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AssigneeProtein Engineering Corporation
InventorsRobert C. Ladner, Sonia K. Guterman, Bruce L. Roberts, William Markland, Arthur C. Ley, Rachel B. Kent
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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.
A virus bearing on its outer surface a chimeric binding protein, said protein comprising (i) a proteinaceous binding domain, other than a single chain antibody, which is sufficiently stable in structure to have a melting point of at least 40.degree. C., and which binds to a target:, other than the variable domain of an antibody, sufficiently strongly so that the dissociation constant of the binding domain:
A chimeric binding protein comprising (i) a proteinaceous binding domain, other than a single chain antibody, which is sufficiently stable in structure to have a melting point of at least 40.degree. C., and which binds to a target, other than the variable domain of an antibody, sufficiently strongly so that the disassociation constant of the binding domain:
A fusion protein comprising (a) a carrier protein moiety essentially corresponding to a mature gene III protein of a filamentous phage, said carrier protein moiety acting, when the fusion protein is produced in a suitable host cell infected by the phage, to cause the display of the fusion protein or a processed form thereof on the surface of the phage, and (b) a foreign peptide or protein coupled to the amino terminal of said carrier protein moiety.
A fusion protein comprising (a) at least a functional portion of a mature gene VIII protein of a filamentous phage, said portion acting, when the fusion protein is produced in a suitable host cell infected by the phage to cause the display of the fusion protein or a processed form thereof on the surface of the phage, and (b) a foreign peptide or protein coupled to said functional portion of said mature gene VIII protein.
Dependencies are inferred from the claim text.