Patent ID: 8716195

Claim:
A method of producing a library of polynucleotides encoding at least one complementarity determining region (CDR), wherein the method comprises: (a) determining the CDR amino acid sequence variation present in a reference antibody library that comprises naturally-occurring CDR amino acid regions, wherein the CDR sequence variation is determined at each amino acid residue position of the CDR; (b) aligning a query CDR peptide sequence from an antibody against a target antigen with the CDR sequences of a reference antibody library; and (c) synthesizing a library of polynucleotides encoding CDR sequences, wherein for the majority of library CDR sequences synthesized: (i) the amino acid residue encoded at any single position within a CDR sequence is identical to an amino acid residue at the corresponding aligned position of the query CDR peptide sequence from an antibody against a candidate antigen; or (ii) is a predetermined amino acid residue(s) if an identical amino acid residue for the query CDR peptide sequence at the position being aligned does not occur in the reference library; wherein the library of polynucleotides encodes CDR analogs comprising CDR-HI, CDR-H2, and CDR-H3 sequences as shown in any of CDR-H1, CDR-H2, and CDR-H3 cohort library sequences, respectively, in any of FIG. 13 and FIG. 16-27 ; and wherein the library of polynucleotides encodes CDR analogs comprising CDR-L1, CDR-L2, and CDR-L3 sequences as shown in any of CDR-L1, CDR-L2, CDR-L3 cohort library sequences, respectively, in any of FIG. 13 and FIG. 16-27 ; and whereby a library of polynucleotides is provided that encodes CDR analogs of the query CDR peptide sequence from an antibody against a target antigen, the CDR analogs being enriched for naturally occurring amino acid residues at one or more residue positions.