Binding molecules specific for HBV envelope protein
AssigneeImmunocore Limited
InventorsMary Marguerita Connolly, Sara Crespillo Torreño, Richard Suckling, Marcin Dembek, Jose Donoso, Katrin Wiederhold, Andrew Knox
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Abstract
The present invention relates to specific binding molecules that bind the HLA-A*02 restricted peptide GLSPTVWLSV (SEQ ID NO: 1) derived from HBV envelope protein. The specific binding molecules may comprise alpha and/or beta TCR variable domains and may comprise non-natural mutations within the alpha and/or beta variable domains relative to a native TCR. The specific binding molecules of the invention are particularly suitable for use as novel immunotherapeutic reagents for the treatment of infectious or malignant disease.
Claims20
A specific binding molecule having the property of binding to a GLSPTVWLSV (SEQ ID NO:
- 1) HLA-A*02 complex and/or a GLSPTVWLSA (SEQ ID NO:
- 17) HLA-A*02 complex and comprising a T cell receptor (TCR) alpha chain variable domain and 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 specific binding molecule has one of the following combinations of TCR alpha chain variable domain CDRs and TCR beta chain variable domain CDRs:
- a) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 19 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 26, 22 and 30, respectively;
- b) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 19 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 27, 22 and 31, respectively;
- c) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 19 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 21, 22 and 32, respectively;
- d) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 19 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 21, 29 and 31, respectively;
- e) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 19 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 28, 22 and 31, respectively;
- f) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 24 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 27, 22 and 31, respectively;
- or
- g) TCR alpha chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 18, 24 and 25, respectively, and TCR beta chain variable domain CDR1, CDR2 and CDR3 sequences provided in SEQ ID NOs:
- 28, 22 and 31, respectively.
A specific binding molecule-anti-CD3 fusion molecule, wherein the specific binding molecule-anti-CD3 fusion molecule comprises a TCR alpha chain variable domain which comprises an amino acid sequence selected from SEQ ID NOs:
- 4-6 and a TCR beta chain variable domain which comprises an amino acid sequence selected from SEQ ID NOs:
- 7-11, and wherein an anti-CD3 antibody is covalently linked to the N-terminus or the C-terminus of the TCR beta chain variable domain via a linker sequence selected from SEQ ID NOs:
- 33-41.
Dependencies are inferred from the claim text.