Solution and Solid State Studies of Model Systems and
Pharmaceutical Monoclonal Antibodies (mAbs)

 

Nicholas Clark1*, Max Watson1*, Hyo Jin Lee2, Arnold McAuley2, Hirsh Nanda1, Susan Krueger1, and Joseph E. Curtis1

 

*Co-presenters, 1NIST Center for Neutron Research, Gaithersburg, MD; 2AMGEN Inc., Thousand Oaks, CA

 

The pharmaceutical industry is interested in the preservation of protein-based drugs through many methods including; high concentration solutions, lyophilized formulations (hydrated powders) and freezing of solutions.  Here we used a hybrid approach combining solution and solid-state small-angle neutron scattering (SANS) data with in silico molecular dynamics to better understand the types of interparticle interactions that occur in high-concentration protein solutions.  We tested the ability of NaCl to screen the solution interactions and we have shown that NaCl and protein concentration do not affect the packing density of proteins in ice.  These model protein studies are being extended to monoclonal antibodies (mAbs). Through this research we hope to better understand the root causes of crystallization, aggregation and irreversible protein misfolding, which are all known impediments to drug-product development and patient delivery.