Updated on 3 October 2012
Scientists have developed specific mutations that increase the stability of antibody molecules (Image courtesy: Garvan Institute of Medical Research)
Singapore: One of the most challenging tasks ahead of pharmaceutical companies is to create antibodies that are stable enough to meet stringent requirements necessary for production in large quantities, injection into patients and long-term storage.
Antibodies often display limited stability and succumb to the stresses imposed during their manufacture, storage and use. In particular, protein aggregation often leads to failures in formulation of otherwise promising drugs. Until now such problems had to be handled on a case-by-case basis, with many monoclonals ultimately failing formulation studies. Dr Daniel Christ, director, antibody development laboratory, Garvan Institute of Medical Research; Dr Kip Dudgeon, post-doctoral research fellow, Garvan Institute of Medical Research; and Romain Rouet have developed specific mutations that increase the stability of antibody molecules.
In a conversation with BioSpectrum, Dr Christ and Dr Dudgeon talk about the importance of this breakthrough in the antibodies field. "Monoclonal antibodies have come of age and now represent more than half of all drugs entering clinical studies. Recent research in our laboratory has outlined a general strategy to overcome the limited stability and high aggregation propensity of human antibodies."
"More specifically, we have identified specific positions within antibody variable domains that control aggregation. Importantly, these mutations are independent of antibody sequence variation at other positions and compatible with antigen binding. We have been able to successfully apply these mutations not only to antibody libraries, but also managed to retrofit existing drugs such as the breast cancer drug Herceptin (Trastuzumab).
Our mutations allow the proteins to withstand extreme conditions (such as heating to 90°), while simultaneously increasing expression, purification and concentration yields," they added.