Developing a New Generation of TNFα Antagonists for the Treatment of Rheumatoid Arthritis

Derivation of CDP870 from a murine TNFα -specific MAb using recombinant DNA technology and protein engineering. The cloned murine variable light and heavy chain cDNAs are modified to insert human framework sequences, and thus only the CDR sequences remain from the original mouse monoclonal antibody. Because this may reduce affinity for the original antigen, additional site-specific mutations may be necessary within the CDR sequences. Because the native Fab is typicall not glycosylated, CDP-870 can be expressed in bocterial cells; PEG is conjugted to the purified humanized molecule.