Methods of reducing apolipoprotein C-III

• US 10,675,263 B2
• Filed: 11/14/2018
• Issued: 06/09/2020
• Est. Priority Date: 02/06/2013
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Manku, Mehar, Osterloh, Ian, Wicker, Pierre, Braeckman, Rene, Soni, Paresh, Zakrzewski, Joseph S.
• Primary Examiner(s): Tran, My-Chau T.
• Application Number:
  US16/190,412
• Publication Number:
  US 20190083444A1
• Time in Patent Office: 573 Days
• CPC Class Codes: A61K 31/23 of acids having a carboxyl group bound to a chain of seven or more carbon atoms
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Claims

1. A method of reducing an apolipoprotein C3 (APOC3 ) level of a subject on statin therapy and having baseline fasting triglycerides of about 200 mg/dl to about 499 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of ethyl eicosapentaenoate per day, wherein the composition comprises less than about 1%, by weight of all fatty acids present, docosapentaenoic acid.

2. The method of claim 1, wherein the APOC3 level is reduced by at least about 5%.

3. The method of claim 1, wherein the APOC3 level is reduced by at least about 15%.

4. The method of claim 1, wherein about 2 g per day of ethyl eicosapentaenoate is administered to the subject.

5. The method of claim 1, wherein about 3.8 g to about 4 g per day of ethyl eicosapentaenoate is administered to the subject.

6. The method of claim 1, wherein the pharmaceutical composition is administered to the subject daily for a period of 1 to about 12 weeks.

7. The method of claim 1, wherein the reduction in APOC3 level is in comparison to control subjects having fasting triglycerides of about 200 mg/dl to about 499 mg/dl who have received the statin but not the pharmaceutical composition.

8. The method of claim 1, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate.

9. The method of claim 1, wherein the pharmaceutical composition comprises no more than about 10%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.

10. The method of claim 1, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate and no more than about 2%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.

11. A method of reducing an apolipoprotein C3 (APOC3) level of a subject having fasting baseline triglycerides of at least about 500 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of ethyl eicosapentaenoate per day, wherein the composition comprises less than about 1%, by weight of all fatty acids present, docosapentaenoic acid.

12. The method of claim 11, wherein the APOC3 level is reduced by at least about 5%.

13. The method of claim 11, wherein the APOC3 level is reduced by at least about 25%.

14. The method of claim 11, wherein about 2 g per day of ethyl eicosapentaenoate is administered to the subject.

15. The method of claim 11, wherein about 3.8 g to about 4 g per day of ethyl eicosapentaenoate is administered to the subject.

16. The method of claim 11, wherein the pharmaceutical composition is administered to the subject daily for a period of 1 to about 12 weeks.

17. The method of claim 11, wherein the reduction in APOC3 level is in comparison to control subjects having fasting triglycerides of at least about 500 mg/dl who have not received the pharmaceutical composition.

18. The method of claim 11, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate.

19. The method of claim 11, wherein the pharmaceutical composition comprises no more than about 10%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.

20. The method of claim 11, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate and no more than about 2%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.