Combinations of modalities for the treatment of diabetes

Abstract

A method of treating, preventing, or delaying the progression of Type 1 diabetes mellitus by administering an effective amount of a fusion protein composition comprising a T-cell co-stimulation antagonist and a portion of an immunoglobulin molecule and an effective amount of a Type 1 diabetes autoantigen. The method includes, for example, administering a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) molecule and a Type 1 diabetes autoantigen. Pharmaceutical compositions are also provided herewith.

1 .- 19 . (canceled) 
     
     
         20 . A method of treating diabetes mellitus in a subject comprising administering preproinsulin to the subject. 
     
     
         21 . The method of  claim 20 , further comprising administering a T-cell antagonist to the subject. 
     
     
         22 . The method of  claim 21 , wherein the T-cell antagonist comprises a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) fusion protein. 
     
     
         23 . The method of  claim 22 , wherein the CTLA4 fusion protein is abatacept. 
     
     
         24 . The method of  claim 22 , wherein the preproinsulin and CTLA4 fusion protein are administered in the same composition. 
     
     
         25 . The method of  claim 22 , wherein the preproinsulin and CTLA4 fusion protein are administered in separate compositions. 
     
     
         26 . The method of  claim 25 , wherein the preproinsulin and CTLA4 fusion protein are administered simultaneously. 
     
     
         27 . The method of  claim 25 , wherein the preproinsulin and CTLA4 fusion protein are administered sequentially. 
     
     
         28 . The method of  claim 25 , wherein the CTLA4 fusion protein is administered intravenously or subcutaneously. 
     
     
         29 . The method of  claim 28 , wherein the preproinsulin is administered intramuscularly. 
     
     
         30 . The method of  claim 29 , comprising administering from about 250 mg to about 2,000 mg of the CTLA4 fusion protein. 
     
     
         31 . The method of  claim 30 , comprising administering from about 0.5 to about 10 mg of the preproinsulin. 
     
     
         32 . The method of  claim 20 , wherein the preproinsulin is administered in an oil based carrier. 
     
     
         33 . The method of  claim 32 , wherein the oil based carrier is a water-in-oil emulsion. 
     
     
         34 . The method of  claim 33 , wherein the water-in-oil emulsions comprises from 30-70% oil by weight. 
     
     
         35 . The method of  claim 34 , wherein the oil based carrier comprises mannide oleate. 
     
     
         36 . The method of  claim 35 , wherein the preproinsulin and carrier are present in a composition in about a 50/50 w/w ratio. 
     
     
         37 . The method of  claim 36 , wherein the oil based carrier comprises IFA or Mantanide ISA. 
     
     
         38 . The method of  claim 31 , wherein the preproinsulin is administered in a water-in-oil emulsion comprising mannide oleate. 
     
     
         39 . The method of  claim 38 , wherein the preproinsulin and emulsion are present in a composition in about a 50/50 w/w ratio.