BCMA-binding antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11401336-B2
Application number	US-201916971925-A
Country	US
Kind code	B2
Filing date	Feb 20, 2019
Priority date	Feb 21, 2018
Publication date	Aug 2, 2022
Grant date	Aug 2, 2022

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.

First claim

What is claimed is:

1. An antibody that binds to B-Cell Maturation Antigen (BCMA), or a BCMA-binding fragment thereof, comprising:
(A) heavy chain CDR1, CDR2 and CDR3 sequences:
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 SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO:4, respectively.

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

3. An antibody or a BCMA-binding fragment according to claim 1 comprising a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
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.

4. An antibody or BCMA-binding fragment according to claim 1 comprising a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
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.

5. An antibody or BCMA-binding fragment according to claim 1 comprising a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
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.

6. An antibody or BCMA-binding fragment according to claim 1 comprising a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
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.

7. An antibody or BCMA-binding fragment according to claim 1 comprising a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
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.

8. The antibody or binding fragment of claim 1 which comprises a light chain variable SEQ ID NO:1.

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

10. The antibody of claim 1 wherein said antibody is a monoclonal antibody, a chimeric antibody, a diabody, a bispecific antibody, a bispecific Fab 2 , 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.

11. 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, sdFv 2 -Fc, bi-nanobody, tandAb, DART, DART-Fc, scFv-HAS-scFv, or DNL-Fab3.

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

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

14. A polypeptide that comprises:
(A) heavy chain CDR1, CDR2 and CDR3 sequences:
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 SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO:4, respectively; and,
wherein the heavy chain and light chain form an antigen-binding domain which binds BCMA.

15. The polypeptide of claim 14 , 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.

16. A polypeptide according to claim 14 that comprises a light chain variable sequence SEQ ID NO: 1.

17. A polypeptide according to claim 14 that comprises a heavy chain variable sequence SEQ ID NO:6, SEQ ID NO:17, SEQ ID NO:28, SEQ ID NO:39, or SEQ ID NO:50.

18. 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 of claim 1 .

Assignees

• Celgene Corp

Inventors

• Abbasian Mahan
• Chan Henry
• Hariharan Kandasamy
• Sun Jeonghoon
• Wurmser Andrew

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• A61K47/68

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title