Monoclonal antibodies for use in diagnosis and treatment of colorectal cancer

A molecule which (i) binds membrane-bound human carcinoembryonic antigen, and (ii) binds a hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein (SEQ ID NO:

• 32) and joined (N-C) to residues 490 to C-terminus of human carcino embryonic antigen (SEQ ID NO:
• 36), but (iii) does not bind to human biliary glycoprotein and (iv) does not bind a hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to 643 of human carcino embryonic antigen which is soluble and is secreted from a COS cell, but excluding an intact mouse monoclonal antibody comprising an IgG.sub.1 group IIA heavy chain and a kappa group V light chain wherein in the said intact mouse monoclonal antibody the sequence of the V.sub.H chain is
• QVKLQQSGPELKKPGETVKISCKASGYTFTVFGMNW (SEQ ID NO:
• 1) VKQAPGKGLKWMGWINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLK NEDTAKYFCARWDFYDYVEAMDYWGQGTTVTVSS, or wherein in the said intact mouse monoclonal antibody the sequence of the V.sub.H chain is as given immediately above but the first amino acid residue of the V.sub.H CDR1 is glutamine and in either case the sequence in the said intact monoclonal antibody of the V.sub.L chain is
• GDIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAW (SEQ ID NO:
• 2) YQQKPGQSPKALIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEY FCHQYYTYPLFTFGSGTKLEMKR. -2. A molecule according to claim 1 wherein the molecule is a monospecific
• antibody. 3. A molecule according to claim 1 which is an antibody comprising a human framework region and at least the complementarity determining regions of the V.sub.H chain and V.sub.L chain as defined in claim 1 wherein for the V.sub.H chain CDR1 is VFGMN (SEQ ID NO:
• 3), CDR2 is WINTKTGEATYVEEFKG (SEQ ID NO:
• 4) AND CDR3 is WDFYDYVEAMDY (SEQ ID NO:
• 5) and for the V.sub.L chain CDR1 is KASQNVGTNVA (SEQ ID NO:
• 6), CDR2 is
• SASYRYS (SEQ ID NO:
• 7) and CDR3 is HQYYTYPLFT (SEQ ID NO:
• 8). 4. A molecule according to claim 3 wherein the antibody is a monoclonal
• antibody. 5. A molecule according to claim 1 further comprising a directly
• or indirectly cytotoxic moiety. 6. A molecule according to claim 1 further
• comprising a readily-detectable label. 7. A molecule according to claim 1
• for use in medicine. 8. A medicament for diagnosing or treating colorectal
• carcinoma comprising a molecule according to claim 1. 9. A method for diagnosing or treating colorectal carcinoma comprising administering to a person a composition comprising the molecule according to claim 1 and,
• optionally, a non-pyrogenic diluent. 10. A process for making a monospecific antibody as defined in claim 2, the process comprising screening a pool of antibodies to select those monospecific antibodies which bind (i) human carcinoembryonic antigen, (ii) bind a hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to 668 of human carcinoembryonic antigen, but
• (iii) do not bind to human biliary glycoprotein. 11. A process according to claim 10 wherein the monospecific antibody is a monoclonal antibody and
• the pool of antibodies is a pool of monoclonal antibodies. 12. A process according to claim 10 wherein the antibodies within the pool comprise
• antibodies produced by recombinant DNA methods. 13. A process according to claim 12 wherein the binding sites of the antibodies are displayed on the
• surface of a replicating vector. 14. A process according to claim 13
• wherein the replicating vector is a bacteriophage. 15. A monospecific antibody obtainable by the process of claim 10 but excluding an intact mouse monoclonal antibody comprising an IgG.sub.1 group IIA heavy chain and a kappa group V light chain wherein in the said intact mouse monoclonal antibody the sequence of the V.sub.H chain is
• QVKLQQSGPELKKPGETVKISCKASGYTFTVFGMNW (SEQ ID NO:
• 1) VKQAPGKGLKWMGWINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLK NEDTAKYFCARWDFYDYVEAMDYWGQGTTVTVSS, or wherein in the said intact mouse monoclonal antibody the sequence of the V.sub.H chain is as given immediately above but the first amino acid residue of the V.sub.H CDR1 is glutamine;
• and in either case the sequence in the said intact monoclonal antibody of the V.sub.L chain is
• GDIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAW (SEQ ID NO:
• 2) YQQKPGQSPKALIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEY FCHQYYTYPLFTFGSGTKLEMKR. 16. A hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to 668 of human 17. A hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to 643
• of human carcinoembryonic antigen. 18. A hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to 644 of human carcinoembryonic antigen joined (N-C) to residues 391
• to 430 of human biliary glycoprotein. 19. A hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to 642 of human carcinoembryonic antigen joined (N-C) to residues 387 to 430 of human biliary glycoprotein.