# US 10,864,252 B2 · Anti-SSX-2 T cell receptors and related materials and methods of use

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- Number: US 10,864,252 B2
- Document ID: US10864252B2
- Status: Granted
- Kind: B2
- Application number: 16/173,701
- Filed: 2018-10-29
- Published: 2019-02-21
- Granted: 2020-12-15
- Earliest claimed: 2010-09-21
- Assignees: The United States of Americans 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: Richard A. Morgan; Nachimuthu Chinnasamy; Steven A. Rosenberg
- Web page: https://patentgrep.com/patent/US10864252B2

## CPC

- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/08: of the prostate
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/30: from tumour cells
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- C07K 2319/00: Fusion polypeptide
- 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
- 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)
- 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 synovial sarcoma X Breakpoint (SSX)-2. 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

A recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding a T cell receptor (TCR) having antigenic specificity for synovial sarcoma X Breakpoint (SSX)-2 (SEQ ID NO: 1),
wherein the TCR comprises SEQ ID NOs: 19 and 20.

### Claim 2 (depends on 1)

The recombinant expression vector of claim 1, wherein the TCR also recognizes any one or more of SSX-3 (SEQ ID NO: 3), SSX-4 (SEQ ID NO: 4), SSX-5 (SEQ ID NO: 5), SSX-9 (SEQ ID NO: 6), and SSX-10 (SEQ ID NO: 7).

### Claim 3 (depends on 1)

The recombinant expression vector of claim 1, wherein the TCR has antigenic specificity for an SSX-2 peptide comprising KASEKIFYV (SEQ ID NO: 2).

### Claim 4 (depends on 1)

The recombinant expression vector of claim 1, wherein the TCR recognizes any one or more of KVSEKIVYV (SEQ ID NO: 8), KSSEKIVYV (SEQ ID NO: 9), KASEKIIYV (SEQ ID NO: 10), KSSEKIIYV (SEQ ID NO: 11), and KASEKILYV (SEQ ID NO: 12).

### Claim 5 (depends on 1)

The recombinant expression vector of claim 1, wherein the TCR further comprises SEQ ID NOs: 21 and 22.

### Claim 6 (depends on 1)

The recombinant expression vector of claim 1, wherein the TCR comprises:
a) SEQ ID NO: 23 and 24 or
b) SEQ ID NO: 25 and 26.

### Claim 7

A recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequences of SEQ ID NOs: 13-18.

### Claim 8 (depends on 7)

The recombinant expression vector of claim 7, wherein the polypeptide comprises the amino acid sequences of SEQ ID NOs: 19 and 20.

### Claim 9 (depends on 8)

The recombinant expression vector of claim 8, wherein the polypeptide comprises:
a) SEQ ID NO: 23 and 24; or
b) SEQ ID NO: 25 and 26.

### Claim 10

A recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding a protein comprising a first polypeptide chain comprising SEQ ID NO: 19 and a second polypeptide chain comprising SEQ ID NO: 20.

### Claim 11 (depends on 10)

The recombinant expression vector of claim 10, wherein the protein comprises:
a) a first polypeptide chain comprising SEQ ID NO: 23 and a second polypeptide chain comprising SEQ ID NO: 24; or
b) a first polypeptide chain comprising SEQ ID NO: 25 and a second polypeptide chain comprising SEQ ID NO: 26.

### Claim 12 (depends on 10)

The recombinant expression vector of claim 10, wherein the protein is a fusion protein.

### Claim 13 (depends on 10)

The recombinant expression vector of claim 10, wherein the protein is a recombinant antibody.

### Claim 14 (depends on 1)

The recombinant expression vector of claim 1, wherein the vector is a retroviral vector.

### Claim 15 (depends on 1)

An isolated host cell comprising the recombinant expression vector of claim 1.

### Claim 16 (depends on 15)

The isolated host cell of claim 15, wherein the cell is a peripheral blood lymphocyte (PBL).

### Claim 17 (depends on 16)

The isolated host cell of claim 16, wherein the PBL is a CD8+ T cell or a CD4+ T cell.

### Claim 18 (depends on 15)

A population of cells comprising at least one host cell of claim 15.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising the recombinant expression vector of claim 1 and a pharmaceutically acceptable carrier.

### Claim 20 (depends on 18)

A method of detecting the presence of cancer which expresses the amino acid sequence of KASEKIFYV (SEQ ID NO: 2) presented by an HLA-A2 molecule in a host, comprising:
(a) contacting a sample comprising cells of the cancer with the population of cells of claim 18, thereby forming a complex, and
(b) detecting the complex,
wherein detection of the complex is indicative of the presence of the cancer which expresses the amino acid sequence of KASEKIFYV (SEQ ID NO: 2) presented by the HLA-A2 molecule in the host.

### Claim 21 (depends on 18)

A method of treating cancer which expresses the amino acid sequence of KASEKIFYV (SEQ ID NO: 2) presented by an HLA-A2 molecule in a host, comprising administering to the host the population of cells of claim 18, in an amount effective to treat the cancer which expresses the amino acid sequence of KASEKIFYV (SEQ ID NO: 2) presented by the HLA-A2 molecule in the host, wherein the cancer is ovarian cancer, glioma, melanoma, or hepatocellular carcinoma.

### Claim 22 (depends on 20)

The method of claim 20, wherein the cancer is selected from the group consisting of head-neck cancer, ovarian cancer, lung cancer, glioma, melanoma, renal cancer, lymphoma, colon cancer, pancreatic cancer, breast cancer, prostate cancer, synovial sarcoma, osteogenic sarcoma, leiomyosarcoma uteri, and hepatocellular carcinoma.

### Claim 23 (depends on 20)

The method of claim 20, wherein the host cells comprise the recombinant expression vector and are autologous to the host.

### Claim 24 (depends on 21)

The method of claim 21, further comprising administering 5-aza-2′-deoxycytidine (DAC) to the host.

### Claim 25 (depends on 18)

A pharmaceutical composition comprising the population of cells of claim 18 and a pharmaceutically acceptable carrier.