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US 12,180,261 B2Granted
T cell receptors
AssigneeAdaptimmune Limited
InventorsNicholas Tribble, William Lawrance, Eleanor Bagg
Life of this patent
Estimating the term…
Abstract
The present invention relates to T cell receptors (TCRs) which bind the HLA-A*0201 restricted peptide GVYDGEEHSV (SEQ ID NO: 1) derived from the MAGE-B2 protein. The TCRs of the invention demonstrate excellent specificity profiles for this MAGE epitope. Also provided are nucleic acids encoding the TCRs, cells engineered to present the TCRs, cells harbouring expression vectors encoding the TCRs and pharmaceutical compositions comprising the TCRs, nucleic acids or cells of the invention.
Claims20
A T cell receptor (TCR) that comprises a TCR alpha chain variable domain and a TCR beta chain variable domain, wherein:
- (A) the TCR alpha chain variable domain is comprised in a sequence in which:
- (i) amino acid residues 1-27 has (a) at least 90% identity to the sequence of amino acid residues 1-27 of SEQ ID No:
- 3 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 1-27 of SEQ ID No:
- 3;
- (ii) amino acid residues 28-33 is amino acid residues 28-33 of SEQ ID NO:
- 3;
- (iii) amino acid residues 34-47 has (a) at least 90% identity to the sequence of amino acid residues 34-47 of SEQ ID NO:
- 3 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 34-47 of SEQ ID No:
- 3;
- (iv) amino acid residues 48-53 is amino acid residues 48-53 of any of SEQ ID NOs:
- 3 or 7;
- (v) amino acid residues 54-90 has (a) at least 90% identity to the sequence of amino acid residues 54-90 of SEQ ID No:
- 3 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 54-90 of SEQ ID No:
- 3;
- and
- (vi) amino acid residues 91-105 is amino acid residues 91-105 of SEQ ID NO:
- 3;
- and
- (B) the TCR beta chain variable domain is comprised in a sequence in which:
- (i) amino acid residues 1-45 has (a) at least 90% identity to the amino acid sequence of residues 1-45 of SEQ ID No:
- 4 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 1-45 of SEQ ID No:
- 4;
- (ii) amino acid residues 46-50 is amino acid residues 46-50 of SEQ ID NO:
- 4;
- (iii) amino acid residues 51-67 has (a) at least 90% identity to the sequence of amino acid residues 51-67 of SEQ ID NO:
- 4 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 51-67 of SEQ ID No:
- 4;
- (iv) amino acid residues 68-72 is amino acid residues 68-72 of SEQ ID NO:
- 4 or 11;
- (v) amino acid residues 73-109 has (a) at least 90% identity to the sequence of amino acid residues 73-109 of SEQ ID NO:
- 4 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 73-109 of SEQ ID No:
- 4;
- and
- (vi) amino acid residues 110-123 is amino acid residues 110-123 of any one of SEQ ID NOs:
- 10, 11 or 12, or amino acid residues 110-123 of SEQ ID NO:
- 4 provided that amino acid residues 48-53 of the TCR alpha chain variable domain is amino acid residues 48-53 of SEQ ID NO:
- 7.
34 more elements
An isolated or non-naturally occurring cell presenting a TCR encoded by a nucleic acid, wherein the nucleic acid encodes a TCR that comprises:
- (A) a TCR alpha chain variable domain in which:
- (i) amino acid residues 1-27 has (a) at least 90% identity to the sequence of amino acid residues 1-27 of SEQ ID No:
- 3 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 1-27 of SEQ ID No:
- 3;
- (ii) amino acid residues 28-33 is amino acid residues 28-33 of SEQ ID NO:
- 3;
- (iii) amino acid residues 34-47 has (a) at least 90% identity to the sequence of amino acid residues 34-47 of SEQ ID NO:
- 3 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 34-47 of SEQ ID No:
- 3;
- (iv) amino acid residues 48-53 is amino acid residues 48-53 of any of SEQ ID NOs:
- 3 or 7;
- (v) amino acid residues 54-90 has (a) at least 90% identity to the sequence of amino acid residues 54-90 of SEQ ID No:
- 3 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 54-90 of SEQ ID No:
- 3;
- and
- (vi) amino acid residues 91-105 is amino acid residues 91-105 of SEQ ID NO:
- 3;
- and
- (B) the TCR beta chain variable domain is comprised in a sequence in which:
- (i) amino acid residues 1-45 has (a) at least 90% identity to the amino acid sequence of residues 1-45 of SEQ ID No:
- 4 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 1-45 of SEQ ID No:
- 4;
- (ii) amino acid residues 46-50 is amino acid residues 46-50 of SEQ ID NO:
- 4;
- (iii) amino acid residues 51-67 has (a) at least 90% identity to the sequence of amino acid residues 51-67 of SEQ ID NO:
- 4 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 51-67 of SEQ ID No:
- 4;
- (iv) amino acid residues 68-72 is amino acid residues 68-72 of SEQ ID NO:
- 4 or 11;
- (v) amino acid residues 73-109 has (a) at least 90% identity to the sequence of amino acid residues 73-109 of SEQ ID NO:
- 4 or (b) one, two or three amino acid insertions, deletions or substitutions relative to amino acid residues 73-109 of SEQ ID No:
- 4;
- and
- (vi) amino acid residues 110-123 is amino acid residues 110-123 of any one of SEQ ID NOs:
- 10, 11 or 12, or amino acid residues 110-123 of SEQ ID NO:
- 4, provided that amino acid residues 48-53 of the TCR alpha chain variable domain is amino acid residues 48-53 of SEQ ID NO:
- 7.
34 more elements
Dependencies are inferred from the claim text.