Granted Patent
B2
US 12,522,667 · App. 17/510,099 · Granted Jan 13, 2026
Chimeric antigen receptors (CARs) having mutations in the fc spacer region and methods for their use
Inventors:
Stephen J. Forman (Duarte, CA); Christine E. Brown (Duarte, CA); Armen Mardiros (Glendale, CA)
Assignee:
City of Hope
C07K16/30A61K39/39558A61K40/11A61K40/31A61K40/4211A61K45/06C07K14/7051C07K14/70517C07K14/70521C07K14/71C07K16/00C07K16/2803C07K16/2866A61K2239/17A61K2239/31A61K2239/38C07K2317/524C07K2317/526C07K2317/53C07K2317/56C07K2317/622C07K2317/92C07K2319/00C07K2319/02C07K2319/03C07K2319/30C07K2319/33
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Abstract
Chimeric antigen receptors that include an antigen recognition domain; a spacer domain derived from a modified immunoglobulin Fc region having one or more mutations in its CH2 region resulting in impaired binding to an FcR; and an intracellular signaling domain.
Claims (11)
1 . A recombinant chimeric antigen receptor (CAR) comprising:
an antigen recognition domain that targets a cancer associated antigen selected from the group consisting of CD19, CD20, CD123, HER2, IL-13 receptor α2, prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), and tumor-associated glycoprotein-72 (TAG-72);
a spacer domain comprising the amino acid sequence ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT KPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEA LHNHYTQKSLSLSLGK (SEQ ID NO: 19);
a transmembrane domain;
a co-stimulatory intracellular signaling domain selected from the group consisting of: CD28, ICOS, OX40, CD27, DAP10, 4-1BB, p56lck, and 2B4; and
a T cell receptor (TCR) zeta chain signaling domain.
2 . The chimeric antigen receptor of claim 1 , wherein the co-stimulatory intracellular signaling domain is 4-1BB.
3 . The chimeric antigen receptor of claim 1 , wherein the co-stimulatory intracellular signaling domain is CD28.
4 . The chimeric antigen receptor of claim 1 , wherein the antigen recognition domain targets IL-13 receptor α2.
5 . The chimeric antigen receptor of claim 1 , wherein the antigen recognition domain is an scFv.
6 . The chimeric antigen receptor of claim 5 , wherein the antigen recognition domain is an scFv that targets CD19 and comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO:1 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 2.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Jan 4, 2024
From: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066204/0878 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 26, 2021
From: FORMAN, STEPHEN J.; BROWN, CHRISTINE E.; JONNALAGADDA, UMA MAHESWARA RAO; MARDIROS, ARMEN
To: CITY OF HOPE
Reel/Frame 057910/0858 →
Continuity (4)
Continuation
15111384
Provisional Application
61926881
· Jan 13, 2014
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