Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases

Rogers, J.; Schoepp, R.J.; Schröder, O.; Clements, T.L.; Holland, T.F.; Li, J.Q.; Li, J.; Lewis, L.M.; Dirmeier, R.P.; Frey, G.J.; Tan, X.; Wong, K.; Woodnutt, G.; Keller, M.; Reed, D.S.; Kimmel, B.E.; Tozer, E.C.

To overcome these limitations, a novel method for the fast and efficient humanization of antibodies was developed called HuFR TM . In this method, the synthetic mouse CDR fragments were ligated to pools of consensus framework sequences to obtain full-length variable heavy and light chain domains. The framework library sequences were designed such that the same set of sequences can be used to ligate to the CDR regions of any antibody in which humanization is desired. A similar method to HuFR TM called framework shuffling has recently been described by Dall'Aqua et al. (2005) . In this method, framework shuffling uses sequences derived from germline sequences and the CDRs are linked by PCR. The significant disadvantage to this approach is that for each antibody, a whole new set of PCR primers needs to be designed.