Methods of using fix polypeptides

Abstract

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 - 130 . (canceled) 
     
     
         131 . 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 an FcRn binding partner;   (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. 
     
     
         132 . The method of  claim 131 , wherein the pharmaceutical composition comprises polysorbate 80. 
     
     
         133 . The method of  claim 131 , wherein each of the multiple doses of the chimeric FIX polypeptide is 50 IU/kg to 100 IU/kg. 
     
     
         134 . The method of  claim 131 , wherein each of the multiple doses of the chimeric FIX polypeptide is 100 IU/kg. 
     
     
         135 . The method of  claim 131 , 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. 
     
     
         136 . The method of  claim 135 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 4. 
     
     
         137 . The method of  claim 135 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 3. 
     
     
         138 . The method of  claim 135 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 2. 
     
     
         139 . The method of  claim 131 , wherein each of the multiple doses is for individualized interval prophylaxis of one or more spontaneous bleeding episodes. 
     
     
         140 . The method of  claim 139 , wherein the annualized bleeding rate of the one or more spontaneous bleeding episodes is reduced to less than 4. 
     
     
         141 . The method of  claim 131 , wherein the dosing interval is every 7 days to 14 days. 
     
     
         142 . The method of  claim 131 , wherein each of the multiple doses is about 25 IU/kg to about 50 IU/kg and the dosing interval is about 7 days. 
     
     
         143 . The method of  claim 142 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 4. 
     
     
         144 . The method of  claim 142 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 3. 
     
     
         145 . The method of  claim 142 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 2. 
     
     
         146 . The method of  claim 131 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 1. 
     
     
         147 . The method of  claim 131 , wherein each of the multiple doses is 25 IU/kg to 50 IU/kg. 
     
     
         148 . The method of  claim 131 , wherein the human FIX comprises amino acids 1 to 415 of SEQ ID NO: 2. 
     
     
         149 . The method of  claim 148 , wherein each of the multiple doses is about 50 IU/kg and the dosing interval is about 7 days. 
     
     
         150 . The method of  claim 148 , wherein each of the multiple doses is about 100 IU/kg and the dosing interval is about 10 days.