Exendin Agonist Analogs to Treat Diabetes

• US 20090176704A1
• Filed: 08/29/2008
• Published: 07/09/2009
• Est. Priority Date: 01/07/1997
• Status: Active Grant

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Young, Andrew, Beeley, Nigel Robert Arnold, Prickett, Kathryn S., Bhavsar, Sunil
• Granted Patent: US 7,700,549 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides

Abstract

Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.

Claims

1. A method for treating diabetes in a subject in need thereof comprising peripherally administering to the subject a therapeutically effective amount of an exendin agonist analog to treat diabetes in the subject.

2. The method of claim 1, wherein the administration is by injection.

3. The method of claim 1, wherein the administration is intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal, or pulmonary.

4. The method of claim 1, wherein the exendin agonist analog comprises the amino acid sequence of SEQ ID NO:

3;

5. The method of claim 4, wherein Xaa₉ is Leu or pentylglycine.

6. The method of claim 4, wherein the exendin agonist analog of SEQ ID NO:

3 comprises the amino acid sequence of SEQ ID NO;

9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, or 39.

7. The method of claim 4, wherein the exendin agonist analog of SEQ ID NO:

3 comprises the amino acid sequence of SEQ ID NO;

9, 10, 21, 22, 23, 26, 28, 34, 35, or 39.

8. The method of claim 7, wherein the exendin agonist analog of SEQ ID NO:

3 comprises the amino acid sequence of SEQ ID NO;

10.

9. The method of claim 1, wherein the exendin agonist analog comprises the amino acid sequence of SEQ ID NO:

4;

10. The method of claim 1, wherein the exendin agonist analog comprises the amino acid sequence of SEQ ID NO:

5;

11. The method of claim 1, further comprising administering a therapeutically effective amount of amnylin, an amylin agonist, a calcitonin, a leptin, a cholecystokinin, or a combination of two or more thereof.

12. The method of claim 1, further comprising administering a therapeutically effective amount of ^25,28,29pro human amylin.

13. The method of claim 1, further comprising administering a therapeutically effective amount of cholecystokinin octopeptide.

14. The method of claim 1, wherein the diabetes is Type II diabetes.

15. The method of claim 1, wherein the diabetes is non-insulin dependent diabetes.

16. The method of claim 1, wherein said exendin agonist analog is administered as a single or divided dose to said subject from about 0.1 μ

g/kg/day to about 100 μ

g/kg/day.

17. The method of claim 1, wherein said exendin agonist analog is administered at a dose of from about 0.1 μ

g/kg/day to about 10 μ

g/kg/day.

18. The method of claim 1, wherein said exendin agonist analog is administered at a dose of from about 0.1 μ

g/kg/day to about 1 μ

g/kg/day.

19. The method of claim 1, wherein the subject is human.

20. A method for treating diabetes in a subject in need thereof comprising peripherally administering to the subject a therapeutically effective amount of an exendin agonist analog comprising the amino acid sequence of any one of SEQ ID NOs. 9-188 to treat diabetes in the subject.