# US 10,370,427 B2 · Influenza-specific T-cell receptor and its uses in the detection, prevention and/or treatment of influenza

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- Number: US 10,370,427 B2
- Document ID: US10370427B2
- Status: Granted
- Kind: B2
- Application number: 15/106,292
- Filed: 2014-12-18
- Published: 2016-10-13
- Granted: 2019-08-06
- Earliest claimed: 2013-12-19
- Assignees: Friedrich-Alexander-Universität Erlangen-Nürnberg
- Applicants: Friedrich-Alexander Universität Erlangen-Nürnberg
- Inventors: Thomas Harrer; Angela Hückelhoven
- Web page: https://patentgrep.com/patent/US10370427B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- G01N 33/56983: {Viruses}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/70: containing domain for protein-protein interaction
- G01N 2333/11: Orthomyxoviridae, e.g. influenza virus
- 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)
- 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)

## Abstract

The present invention relates to specific T-cell receptor a-chains, T-cell receptor β-chains and T-cell receptors comprising said T-cell receptor a-chain and/or β-chain. In particular, the invention relates to T-cell receptors and/or chains binding to the influenza matrix peptide GILGFVFTL (GL9 peptide) presented by Human Leukocyte antigen A2 (HLA-A2) molecules. The present invention further relates to soluble TCR constructs, chimeric TCRs, nucleic acids, expression constructs and cells comprising said TCR a-chain and/or β-chain or the respective TCR. The present invention further relates to the use of the TCR a-chain and/or β-chain or the respective TCR or the soluble TCR constructs or chimeric TCRs as a medicament, preferably in the detection, prevention and/or treatment of influenza. The present invention further relates to methods of detecting, preventing and/or treating influenza.

## Claims

### Claim 1

A T-cell receptor comprising:
A) a T-cell receptor α-chain, wherein said T-cell receptor α-chain comprises the amino acid sequence of LNTNAGKSTFGDGTTLTVKP (SEQ ID NO: 1) and
B) a T-cell receptor (β-chain, wherein said T-cell receptor β-chain comprises the amino acid sequence of TSGTEAFFGQGTRLTVV (SEQ ID NO: 3),
wherein the T-cell receptor α-chain and the T-cell receptor β-chain are linked to each other via a linker.

### Claim 2 (depends on 1)

The T-cell receptor of claim 1, wherein said T-cell receptor α-chain comprises the amino acid sequence of SEQ ID NO: 2.

### Claim 3 (depends on 1)

The T-cell receptor of claim 1, wherein said T-cell receptor β-chain comprises the amino acid sequence of SEQ ID NO: 4.

### Claim 4

A T-cell receptor (TCR) comprising:
(i) a T cell receptor α-chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and
(ii) a T-cell receptor β-chain comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4,
wherein the T-cell receptor α-chain and the T-cell receptor β-chain are linked to each other via a linker.

### Claim 5 (depends on 1)

A soluble T-cell receptor (sTCR) construct comprising:
(1) at least one of
the T-cell receptor α-chain according to claim 1, and
the T-cell receptor β-chain according to claim 1, and
(2) at least one fusion component selected from
Fc receptors and/or Fc domains,
cytokines,
toxins, and
antibodies,
wherein the at least one T-cell receptor chain (1) is bound to the fusion component(s) (2), and wherein the soluble T-cell receptor further comprises a label.

### Claim 6 (depends on 1)

A chimeric T-cell receptor comprising at least one of:
A) the T-cell receptor α-chain of claim 1,
B) the T-cell receptor β-chain of claim 1 and
C) a T-cell receptor (TCR) comprising:
(i) a T cell receptor α-chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and
(ii) a T-cell receptor β-chain comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4,
wherein the TCR α-chain and/or the TCR β-chain is/are fused to CD3-zeta chain(s).

