# US 10,117,896 B2 · Use of a trans-signaling approach in chimeric antigen receptors

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

- Number: US 10,117,896 B2
- Document ID: US10117896B2
- Status: Granted
- Kind: B2
- Application number: 14/044,569
- Filed: 2013-10-02
- Published: 2014-04-10
- Granted: 2018-11-06
- Earliest claimed: 2012-10-05
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Daniel J. Powell, Jr.; Carl H. June
- Web page: https://patentgrep.com/patent/US10117896B2

## CPC

- C07K 16/30: from tumour cells
- 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 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4}
- A61K 40/4211: {CD19 or B4}
- A61K 40/4255: {Mesothelin [MSLN]}
- A61K 40/4257: {Mucins, e.g. MUC-1}
- A61P 35/00: Antineoplastic agents
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12N 5/0636: {T lymphocytes}
- A61K 2239/29: Multispecific CARs
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/59: Reproductive system, e.g. uterus, ovaries, cervix or testes
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C12N 2510/00: Genetically modified cells
- 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 provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

## Claims

### Claim 1

A trans-signaling composition comprising a nucleic acid molecule comprising a sequence encoding a first chimeric antigen receptor (CAR) and a second CAR, wherein the first CAR comprises a first antigen binding domain that binds mesothelin, a first CD8α hinge region, a CD8α transmembrane domain, and an intracellular CD3z signaling domain of a T cell receptor, and wherein the second CAR comprises a second antigen binding domain that binds folate receptor (FRa), a second CD8α hinge region, a CD28 transmembrane domain, and a CD28 intracellular domain, and wherein the first and second antigen binding domain is an antibody or fragment thereof, and wherein the nucleic acid sequence comprises SEQ ID NO: 4 and SEQ ID NO: 6.