Methods for glucagon suppression using modified exendins

• US 7,407,932 B2
• Filed: 10/19/2006
• Issued: 08/05/2008
• Est. Priority Date: 01/14/1999
• Status: Expired due to Fees

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Young, Andrew A., Gedulin, Bronislava
• Primary Examiner(s): Carlson; Karen Cochrane
• Assistant Examiner(s): Liu; Samuel W
• Application Number:
  US11/584,114
• Publication Number:
  US 20070037750A1
• Time in Patent Office: 656 Days
• Field of Search: 530/308, 530/322, 530/324, 530/402
• US Class Current: 514/11.7
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 17/00 Drugs for dermatological disorders
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides

Abstract

Methods for use of an exendin, an exendin agonist, or a modified exendin or exendin agonist having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, for lowering glucagon levels and/or suppressing glucagon secretion in a subject are provided. These methods are useful in treating hyperglucagonemia and other conditions that would be benefited by lowering plasma glucgon or suppressing glucagon secretion.

Claims

1. A modified exendin agonist peptide or exendin agonist analog peptide wherein one or more amino acid residues is acylated with a dicarboxylic acid;

wherein the amino acid residues are an internal lysine residue, an N-terminal amino acid residue, a C-terminal amino acid residue, or a combination of two or more thereof.

2. The peptide of claim 1, wherein the acylated amino acid residue comprises a side chain having a dicarboxylic acid group.

3. The peptide of claim 1, wherein the acylated amino acid residue is a C-terminal lysine residue.

4. The peptide of claim 1, wherein the peptide comprises a plurality of amino acid residues comprising dicarboxylic groups.

5. The peptide of claim 1, wherein the dicarboxylic group is linked to an epsilon amino group of a lysine residue.

6. The peptide of claim 1, wherein the peptide comprises an amino acid sequence according to any of SEQ ID NOs. 1-239.

7. An exendin-4 agonist peptide wherein one or more amino acid residues is acylated with a dicarboxylic acid;

wherein the amino acid residues are an internal lysine residue, an N-terminal amino acid residue, a C-terminal amino acid residue, or a combination of two or more thereof.