Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids

• US 10,406,130 B2
• Filed: 01/25/2017
• Issued: 09/10/2019
• Est. Priority Date: 03/15/2016
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Mason, Richard Preston
• Primary Examiner(s): Hui, San Ming R
• Application Number:
  US15/415,667
• Publication Number:
  US 20170333377A1
• Time in Patent Office: 958 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil

Abstract

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

Claims

1. A method of treating or preventing atherosclerosis in a subject having a high baseline serum glucose level of at least 126 mg/dL and a baseline triglyceride level of about 200 mg/dL to 499 mg/dL, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof and further comprising a step of determining a baseline oxidized sdLDL level in the subject prior to administering to the subject the pharmaceutical composition.

2. The method of claim 1, wherein the pharmaceutical composition comprises at least 80%, at least 90%, at least 95%, or at least 96%, by weight of all fatty acids (and/or derivatives thereof) present, eicosapentaenoic acid or a derivative thereof.

3. The method of claim 1, wherein the pharmaceutical composition comprises no docosahexaenoic acid or esters thereof.

4. The method of claim 1, wherein the reduction or prevention occurs by a free radical chain-breaking mechanism.

5. The method of claim 1 further comprising determining a second oxidized sdLDL level in the subject after administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level and/or wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has not received the pharmaceutical composition.

6. The method of claim 5, wherein the method further comprises administering atorvastatin and/or o-hydroxyatorvastatin to the subject.

7. The method of claim 6, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has received the atorvastatin and/or the o-hydroxyatorvastatin but not the pharmaceutical composition.

8. The method of claim 6, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has received the pharmaceutical composition but not the o-hydroxyatorvastatin.

9. The method of claim 1, wherein the subject is on statin therapy, optionally stable statin therapy.

10. The method of claim 1, wherein the subject is diabetic.

11. The method of claim 1, wherein the high baseline serum glucose level is a fasting serum glucose level of at least 160 mg/dL.

12. The method of claim 1, wherein the high baseline serum glucose level is a non-fasting serum glucose level of at least 200 mg/dL.