Novel Antibody Constructs and Alternative Scaffolds
Engineering, New Targets and Lead Selection
4-5 November 2013
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14:00 Chairperson’s Opening Remarks
Arne Skerra, Ph.D., Professor, Technische Universität Munich; Co-Founder, Pieris AG, Germany
14:05 Doing It the Other Way Round: Using High-Throughput Human Monoclonal Antibody Generation to Identify New Drug Targets
Stefan Dübel, Ph.D., Director, Biotechnology and Bioinformatics, Institute of Biochemistry, Technische Universität Braunschweig
Current high content screening methods failed to deliver the expected abundance of new drug targets. Our capability to rapidly generate panels consisting of hundreds to thousands of different monoclonal human antibodies for research allows one to overcome these limitations, by comparing not only expression but also the role of individual posttranslational modifications and, most important, the spatial “togetherness” of >100 different proteins per individual healthy vs. disease sample with 40nm resolution.
14:35 Deep Sequencing of Phage Display Panning Output Pools to Guide Antibody Lead Selection
Stefan Ewert, Ph.D., Senior Investigator, NIBR Biologics Center, Novartis Pharma AG
The presentation will show examples how Deep Sequencing of Phage Display panning output pools could guide antibody lead selection with focus on achieving diversity regarding e.g. antigen cross-reactivity profile and biophysical properties.
15:05 Controlling Cellular Signaling with Ultraspecific Binding Proteins
Shohei Koide, Ph.D., Professor, Biochemistry and Molecular Biology, University of Chicago
Using two alternative scaffold platforms, FN3 monobody and affinity clamp, we have developed a series of binding proteins to targets involved in cell signaling. Intracellular expression followed by mass spectroscopy-based proteomics establishes that these binding proteins are exquisitely specific to a single target in the cell. We use these binding proteins to precisely dissect and control cellular signaling, including cancer progression and stem cell development, and determine drugability of targets.
15:35 Discovering Novel Antibody Targets, Antibody Off-Targets, and Uncovering Receptors for Protein Ligands Using Retrogenix’s Powerful Deconvolution Technology
Jim Freeth, Ph.D., Managing Director, Retrogenix, UK
Selecting antibodies by phenotype, rather than against a pre-determined target, leads to novel, disease-relevant antibody targets. Retrogenix’s Cell Microarray technology overcomes the target deconvolution hurdle, with high success rates. The technology also provides a powerful approach to identify potential off-target activities to guide lead selection, and to identify previously unknown receptors of protein ligands.
15:50 A Unified Framework for Computer-Aided Biologics Design
Andrew Henry, Principal Scientist, Chemical Computing Group
Protein engineering plays a pivotal role in modulating the function, activity and physical properties of biologics. Representative strategies employed in protein engineering include rationale protein design and directed evolution. In general, disparate work has been done in applying computer-aided biologics design (CABD) to protein engineering for the development of novel biological therapeutics. Here, we establish a unified framework of protein engineering tools and investigate its applicability to modulation of protein properties: affinity and stability.
16:05 Refreshment Break
16:35 Isolation and Optimization of Novel Anti-GPCR Antibodies
Julie Douthwaite, Ph.D. Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune LLC
G protein coupled receptors (GPCR’s) represent a challenging target class for the isolation and optimization of therapeutic biologics. In this work we have used a combination of immunization and phage display to isolate antibodies capable of potently blocking the activity of the formyl peptide receptor (FPR). Using combinatorial mutagenesis approaches, significant improvements to both affinity and species cross-reactivity of the lead molecules are demonstrated, resulting in antibodies that show significant potency in cellular disease assays.
17:05 Hexavalent TRAIL-Receptor-Agonists with Enhanced Therapeutic Properties: Underlying Engineering Concept and in vivo Activity Profile
Oliver Hill, Ph.D., Vice President, Molecular Biology, Apogenix GmbH
Apogenix has engineered a TRAIL mimetic with three Apo2L/TRAIL protomer subsequences fused into one polypeptide chain. This trivalent single-chain-TRAIL-receptor-binding-domain (scTRAIL-RBD) was fused to the Fc-part of human IgG1 to create a hexavalent scTRAIL-RBD-FC fusion protein. In vitro, the hexavalent agonist induces superior clustering of TRAIL-Rs and subsequent apoptotic cell death of sensitive tumor cell lines. In contrast to bivalent agonistic TRAIL-R2 antibodies, its potent anti-tumor efficacy in vivo is independent of Fc-receptor based multimerisation events.
17:35 Improving PK and Cholesterol Lowering by a pH-Sensitive Anti-PCSK9-Antibody
Javier Chaparro-Riggers, Associate Research Fellow, Protein Engineering, Rinat-Pfizer, Inc.
Target-mediated clearance and high antigen load can hamper the efficacy and dosage of many antibodies. pH-sensitive binding of the antibody to its antigen can improve the PK and PD in such cases. We improve the PK and extend cholesterol lowering in rodents and non-human primates by engineering a pH-sensitive anti-PCSK9 antibody variant and we can show that this effect is FcRn dependent.
18:05 Welcome Reception in the Exhibit Hall with Poster Viewing
19:05 End of Day One
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