Free sulfhydryl measurement as an indicator of antibody stability

Monoclonal antibodies are a major subclass of biopharmaceuticals. They are structurally different from other biopharmaceuticals in size and quaternary structure. Here we demonstrate a correlation between chemical stability of antibodies and thermal stability. We show that overall thermal protein stability can be predicted based on the measurement of free sulfhydryl (-SH) content on applying mildly denaturing conditions. We propose that this method can be adapted to a high-throughput screening format and used either as an absolute measure of thermal stability or for ranking a panel of possible variants.