# US 11,026,975 B2 · Chimeric antigen receptor (CAR) binding to BCMA, and uses thereof

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- Number: US 11,026,975 B2
- Document ID: US11026975B2
- Status: Granted
- Kind: B2
- Application number: 16/650,327
- Filed: 2019-01-31
- Published: 2020-12-03
- Granted: 2021-06-08
- Earliest claimed: 2018-02-01
- Assignees: Nanjing IASO Biotherapeutics Co., Ltd.; Innovent Biologics (Suzhou) Co., Ltd.
- Applicants: Nanjing Iaso Biotherapeutics Co., Ltd.; Innovent Biologics (Suzhou) Co., Ltd.
- Inventors: Jianfeng Zhou; Junjian Liu; Guang Hu; Yongkun Yang; Guangrong Meng; Wenjing Gao; Yuyu Wang; Panpan Niu
- Web page: https://patentgrep.com/patent/US11026975B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- 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}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 35/00: Antineoplastic agents
- C07K 14/54: Interleukins [IL]
- C07K 14/70517: {CD8}
- C07K 14/715: for cytokines; for lymphokines; for interferons
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C12N 5/0636: {T lymphocytes}
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 15/62: DNA sequences coding for fusion proteins
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N 15/86: Viral vectors
- A01K 2207/12: Animals modified by administration of exogenous cells
- A01K 2227/105: Murine
- A01K 2267/0331: Animal model for proliferative diseases
- A61K 2039/505: {comprising antibodies}
- 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 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2319/03: containing a transmembrane segment
- C12N 2510/00: Genetically modified cells
- C12N 2740/16043: 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS

## Abstract

The invention provides a chimeric antigen receptor (CAR) which can specifically bind to a BCMA protein comprising a BCMA binding structural domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain. The invention also provides uses of the CAR in treating diseases or conditions linked to the expression of BCMA.

## Claims

### Claim 1

A chimeric antigen receptor (CAR), wherein the CAR comprises a B-cell maturation antigen (BCMA) binding domain, a transmembrane domain, a costimulatory domain and an intracellular signal transduction domain, the BCMA-binding domain comprises an antibody or a fragment thereof capable of specifically binding-a BCMA protein, and the antibody comprises a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2) and a heavy chain complementary determining region 3 (HCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 9, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 10, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 11; and wherein the antibody comprises a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2) and a light chain complementary determining region 3 (LCDR3), and wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 17, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 18, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 19.

### Claim 2 (depends on 1)

The CAR of claim 1, wherein the antibody comprises a heavy chain variable region, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7.

### Claim 3 (depends on 1)

The CAR of claim 1, wherein the antibody comprises a light chain variable region, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 15.

### Claim 4 (depends on 1)

The CAR of claim 1, wherein the antibody is a single-chain antibody fragment.

### Claim 5 (depends on 1)

The CAR of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 43.

### Claim 6 (depends on 1)

The CAR of claim 1, wherein the transmembrane domain comprises a transmembrane domain from a protein selected from a group consisting of σ, β or ζ chain of the T cell receptor, CD28, CD3e, CD45, CD4, CD5, CD8a, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154.

### Claim 7 (depends on 1)

The CAR of claim 1, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 27.

### Claim 8 (depends on 1)

The CAR of claim 1, wherein the costimulatory domain comprises a costimulatory domain from a protein selected from a group consisting of CD28, 4-1BB, OX-40 and ICOS.

### Claim 9 (depends on 1)

The CAR of claim 1, wherein the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 31.

### Claim 10 (depends on 1)

The CAR of claim 1, wherein the intracellular signal transduction domain comprises a signal transduction domain from CD3t.

### Claim 11 (depends on 1)

The CAR of claim 1, wherein the intracellular signal transduction domain comprises the amino acid sequence of SEQ ID NO: 33.

### Claim 12 (depends on 1)

The CAR of claim 1, wherein the CAR further comprises a hinge region linking the BCMA-binding domain to the transmembrane domain.

### Claim 13 (depends on 1)

The CAR of claim 1, wherein the CAR is further linked to a signal peptide.

### Claim 14 (depends on 1)

The CAR of claim 1, comprising the amino acid sequence of SEQ ID NO: 49 or SEQ ID NO: 51.

### Claim 15 (depends on 1)

An isolated nucleic acid molecule, encoding the CAR of claim 1.

### Claim 16 (depends on 15)

A vector, comprising the nucleic acid molecule of claim 15.

### Claim 17 (depends on 16)

A method of preparing an immune effector cell, comprising introducing the vector of claim 16 into the immune effector cell.

### Claim 18 (depends on 1)

An immune effector cell, comprising the CAR of claim 1.

### Claim 19 (depends on 18)

A composition, comprising the immune effector cell of claim 18.

### Claim 20 (depends on 1)

A method for treating a plasmocyte malignancy disease, comprising administering the CAR of claim 1.

### Claim 21 (depends on 20)

The use method of claim 20, wherein the plasmocyte malignancy disease is a multiple myeloma.