Methods for reducing lipoprotein(a) levels by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9)

• US 10,076,571 B2
• Filed: 09/12/2012
• Issued: 09/18/2018
• Est. Priority Date: 09/16/2011
• Status: Active Grant

• Current Assignee: Regeneron Pharmaceuticals Incorporated
• Original Assignee: Regeneron Pharmaceuticals Incorporated
• Inventors: Swergold, Gary
• Primary Examiner(s): Wen, Sharon X
• Application Number:
  US13/611,405
• Publication Number:
  US 20130243784A1
• Time in Patent Office: 2,197 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/40 against enzymes

Abstract

The present invention provides methods for reducing lipoprotein(a) (Lp(a)) in patients. The methods of the present invention comprise selecting a patient who exhibits elevated serum Lp(a), and administering to the patient a pharmaceutical composition comprising a PCSK9 inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody such as the exemplary antibody referred to herein as mAb316P.

Claims

1. A method for reducing lipoprotein(a) (“

Lp(a)”

) levels, the method comprising selecting a patient who exhibits elevated serum Lp(a), and administering to the patient a pharmaceutical composition comprising a PCSK9 inhibitor, wherein the PCSK9 inhibitor is an antibody or antigen-binding fragment thereof that specifically binds PCSK9, wherein the antibody or antigen binding fragment thereof comprises the heavy and light chain CDRs of a HCVR/LCVR amino acid sequence pair selected from the group consisting of SEQ ID NOs;

90/92 and 218/226.

2. The method of claim 1, wherein the patient is selected on the basis of a serum Lp(a) level greater than about 20 mg/dL.

3. The method of claim 2, wherein the patient is selected on the basis of a serum Lp(a) level greater than about 100 mg/dL.

4. The method of claim 1, wherein prior to or at the time of administration of the pharmaceutical composition, the patient is diagnosed with or identified as being at risk of developing a cardiovascular disease or disorder.

5. The method of claim 4, wherein the cardiovascular disease or disorder is selected from the group consisting of coronary artery disease, acute myocardial infarction, asymptomatic carotid atherosclerosis, stroke, and peripheral artery occlusive disease.

6. The method of claim 4, wherein the cardiovascular disease or disorder is hypercholesterolemia.

7. The method of claim 6, wherein the hypercholesterolemia is heterozygous Familial Hypercholesterolemia (heFH).

8. The method of claim 6, wherein the hypercholesterolemia is not Familial Hypercholesterolemia (nonFH).

9. The method of claim 1, wherein prior to or at the time of administration of the pharmaceutical composition, the patient is diagnosed with or identified as being at risk of developing a thrombotic occlusive disease or disorder.

10. The method of claim 9, wherein the thrombotic occlusive disease or disorder is selected from the group consisting of pulmonary embolism and central retinal vein occlusion.

11. The method of claim 1, wherein the pharmaceutical composition comprises 20 mg to 200 mg of the PCSK9 inhibitor.

12. The method of claim 11, wherein the pharmaceutical composition comprises 50 mg to 150 mg of the PCSK9 inhibitor.

13. The method of claim 12, wherein the pharmaceutical composition comprises 50 mg of the PCSK9 inhibitor.

14. The method of claim 12, wherein the pharmaceutical composition comprises 100 mg of the PCSK9 inhibitor.

15. The method of claim 12, wherein the pharmaceutical composition comprises 150 mg of the PCSK9 inhibitor.

16. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:

220, 222, 224, 228, 230 and 232.

17. The method of claim 16, wherein the antibody or antigen-binding fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO:

218 and an LCVR having the amino acid sequence of SEQ ID NO;

226.

18. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:

76, 78, 80, 84, 86 and 88.

19. The method of claim 18, wherein the antibody or antigen-binding fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO:

90 and an LCVR having the amino acid sequence of SEQ ID NO;

92.

20. The method of claim 1, wherein the antibody or antigen-binding fragment thereof binds to the same epitope on PCSK9 as an antibody comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs:

220, 222, 224, 228, 230 and 232;

or SEQ ID NOs;

76, 78, 80, 84, 86 and 88.

21. The method of claim 1, wherein the antibody or antigen-binding fragment thereof competes for binding to PCSK9 with an antibody comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs:

220, 222, 224, 228, 230 and 232;

or SEQ ID NOs;

76, 78, 80, 84, 86 and 88.

22. The method of claim 1, wherein the patient is on a therapeutic statin regimen at the time of or just prior to administration of the pharmaceutical composition.

23. The method of claim 22, wherein the therapeutic statin regimen comprises a statin selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pitavastatin, rosuvastatin, fluvastatin, lovastatin and pravastatin.

24. The method of claim 23, wherein the statin is atorvastatin.

25. The method of claim 1, wherein the patient is not on a therapeutic statin regimen at the time of administration of the pharmaceutical composition.