US 12,331,129 B2
Chimeric receptors targeting ADGRE2 and/or CLEC12A and uses thereof
Michel Sadelain, New York, NY (US); Sascha P. Haubner, New York, NY (US); Jorge Mansilla-Soto, Forest Hills, NY (US); Xingyue He, Cambridge, MA (US); and Gary Shapiro, Cambridge, MA (US)
Assigned to MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US); SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH, New York, NY (US); MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES, New York, NY (US); and MILLENNIUM PHARMACEUTICALS, INC., Cambridge, MA (US)
Filed by MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US); MILLENNIUM PHARMACEUTICALS, INC., Cambridge, MA (US); SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH, New York, NY (US); and MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES, New York, NY (US)
Filed on Apr. 25, 2022, as Appl. No. 17/728,183.
Claims priority of provisional application 63/287,655, filed on Dec. 9, 2021.
Claims priority of provisional application 63/179,799, filed on Apr. 26, 2021.
Prior Publication US 2022/0363775 A1, Nov. 17, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01)
CPC C07K 16/2896 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/464402 (2023.05); A61K 39/464412 (2023.05); A61K 39/464429 (2023.05); A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70521 (2013.01); C07K 14/70578 (2013.01); C07K 16/2851 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2239/29 (2023.05); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05); C07K 2317/24 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01)] 66 Claims
OG exemplary drawing
 
1. A cell comprising a chimeric antigen receptor (CAR) and a chimeric co-stimulatory receptor (CCR), wherein
a) the CAR comprises an extracellular antigen-binding domain that binds to ADGRE2, a transmembrane domain, and an intracellular domain, wherein the extracellular antigen-binding domain comprises a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 33, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 35; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 36, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 37, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 38; and
b) the CCR comprises an extracellular antigen-binding domain that binds to CLEC12A, a transmembrane domain, and an intracellular domain, wherein the extracellular antigen-binding domain comprises:
i) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 69, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 71; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 72, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 74;
ii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 85;
iii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 89, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 91; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 92, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 93, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 94;
iv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 89, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 98; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 99, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 93, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 94;
v) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 103, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 104, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 105;
vi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 109, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 103, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 110, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 73, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 85;
vii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 89, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 114; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 115, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 93, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 116; or
viii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 120, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 121, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 123, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 124, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 125.