Glucagon analogs exhibiting GIP receptor activity

• US 9,340,600 B2
• Filed: 06/18/2013
• Issued: 05/17/2016
• Est. Priority Date: 06/21/2012
• Status: Active Grant

• Current Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Original Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Inventors: DiMarchi, Richard D.
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US13/920,188
• Publication Number:
  US 20140011738A1
• Time in Patent Office: 1,064 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/26 Glucagons
• 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: C07K 14/605 Glucagons

Abstract

Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

Claims

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

18 with up to 3 amino acid modifications, wherein the peptide comprises (i) His at position 1;

(ii) AIB at position 2;

(iii) Glu at position 16;

(iv) Arg at position 17;

(v) Ala at position 18;

(vi) Ala at position 19;

(vii) Gln at position 20;

(viii) Leu at position 27;

(ix) Gly at position 29;

(x) Gly at position 30;

(xi) Ala at position 35;

or (xii) a combination thereof.

4. A dimer or multimer comprising two or more peptides of claim 1.

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

6. A pharmaceutical composition comprising a peptide of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

10. A method of reducing weight gain or inducing weight loss in a subject in need thereof, comprising administering to a patient in need thereof a pharmaceutical composition of claim 6 in an amount effective to reduce weight gain or induce weight loss.

11. A method of treating diabetes, comprising administering to a patient in need thereof a pharmaceutical composition of claim 6 in an amount effective to lower blood glucose levels, thereby treating diabetes.

2. A peptide comprising a sequence selected from the group consisting of SEQ ID NO:

15-18, 43 and 44.

3. The peptide of claim 2, comprising the sequence of SEQ ID NO:

18.

7. A dimer or multimer comprising two or more peptides of claim 2.

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

9. A pharmaceutical composition comprising a peptide of claim 2 and a pharmaceutically acceptable carrier, diluent, or excipient.

12. A method of reducing weight gain or inducing weight loss in a subject in need thereof, comprising administering to a patient in need thereof a pharmaceutical composition of claim 9 in an amount effective to reduce weight gain or induce weight loss.

13. A method of treating diabetes, comprising administering to a patient in need thereof a pharmaceutical composition of claim 9 in an amount effective to lower blood glucose levels, thereby treating diabetes.