If VLa and VLb light chain homology > 80%, design a VLc based on VLa via computer aided design: Maintain VHaVLc’s affinity as close as that of VHaVLa, allow VHbVLc to have reduced affinity compared to VHbVLb.
If VLa and VLb light chain homology < 80%, construct phage ScFV library: VHs of the ScFV library are human germline VH library VLs of the ScFV library are VLa and its mutants derived from error prone PCR at less than 20% of mutation frequency.
Use computer aided design to separate the biochemical and biophysical features of VHa and VHb in order to isolate AB from AA and BB at a higher efficiency.
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