# US 11,306,155 B2 · Methods for treating patients with heterozygous familial hypercholesterolemia (heFH) with an anti-PCSK9 antibody

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- Number: US 11,306,155 B2
- Document ID: US11306155B2
- Status: Granted
- Kind: B2
- Application number: 16/707,492
- Filed: 2019-12-09
- Published: 2020-07-09
- Granted: 2022-04-19
- Earliest claimed: 2014-07-16
- Assignees: Sanofi Biotechnology; Regeneron Pharmaceuticals, Inc.
- Applicants: Sanofi Biotechnology; Regeneron Pharmaceuticals, Inc.
- Inventors: Marie Baccara-Dinet; Corinne Hanotin; Laurence Bessac; Umesh Chaudhari; Robert C. Pordy; William J. Sasiela; Daniel A. Schwemmer Gipe
- Web page: https://patentgrep.com/patent/US11306155B2

## CPC

- C07K 16/40: against enzymes
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides methods for treating hypercholesterolemia. The methods of the present invention comprise administering to patients with heterozygous familial hypercholesterolemia 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. The methods of the present invention are useful for treating patients with heterozygous familial hypercholesterolemia who are not adequately controlled by maximum tolerated dose statin therapy with or without other lipid lowering therapy.

## Claims

### Claim 1

A method for reducing low density lipoprotein cholesterol (LDL-C) comprising:
administering to a patient in need thereof one or more doses of 75 mg at a frequency of once every two weeks of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin/kexin type 9 (PCSK9), wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR) having the amino acid sequences of SEQ ID NOs: 1 and 6, respectively,
wherein the patient has heterozygous familial hypercholesterolemia (heFH), and wherein prior to treatment the patient has a serum LDL-C concentration of greater than or equal to 100 mg/dL without a history of documented cardiovascular disease.

### Claim 2 (depends on 1)

The method of claim 1, wherein the diagnosis of heFH is made either by genotyping or clinical criteria, and wherein the clinical criteria is either the Simon Broome Register Diagnostic Criteria for Heterozygous Familial Hypercholesterolemia, or the WHO/Dutch Lipid Network criteria with a score >8.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered to the patient in combination with the maximally tolerated dose of statin therapy.

### Claim 4 (depends on 1)

The method of claim 1, wherein the maximally tolerated dose of statin therapy comprises a daily dose of 40 mg to 80 mg of atorvastatin, a daily dose of 20 mg to 40 mg of rosuvastatin, or a daily dose of 80 mg of simvastatin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered to the patient in combination with at least one other lipid lowering therapy.

### Claim 6 (depends on 1)

The method of claim 1, wherein treatment with the antibody or antigen-binding fragment thereof for 24 weeks reduces the patient's low density lipoprotein cholesterol (LDL-C) by at least 40%.

### Claim 7

A method for reducing low density lipoprotein cholesterol (LDL-C) comprising:
administering to a patient in need thereof one or more doses of 75 mg at a frequency of once every two weeks of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin/kexin type 9 (PCSK9), wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR) having the amino acid sequences of SEQ ID NOs: 1 and 6, respectively,
wherein the patient has heterozygous familial hypercholesterolemia (heFH) that is inadequately controlled by a maximally tolerated dose of statin therapy, wherein prior to treatment the patient has a serum LDL-C concentration of greater than or equal to 100 mg/dL without a history of documented cardiovascular disease, and wherein:
(a) the 75 mg dose is maintained if the patient's LDL-C measured after five or more doses is lower than 70 mg/dL; or
(b) the 75 mg dose is discontinued if the patient's LDL-C measured after five or more doses is greater than or equal to 70 mg/dL, and the antibody or antigen-binding fragment thereof that specifically binds PCSK9 is subsequently administered to the patient at a dose of 150 mg at a frequency of once every two weeks.

### Claim 8 (depends on 7)

The method of claim 7, wherein the diagnosis of heFH is made either by genotyping or clinical criteria, and wherein the clinical criteria is either the Simon Broome Register Diagnostic Criteria for Heterozygous Familial Hypercholesterolemia, or the WHO/Dutch Lipid Network criteria with a score >8.

### Claim 9 (depends on 7)

The method of claim 7, wherein the antibody or antigen-binding fragment thereof is administered to the patient in combination with the maximally tolerated dose of statin therapy.

### Claim 10 (depends on 7)

The method of claim 7, wherein the maximally tolerated dose of statin therapy comprises a daily dose of 40 mg to 80 mg of atorvastatin, a daily dose of 20 mg to 40 mg of rosuvastatin, or a daily dose of 80 mg of simvastatin.

### Claim 11 (depends on 7)

The method of claim 7, wherein the antibody or antigen-binding fragment thereof is administered to the patient in combination with at least one other lipid lowering therapy.

### Claim 12 (depends on 7)

The method of claim 7, wherein treatment with the antibody or antigen-binding fragment thereof for 24 weeks reduces the patient's low density lipoprotein cholesterol (LDL-C) by at least 40%.

### Claim 13 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered subcutaneously.

### Claim 14 (depends on 7)

The method of claim 7, wherein the antibody or antigen-binding fragment thereof is administered subcutaneously.