# US 12,304,968 B2 · T-cells expressing anti-LIV1 chimeric antigen receptor

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- Number: US 12,304,968 B2
- Document ID: US12304968B2
- Status: Granted
- Kind: B2
- Application number: 16/677,267
- Filed: 2019-11-07
- Published: 2020-07-23
- Granted: 2025-05-20
- Earliest claimed: 2018-11-07
- Assignees: Crispr Therapeutics AG
- Applicants: Crispr Therapeutics AG
- Inventors: Jonathan Alexander Terrett; Jason Sagert
- Web page: https://patentgrep.com/patent/US12304968B2

## CPC

- C07K 16/3015: {Breast}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- 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 40/32: T-cell receptors [TCR]
- A61K 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/421: {Immunoglobulin superfamily}
- A61P 35/00: Antineoplastic agents
- C07K 14/4717: {Plasma globulins, lactoglobulin}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- 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 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C12N 5/0636: {T lymphocytes}
- C12N 9/226: {Class 2 CAS enzyme complex, e.g. single CAS protein}
- C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity}
- C12N 15/85: for animal cells
- C12N 15/86: Viral vectors
- 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 2039/812: {Breast}
- A61K 2039/868: {kidney}
- A61K 2239/49: Breast
- A61K 2239/56: Kidney
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- C12N 2502/30: tumour cells
- C12N 2502/99: genetically modified cells
- C12N 2510/00: Genetically modified cells
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2800/80: Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
- 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

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer, such as LIV1+ malignancies.

## Claims

### Claim 1

An engineered T cell comprising a nucleic acid encoding a chimeric antigen receptor (CAR) encoded by the nucleotide sequence of any one of SEQ ID NOs: 49, 51, 104, and 108.

### Claim 2 (depends on 1)

The engineered T cell of claim 1 further comprising a disrupted T cell receptor alpha chain constant region (TRAC) gene.

### Claim 3 (depends on 2)

The engineered T cell of claim 2, wherein the nucleic acid encoding the CAR is inserted into the disrupted TRAC gene.

### Claim 4 (depends on 2)

The engineered T cell of claim 2, wherein the disrupted TRAC gene comprises the nucleotide sequence of any one of SEQ ID NOs: 63, 64, 107, and 111.

### Claim 5 (depends on 2)

The engineered T cell of claim 2, wherein the disrupted TRAC gene comprises the nucleotide sequence of SEQ ID NO: 107.

### Claim 6 (depends on 1)

The engineered T cell of claim 1 further comprising a disrupted beta-2-microglobulin (β2M) gene.

### Claim 7 (depends on 1)

The engineered T cell of claim 1, wherein the CAR further comprises a CD28 co-stimulatory domain or a 41BB co-stimulatory domain.

### Claim 8 (depends on 7)

The engineered T cell of claim 7, wherein the CAR further comprises a CD3 cytoplasmic signaling domain.

### Claim 9 (depends on 1)

The engineered T cell of claim 1, wherein the T cell is a human T cell.

### Claim 10 (depends on 1)

A population of cells comprising the engineered T cell of claim 1, wherein at least 15% or at least 50% of the engineered T cells of the population express the CAR.

### Claim 11 (depends on 1)

The engineered T cell of claim 1, wherein the CAR comprises an anti-LIV1 scFv having the amino acid sequence of SEQ ID NO: 83.

### Claim 12 (depends on 1)

The engineered T cell of claim 1, wherein the CAR comprises the amino acid sequence of SEQ ID NO: 105.