# US 11,998,607 B2 · T cell receptors and immune therapy using the same

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- Number: US 11,998,607 B2
- Document ID: US11998607B2
- Status: Granted
- Kind: B2
- Application number: 16/826,946
- Filed: 2020-03-23
- Published: 2020-08-13
- Granted: 2024-06-04
- Earliest claimed: 2016-12-08
- Assignees: Immatics Biotechnologies GmbH
- Applicants: Immatics Biotechnologies GmbH
- Inventors: Leonie Alten; Sebastian Bunk; Dominik Maurer; Claudia Wagner
- Web page: https://patentgrep.com/patent/US11998607B2

## CPC

- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 39/0011: {Cancer antigens}
- A61K 39/001186: {MAGE}
- 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 40/4268: {MAGE}
- A61K 40/4269: {NY-ESO}
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61P 35/00: Antineoplastic agents
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 5/00: Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor; (plant reproduction by tissue culture techniques A01H4/00)
- C12N 5/0636: {T lymphocytes}
- C12N 15/85: for animal cells
- 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)
- A61K 2039/572: {cytotoxic response}
- C07K 14/70514: {CD4}
- C07K 14/70517: {CD8}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention pertains to antigen recognizing constructs against tumor associated antigens (MAGEA1). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

## Claims

### Claim 1

An antigen recognizing construct, comprising
a first T cell receptor (TCR) variable chain region comprising
a complementarity determining region (CDR)1 comprising SEQ ID NO: 49,
a CDR2, and
a CDR3 comprising SEQ ID NO: 51, and
a second TCR variable chain region comprising
a CDR1 comprising SEQ ID NO: 55,
a CDR2, and
a CDR3 comprising SEQ ID NO: 57,
wherein each of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, and SEQ ID NO: 57 comprises at most one conservative amino acid substitution.

### Claim 2 (depends on 1)

The antigen recognizing construct of claim 1, wherein the antigen recognizing construct binds to a peptide of SEQ ID NO: 133 in a complex with an MHC class I molecule.

### Claim 3 (depends on 1)

The antigen recognizing construct of claim 1, wherein the soluble antigen recognizing construct does not selectively bind any of the peptides set forth in SEQ ID NO: 143 to 152.

### Claim 4 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region comprises a CDR2 comprising SEQ ID NO: 50 and the second TCR variable chain region comprises a CDR2 comprising SEQ ID NO: 56.

### Claim 5 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain comprising SEQ ID NO: 49,
a CDR2α chain comprising SEQ ID NO: 50, and
a CDR3α chain comprising SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain comprising SEQ ID NO: 55,
a CDR2β chain comprising SEQ ID NO: 56, and
a CDR3β chain comprising SEQ ID NO: 57,
wherein each of SEQ ID NOs: 49 and 55 comprise at most one conservative amino acid substitution.

### Claim 6 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain comprising SEQ ID NO: 49,
a CDR2α chain comprising SEQ ID NO: 50, and
a CDR3α chain comprising SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain comprising SEQ ID NO: 55,
a CDR2β chain comprising SEQ ID NO: 56, and
a CDR3β chain comprising SEQ ID NO: 57,
wherein each of SEQ ID NOs: 50 and 56 comprise at most one conservative amino acid substitution.

### Claim 7 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain comprising SEQ ID NO: 49,
a CDR2α chain comprising SEQ ID NO: 50, and
a CDR3α chain comprising SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain comprising SEQ ID NO: 55,
a CDR2β chain comprising SEQ ID NO: 56, and
a CDR3β chain comprising SEQ ID NO: 57,
wherein each of SEQ ID NOs: 51 and 57 comprises at most one conservative amino acid substitution.

### Claim 8 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain consisting of SEQ ID NO: 49,
a CDR2α chain consisting of SEQ ID NO: 50, and
a CDR3α chain comprising SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain consisting of SEQ ID NO: 55,
a CDR2β chain consisting of SEQ ID NO: 56, and
a CDR3β chain comprising SEQ ID NO: 57.

### Claim 9 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain comprising SEQ ID NO: 49,
a CDR2α chain consisting of SEQ ID NO: 50, and
a CDR3α chain comprising SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain comprising SEQ ID NO: 55,
a CDR2β chain consisting of SEQ ID NO: 56, and
a CDR3β chain comprising SEQ ID NO: 57.

### Claim 10 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain consisting of SEQ ID NO: 49,
a CDR2α chain comprising SEQ ID NO: 50, and
a CDR3α chain consisting of SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain consisting of SEQ ID NO: 55,
a CDR2β chain comprising SEQ ID NO: 56, and
a CDR3β chain consisting of SEQ ID NO: 57.

### Claim 11 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain comprising SEQ ID NO: 49,
a CDR2α chain comprising SEQ ID NO: 50, and
a CDR3α chain consisting of SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain comprising SEQ ID NO: 55,
a CDR2β chain comprising SEQ ID NO: 56, and
a CDR3β chain consisting of SEQ ID NO: 57.

### Claim 12 (depends on 1)

The antigen recognizing construct of claim 1, wherein
the first TCR variable chain region comprises
a CDR1α chain consisting of SEQ ID NO: 49,
a CDR2α chain consisting of SEQ ID NO: 50, and
a CDR3α chain consisting of SEQ ID NO: 51, and
the second TCR variable chain region comprises
a CDR1β chain consisting of SEQ ID NO: 55,
a CDR2β chain consisting of SEQ ID NO: 56, and
a CDR3β chain consisting of SEQ ID NO: 57.

### Claim 13 (depends on 1)

The antigen recognizing construct of claim 1, wherein the antigen recognizing construct is an αβ-T cell receptor (TCR) or a derivative or fragment thereof, or a 76 TCR or a derivative or fragment thereof.

### Claim 14 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region comprises at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 52 or the second TCR variable chain region comprises at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 58.

### Claim 15 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region comprises the amino acid sequence of SEQ ID NO: 52 or the second TCR variable chain region comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 16 (depends on 1)

A nucleic acid or nucleic acids encoding the antigen recognizing construct of claim 1.

### Claim 17 (depends on 16)

An expression vector comprising the nucleic acid(s) of claim 16 operably linked to at least one promoter sequence.

### Claim 18 (depends on 17)

A host cell transformed with the expression vector of claim 17.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising the antigen recognizing construct of claim 1.

### Claim 20 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region comprises at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 52 or the second TCR variable chain region comprises at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 58.

### Claim 21 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region comprises at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 52 and the second TCR variable chain region comprises at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 58.

### Claim 22 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region comprises at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 52 and the second TCR variable chain region comprises at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 58.

### Claim 23 (depends on 6)

The antigen recognizing construct of claim 6, wherein the first TCR variable chain region comprises the amino acid sequence of SEQ ID NO: 52 and the second TCR variable chain region comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 24 (depends on 1)

The antigen recognizing construct of claim 1, wherein the first TCR variable chain region consists of the amino acid sequence of SEQ ID NO: 52 and the second TCR variable chain region consists of the amino acid sequence of SEQ ID NO: 58.

### Claim 25

An antigen recognizing construct comprising a first TCR chain comprising the amino acid sequence of SEQ ID NO: 54 and a second TCR chain comprising the amino acid sequence of SEQ ID NO: 60.