Patent ID: 6986986

Claim:
A method of screening a display library to isolate a member of the library that binds to a multimeric protein having two different subunits, comprising: (a) providing a library of replicable genetic packages, wherein a replicable genetic package is a cell, spore or virus, wherein a library member comprises a replicable genetic package capable of displaying from its outersurface an antibody chain comprising a variable domain to be screened for binding to the multimeric protein encoded by a segment of a genome of the package, the antibody chain varying between library members, wherein at least some library members display antibody chains, (b) contacting the library members with a multimeric protein comprising two different subunits and with subunits of the multimeric protein in a form not associated with each other; (c) isolating a library member encoding an antibody chain that binds to the multimeric protein and not to the subunits in the form not associated with each other wherein the replicable genetic package further encodes a tag expressed as a fusion protein with the antibody chain, the tag being the same in different library members, and the method further comprises contacting library members with a receptor with specific affinity for the tag and isolating library members that bind to immobilized receptor before performing step (b).