# US 10,117,918 B2 · Antigen-specific T cell receptors and T cell epitopes

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- Number: US 10,117,918 B2
- Document ID: US10117918B2
- Status: Granted
- Kind: B2
- Application number: 15/392,677
- Filed: 2016-12-28
- Published: 2017-04-27
- Granted: 2018-11-06
- Earliest claimed: 2010-09-20
- Assignees: BioNTech Cell & Gene Therapies GmbH; Translationale Onkologie an der Universitatsmedizin der Johannes Gutenberg-Universitat Mainz gemeinnutzige GmbH
- Applicants: Ugur Sahin; Ozlem Tureci; Petra Simon; Tana Omokoko
- Inventors: Ugur Sahin; Ozlem Tureci; Petra Simon; Tana Omokoko
- Web page: https://patentgrep.com/patent/US10117918B2

## CPC

- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- A61K 39/12: Viral antigens
- 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 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/4267: {Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE}
- A61K 40/4269: {NY-ESO}
- A61K 40/46: Viral antigens
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/22: for herpes viruses
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/005: from viruses
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 5/0636: {T lymphocytes}
- C12N 9/16: acting on ester bonds (3.1)
- C12N 15/85: for animal cells
- C12Y 301/03048: Protein-tyrosine-phosphatase (3.1.3.48)
- G01N 33/5017: {for testing neoplastic activity}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- C12N 2510/00: Genetically modified cells
- C12N 2710/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- G01N 2333/916: acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
- 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)
- C12Y: ENZYMES
- 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 present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

## Claims

### Claim 1

A nucleic acid encoding a T cell receptor selected from the group consisting of:
(I) a T cell receptor comprising:
(i) a T cell receptor α-chain comprising all three CDR sequences of T cell receptor α-chain of SEQ ID NO: 46, and
(ii) a T cell receptor β-chain comprising all three of the CDR sequences of T cell receptor β-chain of SEQ ID NO: 47; and
(II) a T cell receptor comprising:
(i) a T cell receptor α-chain comprising the T cell receptor α-chain sequence of SEQ ID NO: 46, and
(ii) a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: 47.

### Claim 2

An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor α-chain comprising the T cell receptor α-chain sequence of SEQ ID NO: 46 and a nucleic acid encoding a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: 47 or (ii) a nucleic acid encoding a T cell receptor comprising the T cell receptor α-chain sequence of SEQ ID NO: 46 and the T cell receptor β-chain sequence of SEQ ID NO: 47.

### Claim 3 (depends on 2)

A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 2.

### Claim 4

An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor α-chain comprising all three of the CDR sequences of the T cell receptor α-chain sequence of SEQ ID NO: 46 and a nucleic acid encoding a T cell receptor β-chain comprising all three of the CDR sequences of the T cell receptor β-chain sequence of SEQ ID NO: 47 or (ii) a nucleic acid encoding a T cell receptor comprising all three of the CDR sequences of the T cell receptor α-chain sequence of SEQ ID NO: 46 and all three of the CDR sequences the T cell receptor β-chain sequence of SEQ ID NO: 47.

### Claim 5 (depends on 4)

A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 4.

### Claim 6 (depends on 2)

The antigen-specific lymphoid cell of claim 2, wherein the nucleic acid is RNA.

### Claim 7 (depends on 6)

The antigen-specific lymphoid cell of claim 6, wherein the RNA is in vitro transcribed RNA (IVT RNA).

### Claim 8 (depends on 2)

The antigen-specific lymphoid cell of claim 2, wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.

### Claim 9 (depends on 2)

The antigen-specific lymphoid cell of claim 2, wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.

### Claim 10 (depends on 4)

The antigen-specific lymphoid cell of claim 4, wherein the nucleic acid is RNA.

### Claim 11 (depends on 10)

The antigen-specific lymphoid cell of claim 10, wherein the RNA is in vitro transcribed RNA (IVT RNA).

### Claim 12 (depends on 4)

The antigen-specific lymphoid cell of claim 4, wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.

### Claim 13 (depends on 4)

The antigen-specific lymphoid cell of claim 4, wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.