IP Library › Granted Patent US 8,916,681

Granted Patent B2

US 8,916,681 · App. 12/681,857 · Granted Dec 23, 2014

Compound, use and method

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 8,916,681
App. No.: 12/681,857
Granted: Dec 23, 2014
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention relates to the use of an antagonist of kisspeptin in the manufacture of a medicament for the treatment of a condition induced and/or worsened by kisspeptin activity in an individual. The invention also provides certain defined peptide molecules, which may act as an antagonist of kisspeptin, which are of use in treating a condition induced and/or worsened by kisspeptin activity in an individual. In addition, the invention provides methods of identifying and/or using antagonists of kisspeptin and/or the defined peptides, and pharmaceutical compositions thereof.

Claims (131)

1. A peptide molecule comprising the sequence:

X 1 -G/W- X 2 -R/(D)R- X 3

(SEQ ID NO: 3)

wherein:

X 1 is F or A or any D-amino-acid residue;

X 2 is L or A or any D-amino-acid residue;

X 3 is F or W;

wherein the C-terminal amino acid residue of the peptide molecule contains group z which removes the charge on that residue; and,

wherein the peptide molecule further comprises the sequence: R-R-M-K-W-K-K-Y (SEQ ID NO: 20) at the N-terminus;

and further wherein the peptide sequence is not:

F-G-L-R-F;

(SEQ ID NO: 4)

F-G-L-R-W;

(SEQ ID NO: 5)

F-G-(D)F-R-F;

(SEQ ID NO: 6)

F-G-A-R-W;

(SEQ ID NO: 7)

F-G-L-(D)R-W;

(SEQ ID NO: 8)

F-G-(D)L-R-W;

(SEQ ID NO: 9)

A-G-L-R-W;

(SEQ ID NO: 17)

(D)F-G-L-R-W

(SEQ ID NO: 10).

2. The peptide molecule according to claim 1 , wherein X 1 is (D)F.

3. The peptide molecule according to claim 1 , wherein X 2 is a D-amino-acid residue selected from the group consisting of: (D)F, (D)L and (D)W.

4. The peptide molecule according to claim 1 , wherein the peptide sequence is selected from the group consisting of:

(D)F-W-L-R-W;

(SEQ ID NO: 11)

and

F-G-(D)W-R-F

(SEQ ID NO: 12).

5. The peptide molecule according to claim 1 , wherein the N-terminal residue contains group y which removes the charge on that residue.

6. The peptide molecule of claim 1 , wherein z is NH 2 or N-propylamide or N-ethylamide (NHEt) or N-methylamide or N-butylamide.

7. A pharmaceutical composition comprising an effective amount of a peptide molecule according to claim 1 , and a pharmaceutically-acceptable excipient or diluent.

8. A peptide molecule comprising the sequence:

X A - X B - X C -N- X D - X E -G- X F -R-F

(SEQ ID NO: 29)

wherein:

X A is Y or any D-amino-acid residue;

X B is N or any D-amino acid residue;

X C is W or any D-amino acid residue;

X D is G or S or any D-amino acid residue;

X E is F or (D)W or (D)L;

X F is W or L or any D-amino acid residue;

wherein the C-terminal amino acid residue of the peptide molecule contains group z which removes the charge on that residue; and

wherein the peptide molecule further comprises the sequence: R-R-M-K-W-K-K-Y (SEQ ID NO: 20) at the N-terminus;

and further wherein the peptide sequence is not:

Y-N-W-N-S-F-G-L-R-F;

(SEQ ID NO: 30)

(D)Y-(D)N-W-N-S-F-G-W-R-F;

(SEQ ID NO: 31)

(D)Y-(D)N-W-N-G-F-G-W-R-F;

(SEQ ID NO: 32)

(D)Y-(D)N-W-N-S-F-G-(D)W-R-F;

(SEQ ID NO: 33)

(D)Y-(D)N-W-N-G-F-G-(D)W-R-F

(SEQ ID NO: 34).

9. The peptide molecule according to claim 8 , wherein X A is a D-amino-acid residue selected from the group consisting of: (D)F and (D)Y and (D)A.

10. The peptide molecule according to claim 8 , wherein X B is a D-amino-acid residue selected from the group consisting of: (D)A and (D)N.

