# US 11,299,552 B2 · Eliminating MHC restriction from the T cell receptor as a strategy for immunotherapy

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

- Number: US 11,299,552 B2
- Document ID: US11299552B2
- Status: Granted
- Kind: B2
- Application number: 16/177,740
- Filed: 2018-11-01
- Published: 2019-02-21
- Granted: 2022-04-12
- Earliest claimed: 2016-05-02
- Assignees: University of Kansas
- Applicants: University of Kansas
- Inventors: Thomas Yankee; John Szarejko
- Web page: https://patentgrep.com/patent/US11299552B2

## CPC

- C07K 16/3092: {against tumour-associated mucins}
- A61K 38/179: {for growth factors; for growth regulators}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- C07K 14/495: Transforming growth factor [TGF]
- C07K 14/65: Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70532: {B7 molecules, e.g. CD80, CD86}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C07K 16/3084: {against tumour-associated gangliosides}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 15/62: DNA sequences coding for fusion proteins
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/42: containing a HA(hemagglutinin)-tag
- 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 disclosure generally relates to chimeric antigen receptors, more specifically to chimeric antigen receptor compositions and methods for use of the same. The present disclosure also provides for nucleic acid molecules and expression vectors for making and using the chimeric antigen receptors and for co-receptor signaling using such chimeric antigen receptors. The present disclosure also provides methods of treatment using such compositions. The chimeric antigen receptors of the present disclosure interact with the endogenous T-cell receptor complex enabling physiological control of signaling and T-cell response and can be combined with ligands such as co-stimulatory ligands for further controlling and influencing T-cell activation and response.

## Claims

### Claim 1

A nucleic acid molecule encoding a chimeric antigen receptor, the chimeric antigen receptor comprising: a T-cell receptor beta chain constant region and a T-cell receptor alpha chain constant region, wherein the T-cell receptor beta chain constant region is fused to a single chain variable fragment (scFv) that specifically binds to a tumor specific antigen, wherein the chimeric antigen receptor does not include a T-cell receptor beta chain variable region and a T-cell alpha chain variable region, and wherein the T-cell receptor beta chain constant region is configured to complex with the T-cell receptor alpha chain constant region through a non-endogenous disulfide bond, wherein the non-endogenous disulfide bond (a) arises from introducing cysteine mutations in the T-cell receptor alpha chain constant region and the T-cell receptor beta chain constant region and (b) promotes pairing of exogenous T-cell receptor alpha chain constant region and T-cell receptor beta chain constant region, wherein the cysteine mutations in the T-cell receptor alpha chain constant region and the T-cell receptor beta chain constant region are T42C and S57C, respectively.

### Claim 2 (depends on 1)

The nucleic acid molecule of claim 1, wherein the T-cell receptor beta chain constant region comprises an amino acid sequence of SEQ ID NO: 3.

### Claim 3 (depends on 1)

The nucleic acid molecule of claim 1, wherein the T-cell receptor alpha chain constant region comprises an amino acid sequence of SEQ ID NO: 5.

### Claim 4 (depends on 1)

The nucleic acid molecule of claim 1, wherein the tumor specific antigen is selected from the group consisting of disialoganglioside GD2 (GD2), mucin 1 (MUC1), prostate-specific membrane antigen (PSMA), human epidermal growth factor receptor 2 (Her2), mucin 16 (MUC16), melanoma-associated antigen 1(MAGE-A1), carbonic anhydrase 9 (CAIX), b-lymphocyte surface antigen CD19 (CD19), prominin-1 (CD133), CD33 antigen (CD33), CD38 antigen (CD38), neural cell adhesion molecule (CD56), interleukin-3 receptor (CD123), and b-lymphocyte antigen CD20 (CD20).

### Claim 5 (depends on 1)

A modified T lymphocyte that comprises (a) a nucleic acid molecule according to claim 1 and (b) a nucleic acid molecule encoding a 4-1BB ligand (4-1BBL) fused to a scFv that specifically binds to a tumor-specific antigen.

### Claim 6 (depends on 5)

The modified T lymphocyte of claim 5, wherein the nucleic acid molecule encoding the 4-1BBL fused to the scFv includes 4-1BBL that lacks its transmembrane domain.

### Claim 7 (depends on 5)

The modified T lymphocyte of claim 5, wherein the nucleic acid molecule encoding the 4-1BBL fused to the scFv includes 4-1BBL that has a mutation in its trimerization domain.

### Claim 8 (depends on 5)

The modified T lymphocyte of claim 5, wherein the nucleic acid molecule encoding the 4-1BBL fused to the scFv includes 4-1BBL that (i) lacks its transmembrane domain and (ii) has a mutation in its trimerization domain.