Specific binding molecules
OwnerChandramouli CHILLAKURI, Jorge DIAS DO NASCIMENTO +5inventors
InventorsChandramouli CHILLAKURI, Jorge DIAS DO NASCIMENTO, Conor HAYES, James PARKER, Peter JAMES, Ronan O'DWYER, Andrew POOLE
Life of this patent
Estimating the term…
Abstract
The present invention relates to specific binding molecules, such as T cell receptors (TCRs), that bind the HLA-A*02 restricted peptide KVLEYVIKV (SEQ ID NO: 1) derived from the germline cancer antigen MAGEA1. The specific binding molecules may comprise non-natural mutations within the alpha and/or beta variable domains relative to a native MAGEA1 TCR. The specific binding molecules of the invention are particularly suitable for use as novel immunotherapeutic reagents for the treatment of malignant disease.
Claims26
A specific binding molecule having the property of binding to KVLEYVIKV (SEQ ID NO:
- 1) HLA-A*02 complex and/or KVLEYVIKV (SEQ ID NO:
- 1) HLA-A*02 complex and comprising a TCR alpha chain variable domain and/or a TCR beta chain variable domain each of which comprises FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 where FR is a framework region and CDR is a complementarity determining region, wherein
- the alpha chain CDRs have the following sequences:
- CDR1-
- (SEQ ID NO:
- 15)
- SSVPPY
- CDR2-
- (SEQ ID NO:
- 16)
- YTSAATLV
- CDR3-
- (SEQ ID NO:
- 17)
- AARPSSSNTGKLI
- optionally with one or more mutations therein,
- and/or
- (b) the beta chain CDRs have the following sequences:
- CDR1-
- (SEQ ID NO:
- 18)
- PRHDT
- CDR2-
- (SEQ ID NO:
- 19)
- FYEKMQ
- CDR3-
- (SEQ ID NO:
- 20)
- ASSFTGFDEQF
- optionally with one or more mutations therein
A specific binding molecule-anti-CD3 fusion molecule, comprising an alpha chain variable domain which comprises:
- an amino acid sequence selected from SEQ ID NOs:
- 4-6 or a sequence having at least 90% identity thereto,
- a beta chain variable domain which comprises an amino acid sequence selected from SEQ ID NO:
- 7-9 or a sequence having at least 90% identity thereto, and
- an anti-CD3 antibody, optionally comprising an amino acid sequence selected from SEQ NOS:
- 12-14, covalently linked to the N-terminus or C-terminus of the beta chain, optionally via a linker sequence.
-25. (canceled)
Dependencies are inferred from the claim text.