# US 11,077,140 B2 · Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes

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

- Number: US 11,077,140 B2
- Document ID: US11077140B2
- Status: Granted
- Kind: B2
- Application number: 16/135,678
- Filed: 2018-09-19
- Published: 2019-01-03
- Granted: 2021-08-03
- Earliest claimed: 2007-03-30
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Memorial Sloan-Kettering Cancer Center
- Inventors: Michel Sadelain; Matthias Stephan
- Web page: https://patentgrep.com/patent/US11077140B2

## CPC

- C12N 5/0636: {T lymphocytes}
- A61K 38/2013: {IL-2}
- A61K 38/217: {IFN-gamma}
- 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 40/4224: {Molecules with a "CD" designation not provided for elsewhere}
- A61K 40/4276: {Prostate specific membrane antigen [PSMA]}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 13/08: of the prostate
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 31/16: for influenza or rhinoviruses
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 33/00: Antiparasitic agents
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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 15/85: for animal cells
- A61K 2035/122: {for inducing tolerance or supression of immune responses}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2239/31: characterized by the route of administration
- C12N 2501/25: Tumour necrosing factors [TNF]
- C12N 2501/51: B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
- C12N 2501/599: with CD designations not provided for elsewhere
- C12N 2510/00: Genetically modified cells
- C12N 2799/04: in vivo
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

## Claims

### Claim 1

A method of treating leukemia or ovarian cancer in a subject, comprising administering an effective amount of immunoresponsive cells to the subject, wherein the immunoresponsive cell comprises:
a) a chimeric antigen receptor (CAR) that binds to a tumor antigen expressed by leukemia or ovarian cancer, and b) a nucleic acid molecule encoding a recombinant IL-12.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

The method of claim 1, wherein the cell comprises a cytotoxic T lymphocyte.

### Claim 4 (depends on 1)

The method of claim 1, wherein the nucleic acid molecule is comprised on a vector.

### Claim 5 (depends on 4)

The method of claim 4, wherein the vector is a viral vector.

### Claim 6 (depends on 5)

The method of claim 5, wherein the vector is a retroviral vector.

### Claim 7 (depends on 6)

The method of claim 6, wherein the retroviral vector is a gamma-retroviral vector or a lentiviral vector.

### Claim 8 (depends on 1)

The method of claim 1, wherein the tumor antigen is CD19.

### Claim 9 (depends on 1)

The method of claim 1, wherein the tumor antigen is expressed by a tumor expressing CD19.

### Claim 10 (depends on 1)

The method of claim 1, wherein the CAR comprises a ζ chain signaling domain.

### Claim 11 (depends on 1)

The method of claim 1, wherein the CAR further comprises a domain that provides a costimulatory signal.

### Claim 12 (depends on 1)

The method of claim 1, wherein the CAR comprises a CD28 signaling element.

### Claim 13 (depends on 1)

The method of claim 1, wherein the immunoresponsive cell is a T cell, and the tumor antigen is expressed by ovarian cancer.

### Claim 14 (depends on 1)

The method of claim 1, wherein the immunoresponsive cell is a T cell, and the tumor antigen is expressed by leukemia.

### Claim 15 (depends on 1)

The method of claim 1, wherein the leukemia is acute lymphocytic leukemia.