Use of exendins for the reduction of food intake

• US 6,956,026 B2
• Filed: 01/07/1998
• Issued: 10/18/2005
• Est. Priority Date: 01/07/1997
• Status: Expired due to Term

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Beeley, Nigel Robert Arnold, Bhavsar, Sunil
• Primary Examiner(s): Weber, Jon
• Assistant Examiner(s): Mohamed, Abdel A.
• Application Number:
  US09/003,869
• Publication Number:
  US 20020137666A1
• Time in Patent Office: 2,841 Days
• Field of Search: 514/2, 514/12, 530/300, 530/324, 424/185.1
• US Class Current: 514/4.8
• 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 food intake in a subject desirous or in need of reducing food intake, comprising peripherally administering to said subject an amount of an exendin effective to reduce food intake.

2. The method according to claim 1, wherein said peripheral administration is by injection.

3. The method according to claim 1, wherein said peripheral administration is selected from the group consisting of intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, oral administration, topical administration, transmucosal administration, and pulmonary administration.

4. The method according to claim 1, wherein about 10 μ

g/70 kg to about 5 mg/70 kg of the exendin is administered per day in single or divided doses.

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

g/70 kg to about 2 mg/70 kg of the exendin is administered per day in single or divided doses.

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

g/70 kg to about 500 μ

g/70 kg of the exendin is administered per day in single or divided doses.

7. The method according to claim 1, wherein about 0.1 μ

g/kg to about 100 μ

g/kg of the exendin is administered per day in single or divided doses.

8. The method according to claim 1, wherein about 0.1 μ

g/kg to about 10 μ

g/kg of the exendin is administered per day in single or divided doses.

9. The method according to claim 1, wherein about 0.1 μ

g/kg to about 1 μ

g/kg of the exendin is administered per day in single or divided doses.

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

11. The method of claim 1, wherein said subject suffers from Type II diabetes.

12. The method of claim 1, wherein said subject suffers from an eating disorder.

13. The method of claim 1, wherein said subject suffers from an insulin-resistance syndrome.

14. The method of claim 1, wherein said exendin is exendin-3.

15. The method of claim 1, wherein said exendin is exendin-4.

16. The method of claim 1, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting of an amylin agonist, a leptin, and a cholecystokinin (CCK).

17. A method for reducing appetite in a subject desirous or in need of reducing appetite, comprising peripherally administering to said subject an amount of an exendin effective to reduce appetite.

18. The method according to claim 17, wherein said peripheral administration is by injection.

19. The method according to claim 17, wherein said peripheral administration is selected from the group consisting of intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, oral administration, topical administration, transmucosal administration, and pulmonary administration.

20. The method according to claim 17, wherein about 10 μ

g/70 kg to about 5 mg/70 kg of the exendin is administered per day in single or divided doses.

21. The method according to claim 17, wherein about 10 μ

g/70 kg to about 2 mg/70 kg of the exendin is administered per day in single or divided doses.

22. The method according to claim 17, wherein about 10 μ

g/70 kg to about 500 μ

g/70 kg of the exendin is administered per day in single or divided doses.

23. The method according to claim 17, wherein about 0.1 μ

g/kg to about 100 μ

g/kg of the exendin is administered per day in single or divided doses.

24. The method according to claim 17, wherein about 0.1 μ

g/kg to about 10 μ

g/kg of the exendin is administered per day in single or divided doses.

25. The method according to claim 17, wherein about 0.1 μ

g/kg to about 1 μ

g/kg of the exendin is administered per day in single or divided doses.

26. The method of claim 17, wherein said subject is human.

27. The method of claim 17, wherein said subject suffers from Type II diabetes.

28. The method of claim 17, wherein said subject suffers from an eating disorder.

29. The method of claim 17, wherein said subject suffers from an insulin-resistance syndrome.

30. The method of claim 17, wherein said exendin is exendin-3.

31. The method of claim 17, wherein said exendin is exendin-4.

32. The method of claim 17, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting of an amylin agonist, a leptin, and a cholecystokinin (CCK).

33. A method for reducing food intake in a subject desirous or in need of reducing food intake comprising peripherally administering to said subject an amount of exendin-4 effective to reduce food intake.

