How can we engineer improved therapeutic proteins and antibodies?
Our understanding of protein structure-function relationships will be reviewed, including a special focus on the diversity generation of antibody binding surfaces. Together with the extensive clinical experience from many protein therapeutics, these approaches provide insights into the best strategies for designing and improving diverse aspects of therapeutic protein function. Not only is amino acid sequence amenableto engineering, but glycan structures and other modifications may also be engineered.
This course will focus on the engineering and enhancement of antibodies and antibody-likescaffolds of particular interest in current therapeutic development. Examples will include work on antibody fragment affinity improvement by 100-fold to low pM affinity. A background in biochemistry and molecular biology isuseful, as the course is designed to progress rapidly from simple to advanced concepts.
Course Agenda
- Understanding protein and antibody structure – an introduction
- Sources of proteins and antibodies
- Immunization approaches for antibodies
- Monovalent vs. multivalent display technologies
- Library size and design
- Improving a lead protein or antibody
- Engineering by design vs. by random mutation
- Improving manufacturing by protein engineering methods
- Glycosylation engineering – function and homogeneity
- Other protein modifications
- Reducing immunogenicity by engineering
- Creating bispecific and multispecific antibodies
- Adding firepower: Antibody-drug conjugates (ADCs)
- Expression of antibodies and fragments for discovery and testing
- Manufacturing platforms for antibodies and fragments
Instructor: David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC
Dr. Bramhill has over 20 years experience in biologics, both in large biopharma and startup biotech companies. He has experience in isolating and improving antibodies using phage display and is an inventor on library design techniques for small scaffolds. He also has experience in diverse expression systems for producing antibodies, antibody fragments and different scaffolds. He has taught numerous technical courses for over 10 years at international conferences.