Compounds and their effects on feeding behaviour

• US 8,101,576 B2
• Filed: 12/13/2007
• Issued: 01/24/2012
• Est. Priority Date: 12/13/2006
• Status: Expired due to Fees

• Current Assignee: Imperial Innovations Limited (Imperial College London)
• Original Assignee: Imperial Innovations Limited (Imperial College London)
• Inventors: Bloom, Stephen Robert
• Primary Examiner(s): Tsang, Cecilia J
• Assistant Examiner(s): GUDIBANDE, SATYANARAYAN R
• Application Number:
  US11/956,266
• Publication Number:
  US 20090181885A1
• Time in Patent Office: 1,503 Days
• Field of Search: None
• US Class Current: 514/21.3
• 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 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• 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: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• 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
• CPC Class Codes: A61Q 19/06 for countering cellulitis
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 14/5759 Products of obesity genes, e.g. leptin, obese (OB), tub, fat
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

The invention features peptides for the treatment or prevention of obesity, diabetes or co-morbidities of obesity; for reduction of appetite, food intake, calorie intake, body weight, or body weight gain; and for increase of energy expenditure in a subject.

Claims

1. A peptide comprising the amino acid sequence:

2. The peptide as claimed in claim 1, wherein

Xaa15 Xaa16 Xaa17 Xaa18 Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 is selected from the group consisting of:

3. The peptide as claimed in claim 1, wherein Xaa1 Xaa2 Xaa3 is selected from the group consisting of His1 Ser2 Gln3, D-His1 Ser2 Gln3, D-His1 Ala2 Gln3, and D-His1 Ala2 Asp3.

4. The peptide as claimed in claim 1, wherein Xaa27 Xaa28 Xaa29 Xaa30 Xaa31 Xaa32 is selected from the group consisting of Lys27 Asn28 Ala29 Gly30 Pro31 Ser32 (SEQ ID NO:

380), and Lys27 Asn28 Gly29 Gly30 Pro31 Ser32 (SEQ ID NO;

381).

5. The peptide as claimed in claim 1 having an amino acid sequence selected from the group consisting of:

6. The peptide as claimed in claim 1, wherein the peptide is a peptide conjugate comprising an additional extension moiety of sequence -A-B-C, wherein:

A is absent or 1, 2, 3 or 4 Ala residues or 1, 2, 3 or 4 Glu residues

B is absent or 1, 2, 3 or 4 Ala residues or 1, 2, 3 or 4 Glu residues

provided that A and B do not both comprise Ala residues, and that A and B do not both comprise Glu residues; and

C is Lys, or Lys with an acid selected from capric acid, lauric acid, myristic acid, palmitic acid, stearic acid and arachidic acid, attached via its —

COOH group to the —

NH₂ group of the Lys side chain by means of a peptide bond.

7. The peptide conjugate as claimed in claim 6, wherein A or B or both A and B are absent.

8. The peptide conjugate as claimed in claim 6, wherein A is one Glu residue, and B is one Ala residue.

9. The peptide conjugate as claimed in claim 6, wherein C is a Lys residue.

10. The peptide conjugate as claimed in claim 6, wherein:

C is a Lys residue with lauric acid attached via its —

COOH group to the —

NH2 group of the Lys side chain by means of a peptide bond,

C is a Lys residue with myristic acid attached via its —

COOH group to the —

NH2 group of the Lys side chain by means of a peptide bond,

C is a Lys residue with palmitic acid attached via its —

COOH group to the —

NH2 group of the Lys side chain by means of a peptide bond,

C is a Lys residue with stearic acid attached via its —

COOH group to the —

NH2 group of the Lys side chain by means of a peptide bond,

C is a Lys residue with arachidic acid attached via its —

COOH group to the —

NH2 group of the Lys side chain by means of a peptide bond,

C is a Lys residue with capric acid attached via its —

COOH group to the —

NH2 group of the Lys side chain by means of a peptide bond.

11. The peptide conjugate according to claim 6 having a structure sequence selected from the group consisting of:

12. The peptide according to claim 1 having a structure sequence selected from the group consisting of:

13. The peptide according to claim 1 having a structure sequence selected from the group comprising:

14. A pharmaceutical composition comprising a peptide as claimed in claim 1 and one or more pharmaceutically acceptable carriers.

15. The pharmaceutical composition as claimed in claim 14 which is for peripheral administration.

16. The pharmaceutical composition as claimed in claim 14 which is for administration subcutaneously, intravenously, intramuscularly, intranasally, transdermally, transmucosally, orally, bucally, sublingually or via the lungs.

17. A method of treating obesity in a subject in need thereof comprising administering to the subject a peptide according to claim 1.

18. A method of reducing appetite in a subject in need thereof comprising administering to the subject a peptide according to claim 1.

19. The method as claimed in claim 18, wherein the subject is overweight.

20. The method as claimed in claim 18, wherein the subject is obese.

21. The method as claimed in claim 18, wherein the subject is diabetic.

22. The method of claim 17, wherein the peptide is administered peripherally.

23. The method of claim 17, wherein the peptide is administered subcutaneously, intravenously, intramuscularly, intranasally, transdermally, transmucosally, orally, bucally, sublingually or via the lungs.

24. The method of any one of claims 20 to 21, wherein the peptide is administered peripherally.

25. The method of any one of claims 20 to 21, wherein the peptide is administered subcutaneously, intravenously, intramuscularly, intranasally, transdermally, transmucosally, orally, bucally, sublingually or via the lungs.

26. The peptide of claim 1, further comprising a fusion partner.

27. The peptide of claim 26, wherein the fusion partner is an antibody or fragment thereof.

28. A pharmaceutical composition comprising a peptide as claimed in claim 5 and one or more pharmaceutically acceptable carriers.

29. A method of treating obesity or reducing appetite in a subject in need thereof, comprising administering to the subject a peptide according to claim 5.

30. The method of claim 29, wherein the subject is overweight.

31. The method of claim 29, wherein the subject is obese.

32. The method of claim 29, wherein the subject is diabetic.

33. The method of claim 29, wherein the peptide is administered peripherally.

34. The peptide as claimed in claim 1 having an amino acid sequence selected from the group consisting of:

35. The peptide of claim 34, wherein the peptide comprises a fusion partner, which is an antibody or fragment thereof.

36. A pharmaceutical composition comprising a peptide as claimed in claim 34 and one or more pharmaceutically acceptable carriers.

37. A method of treating obesity or reducing appetite in a subject in need thereof, comprising administering to the subject a peptide according to claim 34.

38. The method of claim 37, wherein the subject is overweight.

39. The method of claim 37, wherein the subject is obese.

40. The method of claim 37, wherein the subject is diabetic.

41. The method of claim 37, wherein the peptide is administered peripherally.