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 trough level of the plasma FIX activity after each administration is at least 3 IU/dL after six days, and wherein the administration treats the human subject by reducing the frequency of spontaneous bleeding.
2. The method claim 1 , wherein each of the multiple doses is from about 50 IU/kg to about 60 IU/kg.
3. The method claim 1 , wherein each of the multiple doses is from about 70 IU/kg to about 80 IU/kg.
4. The method of claim 2 , wherein each of the multiple doses is from about 90 IU/kg to about 100 IU/kg.
5. The method of claim 1 , wherein each of the multiple doses is 60 IU/kg to 70 IU/kg.
6. The method of claim 1 , wherein each of the multiple doses is 50 IU/kg, 55 IU/kg, 60 IU/kg, 65 IU/kg, 70 IU/kg, 75 IU/kg, 80 IU/kg, 85 IU/kg, 90 IU/kg, 95 IU/kg, or 100 IU/kg.
7. The method of claim 1 , wherein the dosing interval is 14 days.
8. The method of claim 2 , wherein the dosing interval is 14 days.
9. The method of claim 3 , wherein the dosing interval is 14 days.
10. The method of claim 5 , wherein the dosing interval is 14 days.
11. The method of claim 1 , wherein the FcRn BP comprises Fc.
12. The method of claim 4 , wherein the FcRn BP comprises Fc.
13. The method of claim 9 , wherein the FcRn BP comprises albumin.
14. The method of claim 10 , wherein the FcRn BP comprises albumin.
15. The method of claim 14 , wherein each of the multiple doses is 75 IU/kg.
16. The method of claim 15 , wherein the dosing interval is 14 days.
17. The method of claim 13 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
18. The method of claim 14 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
19. The method of claim 15 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
20. The method of claim 1 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
21. The method of claim 7 , wherein the FIX is at least 95% identical to amino acids 1 to 415 of SEQ ID NO:2.
22. The method of claim 1 , wherein the FIX is at least 95% identical to amino acids 1 to 415 of SEQ ID NO:2.
23. The method of claim 1 , wherein the chimeric FIX polypeptide exhibits an incremental recovery (K-Value) (activity; observed) of about 1.15 IU/dL per IU/kg.
24. The method of claim 1 , wherein the trough level of the plasma FIX activity after each administration is at least about 5 IU/dL after six days.
25. The method of claim 7 , wherein the trough level of the plasma FIX activity after each administration is at least about 5 IU/dL after six days.
26. The method of claim 8 , wherein the trough level of the plasma FIX activity after each administration is at least about 5 IU/dL after six days.
27. The method of claim 9 , wherein the trough level of the plasma FIX activity after each administration is at least about 5 IU/dL after six days.
28. The method of claim 10 , wherein the trough level of the plasma FIX activity after each administration is at least about 5 IU/dL after six days.
29. The method of claim 16 , wherein the trough level of the plasma FIX activity after each administration is at least about 5 IU/dL after six days.