# US 2020/0399386 A1 · Bcma-binding antibodies and uses thereof

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- Number: US 2020/0399386 A1
- Document ID: US20200399386A1
- Status: Published application
- Kind: A1
- Application number: 16/971,925
- Filed: 2019-02-20
- Published: 2020-12-24
- Earliest claimed: 2018-02-21
- Assignees: Celgene Corporation
- Applicants: Celgene Corporation
- Inventors: Mahan Abbasian; Henry Chan; Kandasamy Hariharan; Jeonghoon Sun; Andrew Wurmser
- Web page: https://patentgrep.com/patent/US20200399386A1

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/565: Complementarity determining region [CDR]
- 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

Antibody species that bind B-Cell Maturation Antigen (BCMA) are provided as well as methods of depleting BCMA-expressing cells in a patient in need thereof, comprising administering a therapeutically effective amount of the antibody species or an entity comprising a BCMA binding fragment thereof. Methods of treating B cell-related disorders associated with BCMA expression in a patient in need thereof are provided, comprising administering to the patient a therapeutically effective amount of the antibody species or an entity comprising a BCMA binding fragment thereof.

## Claims

### Claim 1

An antibody that binds to B-Cell Maturation Antigen (BCMA), or a BCMA-binding fragment thereof, comprising
(A) heavy chain CDR1, CDR2 or CDR3 sequences of:
a. SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
b. SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12, respectively;
c. SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, respectively;
d. SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, respectively;
e. SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively;
f. SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively;
g. SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31, respectively;
h. SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, respectively;
i. SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37, respectively;
j. SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, respectively;
k. SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, respectively;
l. SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, respectively;
m. SEQ ID NO:51, SEQ ID NO:52 and SEQ ID NO:53, respectively;
n. SEQ ID NO:54, SEQ ID NO:55 and SEQ ID NO:56, respectively; or
o. SEQ ID NO:57, SEQ ID NO:58 and SEQ ID NO:59, respectively; and
(B) light chain CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4, respectively.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The antibody or BCMA-binding fragment thereof, of claim 1, wherein said antibody comprises light chain CDR1, CDR2 and CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively.

### Claim 4 (depends on 1)

An antibody that binds to BCMA, or a BCMA-binding fragment thereof according to claim 1, comprising a light chain comprising CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences of:
a. SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
b. SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively; or
c. SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, respectively.

### Claim 5 (depends on 1)

An antibody that binds to BCMA, or a BCMA-binding fragment thereof according to claim 1, comprising a light chain comprising CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences of:
a. SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, respectively;
b. SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively; or
c. SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively.

### Claim 6 (depends on 1)

An antibody that binds to BCMA, or a BCMA-binding fragment thereof according to claim 1, comprising a light chain comprising CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences of:
a. SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31, respectively;
b. SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, respectively; or
c. SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37, respectively.

### Claim 7 (depends on 1)

An antibody that binds to BCMA, or a BCMA-binding fragment thereof according to claim 1, comprising a light chain comprising CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences of:
a. SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, respectively;
b. SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, respectively; or
c. SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, respectively.

### Claim 8 (depends on 1)

An antibody that binds to BCMA, or a BCMA-binding fragment thereof according to claim 1, comprising a light chain comprising CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences of:
a. SEQ ID NO:51, SEQ ID NO:52 and SEQ ID NO:53, respectively;
b. SEQ ID NO:54, SEQ ID NO:55 and SEQ ID NO:56, respectively; or
c. SEQ ID NO:57, SEQ ID NO:58 and SEQ ID NO:59, respectively.

### Claim 9 (depends on 1)

The antibody or binding fragment thereof of claim 1, which comprises the light chain variable sequence of SEQ ID NO:1.

### Claim 10 (depends on 1)

The antibody or binding fragment thereof of claim 1, which comprises the heavy chain variable sequence of SEQ ID NO:6, SEQ ID NO:17, SEQ ID NO:28, SEQ ID NO:39, or SEQ ID NO:50.

### Claim 11 (depends on 1)

The antibody of claim 1, wherein said antibody is a monoclonal antibody, a chimeric antibody, a diabody, a bispecific antibody, a bispecific Fab2, a bispecific (mab)2, a humanized antibody, an artificially-generated human antibody, bispecific T-cell engager, bispecific NK cell engager, or a single chain antibody.

