# US 11,306,131 B2 · T cell receptors recognizing HLA-A1- or HLA-CW7-restricted mage

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- Number: US 11,306,131 B2
- Document ID: US11306131B2
- Status: Granted
- Kind: B2
- Application number: 16/144,226
- Filed: 2018-09-27
- Published: 2019-01-17
- Granted: 2022-04-19
- Earliest claimed: 2011-09-15
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Inventors: Paul F. Robbins; Steven A. Rosenberg; Shiqui Zhu; Steven A. Feldman; Richard A. Morgan
- Web page: https://patentgrep.com/patent/US11306131B2

## CPC

- A61P 35/00: Antineoplastic agents
- C07K 14/70503: {Immunoglobulin superfamily}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/4268: {MAGE}
- A61K 40/4269: {NY-ESO}
- A61P 35/02: specific for leukemia
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 16/2803: {against the immunoglobulin superfamily}
- G01N 33/575: for cancer
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2318/20: Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.

## Claims

### Claim 1

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a T cell receptor (TCR) having antigenic specificity for MAGE-A12 presented by HLA-Cw7, wherein the TCR comprises the amino acid sequences of SEQ ID NOs: 26-31.

### Claim 2 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR has antigenic specificity for a MAGE-A12 epitope comprising VRIGHLYIL (SEQ ID NO: 4).

### Claim 3 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR comprises the amino acid sequences of SEQ ID NOs: 32-33.

### Claim 4 (depends on 3)

The isolated or purified nucleic acid of claim 3, wherein the TCR comprises the amino acid sequences of SEQ ID NOs: 34-35.

### Claim 5

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises the amino acid sequences of SEQ ID NOs: 26-31.

### Claim 6 (depends on 5)

The isolated or purified nucleic acid of claim 5, wherein the polypeptide comprises the amino acid sequences of SEQ ID NOs: 32-33.

### Claim 7 (depends on 6)

The isolated or purified nucleic acid of claim 6, wherein the polypeptide comprises the amino acid sequences of SEQ ID NOs: 34-35.

### Claim 8

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a protein, wherein the protein comprises:
a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 26-28; and
a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 29-31.

### Claim 9 (depends on 8)

The isolated or purified nucleic acid of claim 8, wherein the protein comprises:
a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 32; and
a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 33.

### Claim 10 (depends on 9)

The isolated or purified nucleic acid of claim 9, wherein the protein comprises:
a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 34; and
a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 35.

### Claim 11 (depends on 8)

The isolated or purified nucleic acid of claim 8, wherein the protein is a fusion protein.

### Claim 12 (depends on 8)

The isolated or purified nucleic acid of claim 8, wherein the protein is a recombinant antibody.

### Claim 13 (depends on 1)

The isolated or purified nucleic acid of claim 1, comprising a nucleotide sequence comprising SEQ ID NO: 47.

### Claim 14 (depends on 1)

An isolated or purified nucleic acid comprising a nucleotide sequence which is complementary to the nucleotide sequence of the nucleic acid of claim 1.

### Claim 15 (depends on 1)

An isolated or purified nucleic acid comprising a nucleotide sequence which hybridizes under stringent conditions to the nucleotide sequence of the nucleic acid of claim 1.

### Claim 16 (depends on 1)

A recombinant expression vector comprising the nucleic acid of claim 1.

### Claim 17 (depends on 16)

An isolated host cell comprising the recombinant expression vector of claim 16.

### Claim 18 (depends on 17)

The isolated host cell of claim 17, wherein the cell is a peripheral blood lymphocyte (PBL).

### Claim 19 (depends on 18)

The isolated host cell of claim 18, wherein the PBL is a T cell.

### Claim 20 (depends on 17)

The isolated host cell of claim 17, wherein the cell is a tumor infiltrating lymphocyte (TIL).

### Claim 21 (depends on 17)

A population of cells comprising at least one host cell of claim 17.

### Claim 22 (depends on 21)

A pharmaceutical composition comprising the population of cells of claim 21 and a pharmaceutically acceptable carrier.

### Claim 23 (depends on 21)

A method of detecting the presence of cancer in a host, comprising:
(i) contacting a sample comprising cells of the cancer with the population of cells of claim 21, thereby forming a complex, and
(ii) detecting the complex,
wherein detection of the complex is indicative of the presence of cancer in the host and
wherein the cancer is melanoma or urinary bladder cancer and the cancer expresses a MAGE-A12 epitope comprising VRIGHLYIL (SEQ ID NO: 4) presented by HLA-Cw7.

### Claim 24 (depends on 21)

A method of treating cancer in a host, comprising administering to the host the population of cells of claim 21, in an amount effective to treat cancer in the host, wherein the cancer is melanoma or urinary bladder cancer and the cancer expresses a MAGE-A12 epitope comprising VRIGHLYIL (SEQ ID NO: 4) presented by HLA-Cw7.

### Claim 25 (depends on 23)

The method of claim 23, wherein the host cell is a cell that is autologous to the host.

### Claim 26 (depends on 23)

The method of claim 23, wherein the cells of the population are cells that are autologous to the host.