IP Library › Granted Patent US 10,947,314
Granted Patent B2
US 10,947,314 · App. 16/732,089 · Granted Mar 16, 2021

Antibodies targeting b-cell maturation antigen and methods of use

Inventors: Renier J. Brentjens (New York, NY); Eric L. Smith (New York, NY); Cheng Liu (Emeryville, CA)
Assignees: MEMORIAL SLOAN KETTERING CANCER CENTER; EUREKA THERAPEUTICS, INC.
C07K16/2878A61K47/6849A61P35/00C07K14/70575C07K16/2896G01N33/6863C07K2317/21C07K2317/24C07K2317/34C07K2317/622C07K2317/92C07K2319/21C07K2319/30C07K2319/42G01N2333/70578
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Quick Facts
Patent No.
US 10,947,314
App. No.
16/732,089
Granted
Mar 16, 2021
Kind
B2
Abstract

The presently disclosed subject matter provides antibodies that bind to B-cell maturation antigen (BCMA) and methods of using the same.

Claims (57)

1. An anti-B Cell Maturation Antigen (BCMA) single chain variable fragment (scFv), comprising a heavy chain variable region and a light chain variable region, wherein:

(a) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 167, 168, and 169, respectively and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 170, 171, and 172, respectively;

(b) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 185, 186, and 187, respectively and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 188, 189, and 190, respectively; or

(c) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 122, 123, and 124, respectively.

2. The anti-BCMA scFv of claim 1 , wherein:

(a) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:54;

(b) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:66; or

(c) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:22.

3. The anti-BCMA scFv of claim 1 , wherein:

(a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54;

(b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66; or

(c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22.

4. The anti-BCMA scFv of claim 1 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 167, 168, and 169, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 170, 171, and 172, respectively.

5. The anti-BCMA scFv of claim 4 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54.

6. The anti-BCMA scFv of claim 1 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 185, 186, and 187, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 188, 189, and 190, respectively.

7. The anti-BCMA scFv of claim 6 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66.

8. The anti-BCMA scFv of claim 1 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 122, 123, and 124, respectively.

9. The anti-BCMA scFv of claim 8 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22.

10. The anti-BCMA scFv of claim 1 , wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO:85, SEQ ID NO:88, or SEQ ID NO:77.

11. A nucleic acid molecule that encodes the anti-BCMA scFv of claim 1 .

12. A nucleic acid molecule that encodes an anti-BCMA antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, wherein:

(a) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 167, 168, and 169, respectively and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 170, 171, and 172, respectively;

(b) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 185, 186, and 187, respectively and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 188, 189, and 190, respectively; or

(c) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 122, 123, and 124, respectively.

13. The nucleic acid molecule of claim 12 , wherein:

(a) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:54;

(b) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:66; or

(c) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:22.

14. The nucleic acid molecule of claim 12 , wherein:

(a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54;

(b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66; and

(c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22.

15. The nucleic acid molecule of claim 12 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 167, 168, and 169, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 170, 171, and 172, respectively.

16. The nucleic acid molecule of claim 15 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54.

17. The nucleic acid molecule of claim 12 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 185, 186, and 187, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 188, 189, and 190, respectively.

18. The nucleic acid molecule of claim 17 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66.

19. The nucleic acid molecule of claim 12 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 122, 123, and 124, respectively.

20. The nucleic acid molecule of claim 19 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22.

21. A pharmaceutical composition comprising the anti-BCMA scFv of claim 1 and a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising an anti-BCMA antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, and a pharmaceutically acceptable carrier, wherein:

(a) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 167, 168, and 169, respectively and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 170, 171, and 172, respectively;

(b) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 185, 186, and 187, respectively and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 188, 189, and 190, respectively; or

(c) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 122, 123, and 124, respectively.

23. The pharmaceutical composition of claim 22 , wherein:

(a) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:54;

(b) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:66; or

(c) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:22.

24. The pharmaceutical composition of claim 22 , wherein:

(a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54;

(b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66; or

(c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22.

25. The pharmaceutical composition of claim 22 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 167, 168, and 169, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 170, 171, and 172, respectively.

26. The pharmaceutical composition claim 25 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54.

27. The pharmaceutical composition of claim 22 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 185, 186, and 187, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 188, 189, and 190, respectively.

28. The pharmaceutical composition of claim 27 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66.

29. The pharmaceutical composition of claim 22 , wherein the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOs: 122, 123, and 124, respectively.

30. The pharmaceutical composition of claim 29 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2021
From: LIU, CHENG
To: EUREKA THERAPEUTICS, INC.
Reel/Frame 056284/0861 →
CONFIRMATORY PATENT ASSIGNMENT Recorded Apr 14, 2021
From: SMITH, ERIC L.
To: MEMORIAL SLOAN-KETTERING CANCER CENTER
Reel/Frame 055926/0284 →
CONFIRMATORY PATENT ASSIGNMENT Recorded Mar 11, 2021
From: BRENTJENS, RENIER J.
To: MEMORIAL SLOAN-KETTERING CANCER CENTER
Reel/Frame 055618/0192 →
Continuity (4)
Continuation 15613986 · Jun 5, 2017
Continuation PCTUS2015064119 · Dec 4, 2015
Provisional Application 62088246 · Dec 5, 2014
Related Publication 20200123266A1 · Apr 23, 2020
Cited By (4)
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