Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9)

• US 10,111,953 B2
• Filed: 05/29/2014
• Issued: 10/30/2018
• Est. Priority Date: 05/30/2013
• Status: Active Grant

• Current Assignee: Regeneron Pharmaceuticals Incorporated
• Original Assignee: Regeneron Pharmaceuticals Incorporated
• Inventors: Swergold, Gary, Sasiela, William J., Pordy, Robert C.
• Primary Examiner(s): Wen, Sharon X
• Application Number:
  US14/290,544
• Publication Number:
  US 20140356371A1
• Time in Patent Office: 1,615 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 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
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention provides methods for reducing various lipoprotein fractions in the serum of patients. The methods of the invention include reducing serum remnant cholesterol, and/or the serum concentration of one or more LDL-C subfractions in a patient. The methods of the present invention comprise selecting a patient who exhibits elevated serum lipoproteins, 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 in a patient the serum concentration of IDL-C;

the method comprising selecting a patient with elevated serum IDL-C, and administering to the patient a pharmaceutical composition comprising a PCSK9 inhibitor;

wherein the patient is otherwise healthy except for exhibiting elevated serum IDL-C; and

wherein the PCSK9 inhibitor is an antibody or antigen-binding fragment of an antibody that specifically binds PCSK9 and 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 serum IDL-C is reduced in the patient by at least about 50% to about 56% from baseline following administration of the pharmaceutical composition.

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

4. The method of claim 3, wherein the pharmaceutical composition comprises 75 mg or 150 mg of the PCSK9 inhibitor.

5. 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.

6. The method of claim 5, 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.

7. 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.

8. The method of claim 7, 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.

9. 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.

10. The method of claim 9, wherein the therapeutic statin regimen comprises a statin selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pitavastatin, rosuvastatin, fluvastatin, lovastatin and pravastatin.

11. The method of claim 10, wherein the statin is atorvastatin.

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