Amylin and calcitonin receptor agonist

Patent metadata

Field	Value
Publication number	US-10174082-B2
Application number	US-201715417671-A
Country	US
Kind code	B2
Filing date	Jan 27, 2017
Priority date	Sep 4, 2014
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

The present invention relates to peptides comprising an amino acid sequence SEQ ID NO: 1 (EASELSTAALGRLSAELHELATLPRTETGPESP), analogs and derivatives thereof and pharmaceutical compositions comprising such peptides and derivatives. This invention further regards the use of these peptides according to SEQ ID NO: 1, analogs and derivatives thereof as medicaments.

First claim

The invention claimed is:

1. A mimylin peptide comprising a sequence which is at least 66% identical to EASELSTAALGRLSAELHELATLPRTETGPESP (SEQ ID NO: 1) and does not comprise any N.

2. The mimylin peptide according to claim 1 , wherein said mimylin peptide comprises up to 11 of the following amino acids or modifications relative to SEQ ID NO: 1:
a. E or no amino acid in position −1,
b. E, A or no amino acid in position 1,
c. A, L or P in position 2,
d. S or P in position 3,
e. E, P, K, Q or G in position 4,
f. L, V, I or H in position 5,
g. S, T or H in position 6,
h. T in position 7,
i. L or A in position 8,
j. A, V, I, S or Tin position 9,
k. L, A, I, H or V in position 10,
l. G in position 11,
m. R, H or K in position 12,
n. L in position 13,
o. S, T or E in position 14,
p. A, Q, E, e or T in position 15,
q. E, R, K or Q in position 16,
r. L or I in position 17,
s. H or A in position 18,
t. E, R or K in position 19,
u. L, I or V in position 20,
v. A, Q, S, E or T in position 21,
w. T in position 22,
x. L or Y in position 23,
y. P in position 24,
z. R, P, H or K in position 25,
aa. T in position 26,
bb. E, Q, G or K in position 27,
cc. T or P in position 28,
dd. G in position 29,
ee. P, S or T in position 30,
ff. E, Q, G, A, P or K in position 31,
gg. T, S, H, P or A in position 32,
hh. P, Y, H, F, L, S, G or A in position 33,
ii. G or K in position 34 or no amino acid.

3. The mimylin peptide according to claim 1 , wherein said mimylin peptide comprises up to 11 of the following amino acids or modifications relative to SEQ ID NO: 1:
a. E or no amino acid in position −1,
b. E in position 1,
c. A, L or P in position 2,
d. S or P in position 3,
e. E, P, K, Q or G in position 4,
f. L, V, I or H in position 5,
g. S in position 6,
h. T in position 7,
i. A in position 8,
j. A, V, or I in position 9,
k. L, or I in position 10,
l. G in position 11,
m. R, H or K in position 12,
n. L in position 13,
o. S, T or E in position 14,
p. A in position 15,
q. E in position 16,
r. L or I in position 17,
s. H or A in position 18,
t. E in position 19,
u. L in position 20,
v. A in position 21,
w. T in position 22,
x. L or Y in position 23,
y. P in position 24,
z. R in position 25,
aa. T in position 26,
bb. E in position 27,
cc. T or P in position 28,
dd. G in position 29,
ee. P, S or T in position 30,
ff. E or G in position 31,
gg. S or T in position 32,
hh. P or Y in position 33,
ii. G or K in position 34 or no amino acid.

4. The mimylin peptide according to claim 1 , wherein position 30 is S and position 31 is G, wherein the amino acid numbering corresponds to SEQ ID NO: 1.

5. The mimylin peptide according to claim 1 , wherein position 9 is V and/or position 1 is E, wherein the amino acid numbering corresponds to SEQ ID NO: 1.

6. The mimylin peptide according to claim 1 , wherein position 33 is P, wherein the amino acid numbering corresponds to SEQ ID NO: 1.

7. The mimylin peptide according to claim 1 , wherein said peptide has a c-terminal amide.

8. The mimyin peptide according to claim 1 , wherein said mimylin peptide is derivatised in the N-terminal amino acid or any K within said mimylin peptide sequence.

