Factor IX polypeptide formulations

1. A method of administering a rFIXFc polypeptide to a hemophilia B subject in need of prophylaxis, comprising intravenously administering to the subject a pharmaceutical composition comprising:

(a) the rFIXFc polypeptide, wherein the rFIXFc polypeptide comprises human Factor IX fused to a Fc domain of a human antibody and has long-acting Factor IX activity;

(b) between about 10 mg/ml and about 20 mg/ml of sucrose;

(c) between about 20 mg/ml and about 40 mg/ml of mannitol;

(d) between about 3 mg/ml and about 4 mg/ml of sodium chloride (NaCl);

(e) between about 3 mg/ml and about 6 mg/ml of L-histidine; and

(f) between about 0.08 mg/ml and about 0.2 mg/ml of polysorbate 20 or polysorbate 80,

wherein the administration reduces the frequency of bleeding episodes in the subject.

2. A method of administering a rFIXFc polypeptide to a hemophilia B subject in need of treatment of a minor to moderate bleeding episode, comprising intravenously administering to the subject a pharmaceutical composition comprising:

(a) the rFIXFc polypeptide, wherein the rFIXFc polypeptide comprises human Factor IX fused to a Fc domain of a human antibody and has long-acting Factor IX activity;

(b) between about 10 mg/ml and about 20 mg/ml of sucrose;

(c) between about 20 mg/ml and about 40 mg/ml of mannitol;

(d) between about 3 mg/ml and about 4 mg/ml of sodium chloride (NaCl);

(e) between about 3 mg/ml and about 6 mg/ml of L-histidine; and

(f) between about 0.08 mg/ml and about 0.2 mg/ml of polysorbate 20 or polysorbate 80,

wherein the administration controls, alleviates, or reverses the bleeding episode.

3. A method of administering a rFIXFc polypeptide to a hemophilia B subject in need of surgical prophylaxis, comprising intravenously administering to the subject a pharmaceutical composition comprising:

(a) the rFIXFc polypeptide, wherein the rFIXFc polypeptide comprises human Factor IX fused to a Fc domain of a human antibody and has long-acting Factor IX activity;

(b) between about 10 mg/ml and about 20 mg/ml of sucrose;

(c) between about 20 mg/ml and about 40 mg/ml of mannitol;

(d) between about 3 mg/ml and about 4 mg/ml of sodium chloride (NaCl);

(e) between about 3 mg/ml and about 6 mg/ml of L-histidine; and

(f) between about 0.08 mg/ml and about 0.2 mg/ml of polysorbate 20 or polysorbate 80,

wherein the administration controls bleeding in the subject during and after surgery.

4. The method of claim 3 , further comprising administering an additional dose of the pharmaceutical composition at about 80 IU/kg after about 6 to 10 hours if needed to control post-operative bleeding.

5. A method of reducing a hemophilia B subject's annualized bleeding rate, comprising administering fixed or individualized doses of a pharmaceutical composition comprising:

(a) a rFIXFc polypeptide, wherein the rFIXFc polypeptide comprises human Factor IX fused to a Fc domain of a human antibody and has long-acting Factor IX activity;

(b) between about 10 mg/ml and about 20 mg/ml of sucrose;

(c) between about 20 mg/ml and about 40 mg/ml of mannitol;

(d) between about 3 mg/ml and about 4 mg/ml of sodium chloride (NaCl);

(e) between about 3 mg/ml and about 6 mg/ml of L-histidine; and

(f) between about 0.08 mg/ml and about 0.2 mg/ml of polysorbate 20 or polysorbate 80,

prophylactically at regular or individualized dosing intervals.

6. The method of claim 5 , wherein the pharmaceutical composition is administered to the subject by a fixed dose at a fixed dosing interval.

7. The method of claim 6 , wherein the fixed dose of the pharmaceutical composition is about 50 IU/kg, and the fixed dosing interval is about one week.

8. The method of claim 6 , wherein the fixed dose of the pharmaceutical composition is about 100 IU/kg, and the fixed dosing interval is between about 10 days and about 14 days.

9. The method of claim 5 , wherein the pharmaceutical composition is administered to the subject at an individualized dose at a fixed dosing interval.

10. The method of claim 9 , wherein the fixed dosing interval is about one week.

11. The method of claim 9 , wherein the individualized dose is adjusted to achieve a plasma trough level of FIX activity of between about 1 IU/dl and about 3 IU/dl.

12. The method of claim 9 , wherein the individualized dose is between about 30 IU/kg and about 60 IU/kg, administered about once weekly.

13. The method of claim 9 , wherein the subject's annualized bleeding rate is reduced by about 70% to about 90% over the average annualized bleeding rate of hemophilia B subjects being treated by episodic or on-demand dosing.

14. The method of claim 5 , wherein the pharmaceutical composition is administered to the subject at a fixed dose at an individualized dosing interval.

15. The method of claim 14 , wherein the fixed dose is about 100 IU/kg.

16. The method of claim 14 , wherein the individualized dosing interval is adjusted to achieve a plasma trough level of FIX activity of between about 1 IU/dl and about 3 IU/dl.

17. The method of claim 14 , wherein the individualized dosing interval is between about 10 days to about 14 days.

18. The method of claim 14 , wherein the subject's annualized bleeding rate is reduced by about 80% to about 95% over the average annualized bleeding rate of hemophilia B subjects being treated by episodic or on-demand dosing.

19. The method of claim 5 , wherein the pharmaceutical composition comprises 200, 500, 1000, 2000, 3000, or 4000 IU/vial of the rFIXFc polypeptide.