Glucagon antagonist-GIP agonist conjugates and compositions for the treatment of metabolic disorders and obesity

• US 8,551,946 B2
• Filed: 01/26/2011
• Issued: 10/08/2013
• Est. Priority Date: 01/27/2010
• Status: Expired due to Fees

• Current Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Original Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Inventors: Dimarchi, Richard D., Ma, Tao
• Primary Examiner(s): Shafer, Shulamith H
• Application Number:
  US13/575,363
• Publication Number:
  US 20120322725A1
• Time in Patent Office: 986 Days
• Field of Search: None
• US Class Current: 514/7.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

Provided herein are peptide combinations comprising a GIP agonist peptide and a glucagon antagonist peptide. In some embodiments, the peptide combination is provided as a composition, e.g., a pharmaceutical composition, while in other embodiments, the peptide combination is provided as a kit. In yet other embodiments, the peptide combination is provided as a conjugate, e.g., a fusion peptide, a heterodimer. In specific aspects, the GIP agonist peptide is an analog of native human glucagon. In specific aspects, the glucagon antagonist peptide is an analog of native human glucagon. In some embodiments, the GIP agonist peptide is covalently attached to the glucagon antagonist peptide via a linker. Methods of treating a disease, e.g., a metabolic disorder, such as diabetes and obesity, comprising administering the peptide compositions described herein are further provided.

Claims

1. A peptide comprising the amino acid sequence of SEQ ID NO:

30, or a pharmaceutically acceptable salt thereof.

2. A conjugate comprising the peptide of claim 1 and a heterologous moiety.

3. A dimer or multimer comprising the peptide of claim 1 and a heterologous peptide or polypeptide.

4. A pharmaceutical composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.

5. A method of lowering body weight in a patient, in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 4.

6. A method of reducing blood glucose levels in a patient, in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 4.

7. A method of treating diabetes in a patient, in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 4.

8. A method of treating obesity in a patient, in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 4.

9. A peptide comprising an amino acid sequence selected from the group of:

SEQ ID NO;

29, SEQ ID NO;

30, SEQ ID NO;

31, SEQ ID NO;

32, SEQ ID NO;

33, SEQ ID NO;

35, SEQ ID NO;

36, SEQ ID NO;

34, SEQ ID NO;

28, and SEQ ID NO;

26.

10. The peptide of claim 9, comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

29 or SEQ ID NO;

30 or SEQ ID NO;

31 or SEQ ID NO;

32.

11. A conjugate comprising the peptide of claim 9 and a heterologous moiety.

12. A dimer or multimer comprising the peptide of claim 9 and a heterologous peptide or polypeptide.

13. A pharmaceutical composition comprising the peptide of claim 9 and a pharmaceutically acceptable carrier.

14. A method of lowering body weight in a patient in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 13.

15. A method of reducing blood glucose levels in a patient in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 13.

16. A method of treating diabetes in a patient in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 13.

17. A method of treating obesity in a patient in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 13.