# US 2015/0147302 A1 · Therapeutically useful molecules

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- Number: US 2015/0147302 A1
- Document ID: US20150147302A1
- Status: Published application
- Kind: A1
- Application number: 14/469,387
- Filed: 2014-08-26
- Published: 2015-05-28
- Earliest claimed: 2003-12-06
- Assignees: Imperial Innovations Limited
- Applicants: Imperial Innovations Limited
- Inventors: Hans Josef Stauss; Liquan Gao; Shao-An Xue
- Web page: https://patentgrep.com/patent/US20150147302A1

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- 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 40/4243: {Wilms tumor 1 [WT1]}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C12N 5/0636: {T lymphocytes}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- C12N 2740/10043: viral genome or elements thereof as genetic vector
- 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)

## Abstract

A T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs): CDR1α: SSYSPS CDR2α: YTSAATL CDR3α: VVSPF-SGGGADGLT or comprising or consisting of SPPSGGGADGLT and the beta chain portion contains three complementarity determining regions (CDRs): CDR1β: DFQATT CDR2β: SNEGSKA CDR3β: comprising SARDGGEG or comprising or consisting of RDGGEGSETQY, or wherein up to three amino acid residues in one or more CDRs are replaced by another amino acid residue. The invention also includes polynucleotides encoding the TCR molecules, and host cells containing the said polynucleotides. Patient derived T cells may have the polynucleotides encoding the TCR molecules introduced therein, and the engineered T cells may be introduced into the patient in order to combat a WT1-expressing malignancy.

## Claims

### Claim 1

An isolated T cell receptor (TCR) molecule containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs):
CDR1α: SSYSPS (SEQ ID NO: 2);
CDR2α: YTSAATL (SEQ ID NO: 3); and
CDR3α: VVSPFSGGGADGLT (SEQ ID NO: 4) or
wherein the alpha chain portion contains three CDRs:
CDR1α: SSYSPS (SEQ ID NO: 2);
CDR2α: YTSAATL (SEQ ID NO: 3); and
CDR3α: comprising or consisting of SPFSGGGADGLT (SEQ ID NO: 5) and
wherein the beta chain portion contains three CDRs:
CDR1β: DFQATT (SEQ ID NO: 6);
CDR2β: SNEGSKA (SEQ ID NO: 7); and
CDR3β: comprising SARDGGEG (SEQ ID NO: 8) or
wherein the beta chain portion contains three CDRs:
CDR1β: DFQATT (SEQ ID NO: 6);
CDR2β: SNEGSKA (SEQ ID NO: 7); and
CDR3β: comprising or consisting of RDGGEGSETQY (SEQ ID NO: 9),
or a variant of said TCR molecule wherein up to one amino acid residue in one or more of the six CDRs is replaced by another amino acid residue.

### Claim 2 (depends on 1)

The TCR molecule according to claim 1 wherein CDR3α has the amino acid sequence VVSPFSGGGADGLT (SEQ ID NO: 4).

### Claim 3 (depends on 1)

The TCR molecule according to claim 1 wherein CDR3α has the amino acid sequence SPFSGGGADGLT (SEQ ID NO: 5).

### Claim 4 (depends on 1)

The TCR molecule according to claim 1 wherein CDR3β has the amino acid sequence SARDGGEG (SEQ ID NO: 8).

### Claim 5 (depends on 1)

The TCR molecule according to claim 1 wherein CDR3β has the amino acid sequence RDGGEGSETQY (SEQ ID NO: 9).

### Claim 6 (depends on 1)

The TCR molecule according to claim 1 wherein the alpha chain portion and the beta chain portion are present on different polypeptide chains.

### Claim 7 (depends on 1)

The TCR molecule according to claim 1 wherein the alpha chain portion and the beta chain portion are present in the same polypeptide chain.

### Claim 8 (depends on 1)

The TCR molecule according to claim 1 wherein the CDRs are grafted to a human framework region.

### Claim 9 (depends on 8)

The TCR molecule according to claim 8 wherein the alpha chain portion has the amino acid sequence given in FIG. 2.

### Claim 10 (depends on 8)

The TCR molecule according to claim 8 wherein the beta chain portion has the amino acid sequence given in FIG. 4.

### Claim 11 (depends on 1)

The TCR molecule according to claim 1 which is soluble.

### Claim 12 (depends on 1)

A polynucleotide encoding the alpha chain portion of the TCR molecule of claim 1.

### Claim 13 (depends on 1)

A polynucleotide encoding the beta chain portion of the TCR molecule of claim 1.

### Claim 14 (depends on 7)

A polynucleotide encoding the TCR molecule of claim 7.

### Claim 15 (depends on 14)

An expression vector comprising the polynucleotide of claim 14.

### Claim 16

(canceled)

### Claim 17 (depends on 15)

A host cell comprising the expression vector of claim 15.

### Claim 18 (depends on 17)

The host cell according to claim 17 which is a T cell.

### Claim 19

(canceled)

### Claim 20 (depends on 1)

A method of combating a WT1-expressing malignancy in a patient, the method comprising introducing into the patient a T cell, which is modified to express the TCR molecule of claim 1.

### Claim 21

(canceled)

### Claim 22 (depends on 20)

The method according to claim 20 wherein the WT1-expressing malignancy is breast cancer, colon cancer, lung cancer, leukaemia, ovarian cancer, melanoma, head and neck cancer, thyroid cancer, glioblastoma or sarcoma.

### Claim at position 23

23-27. (canceled)

### Claim 28 (depends on 1)

The TCR molecule according to claim 1 wherein the variant has up to one amino acid substitution in only CDR3α and/or CDR3β.

### Claim 29 (depends on 1)

The TCR molecule according to claim 1 wherein the replaced amino acid residue in one or more of the six CDRs is a conservative amino acid substitution.