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

Generation of a recombinant human antibody (Humira™) from a murine TNFα -specific MAb and human variable gene phage display libraries. Two phage libraries containing the TNF-specific VL and VH sequences from the murine hybridoma cells paired with random VH and VL sequences derived from human B-cells are screened for binding to TNFα. The paired human VH and VL sequences from positive clones express phage-displayed human Fab molecules that bind to TNFα but require additional site-specific mutations in the CDRs to increase binding affinity to an acceptable level.