Methods of using FIX polypeptides
The present invention provides methods of administering long-acting Factor IX; methods of administering long-acting, chimeric and hybrid polypeptides comprising Factor IX; and methods of producing such chimeric and hybrid polypeptides using cells.
1. A method of reducing or decreasing an annualized bleeding rate in a human subject with hemophilia B, comprising administering to the subject multiple doses of a pharmaceutical composition comprising:
(a) a chimeric Factor IX(FIX) polypeptide comprising human FIX and a first Fc region;
(b) sucrose;
(c) mannitol; and
(d) polysorbate 20 or polysorbate 80 ,
wherein each of the multiple doses comprises 10 IU/kg to 200 IU/kg of the chimeric FIX polypeptide wherein each of the multiple doses is administered at a dosing interval of about 7 days to about 14 days, wherein the annualized bleeding rate of the bleeding episodes is reduced to less than 5; and wherein the bleeding episodes are spontaneous bleeding episodes.
2. The method of claim 1 , wherein each of the multiple doses of the chimeric FIX polypeptide is 50 IU/kg to 100 IU/kg.
3. The method of claim 1 , wherein each of the multiple doses is about 50 IU/kg or about 100 IU/kg and the dosing interval is about 10 days to about 14 days.
4. The method of claim 1 , wherein each of the multiple doses is for individualized interval prophylaxis of one or more spontaneous bleeding episodes.
5. The method of claim 4 , wherein the annualized bleeding rate of the one or more spontaneous bleeding episodes is reduced to less than 4.
6. The method of claim 1 , wherein the dosing interval is every 7 days to 14 days.
7. The method of claim 1 , wherein each of the multiple doses is about 25 IU/kg to about 50 IU/kg and the dosing interval is about 7 days.
8. The method of claim 1 , wherein the chimeric FIX polypeptide further comprises a second Fc region.
9. The method of claim 1 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 1.
10. The method of claim 1 , wherein each of the multiple doses is 25 IU/kg to 50 IU/kg.
11. The method of claim 1 , wherein the chimeric FIX polypeptide comprises a first subunit comprising an amino acid sequence at least 99% identical to SEQ ID NO: 2, and a second subunit comprising an amino acid sequence at least 99% identical to SEQ ID NO: 4.
12. The method of claim 1 , wherein the chimeric FIX polypeptide comprises a first subunit comprising amino acids 1 to 641 of SEQ ID NO: 2, and a second subunit comprising amino acids 1 to 226 of SEQ ID NO: 4.
13. The method of claim 12 , wherein each of the multiple doses is about 50 IU/kg and the dosing interval is about 7 days.
14. The method of claim 12 , wherein each of the multiple doses is about 100 IU/kg and the dosing interval is about 10 days.
15. The method of claim 3 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 4.
16. The method of claim 3 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 3.
17. The method of claim 3 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 2.
18. The method of claim 7 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 4.
19. The method of claim 7 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 3.
20. The method of claim 7 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 2.