Levich Institute Seminar Announcement, 02/02/2016
Steinman Hall, Room #312
(Chemical Engineering Conference Room)
Dr. Jai Pathak
Drug Product Manufacturing Group
"Viscoelasticity of Crowded Monoclonal Antibody Solutions: Chain Conformation Does Matter"
I will first discuss how molecular conformation and inter-molecular interactions affect transport properties in monoclonal antibody solutions. I will discuss the solution behavior of a self-associating monoclonal antibody (“mAb1”) and a non-self-associating mAb (“mAb2”). Self-association was verified by analytical ultracentrifugation. Circular Dichroism reveals that the tertiary structure of mAb2 changes appreciably with concentration. Conversely, mAb1 shows weak conformational changes. Capillary differential scanning calorimetry also indicates conformational instability. At low pH (3.0) we prove that both mAbs exist in an expanded conformation. For pH > 3.0, mAb2 shows evidence of conformational transitions with concentration, while mAb1 shows comparatively weaker conformational transitions. These conformational transitions are important contributors to the concentration-dependent viscoelasticity, which increases steeply at pH 3.0 for both mAbs: mab1 even gels at 120 mg/mL antibody concentration, due to exposure of hydrophobic patches in the open conformation. Our key finding is that chain conformation is a critical determinant of solution viscoelasticity, in addition to inter-molecular interactions.
BRIEF ACADEMIC/EMPLOYMENT HISTORY
Ph.D. Penn. State (2001); post-docs at NIST (2001-2006) and NRL (2006 – 2008); at MedImmune since. Dec. 2008. Currently leading tech. transfer for a Phase III oncology drug for commercial manufacturing. Also active in publishing independently and also in collaborations currently with NIST and Stanford Univ. (Prof. Gerald Fuller).
RECENT RESEARCH INTERESTS
Viscoelasticity of monoclonal antibody solutions, flow instabilities at air/water, solid/water and oil/water interfaces of biologics