Amylin receptor agonists

Patent metadata

Field	Value
Publication number	US-12116388-B2
Application number	US-202318512512-A
Country	US
Kind code	B2
Filing date	Nov 17, 2023
Priority date	Dec 22, 2022
Publication date	Oct 15, 2024
Grant date	Oct 15, 2024

Abstract

The invention relates to a compound comprising an amylin receptor agonist. The invention also relates to a pharmaceutical composition, suitable for but not limited to oral administration, which comprises such a compound. The compound and pharmaceutical composition comprising it may be used for the medical treatment of subjects with overweight, obesity and associated co-morbidities.

First claim

The invention claimed is:

1. An amylin receptor agonist according to Formula I (SEQ ID NO: 36):
AX 2 X 3 LX 5 TX 7 QTX 10 RLAEFLHHX 19 X 20 X 21 X 22 FGX 25 IX 27 X 28 X 29 TX 31 VGX 34 X 35 TX 37 ,
wherein
X 2 is S or G,
X 3 is H, S, Q, or E,
X 5 is S,
X 7 is A,
X 10 is Q or A,
X 19 is S or absent,
X 20 is S or absent,
X 21 is D or absent,
X 22 is N, P or absent,
X 25 is A or P,
X 27 is L or P,
X 28 is S or P,
X 29 is S or P,
X 31 is D,
X 34 is S or P,
X 35 is N, D, or E, and
X 37 is P.

2. The amylin receptor agonist according to claim 1 ,
wherein
X 27 X 28 X 29 is selected from LPP or PSS.

3. The amylin receptor agonist according to claim 2 , comprising a peptide selected from the following:

(SEQ ID NO: 13)

AGELSTAQTARLAEFLHHFGPILPPTDVGSETP,

(SEQ ID NO: 16)

ASQLSTAQTARLAEFLHHSSDNFGPILPPTDVGSNTP,

and

(SEQ ID NO: 19)

ASHLSTAQTARLAEFLHHSSDPFGAIPSSTDVGPDTP,

wherein the peptide comprises a C-terminal amide.

4. The amylin receptor agonist according to claim 1 , further comprising a protraction moiety.

5. The amylin receptor agonist according to claim 4 , wherein the protraction moiety represented by formula (A)-(B) is attached via linker (A) to the alpha position of the A at position 1.

6. The amylin receptor agonist according to claim 5 , wherein the amino acid at position 25 is A or P when the protraction moiety is attached to the A at position 1.

7. The amylin receptor agonist according to claim 5 , wherein protractor (B) of the protraction moiety represented by formula (A)-(B) comprises a C-14 diacid, C-16 diacid, C-18 diacid, or C-20 diacid.

8. The amylin receptor agonist according to claim 5 , wherein the linker (A) of the protraction moiety comprises a moiety according to Chem. 8a:

9. The amylin receptor agonist according to claim 7 , selected from the following:

10. A pharmaceutical composition comprising the amylin receptor agonist according to claim 1 , one or more pharmaceutically acceptable excipients, and/or pharmaceutically acceptable salt, ester, or amide forms thereof.

11. A pharmaceutical composition comprising the amylin receptor agonist peptide according to claim 3 , one or more pharmaceutically acceptable excipients, and/or pharmaceutically acceptable salt, ester, or amide forms thereof.

12. A pharmaceutical composition comprising the amylin receptor agonist according to claim 9 , one or more pharmaceutically acceptable excipients, and/or pharmaceutically acceptable salt, ester, or amide forms thereof.

13. A method of treating diabetes, cardiovascular disease, non-alcoholic steatohepatitis (NASH), cognitive impairment, and/or a Body Mass Index (BMI) of 27 or more, comprising administering to a subject in need of such treatment a pharmaceutically effective amount of the pharmaceutical composition according to claim 10 .

14. A method of treating diabetes, cardiovascular disease, NASH, cognitive impairment, and/or a BMI of 27 or more, comprising administering to a subject in need of such treatment a pharmaceutically effective amount of the pharmaceutical composition according to claim 11 .

15. A method of treating diabetes, cardiovascular disease, NASH, cognitive impairment, and/or a BMI of 27 or more, comprising administering to a subject in need of such treatment a pharmaceutically effective amount of the pharmaceutical composition according to claim 12 .

Assignees

• Novo Nordisk As

Inventors

• Joergensen Cecilie Mia
• Kruse Thomas
• Lau Jesper F

Classifications

• A61K38/00

  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 title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07K14/72

  for hormones {(for neuromediators C07K14/70571)} · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07K14/4705 Primary

  stimulating, promoting or activating activity · CPC title