US 12,247,060 B2
Calreticulin binding constructs and engineered T cells for the treatment of diseases
Andreas Loew, Cambridge, MA (US); and Brian Edward Vash, Cambridge, MA (US)
Assigned to Marengo Therapeutics, Inc., Cambridge, MA (US)
Appl. No. 16/960,704
Filed by MARENGO THERAPEUTICS, INC., Cambridge, MA (US)
PCT Filed Jan. 9, 2019, PCT No. PCT/US2019/012900
§ 371(c)(1), (2) Date Jul. 8, 2020,
PCT Pub. No. WO2019/139987, PCT Pub. Date Jul. 18, 2019.
Claims priority of provisional application 62/615,270, filed on Jan. 9, 2018.
Prior Publication US 2021/0137982 A1, May 13, 2021
Int. Cl. A61K 39/00 (2006.01); A61K 35/17 (2015.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/18 (2006.01); C07K 16/28 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 35/17 (2013.01); A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/4644 (2023.05); C07K 14/70521 (2013.01); C07K 14/70578 (2013.01); C07K 16/18 (2013.01); C07K 16/28 (2013.01); C07K 2317/565 (2013.01); C07K 2317/92 (2013.01); C07K 2319/03 (2013.01)] 24 Claims
 
1. A composition comprising a nucleic acid comprising a sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antibody domain comprising a mutant calreticulin binding domain, a transmembrane domain, and an intracellular domain comprising an intracellular signaling domain;
wherein the mutant calreticulin binding domain comprises a heavy chain variable domain (VH) comprising an amino acid sequence with at least 77% sequence identity to SEQ ID NO: 1 or an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 2 and a light chain variable domain (VL), wherein:
(I) the VH comprises a heavy chain complement determining region 1 (HC CDR1) with the amino acid sequence of SEQ ID NO: 7, a HC CDR2 with the amino acid sequence of SEQ ID NO: 8, and a HC CDR3 with the amino acid sequence of SEQ ID NO: 9; and the VL comprises a light chain CDR1 (LC CDR1) with the amino acid sequence of SEQ ID NO: 13, a LC CDR2 with the amino acid sequence of SEQ ID NO: 14, and a LC CDR3 with the amino acid sequence of SEQ ID NO: 15;
(II) the VH comprises a HC CDR1 with the amino acid sequence of SEQ ID NO: 10, a HC CDR2 with the amino acid sequence of SEQ ID NO: 11, and a HC CDR3 with the amino acid sequence of SEQ ID NO: 12; and the VL comprises a LC CDR1 with the amino acid sequence of SEQ ID NO: 13, a LC CDR2 with the amino acid sequence of SEQ ID NO: 14, and a LC CDR3 with the amino acid sequence of SEQ ID NO: 15; or
(III) the VH comprises a HC CDR1 with the amino acid sequence of SEQ ID NO: 10, a HC CDR2 with the amino acid sequence of SEQ ID NO: 11, and a HC CDR3 with the amino acid sequence of SEQ ID NO: 16; and the VL comprises a LC CDR1 with the amino acid sequence of SEQ ID NO: 13, a LC CDR2 with the amino acid sequence of SEQ ID NO: 14, and a LC CDR3 with the amino acid sequence of SEQ ID NO: 15.