2015 Archived Content

Thursday, 5 November 17:30 – 20:30, To Include Dinner

17:15 – 17:30 Dinner Short Course Registration

SC6: Troubleshooting and Engineering of Antibody Constructs

Schaefer JonasJonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich

Julia NeugebauerJulia Neugebauer, Ph.D., Associate Director, Leader Discovery Programs, MorphoSys AG

Recombinant antibodies vary widely in their biophysical characteristics, from stable monomers to metastable aggregation-prone oligomers. In particular, antibody variable domains differ in their intrinsic thermodynamic stability and may require labour-intensive engineering. It is therefore essential to implement antibody engineering strategies in screening and initial characterisation project phases in order to avoid time and cost consuming optimisation strategies in later development. In addition, it is critical to understand how the poor stability of individual variable domains not only limits the biophysical properties of small fragments, but also affects the production yield, stability and homogeneity of full-length IgGs containing these domains.

  • Setup suitable screening campaigns in order to reduce intense engineering efforts
  • Implement stability assessment & engineering strategies early in the discovery phase
  • Combine different engineering strategies to improve desired features and remove liabilities
  • Use sequence or structure-based engineering to optimise your antibody’s biophysical properties
  • Optimize your choices of the best possible format for your antibody
  • Improve your expression strategies for different immunoglobulin products
  • Tackle the analytical challenges of multi-domain proteins