# US 11,993,659 B2 · BCMA targetting antibodies, chimeric antigen receptors, and uses thereof

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- Number: US 11,993,659 B2
- Document ID: US11993659B2
- Status: Granted
- Kind: B2
- Application number: 18/062,109
- Filed: 2022-12-06
- Published: 2023-05-25
- Granted: 2024-05-28
- Earliest claimed: 2021-08-16
- Assignees: Utc Therapeutics (Shanghai) Co., Ltd.
- Applicants: Utc Therapeutics (Shanghai) Co., Ltd.
- Inventors: Yangbing Zhao; Wei Pan; Xiaojun Liu
- Web page: https://patentgrep.com/patent/US11993659B2

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- 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
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 5/0636: {T lymphocytes}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/23: On/off switch
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K 2317/21: from primates, e.g. man
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C12N 2501/2302: Interleukin-2 (IL-2)
- C12N 2501/51: B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
- C12N 2501/515: CD3, T-cell receptor complex
- 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)
- 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)

## Abstract

Disclosed herein are anti-BCMA antibodies and antigen-binding fragments, chimeric antigen receptors (“CARs”) having these anti-BCMA antibodies and antigen-binding fragments (“BCMA CARs”) and genetically modified immune effector cells having such BCMA CARs. Polynucleotides encoding the anti-BCMA antibodies and antigen-binding fragments and BCMA CARs are also provided herein. Compositions comprising anti-BCMA antibodies and antigen-binding fragments and BCMA CARs are also provided herein. The present disclosure also relates to use of the anti-BCMA antibodies and antigen-binding fragments and genetically modified immune effector cells having such BCMA CARs in cancer treatment.

## Claims

### Claim 1

An antibody or antigen-binding fragment thereof that specifically binds BCMA (B-cell maturation antigen), comprising
a light variable region (VL) comprising CDR1, CDR2, and CDR3; and
a heavy chain variable region (VH) comprising CDR1, CDR2 and CDR3,
wherein
(a) the VL CDR1, CDR2 and CDR3 have the amino acid sequences of SEQ ID NOs:1, 2, and 3, respectively; and
(b) the VH CDR1, CDR2 and CDR3 have the amino acid sequences of SEQ ID NOs:4, 5, and 6, respectively.

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment of claim 1, comprising a VL and a VH, wherein the VL and VH have the amino acid sequences of SEQ ID NO:7 and 8 respectively.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment of claim 1 that is a monoclonal antibody or antigen-binding fragment thereof.

### Claim 4 (depends on 1)

The antibody or antigen-binding fragment of claim 1 that is selected from the group consisting of an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, and an IgG4 antibody.

### Claim 5 (depends on 1)

The antibody or antigen-binding fragment of claim 1 that is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, a Fv, a scFv, a (scFv)2.

### Claim 6 (depends on 1)

The antibody or antigen-binding fragment of claim 1 that is a human antibody or antigen-binding fragment thereof.

### Claim 7 (depends on 1)

A Chimeric Antigen Receptor (CAR) that specifically binds BCMA, comprising, from N-terminus to C-terminus:
(a) a BCMA-binding domain that comprises the antibody or antigen-binding fragment of claim 1;
(b) a transmembrane domain; and
(c) a cytoplasmic domain.

### Claim 8 (depends on 7)

The CAR of claim 7, wherein the transmembrane domain is derived from CD8, CD28, CD3ζ, CD4, 4-1BB, OX40, ICOS, CTLA-4, PD-1, LAG-3, 2B4, BTLA, TCR α chain, TCR β chain, or TCR ζ chain, CD3ε, CD45, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, or CD154.

### Claim 9 (depends on 7)

The CAR of claim 7, wherein the transmembrane domain comprises a CD8 transmembrane region or a CD28 transmembrane region.

### Claim 10 (depends on 7)

The CAR of claim 7, wherein the cytoplasmic domain comprises one or more signaling domains derived from CD3ζ, FcRγ, FcγRIIa, FcRβ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b, DAP10, or DAP12.

### Claim 11 (depends on 7)

The CAR of claim 7, wherein the cytoplasmic domain further comprises one or more co-stimulatory domains derived from CD28, 4-1BB (CD137), OX40, ICOS, DA-P10, 2134, CD27, CD)30, CD40, CD2, CD7, LIGHT, GITR, a TLR, DR3, or CD43.

### Claim 12 (depends on 7)

The CAR of claim 7, wherein the cytoplasmic domain comprises a CD3ζ signaling domain and a 4-1BB co-stimulatory domain, or the cytoplasmic domain comprises a CD3ζ signaling domain and a CD28 co-stimulatory domain.

### Claim 13 (depends on 7)

The CAR of claim 7, further comprising a CD8 hinge between the antibody or antigen-binding fragment and the transmembrane domain.

### Claim 14 (depends on 7)

The CAR of claim 7 comprising the amino acid sequence of SEQ ID NO:15.

### Claim 15 (depends on 7)

An isolated cell comprising a polynucleotide encoding the CAR of claim 7.

### Claim 16 (depends on 15)

The isolated cell of claim 15 that is an immune effector cell.

### Claim 17 (depends on 15)

The isolated cell of claim 15 that is derived from a cell isolated from peripheral blood or bone marrow.

### Claim 18 (depends on 15)

The isolated cell of claim 15 that is derived from a cell differentiated in vitro from a stem or progenitor cell selected from the group consisting of a T cell progenitor cell, a hematopoietic stem and progenitor cell, a hematopoietic multipotent progenitor cell, an embryonic stem cell, and an induced pluripotent cell.

### Claim 19 (depends on 15)

The isolated cell of claim 15 that is a T cell or a NK cell.

### Claim 20 (depends on 15)

The isolated cell of claim 15 that is a cytotoxic T cell, a helper T cell, a gamma delta T, a CD4+/CD8+ double positive T cell, a CD4+ T cell, a CD8+ T cell, a CD4/CD8 double negative T cell, a CD3+ T cell, a naive T cell, an effector T cell, a helper T cell, a memory T cell, a regulator T cell, a Th0 cell, a Th cell, a Th2 cell, a Th3 (Treg) cell, a Th9 cell, a Th17 cell, a Thαβ helper cell, a Tfh cell, a stern memory TSCM cell, a central memory TCM cell, an effector memory TEM cell or an effector memory TEMRA cell.

### Claim 21 (depends on 1)

A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment of claim 1, wherein the cancer is a BCMA-expressing cancer.

### Claim 22 (depends on 21)

The method of claim 21, further comprising administering an additional therapy to the subject.

### Claim 23 (depends on 21)

The method of claim 21, wherein the subject is a human.

### Claim 24 (depends on 21)

The method of claim 21, wherein the cancer is a solid tumor or a hematological cancer.

### Claim 25 (depends on 21)

The method of claim 21, wherein the cancer is a B cell malignancy.

### Claim 26 (depends on 21)

The method of claim 21, wherein the cancer is a lymphoma, a leukemia, or a plasma cell malignancy.

### Claim 27 (depends on 21)

The method of claim 21, wherein the caner is multiple myeloma (MM), Waldenstrom macroglobulinemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma.