Modification of feeding behavior

• US 20050176630A1
• Filed: 09/24/2002
• Published: 08/11/2005
• Est. Priority Date: 09/24/2001
• Status: Active Grant

• Current Assignee: Imperial Innovations Limited (Imperial College London), Oregon Health & Science University
• Original Assignee: Imperial Innovations Limited (Imperial College London)
• Inventors: Cowley, Michael, Low, Malcolm, Small, Caroline Jane, Butler, Andrew, Bloom, Stephen Robert, Cone, Roger, Batterham, Rachel Louise, Ghatel, Mohammad Ali
• Granted Patent: US 7,459,432 B2
• Time in Patent Office: Days
• US Class Current: 514/4.900
• 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, or increasing energy expenditure in a subject, comprising peripherally administering a to said subject an amount of PYY effective to achieve physiological levels of PYY_3-36 observed tpostprandially or an amount of a PYY agonist effective to mimic physiological levels of PYY_3-36 observed postprandially, thereby decreasing the calorie intake, food intake or appetite, or increasing energy expenditure in said subject.

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

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

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

5. The method of claim 1, wherein peripherally administering PYY or said agonist thereof comprises subcutaneous, intravenous, intramuscular, intranasal, transdermal, intracistemal, intravaginal, intraperitoneal, oral, topical, transmucosal, buccal, rectal or sublingual administration or pulmonary inhalation.

6. The method of claim 25, wherein peripherally administering PYY or said agonist thereof comprises administering about 45 to about 135 pmol of said PYY or agonist thereof per kilogram body weight of said subject.

7. The method of claim 6, wherein peripherally administering PYY or said agonist thereof comprises administering about 72 pmol of said PYY or agonist thereof per kilogram body weight of said subject.

8. The method of claim 1, wherein peripherally administering PYY or said agonist thereof comprises administering said PYY or agonist thereof to said subject at least 30 minutes prior to a meal.

9. The method of claim 28, wherein peripherally administering of PYY or said agonist thereof comprises administering said PYY or agonist thereof to said subject in a multitude of doses, wherein each dose in the multitude of doses comprises administration of about 0.5 to about 135 pmol of said PYY or agonist thereof per kilogram of body weight of said subject at least about 30 minutes prior to a meal.

10. The method of claim 35, further comprising administering a therapeutically effective amount of amfepramone (diethylpropion), phentermine, mazindol, phenylpropanolamine, fenfluramine, dexfenfluramine, or fluoxetine to said subject.

11. The method of claim 1, wherein said PYY or agonist thereof is administered to said subject in an amount effective to decrease calorie intake for a period of at least about 2 hours.

12. The method of claim 11, wherein said PYY or agonist thereof is administered to said subject in an amount effective to decrease calorie intake for a period of about 2 to 24 hours.

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

14. The method of claim 34, wherein said PYY agonist comprises a molecule that specifically binds the Y2 receptor.

15. The method of claim 14, wherein said PYY agonist increases the expression of c-fos in a section of an arcuate nucleus contacted with said PYY agonist.

16. The method of claim 34, wherein said PYY agonist specifically binds to a neuropeptide Y neuron and inhibits an activity of a neuropeptide Y neuron.

17. The method of claim 16, wherein said PYY agonist decreases the action potential firing rate of said neuropeptide Y neuron.

18. The method of claim 16, wherein said neuropeptide Y neuron synapses with a proopiomelanocortin neuron, and wherein binding of said PYY agonist to said neuropeptide Y neuron results in an increased activity of said proopiomelanocortin neuron.

19. The method of claim 18, wherein the decreased activity of said neuropeptide Y neuron results in an increase in action potential firing on said proopiomelanocortin neuron.

20. The method of claim 1, wherein appetite is decreased in said subject.

21. The method of claim 20, wherein food intake is decreased in said subject.

22. The method of claim 21, wherein calorie intake is decreased in said subject.

23. The method of claim 1, wherein said method prevents or reduces weight gain in said subject.

24. The method of claim 1 wherein said method induces or promotes weight loss in said subject.

25. The method of claim 1, wherein peripherally administering PYY or said agonist thereof comprises administering about 0.5 to about 135 pmol of said PYY or agonist thereof per kilogram body weight of said subject.

