# US 12,180,484 B2 · Chimeric antigen receptors targeting B-cell maturation antigen

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- Number: US 12,180,484 B2
- Document ID: US12180484B2
- Status: Granted
- Kind: B2
- Application number: 17/745,067
- Filed: 2022-05-16
- Published: 2023-01-05
- Granted: 2024-12-31
- Earliest claimed: 2012-04-11
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Inventors: James N. Kochenderfer
- Web page: https://patentgrep.com/patent/US12180484B2

## CPC

- C12N 15/62: DNA sequences coding for fusion proteins
- 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 40/4215: {Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/18: against material from animals or humans
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/505: {comprising antibodies}
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2319/00: Fusion polypeptide
- C07K 2319/03: containing a transmembrane segment
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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)

## Abstract

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

## Claims

### Claim 1

A human T cell comprising a nucleic acid that encodes a chimeric antigen receptor (CAR) comprising:
(a) an antigen recognition moiety that binds human B-Cell Maturation Antigen (BCMA);
(b) a CD8α hinge domain;
(c) a CD8α transmembrane domain;
(d) a 4-1BB intracellular T cell signaling domain; and
(e) a CD3ζ intracellular T cell signaling domain.

### Claim 2 (depends on 1)

The human T cell of claim 1, wherein the antigen recognition moiety is an antigen binding portion of an antibody.

### Claim 3 (depends on 1)

The human T cell of claim 1, wherein the antigen recognition moiety comprises a variable region.

### Claim 4 (depends on 1)

The human T cell of claim 1, wherein the antigen recognition moiety comprises two variable regions.

### Claim 5 (depends on 3)

The human T cell of claim 3, wherein the antigen recognition moiety comprises a heavy chain variable (VH) region.

### Claim 6 (depends on 1)

The human T cell of claim 1, wherein the antigen recognition moiety comprises a complementarity determining region (CDR) 1, a CDR2 and a CDR3.

### Claim 7 (depends on 5)

The human T cell of claim 5, wherein the VH region comprises VH CDR1, VH CDR2 and VH CDR3.

### Claim 8 (depends on 4)

The human T cell of claim 4, wherein each of the variable regions comprises a CDR1, CDR2 and CDR3.

### Claim 9 (depends on 1)

The human T cell of claim 1, wherein the CAR further comprises a signal sequence.

### Claim 10 (depends on 9)

The human T cell of claim 9, wherein the signal sequence is a CD8α signal sequence.

### Claim 11 (depends on 1)

The human T cell of claim 1, wherein the CD32 intracellular T cell signaling domain comprises the CD32 intracellular T cell signaling domain in SEQ ID NO: 10.

### Claim 12 (depends on 1)

The human T cell of claim 1, wherein the 4-1BB intracellular T cell signaling domain comprises the 4-1BB intracellular T cell signaling domain in SEQ ID NO: 10.

### Claim 13 (depends on 1)

The human T cell of claim 1, wherein the CD35 intracellular T cell signaling domain comprises the CD3ζ intracellular T cell signaling domain in SEQ ID NO: 10 and the 4-1BB intracellular T cell signaling domain comprises the 4-1BB intracellular T cell signaling domain in SEQ ID NO: 10.

### Claim 14 (depends on 1)

The human T cell of claim 1, wherein the CD8a transmembrane domain is the CD8α transmembrane domain of SEQ ID NO: 10.

### Claim 15 (depends on 1)

The human T cell of claim 1, wherein the CD32 intracellular T cell signaling domain comprises the CD32 intracellular T cell signaling domain in SEQ ID NO: 10; the 4-1BB intracellular T cell signaling domain comprises the 4-1BB intracellular T cell signaling domain in SEQ ID NO: 10 and the CD8α transmembrane domain is the CD8α transmembrane domain of SEQ ID NO: 10.

### Claim 16 (depends on 10)

The human T cell of claim 10, wherein the signal sequence is the CD8α signal sequence of SEQ ID NO: 10.

### Claim 17 (depends on 9)

The human T cell of claim 9, wherein the CD3ζ intracellular T cell signaling domain comprises the CD32 intracellular T cell signaling domain in SEQ ID NO: 10; the 4-1BB intracellular T cell signaling domain comprises the 4-1BB intracellular T cell signaling domain in SEQ ID NO: 10; the CD8α transmembrane domain is the CD8α transmembrane domain of SEQ ID NO: 10 and the signal sequence is the CD8α signal sequence of SEQ ID NO: 10.

### Claim 18 (depends on 1)

The human T cell of claim 1, wherein the T cell is from a human subject having multiple myeloma.

### Claim 19 (depends on 1)

The human T cell of claim 1, wherein the human T cell is a tumor infiltrating T cell.

### Claim 20 (depends on 1)

The human T cell of claim 1, wherein the human T cell is a CD4+ T cell, a CD8+ T cell, or a memory T cell.