34. The method according to claim 33, wherein said peripheral administration is by injection.

35. The method according to claim 33, wherein said peripheral administration is selected from the group consisting of intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, oral administration, topical administration, transmucosal administration, and pulmonary administration.

36. The method according to claim 33, wherein about 10 μ

g/70 kg to about 5 mg/70 kg of the exendin-4 is administered per day in single or divided doses.

37. The method according to claim 33, wherein about 10 μ

g/70 kg to about 2 mg/70 kg of the exendin-4 is administered per day in single or divided doses.

38. The method according to claim 33, wherein about 10 μ

g/70 kg to about 500 μ

g/70 kg of the exendin-4 is administered per day in single or divided doses.

39. The method according to claim 33, wherein about 0.1 μ

g/kg to about 100 μ

g/kg of the exendin-4 is administered per day in single or divided doses.

40. The method according to claim 33, wherein about 0.1 μ

g/kg to about 10 μ

g/kg of the exendin-4 is administered per day in single or divided doses.

41. The method according to claim 33, wherein about 0.1 μ

g/kg to about 1 μ

g/kg of the exendin-4 is administered per day in single or divided doses.

42. The method of claim 33, wherein said subject is human.

43. The method of claim 33, wherein said subject suffers from Type II diabetes.

44. The method of claim 33, wherein said subject suffers from an eating disorder.

45. The method of claim 33, wherein said subject suffers from an insulin-resistance syndrome.

46. The method of claim 33, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting of an amylin agonist, a leptin, and a cholecystokinin (CCK).

47. A method for reducing appetite in a subject desirous or in need of reducing appetite, comprising peripherally administering to said subject an amount of exendin-4 effective to reduce appetite.

48. The method according to claim 47, wherein said peripheral administration is by injection.

49. The method according to claim 47, wherein said peripheral administration is selected from the group consisting of intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, oral administration, topical administration, transmucosal administration, and pulmonary administration.

50. The method according to claim 47, wherein about 10 μ

g/70 kg to about 5 mg/70 kg of the exendin-4 is administered per day in single or divided doses.

51. The method according to claim 47, wherein about 10 μ

g/70 kg to about 2 mg/70 kg of the exendin-4 is administered per day in single or divided doses.

52. The method according to claim 47, wherein about 10 μ

g/70 kg to about 500 μ

g/70 kg of the exendin-4 is administered per day in single or divided doses.

53. The method according to claim 47, wherein about 0.1 μ

g/kg to about 100 μ

g/kg of the exendin-4 is administered per day in single or divided doses.

54. The method according to claim 47, wherein about 0.1 μ

g/kg to about 10 μ

g/kg of the exendin-4 is administered per day in single or divided doses.

55. The method according to claim 47, wherein about 0.1 μ

g/kg to about 1 μ

g/kg of the exendin-4 is administered per day in single or divided doses.

56. The method of claim 47, wherein said subject is human.

57. The method of claim 47, wherein said subject suffers from Type II diabetes.

58. The method of claim 47, wherein said subject suffers from an eating disorder.

59. The method of claim 47, wherein said subject suffers from an insulin-resistance syndrome.

60. The method of claim 47, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting of an amylin agonist, a leptin, and a cholecystokinin (CCK).

61. A method for reducing food intake in a subject desirous or in need of reducing body weight, comprising peripherally administering to said subject an amount of exendin-4 effective to lower a plasma lipid level.

62. The method according to claim 61, wherein said peripheral administration is by injection.

63. The method according to claim 61, wherein said peripheral administration is selected from the group consisting of intravenous administration intraperitoneal administration, subcutaneous administration, intramuscular administration, oral administration, topical administration, transmucosal administration, and pulmonary administration.

64. The method of claim 61, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting of an amylin agonist, a leptin, and a cholecystokinin (CCK).

65. A method for reducing appetite in a subject desirous or in need of reducing body weight, comprising peripherally administering to said subject an amount of exendin-4 effective to lower a plasma lipid level.

66. The method according to claim 65, wherein said peripheral administration is by injection.

67. The method according to claim 65, wherein said peripheral administration is selected from the group consisting of intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, oral administration, topical administration, transmucosal administration, and pulmonary administration.

68. The method of claim 65, further comprising administering a therapeutically effective amount of one or more compounds selected from the group consisting of an amylin agonist, a leptin, and a cholecystokinin (CCK).