Modification of feeding behavior using PYY and GLP-1

• US 8,058,233 B2
• Filed: 01/10/2003
• Issued: 11/15/2011
• Est. Priority Date: 06/28/2002
• 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 James Duncan, Butler, Andrew, Bloom, Stephen Robert, Small, Caroline Jane, Batterham, Rachel Louise, Ghatei, Mohammad Ali
• Primary Examiner(s): DESAI, ANAND U
• Application Number:
  US10/501,411
• Publication Number:
  US 20060014678A1
• Time in Patent Office: 3,231 Days
• Field of Search: None
• US Class Current: 514/2
• 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 38/1709 from mammals
• 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 38/2271 Neuropeptide Y
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering PYY or an agonist thereof and GLP-1 or an agonist thereof to the subject, simultaneously or sequentially, 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, which comprises peripherally administering prior to a meal to said subject PYY_3-36 (peptide YY amino acids 3 to 36) from 5 to 100 nmoles per 70 to 75 kilogram body weight of the subject and a therapeutically effective amount of GLP-1 (glucagon-like peptide 1) or an agonist thereof.

2. A method as claimed in claim 1, wherein the PYY_3-36 and the GLP-1 or agonist thereof are administered to said subject sequentially.

3. A method as claimed in claim 2, wherein the PYY_3-36 and the GLP-1 or agonist thereof are administered to said subject via different routes.

4. A method as claimed in claim 1, wherein the subject is overweight.

5. A method as claimed in claim 1, wherein the subject is obese.

6. A method as claimed in claim 1, wherein the subject is diabetic.

7. A method as claimed in claim 1, wherein the peripheral administration is subcutaneous, intravenous, intramuscular, intranasal, transdermal, intraperitoneal, oral, topical, transmucosal, or sublingual administration or pulmonary inhalation.

10. A method as claimed in claim 1, wherein the PYY_3-36 or the GLP-1 or agonist thereof is peripherally administered to the subject at least 30 minutes prior to a meal.

11. A method as claimed in claim 1, wherein the GLP-1 agonist is exendin-4 or a derivative thereof that is a GLP-1 agonist.

12. A method as claimed in claim 1, further comprising administering a therapeutically effective amount of amfepramone (diethylpropion), phentermine, mazindol, phenylpropanolamine, fenfluramine, dexfenfluramine, or fluoxetine to said subject.

13. A method as claimed in claim 1, wherein the PYY_3-36 and the GLP-1 or agonist thereof are administered to said subject simultaneously.

14. A method as claimed in claim 1, which comprises administering PYY_3-36 to the subject subcutaneously at a dose of 10 nmoles, 20 nmoles, 30 nmoles or 40 nmoles per 70 to 75 kilograms body weight of the subject.

15. A method as claimed in claim 1, which comprises administering PYY_3-36 to the subject subcutaneously at a dose of 20 to 60 nmoles per 70 to 75 kilogram body weight of the subject.

16. A method as claimed in claim 1, which comprises administering PYY_3-36 to the subject subcutaneously at a dose of 35 to 45 nmoles per 70 to 75 kilogram body weight of the subject.

17. A method as claimed in claim 7, wherein the peripheral administration is subcutaneous administration.

18. The method as claimed in claim 1, wherein the peripheral administration is peripheral injection in a pulse dose.

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

20. A method as claimed in claim 1, wherein the PYY_3-36 is peripherally administered to the subject at least 30 minutes prior to a meal.

21. A method as claimed in claim 1, wherein the PYY_3-36 is modified by amidation, glycosylation, acylation, sulfation, phosphylation, cyclization, lipidization or pegylation.

22. A method as claimed in claim 1, wherein 0.1 to 3.2 nmoles of the GLP-1 or agonist thereof per kilogram body weight of the subject is peripherally administered.

24. The methods of claim 1, 8 or 23, wherein PYY_3-36 comprises peptide YY amino acids 3 to 36 of SEQ ID NOs:

1, 5-12, 189 or 190, or a single point mutation or a double point mutation thereof.

25. A method as claimed in claim 1, wherein the peripheral administration is intravenous administration.

26. The method of claim 1, wherein the peripheral administration is subcutaneous administration.

27. The method of claim 1, wherein the peripheral administration is oral administration.

28. The method of claim 1, wherein the peripheral administration is by pulmonary inhalation.

8. A method for decreasing calorie intake, food intake or appetite in a human subject in need thereof, which comprises peripherally administering prior to a meal to said subject PYY_3-36 (peptide YY amino acids 3 to 36) from 45 to 135 pmoles per kilogram body weight of the subject and a therapeutically effective amount of GLP-1 (glucagon-like peptide 1) or an agonist thereof.

9. A method as claimed in claim 8, wherein about 72 pmoles of PYY_3-36 per kilogram body weight of the subject are peripherally administered.

23. A method for treating obesity in a human subject in need of treatment, which comprises peripherally administering prior to a meal to said subject PYY_3-36 (peptide YY amino acids 3 to 36) from 5 to 100 nmoles per 70 to 75 kilogram body weight of the subject and a therapeutically effective amount of GLP-1 (glucagon-like peptide 1) or an agonist thereof.