Patent ID: 7985840

Claim:
A library comprising a plurality of distinct polypeptides each comprising a heavy chain variable domain and a light chain variable domain, wherein each heavy chain variable domain comprises a variant CDRH3 region that comprises an amino acid sequence: (X 1 )-X 2 -X 3 -X 4 -X 5 -X 6 wherein X 1 is any naturally occurring amino acid encoded by a codon set of NNK, NNS, DVK, NVT, XYZ or is tryptophan or glycine or mixtures thereof, and n=4 to 14; X 2 is any naturally occurring amino acid encoded by a codon set of KSG, DVK, DSG, NVT, KSG, NNS, XYZ, NNK or is tyrosine, phenylalanine, serine, alanine, glycine, leucine, or tryptophan; X 3 is missing when X 2 is phenylalanine or leucine, or if present, is alanine, valine, aspartic acid or glycine; X 4 is missing when X 2 is phenylalanine or leucine, or if present, is methionine; X 5 is aspartic acid, alanine, valine, or glycine; and X 6 is tyrosine or valine; and a variant CDRH1 and a variant CDRH2, wherein each of the variant CDRH1 and the variant CDRH2 has a variant amino acid at all solvent accessible and highly diverse amino acid positions, wherein CDRH1 comprises a variant amino acid at amino acid positions 28, 30, 31, 32 and 33; and CDRH2 comprises a variant amino acid at amino acid positions 50, 52, 53, 54, 56 and 58, the amino acid position numbering corresponding to the Kabat numbering system; and wherein each variant amino acid is encoded by a nonrandom codon set, and wherein at least 70% of the amino acids encoded by the nonrandom codon set are target amino acids for each of those positions in known antibody variable domains and 30% or less of the amino acids encoded by the nonrandom codon set are nontarget amino acids.