Exendins and exendin agonists for weight reduction and obesity

• US 7,741,269 B2
• Filed: 07/20/2004
• Issued: 06/22/2010
• Est. Priority Date: 08/08/1996
• Status: Expired due to Fees

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Gedulin, Bronislava, Young, Andrew A., Bhavsar, Sunil
• Primary Examiner(s): Desai; Anand U
• Assistant Examiner(s): LIU, SAMUEL W
• Application Number:
  US10/895,909
• Publication Number:
  US 20050043238A1
• Time in Patent Office: 2,163 Days
• Field of Search: 514/2
• US Class Current: 514/4.9
• 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 reducing body weight in a human in need thereof comprising identifying a human in need of a reduction in body weight, and administering to the human a therapeutically effective amount of an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO:

2 to reduce body weight.

2. The method of claim 1, wherein the therapeutically effective amount is 10 μ

g per day to 1 mg per day.

3. The method of claim 1, wherein the therapeutically effective amount is 0.1 μ

g/kg/day to 10 μ

g/kg/day.

4. The method of claim 1, comprising parenterally administering the exendin-4 peptide.

5. The method of claim 1, comprising administering the exendin-4 peptide by peripheral injection.

6. The method of claim 1, wherein administration is intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal, transdermal, nasal, or pulmonary inhalation.

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

8. The method of claim 1, further comprising administering a therapeutically effective amount of pramlintide.

9. The method of claim 1, further comprising administering a therapeutically effective amount of at least one additional compound that is used to reduce body weight.

10. A method for reducing body weight in a human in need thereof comprising identifying a human in need of a reduction in body, and administering to the human a therapeutically effective amount of an exendin peptide or an exendin agonist analog peptide to reduce body weight.

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

1 or SEQ ID NO;

2.

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

3, 4, or 5.

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

6, 7, 8, 9, 40, or 41.

14. The method of claim 10, wherein the exendin peptide or the exendin agonist analog peptide comprises the amino acid sequence of any one of SEQ ID NOs:

10-39 and 42-188.

15. The method of claim 10, wherein the therapeutically effective amount is 10 μ

g per day to 5 mg per day.

16. The method of claim 10, wherein the therapeutically effective amount is human 0.1 μ

g/kg/day to 100 μ

g/kg/day.

17. The method of claim 10, comprising administering the exendin peptide or the exendin agonist analog peptide by peripheral injection.

18. The method of claim 10, wherein administration is intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal, transdermal, nasal, or pulmonary inhalation.

19. The method of claim 10, further comprising administering a therapeutically effective amount of an amylin, an amylin agonist, a leptin, a calcitonin, a cholecystokinin, or a combination of two or more thereof.

20. The method of claim 10, further comprising administering a therapeutically effective amount of pramlintide.

21. The method of claim 10, further comprising administering a therapeutically effective amount of at least one additional compound that is used to reduce body weight.

22. A method for treating obesity in a human in need thereof comprising identifying a human in need of treatment for obesity, and administering to the human a therapeutically effective amount of an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO:

2 to treat obesity.

23. The method of claim 22, wherein the therapeutically effective amount is 10 μ

g per day to 1 mg per day.

24. The method of claim 22, wherein the therapeutically effective amount is 0.1 μ

g/kg/day to 10 μ

g/kg/day.

25. The method of claim 22, comprising parenterally administering the exendin-4 peptide.

26. The method of claim 22, comprising administering the exendin-4 peptide by peripheral injection.

27. The method of claim 22, wherein administration is intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal, transdermal, nasal, or pulmonary inhalation.

28. The method of claim 22, further comprising administering a therapeutically effective amount of an amylin, an amylin agonist, a leptin, a calcitonin, a cholecystokinin, or a combination of two or more thereof.

29. The method of claim 22, further comprising administering a therapeutically effective amount of pramlintide.

30. The method of claim 22, further comprising administering a therapeutically effective amount of at least one additional compound that is used to reduce body weight.

31. A method for treating obesity in a human in need thereof comprising identifying a human in need of treatment for obesity, and administering to the human a therapeutically effective amount of an exendin peptide or an exendin agonist analog peptide to treat obesity.

32. The method of claim 31, wherein the exendin peptide or the exendin agonist analog peptide comprises the amino acid sequence of SEQ ID NO:

1 or SEQ ID NO;

2.

33. The method of claim 31, wherein the exendin peptide or the exendin agonist analog peptide comprises the amino acid sequence of SEQ ID NO:

3, 4, or 5.

34. The method of claim 31, wherein the exendin peptide or the exendin agonist analog peptide comprises the amino acid sequence of SEQ ID NO:

6, 7, 8, 9, 40, or 41.

35. The method of claim 31, wherein the exendin peptide or the exendin agonist analog peptide comprises the amino acid sequence of any one of SEQ ID NOs:

10-39 and 42-188.

36. The method of claim 31, wherein the therapeutically effective amount is 10 μ

g per day to 5 mg per day.

37. The method of claim 31, wherein the therapeutically effective amount is human 0.1 μ

g/kg/day to 100 μ

g/kg/day.

38. The method of claim 31, comprising administering the exendin peptide or the exendin agonist analog peptide by peripheral injection.

39. The method of claim 31, wherein administration is intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal, transdermal, nasal, or pulmonary inhalation.

40. The method of claim 31, further comprising administering a therapeutically effective amount of an amylin, an amylin agonist, a leptin, a calcitonin, a cholecystokinin, or a combination of two or more thereof.

41. The method of claim 31, further comprising administering a therapeutically effective amount of pramlintide.

42. The method of claim 31, further comprising administering a therapeutically effective amount of at least one additional compound that is used to reduce body weight.

43. A method for reducing body weight in a human in need thereof comprising identifying a human in need of a reduction in body weight, and subcutaneously administering to the human from 0.1 μ

g/kg/day to 10 μ

g/kg/day of an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO;

2 to reduce body weight.

44. A method for treating obesity in a human in need thereof comprising identifying a human in need of treatment for obesity, and subcutaneously administering to the human from 0.1 μ

g/kg/day to 10 μ

g/kg/day of an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO;

2 to treat obesity.