US 11,753,456 B2
T cell receptors
Nicholas Tribble, Abingdon (GB); William Lawrance, Abingdon (GB); and Eleanor Bagg, Abingdon (GB)
Assigned to Adaptimmune Limited, Abingdon (GB)
Filed by Adaptimmune Limited, Abingdon (GB)
Filed on Oct. 14, 2021, as Appl. No. 17/501,200.
Application 17/501,200 is a continuation of application No. 16/154,270, filed on Oct. 8, 2018, abandoned.
Application 16/154,270 is a continuation in part of application No. PCT/EP2017/058578, filed on Apr. 10, 2017.
Claims priority of application No. 1606156 (GB), filed on Apr. 8, 2016.
Prior Publication US 2022/0025013 A1, Jan. 27, 2022
Int. Cl. C07K 14/725 (2006.01); C07K 14/47 (2006.01); A61P 35/00 (2006.01); A61K 35/17 (2015.01); A61K 38/00 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 14/4748 (2013.01); A61K 38/00 (2013.01)] 18 Claims
 
1. A T cell receptor (TCR) having binding specificity to GVYDGEEHSV (SEQ ID NO: 2) in complex with HLA-A*0201 and GVYDGREHTV (SEQ ID NO: 1) in complex with HLA-A*0201, wherein the TCR comprises a TCR alpha chain variable domain (Vα) comprising complementarity determining regions (CDR) Vα CDR1, Vα CDR2 and Vα CDR3 and a TCR beta chain variable domain (Vβ) comprising Vβ CDR1, CDR2 and Vβ CDR3, wherein
the Vα CDR1 comprises amino acid residues 28-33 of SEQ ID NO: 3;
the Vα CDR2 comprises amino acid residues 48-53 of SEQ ID NO: 3, or amino acid residues 48-53 of SEQ ID NO: 3 with an M51T or M51N substitution;
the Vα CDR3 comprises amino acid residues 91-105 of SEQ ID NO: 3, or amino acid residues 91-105 of SEQ ID NO: 3 with an S94T or S94N substitution;
the Vβ CDR1 comprises amino acid residues 46-50 of SEQ ID NO: 4;
the Vβ CDR2 comprises amino acid residues 68-72 of SEQ ID NO: 4, or amino acid residues 68-72 of SEQ ID NO: 4 with an S68A substitution; and
the Vβ CDR3 comprises amino acid residues 110-123 of SEQ ID NO: 4, or amino acid residues 110-123 of SEQ ID NO: 4 with a substitution selected from the group consisting of (a) S113T, (b) S113N, (c) N119V, (d) N119G, and (e) S113T and N119E, and
wherein at least one of the Vα CDR2, Vα CDR3, Vβ CDR2, and Vβ CDR3 includes one of the corresponding substitutions.