IP Library › Granted Patent US 12,447,178
Granted Patent B2
US 12,447,178 · App. 18/395,996 · Granted Oct 21, 2025

Method of treatment using anti-CD19 rituximab-resistant chimeric antigen receptors

Inventors: Thomas Charles Pertel (San Mateo, CA); Barbra Johnson Sasu (San Francisco, CA); Mark W. Leonard (Burlingame, CA)
Assignee: Allogene Therapeutics, Inc.
A61K35/17A61K40/11A61K40/31A61K40/4211A61P35/00C07K14/70517C07K14/70596C07K16/2803C12N5/0636A61K2039/505A61K2239/38C07K2317/76C07K2319/33C12N2510/00C12N2740/15043
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Quick Facts
Patent No.
US 12,447,178
App. No.
18/395,996
Granted
Oct 21, 2025
Kind
B2
Abstract

Provided herein are polynucleotides encoding chimeric antigen receptors (CARs) comprising a CD19 antigen binding domain that specifically binds to CD19 and is resistant to rituximab binding; and immune cells comprising these CD19-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using these CD19-specific CARs, and immune cells comprising these CD19-specific CARs.

Claims (21)

1. A method of treating a CD19-expressing cancer or malignancy in a subject in need thereof comprising administering to the subject an engineered immune cell that comprises an isolated polynucleotide encoding a polypeptide comprising an anti-CD19 chimeric antigen receptor (CAR) that comprises the amino acid sequence of SEQ ID NO: 9, wherein the polypeptide does not comprise a rituximab binding site, wherein the polynucleotide comprises a nucleic acid sequence having at least 90% identity to SEQ ID NO: 3 and a short EF1a promoter that is capable of expressing the anti-CD19 chimeric antigen receptor (CAR) in a mammalian T cell, and wherein the short EF1a promoter comprises the nucleic acid sequence of SEQ ID NO:16 and does not comprise the nucleic acid sequence of SEQ ID NO:39.

2. The method of claim 1 , wherein the CD19-expressing cancer or malignancy is Non-Hodgkin lymphoma (NHL).

3. The method of claim 1 or 2 , wherein the subject has been treated or is currently being treated with rituximab.

4. The method of claim 1 , wherein the polypeptide further comprises a safety switch.

5. The method of claim 4 , wherein the safety switch is linked to the CD19 CAR using a linker peptide.

6. The method of claim 4 , wherein the safety switch is linked to the anti-CD19 CAR using a T2A linker.

7. The method of claim 4 , wherein the safety switch comprises an antibody binding site.

8. The method of claim 4 , wherein the safety switch comprises a mutated CD20 rituximab mimotope.

9. The method of claim 4 , wherein the polypeptide comprises a CD34 epitope.

10. The method of claim 9 , wherein the CD34 epitope is a QBEND-10 epitope.

11. The method of claim 1 , wherein the polypeptide further comprises a CD8 hinge/transmembrane domain.

12. The method of claim 1 , wherein the polynucleotide encodes a polypeptide that comprises any one of the amino acid sequences of SEQ ID NOs: 11-14.

13. The method of claim 1 , wherein the polynucleotide comprises a nucleic acid sequence having at least 95% identity to SEQ ID NO: 3.

14. The method of claim 1 , wherein the polynucleotide comprises a nucleic acid sequence having at least 96% identity to SEQ ID NO: 3.

15. The method of claim 1 , wherein the polynucleotide comprises a nucleic acid sequence having at least 98% identity to SEQ ID NO: 3.

16. The method of claim 1 , wherein the polynucleotide comprises a nucleic acid sequence having at least 99% identity to SEQ ID NO: 3.

17. The method of claim 1 , wherein the polynucleotide comprises the nucleic acid sequence shown in SEQ ID NO: 3.

18. The method of claim 1 , wherein the engineered immune cell is a T cell, tumor infiltrating lymphocyte (TIL), NK cell, TCR-expressing cell, dendritic cell, or NK-T cell.

19. The method of claim 18 , wherein the T cell is an autologous T cell.

20. The method of claim 18 , wherein the T cell is an allogeneic T cell.

21. The method of claim 1 , wherein the engineered cell is resistant to rituximab.

Continuity (4)
Division 16857573 · Apr 24, 2020
Provisional Application 63005041 · Apr 3, 2020
Provisional Application 62839455 · Apr 26, 2019
Related Publication 20240277763A1 · Aug 22, 2024
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