2016 Archived Content

SC2: Mutation and Selection Strategies Beyond Affinity Optimisation

Orla Cunningham, Ph.D., Director, Global Biotherapeutic Technologies, Pfizer, Inc.

Matthew Lambert, Ph.D., Principal Scientist, Global Biotherapeutic Technologies, Pfizer’s, Inc.

In therapeutic antibody discovery, few lead molecules meet all of the demands required of a truly manufacturable drug. Most lead candidates require some form of engineering and optimization. This course will begin with an introduction to the multiple display technology platforms, mutagenesis strategies and library generation options that exist to enable antibody optimization. In the simplest application, generated libraries can be selected for improved antigen binding. However, increasingly these strategies are being used for more complex applications from humanization to ortholog cross-reactivity, stability, solubility and specificity optimizations. This workshop will use case studies to help attendees navigate the complex workflows and technological options available to ensure success.

This course will cover

  • Display technologies
  • Optimization library design, build & selection strategies
  • Case studies using novel strategies for therapeutic optimization
    • CDR-based binary substitution for ultra-humanization
    • Stability & solubility engineering
    • Combining rational & Darwinian approaches for optimal affinity