Methods of treating diabetes with albumin-conjugated exendin peptides

• US 7,683,030 B2
• Filed: 03/11/2008
• Issued: 03/23/2010
• Est. Priority Date: 04/30/1999
• Status: Expired due to Term

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Young, Andrew A., Prickett, Kathryn S.
• Primary Examiner(s): Desai; Anand U
• Assistant Examiner(s): LIU, SAMUEL W
• Application Number:
  US12/046,038
• Publication Number:
  US 20080176802A1
• Time in Patent Office: 742 Days
• Field of Search: None
• US Class Current: 514/7.3
• 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

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 diabetes, postprandial hyperglycemia, or impaired glucose tolerance comprising administering to a human in need of treatment for diabetes, postprandial hyperglycemia, or impaired glucose tolerance a therapeutically effective amount of exendin-4 or agonist exendin-4 peptide analog linked to albumin through the C-terminal or N-terminal amino acid of the exendin-4 or agonist exendin-4 peptide analog.

2. The method of claim 1, wherein the exendin-4 or agonist exendin-4 peptide analog is linked to albumin through an amino, or carboxyl group of the exendin-4 or agonist exendin-4 peptide analog.

3. The method of claim 2, wherein the exendin-4 or agonist exendin-4 peptide analog is linked to albumin through an amino group of the exendin-4 or agonist exendin-4 peptide analog.

4. The method of claim 3, wherein the agonist exendin-4 peptide analog is linked to albumin through the epsilon amino group of a lysine amino acid of the agonist exendin-4 peptide analog.

5. The method of claim 4, wherein the agonist exendin-4 peptide analog linked to albumin is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

6. The method of claim 5, wherein the pharmaceutical composition is administered peripherally.

7. The method of claim 5, wherein the pharmaceutical composition is administered subcutaneously.

8. The method of claim 1, wherein the exendin-4 or agonist exendin-4 peptide analog is linked to albumin through the C-terminal amino acid of the exendin-4 or agonist exendin-4 peptide analog.

9. A method for treating diabetes, postprandial hyperglycemia, or impaired glucose tolerance comprising administering to a human in need of treatment for diabetes, postprandial hyperglycemia, or impaired glucose tolerance a therapeutically effective amount of an agonist exendin-4 peptide analog linked to albumin, wherein the agonist exendin-4 peptide analog comprises the following amino acid sequence:

10. The method of claim 9, wherein the agonist exendin-4 peptide analog is linked to albumin through the N-terminal or C-terminal amino acid of the agonist exendin-4 peptide analog.

11. The method of claim 10, wherein the agonist exendin-4 peptide analog is linked through the C-terminal amino acid of the agonist exendin-4 peptide analog.

12. The method of claim 9, wherein the agonist exendin-4 peptide analog is linked through the epsilon amino group of a lysine amino acid.

13. The method of claim 12, wherein the agonist exendin-4 peptide analog linked to albumin is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

14. The method of claim 13, wherein the pharmaceutical composition is administered peripherally.

15. The method of claim 13, wherein the pharmaceutical composition is administered subcutaneously.