# US 2020/0399346 A1 · Co-stimulatory domains for use in genetically-modified cells

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- Number: US 2020/0399346 A1
- Document ID: US20200399346A1
- Status: Published application
- Kind: A1
- Application number: 17/016,016
- Filed: 2020-09-09
- Published: 2020-12-24
- Earliest claimed: 2016-10-04
- Assignees: Precision BioSciences, Inc.
- Applicants: Precision BioSciences, Inc.
- Inventors: Derek Jantz; Aaron Martin; Daniel T. MacLeod
- Web page: https://patentgrep.com/patent/US20200399346A1

## CPC

- C07K 14/7151: {for tumor necrosis factor [TNF], for lymphotoxin [LT]}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4211: {CD19 or B4}
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C12N 5/0636: {T lymphocytes}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 9/90: Isomerases (5.)
- C12Y 502/01008: Peptidylprolyl isomerase (5.2.1.8), i.e. cyclophilin
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising antibodies}
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C12N 2501/2302: Interleukin-2 (IL-2)
- C12N 2740/15043: viral genome or elements thereof as genetic vector
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- 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)
- C12Y: ENZYMES

## Abstract

The present disclosure provides novel co-stimulatory domains useful in genetically-modified cells to promote cell proliferation and/or promote cytokine secretion after antigen recognition. For example, disclosed herein are genetically-modified cells comprising a chimeric antigen receptor or an inducible regulatory construct incorporating the co-stimulatory domains disclosed herein. Also disclosed herein are plasmids and viral vectors comprising a nucleic acid sequence encoding the co-stimulatory domains, and methods of administering compositions comprising the novel co-stimulatory domains to subjects in order to reduce the symptoms, progression, or occurrence of disease, such as cancer.

## Claims

### Claim at position 1

-62. (canceled)

### Claim 63

A co-stimulatory domain comprising an amino acid sequence set forth in SEQ ID NO: 8.

### Claim 64 (depends on 63)

A chimeric antigen receptor (CAR) comprising an extracellular ligand-binding domain, a transmembrane domain, and an intracellular domain, wherein said intracellular domain comprises said co-stimulatory domain of claim 63 and an intracellular signaling domain.

### Claim 65 (depends on 64)

The CAR of claim 64, wherein said intracellular signaling domain comprises a CD3 ζ intracellular signaling domain.

### Claim 66 (depends on 64)

The CAR of claim 64, wherein said transmembrane domain comprises a CD8 alpha transmembrane domain.

### Claim 67 (depends on 64)

The CAR of claim 64, wherein said extracellular ligand-binding domain comprises a single-chain variable fragment (scFv).

### Claim 68 (depends on 64)

The CAR of claim 64, wherein said extracellular ligand-binding domain has specificity for a tumor antigen.

### Claim 69 (depends on 63)

A genetically-modified eukaryotic cell comprising said co-stimulatory domain of claim 63.

### Claim 70 (depends on 64)

A genetically-modified eukaryotic cell comprising said CAR of claim 64.

### Claim 71 (depends on 69)

The genetically-modified eukaryotic cell of claim 69, wherein said genetically-modified eukaryotic cell is a genetically-modified human T cell.

### Claim 72 (depends on 70)

The genetically-modified eukaryotic cell of claim 70, wherein said genetically-modified eukaryotic cell is a genetically-modified human T cell.

### Claim 73 (depends on 69)

The genetically-modified eukaryotic cell of claim 69, wherein said genetically-modified eukaryotic cell is a genetically-modified human natural killer (NK) cell.

### Claim 74 (depends on 70)

The genetically-modified eukaryotic cell of claim 70, wherein said genetically-modified eukaryotic cell is a genetically-modified human NK cell.

### Claim 75 (depends on 71)

A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and said genetically-modified human T cell of claim 71.

### Claim 76 (depends on 72)

A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and said genetically-modified human T cell of claim 72.

### Claim 77 (depends on 73)

A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and said genetically-modified human NK cell of claim 73.

### Claim 78 (depends on 74)

A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and said genetically-modified human NK cell of claim 74.