### Claim 7 (depends on 1)

An expression construct comprising a nucleic acid encoding at least one of the following:
I) a T-cell receptor comprising
A) a T-cell receptor α-chain, wherein said T-cell receptor α-chain comprises the amino acid sequence of LNTNAGKSTFGDGTTLTVKP (SEQ ID NO: 1) and
B) a T-cell receptor β-chain, wherein said T-cell receptor (β-chain comprises the amino acid sequence of TSGTEAFFGQGTRLTVV (SEQ ID NO: 3);
II) A T-cell receptor (TCR) comprising:
(i) a T cell receptor α-chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and
(ii) a T-cell receptor β-chain comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4;
III) A soluble T-cell receptor (sTCR) construct comprising:
(1) at least one of
the T-cell receptor α-chain according to claim 1, and
the T-cell receptor β-chain according to claims 1, and
(2) at least one fusion component selected from
Fc receptors and/or Fc domains,
cytokines,
toxins, and
antibodies,
wherein the at least one T-cell receptor chain (1) is bound to the fusion component(s) (2), and wherein the soluble T-cell receptor further comprises a label; and
IV) A chimeric T-cell receptor comprising at least one of:
A) the T-cell receptor α-chain of claim 1,
B) the T-cell receptor β-chain of claim 1 and
C) a T-cell receptor (TCR) comprising:
(i) a T cell receptor α-chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and
(ii) a T-cell receptor β-chain comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO:4,
wherein the TCR α-chain and/or the TCR β-chain is/are fused to CD3-zeta chain(s).

### Claim 8 (depends on 7)

The expression construct of claim 7, comprising:
the nucleic acid encoding the amino acid sequence of SEQ ID NO: 1 and/or SEQ ID NO: 3, or the nucleotide sequence of SEQ ID NO: 5 and/or SEQ ID NO: 7, or their complementary sequence(s) or sequence(s) that have at least 95% identity to the nucleotide sequence of SEQ ID NO: 5, and/or comprising the nucleic acid encoding the amino acid sequence of SEQ ID NO: 2 and/or SEQ ID NO: 4, the nucleotide sequence of SEQ ID NO: 6 and/or SEQ ID NO: 8, or their complementary sequence(s) or sequence(s) that have at least 95% identity to the nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 8.

### Claim 9 (depends on 7)

The expression construct of claim 7, wherein said construct further comprises promoter and terminator sequences.

### Claim 10 (depends on 7)

An isolated cell comprising the expression construct of claim 7.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising one or more of:
I) a T-cell receptor comprising
A) a T-cell receptor α-chain, wherein said T-cell receptor α-chain comprises the amino acid sequence of LNTNAGKSTFGDGTTLTVKP (SEQ ID NO: 1) and
B) a T-cell receptor β-chain, wherein said T-cell receptor β-chain comprises the amino acid sequence of TSGTEAFFGQGTRLTVV (SEQ ID NO: 3),
wherein the T-cell receptor α-chain and the T-cell receptor β-chain are linked to each other via a linker;
II) a T-cell receptor (TCR) comprising:
(i) a T cell receptor α-chain comprising the amino acid sequence of SEQ ID NO: 1or SEQ ID NO: 2, and
(ii) a T-cell receptor β-chain comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4,
wherein the T-cell receptor α-chain and the T-cell receptor β-ehain are linked to each other via a linker;
III) a soluble T-cell receptor (sTCR) construct comprising:
(1) at least one of
the T-cell receptor α-chain according to claim 1, and
the T-cell receptor β-chain according to claim 1, and
(2) at least one fusion component selected from
Fc receptors and/or Fc domains,
cytokines,
toxins, and
antibodies,
wherein the at least one T-cell receptor chain (1) is bound to the fusion component(s) (2), and wherein the soluble T-cell receptor further comprises a label; and
IV) a chimeric T-cell receptor comprising at least one of:
A) the T-cell receptor α-chain of claim 1,
B) the T-cell, receptor βchain of claim 1 and
C) a T-cell receptor (TCR) comprising:
(i) a T cell receptor α-chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and
(ii) a T-cell receptor β-chain comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4,
wherein the TCR α-chain and/or the TCR β-chain is/are fused to CD3-zeta chain(s); and
V) an expression construct comprising a nucleic acid encoding at least one of I) through IV) above, or an isolated cell comprising said nucleic acid, and, optionally, a pharmaceutically-acceptable excipient.