Directed evolution of novel binding proteins (US5571698)


	Parent Case:			This is a continuation of application Ser. No. 07/664,989 filed Mar. 1, 1991, now U.S. Pat. No. 5,223,409, which is a continuation-in-part of application Ser. No. 07/487,063 filed Mar. 2, 1990, now abandoned, which is a continuation-in-part of application Ser. No. 07/240,160 filed Sep. 2, 1988, now abandoned, the contents of all of which are hereby incorporated by reference.
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	First Claim: Show all 83 claims			We claim: 1. A method of obtaining a nucleic acid encoding a binding protein having a proteinaceous binding domain that binds a predetermined target material comprising: a) preparing a variegated population of amplifiable genetic packages, said genetic packages being selected from the group consisting of cells, spores and viruses, each said genetic package being genetically alterable and having an outer surface including a genetically determined outer surface protein, each package including a first nucleic acid construct coding for a chimeric potential binding protein, each said chimeric protein comprising and each said construct comprising nucleic acid encoding (i) a potential binding domain which is a mutant of a predetermined domain of a predetermined parental protein other than a single chain antibody, and (ii) an outer surface transport signal for obtaining the display of the potential binding domain on the outer surface of the genetic package, the expression of which construct results in the display of said chimeric potential binding protein and its potential binding domain on the outer surface of said genetic package; and wherein said variegated population of genetic packages collectively display a plurality of different potential binding domains, the differentiation among said plurality of different potential binding domains occurring through the at least partially random variation of one or more predetermined amino acid positions of said parental binding domain to randomly obtain at each said position an amino acid belonging to a predetermined set of two or more amino acids; the amino acids of said set occurring at said position in statistically predetermined expected proportions, said genetic packages being amplifiable in cell culture and separable on the basis of the potential binding domain displayed thereon, b) causing the expression of said chimeric potential binding proteins and the display of said potential binding domains on the outer surface of said packages; c) contacting said packages with the predetermined target material such that said potential binding domains and the target material may interact; d) separating packages displaying a potential binding domain that binds the target material from packages that do not so bind, and e) recovering at least one package displaying on its outer surface a chimeric binding protein comprising a successful binding domain (SBD) which bound said target, said package comprising nucleic acid encoding said successful binding domain, and amplifying said SBD-encoding nucleic acid in vivo or in vitro, with the proviso that when the target is an antibody, the predetermined parental protein is not an antigen specifically bound by that antibody.
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	Forward References:			Show 148 U.S. patent(s) that reference this one

U.S. References:

Go to Result Set: All U.S. references | Forward references (148) | Backward references (20) | Citation Link

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Foreign References:

Publication	Date	IPC Code	Assignee	Title
EP0286239	1988-06	C12N 15/00	NEW ENGLAND BIOLABS INC	Production and purification of a protein fused to a binding protein
EP0285123	1988-06	C12N 9/26	Cultor Ltd.	A method for complete mutagenesis of nucleic acids
WO8801649	1988-03	A61K 38/00	GENEX CORPORATION	SINGLE POLYPEPTIDE CHAIN BINDING MOLECULES
WO8806601	1988-09	A61K 38/00	GENEX CORPORATION	GENE REPRESSORS
WO8806630	1988-09	C07K 16/00	GENEX CORPORATION	METHOD FOR THE PREPARATION OF BINDING MOLECULES
WO9118980	1991-12	C07K 14/00	CETUS CORP	COMPOSITIONS AND METHODS FOR IDENTIFYING BIOLOGICALLY ACTIVE MOLECULES
WO9119818	1991-12	C12N 1/21	AFFYMAX TECH NV	PEPTIDE LIBRARY AND SCREENING SYSTEMS
WO9206204	1992-04	C07K 14/00	IXSYS, INC.	SURFACE EXPRESSION LIBRARIES OF HETEROMERIC RECEPTORS
WO9206176	1992-04	C12N 1/21	IXSYS INC	SURFACE EXPRESSION LIBRARIES OF RANDOMIZED PEPTIDES
WO9211272	1992-07	C07H 15/12	IXSYS, INC.	OPTIMIZATION OF BINDING PROTEINS