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 controlling a bleeding episode in a human subject having hemophilia B, comprising intravenously administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of about 7 days between two doses, wherein the FcRn BP comprises Fc or albumin and wherein the subject exhibits a trough level of the plasma FIX activity of at least 3 IU/dL after six days each administration.
2. A method of prophylactic treatment of hemophilia B in a human subject in need thereof, comprising administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of about 7 days between two doses, wherein the FcRn BP comprises Fc or albumin and wherein the subject exhibits a trough level of the plasma FIX activity of at least 3 IU/dL after six days each administration.
3. The method of claim 1 , wherein the dosing interval is 7 days.
4. The method of claim 1 , wherein each of the multiple doses is 25 IU/kg to 40 IU/kg.
5. The method of claim 3 , wherein each of the multiple doses is about 25 IU/kg, about 30 IU/kg, about 35 IU/kg, about 40 IU/kg, about 45 IU/kg, or about 50 IU/kg.
6. The method of claim 1 , wherein the Factor IX is at least 90% identical to amino acids 1 to 415 of SEQ ID NO:2.
7. The method of claim 1 , wherein the chimeric polypeptide is a hybrid and comprises a second polypeptide in association with the chimeric polypeptide, wherein the second polypeptide comprises a second FcRn BP.
8. The method of claim 1 , wherein the FcRn BP comprises Fc.
9. The method of claim 1 , wherein the FcRn BP comprises albumin.
10. The method of claim 5 , wherein each of the multiple doses is about 25 IU/kg.
11. The method of claim 5 , wherein each of the multiple doses is about 30 IU/kg.
12. The method of claim 5 , wherein each of the multiple doses is about 35 IU/kg.
13. The method of claim 5 , wherein each of the multiple doses is about 40 IU/kg.
14. The method of claim 5 , wherein each of the multiple doses is about 45 IU/kg.
15. The method of claim 5 , wherein each of the multiple doses is about 50 IU/kg.
16. The method of claim 1 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 5 IU/dL after six days each administration.
17. The method of claim 4 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 5 IU/dL after six days each administration.
18. The method of claim 1 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 4 IU/dL after six days each administration.
19. The method of claim 4 , wherein the subject exhibits a trough level of the plasma FIX activity of at least 4 IU/dL after six days each administration.
20. The method of claim 4 , wherein the FcRn BP comprises Fc.
21. The method of claim 4 , wherein the FcRn BP comprises albumin.
22. The method of claim 1 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
23. The method of claim 9 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
24. The method of claim 21 , wherein the chimeric FIX polypeptide further comprises a linker joining FIX with the FcRn BP.
25. The method of claim 4 , wherein the dosing interval is 7 days.