11. The peptide molecule according to claim 8 , wherein when one of X A or X B is (D)Y, the other is not (D)N.

12. The peptide molecule according to claim 8 , wherein X A and X B are not both a D-amino acid residue.

13. The peptide molecule according to claim 8 , wherein when X F is (D)W, X A is (D)F.

14. The peptide molecule according to claim 8 , wherein X C is a D-amino-acid residue selected from the group consisting of: (D)A and (D)W.

15. The peptide molecule according to claim 8 , wherein X D is a D-amino-acid residue selected from the group consisting of: (D)A and (D)W.

16. The peptide molecule according to claim 8 , wherein when X D is S, X F is (D)W and/or X A is not (D)Y.

17. The peptide molecule according to claim 8 , wherein when X D is S, X F is (D)W and/or X A is (D)A.

18. The peptide molecule according to claim 8 , wherein X F is a D-amino-acid residue selected from the group consisting of: (D)L and (D)W.

19. The peptide molecule according to claim 8 , wherein when X E and X F are both (D)W, X A is not (D)Y.

20. The peptide molecule according to claim 8 , wherein when X E and X F are both (D)W, X A is (D)A.

21. The peptide molecule according to claim 8 , wherein the N-terminal residue contains group y which removes the charge on that residue.

22. The peptide molecule according to claim 8 , wherein the peptide sequence is selected from the group consisting of:

a) Y-N-W-N-G-F-G-L-R-F. z ;

(SEQ ID NO: 35)

b) Y-N-W-N-G-F-G-(D)L-R-F. z ;

(SEQ ID NO: 36)

c) Y-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 37)

and,

d) Y-N-W-N-G-(D)W-G-L-R-F. z

(SEQ ID NO: 38).

23. The peptide molecule of claim 8 , wherein z is NH 2 or N-propylamide or N-ethylamide (NHEt) or N-methylamide or N-butylamide.

24. A pharmaceutical composition comprising an effective amount of a peptide molecule according claim 8 , and a pharmaceutically-acceptable excipient or diluent.

25. The peptide molecule wherein the peptide sequence is selected from the group consisting of:

(SEQ ID NO: 35)

a) Y-N-W-N-G-F-G-L-R-F. z ;

(SEQ ID NO: 36)

b) Y-N-W-N-G-F-G-(D)L-R-F. z ;

(SEQ ID NO: 37)

c) Y-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 38)

d) Y-N-W-N-G-(D)W-G-L-R-F. z ;

(SEQ ID NO: 39)

e) ac.Y-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 40)

f) ac.Y-N-W-N-(D)W-F-G-(D)W-R-F. z ;

(SEQ ID NO: 41)

g) ac.(D)Y-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 42)

h) ac.Y-N-(D)W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 43)

i) ac.Y-(D)N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 44)

j) ac.Y-N-W-N-(D)A-F-G-(D)W-R-F. z ;

(SEQ ID NO: 45)

k) ac.(D)A-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 46)

l) ac.Y-N-(D)A-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 47)

m) ac.Y-(D)A-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 48)

n) ac.(D)W-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 49)

o) ac.(D)F-N-W-N-G-F-G-(D)W-R-F. z ;

(SEQ ID NO: 50)

p) ac.(D)Y-N-W-N-G-(D)W-G-(D)W-R-F. z ;

(SEQ ID NO: 51)

q) ac.(D)A-N-W-N-G-(D)W-G-(D)W-R-F. z ;

(SEQ ID NO: 52)

r) ac.(D)A-N-W-N-S-F-G-(D)W-R-F. z ;

(SEQ ID NO: 53)

s) ac.(D)A-N-W-N-G-F-G-W-R-F. z ;

(SEQ ID NO: 54)

t) ac.(D)A-N-W-N-(D)S-F-G-(D)W-R-F. z ;

and

(SEQ ID NO: 55)

u) ac.(D)A-N-W-N-G-F-G-(D)L-R-F. z .

Assignments (2)

CHANGE OF ADDRESS Recorded Mar 21, 2011

From: MEDICAL RESEARCH COUNCIL

To: MEDICAL RESEARCH COUNCIL

Reel/Frame 025990/0240 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2010

From: MILLAR, ROBERT PETER; ROSEWEIR, ANTONIA KATHRYN

To: MEDICAL RESEARCH COUNCIL

Reel/Frame 024406/0720 →