Therapeutic antibodies are the fastest growing segment of the pharmaceutical industry. Fully human antibodies are ideal for therapeutic development since they are not normally immunogenic and carry all the necessary effector functions. Several different approaches have been pursued by others to obtain fully human antibodies, but to date, each has its limitations including issues with affinity, specificity, degree of “humanness”, developability, and speed in obtaining ideal antibodies.
To address these issues, AvantGen has evaluated more than 300,000 human antibodies derived from 500 individuals and generated a database where the frequencies of each amino acid at each position of all 6 CDRs in the light and heavy chains were determined for each of the human antibody germline variable regions.
AvantGen is using these data to design and construct human antibody libraries for novel antibody discovery and antibody optimization that more closely match natural human antibodies in vivo than other synthetic human antibody libraries.
The following Figure represents one of amino acid frequencies used in 3 CDRs of human heavy chain germline VH1-69. Highly biased usage of amino acids at the CDR positions is evident.
Percent of each amino acid used at each CDR position was rounded to the nearest 5%. Residues other than the germline residue at each position are shown.