Challenges in Formulating Concentrated Protein Solutions: Viscosity and Stability

monoclonal antibody drug protein

Department of Chemical Engineering and Materials Science

Location: Burchard 104

Speaker: Yun Liu, NIST Center for Neutron Research (NCNR)

Abstract

Monoclonal antibodies (mAbs) are a class of Y shaped proteins with three domains. And mAb based therapeutic drugs have been the fastest growing sector of the pharmaceutical industry for many years. However, predicting the viscosity and stability of concentrated mAb solutions have long been a grand challenge for the industry. For example, abnormally high viscosity at a protein concentration larger than 100 mg/ml has been a major obstacle for the industry to use the desired subcutaneous injection method for many mAbs. In this talk, I will show our recent effort to study the structures and dynamics of a few mAb systems that help understand the behavior of concentrated protein solutions and provide physical insights into these challenging issues. Using neutron spin echo to study protein motions at nanosecond level, we demonstrated that the formation of small dynamic clusters in concentrated protein solutions are the driven force for the increase viscosity of the investigated mAbs. With the same technique, we are able to measure the internal domain motions of mAbs at nanoseconds time scale. We observed that when increasing temperature to destabilize proteins, there are increased internal domain motions well before the denature temperature of a protein, which imply that the stability of proteins could be potentially correlated with the enhanced internal domain motions.

Biography

Yun Liu

Dr. Yun Liu is currently a physicist at NIST Center for Neutron Research (NCNR) and also an affiliated full professor at Department of Chemical & Biomolecular Engineering in University of Delaware. His research interests cover colloidal science, biophysics, pharmaceutical materials, and gas adsorption and desorption in porous materials with over 160 publications. After obtaining his Ph.D. in Nuclear Science & Engineering Department at MIT, he joined NCNR first as a postdoc and then became an instrument scientist at NCNR. He received the Science Prize of Neutron Scattering Society of America in 2016 for discovering dynamic cluster ordering in complex colloidal systems and the Silver Medal of US Department of Commerce in 2019 for his research on pharmaceutical materials.

Host: Prof. Pin-Kuang Lai