Patent ID: 6994982

Claim:
A method of identifying nucleic acid that encodes a polypeptide that binds to a target protein of mammals wherein said polypeptide does not bind to the target protein in its native environment, said method comprising: (a) constructing an expression library using a process comprising: (i) producing nucleic acid fragments consisting of 90 base pairs to 120 base pairs in length from genomic DNAs known sequence from a plurality of genomes of different microorganisms or eukaryotes selected from the group consisting of Fugu rubripes, Caenorhabditis elegans, Saccharomyces cerevisiae, E. coli, Aquifex aeliteus, Methanococcus jannaschii, Bacillus subtilis, Haemophilus influenzae, Helicobacter pylori, Neisseria meningiditis, Syncchocystis sp. Bordetella pertussis, Pasteurella multocida, Pseudomonas aeruginosa, Borrelia burgdorferi, Methanobacterium thermautotrophicum, Mycoplasma pneumoniae, Archaeoglobus fulgidis and Vibrio Harvey; (ii) combining the nucleic acid fragments from each genomic in an amount that is proportional to the complexity and size of the genome of said microorganism or eukaryote, thereby enhancing nucleotide sequence diversity among the combined nucleic acid fragments compared to the diversity of sequences in each genome; (iii) inserting the combined fragments at (ii) into an expression vector in operable connection with a promoter sequence that confers expression on said fragment in a yeast or bacterial cell, thereby producing a recombinant vector; and (iv) introducing the recombinant vector at (iii) into a bacteriophage or a yeast cell or bacterial cell such that a nucleic acid fragment contained therein is expressed to produce a polypeptide; (b) screening said expression library by a process comprising determining the binding of the encoded polypeptide to the target protein of mammals to thereby identify a nucleic acid fragment that encodes a polypeptide that binds to the target protein; and (c) selecting a nucleic acid fragment at (b) that encodes a polypeptide that binds to the target protein but not in its native environment.