METHODS OF USING CTLA4Ig SUBCUTANEOUS FORMULATIONS

Abstract

The present invention relates generally to stable formulations comprising CTLA4Ig molecules, including lyophilized, and liquid formulations for administration via various routes including, for example, routes such as intravenous (IV) and subcutaneous(SC) for treating immune system diseases and tolerance induction.

1 . A method of treating rheumatoid arthritis in a subject comprising administering to the subject an effective amount of a formulation comprising:
 a) a CTLA4Ig molecule comprising amino acid residues 26-382 of SEQ ID NO:2, amino acid residues 26-383 of SEQ ID NO:2, amino acid residues 27-382 of SEQ ID NO:2 and/or amino acid residues 27-383 of SEQ ID NO:2 at a concentration of about 125 mg/ml;   b) sucrose;   c) phosphate buffer;   d) poloxamer 188; and   e) a pharmaceutically acceptable aqueous carrier;   wherein the pH is between 6 and 8;   wherein the viscosity is between 9 and 20 cps;   wherein the formulation is suitable for subcutaneous administration;   wherein the formulation is stable when stored at 2 to 8° C. for at least 12 months; and   wherein the formulation is administered once weekly in a volume of about 1 ml.   
     
     
         2 . The method of  claim 1 , wherein the CTLA4Ig molecule is abatacept. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 2 , wherein the concentration of sucrose is about 170 mg/ml. 
     
     
         5 - 10 . (canceled) 
     
     
         11 . The method of  claim 2 , wherein the concentration of the phosphate buffer is at least about 10 mM. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . The method of  claim 2 , wherein the concentration of poloxamer 188 is about 8 mg/ml. 
     
     
         16 . The method of  claim 2 , wherein the pharmaceutically acceptable aqueous carrier is sterile water. 
     
     
         17 . The method of  claim 2 , wherein the formulation is stable when stored at 2 to 8° C. for at least 18 months. 
     
     
         18 . The method of  claim 1 , wherein the formulation is stable when stored at 2 to 8° C. for at least 24 months. 
     
     
         19 . The method of  claim 1 , wherein the percentage of CTLA4Ig high molecular weight species in the formulation is less than about 10%. 
     
     
         20 . The method of  claim 1 , wherein the percentage of CTLA4Ig high molecular weight species in the formulation is less than about 5%. 
     
     
         21 . The method of  claim 1 , wherein the percentage of CTLA4Ig high molecular weight species in the formulation is less than about 3%. 
     
     
         22 . The method of  claim 1 , wherein the pH is between 6 and 7.8. 
     
     
         23 . The method of  claim 1 , wherein the pH is between 6 and 7.2. 
     
     
         24 . The method of  claim 1 , wherein the viscosity is between 9 and 15 cps. 
     
     
         25 . The method of  claim 1 , wherein the viscosity is between 12 and 15 cps. 
     
     
         26 . The method of  claim 1 , wherein the formulation further comprises an osmolality between 250-800 mOsm/kgH 2 O. 
     
     
         27 . The method of  claim 26 , wherein the osmolality is between 700-800 mOsm/kgH 2 O. 
     
     
         28 - 85 . (canceled)