2013 Archived Content
 

Engineering Stream

14th Annual
Engineering Antibodies

Challenging Targets, Next Generation Research Methods and Antibody Therapeutics for Autoimmune Diseases

May 1-2, 2013

The field of antibody engineering is at an exciting point in its development, with new generations of therapeutic antibodies now reaching the market, great advances in protein science and a body of clinical evidence that can be used to inform the development of safe, highly effective therapies for unmet medical needs. Engineering Antibodies combines groundbreaking discovery stage work in target identification, challenging targets and protein engineering with the application of these foundations to new biotherapeutics.

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 Tuesday, April 30 from 4:15 - 5:30 PLENARY KEYNOTE PANEL 

Conventional vs. Non-Conventional Formats 

 Janice ReichertModerator: Janice Reichert, Ph.D., Editor-in-Chief, mAbs; Managing Director, Reichert Biotechnology Consulting LLC
With the explosion in the number of formats available, what are the potential benefits and risks to patients? This panel will discuss the realistic outlook and uncertainties with developing a diverse array of non-canonical antibodies in terms of immunogenicity, safety, competitive marketplace, commercial development, business strategies, regulatory approval, target validation and clinical development.
 

Panelists: 

David Meininger David Meininger, Ph.D., MBA, Executive Director, Molecular Discovery, Merck





 

Tillman GerngrossTillman Gerngross, Ph.D., CEO and Co-Founder, Adimab LLC; Professor, Bioengineering, Thayer School of Engineering, Dartmouth College





 

Trudi VeldmanTrudi Veldman, Ph.D., Senior Director, Biologics Generation, AbbVie





 


WEDNESDAY, MAY 1

7:00 am Conference Registration

OMT 7:45 Breakfast Presentation: OmniRat and OmniMouse – Naturally Optimized Human Antibodies

Roland Buelow, Ph.D., CEO, Open Monoclonal Technology, Inc.

OMT developed a humanized rat (OmniRatTM) and mouse (OmniMouseTM) carrying a chimeric IgH locus together with fully human light-chain loci. Following immunization, such animals perform as efficiently as normal animals in yielding high affinity serum IgG. Monoclonal antibodies, comprising fully human variable regions with sub-nanomolar antigen affinity and carrying extensive somatic mutations, are readily obtainable.


Structural and Sequencing Methods for Antibody Screening and Design 

8:30 Chairperson’s Opening Remarks

Susanne Gräslund, Ph.D., Principal Investigator, Biotechnology, Structural Genomics Consortium, Canada

8:40 A Family-Based Approach to Study Proteins Involved in Epigenetic Signaling

Susanne GräslundSusanne Gräslund, Ph.D., Principal Investigator, Biotechnology, Structural Genomics Consortium, Canada

The SGC classifies human proteins according to conserved domain types to produce soluble proteins for structural investigations, development of small molecule "chemical probes" and generation of recombinant antibodies. I will present our platform for production of these soluble protein domains in E. coli and BVES and their use as antigens for recombinant antibody production.

9:10 Functional Single-Cell Hybridoma Screening Using Droplet-Based Microfluidics

Christoph MertenChristoph Merten, Ph.D., Group Leader, Principal Investigator, Genome Biology Unit, European Molecular Biology Laboratory, Germany

We have optimized droplet-based microfluidic systems for cell-based assays, including a fully integrated system in which individual cells are encapsulated and assayed directly for the release of antibodies inhibiting drug targets. The technology facilitates screening more than 20 clones per second and may allow the identification of potent therapeutic antibodies from human disease survivors.

9:40 Molecular Computational Tools for Designing and Screening of Stable Antibodies

Neeraj AgrawalNeeraj J. Agrawal, Ph.D., Postdoctoral Associate, Chemical Engineering, Massachusetts Institute of Technology

We present computational molecular tools for identifying aggregation prone regions on antibodies and for ranking antibodies according to aggregation propensities. These tools can incorporate developability and manufacturability early in the protein drug development and reduce overall time from discovery to launch. These tools offer a rational approach to systematically design aggregation-resistant proteins.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing


Antibody Mixtures and Combinations 

11:10 Simultaneous Inhibition of EGFR, HER2 and HER3 by an Antibody Mixture (Pan-HER) Provides Broad and Potent Tumor Inhibition 

Johan LanttoJohan Lantto, Ph.D., Principal Scientist, Project Leader, Symphogen A/S, Denmark

Symphogen has generated Pan-HER, a mixture of mAbs specifically targeting EGFR, HER2 and HER3, which all play an important role in the development and progression of human cancer. Pan-HER displays broad and potent tumor inhibition in preclinical models and prevents compensatory receptor up-regulation/activation. The presented data indicate that Pan-HER is superior to existing targeted therapies in dealing with both primary and acquired resistance due to tumor heterogeneity and plasticity.

 

11:40 Mechanisms of Action of MM-151, a Triobody™ Targeting EGFR: Has EGFR Met Its Match?

Jeff KearnsJeffrey. D. Kearns, Ph.D., Senior Scientist, Translational Research, Merrimack Pharmaceuticals, Inc.

A systems analysis was performed to identify how to inhibit the signaling amplification of the EGFR/ERK network. A model-driven kinetic engineering strategy was implemented to guide development of a mixture of three fully human monoclonal antibodies directed against distinct non-overlapping epitopes on EGFR. Preclinical studies reveal improvement in functional activity versus existing anti-EGFR biologics.


