IP Library › Granted Patent US 9,765,342
Granted Patent B2
US 9,765,342 · App. 14/389,677 · Granted Sep 19, 2017

Chimeric antigen receptors targeting B-cell maturation antigen

Inventor: James Noble Kochenderfer (Bethesda, MD)
Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
C12N15/62C07K14/7051C07K14/70503C07K14/70517C07K14/70521C07K14/70578C07K16/18C07K16/2878A61K48/00A61K2039/505C07K2317/73C07K2319/00C07K2319/03
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Quick Facts
Patent No.
US 9,765,342
App. No.
14/389,677
Granted
Sep 19, 2017
Kind
B2
Abstract

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Claims (19)

1. A chimeric antigen receptor (CAR) comprising an antigen recognition moiety and a T-cell activation moiety, wherein the T-cell activation moiety comprises a transmembrane domain, wherein the antigen recognition moiety is directed against B-cell Maturation Antigen (BCMA).

2. The CAR of claim 1 , wherein the antigen recognition moiety comprises a monoclonal antibody directed against BCMA, or an antigen-binding portion thereof.

3. The CAR of claim 2 , wherein the antigen recognition moiety comprises a variable region of a monoclonal antibody directed against BCMA.

4. The CAR of claim 2 , wherein the antigen recognition moiety comprises an antigen binding fragment of a monoclonal antibody directed against BCMA.

5. The CAR of claim 2 , wherein the antigen recognition moiety comprises a single chain variable fragment (scFv) directed against BCMA.

6. The CAR of claim 1 , wherein the transmembrane domain is a CD28 transmembrane domain or a CD8a transmembrane domain.

7. The CAR of claim 1 , wherein the T-cell activation moiety comprises a T-cell signaling domain of any one of the following proteins: a human CD8-alpha protein, a human CD28 protein, a human CD3-zeta protein, a human FcRγ protein, a CD27 protein, an OX40 protein, a human 4-1BB protein, or any combination of the foregoing.

8. The CAR of claim 7 , wherein the T-cell activation moiety comprises a T-cell signaling domain of a human 4-1BB protein.

9. The CAR of claim 7 , wherein the T-cell activation moiety comprises a T-cell signaling domain of a human 4-1BB protein and a human CD3-zeta protein.

10. The CAR of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12.

11. The CAR of claim 1 , wherein the antigen recognition moiety comprises the (i) heavy chain complementarity determining region (CDR)1, (ii) heavy chain CDR2, (iii) heavy chain CDR3, (iv) light chain CDR1, (v) light chain CDR2, and (vi) light chain CDR3 of one amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

12. The CAR of claim 1 , wherein the antigen recognition moiety comprises the (i) heavy Chain variable region and (ii) light chain variable region of one amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

13. A nucleic acid encoding the CAR of claim 1 .

14. The nucleic acid of claim 13 , wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12.

15. The nucleic acid of claim 13 , wherein the antigen recognition moiety of the CAR comprises the (i) heavy chain CDR1, (ii) heavy Chain CDR2, (iii) heavy chain CDR3, (iv) light chain CDR1, (v) light chain CDR2, and (vi) light chain CDR3 of one amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

16. The nucleic acid of claim 13 , wherein the antigen recognition moiety of the CAR comprises the (i) heavy chain variable region and (ii) light chain variable region of one amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

17. A vector comprising a nucleic acid sequence encoding the CAR of claim 1 .

18. The vector of claim 17 , wherein the antigen recognition moiety comprises the (i) heavy chain CDR1, (ii) heavy chain CDR2, (iii) heavy chain CDR3, (iv) light chain CDR1, (v) light chain CDR2, and (vi) light chain CDR3 of one amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

19. An isolated host cell which expresses the CAR of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 10, 2014
From: KOCHENDERFER, JAMES NOBLE
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 034132/0828 →
Continuity (2)
Provisional Application 61622600 · Apr 11, 2012
Related Publication 20150051266A1 · Feb 19, 2015