Exendins and exendin agonists modified with albumin

• US 7,608,692 B2
• Filed: 04/11/2008
• Issued: 10/27/2009
• 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:
  US12/101,689
• Publication Number:
  US 20080214467A1
• Time in Patent Office: 564 Days
• Field of Search: None
• US Class Current: 530/387.3
• 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. An agonist exendin-4 peptide analog linked to one albumin through the N-terminal or C-terminal amino acid of said agonist exendin-4 peptide analog.

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

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

4. The agonist exendin-4 peptide analog linked to one albumin according to claim 3, wherein the agonist exendin-4 peptide analog is linked to the one albumin through the C-terminal amino acid of the agonist exendin-4 peptide analog.

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

6. A pharmaceutical composition comprising the agonist exendin-4 peptide analog linked to one albumin according to claim 1 and a pharmaceutically acceptable carrier.

7. An agonist exendin-4 peptide analog linked to one albumin through the N-terminal or C-terminal amino acid of said agonist exendin-4 peptide analog, wherein the agonist exendin-4 peptide analog comprises the amino acid sequence of:

His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly(SEQ ID NO;

     3).

8. The agonist exendin-4 peptide analog linked to one albumin according to claim 7, wherein the agonist exendin-4 peptide analog 4 is linked to the one albumin through an amino or carboxyl group of the agonist exendin-4 peptide analog.

9. The agonist exendin-4 peptide analog linked to one albumin according to claim 8, wherein the agonist exendin-4 peptide analog is linked to the one albumin through an amino group of the agonist exendin-4 peptide analog.

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

11. The agonist exendin-4 peptide analog linked to one albumin according to claim 10, wherein the agonist exendin-4 peptide analog is linked to the one albumin through the epsilon amino group of a lysine amino acid of the agonist exendin-4 peptide analog.

12. A pharmaceutical composition comprising the agonist exendin-4 peptide analog linked to one albumin according to claim 7 and a pharmaceutically acceptable carrier.