IP Library › Granted Patent US 12,473,359
Granted Patent B2
US 12,473,359 · App. 17/696,249 · Granted Nov 18, 2025

Chimeric antigen receptors targeting CD-19

Inventor: James N. Kochenderfer (Bethesda, MD)
Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
C07K16/2803A61K40/11A61K40/31A61K40/4211C07K14/705C07K14/7051C07K14/70517C07K14/70521C07K14/70535C07K14/70578C07K16/3061C12N5/0636A61K2239/13A61K2239/31A61K2239/48C07K2317/21C07K2317/622C07K2317/70C07K2319/00C07K2319/02C07K2319/03C07K2319/33C07K2319/74C12N2510/00
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Quick Facts
Patent No.
US 12,473,359
App. No.
17/696,249
Granted
Nov 18, 2025
Kind
B2
Abstract

The invention is directed to a chimeric antigen receptor (CAR) directed against CD19, which comprises an amino acid sequence of any one of SEQ ID NO: 1-SEQ ID NO: 13. The invention also provides T-cells expressing the CAR and methods for destroying malignant B-cells.

Claims (54)

1 . A chimeric antigen receptor (CAR) directed against CD19, wherein the CAR comprises the amino acid sequence of SEQ ID NO: 1.

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

3 . A vector comprising the nucleic acid of claim 2 .

4 . A cell comprising the nucleic acid of claim 2 .

5 . The cell of claim 4 , wherein the cell is a eukaryotic cell.

6 . The cell of claim 4 , wherein the cell is a peripheral blood lymphocyte (PBL), a peripheral blood mononuclear cell (PBMC), a natural killer (NK) cell, or a T-cell.

7 . The cell of claim 6 , wherein the cell is a T-cell.

8 . The cell of claim 6 , wherein the cell is a NK cell.

9 . A pharmaceutical composition comprising the cell of claim 6 and a pharmaceutically acceptable carrier.

10 . A chimeric antigen receptor (CAR) comprising amino acids 267-502 of the amino acid sequence of SEQ ID NO: 1 and an antigen binding domain of a human anti-CD19 antibody.

11 . A method of eliciting an antigen-specific response against a CD19-expressing cell, the method comprising contacting a cell comprising the CAR of claim 1 with the CD19-expressing cell.

12 . The method of claim 11 , wherein the cell is a PBL, a PBMC, a NK cell, or a T-cell.

13 . The method of claim 12 , wherein the cell is a T-cell.

14 . The method of claim 12 , wherein the cell is a NK cell.

15 . The method of claim 11 , wherein the CD19-expressing cell is a B cell.

16 . The method of claim 13 , wherein the contacting induces cytotoxicity of the CD19-expressing cell.

17 . A method of making a cell expressing a CAR, the method comprising introducing a vector encoding the CAR of claim 1 into a T cell or a NK cell.

18 . A method of making a cell expressing a chimeric receptor, the method comprising introducing a vector encoding the receptor CAR of claim 10 into a T cell or a NK cell.

19 . A method for determining the activity of a T cell expressing the CAR of claim 1 , the method comprising:

(a) contacting the T cell with a CD19-expressing cell;

(b) measuring cytotoxicity of the CD19-expressing cell following step (a); and

(c) comparing the cytotoxicity of the CD19-expressing cell measured in step (b) to cytotoxicity of a negative control CD19-expressing cell measured in the presence of a T cell that does not express the CAR.

20 . A method for determining the specificity of a T cell expressing the CAR of claim 1 , the method comprising:

(a) contacting the T cell with a CD19-expressing cell;

(b) measuring IFNγ and/or CD107a production by the T cell following step (a); and

(c) comparing the IFNγ and/or CD107a production measured in step (b) to IFNγ and/or CD107a production measured in a negative control with a CD19-negative cell.

21 . A nucleic acid encoding the CAR of claim 10 .

22 . A vector comprising the nucleic acid of claim 21 .

23 . A cell comprising the nucleic acid of claim 21 .

24 . The cell of claim 23 , wherein the cell is a eukaryotic cell.

25 . The cell of claim 23 , wherein the cell is a peripheral blood lymphocyte (PBL), a peripheral blood mononuclear cell (PBMC), a natural killer (NK) cell, or a T-cell.

26 . A pharmaceutical composition comprising the cell of claim 25 and a pharmaceutically acceptable carrier.

27 . A method of eliciting an antigen-specific response against a CD19-expressing cell, the method comprising contacting the cell of claim 25 with the CD19-expressing cell.

28 . A method of making a cell expressing a CAR, the method comprising introducing the nucleic acid of claim 21 into a cell.

29 . A chimeric antigen receptor (CAR) directed against CD19, comprising:

(a) an antigen binding domain of a human anti-CD19 antibody, comprising amino acids 22-266 of the amino acid sequence of SEQ ID NO: 1; and

(b) an extracellular spacer;

(c) a transmembrane domain; and

(d) an intracellular T-cell signaling domain from a human CD3g molecule.

30 . The CAR of claim 29 , wherein the extracellular spacer comprises a human CD8a hinge.

31 . The CAR of claim 30 , wherein the human CD8a hinge comprises amino acids 267-321 of SEQ ID NO: 1.

32 . The CAR of claim 29 , wherein the transmembrane domain is from a human CD8a molecule.

33 . The CAR of claim 32 , wherein the transmembrane domain comprises amino acids 322-342 of SEQ ID NO: 1.

34 . The CAR of claim 29 , wherein the intracellular T-cell signaling domain from the human CD32 molecule comprises amino acids 391-502 of SEQ ID NO: 1.

35 . The CAR of claim 29 , wherein the CAR further comprises an intracellular T-cell signaling domain from a human CD28 molecule.

36 . The CAR of claim 35 , wherein the intracellular T-cell signaling domain from the human CD28 molecule comprises amino acids 351-390 of SEQ ID NO: 1.

37 . A nucleic acid encoding the CAR of claim 29 .

38 . A vector comprising the nucleic acid of claim 37 .

39 . A cell comprising the nucleic acid of claim 37 .

40 . The cell of claim 39 , wherein the cell is a eukaryotic cell.

41 . The cell of claim 39 , wherein the cell is a PBL, a PBMC, a NK cell, or a T-cell.

42 . A pharmaceutical composition comprising the cell of claim 41 and a pharmaceutically acceptable carrier.

43 . A method of eliciting an antigen-specific response against a CD19-expressing cell, the method comprising contacting the cell of claim 41 with the CD19-expressing cell.

44 . A method of making a cell expressing a CAR, the method comprising introducing the nucleic acid of claim 37 into a cell.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 24, 2024
From: KOCHENDERFER, JAMES N.
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 066225/0850 →
Continuity (5)
Continuation 17557845 · Dec 21, 2021
Continuation 16360281 · Mar 21, 2019
Continuation 15315533
Provisional Application 62006313 · Jun 2, 2014
Related Publication 20220204619A1 · Jun 30, 2022
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