OPIOID AGONIST PEPTIDES AND USES THEREOF

• US 20190076400A1
• Filed: 09/11/2018
• Published: 03/14/2019
• Est. Priority Date: 09/11/2017
• Status: Active Grant

• Current Assignee: Protagonist Therapeutics, Inc.
• Original Assignee: Protagonist Therapeutics, Inc.
• Inventors: Anandan, Sampath Kumar, Zhang, Jie, Bhandari, Ashok, Bourne, Gregory Thomas, Frederick, Brian Troy, Mattheakis, Larry C., Liu, David
• Granted Patent: US 10,278,957 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/38 Albumins
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids

Abstract

The invention is directed to opioid agonist peptides and their use.

Claims

1. An opioid agonist peptide comprising or consisting of an amino acid sequence of Formula Ia:

2. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is according to Formula XIIIa, XIIIb, or XIIIc:

3. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein X3 is (D)Phe, Phe, Bip, His, Aba, Trp, homo-Phe, 1-Nal, Phe(4-F), Phe(4-CN), Tic, Phe(3,4-dichloro), Phe(4-tBu), Phe(3,4-dimethoxy), DPA, Gly, Sar, THP, Ala, Leu, Ile, Val, Aib, or Ala.

4. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the amino acid sequence is according to Formula XIVa, XIVb, or XIVc:

5. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein X2 is (D)Glu, (D)Arg, N(Me)-(D)Ala, (D)Ala, (D)Tic, (D)Lys, (D)Orn, (D)Thr, (D)Asp, or (D)Tyr.

6. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the amino acid sequence is according to Formula XVa, XVb, XVc, XVd, XVIa, XVIb, XVIc, or XVId:

7. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein X5 is (D)Glu, (D)Arg, N(Me)-(D)Ala, (D)Ala, (D)Tic, (D)Lys, (D)Orn, (D)Thr, (D)Asp, or (D)Tyr, Sar, N(Me)Phg, N(Me)Cha, N(Me)Tyr, N(Me)Nle, N(Me)Ile, N(Me)Ala, N(Me)Val, N(Me)Leu, N(Me)Phe.

8. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the amino acid sequence is according to Formula XVIIa, XVIIb, XVIIc, XVIId, XVIIe, XVIIf, XVIIg, XVIIh, XVIIi, XVIIj, XVIIk, XVIIl, XVIIIa, XVIIIb, XVIIIc, XVIIId, XVIIIe, XVIIIf, XVIIIg, XVIIIh, XVIIIi, XVIIIj, XVIIIk, or XVIIIl:

9. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 2, wherein R¹ is H.

10. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is:

11. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is:

12. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is:

13. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is:

14. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is:

15. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is:

16. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is H-DMT-a-G-bhF-Sar-NH₂(SEQ ID NO:

43).

17. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is H-DMT-(D)Thr-G-bhF-N(Me)Ala-OH (SEQ ID NO:

183).

18. The opioid agonist peptide or pharmaceutically acceptable salt or solvate thereof of claim 1, wherein the peptide is H-Phe(2,6-dimethyl-4-CONH₂)-a-G-bhF-Sar-NH₂(SEQ ID NO:

70).

19. A pharmaceutical composition comprising the opioid agonist peptide or pharmaceutically acceptable salt thereof of claim 1, and a pharmaceutically acceptable diluent, carrier, or excipient.

20. (canceled)