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7:00 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Sachdev Sidhu, Ph.D., Banting & Best Medical Research, University of Toronto
8:40 Phage Display Traps for Protein Conformation and Specific Composition
James A. Wells, Ph.D., Department of Pharmaceutical Chemistry, University of California, San Francisco
Phage display continues to represent one of the most powerful and unbiased selection technologies. One of the key advantages is that one can have complete control of the antigen state and composition without the worry of in vivo processing or proteolysis. We’ll present two such examples demonstrating the exquisite directed selectivity for a specific enzyme conformation and a peptide composition.
9:10 Research and Development of Next-Generation of Antibody-Based Therapeutics: Challenges and Opportunities
Zhenping Zhu, M.D., Ph.D., Vice President and Global Head, Protein Sciences & Design, Novartis Biologics
Recent clinical success with antibody-based therapeutics has led to an upsurge in the development of these agents. Since 1994 the US FDA has approved 23 therapeutic antibodies. In addition, there are several hundreds of antibodies currently being tested in late-stage, pre-clinical and clinical settings worldwide for a variety of disease indications. This presentation will discuss the current status and future trends, focusing on emerging novel technologies and their impact, in the discovery and development of next generation antibody-based therapeutics.
9:40 Next-Generation Biologics
Herren Wu, Ph.D., Vice President, Antibody Discovery & Protein Engineering, MedImmune
10:10 Grand Opening Coffee Break in Exhibit Hall
11:10 Q&A with Keynote Presenters
Moderator: Lutz Jermutus, Ph.D., Director of Research & Technology, MedImmune
Will monoclonal antibodies become a commodity for the top ten pharma companies world-wide?
What will drive differentiation in biologics?
With greater dependence on publicly funded research for target identification and validation, where will new antibody targets come from?
What are the advantages for considering next-generation biologics?
11:35 Chairperson’s Remarks
Andrew M. Bradbury, M.B. B.S., Ph.D., Staff Scientist, Biosciences, Los Alamos National Laboratory
11:40 Antibody Generation and Engineering Using Adaptor-Directed Phage and Yeast Display of Structure-Based Libraries
Mark Hsieh, Ph.D., Research Fellow, Biologics Research, Merck & Co., Inc.
We will present a novel and integrated platform for antibody generation and engineering using adaptor-directed phage and yeast display of structure-based designer libraries with superior biophysical and biological properties. These antibodies are designed to balance their structural and chemical diversity in capturing the distinct epitopes of different antigens. The adaptor-directed approach is used for functional selection of designed antibody libraries that can be tailored to hit diverse targets or leads. The power of our technology is in generating superior therapeutic antibodies by combining both antibody library design with robust phage and yeast selection systems.
12:10 pm Determination of the True Diversity of a Human Antibody Library and Insights into the Human Antibody Repertoire, Using Next Generation DNA Sequencing
Jaume Pons, Ph.D., Vice President & CSO, Research, Rinat Pfizer
To date, the diversity of large libraries is typically estimated based on the number of colonies obtained after library transformation. This method gives the upper limit of possible diversity of the library, but sequence diversity can be significantly lower. To solve this problem, we have used next-generation DNA sequencing, and adapted bioinformatics methods, to determine the true diversity of antibody libraries. Furthermore, when the libraries are cloned from human donors, deep sequencing also gives information about the human antibody repertoire.
12:40 Luncheon Presentation I Sponsored by
In Vitro Evolution of Allergy Vaccine Candidates with Reduced IgE-Binding and T-Cell Activation Capacity
Ola Nilsson Ph.D., Department of Medicine Solna, Karolinska Institute
Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses.
1:10 Luncheon Presentation II (Sponsor Opportunity Available)
2:00 Chairperson’s Remarks
Lutz Jermutus, Ph.D., Director of Research - Technology, MedImmune
2:05 Selection and Engineering of Antibodies Targeting Membrane Proteins
Eric V. Shusta, Ph.D., Assistant Professor, Chemical & Biological Engineering, University of Wisconsin, Madison
Membrane proteins are challenging to work with in terms of antibody selection, engineering, and antigen identification as a result of their insolubility in aqueous solutions. We have therefore developed a platform for antibody engineering using cell lysates as antigen sources. Such approaches are compatible with membrane protein targets, subcellular selections, and the rapid assessment of antibody specificity.
