# US 10,946,105 B2 · Peptides derived from transient receptor potential cation channel subfamily M member 1 (TRPM1), complexes comprising such peptides bound to MHC molecules

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- Number: US 10,946,105 B2
- Document ID: US10946105B2
- Status: Granted
- Kind: B2
- Application number: 15/778,206
- Filed: 2016-11-23
- Published: 2018-12-06
- Granted: 2021-03-16
- Earliest claimed: 2015-11-23
- Assignees: Immunocore Limited
- Applicants: Immunocore Limited; Adaptimmune Limited
- Inventors: Alex Powlesland; Maurits Kleijnen; Meidai Sun
- Web page: https://patentgrep.com/patent/US10946105B2

## CPC

- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- A61P 35/00: Antineoplastic agents
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- 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)

## Abstract

The present invention relates to novel peptides derived from Transient receptor potential cation channel subfamily M member 1 (TRPM1), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.

## Claims

### Claim 1

A method of treating cancer in a subject, comprising:
administering to the subject a therapeutically effective amount of a binding moiety capable of specifically binding a polypeptide
wherein the polypeptide comprises:
(a) the amino acid sequence of any one of SEQ ID NOS: 1-16, or
(b) the amino acid sequence of any one of SEQ ID NOs: 1-16 with the exception of 1, 2 or 3 amino acid substitutions and/or 1, 2 or 3 amino acid insertions, and/or 1, 2 or 3 amino acid deletions, and
wherein the polypeptide is capable of forming a complex with a Major Histocompatibility Complex (MHC) molecule.

### Claim 2 (depends on 1)

The method of claim 1, wherein the polypeptide is 8 to 16 amino acids in length.

### Claim 3 (depends on 2)

The method of claim 2, wherein the polypeptide is 9 amino acids in length.

### Claim 4 (depends on 3)

The method of claim 3, wherein the polypeptide has the amino acid sequence of SEQ ID NO: 12.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cancer is uveal melanoma.

### Claim 6 (depends on 1)

The method of claim 1, wherein the binding moiety is capable of specifically binding the polypeptide when it is in complex with the MHC molecule.

### Claim 7 (depends on 6)

The method of claim 6, wherein the MHC molecule is MHC class I.

### Claim 8 (depends on 7)

The method of claim 7, wherein the MHC class I molecule is HLA-A*02.

### Claim 9 (depends on 1)

The method of claim 1, wherein the binding moiety is a T cell receptor (TCR) or an antibody.

### Claim 10 (depends on 9)

The method of claim 9, wherein the binding moiety is a TCR.

### Claim 11 (depends on 10)

The method of claim 10, wherein the TCR is a heterodimeric TCR comprising an alpha chain and a beta chain.

### Claim 12 (depends on 11)

The method of claim 11, wherein the alpha chain and the beta chain of the heterodimeric TCR each comprises a variable region and a constant region.

### Claim 13 (depends on 12)

The method of claim 12, wherein each variable region comprises three hypervariable complementarity determining regions (CDRs) embedded in a framework sequence: CDR1, CDR2, and CDR3.

### Claim 14 (depends on 10)

The method of claim 10, wherein the TCR is on the surface of a cell.

### Claim 15 (depends on 6)

The method of claim 6, wherein the binding moiety and/or the complex is conjugated to a detectable label.

### Claim 16 (depends on 15)

The method of claim 15, wherein the detectable label is selected from biotin, fluorescent streptavidin, a fluorescent or luminescent label, a radiolabel, or a peptide tag.

### Claim 17 (depends on 16)

The method of claim 16, wherein the peptide tag is selected from a FLAG tag, a MYC tag, an HA tag, a GST tag, a Strep tag, or a poly-histidine (His) tag.

### Claim 18

A method of treating uveal melanoma, comprising:
administering to the subject a therapeutically effective amount of an heterodimeric TCR capable of specifically binding a polypeptide having the sequence of SEQ ID NO: 12 in complex with HLA-A*02.
