A SINGLE-CHAIN ANTIGEN-BINDING PROTEIN THAT BINDS CEA

GENEX SCIENTISTS HAVE DEVELOPED PROPRIETARY TECHNOLOGY FOR THE DESIGN OF GENES WHICH CODE FOR THE VARIABLE REGIONS OF ANTIBODY MOLECULES LINKED BY POLYPEPTIDE LINKERS. THE GENESCODE FOR BOTH V(L) AND V(H) REGIONS AND THE RESULTING PROTEIN IS SYNTHESIZED AS A SINGLE POLYPEPTIDE CHAIN IN E. COLI. AFTER PURIFICATION AND REFOLDING THE SINGLE-CHAIN ANTIGEN BINDING PROTEIN (SCABP), DERIVED FROM A PROPRIETARY ANTI-BOVINE GROWTH HORMONE (BGH) MONOCLONAL ANTIBODY, BINDS SPECIFICALLY TO BGH. DURING PHASE I, THE ANTI-BGH SCABP WILL BE CONVERTED TO AN ANTI-CARCINOEMBRYONIC ANTIGEN (CEA) SCABP BY INSERTING THE COMPLEMENTARITY-DETERMINING REGIONS (CDRS) FROM AN ANTI-CEA MONOCLONAL ANTIBODY INTO THE SCABP FRAMEWORK BY OLIGONUCLEOTIDE-DIRECTED MUTAGENESIS. THE ANTI-CEA SCABP WILL THEN BE EXPRESSED IN E. COLI, AND THE PROTEIN WILL BE PURIFIED, REFOLDED AND ASSAYED FOR ACTIVITY. IN PHASE II, THE ANTI-CEA SCABP WILL BE USED AS A MODEL FOR THE IMAGING AND THERAPY OF TUMORS WHICH PRODUCE CEA.