Materials Summer School Keynote: Use of Multiple Analytical Techniques to Better Understand the Origins of High Viscosity Biopharmaceutical Products

Abstract: 

Materials analysis is a very broad field in terms of material types and methods of analysis.  The methods and interpretation of the data is less complex if the interactions between atoms/molecules of the tested material are persistent on the timescale of the analysis.  Monoclonal antibodies (MAbs) contribute to a very large fraction of the biotech products currently in development.  Increasingly, immunological indications have been targeted which require at home administration by subcutaneous injection.  This requires increasingly high concentrations of proteins, up to 200mg/mL.  Many, but not all, of these MAbs have exceedingly high viscosities at these concentrations making manufacturing and administration difficult, if not impossible.  There is a great effort to understand the molecular sources of high viscosity with a goal of predicting high viscosity molecules based only on the amino acid sequence!  This could be used very early in development, even at one of the earliest step in development:  molecule selection.  This would save time, lower cost, and increase the likelihood of development success.  The protein-protein interactions that are believed to result in high viscosity are transient and difficult to assess.  Many groups have studied these molecules and solutions by many methods:  scanning and transmission electron microscopy, small angle X-ray scattering, small angle neutron scattering, static light scattering, photon correlation spectroscopy, dielectric relaxation spectroscopy, transient electric birefringence, to name a few.  I suspect that many students taking this course will be familiar with many of these.  Results of experiments done at Genentech on MAbs as well as that of other industrial and academic investigators will be described.  Included in this presentation is a glimpse of what the molecule may actually “look” like by running in silico molecular dynamics simulations.  The use of multiple techniques can provide significant insight into the source of molecules that demonstrate high viscosity.

 

Speaker Bio:

Dr. Patapoff is currently a Staff Scientist in the Early Stage Pharmaceutical Department at Genentech. He received his B.A. in chemistry and his B.S. in biology from the University of California – Irvine in 1978, and a Ph.D. in 1985 from the University of Oregon, Department of Chemistry studying the vibrational characteristics of biologically interesting molecules (protein and DNA) using Raman Spectroscopy. From 1985 to 1987, he was a postdoctoral fellow at the University of Oregon where he built an intra-cavity laser Raman microscope. He then worked for two years at Lockheed Missiles and Space in the electro-optics and astronomics divisions followed by two years at a small start-up biotech formulating insulin for intra-nasal delivery. In 1991, Dr. Patapoff began working at Genentech where he is still employed. During the last 22 years at Genentech, Dr. Patapoff has contributed to the formulation of several approved drugs, was the Director of the Pharmaceutical Research and Development department for 5 years, and is currently involved in drug delivery, predicting protein stability and conformations using in-silico analysis, and contributing to multiple internal development projects.

Division(s):

Speaker: Thomas W. Patapoff, Ph.D.

Speaker Institution: Genentech, Inc. - A Member of the Roche Group

Speaker Website: http://www.gene.com/

Event Date: 06-06-2014

Event Time: 9:00 AM

Event Location: Chemistry A101

Mixer Time: 8:45 AM

Mixer Location: Chemistry B101E

Host: Chris Rithner