T-CELL RECEPTORS CONTAINING A NON-NATIVE DISULFIDE INTERCHAIN BOND LINKED TO THERAPEUTIC AGENTS

WIPO Patent Application WO2006037960

A3

The present invention provides a dimeric TCR (dTCR) or single-chain TCR (scTCR) associated with selected therapeutic agents, wherein said TCR comprises a first segment constituted by an amino acid sequence corresponding to a TCR a chain variable domain sequence fused to the N terminus of an amino acid sequence corresponding to a TCR a chain constant domain extracellular sequence, a second segment constituted by an amino acid sequence corresponding to a TCR ß chain variable domain fused to the N terminus of an amino acid sequence corresponding to TCR ß chain constant domain extracellular sequence, a disulfide bond between the first and second chains, said disulfide bond being one which has no equivalent in native aß T cell receptors, and in the case of said scTCRs further comprising a linker sequence linking the C terminus of the first segment to the N terminus of the second segment, or vice versa, the length of the linker sequence and the position of the disulfide bond being such that the variable domain sequences of the first and second segments are mutually orientated substantially as in native aß T cell receptors.

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JAKOBSEN BENT KARSTEN (GB)
ANDERSEN TORBEN BENT (GB)

PCT/GB2005/003752

August 03, 2006

September 29, 2005

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AVIDEX LTD (GB)
JAKOBSEN BENT KARSTEN (GB)
ANDERSEN TORBEN BENT (GB)

C07K14/725; A61K35/14; A61P35/00; A61P37/02; C12N5/08; C12N5/10; C12N15/12; G01N33/566

WO2004050705A2	2004-06-17
WO2004033685A1	2004-04-22
WO2004044004A2	2004-05-27
WO2004074322A1	2004-09-02
WO2003020763A2	2003-03-13

REITER Y ET AL: "CONSTRUCTION OF A FUNCTIONAL DISULFIDE-STABILIZED TCR FV INDICATES THAT ANTIBODY AND TCR FV FRAMEWORKS ARE VERY SIMILAR IN STRUCTURE", IMMUNITY, CELL PRESS, US, vol. 2, no. 3, March 1995 (1995-03-01), pages 281 - 287, XP009004075, ISSN: 1074-7613
BOULTER JONATHAN M ET AL: "Stable, soluble T-cell receptor molecules for crystallization and therapeutics.", PROTEIN ENGINEERING. SEP 2003, vol. 16, no. 9, September 2003 (2003-09-01), pages 707 - 711, XP002379684, ISSN: 0269-2139

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