Granted Patent B2

US 12,570,716 · App. 17/758,959 · Granted Mar 10, 2026

Inventors: Michael C. Jensen (Seattle, WA); James F. Matthaei (Seattle, WA); Joseph K. Cheng (Seattle, WA)

Assignee: Seattle Children's Hospital

C07K14/7051A61K40/11A61K40/31A61K40/414A61K2239/31A61K2239/47A61K2239/49

Abstract

Claims (26)

1 . A chimeric antigen receptor (CAR) comprising:

a ligand binding domain which specifically binds to a dinitrophenol (DNP) moiety, wherein the ligand binding domain comprises (i) an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:1, SEQ ID NO:7 or SEQ ID NO:12; or (ii) an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11;

a spacer;

a transmembrane domain; and

an intracellular signaling domain.

2 . A system comprising:

(a) an effector cell comprising the CAR of claim 1 ; and

(b) a composition comprising a dinitrophenol (DNP) moiety, wherein the CAR specifically binds to the DNP moiety.

3 . The system of claim 2 , wherein the DNP moiety is attached to the target cell via an antibody or antigen binding fragment thereof that binds to the target cell; or via a lipid integrated into the target cell's surface.

4 . The system of claim 3 , wherein the target cell is a cancer cell.

5 . The system of claim 4 , wherein the cancer cell is selected from the group consisting of a breast cancer cell, brain cancer cell, colon cancer cell, renal cancer cell, pancreatic cancer cell, and ovarian cancer cell.

6 . The CAR of claim 1 , wherein the ligand binding domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in any of SEQ ID NO:1, SEQ ID NO:9 and SEQ ID NO:10.

7 . The CAR of claim 1 , wherein the ligand binding domain comprises an amino acid sequence having at least 96% sequence identity to SEQ ID NO:1.

8 . The CAR of claim 1 , wherein the spacer comprises an IgG4 hinge domain, an IgG4 hinge-CH3 domain, or an IgG4 hinge-CH2-CH3 domain.

9 . The CAR of claim 1 , wherein the spacer has a length of at least 229 consecutive amino acid residues.

10 . The CAR of claim 1 , wherein the spacer comprises the amino acid sequence set forth in SEQ ID NO:20.

11 . The CAR of claim 1 , wherein the transmembrane domain comprises a CD28 transmembrane domain, and the intracellular signaling domain comprises a portion of CD3 zeta and/or a portion of 4-1BB.

12 . The system of claim 2 , wherein the ligand binding domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in any of SEQ ID NO:1, SEQ ID NO:9 and SEQ ID NO:10.

13 . The system of claim 2 , wherein the ligand binding domain comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:1 or SEQ ID NO:2.

14 . The system of claim 2 , wherein the spacer comprises an IgG4 hinge domain, an IgG4 hinge-CH3 domain, or an IgG4 hinge -CH2-CH3 domain.

15 . The system of claim 2 , wherein the spacer has a length of at least 229 consecutive amino acid residues.

16 . The system of claim 2 , wherein the spacer comprises the amino acid sequence set forth in SEQ ID NO:20.

17 . The system of claim 2 , wherein the transmembrane domain comprises a CD28 transmembrane domain, and the intracellular signaling domain comprises a portion of CD3 zeta and/or a portion of 4-1BB.

18 . The system of claim 2 , wherein the DNP moiety is joined to a phospholipid.

19 . The system of claim 18 , wherein the phospholipid is a phospholipid ether (PLE).

20 . The system of claim 19 , wherein the DNP moiety is joined to the PLE by a PEG spacer, and the DNP moiety joined to the PLE by the PEG spacer comprises a structure:

Assignments (1)

Continuity (2)

References Cited (400)