United States Patent 5,837,500
Ladner , et al. November 17, 1998
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Directed evolution of novel binding proteins
Abstract
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.
Inventors: Ladner; Robert Charles (Ijamsville, MD); Gutterman; Sonia Kosow (Belmont, MA); Roberts; Bruce Lindsay (Milford, MA); Markland; William (Milford, MA); Ley; Arthur Charles (Newton, MA); Kent; Rachel Baribault (Boxborough, MA)
Assignee: Dyax, Corp. (Cambridge, MA)
Appl. No.: 415922
Filed: April 3, 1995
...This application is is a continuation of Ladner, Guterman, Roberts, Markland, Ley and Kent, Ser. No. 08/009,319, filed Jan. 26, 1993, now patented, which is a division of Ladner, et al., Ser. No. 07/664,989, filed Mar. 1, 1991, now patented (U.S. Pat. No. 5,223,409; issued Jan. 9, 1993), which is a continuation-in-part of Ladner, Guterman, Roberts, and Markland, Ser. No. 07/487,063, filed Mar. 2, 1990, now abandoned, which is a continuation-in-part of Ladner and Guterman, Ser. No. 07/240,160, filed Sep. 2, 1988, now abandoned. Ser. No. 07/487,063 claimed priority under 35 U.S.C. 119 from PCT Application No. PCT/US89/03731, filed Sep. 1, 1989. All of the foregoing applications are hereby incorporated by reference...
164.195.100.11
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(previous patent no.s are 5,571,698; 5,403,484; 5,223,409 ) |
