Methods for producing members of specific binding pairs

A method of producing one or a selected population of multichain polypeptide members of a specific binding pair (sbp members) comprising:

• (a) a first polypeptide chain comprising an antibody heavy chain variable domain and a second polypeptide chain comprising an antibody light chain variable domain, or
• (b) a first polypeptide chain comprising an antibody light chain variable domain and a second polypeptide chain comprising an antibody heavy chain variable domain,
• and specific for a counterpart specific binding pair member of interest, which method comprises:
• (i) introducing into host cells
• (A) first vectors comprising nucleic acid encoding a genetically diverse population of said first polypeptide chain fused to a component of a secreted replicable genetic display package (rgdp) for display of said first polypeptide chains at the surface of rgdps, and
• (B) second vectors comprising nucleic acid encoding a unique or restricted population of said second polypeptide chain;
• said first vectors being packaged in infectious rgdps and said introducting of said first vectors into host cells being by infection into host cells harboring said second vectors, or
• said second vectors being packaged in infectious rgdps and said introducing of said second vectors into host cells being by infection into host cells harboring said first vectors;
• (ii) expressing said first and second polypeptide chains within the host cells to form a library of said multichain sbp members displayed by rgdps,
• said genetically diverse population of first polypeptide chains being expressed from nucleic acid that is packaged using said rgdp component, whereby each said rgdp contains genetic material which encodes a first polypeptide chain of the sbp member displayed at its surface;
• (iii) selecting by affinity with said counterpart sbp member of interest multichain sbp members specific for said counterpart sbp member associated in their respective rgdps with nucleic acid encoding a said first polypeptide chain of said multichain sbp members;
• (iv) combining said first polypeptide chains of multichain sbp members selected in step (iii) with a genetically diverse population of second polypeptide chains of multichain sbp members, the said second polypeptide chains being fused to a component of a rgdp which thereby displays them at the surface of rgdps, the said combining forming a library of multichain sbp members from which one or more multichain sbp members for said counterpart sbp member of interest are selectable by affinity with said counterpart sbp member of interest.