Granted Patent B2

US 12,453,780 · App. 17/355,703 · Granted Oct 28, 2025

Inventors: Javed Khan (Derwood, MD); Sivasubramanian Baskar (Ellicott City, MD); Rimas J. Orentas (Seattle, WA); Dimiter S. Dimitrov (Pittsburgh, PA); Zhongyu Zhu (Frederick, MD); Tai Chi Cheuk (Germantown, MD)

Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services

A61K47/6849A61K39/39558A61K47/6803A61K47/68031A61K47/6911A61P35/00C07K16/2863C07K2317/622C07K2317/77C07K2317/92

Abstract

Claims (24)

1. A chimeric antigen receptor (CAR) comprising:

a monoclonal antibody that binds fibroblast growth factor receptor 4 (FGFR4), or antigen-binding fragment thereof, comprising a variable heavy (VH) domain and a variable light (VL) domain, wherein the VH domain of the antibody comprises the complementarity determining region 1 (CDR), CDR2, and CDR3 sequences of SEQ ID NO: 3 and the VL domain of the antibody comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 4;

a transmembrane domain; and

a signaling domain,

wherein the VH domain CDR1, CDR2 and CDR3 sequences respectively comprise residues 26-33, 52-59 and 98-111 of SEQ ID NO: 3, and the VL domain CDR1, CDR2 and CDR3 sequences respectively comprise residues 27-32, 50-52 and 88-98 of SEQ ID NO: 4.

2. The CAR of claim 1 , wherein the amino acid sequence of the VH domain is at least 90% identical to SEQ ID NO: 3 and the amino acid sequence of the VL domain is at least 90% identical to SEQ ID NO: 4.

3. The CAR of claim 1 , wherein the amino acid sequence of the VH domain comprises SEQ ID NO: 3 and the amino acid sequence of the VL domain comprises SEQ ID NO: 4.

4. The CAR of claim 1 , wherein the antigen-binding fragment is a single chain variable fragment (scFv).

5. The CAR of claim 1 , wherein the monoclonal antibody or antigen-binding fragment is a fully human antibody or antigen-binding fragment.

6. The CAR of claim 1 , wherein the monoclonal antibody or antigen-binding fragment is a chimeric, synthetic, or humanized antibody or antigen-binding fragment.

7. The CAR of claim 1 , wherein the transmembrane domain comprises a CD28 transmembrane domain.

8. The CAR of claim 7 , wherein the CD28 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 57.

9. The CAR of claim 1 , wherein the signaling domain comprises a CD28, CD137 or CD3ζ signaling domain.

10. The CAR of claim 9 , wherein the CD28 signaling domain comprises the amino acid sequence of SEQ ID NO: 58.

11. The CAR of claim 1 , wherein the transmembrane and signaling domains comprise the amino acid sequence of SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 66 or SEQ ID NO: 67.

12. An isolated cell expressing the CAR of claim 1 .

13. The isolated cell of claim 12 , which is a cytotoxic T lymphocyte (CTL).

14. A composition comprising the CAR of claim 1 and a pharmaceutically acceptable carrier.

15. The CAR of claim 4 , wherein the amino acid sequence of the scFv comprises SEQ ID NO: 38.

16. The CAR of claim 4 , wherein the amino acid sequence of the scFv comprises SEQ ID NO: 41.

17. The CAR of claim 1 , wherein the transmembrane domain comprises a CD8 transmembrane domain.

18. The CAR of claim 17 , wherein the CD8 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 60 or SEQ ID NO: 61.

19. The CAR of claim 9 , wherein the CD137 signaling domain comprises the amino acid sequence of SEQ ID NO: 62 or SEQ ID NO: 63.

20. The CAR of claim 9 , wherein the CD3ζ signaling domain comprises the amino acid sequence of SEQ ID NO: 64.

Assignments (2)

Continuity (3)

References Cited (20)