In order to obtain a novel binding protein against a chosen target, DNA
molecules, each encoding a protein comprising one of a family of similar
potential binding domains and a structural signal calling for the display
of the protein on the outer surface of a chosen bacterial cell, bacterial
spore or phage (genetic package) are introduced into a genetic package.
The protein is expressed and the potential binding domain is displayed on
the outer surface of the package. The cells or viruses bearing the
binding domains which recognize the target molecule are isolated and
amplified. The successful binding domains are then characterized. One or
more of these successful binding domains is used as a model for the
design of a new family of potential binding domains, and the process is
repeated until a novel binding domain having a desired affinity for the
target molecule is obtained. In one embodiment, the first family of
potential binding domains is related to bovine pancreatic trypsin
inhibitor, the genetic package is M13 phage, and the protein includes the
outer surface transport signal of the M13 gene III protein.