Modification of feeding behavior

• US 8,217,001 B2
• Filed: 08/29/2008
• Issued: 07/10/2012
• Est. Priority Date: 09/24/2001
• Status: Expired due to Fees

• Current Assignee: Imperial Innovations Limited (Imperial College London), Oregon Health & Science University
• Original Assignee: Imperial Innovations Limited (Imperial College London), Oregon Health & Science University
• Inventors: Cowley, Michael, Cone, Roger, Low, Malcolm, Butler, Andrew, Bloom, Stephen Robert, Small, Caroline Jane, Batterham, Rachel Louise, Ghatei, Mohammad Ali
• Primary Examiner(s): Kosson, Rosanne
• Application Number:
  US12/202,197
• Publication Number:
  US 20090209461A1
• Time in Patent Office: 1,411 Days
• Field of Search: 514/5.2, 514/21.3, 530/303, 530/324
• US Class Current: 514/5.2
• 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: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, thereby decreasing the calorie intake of the subject.

Claims

1. A method for decreasing calorie intake, food intake or appetite in a human subject in need thereof, comprising peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, wherein the PYY or agonist thereof is administered at a dose of 1 to 100 nmoles per 70 to 75 kg of body weight of said subject by subcutaneous, intravenous, intramuscular, or intraperitoneal administration.

2. The method of claim 1, wherein the subject is overweight.

3. The method of claim 1, wherein the subject is obese.

4. The method of claim 1, wherein the subject is diabetic.

5. The method of claim 1, wherein peripherally administering PYY or the agonist thereof comprises administering about 45 to about 135 pmol per kilogram body weight of the subject.

6. The method of claim 1, wherein peripherally administering the therapeutically effective amount of PYY or the agonist thereof comprises administration of about 45 to about 135 pmol per kilogram of body weight at least 30 minutes prior to a meal.

7. The method of claim 1, further comprising administering a therapeutically effective amount of amfepramone (diethylpropion), phentermine, mazindol, phenylpropanolamine, fenfluramine, dexfenfluramine, or fluoxetine.

8. The method of claim 1, wherein the PYY or the agonist thereof is administered in an amount sufficient to decrease calorie intake for a period of at least 2 hours.

9. The method of claim 1, wherein the PYY or the agonist thereof is PYY_3-36.

10. The method of claim 9, wherein the PYY_3-36 is administered by a subcutaneous route.

11. The method of claim 1, wherein the PYY agonist comprises a molecule that specifically binds the Y2 receptor.

12. The method of claim 1, wherein the PYY or agonist thereof is administered to the subject at least 30 minutes prior to a meal.

13. The method of claim 1, wherein the PYY or agonist thereof is administered subcutaneously at a dose of 90 nmoles or less per 70 to 75 kg of body weight of said subject.

14. The method of claim 1, wherein the PYY or agonist thereof is administered subcutaneously at a dose from 1 to 90 nmoles per 70 to 75 kg of body weight of said subject.

15. The method of claim 1, wherein the PYY or agonist thereof is administered subcutaneously at a dose from 5 to 80 nmoles per 70 to 75 kg of body weight of said subject.

16. The method of claim 1, wherein the PYY or agonist thereof comprises the amino acid sequence of SEQ ID NO:

334, or a mutant thereof having up to 4 amino acid deletions, insertions or substitutions.

17. The method of claim 16, wherein the PYY_3-36 is modified by amidation, glycosylation, acylation, sulfation, phosphorylation, cyclisation, lipidisation, pegylation or by fusion to another protein or polypeptide.

18. The method of claim 16, further comprising administering an additional appetite suppressant to said subject.

19. The method of claim 1, wherein the peripheral administration comprises administration in a sustained or controlled release preparation or from a pump or implantable drug infusion device.

20. A method for treating obesity in a human subject in need thereof, comprising peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, wherein the PYY or agonist thereof is administered at a dose of 1 to 100 nmoles per 70 to 75 kg of body weight of said subject by subcutaneous, intravenous, intramuscular, or intraperitoneal administration.

21. The method of claim 20, wherein the subject is diabetic.

22. The method of claim 20, wherein peripherally administering PYY or the agonist thereof comprises administering about 45 to about 135 pmol per kilogram body weight of the subject.

23. The method of claim 20, wherein peripherally administering PYY or the agonist thereof comprises administering about 72 pmol per kilogram body weight of the subject.

24. The method of claim 20, wherein peripherally administering the therapeutically effective amount of PYY or the agonist thereof comprises administering PYY or an agonist thereof to the subject in a multitude of doses, wherein each dose in the multitude of doses comprises administration of about 45 to about 135 pmol per kilogram of body weight at least 30 minutes prior to a meal.

25. The method of claim 20, further comprising administering a therapeutically effective amount of amfepramone (diethylpropion), phentermine, mazindol, phenylpropanolamine, fenfluramine, dexfenfluramine, or fluoxetine.

26. The method of claim 20, wherein the PYY or the agonist thereof is administered in an amount sufficient to decrease calorie intake for a period of at least 2 hours.

27. The method of claim 20, wherein the PYY agonist comprises a molecule that specifically binds the Y2 receptor.

28. The method of claim 20, wherein the PYY or the agonist thereof is PYY_3-36.

29. The method of claim 28 wherein the PYY_3-36 is administered by a subcutaneous route.

30. The method of claim 20, wherein the PYY or agonist thereof is administered to the subject at least 30 minutes prior to a meal.

31. The method of claim 20, wherein the PYY or agonist thereof is administered subcutaneously at a dose of 90 nmoles or less per 70 to 75 kg of body weight of said subject.

32. The method of claim 20, wherein the PYY or agonist thereof is administered subcutaneously at a dose from 1 to 90 nmoles per 70 to 75 kg of body weight of said subject.

33. The method of claim 20, wherein the PYY or agonist thereof is administered subcutaneously at a dose from 5 to 80 nmoles per 70 to 75 kg of body weight of said subject.

34. The method of claim 20, wherein the PYY or agonist thereof comprises the amino acid sequence of SEQ ID NO:

334, or a mutant thereof having up to 4 amino acid deletions, insertions or substitutions.

35. The method of claim 34, wherein the PYY_3-36 is modified by amidation, glycosylation, acylation, sulfation, phosphorylation, cyclisation, lipidisation, pegylation or by fusion to another protein or polypeptide.

36. The method of claim 34, further comprising administering an additional appetite suppressant to said subject.

37. The method of claim 20, wherein the peripheral administration comprises administration in a sustained or controlled release preparation or from a pump or implantable drug infusion device.

38. A method for decreasing calorie intake, food intake or appetite in a subject in need thereof, comprising peripherally administering a PYY or an agonist thereof to the subject at a dose of 1 to 100 nmoles per 70 to 75 kg of body weight of said subject by subcutaneous, intravenous, intramuscular, or intraperitoneal administration.