Patent ID: 8337841

Claim:
A screening method comprising: (a) providing a first plurality of bacterial host cells secreting a first Fd of a single antibody species that binds to a first antigen; (b) introducing an antibody light chain phage library encoding a plurality of different light chains, each linked to a bacterial secretion signal and a phage membrane anchor domain, into the first plurality of host cells to cause secretion of phage libraries presenting two-chain antibody fragments, each antibody fragment comprising the first Fd and a light chain; (c) selecting a phage library that displays antibody fragments that bind specifically to the first antigen; (d) introducing the phage library selected in step (c) into a second plurality of bacterial host cells secreting a second Fd that is different from the first Fd and is the Fd of a single antibody species that binds to a second antigen different from the first antigen, to create phage libraries presenting two-chain antibody fragments, each comprising the second Fd and a light chain; and (e) selecting, from the phage libraries created in step (d), a phage library that displays two-chain antibody fragments that bind specifically to the second antigen.