Peptide YY analogs
The present invention relates to novel analogs of PYY that have an improved therapeutic profile when compared to native human PYY. These novel PYY analogs are useful in the treatment of obesity, diabetes, and other disorders.
1. A polypeptide comprising the amino acid sequence:
ProLysProGluAlaProGlyLysAspAlaSerProGluGluTrpAsnArgTyrTyrAla AspLeuArgHisTyrLeuAsnTrpLeuThrArgGlnArgTyr (SEQ ID NO:38).
2. A pharmaceutical combination comprising a polypeptide according to claim 1 and exendin-4.
3. A pharmaceutical combination comprising a polypeptide according to claim 1 and GLP-1.
4. A pharmaceutical composition comprising a polypeptide according to claim 1 and a pharmaceutically acceptable carrier.
5. A method of treating Type 2 Diabetes Mellitus in a human subject, said method comprising administering a polypeptide according to claim 1 to a subject in need thereof.
6. The method according to claim 5 , wherein 0.05-100 μg of the polypeptide is administered to the subject per day.
7. A method of treating obesity in a human subject, said method comprising administering a polypeptide according to claim 1 to a subject in need thereof.
8. The method according to claim 7 , wherein 0.05-100 μg of the polypeptide is administered to the subject per day.
9. A pharmaceutical combination comprising a polypeptide according to claim 2 and exendin-4.
10. A polypeptide consisting of the amino acid sequence:
ProLysProGluAlaProGlyLysAspAlaSerProGluGluTrpAsnArgTyrTyrAla AspLeuArgHisTyrLeuAsnTrpLeuThrArgGlnArgTyr (SEQ ID NO:38).
11. A pharmaceutical combination comprising a polypeptide according to claim 10 and exendin-4.
12. A pharmaceutical combination comprising a polypeptide according to claim 10 and GLP-1.
13. A pharmaceutical composition comprising a polypeptide according to claim 10 and a pharmaceutically acceptable carrier.
14. A method of treating Type 2 Diabetes Mellitus in a human subject, said method comprising administering a polypeptide according to claim 10 to a subject in need thereof.
15. The method according to claim 14 , wherein 0.05-100 μg of the polypeptide is administered to the subject per day.
16. A method of treating obesity in a human subject, said method comprising administering a polypeptide according to claim 10 to a subject in need thereof.
17. The method according to claim 16 , wherein 0.05-100 μg of the polypeptide is administered to the subject per day.
18. A polypeptide consisting of the amino acid sequence:
ProLysProGluAlaProGlyLysAspAlaSerProGluGluTrpAsnArgTyrTyrAla AspLeuArgHisTyrLeuAsnTrpLeuThrArgGlnArgTyr-NH2 (SEQ ID NO:7).
19. A pharmaceutical combination comprising a polypeptide according to claim 18 and exendin-4.
20. A pharmaceutical combination comprising a polypeptide according to claim 18 and GLP-1.
21. A pharmaceutical composition comprising a polypeptide according to claim 18 and a pharmaceutically acceptable carrier.
22. A method of treating Type 2 Diabetes Mellitus in a human subject, said method comprising administering a polypeptide according to claim 18 to a subject in need thereof.
23. The method according to claim 22 , wherein 0.05-100 μg of the polypeptide is administered to the subject per day.
24. A method of treating obesity in a human subject, said method comprising administering a polypeptide according to claim 18 to a subject in need thereof.
25. The method according to claim 24 , wherein 0.05-100 μg of the polypeptide is administered to the subject per day.
26. A salt form of the polypeptide consisting of:
ProLysProGluAlaProGlyLysAspAlaSerProGluGluTrpAsnArgTyrTyrAla AspLeuArgHisTyrLeuAsnTrpLeuThrArgGlnArgTyr-NH2 (SEQ ID NO:7).
27. The polypeptide according to claim 26 , wherein said salt is an acetate salt.
28. The polypeptide according to claim 26 , wherein said salt is the acetic acid salt.
29. A pharmaceutical combination comprising a polypeptide according to claim 26 and GLP-1.
30. A pharmaceutical composition comprising a polypeptide according to claim 26 and a pharmaceutically acceptable carrier.
31. A method of treating Type 2 Diabetes Mellitus in a human subject, said method comprising administering a polypeptide according to claim 26 to a subject in need thereof.
32. A method of treating obesity in a human subject, said method comprising administering a polypeptide according to claim 26 to a subject in need thereof.
33. A pharmaceutical combination comprising an acetate salt form of the polypeptide comprising:
ProLysProGluAlaProGlyLysAspAlaSerProGluGluTrpAsnArgTyrTyrAla AspLeuArgHisTyrLeuAsnTrpLeuThrArgGlnArgTyr (SEQ ID NO:38) and exendin-4.
34. A method of treating Type 2 Diabetes Mellitus in a human subject, said method comprising administering the pharmaceutical combination according to claim 33 to a subject in need thereof.
35. A method of treating obesity in a human subject, said method comprising administering the pharmaceutical combination according to claim 33 to a subject in need thereof.
36. A pharmaceutical combination comprising an acetate salt form of the polypeptide comprising:
ProLysProGluAlaProGlyLysAspAlaSerProGluGluTrpAsnArgTyrTyrAla AspLeuArgHisTyrLeuAsnTrpLeuThrArgGlnArgTyr-NH2 (SEQ ID NO: 7) and exendin-4.
37. A method of treating Type 2 Diabetes Mellitus in a human subject, said method comprising administering the pharmaceutical combination according to claim 36 to a subject in need thereof.
38. A method of treating obesity in a human subject, said method comprising administering the pharmaceutical combination according to claim 36 to a subject in need thereof.