Exendins, exendin agonists, and methods for their use

• US 20030087821A1
• Filed: 06/28/2002
• Published: 05/08/2003
• Est. Priority Date: 01/07/1997
• Status: Active Grant

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Kathryn S. Prickett, Nigel Robert Arnold Beeley, Sunil Bhavsar
• Inventors: Beeley, Nigel Robert Arnold, Prickett, Kathryn S., Bhavsar, Sunil
• Granted Patent: US 6,989,366 B2
• Time in Patent Office: Days
• US Class Current: 514/12
• 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 conditions or disorders which can be alleviated by reducing food intake in a subject comprising administering to said subject a therapeutically effective amount of an exendin or an exendin agonist.

2. The method according to claim 1 wherein said exendin or exendin agonist is administered parenterally.

3. The method according to claim 2 wherein said parenteral administration is by injection.

4. The method according to claim 3 wherein the injection is a peripheral injection.

5. The method according to claim 1 wherein about 10 μ

g-30 μ

g to about 5 mg of the exendin or exendin agonist is administered per day.

6. The method according to claim 1 wherein about 10 μ

g-30 μ

g to about 2 mg of the exendin or exendin agonist is administered per day.

7. The method according to claim 1, wherein about 30 μ

g to about 500 μ

g of the exendin or exendin agonist is administered per day.

8. The method of claim 1 wherein said condition or disorder is obesity.

9. The method of claim 1 wherein said condition or disorder is Type II diabetes.

10. The method of claim 1 wherein said subject is human.

11. The method of claim 1 wherein said condition or disorder is an eating disorder.

12. The method of claim 1 wherein said condition or disorder is insulin-resistance syndrome.

16. The method according to any of claims 1-15 wherein said exendin is exendin-3.

17. The method according to any of claims 1-15 wherein said exendin is exendin-4.

18. The method according to any of claims 1-15 wherein said exendin agonist is selected from the group consisting of exendin-4 (1-30), exendin-4 (1-30) amide, exendin-4 (1-28) amide, ¹⁴Leu, ²⁵Phe exendin-4 amide, ¹⁴Leu, ²⁵Phe exendin-4 (1-28) amide, and ¹⁴Leu, ²²Ala, ²⁵Phe exendin-4 (1-28) amide.

19. The method according to any of claims 1-15, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting essential, of an amylin agonist, a leptin, and a CCK.

20. The method according to any of claims 1-15 wherein said exendin agonist is an exendin agonist according to Formula I.

21. The method according to any of claims 1-15 wherein said exendin agonist is an ekendin agonist according to Formula II.

22. The method according to any of claims 1-15 wherein said exendin agonist is an exendin agonist according to Formula III.

24. The pharmaceutical composition according to claim 21, wherein said exendin is exendin-3.

25. The pharmaceutical composition according to claim 21 wherein said exendin is exendin-4.

26. The pharmaceutical composition according to claim 21 wherein said exendin agonist is selected from the group consisting of exendin-4 (1-30), exendin-4 (1-30) amide, exendin-4 (1-28) amide, ¹⁴Leu, ²⁵Phe exendin-4 amide, ¹⁴Leu, ²⁵Phe exendin-4 (1-28) amide, and ¹⁴Leu, ²²Ala, ²⁵Phe exendin-4 (1-28) amide.

27. The pharmaceutical composition of claim 21 wherein said therapeutically effective amount is a therapeutically effective amount for a human subject.

31. The pharmaceutical composition according to any of claims 21-28, further comprising a therapeutically effective amount of one or more compounds selected from the group consisting essentially of an amylin agonist, a leptin, and a CCK.

13. A method for reducing the appetite of a subject comprising administering to said subject an appetite-lowering amount of an exendin or an exendin agonist.

14. A method for reducing the weight of a subject comprising administering to said subject a therapeutically effective amount of an exendin or an exendin agonist.

15. A method for lowering plasma lipids comprising administering to said subject a therapeutically effective amount of an exendin or an exendin agonist.

23. A pharmaceutical composition for use in the treatment of conditions or disorders associated with hypernutrition comprising a therapeutically effective amount of an exendin or exendin agonist in association with a pharmaceutically acceptable carrier.

28. A pharmaceutical composition for use in reducing the appetite of a subject comprising a therapeutically effective amount of an exendin or exendin agonist in association with a pharmaceutically acceptable carrier.

29. A pharmaceutical composition for use in reducing the weight of a subject comprising a therapeutically effective amount of an exendin or exendin agonist in association with a pharmaceutically acceptable carrier.

30. A pharmaceutical composition for use in lowering the plasma lipid level of a subject comprising a therapeutically effective amount of an exendin or exendin agonist in association with a pharmaceutically acceptable carrier.