Patent ID: 7117096

Claim:
A method for constructing a library of antibodies based on a structure of a lead antibody, the method comprising: providing an amino acid sequence of the variable region of the heavy chain (V H ) or light chain (V L ) of a lead antibody, the lead antibody having a known three dimensional structure which is defined as a lead structural template; identifying the amino acid sequences in the complementarity determining regions (CDRs) of the lead antibody; selecting one of the CDRs in the V H or V L region of the lead antibody; providing an amino acid sequence that comprises at least 3 consecutive amino acid residues in the selected CDR, the selected amino acid sequence being a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; selecting from the plurality of tester protein sequences at least two peptide segments that have at least 10% sequence identity with the lead sequence, the selected peptide segments forming a hit library; determining if each of the selected peptide segments in the hit library is structurally compatible with the lead structural template using an energy-based scoring function; selecting the peptide segments in the hit library that have an equal or lower energy score than that of the lead sequence, which indicates that the selected peptide segments are structurally compatible with the lead structural template displaying the selected peptide segments in the hit library ; and constructing a library of antibodies based on the selected peptide segments in the hit library.