# US 12,760,084 B2 · Compositions and methods of T cell receptor VB family member targeting for the treatment of T cell associated disease

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- Number: US 12,760,084 B2
- Document ID: US12760084B2
- Status: Granted
- Kind: B2
- Application number: 17/759,679
- Filed: 2021-01-29
- Published: 2023-04-06
- Granted: 2026-10-13
- Earliest claimed: 2020-01-29
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Daniel J. Powell; Stephen J. Schuster; Lauren Shaw
- Web page: https://patentgrep.com/patent/US12760084B2

## 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 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/4211: {CD19 or B4}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61K 40/50: characterised by the use of allogeneic cells
- 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
- 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)

## Abstract

Provided is a chimeric antigen receptor (CAR) comprising a domain that binds a Vβ region of a T cell receptor. Also provided is a T cell genetically modified to express the CAR, and methods for treating cancer in a subject in need thereof.

## Claims

### Claim 1

A CAR comprising an extracellular domain that binds a Vβ region of a T cell receptor, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular signaling domain comprises a costimulatory signaling region;
wherein the extracellular domain that binds a Vβ region is selected from the group consisting of an antibody, a Fab, and an scFv; and
wherein the extracellular domain comprises a light chain variable region (VL) comprising three light chain complementarity determining regions 1-3 (LCDR1-3) and a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions 1-3 (HCDR1-3), and wherein the Vβ region is:
(a) Vβ12, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 62-64, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 58-60, respectively;
(b) Vβ5.1, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 102-104, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 98-100, respectively; or
(c) Vβ4, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 94-96, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 90-92, respectively.

### Claim 2 (depends on 1)

The CAR of claim 1, wherein the Vβ region is Vβ12, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 62-64, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 58-60, respectively.

### Claim 3 (depends on 1)

The CAR of claim 1, wherein the Vβ region is:
(a) Vβ12, wherein the VH and VL comprise the sequence of SEQ ID NO: 57 and 61, respectively;
(b) Vβ5.1, wherein the VH and VL comprise the sequence of SEQ ID NO: 97 and 101, respectively; or
(c) Vβ4, wherein the VH and VL comprise the sequence of SEQ ID NO: 89 and 93, respectively.

### Claim 4 (depends on 1)

The CAR of claim 1, wherein the extracellular domain comprises an scFv encoded by a nucleotide sequence, wherein the Vβ region is
(a) Vβ12, wherein the nucleotide sequence comprises the sequence of SEQ ID NO: 33 or 34;
(b) Vβ5.1, wherein the nucleotide sequence comprises the sequence of SEQ ID NO: 43 or 44; or
(c) Vβ4, wherein the nucleotide sequence comprises the sequence of SEQ ID NO: 41 or 42.

### Claim 5 (depends on 1)

The CAR of claim 1, wherein the costimulatory signaling region comprises the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and a ligand that specifically binds with CD83.

### Claim 6 (depends on 1)

The CAR of claim 1, wherein the intracellular signaling domain comprises a CD3zeta chain.

### Claim 7 (depends on 1)

The CAR of claim 1, wherein the intracellular signaling domain comprises CD28 and CD3zeta.

### Claim 8 (depends on 1)

The CAR of claim 1, wherein the intracellular signaling domain comprises 4-1BB and CD3zeta.

### Claim 9

A nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain that binds a Vβ region of a T cell receptor, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular signaling domain comprises a costimulatory signaling region;
wherein the extracellular domain that binds a Vβ region is selected from the group consisting of an antibody, a Fab, and a scFv; and
wherein the extracellular domain comprises a light chain variable region (VL) comprising three light chain complementarity determining regions 1-3 (LCDR1-3) and a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions 1-3 (HCDR1-3), and wherein the Vβ region is:
(a) Vβ12, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 62-64, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 58-60, respectively;
(b) Vβ5.1, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 102-104, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 98-100, respectively; or
(c) Vβ4, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 94-96, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 90-92, respectively.

### Claim 10 (depends on 9)

The nucleic acid of claim 9, wherein the Vβ region is Vβ12, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs: 62-64, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs: 58-60, respectively.

### Claim 11 (depends on 9)

The nucleic acid of claim 9, wherein the Vβ region is:
(a) Vβ12, wherein the VH and VL comprise the sequence of SEQ ID NO: 57 and 61, respectively;
(b) Vβ5.1, wherein the VH and VL comprise the sequence of SEQ ID NO: 97 and 101, respectively; or
(c) Vβ4, wherein the VH and VL comprise the sequence of SEQ ID NO: 89 and 93, respectively.

### Claim 12 (depends on 9)

The nucleic acid of claim 9, wherein the extracellular domain comprises an scFv encoded by a nucleotide sequence, wherein the Vβ region is:
(a) Vβ12, wherein the nucleotide sequence comprises the sequence of SEQ ID NO: 33 or 34;
(b) Vβ5.1, wherein the nucleotide sequence comprises the sequence of SEQ ID NO: 43 or 44; or
(c) Vβ4, wherein the nucleotide sequence comprises the sequence of SEQ ID NO: 41 or 42.

### Claim 13 (depends on 9)

The nucleic acid of claim 9, wherein the costimulatory signaling region comprises the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and a ligand that specifically binds with CD83.

### Claim 14 (depends on 9)

The nucleic acid of claim 9, wherein the intracellular signaling domain comprises a CD3zeta chain.

### Claim 15 (depends on 9)

The nucleic acid of claim 9, wherein the intracellular signaling domain comprises CD28 and CD3zeta.

### Claim 16 (depends on 9)

The nucleic acid of claim 9, wherein the intracellular signaling domain comprises 4-1BB and CD3zeta.

### Claim 17 (depends on 9)

The nucleic acid of claim 9, wherein the CAR:
(a) comprises an antigen binding domain that binds Vβ12 and comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 153-158;
(b) comprises an antigen binding domain that binds Vβ4 and comprises and amino acid sequence selected from the group consisting of SEQ ID NOs: 169-170; or
(c) comprises and antigen binding domain that binds Vβ5.1 and comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 171-172.

### Claim 18 (depends on 17)

The nucleic acid of claim 17, comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-6 and 17-20.

### Claim 19 (depends on 18)

A vector comprising the nucleic acid of claim 18.