# US 11,111,294 B2 · T cell receptors and immune therapy using the same

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- Number: US 11,111,294 B2
- Document ID: US11111294B2
- Status: Granted
- Kind: B2
- Application number: 16/733,845
- Filed: 2020-01-03
- Published: 2020-05-07
- Granted: 2021-09-07
- Earliest claimed: 2017-06-30
- Assignees: Immatics Biotechnologies GmbH
- Applicants: Immatics Biotechnologies GmbH
- Inventors: Claudia Wagner; Leonie Alten; Sebastian Bunk; Dominik Maurer
- Web page: https://patentgrep.com/patent/US11111294B2

## CPC

- C07K 16/26: against hormones {; against hormone releasing or inhibiting factors}
- 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 40/42: Cancer antigens
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/8135: {Kazal type inhibitors, e.g. pancreatic secretory inhibitor, ovomucoid}
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/38: against protease inhibitors of peptide structure
- C12N 5/0636: {T lymphocytes}
- C12N 15/85: for animal cells
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/62: comprising only variable region components
- C12N 2015/8518: {expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles}
- 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)
- 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 (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). 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 SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 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

A method of treating a patient who has acute myeloid leukemia, comprising administering to the patient a population of transformed T cells expressing at least one vector encoding a T cell receptor (TCR),
wherein the TCR comprises an alpha chain and a beta chain,
wherein the alpha chain comprises SEQ ID NOs: 97, 98, and 99, and the beta chain comprises SEQ ID NOs: 103, 104, and 105,
wherein the TCR binds to a peptide consisting of the amino acid sequence of ALSVLRLAL (SEQ ID NO: 133) in a complex with an MHC class I molecule.

### Claim 2 (depends on 1)

The method of claim 1, wherein the population of transformed cells are produced by a method comprising
isolating a CD8+ T cell from a subject,
transforming the cell with at least one vector encoding the TCR to produce a transformed cell, and
expanding the transformed cell to produce the population of transformed cells.

### Claim 3 (depends on 2)

The method of claim 2, wherein the subject is the patient.

### Claim 4 (depends on 1)

The method of claim 1, wherein said T cells are CD8+ T cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the TCR comprises
an α chain comprising the amino acid sequence of SEQ ID NO: 102 and a β chain comprising of the amino acid sequence of SEQ ID NO: 108.

### Claim 6 (depends on 1)

The method of claim 1, wherein the MHC class I molecule is HLA-A*02.

### Claim 7 (depends on 1)

The method of claim 1, wherein the population of transformed cells are administered in the form of a pharmaceutical composition.

### Claim 8 (depends on 7)

The method of claim 7, wherein the pharmaceutical composition comprises a chemotherapeutic agent selected from the group consisting of asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and vincristine.

### Claim 9 (depends on 1)

The method of claim 1, wherein the TCR comprises:
a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 97,
a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 98,
a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 99,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 103,
a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 104, and
a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 105.

### Claim 10 (depends on 1)

The method of claim 1, wherein the alpha chain comprises an alpha TCR variable chain region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 100 and the beta chain comprises a beta TCR variable chain region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 106.

### Claim 11 (depends on 1)

The method of claim 1, wherein the alpha chain comprises an alpha chain constant region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 101 and the beta chain comprises a beta chain constant region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107.

### Claim 12 (depends on 1)

The method of claim 1, wherein the alpha chain comprises at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 102 and the beta chain comprises at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108.

### Claim 13 (depends on 1)

The method of claim 1, wherein the alpha chain comprises at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 102 and the beta chain comprises at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108.

### Claim 14 (depends on 1)

The method of claim 1, wherein the TCR comprises:
a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 97,
a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 98,
a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 99,
a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 103,
a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 104, and
a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 105.

### Claim 15 (depends on 1)

The method of claim 1, wherein the TCR comprises:
a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 97,
a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 98,
a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 99,
a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 103,
a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 104, and
a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 105.