2:35 Selection of Single-Domain Antibodies Targeting Brain Vasculature and Their Optimization for Imaging and Therapeutic Applications
Danica Stanimirovic, M.D., Ph.D., Director, Neurobiology, National Research Council, Canada
One of the principal hurdles for translation of both emerging therapeutics and molecular imaging agents for CNS diseases is their delivery across the blood brain barrier. This talk will provide two examples of the selection of single domain antibodies targeting brain vessels using protocols of subtractive panning of phage display libraries against cells or generation of immune libraries against selected brain vascular target(s) and their optimization for applications in brain imaging and therapy.
3:05 Refreshment Break, Poster and Exhibit Viewing
3:45 Harnessing Somatic Hypermutation for Antibody Discovery and Optimization
David King, Ph.D., Vice President, Research, Anaptys Bio
The natural process for antibody generation in man encompasses gene recombination and affinity maturation through AID-induced somatic hypermutation (SHM). AID-induced SHM has been recreated in vitro using a novel mammalian cell display system. This allows SHM to be carried out in controlled conditions with either single antibody heavy and light pairs, resulting in affinity maturation of a specific antibody, or with libraries of antibody genes allowing novel antibody specificities to be discovered and optimized.
4:15 Dissecting and Engineering High-Affinity Antibody-Antigen Interactions: Application to Viral Epitopes
Jonathan R. Lai, Ph.D., Assistant Professor, Department of Biochemistry, Albert Einstein College of Medicine
Detailed analysis of factors governing high-affinity antibody-antigen interactions is crucial to understanding how natural antibodies evolve, and provides information for designing and selecting functional antibody libraries de novo. We used phage-based technologies to understand the molecular basis of a high-affinity HIV-1 antibody, and are developing strategies for identification of new neutralizing viral antibodies from de novo designed repertoires. This work will provide novel reagents for studying viral membrane fusion and explore new avenues for therapeutic or diagnostic applications.
4:45 Problem Solving Break-Out Sessions
Table 1: Antibody-Drug Conjugates
Moderator: Pamela A. Trail, Ph.D., Vice President, Oncology, MedImmune, Inc.
Table 2: Comparing Phage and Yeast Display Libraries
Moderator: Mark Hsieh, Ph.D., Research Fellow, Biologics Research at Merck & Co., Inc.
Table 3: Selection and Engineering of Antibodies Targeting Membrane Proteins
Moderator: Eric V. Shusta, Ph.D., Associate Professor, Chemical & Biological Engineering, University of Wisconsin Madison
• Display platform choice and how it relates to cellular preparations used: whole cells, fractionated cells, detergent-solubilized cells
• Selections/Engineering against known vs. unknown membrane targets
• Identification of unknown membrane antigens targeted by selected antibodies
• Designer antibody selections for cell-specific targeting (e.g. subtractive methods) and function (e.g. endocytosis)
Table 4: Strategies for Building Novel Scaffold Libraries
Moderator: Balaji Rao, Ph.D., Assistant Professor, Chemical Engineering, North Carolina State
Discussion points include:
• Choosing a scaffold
• What areas on the scaffold does one mutagenize?
• Constructing a library using a screening platform (yeast display, phage display etc.)
• Assessing the quality of the library generated
Table 5: Use of Next Gen Sequencing Platform to Bypass Primary Screening
Moderator: Nicolas Fischer, Ph.D., Head of Protein Engineering, NovImmune SA
• Next generation sequencing platforms and their suitability for different library formats
• Use of NSG at different steps of display technology
• Bypassing primary screening or complementing it?
• Implications for better library design
5:45 Networking Cocktail Reception in the Exhibit Hall
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