Patent EA-003944-B1 (EA)
Title: Methods for treatment of diabetes using peptide analogues of insulin
Inventor: GAUR AMITABH
IPC: C07K14/62
Filed: 1999-02-23
Abstract: 1. 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 at least one substitution occurs at a residue selected from the group consisting of residues 12, 13, 15 and 16. 2. The peptide analogue of claim 1, wherein the peptide analogue has a sequence that differs from native human insulin B chain at two amino acid residues. 3. The peptide analogue of claim 1, wherein the peptide analogue has a sequence that differs from native human insulin B chain at three amino acid residues. 4. The peptide analogue of claim 1, wherein an amino acid substitution occurs at residue 19. 5. The peptide analogue of claim 1, wherein at least one amino acid substitution is non-conservative. 6. The peptide analogue of claim 1, wherein residue 12 is substituted. 7. The peptide analogue of claim 6, wherein residue 12 is an alanine residue. 8. The peptide analogue of claim 1, wherein residue 13 is an alanine residue. 9. The peptide analogue of claim 1, wherein residue 15 is substituted. 10. The peptide analogue of claim 9, wherein residue 15 is an alanine residue. 11. The peptide analogue of claim 1, wherein residue 16 is substituted. 12. The peptide analogue of claim 11, wherein residue 16 is an alanine residue. 13. The peptide analogue of any one of claims 6-12, wherein residue 19 is substituted. 14. The peptide analogue of claim 13, wherein residue 19 is an alanine residue. 15. The peptide analogue of claim 1, further comprising residue 24 of human insulin B chain. 16. The peptide analogue of claim 1, wherein the peptide analogue comprises no more than 18 residues of human insulin B chain. 17. The peptide analogue of claim 1, wherein the peptide analogue comprises no more than 16 residues of human insulin B chain. 18. The peptide analogue of claim 1, wherein the peptide analogue comprises no more than 15 residues of human insulin B chain. 19. A peptide analogue consisting essentially of 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 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. 20. A peptide analogue consisting essentially of residues 9 to 24 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 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. 21. A pharmaceutical composition comprising a peptide analogue according to any one of claims 1-18 in combination with a physiologically acceptable carrier or diluent. 22. A method for inhibiting the development of diabetes, comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition according to claim 21. 23. A method for treating diabetes, comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition according to claim 21. 24. 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 residues 16 and 19. 25. A pharmaceutical composition comprising a peptide analogue according to claim 24 in combination with a physiologically acceptable carrier or diluent. 26. A method for inhibiting the development of diabetes, comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition according to claim 25.