26. The method of claim 1, wherein said method induces or increases satiety and sensations of satiety in said subject.

27. The method of claim 1, wherein said method reduces hunger and sensations of hunger in said subject.

28. The method of claim 1, wherein peripherally administering PYY or said agonist thereof comprises administering said PYY or agonist thereof to said subject in multiple or divided doses.

29. The method of claim 1, wherein peripherally administering PYY or said agonist thereof comprises peripherally injecting said PYY or agonist thereof to said subject in a pulse dose.

30. The method of claim 1, wherein peripherally administering PYY or said agonist thereof comprises administering said PYY or agonist thereof to said subject in a slow, sustained or controlled release preparation or from a pump or implantable drug infusion device.

31. The method of claim 1 wherein peripherally administering PYY or said agonist thereof comprises administering a dose of about 5 to about 50 nmol of said PYY or agonist thereof.

32. The method of claim 31, wherein peripherally administering PYY or said agonist thereof comprises administering a dose of about 2 to about 20 nmol of said PYY or agonist thereof.

34. The method of claim 1, wherein a PYY agonist is peripherally administered to said subject.

35. The method of claim 1, further comprising administering a therapeutically effective amount of an additional appetite suppressant to said subject.

36. The method of claim 1, further comprising administering a food intake-reducing agent, plasma glucose-lowering agent or plasma lipid-altering agent to said subject.

37. The method of claim 1, wherein said method maintains a desired body weight or a desired Body Mass Index in said subject.

38. The method of claim 1, wherein said subject has, or is at risk of having, a disorder wherein obesity or being overweight is a risk factor for the disorder.

39. The method of claim 1, wherein said subject has a disorder caused or aggravated by a relatively high nutrient availability.

100. The method of claim 1, wherein said physiological levels of PYY_3-36 observed postprandially are about 40 to 60 pM.

101. The method of claim 100, wherein said physiological levels of PYY_3-36observed postprandially are from about 40 pM to about 50 pM.

102. The method of claim 1, wherein PYY_3-36 is peripherally administered to said subject.

33. The method of claim 33, wherein peripherally administering PYY or said agonist thereof comprises administering a dose of about 10 nmol of said PYY or agonist thereof.

47. A method for decreasing calorie intake, food intake or appetite, or increasing energy expenditure in a subject, comprising peripherally administering to said subject an amount of PYY effective to achieve physiological levels of PYY_3-36 or an amount of a PYY agonist effective to mimic physiological levels of PYY_3-36 thereby decreasing the calorie intake, food intake or appetite, or increasing energy expenditure in said subject.

48-99. -99. (canceled)

103. A method for decreasing calorie intake, food intake or appetite in a subject, comprising peripherally administering to said subject an amount of PYY effective to achieve physiological levels of PYY_3-36 observed postprandially thereby decreasing the calorie intake, food intake or appetite in said subject.

40. The method of claim 103, wherein PYY_3-36 is peripherally administered to said subject.

41. The method of claim 103, wherein peripherally administering said PYY comprises administering about 0.5 to about 135 pmol PYY per kilogram body weight of said subject

42. The method of claim 41, wherein peripherally administering said PYY comprises administering about 45 to about 135 pmol PYY per kilogram body weight of said subject.

43. The method of claim 42, wherein peripherally administering said PYY comprises administering about 72 pmol PYY per kilogram body weight of said subject.

45. The method of claim 4346, wherein peripherally administering said PYY_3-36 comprises administering about 72 pmol of said PYY_3-36 per kilogram body weight of said subject.

104. A method for decreasing calorie intake, food intake or appetite in a subject, comprising peripherally administering to said subject an amount of PYY_3-36 effective to achieve physiological levels of PYY_3-36 observed postprandially, thereby decreasing the calorie intake, food intake or appetite in said subject.

44. The method of claim 104, wherein peripherally administering said PYY_3-36 comprises administering about 0.5 to about 135 pmol of said PYY_3-36 per kilogram body weight of said subject.

46. The method of claim 44, wherein peripherally administering said PYY_3-36 comprises administering about 45 to about 135 pmol of said PYY_3-36 per kilogram body weight of said subject.