9. The mimylin peptide according to claim 1 , wherein said mimylin peptide does not comprise a disulfide bridge between the amino acids in positions 2 and 8, wherein the amino acid numbering corresponds to SEQ ID NO: 1.

10. A mimylin derivative, wherein a mimylin peptide according to claim 1 is derivatised with a side chain comprising a protracting moiety and a linker.

11. The mimylin derivative according to claim 10 , wherein said protracting moiety is a fatty acid or diacid.

12. The mimylin derivative according to claim 10 , which is an agonist of the amylin and calcitonin receptor.

13. A method of treating overweight comprising administering a mimylin peptide according to claim 1 to a subject in need thereof.

14. A method of treating overweight comprising administering a mimylin derivative according to claim 10 to a subject in need thereof.

15. A method of reducing food intake comprising administering a mimylin peptide according to claim 1 to a subject in need thereof.

16. A method of reducing food intake comprising administering a mimylin derivative according to claim 10 to a subject in need thereof.

17. An aqueous pharmaceutical formulation comprising a mimylin derivative according to claim 10 and a pharmaceutically acceptable ingredient.

18. The aqueous pharmaceutical formulation according to claim 17 , wherein said pharmaceutically acceptable ingredient is selected from the group consisting of glycerol, phosphate, propylene glycol, phenol, m-cresol, or a combination of phenol and m-cresol.

19. An aqueous pharmaceutical formulation comprising a mimylin derivative of claim 10 in a concentration of from about 0.001 mM to about 15 mM, phosphate in a range of between about 4 mM to about 12 mM, propylene glycol from about 1 mg/ml to about 30 mg/ml, m-cresol from about 5 mM to about 40 mM, phenol from about 5 mM to about 90 mM, and glycerol from about 1 mg/ml to about 30 mg/ml.

20. An aqueous pharmaceutical formulation comprising a mimylin derivative of claim 10 , 8 mM phosphate, 14 mg/ml propylene glycol, and 58 mM phenol, wherein said mimylin derivative is in a concentration selected from the group consisting of from 0.005 mM to 2 mM, from 0.01 to 0.5 mM, and from 0.0027 mM to 2.7 mM.

21. A mimylin derivative, wherein a mimylin peptide according to claim 1 is derivatised with a side chain comprising a protracting moiety.

22. The mimylin derivative according to claim 21 , wherein said protracting moiety is a fatty acid or diacid.

23. The mimylin derivative according to claim 21 , wherein said protracting moiety is a fatty acid or diacid comprising between 14 and 20 carbon atoms.

24. The mimylin derivative according to claim 21 , which is an agonist of the amylin and calcitonin receptor.

25. A method of treating overweight comprising administering a mimylin derivative according to claim 21 to a subject in need thereof.

26. A method of reducing food intake comprising administering a mimylin peptide according to claim 21 to a subject in need thereof.

27. An aqueous pharmaceutical formulation comprising a mimylin derivative according to claim 21 and a pharmaceutically acceptable ingredient.

28. The aqueous pharmaceutical formulation according to claim 27 , wherein said pharmaceutically acceptable ingredient is selected from the group consisting of glycerol, phosphate, propylene glycol, phenol, m-cresol, or a combination of phenol and m-cresol.

29. An aqueous pharmaceutical formulation comprising a mimylin derivative of claim 21 in a concentration of from about 0.001 mM to about 15 mM, phosphate in a range of between about 4 mM to about 12 mM, propylene glycol from about 1 mg/ml to about 30 mg/ml, m-cresol from about 5 mM to about 40 mM, phenol from about 5 mM to about 90 mM, and glycerol from about 1 mg/ml to about 30 mg/ml.

30. An aqueous pharmaceutical formulation comprising a mimylin derivative of claim 21 , 8 mM phosphate, 14 mg/ml propylene glycol, and 58 mM phenol, wherein said mimylin derivative is in a concentration selected from the group consisting of from 0.05 mM to 2 mM, from 0.01 to 0.5 mM,

Assignees

• Novo Nordisk As

Inventors

• Kruse Thomas
• Schaeffer Lauge
• Dahl Kirsten
• Poulsen Christian
• Raun Kirsten

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07K14/001 Primary

  by chemical synthesis · CPC title