### Claim 12 (depends on 1)

The antibody of claim 1, wherein said antibody is a triomab, knob-in-hole (kih) IgG with common light chain, crossmab, ortho-Fab IgG, DVD-Ig, 2 in 1-IgG, IgG-scFv, sdFv2-Fc, bi-nanobody, tandAb, DART, DART-Fc, scFv-HAS-scFv, or DNL-Fab3.

### Claim 13 (depends on 1)

The antibody of claim 1, wherein said antibody is an antibody-drug conjugate.

### Claim 14 (depends on 1)

The binding fragment of claim 1, which is a single-chain variable fragment (scFv), Fab fragment, or F(ab′)2 fragment.

### Claim 15

A polypeptide that comprises:
(A) the heavy chain CDR1, CDR2 or CDR3 sequences of:
a. SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
b. SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12, respectively;
c. SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, respectively;
d. SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, respectively;
e. SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively;
f. SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively;
g. SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31, respectively;
h. SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, respectively;
i. SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37, respectively;
j. SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, respectively;
k. SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, respectively;
l. SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, respectively;
m. SEQ ID NO:51, SEQ ID NO:52 and SEQ ID NO:53, respectively;
n. SEQ ID NO:54, SEQ ID NO:55 and SEQ ID NO:56, respectively; or
o. SEQ ID NO:57, SEQ ID NO:58 and SEQ ID NO:59, respectively; and
(B) light chain CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4, respectively.

### Claim 16

(canceled)

### Claim 17 (depends on 15)

The polypeptide of claim 15, wherein said polypeptide comprises light chain CDR1, CDR2 and CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively.

### Claim 18

(canceled)

### Claim 19 (depends on 17)

A polypeptide according to claim 17 that comprises the light chain variable sequence of SEQ ID NO:1.

### Claim 20 (depends on 15)

A polypeptide according to claim 15 that comprises the heavy chain variable sequence of SEQ ID NO:6, SEQ ID NO:17, SEQ ID NO:28, SEQ ID NO:39, or SEQ ID NO:50.

### Claim 21

(canceled)

### Claim 22

(canceled)

### Claim 23

(canceled)

### Claim 24

(canceled)

### Claim 25

A polynucleotide encoding a polypeptide comprising
(A) heavy chain CDR1, CDR2 or CDR3 sequences of:
a. SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
b. SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12, respectively;
c. SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, respectively;
d. SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, respectively;
e. SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively;
f. SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively;
g. SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31, respectively;
h. SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, respectively;
i. SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37, respectively;
j. SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, respectively;
k. SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, respectively;
l. SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, respectively;
m. SEQ ID NO:51, SEQ ID NO:52 and SEQ ID NO:53, respectively;
n. SEQ ID NO:54, SEQ ID NO:55 and SEQ ID NO:56, respectively; or
o. SEQ ID NO:57, SEQ ID NO:58 and SEQ ID NO:59, respectively; and
(B) light chain CDR1, CDR2 or CDR3 sequences of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively.

### Claim 26

(canceled)

### Claim 27 (depends on 25)

The polynucleotide of claim 25, wherein said polynucleotide comprises the nucleotide sequence of SEQ ID NO:5, SEQ ID NO:16, SEQ ID NO:27, SEQ ID NO:38, SEQ ID NO:49 or SEQ ID NO:60.

### Claim 28 (depends on 25)

A polynucleotide according to claim 25 that encodes a polypeptide that comprises the light chain variable sequence of SEQ ID NO:1.

### Claim 29 (depends on 25)

A polynucleotide according to claim 25 that encodes a polypeptide that comprises the heavy chain variable sequence of SEQ ID NO:6, SEQ ID NO:17, SEQ ID NO:28, SEQ ID NO:39, or SEQ ID NO:50.

### Claim 30 (depends on 25)

A polynucleotide vector comprising the polynucleotide of claim 25.

### Claim 31

(canceled)

### Claim 32

(canceled)

### Claim 33

(canceled)

### Claim 34 (depends on 30)

A cell comprising the vector of claim 30.

### Claim 35

(canceled)

### Claim 36

(canceled)

### Claim 37

(canceled)

### Claim 38 (depends on 1)

A method of depleting BCMA-expressing cells in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the antibody, or BCMA binding fragment thereof, of claim 1.

### Claim at position 39

-57. (canceled)