Optimization of binding proteins

Claim 1

A method for manipulating nucleic acids so as to optimize the binding characteristics of an encoded binding protein to a particular ligand, said binding protein selected from the group consisting of antibodies and T cell receptors said method comprising the steps of: (a) providing two or more nucleic acids encoding different binding proteins all having binding affinity for said particular ligand, said binding proteins selected from the group consisting of antibodies and T cell receptors, said nucleic acids having at least one set of splicing sites, said set of splicing sites flanking opposite ends of one or more encoded complementarity determining regions (CDRs); (b) mixing said two or more nucleic acids to produce a parent population of mixed nucleic acids encoding said binding proteins; (c) randomly incorporating said one or more encoded CDRs between said two or more nucleic acids through said set of splicing sites to produce a different population of nucleic acids than said parent population, wherein at least one binding protein encoded by said different population is characterized by optimized binding characteristics as compared with a member of the parent population; and (d) selecting from said different population at least one of the nucleic acids encoding a binding protein characterized by optimized binding characteristics as compared with a member of the parent population.