1 , wherein each of the multiple doses is 100 IU/kg.
17. The method of claim 1 , wherein the FcRn BP comprises Fc.
18. The method of claim 1 , wherein the FcRn BP comprises albumin.
19. The method of claim 2 , wherein the FcRn BP comprises albumin.
20. The method of claim 2 , wherein the FcRn BP comprises Fe.
21. The method of claim 4 , wherein the FcRn BP comprises albumin.
22. The method of claim 4 , wherein the FcRn BP comprises Fc.
23. The method of claim 5 , wherein the FcRn BP comprises albumin.
24. The method of claim 1 , wherein the FIX is at least 90% identical to amino acids 1 to 415 of SEQ ID NO:2.
25. The method of claim 18 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRn BP.
26. The method of claim 19 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRn BP.
27. The method of claim 21 , wherein the chimeric FIX polypeptide further comprises a linker joining the FIX and the FcRn BP.
28. The method of claim 5 , wherein the FcRn BP is Fc.