Methods for treatment of diabetes using peptide analogues of insulin

Abstract

The present invention is directed toward peptide analogues of insulin B chain that are generally derived from peptides comprising residues 9 to 23 of the native B chain sequence. The analogues are altered from the native sequence at position 12, 13, 15 and/or 16, and may be additionally be altered at position 19 and/or other positions. Pharmaceutical compositions containing these peptide analogues are provided. The peptide analogues are useful for treating and inhibiting the development of diabetes.

1 - 27 . (canceled)  
     
     
         28 . A peptide analogue comprising residues 9 to 23 of human insulin B chain, wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at between 1 and 4 amino acid positions, and wherein one substitution occurs at residue 19.  
     
     
         29 . The peptide analogue of  claim 28 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at between 2 and 4 amino acid positions, and wherein at least one substitution occurs at a residue selected from the group consisting of residues 12, 13, 15 and 16.  
     
     
         30 . The peptide analogue of  claim 29 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at 4 amino acid positions, and wherein at least one substitution occurs at a residue selected from the group consisting of residues 12, 13, 15 and 16.  
     
     
         31 . The peptide analogue of  claim 29 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at 3 amino acid positions, and wherein at least one substitution occurs at a residue selected from the group consisting of residues 12, 13, 15 and 16.  
     
     
         32 . The peptide analogue of  claim 29 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at 2 amino acid positions, and wherein one substitution occurs at a residue selected from the group consisting of residues 12, 13, 15 and 16.  
     
     
         33 . The peptide analogue of  claim 32 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at residues 12 and 19.  
     
     
         34 . The peptide analogue of  claim 32 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at residues 13 and 19.  
     
     
         35 . The peptide analogue of  claim 32 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at residues 15 and 19.  
     
     
         36 . The peptide analogue of  claim 32 , wherein the peptide analogue differs in sequence from native human insulin B chain residues 9 to 23 due to substitutions at residues 16 and 19.  
     
     
         37 . The peptide analogue of  claim 28 , wherein residue 19 is an alanine residue.  
     
     
         38 . The peptide analogue of  claim 29 , wherein residue 19 is an alanine residue.  
     
     
         39 . The peptide analogue of  claim 32 , wherein residue 19 is an alanine residue.  
     
     
         40 . The peptide analogue of  claim 36 , wherein residue 19 is an alanine residue.  
     
     
         41 . The peptide analogue of  claim 36 , wherein residue 16 is an alanine residue.  
     
     
         42 . The peptide analogue of  claim 32 , wherein the peptide analogue comprises no more than 18 residues of human insulin B chain.  
     
     
         43 . The peptide analogue of  claim 32 , wherein the peptide analogue comprises no more than 16 residues of human insulin B chain.  
     
     
         44 . The peptide analogue of  claim 32 , wherein the peptide analogue comprises no more than 15 residues of human insulin B chain.  
     
     
         45 . A pharmaceutical composition comprising a peptide analogue according to  claim 32  in combination with a physiologically acceptable carrier or diluent.  
     
     
         46 . A pharmaceutical composition comprising a peptide analogue according to  claim 36  in combination with a physiologically acceptable carrier or diluent.  
     
     
         47 . A pharmaceutical composition comprising a peptide analogue according to  claim 40  in combination with a physiologically acceptable carrier or diluent.