Preclinical Development – Biomolecular
2019 PharmSci 360
Monoclonal antibodies (mAbs) have dominated the pharmaceutical market in the last decade and constitute the fastest growing class of therapeutics. However, despite numerous breakthroughs in the field that lead to their clinical implementation, the development and manufacture of mAbs still suffer from the negative impacts of protein aggregation, which can severely compromise the therapeutic efficacy and limit the shelf-life of the pharmaceutical products. To address this, advanced computational methods have been developed to identify regions on the protein surface that are prone to aggregation. In our lab, we have employed molecular biology techniques to introduce additional glycans on the protein that can shield these aggregation-prone regions. This technique was applied on two blockbuster antibodies (Herceptin® and Avastin®), demonstrating important improvements in thermodynamic stability. This glycoengineering method can be translated to other therapeutic proteins as an innovative approach to enhance formulation stability and prevent aggregation.