# US 11,077,144 B2 · CD19 specific chimeric antigen receptor and uses thereof

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- Number: US 11,077,144 B2
- Document ID: US11077144B2
- Status: Granted
- Kind: B2
- Application number: 17/099,608
- Filed: 2020-11-16
- Published: 2021-03-04
- Granted: 2021-08-03
- Earliest claimed: 2013-05-13
- Assignees: Cellectis
- Applicants: Cellectis
- Inventors: Roman Galetto; Julianne Smith; Andrew Scharenberg; Cécile Schiffer-Mannioui
- Web page: https://patentgrep.com/patent/US11077144B2

## CPC

- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- 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 40/4211: {CD19 or B4}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2803: {against the immunoglobulin superfamily}
- C12N 5/0636: {T lymphocytes}
- 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)
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- C12N 2501/39: Steroid hormones
- C12N 2501/51: B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
- C12N 2501/515: CD3, T-cell receptor complex
- C12N 2501/599: with CD designations not provided for elsewhere
- C12N 2502/99: genetically modified cells
- C12N 2510/00: Genetically modified cells
- 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 relates to chimeric antigen receptors (CAR). CARs are able to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties. In particular, the present invention relates to a Chimeric Antigen Receptor in which extracellular ligand binding is a scFV derived from a CD19 monoclonal antibody, preferably 4G7. The present invention also relates to polynucleotides, vectors encoding said CAR and isolated cells expressing said CAR at their surface. The present invention also relates to methods for engineering immune cells expressing 4G7-CAR at their surface which confers a prolonged “activated” state on the transduced cell. The present invention is particularly useful for the treatment of B-cells lymphomas and leukemia.

## Claims

### Claim 1

A CD19 specific CAR comprising, in order from N-terminus to C-terminus:
i) the amino acid sequence of SEQ ID NO: 7;
ii) the amino acid sequence of SEQ ID NO: 13;
iii) the amino acid sequence of SEQ ID NO: 11; and
iv) the amino acid sequence of SEQ ID NO: 10.

### Claim 2 (depends on 1)

The CD19 specific CAR of claim 1, wherein the CAR further comprises a N-terminal signal peptide consisting of the amino acid sequence of SEQ ID NO: 18.

### Claim 3 (depends on 1)

The CD19 specific CAR of claim 1, wherein the CAR has at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 15.

### Claim 4 (depends on 3)

The CD19 specific CAR of claim 3, wherein the CAR has at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 15.

### Claim 5 (depends on 1)

The CD19 specific CAR of claim 1, wherein the CAR is expressed on the surface of a T cell as a part of an allogeneic immunotherapy treatment for cancer expressing CD19.

### Claim 6 (depends on 1)

A nucleic acid encoding the CD19 specific CAR of claim 1.

### Claim 7 (depends on 1)

An isolated T cell expressing the CD19 specific CAR of claim 1.

### Claim 8 (depends on 7)

The isolated T cell of claim 7, wherein the T cell is a cytotoxic T lymphocyte (CTL).

### Claim 9 (depends on 7)

The isolated T cell of claim 7, wherein the T cell is engineered from a donor cell.

### Claim 10

An isolated T cell expressing on the cell surface a CD19 specific CAR comprising at least one extracellular ligand binding domain and at least one intracellular signaling domain, wherein the CD19 specific CAR expressed on the cell surface comprises the amino acid sequence of SEQ ID NO:15 without the signal peptide consisting of the amino acid sequence of SEQ ID NO:18.

### Claim 11 (depends on 10)

The isolated T cell of claim 10, wherein the T cell is a cytotoxic T lymphocyte (CTL).

### Claim 12 (depends on 10)

The isolated T cell of claim 10, wherein the T cell is engineered from a donor cell.

### Claim 13

An isolated T cell expressing on the cell surface a CD19 specific CAR comprising at least one extracellular ligand binding domain and at least one intracellular signaling domain, wherein the CD19 specific CAR expressed on the cell surface has at least 95% sequence identity with the amino acid sequence of SEQ ID NO:15; wherein the CAR comprises an extracellular ligand binding domain comprising the amino acid sequence of SEQ ID NO: 7; a transmembrane and hinge domain comprising the amino acid sequence of SEQ ID NO: 13; a signal transduction domain comprising the amino acid sequence of SEQ ID NO: 11; and a signal transduction domain comprising the amino acid sequence of SEQ ID NO: 10.

### Claim 14 (depends on 13)

The isolated T cell of claim 13, wherein the CD19 specific CAR expressed on the cell surface has at least 99% sequence identity with the amino acid sequence of SEQ ID NO:15.

### Claim 15 (depends on 13)

The isolated T cell of claim 13, wherein the T cell is a cytotoxic T lymphocyte (CTL).

### Claim 16 (depends on 13)

The isolated T cell of claim 13, wherein the T cell is derived from a donor cell.

### Claim 17 (depends on 13)

The isolated T cell of claim 13, wherein the CAR consists of an extracellular ligand binding domain comprising the amino acid sequence of SEQ ID NO: 7; a transmembrane and hinge domain consisting of the amino acid sequence of SEQ ID NO: 13; a signal transduction domain consisting of the amino acid sequence of SEQ ID NO: 11; and a signal transduction domain consisting of the amino acid sequence of SEQ ID NO: 10.