NOVEL COMPOUNDS AND THEIR EFFECTS ON FEEDING BEHAVIOUR

• US 20090181885A1
• Filed: 12/13/2007
• Published: 07/16/2009
• Est. Priority Date: 12/13/2006
• Status: Active Grant

• Current Assignee: Imperial Innovations Limited (Imperial College London)
• Original Assignee: Imperial Innovations Limited (Imperial College London)
• Inventors: Bloom, Stephen Robert
• Granted Patent: US 8,101,576 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• 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 provides a peptide comprising the amino acid sequence given below, together with uses of the peptide and methods associated therewith. The peptide finds particular use as an appetite suppressant and in the treatment of obesity.

Xaa1 Xaa2 Xaa3 Gly4 Thr5 Phe6 Thr7 Ser8 Asp9 Tyr10Ser11 Lys12 Tyr13 Leu14 Xaa15 Xaa16 Xaa17 Xaa18Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 Trp25 Leu26Xaa27 Xaa28 Xaa29 Xaa30 Xaa31 Xaa32 Lys33 Asn34Asn35 Ile36 A1a37; wherein:Xaa2 is His1 or D-His1, Xaa2 is Ser2 or Ala2, Xaa3 is Gln3 or Asp3; Xaa15 Xaa16 Xaa17 Xaa18 Xaa19 Xaa20 Xaa21 Xaa22Xaa23 Xaa24 is: Glu15 Glu16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Leu23 Glu24, Glu15 Glu16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Leu23 Gln24, Glu15 Glu16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Ile23 Glu24, Glu15 Glu16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Ile23 Gln24, Glu15 Glu16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Leu23 Glu24, Glu15 Glu16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Leu23 Gln24, Glu15 Glu16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Ile23 Glu24, Glu15 Glu16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Ile23 Gln24, Glu15 Gln16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Leu23 Glu24, Glu15 Gln16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Leu23 Gln24, Glu15 Gln16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Ile23 Glu24, Glu15 Gln16 Glu17 Leu18 Val19 Lys20 Tyr21 Phe22Ile23 Gln24, Glu15 Gln16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Leu23 Glu24, Glu15 Gln16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Leu23 Gln24, Glu15 Gln16 Glu17 Ile18 Val19 Lys20 Tyr21 Phe22Ile23 Glu24, Glu15 Gln16 Glu17 lle18 Val19 Lys20 Tyr21 Phe22Ile23 Gln24,or Asp15 Ser16 Arg17 Arg18 Ala19 Gln20 Asp21 Phe22Val23 Gln24; Xaa27 Xaa28 Xaa29 Xaa30 Xaa31 Xaa32 is: Met27 Asn28 Thr29 Lys30 Arg31 Asn32, Lys27 Asn28 Ala29 Gly30 Pro31 Ser32,or Lys27 Asn28 Gly29 Gly30 Pro31 Ser32
or a peptide as set out above in which residue Asn34 is replaced with Asp34;
or a peptide as set out above in which Xaa3 is Glu3;
with the proviso that if

Xaa15 Xaa16 Xaa17 Xaa18 Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 is Asp15 Ser16 Arg17 Arg18 Ala19 Gln20 Asp21 Phe22 Val23 Gln24, then Xaa27 Xaa28 Xaa29 Xaa30 Xaa31 Xaa32 is not Met27 Asn28 Thr29 Lys30 Arg31 Asn32.

Claims

1. A peptide comprising the amino acid sequence:

2. A 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. A 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. A 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 and (SEQ ID NO:

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

     381).

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

6. A peptide as claimed in claim 1, wherein the peptide has 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 the group consisting of 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. A peptide as claimed in claim 6, wherein A or B or both A and B are absent.

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

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

10. A peptide 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, or

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

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

13. A 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. A pharmaceutical composition as claimed in claim 14 which is for peripheral administration.

16. A 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 or preventing obesity in a subject in need thereof comprising administering to the subject a peptide according to claim 1.

18. A method of treating or preventing diabetes or a co-morbidity of obesity in a subject in need thereof comprising administering to the subject a peptide according to claim 1.

19. A method of reducing appetite in a subject, reducing food intake in a subject or reducing calorie intake in a subject, reducing body weight in a subject, reducing body weight gain in a subject or increasing energy expenditure in a subject in need thereof comprising administering to the subject a peptide according to claim 1.

20. A method of causing weight loss or preventing weight gain for cosmetic purposes comprising administering to the subject a peptide according to claim 1.

21. A method as claimed in claim 19, wherein the subject is overweight.

22. A method as claimed in claim 17, wherein the subject is obese.

23. A method as claimed in claim 18, wherein the subject is diabetic.

24. The method of claim 17, wherein the peptide or pharmaceutical composition is administered peripherally.

25. The method of claim 17, wherein the peptide or pharmaceutical composition is administered subcutaneously, intravenously, intramuscularly, intrasanally, transdermally, transmucosally, orally, bucally, sublingually or via the lungs.

26. A peptide as claimed in any one of claims 22 to 25, wherein the peptide composition is administered peripherally.

27. A peptide as claimed in any one of claims 22 to 26, wherein the peptide is administered subcutaneously, intravenously, intramuscularly, intranasally, transdermally, transmucosally, orally, bucally, sublingually or via the lungs.

28. A method of causing weight loss or preventing weight gain for cosmetic purposes comprising administering to the subject a peptide according to any of claims 1 to 13 or a pharmaceutical composition according to claim 14 to 16.

29. The method of claim 28, wherein the peptide or pharmaceutical composition is administered peripherally.

30. The method of claim 28 or 29, wherein the peptide or pharmaceutical composition is administered subcutaneously, intravenously, intramuscularly, intranasally, transdermally, transmucosally, orally, bucally, sublingually or via the lungs.