ApoC-II mimetic peptides

Patent metadata

Field	Value
Publication number	US-11136372-B2
Application number	US-201816479183-A
Country	US
Kind code	B2
Filing date	Jan 19, 2018
Priority date	Jan 19, 2017
Publication date	Oct 5, 2021
Grant date	Oct 5, 2021

Abstract

The disclosure provides apolipoprotein C-II (apoC-II) mimetic peptides and methods for treating hypertriglyceridemia in a patient with an effective amount of an apoC-II mimetic peptide.

First claim

The invention claimed is:

1. An isolated apoC-II mimetic peptide of no more than 50 amino acids, comprising from N-terminus to C-terminus a first helical domain, a hinge region, and a second helical domain, wherein the first helical domain is amphipathic, and wherein the apoC-II mimetic peptide is not a peptide of SEQ ID NO: 56, wherein the hinge region comprises a valine.

2. An isolated apoC-II mimetic peptide comprising, from N-terminus to C-terminus, an amphipathic first helical domain, a hinge region, and a second helical domain, wherein the mimetic peptide has a sequence that differs from the full length of SEQ ID NO: 9 by substitution of 0, 1, 2, 3 or 4 residues.

3. An isolated apoC-II mimetic peptide comprising, from N-terminus to C-terminus, an amphipathic first helical domain, a hinge region, and a second helical domain, wherein the mimetic peptide has a sequence with at least 90% sequence identity to the full length of the sequence set forth in SEQ ID NO: 9.

4. The isolated apoC-II mimetic peptide of claim 3 , wherein the mimetic peptide has a sequence with at least 95% sequence identity to the full length of the sequence set forth in SEQ ID NO: 9.

5. The isolated apoC-II mimetic peptide of claim 3 , comprising the sequence set forth in SEQ ID NO: 9.

6. A pharmaceutical composition comprising the mimetic peptide of claim 3 and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is suitable for subcutaneous injection.

8. A method of treating hypertriglyceridemia in a patient, the method comprising administering to the patient the mimetic peptide of claim 3 or the pharmaceutical composition of claim 6 .

9. The method of claim 8 , wherein the hypertriglyceridemia is associated with obesity.

10. The method of claim 8 , wherein the hypertriglyceridemia is associated with diabetes mellitus.

11. The method of claim 8 , wherein the hypertriglyceridemia is associated with alcohol consumption.

12. The method of claim 8 , wherein the hypertriglyceridemia is associated with medication.

13. The method of claim 8 , wherein the hypertriglyceridemia is caused by LPL deficiency.

14. The method of claim 13 , wherein the hypertriglyceridemia is familial LPL deficiency.

15. The method of claim 13 , wherein the LPL deficiency is caused by a mutation in the LPL gene.

16. The method of claim 15 , wherein the mutation leads to reduced LPL enzyme activity.

17. The method of claim 15 , wherein the mutation leads to absent LPL enzyme activity.

18. The method of claim 13 , wherein the LPL deficiency is diagnosed by the absence of LPL activity in serum of the patient.

19. The method of claim 15 , wherein the mutation is detected by DNA sequence analysis.

20. The method of claim 8 , wherein the hypertriglyceridemia is caused by apoC-II deficiency.

21. The method of claim 8 , wherein the hypertriglyceridemia is caused by elevated apoC-III.

22. The method of claim 8 , wherein the pre-treatment serum triglyceride (TG) concentration of the patient is between 150 mg/dL and 199 mg/dL.

23. The method of claim 8 , wherein the pre-treatment serum triglyceride (TG) concentration of the patient is between 200 mg/dL to 499 mg/dL.

24. The method of claim 8 , wherein the pre-treatment serum triglyceride (TG) concentration of the patient is between 500 mg/dL to 999 mg/dL.

25. The method of claim 8 , wherein the pre-treatment serum triglyceride (TG) concentration of the patient is between 1000 mg/dL and 1999 mg/dL.

26. The method of claim 8 , wherein the pre-treatment serum triglyceride (TG) concentration of the patient is equal to or higher than 2000 mg/dL.

27. The method of claim 8 , wherein the patient has developed or is at risk for acute pancreatitis.

28. The method of claim 8 , wherein the patient has developed or is at risk for acute cardiovascular disease.

29. A method of making the mimetic peptide of claim 3 , comprising producing the mimetic peptide recombinantly.

30. A method of making the mimetic peptide of claim 3 , comprising producing the mimetic peptide by chemical synthesis.

Assignees

• The Us Secretary Dept Of Health & Human Services
• Novo Nordisk As

Inventors

• Remaley Alan Thomas
• Ghosh Soumitra Shanker
• Devalaraja Madhav N
• Lo Chih-Hung
• Sviridov Denis O
• Wolska Anna

Classifications

• C07K2319/41

  containing a Myc-tag · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• C07K14/775 Primary

  Apolipopeptides · CPC title

• C07K2319/42

  containing a HA(hemagglutinin)-tag · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title