# US 11,110,123 B2 · T cell-antigen coupler with various construct optimizations

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- Number: US 11,110,123 B2
- Document ID: US11110123B2
- Status: Granted
- Kind: B2
- Application number: 15/929,513
- Filed: 2020-05-06
- Published: 2020-08-20
- Granted: 2021-09-07
- Earliest claimed: 2018-07-17
- Assignees: Triumvira Immunologics USA, Inc.; McMaster University
- Applicants: Triumvira Immunologics USA, Inc.; McMaster University
- Inventors: Jonathan Lorne Bramson; Christopher W. Helsen; Joanne Alicia Hammill; Kenneth Anthony Mwawasi
- Web page: https://patentgrep.com/patent/US11110123B2

## 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 40/31: Chimeric antigen receptors [CAR]
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4}
- A61K 40/4211: {CD19 or B4}
- A61K 40/4215: {Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30}
- A61P 35/00: Antineoplastic agents
- C07K 14/70514: {CD4}
- C07K 14/70517: {CD8}
- C07K 14/82: Translation products from oncogenes
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/32: against translation products of oncogenes
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- A61K 2239/59: Reproductive system, e.g. uterus, ovaries, cervix or testes
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/03: containing a transmembrane segment
- 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

## Abstract

A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.

## Claims

### Claim 1

A HER2 (Human Epidermal Growth Factor Receptor 2) T cell-antigen coupler (HER2-TAC) polypeptide, comprising the amino acid sequence set forth in SEQ ID NO: 66, SEQ ID NO: 68, or SEQ ID NO: 76.

### Claim 2 (depends on 1)

The HER2-TAC polypeptide of claim 1, wherein the amino acid sequence of SEQ ID NO: 66 is encoded by the nucleic acid sequence set forth in SEQ ID NO: 65, the amino acid sequence of SEQ ID NO: 68 is encoded by the nucleic acid sequence set forth in SEQ ID NO: 67, and the amino acid sequence of SEQ ID NO: 76 is encoded by a nucleic acid sequence set forth in SEQ ID NO: 75.

### Claim 3

An engineered T cell, comprising a recombinant expression vector comprising the nucleic acid sequence of SEQ ID NO: 65, SEQ ID NO: 67, or SEQ ID NO: 75, wherein the expression vector encodes a HER2 (Human Epidermal Growth Factor Receptor 2) T cell-antigen coupler (HER2-TAC) polypeptide and the HER2-TAC polypeptide is expressed on the surface of the cell.

### Claim 4 (depends on 3)

A pharmaceutical composition, comprising: (a) the T cell of claim 3; and (b) an excipient.

### Claim 5 (depends on 4)

The pharmaceutical composition of claim 4, wherein the pharmaceutical composition is in a unit dose form.

### Claim 6 (depends on 4)

The pharmaceutical composition of claim 4, wherein the pharmaceutical composition comprises about 1×104 T cells per kg body weight to about 1×108 T cells per kg body weight.

### Claim 7 (depends on 4)

The pharmaceutical composition of claim 4, wherein the pharmaceutical composition comprises about 0.5-2×109 T cells.

### Claim 8

A recombinant expression vector comprising:
(a) a nucleic acid sequence comprising the sequence set forth in SEQ ID NO: 65, SEQ ID NO: 67, or SEQ ID NO: 75; and
(b) a promoter functional in a mammalian cell.

### Claim 9 (depends on 3)

A method for treating a HER2-expressing cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the T cell of claim 3, wherein administration of said T cell results in a reduction in cancer cells in the subject.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cancer is breast cancer, bladder cancer, pancreatic cancer, ovarian cancer, glioblastoma or gastric cancer.

### Claim 11 (depends on 9)

The method of claim 9, wherein the cancer is a carcinoma, a blastoma or a sarcoma.