IP Library › Granted Patent US 10,934,337
Granted Patent B2
US 10,934,337 · App. 16/825,996 · Granted Mar 2, 2021

Anti-BCMA chimeric antigen receptors

Inventors: Yi Zhang (Gaithersburg, MD); C. Andrew Stewart (Frederick, MD); Metin Kurtoglu (Bethesda, MD); Murat V. Kalayoglu (Silver Spring, MD); Michael S. Singer (Chestnut Hill, MA)
Assignee: Cartesian Therapeutics, Inc.
C07K14/70517A61K39/3955A61K39/39558C07K16/2878C07K16/2896C07K16/30A61K2039/505C07K2317/24C07K2317/53C07K2317/565C07K2317/622C07K2317/73C07K2317/76C07K2319/03
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Quick Facts
Patent No.
US 10,934,337
App. No.
16/825,996
Granted
Mar 2, 2021
Kind
B2
Abstract

Provided herein are chimeric antigen receptors (CARs), such as those specific for BCMA, that have improved properties, including increased CAR T cell binding to BCMA and improved CAR T cell killing of BCMA-expressing cancer cells. Use of the CARs in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding the same), and methods are also contemplated.

Claims (113)

1. A chimeric antigen receptor (CAR) comprising:

(i) an anti-B-Cell Maturation Antigen (BCMA) binding domain;

(ii) a transmembrane domain; and

(iii) a cytoplasmic domain,

wherein the anti-BCMA binding domain comprises:

a heavy chain complementarity determining region 1 (CDRH1) comprising any one of SEQ ID NOs: 1-3;

a heavy chain complementarity determining region 2 (CDRH2) comprising any one of SEQ ID NOs: 4-6;

a heavy chain complementarity determining region 3 (CDRH3) comprising any one of SEQ ID NOs: 7-9;

a light chain complementarity determining region 1 (CDRL1) comprising any one of SEQ ID NOs: 10-11;

a light chain complementarity determining region 2 (CDRL2) comprising any one of SEQ ID NOs: 12-15; and

a light chain complementarity determining region 3 (CDRL3) comprising any one of SEQ ID NOs: 16-18;

provided that the anti-BCMA binding domain does not comprise all six of the following:

a CDRH1 comprising SEQ ID NO: 1;

a CDHR2 comprising SEQ ID NO: 4;

a CDHR3 comprising SEQ ID NO: 7;

a CDRL1 comprising SEQ ID NO: 10;

a CDRL2 comprising SEQ ID NO: 12; and

a CDRL3 comprising SEQ ID NO: 16.

2. The CAR of claim 1 , wherein the CDRH3 comprises SEQ ID NO: 7.

3. The CAR of claim 1 , wherein the CDRH3 comprises SEQ ID NO: 8.

4. The CAR of claim 1 , wherein the CDRH3 comprises SEQ ID NO: 9.

5. The CAR of claim 1 , wherein the CDRL3 comprises SEQ ID NO: 16.

6. The CAR of claim 1 , wherein the CDRL3 comprises SEQ ID NO: 17.

7. The CAR of claim 1 , wherein the CDRL3 comprises SEQ ID NO: 18.

8. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 3;

(ii) the CDRH2 comprises SEQ ID NO: 4;

(iii) the CDRH3 comprises SEQ ID NO: 7;

(iv) the CDRL1 comprises SEQ ID NO: 10;

(v) the CDRL2 comprises SEQ ID NO: 12; and

(vi) the CDRL3 comprises SEQ ID NO: 16.

9. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 1;

(ii) the CDRH2 comprises SEQ ID NO: 4;

(iii) the CDRH3 comprises SEQ ID NO: 8;

(iv) the CDRL1 comprises SEQ ID NO: 10;

(v) the CDRL2 comprises SEQ ID NO: 12; and

(vi) the CDRL3 comprises SEQ ID NO: 16.

10. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 1;

(ii) the CDRH2 comprises SEQ ID NO: 4;

(iii) the CDRH3 comprises SEQ ID NO: 7;

(iv) the CDRL1 comprises SEQ ID NO: 11;

(v) the CDRL2 comprises SEQ ID NO: 14; and

(vi) the CDRL3 comprises SEQ ID NO: 17.

11. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 1;

(ii) the CDRH2 comprises SEQ ID NO: 4;

(iii) the CDRH3 comprises SEQ ID NO: 7;

(iv) the CDRL1 comprises SEQ ID NO: 11;

(v) the CDRL2 comprises SEQ ID NO: 14; and

(vi) the CDRL3 comprises SEQ ID NO: 18.

12. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 2;

(ii) the CDRH2 comprises SEQ ID NO: 6;

(iii) the CDRH3 comprises SEQ ID NO: 9;

(iv) the CDRL1 comprises SEQ ID NO: 10;

(v) the CDRL2 comprises SEQ ID NO: 12; and

(vi) the CDRL3 comprises SEQ ID NO: 16.

13. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 3;

(ii) the CDRH2 comprises SEQ ID NO: 5;

(iii) the CDRH3 comprises SEQ ID NO: 8;

(iv) the CDRL1 comprises SEQ ID NO: 10;

(v) the CDRL2 comprises SEQ ID NO: 12; and

(vi) the CDRL3 comprises SEQ ID NO: 16.

14. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 3;

(ii) the CDRH2 comprises SEQ ID NO: 4;

(iii) the CDRH3 comprises SEQ ID NO: 9;

(iv) the CDRL1 comprises SEQ ID NO: 10;

(v) the CDRL2 comprises SEQ ID NO: 12; and

(vi) the CDRL3 comprises SEQ ID NO: 18.

15. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 2;

(ii) the CDRH2 comprises SEQ ID NO: 6;

(iii) the CDRH3 comprises SEQ ID NO: 9;

(iv) the CDRL1 comprises SEQ ID NO: 11;

(v) the CDRL2 comprises SEQ ID NO: 13; and

(vi) the CDRL3 comprises SEQ ID NO: 17.

16. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 1;

(ii) the CDRH2 comprises SEQ ID NO: 4;

(iii) the CDRH3 comprises SEQ ID NO: 7;

(iv) the CDRL1 comprises SEQ ID NO: 10;

(v) the CDRL2 comprises SEQ ID NO: 15; and

(vi) the CDRL3 comprises SEQ ID NO: 16.

17. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 2;

(ii) the CDRH2 comprises SEQ ID NO: 6;

(iii) the CDRH3 comprises SEQ ID NO: 9;

(iv) the CDRL1 comprises SEQ ID NO: 11;

(v) the CDRL2 comprises SEQ ID NO: 14; and

(vi) the CDRL3 comprises SEQ ID NO: 17.

18. The CAR of claim 1 , wherein:

(i) the CDRH1 comprises SEQ ID NO: 2;

(ii) the CDRH2 comprises SEQ ID NO: 6;

(iii) the CDRH3 comprises SEQ ID NO: 9;

(iv) the CDRL1 comprises SEQ ID NO: 11;

(v) the CDRL2 comprises SEQ ID NO: 14; and

(vi) the CDRL3 comprises SEQ ID NO: 18.

19. The CAR of claim 1 , wherein the CDRH1 comprises SEQ ID NO: 1.

20. The CAR of claim 1 , wherein the CDRH1 comprises SEQ ID NO: 2.

21. The CAR of claim 1 , wherein the CDRH1 comprises SEQ ID NO: 3.

22. The CAR of claim 1 , wherein the CDRH2 comprises SEQ ID NO: 4.

23. The CAR of claim 1 , wherein the CDRH2 comprises SEQ ID NO: 5.

24. The CAR of claim 1 , wherein the CDRH2 comprises SEQ ID NO: 6.

25. The CAR of claim 1 , wherein the CDRL1 comprises SEQ ID NO: 10.

26. The CAR of claim 1 , wherein the CDRL1 comprises SEQ ID NO: 11.

27. The CAR of claim 1 , wherein the CDRL2 comprises SEQ ID NO: 12.

28. The CAR of claim 1 , wherein the CDRL2 comprises SEQ ID NO: 13.

29. The CAR of claim 1 , wherein the CDRL2 comprises SEQ ID NO: 14.

30. The CAR of claim 1 , wherein the CDRL2 comprises SEQ ID NO: 15.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2020
From: ZHANG, YI; STEWART, C. ANDREW; KURTOGLU, METIN; KALAYOGLU, MURAT V.; SINGER, MICHAEL S.
To: CARTESIAN THERAPEUTICS, INC.
Reel/Frame 053897/0377 →
Continuity (3)
Continuation PCTUS2020022671 · Mar 13, 2020
Provisional Application 62819068 · Mar 15, 2019
Related Publication 20200291087A1 · Sep 17, 2020
Cited By (1)
US 12,311,033