Methods of Use for Conjugated Exendin Peptides

• US 20080176802A1
• Filed: 03/11/2008
• Published: 07/24/2008
• Est. Priority Date: 04/30/1999
• Status: Active Grant

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: PRICKETT, Kathryn S., Young, Andrew A.
• Granted Patent: US 7,683,030 B2
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.

Claims

1. A method for treating type 2 diabetes in a human in need thereof comprising administering to the human a therapeutically effective amount of a pharmaceutical composition comprising:

(i) an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO. 2 covalently bonded to albumin; and

(ii) a pharmaceutically acceptable carrier;

to treat type 2 diabetes.

2. The method of claim 1, comprising peripherally administering the pharmaceutical composition.

3. The method of claim 1, comprising subcutaneously administering the pharmaceutical composition.

4. The method of claim 1, wherein the exendin-4 peptide is covalently bonded to albumin through an epsilon amino group on a lysine amino acid of the exendin-4 peptide.

5. The method of claim 1, wherein the therapeutically effective amount is from 1 pg to 5 mg.

6. A method for treating diabetes in a human in need thereof comprising administering to the human a therapeutically effective amount of a pharmaceutical composition comprising:

(i) an exendin-4 peptide having the amino acid sequence of SEQ ID NO. 2 covalently bonded to albumin or polyethylene glycol; and

a pharmaceutically acceptable carrier;

to treat diabetes.

7. A method for treating diabetes, postprandial dumping syndrome, postprandial hyperglycemia, impaired glucose tolerance, dyslipidemia, or obesity in a human in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising:

(A) an exendin peptide or an exendin agonist analog peptide covalently bonded to albumin, a polyethylene glycol, gelatin, succinyl-gelatin, (hydroxypropyl)-methacrylamide, a polyamino acid, a fatty acid, a polysaccharide, a lipid amino acid, a dextran, or a combination of two or more thereof, and (B) a pharmaceutically acceptable carrier.

8. The method of claim 7, wherein the diabetes is type 1 diabetes, type 2 diabetes, or gestational diabetes.

9. The method of claim 7, wherein the exendin is an exendin-4.

10. The method of claim 7, wherein the exendin peptide or the exendin agonist analog peptide is covalently bonded to albumin, polyethylene glycol, gelatin, succinyl-gelatin, or (hydroxypropyl)-methacrylamide.

11. The method of claim 7, wherein the exendin peptide or the exendin agonist analog peptide is covalently bonded to albumin or polyethylene glycol.

12. The method of claim 11, wherein the albumin or polyethylene glycol is covalently bonded to (i) an internal lysine amino acid in the exendin peptide or the exendin agonist analog peptide, (ii) an internal aspartic acid amino acid in the exendin peptide or the exendin agonist analog peptide, (iii) an internal glutamic acid amino acid in the exendin peptide or the exendin agonist analog peptide, (iv) an internal cysteine amino acid in the exendin peptide or the exendin agonist analog peptide, (v) a C-terminal amino acid in the exendin peptide or the exendin agonist analog peptide, or (vi) an N-terminal amino acid in the exendin peptide or the exendin agonist analog peptide.

13. A method for reducing appetite or food intake in a human in need of or desirous of a reduction in appetite or food intake comprising administering to the human a therapeutically effective amount of a pharmaceutical composition comprising:

(A) an exendin peptide or an exendin agonist analog peptide covalently bonded to albumin, polyethylene glycol, gelatin, succinyl-gelatin, (hydroxypropyl)-methacrylamide, a polyamino acid, a fatty acid, a polysaccharide, a lipid amino acid, a dextran, or a combination of two or more thereof, and (B) a pharmaceutically acceptable carrier.

14. The method of claim 13, wherein the exendin is an exendin-4.

15. The method of claim 13, wherein the exendin peptide or the exendin agonist analog peptide is covalently bonded to albumin, polyethylene glycol, gelatin, succinyl-gelatin, or (hydroxypropyl)-methacrylamide.

16. The method of claim 13, wherein the exendin peptide or the exendin agonist analog peptide is covalently bonded to albumin or polyethylene glycol.

17. A method for suppressing glucagon secretion, lowering plasma lipid levels, lowering triglyceride levels, or reducing the rate of gastric emptying in a human in need thereof comprising administering to the human a therapeutically effective amount of a pharmaceutical composition comprising:

(A) an exendin peptide or an exendin agonist analog peptide covalently bonded to albumin, polyethylene glycol, gelatin, succinyl-gelatin, (hydroxypropyl)-methacrylamide, a polyamino acid, a fatty acid, a polysaccharide, a lipid amino acid, a dextran, or a combination of two or more thereof; and

(B) a pharmaceutically acceptable carrier.

18. The method of claim 17, wherein the exendin is an exendin-4.

19. The method of claim 17, wherein the exendin peptide or the exendin agonist analog peptide is covalently bonded to albumin, polyethylene glycol, gelatin, succinyl-gelatin, or (hydroxypropyl)-methacrylamide.

20. The method of claim 17, wherein the exendin peptide or the exendin agonist analog peptide is covalently bonded to albumin or polyethylene glycol.