Poor solubility is one of the common challenges encountered during the development of high concentration monoclonal antibody formulations. There is an unmet need for method that can provide predictive information on high concentration behavior of mAbs at the earliest stages in antibody discovery to avoid downstream issues. We explored the utility of extrapolated relative solubility as a measure to rank order mAbs based upon their solution behavior under stressed conditions.  Two approaches were taken to accomplish this: (1) adapting a vapor diffusion technique utilized in traditional crystallization practice and (2) polyethylene glycol (PEG) precipitation and quantified by turbidity. We have validated the two methods by in house mAbs with known high concentration behavior, which demonstrated decent predictability on solubility. Furthermore, we have implemented the assays into high throughput and miniaturized format, capable of screening hundreds of mAbs on their solubility. Such approach holds significant potential to improve initial candidate selection as well as to guide protein engineering efforts to improve the properties of specific mAb candidates.<br/>

High throughput solubility screening for developability assessment during therapeutic antibody discovery

253rd National Meeting (2017)

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