# US 2021/0277089 A1 · Fibronectin based scaffold domain proteins that bind pcsk9

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0277089 A1
- Document ID: US20210277089A1
- Status: Published application
- Kind: A1
- Application number: 17/177,179
- Filed: 2021-02-16
- Published: 2021-09-09
- Earliest claimed: 2010-04-13
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Ray CAMPHAUSEN; Jonathan H. DAVIS; Sharon T. CLOAD; Fabienne M. DENHEZ; Amna SAEED-KOTHE; Dasa LIPOVSEK; Ching-Hsiung Frederick LO; Chee Meng LOW; Bowman MIAO; Tracy S. MITCHELL; Rex A. PARKER; Ginger C. RAKESTRAW; Katie A. RUSSO; Doree F. SITKOFF
- Web page: https://patentgrep.com/patent/US20210277089A1

## CPC

- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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
- C07K 16/18: against material from animals or humans
- C07K 16/40: against enzymes
- C12N 9/6424: {Serine endopeptidases (3.4.21)}
- C07K 2318/20: Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin
- C07K 2319/70: containing domain for protein-protein interaction
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

## Claims

### Claim 1

An isolated nucleic acid molecule encoding a polypeptide comprising a fibronectin type III tenth (10Fn3) domain wherein the 10Fn3 has a BC, DE and FG loop, and wherein the BC loop comprises SEQ ID NO:14, the DE comprises SEQ ID NO:25 and the FG loop comprises SEQ ID NO:37, and wherein the polypeptide binds PCSK9.

### Claim 2 (depends on 1)

The isolated nucleic acid molecule of claim 1, wherein the BC loop comprises nucleotides 67-96 of SEQ ID NO:83, the DE loop comprises nucleotides 157-174 of SEQ ID NO:83 and the FG loop comprises nucleotides 232-270 of SEQ ID NO:83.

### Claim 3

An isolated nucleic acid molecule encoding a polypeptide comprising a 10Fn3 domain wherein the polypeptide comprises SEQ ID NO:82, and wherein the polypeptide binds PCSK9.

### Claim 4 (depends on 3)

The isolated nucleic acid molecule of claim 3, wherein the isolated nucleic acid molecule comprises SEQ ID NO:83.

### Claim 5 (depends on 1)

An expression vector comprising the isolated nucleic acid sequence of claim 1.

### Claim 6 (depends on 3)

An expression vector comprising the isolated nucleic acid sequence of claim 3.

### Claim 7 (depends on 1)

A cell comprising the isolated nucleic acid sequence of claim 1.

### Claim 8 (depends on 3)

A cell comprising the isolated nucleic acid sequence of claim 3.

### Claim 9 (depends on 7)

A method of producing a PCSK9-binding polypeptide comprising culturing the cell of claim 7 under conditions suitable for expressing the polypeptide and purifying the polypeptide.

### Claim 10 (depends on 8)

A method of producing a PCSK9-binding polypeptide comprising culturing the cell of claim 8 under conditions suitable for expressing the polypeptide and purifying the polypeptide.

### Claim 11

A method of treating a PCSK9-related disease or disorder in a subject comprising administering an effective amount of a polypeptide comprising a fibronectin type III tenth (10Fn3) domain wherein the 10Fn3 has a BC, DE and FG loop, and wherein the BC loop comprises SEQ ID NO:14, the DE comprises SEQ ID NO:25 and the FG loop comprises SEQ ID NO:37, and wherein the polypeptide binds PCSK9.

### Claim 12 (depends on 11)

The method of claim 11, wherein the disease or disorder is selected from the group consisting of atherosclerosis, hypercholesterolemia and other cholesterol related diseases.

### Claim 13 (depends on 12)

The method of claim 12, wherein the disease or disorder is atherosclerosis.

### Claim 14 (depends on 12)

The method of claim 12, wherein the disease or disorder is hypercholesterolemia.

### Claim 15 (depends on 12)

The method of claim 12, wherein the disease or disorder is a cholesterol related disease.

### Claim 16

A method of treating a PCSK9-related disease or disorder in a subject comprising administering an effective amount of a polypeptide comprising a 10Fn3 domain wherein the isolated polypeptide comprises SEQ ID NO:82, and wherein the isolated polypeptide binds PCSK9.

### Claim 17 (depends on 16)

The method of claim 16, wherein the disease or disorder is selected from the group consisting of atherosclerosis, hypercholesterolemia and other cholesterol related diseases.

### Claim 18 (depends on 17)

The method of claim 17, wherein the disease or disorder is atherosclerosis.

### Claim 19 (depends on 17)

The method of claim 17, wherein the disease or disorder is hypercholesterolemia.

### Claim 20 (depends on 17)

The method of claim 17, wherein the disease or disorder is a cholesterol related disease.