New Technologies for Antibody Engineering 

Chemical Computing GroupNEW logo 12:10 pm A Uniform Framework for Computer-Aided Biologics Design

Christopher R. Corbeil, Ph.D., Research 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.

Isogenica 12:40 Luncheon Presentation I: Addressing Challenges in Synthetic Antibody Design Using Combinatorial Libraries

Chris Ullman, Ph.D., CSO, Isogenica Ltd.

It is a challenge to surpass the performance of the natural antibody repertoires through synthetic combinatorial approaches. However, Isogenica's Colibra and CIS DNA display technologies have the potential to assemble protein scaffold libraries that have greater functionality and developability than current methodologies. Through design and synthesis, the liabilities of natural and degenerate methods can be removed, additional diversity created thereby enabling protein engineers to generate superior candidates.

SDIX 1:10 Luncheon Presentation II: Multipass Membrane Protein Monoclonal Antibodies by DNA Immunization and High Throughput Flow Cytometry Screening

James W. Stave, Ph.D., Senior Research Fellow, SDIX

Multipass transmembrane proteins like GPCRs and ion channels, are important but challenging targets for therapeutic monoclonal antibody discovery.  Using DNA immunization panels of antibodies were isolated for CXCR4, ADORA2A, and CD20 that were unique, have diverse epitope specificities, and exhibit functional activity as good or better than benchmark therapeutic antibodies.

1:40 Session Break


Antibodies Against Intracellular and Membrane Targets 

2:00 Chairperson’s Remarks

Luis Pardo, Ph.D., Max-Planck Research Group Leader, AG Oncophysiology, Max-Planck Institute of Experimental Medicine, Germany

2:05 Bifunctional TRAIL Antibodies Targeting Kv10.1 Potassium Channels Induce Selective Apoptosis of Tumor Cells

Luis PardoLuis Pardo, Ph.D., Max-Planck Research Group Leader, AG Oncophysiology, Max-Planck Institute of Experimental Medicine, Germany

We designed a single-chain antibody against an extracellular region of Kv10.1 (scFv62) and fused it to the human soluble TRAIL. This scFv62-TRAIL construct induced apoptosis only in Kv10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking Kv10.1 expression. It also induced fratricide killing of Kv10.1-negative tumor cells when co-cultured with Kv10.1-positive cells. 

2:35 Rapid and Reliable Characterization of Fabs for Structural Analysis of an ABC Transporter

JungMin KimJungMin Kim, Ph.D., Postdoctoral Scholar, Pharmaceutical Chemistry, University of California, San Francisco

Phage display Fabs are interesting as they provide a renewable source of Fabs, and are allowed to recognize three-dimensional epitopes of antigens. In addition to a good library and panning, appropriate characterization is required for successful phage display Fab identification. We present methods to characterize phage display Fabs to aid structural analysis of an ABC transporter.


Selexis 3:05 The Selexis SURE CHO-Mplus™ Library: Next Generation Innovation for Addressing Difficult-to-Express Proteins

Andrew Sanford, Vice President, Business Development, Selexis, Inc.

Tackling production bottlenecks with difficult-to-express (DTE) proteins can significantly delay development programs. The SURE CHO-Mplus™ Library, the newest innovation from the SUREtechnology Platform™, consists of 16+ proprietary cell lines specifically designed to address a range of production bottlenecks, including metabolic limitations, trafficking backlogs, improper folding and altered post-translational modifications. The library allows for parallel experimentation to overcome DTE protein development issues in a shorter timeframe.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:20 Problem Solving Breakout Discussions

Concurrent problem solving breakout discussions, open to all attendees, speakers, sponsors, and exhibitors, provide a forum for discussing key issues and meeting potential collaborators. Plan to take part and explore these topics in-depth. Please pick a topic of your choice, find your table and join in.

The Next Generation of Antibodies

Johan Lantto, Ph.D., Principal Scientist, Project Leader, Symphogen A/S, Denmark

  • Multi specific antibodies – good and bad
  • Targeting tumor and tumor stroma
  • Antibody mixtures – where are we?

Microfluidics in Diagnostics and High Throughput Screening

Christoph Merten, Ph.D., Group Leader, Principal Investigator, Genome Biology Unit, European Molecular Biology Laboratory, Germany

  • Experiences with commercially available systems and academic services
  • Limitations (material constraints; biocompatibility, assay duration, etc.)
  • Pros and cons of the various microfluidic formats

Biologics for Autoimmune Diseases

William Stohl, M.D., Ph.D., Professor of Medicine, Division of Rheumatology, Keck School of Medicine, University of Southern California

  • B cell-directed biologics
  • T cell-directed biologics
  • Cytokine-directed biologics

Technologies and Mapping Strategies for Antibody Epitopes

Sam Wu, Ph.D., Senior Scientist, Biologics Research, Janssen R&D

  • Antibody epitopes: A significant factor in therapeutic antibody selection
  • Evaluation of current technologies applied in epitope mapping
  • Discussion on overall strategies in mapping antigen-antibody interactions
 

Blue Sky Bioservices5:20 - 6:30 Networking Reception in the Exhibit Hall with Poster Viewing



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