Cancer Research Technology Limited

Immunogen, Inc.

Anthony R Rees

Braydon Charles Guild

Kerry Chester

Surinder K Sharma

Richard H J Begent

Michael A Roguska

Jan T Pedersen

Daniel I R Spencer

Nigel P Minton

Stephen M Searle

The invention relates to improvements relating to cancer therapy based on the identification of a number of regions of CPG2 which contain epitopes which appear to be involved in the production of a host immune response and which may be modified to alter the immunogenicity in patients. Production of fusions of CPG2 with an antibody, where the CPG2 protein has been tagged provides a CPG2 protein which has reduced immunogenicity. By using partially glycosylated enzyme obtainable by expression, the efficacy of antibody-CPG2 fusions is enhanced.

Modified carboxypeptidase enzymes and their use

The invention relates to a method for providing, via resurfacing, humanized rodent antibodies that have improved therapeutic efficacy due to the presentation of a human surface in the variable region. In the method, (1) position alignments of a pool of antibody heavy and light chain variable regions is generated to give a set of heavy and light chain variable region framework surface exposed positions wherein the alignment positions for all variable regions are at least about 98% identical; (2) a set of heavy and light chain variable region framework surface exposed amino acid residues is defined for a rodent antibody (or fragment thereof); (3) a set of heavy and light chain variable region framework surface exposed amino acid residues that is most closely identical to the set of rodent surface exposed amino acid residues is identified; (4) the set of heavy and light chain variable region framework surface exposed amino acid residues defined in step (2) is substituted with the set of heavy and light chain variable region framework surface exposed amino acid residues identified in step (3), except for those amino acid residues that are within 5 .ANG.ngstroms of any atom of any residue of the complementarity determining regions of the rodent antibody; and (5) the humanized rodent antibody having binding specificity is produced.

Resurfacing of rodent antibodies

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Bath, United Kingdom

Anthony R Rees