# US 12,110,342 B2 · Nucleic acid monoclonal antibodies targeting PCSK9 and methods of use

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- Number: US 12,110,342 B2
- Document ID: US12110342B2
- Status: Granted
- Kind: B2
- Application number: 16/966,513
- Filed: 2019-01-31
- Published: 2020-11-19
- Granted: 2024-10-08
- Earliest claimed: 2018-01-31
- Assignees: The Wistar Institute of Anatomy and Biology
- Applicants: The Wistar Institute of Anatomy and Biology
- Inventors: David Weiner; Makan Khoshnejad; Kar Muthumani; Ami Patel
- Web page: https://patentgrep.com/patent/US12110342B2

## CPC

- C07K 16/40: against enzymes
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 3/06: Antihyperlipidemics
- A61K 2039/505: {comprising antibodies}
- 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

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody or fragment thereof that targets PCSK9. The disclosure also provides a method of preventing and/or treating disease, such as cardiovascular disease or hypercholesterolemia, in a subject using the composition of the invention.

## Claims

### Claim 1

A composition for generating one or more anti-PCSK9 antibodies or antigen-binding fragments thereof in a subject, comprising one or more nucleic acid molecules encoding one or more anti-PCSK9 antibodies or antigen-binding fragments thereof;
wherein the composition comprises:
a) a nucleotide sequence encoding an amino acid sequence having at least about 99% identity over the entire length of at least one amino acid sequence selected from the group of SEQ ID NOs: 1, 3, 5 and 7, wherein the encoded CDRs comprises 100% identity to the CDRs of SEQ ID NO: 1, 3, 5 or 7;
b) a nucleotide sequence having at least about 99% identity over the entire length of at least one nucleotide sequence selected from the group of SEQ ID NOs: 2, 4, 6 and 8, wherein the nucleotide sequences encoding the CDRs comprises 100% identity to the CDR coding sequences of SEQ ID NO:2, 4, 6 and 8; or c) any combination thereof.

### Claim 2 (depends on 1)

The composition of claim 1, comprising a nucleotide sequence encoding a cleavage domain.

### Claim 3 (depends on 1)

The composition of claim 1, comprising a nucleotide sequence encoding a variable heavy chain region and a variable light chain region of the antibody.

### Claim 4 (depends on 1)

The composition of claim 1, comprising a nucleotide sequence encoding a polypeptide comprising a constant heavy chain region and a polypeptide comprising a constant light chain region.

### Claim 5 (depends on 1)

The composition of claim 1, comprising a nucleotide sequence encoding a polypeptide comprising a variable heavy chain region; a constant heavy chain region; a cleavage domain; a variable light chain region; and a constant light chain region.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the nucleotide sequence encodes a leader sequence.

### Claim 7 (depends on 1)

The composition of claim 1, comprising a nucleotide sequence encoding at least one amino acid sequence selected from the group of SEQ ID NOs: 1, 3, 5 and 7.

### Claim 8 (depends on 1)

The composition of claim 1, comprising-a nucleotide sequence having at least about 98% identity over the entire length of at least one nucleotide sequence selected from the group of SEQ ID NOs: 2, 4, 6 and 8.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the one or more nucleic acid molecules are engineered to be in an expression vector.

### Claim 10 (depends on 9)

The composition of claim 9, further comprising a pharmaceutically acceptable excipient.

### Claim 11 (depends on 1)

A method of treating a disease in a subject, the method comprising administering to the subject a composition of claim 1.

### Claim 12 (depends on 11)

The method of claim 11, wherein the disease is cardiovascular disease or hypercholesterolemia.

### Claim 13 (depends on 1)

A method for decreasing an LDL-C in a subject in need thereof, the method comprising administering a composition of claim 1 to the subject.

### Claim 14 (depends on 13)

The method of claim 13, wherein administering the composition comprises an electroporating step.
