# US 12,178,787 B2 · T cell receptors for immunotherapy

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- Number: US 12,178,787 B2
- Document ID: US12178787B2
- Status: Granted
- Kind: B2
- Application number: 16/652,932
- Filed: 2018-10-12
- Published: 2020-07-30
- Granted: 2024-12-31
- Earliest claimed: 2017-10-12
- Assignees: Board of Regents, The University of Texas System
- Applicants: Board of Regents, The University of Texas System
- Inventors: Gregory Lizée; Cassian Yee
- Web page: https://patentgrep.com/patent/US12178787B2

## CPC

- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/4271: {Melanoma antigens}
- C07K 14/435: from animals; from humans
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 5/0636: {T lymphocytes}
- C12N 5/0637: {Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg}
- C12N 15/86: Viral vectors
- A61K 2239/57: Skin; melanoma
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Provided are T cell receptors (TCR) and TCR variable regions that can selectively bind SLC45A2. The TCR may be utilized in various therapies, such as autologous cell transplantation, to treat a cancer, such as a cutaneous melanoma, uveal melanoma, a mucosal melanoma, or a metastatic melanoma. Methods for expanding a population of T cells that target SLC45A2 are also provided.

## Claims

### Claim 1

An engineered T cell receptor (TCR) comprising
(a) an alpha chain comprising a CDR1 having the amino acid of SEQ ID NO:3, a CDR2 having the amino acid sequence of SEQ ID NO:4, and a CDR3 having the amino acid sequence of SEQ ID NO: 5, and a beta chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:8, a CDR2 having the amino acid sequence of SEQ ID NO:9, and a CDR3 having the amino acid sequence of SEQ ID NO:10;
(b) an alpha chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:13, a CDR2 having the amino acid sequence of SEQ ID NO:14, and a CDR3 having the amino acid sequence of SEQ ID NO:15, and a beta chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:18, a CDR2 having the amino acid sequence of SEQ ID NO:19, and a CDR3 having the amino acid sequence of SEQ ID NO:20;
(c) an alpha chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:23, a CDR2 having the amino acid sequence of SEQ ID NO:24, and a CDR3 having the amino acid sequence of SEQ ID NO:25, and a beta chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:28, a CDR2 having the amino acid sequence of SEQ ID NO:29, and a CDR3 having the amino acid sequence of SEQ ID NO:30;
(d) an alpha chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:33, a CDR2 having the amino acid sequence of SEQ ID NO:34, and a CDR3 having the amino acid sequence of SEQ ID NO:35, and a beta chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:38, a CDR2 having the amino acid sequence of SEQ ID NO:39, and a CDR3 having the amino acid sequence of SEQ ID NO:40; or
(e) an alpha chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:43, a CDR2 having the amino acid sequence of SEQ ID NO:44, and a CDR3 having the amino acid sequence of SEQ ID NO:45, and a beta chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:48, a CDR2 having the amino acid sequence of SEQ ID NO:49, and a CDR3 having the amino acid sequence of SEQ ID NO:50.

### Claim 2 (depends on 1)

The TCR of claim 1, wherein the engineered TCR binds HLA-A2.

### Claim 3 (depends on 2)

The TCR of claim 2, wherein the engineered TCR binds HLA-A*0201.

### Claim 4 (depends on 1)

The TCR of claim 1, wherein the engineered TCR binds HLA-A24.

### Claim 5 (depends on 4)

The TCR of claim 4, wherein the engineered TCR binds HLA-A*2402.

### Claim 6 (depends on 1)

The TCR of claim 1, wherein the TCR comprises:
(a) for claim 1 (a), an alpha chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO: 2 and a beta chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO: 7;
(b) for claim 1 (b), an alpha chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO: 12 and a beta chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:17;
(c) for claim 1 (c), an alpha chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:22 and a beta chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:27;
(d) for claim 1 (d), an alpha chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:32 and a beta chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:37; or (e) for claim 1 (e), an alpha chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:42 and a beta chain having at least 90%, 95%, or 99% identity to the amino acid sequence of SEQ ID NO:47.

### Claim 7 (depends on 1)

The TCR of claim 1, wherein the TCR comprises:
(a) for claim 1 (a), an alpha chain of SEQ ID NO: 2 and a beta chain of SEQ ID NO: 7;
(b) for claim 1 (b), an alpha chain of SEQ ID NO: 12 and a beta chain of SEQ ID NO:17;
(c) for claim 1 (c), an alpha chain of SEQ ID NO:22 and a beta chain of SEQ ID NO:27;
(d) for claim 1 (d), an alpha chain of SEQ ID NO:32 and a beta chain of SEQ ID NO:37; or
(e) for claim 1 (e), an alpha chain of SEQ ID NO:42 and a beta chain of SEQ ID NO:47.

### Claim 8 (depends on 6)

The TCR of claim 6, wherein the TCR comprises:
(a) for claim 6 (a), an alpha chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO: 1 and a beta chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO: 6;
(b) for claim 6 (b), an alpha chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:11 and a beta chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO: 16;
(c) for claim 6 (c), an alpha chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:21 and a beta chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO: 26;
(d) for claim 6 (d), an alpha chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:31 and a beta chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO: 36; or (e) for claim 6 (e), an alpha chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:41 and a beta chain encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO: 46.

### Claim 9 (depends on 6)

The TCR of claim 6, wherein the TCR comprises:
(a) for claim 6 (a), an alpha chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 1 and a beta chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 6;
(b) for claim 6 (b), an alpha chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:11 and a beta chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:16;
(c) for claim 6 (c), an alpha chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:21 and a beta chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:26;
(d) for claim 6 (d), an alpha chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:31 and a beta chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:36; or (e) for claim 6 (e), an alpha chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:41 and a beta chain encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:46.

### Claim 10 (depends on 1)

The TCR of claim 1, wherein the TCR is further defined as a soluble TCR, wherein the soluble TCR does not comprise a transmembrane domain.

### Claim 11 (depends on 1)

The TCR of claim 1, further comprising a detectable label.

### Claim 12 (depends on 1)

The TCR of claim 1, wherein the TCR is covalently bound to a therapeutic agent.

### Claim 13 (depends on 1)

A multivalent TCR complex comprising a plurality of TCRs according to claim 1.

### Claim 14 (depends on 13)

The complex of claim 13, wherein the multivalent TCR comprises 2, 3, 4 or more TCRs associated with one another.

### Claim 15 (depends on 1)

A method of treating cancer in a subject comprising administering an effective amount of a host cell engineered to express the TCR of claim 1 to the subject.

### Claim 16 (depends on 15)

The method of claim 15, wherein the subject is identified to have an HLA-A*0201 allele or an HLA-A*2402 allele.

### Claim 17 (depends on 15)

The method of claim 15, wherein the host cell is a TCR-engineered T cell or peripheral blood lymphocyte.

### Claim 18 (depends on 15)

The method of claim 15, wherein the cancer is a melanoma.

### Claim 19 (depends on 15)

The method of claim 15, further comprising lymphodepletion of the subject prior to administration of the cells.

### Claim 20 (depends on 15)

The method of claim 15, wherein the subject is determined to have cancer cells which overexpress SLC45A2.