header
 |  |  |
 |  | |
 |  | |
Registration
Online Registration is Open!
Find Another IBC Event
Scientific Sponsor
Alternate Language Options
Alternate Language Options: 
Document Title
Antibody Engineering Agenda
Antibody Engineering Agenda
|
Pre-Conference Workshop Sunday, December 7, 2008 | SPECIAL EVENING MEETING | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | | |
| Microarrays and Nanotechnology for Antibody Discovery and Analysis | |
| 12:00 | Registration Opens |
| 1:30 | Announcements and Chairperson's Opening Remarks Jamie K. Scott, M.D., Ph.D., Professor and Canada Research Chair in Molecular Immunity, Department of Molecular Biology & Biochemistry, Simon Fraser University, Canada |
|
Nanosensors | |
| 1:45 | A New Generation of Nanostructures for SPR Biosensing and Antibody Research Surface plasmon resonance (SPR) is a widely used technology to determine binding events involving biological species. We will discuss a new type of SPR sensing technology based on nanostructured holes milled on gold films. This new SPR substrate allows measurements in transmission mode, which is ideal for microarray implementation. Moreover, the nanoholes allow further advantages over the current SPR technology in terms of sensitivity and solution delivery. Alexandre G. Brolo, Ph.D., Associate Professor, Department of Chemistry, Department of Chemistry, University of Victoria, Canada |
| 2:15 | Detection of Cellular and Chemical Activity in Nanoliter Volumes Micromachined devices and microfluidics allow for a dramatic reduction of the reaction volume or the confinement of single cells into in vivo like microenvironments. We describe a micromachined Nanocalorimeter to measure the heat generation of chemical reactions or the contraction of cardiac myocytes with nW sensitivity in nanoliter volumes, and a Nanophysiometer, which allows us to trap single cells in chemically controlled nanoliter volumes to measure extracellular acidification and glucose consumption rates, intracellular pH and pCa under physiologically relevant conditions. Franz Josef Baudenbacher, Ph.D., Assistant Professor, Department of Biomedical Engineering, Vanderbilt University |
| 2:45 | Molecular Interaction Studies using Backscattering Interferometry Interferometry is an optical sensing method that has recently been transformed into an ultra-high sensitivity, picoliter volume biosensor. Backscattering interferometry (BSI) employs a simple optical train that consists of a coherent, collimated source, a channel in a microfluidic chip containing a sample, and a position sensing transduction system. BSI is described in detail, and the potential of BSI to be used as an assay platform for performing antibody-antigen interaction assays rapidly, with exceedingly small sample quantities, is demonstrated. Darryl J. Bornhop, Ph.D., Professor, Department of Chemistry, Vanderbilt University |
| 3:15 | Networking Refreshment Break |
| Antibodies for Detection | |
| 3:45 | A Blue-Luminescent Antibody: Mechanism and Applications Antibodies elicited against trans-stilbene have resulted in luminescent complexes that can be harnessed for various biosensor applications. Due to its extremely bright blue luminescence, antibody EP2-19G2 has been of particular interest for mechanistic studies and for its development in biosensor assays. Its structure and light-generating mechanism, as well as several potential applications, will be discussed. Erik W. Debler, Ph.D., Postdoctoral Fellow, Rockefeller University |
| Cell Microarrays | |
| 4:15 | Microwell Arrays for Detecting Single, Antigen-Specific B-lineage Cells We have developed a highly integrated live-cell microarray system for analyzing the cellular responses of individual cells using a microwell-array chip that has up to 234,000 microwells each of which is just large enough to fit a single cell. We have applied the system to detect human antigen-specific B-cells or antibody secreting cells. Our system can produce antigen-specific human monoclonal antibodies from PBL in a week. Hiroyuki Kishi, Ph.D., Associate Professor, Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan |
| 4:45 | Engraved Microarrays for Detecting Single, Antigen-Specific Cells This talk will describe a soft lithographic technique that uses an array of subnanoliter containers to isolate large numbers of individual antibody-secreting cells and print protein microarrays of the corresponding antibodies from each cell. The method enables rapid, high-throughput screening (>106 cells/day) and yields many characteristics of the antibodies in the primary screen, including the specificity, isotype, and affinity of each clone. J. Christopher Love, Ph.D., Assistant Professor, Chemical Engineering, Texaco-Mangelsdorf Career Development Professor in Chemical Engineering, Massachusetts Institute of Technology |
| 5:15 | Close of Workshop Session; Start of Antibody Society General Session |
|
Special Evening Meeting Sunday, December 7, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | | |
|
The Antibody Society: General Session and Discussion of Specific Initiatives on the Preservation and Advancement of Informatics Resources for the Antibody Engineering Field | |
(Open to all registered delegates for Antibody Engineering and Antibody Therapeutics. Workshop registration is not required.) The Antibody Society was formed in 2007 to broadly further the interests of antibody and binder engineering as well as antibody/binder therapeutic development, to ensure advancement of the field while maintaining the safe and thorough testing of future therapeutic agents in our field. The official journal of the Society is PEDS (Protein Engineering, Design and Selection), and members receive a special discount to this and most meetings scientifically sponsored by the Society. The Society represents this increasingly diverse field by supporting the resources that promote successful engineering of recombinant antibodies, single scaffold binders, and other facets of basic and applied research by those in academics and the private sector. The Society also seeks to provide a forum and voice for all aspects of this global field. By joining The Antibody Society, members will help the Society support its goals, including the following:
For further information on how you and your organization can join the Society, please visit the Society website: www.AntibodySociety.org | |
|
Main Conference - Day One Monday, December 8, 2008 | PRE-CONFERENCE WORKSHOP | SPECIAL EVENING MEETING | DAY TWO | DAY THREE | DAY FOUR | | |
| 7:30 | Registration, Networking Coffee |
| 8:00 | Announcements |
| 8:15 | Chairperson's Opening Remarks and Keynote Introduction Dennis R. Burton, Ph.D., Professor, Immunology Department, The Scripps Research Institute |
| Keynote Presentation | |
| 8:30 | Evolving Technologies of Antibody Engineering Multiple technologies underpin the derivation of the different monoclonal antibodies currently used in therapy. However, the derivation of many of these mAbs has ultimately relied on the in vivo processes of antibody gene diversification and antigen-mediated selection in order to obtain the initial antigen combining site: this primary antibody has then usually been refined or humanized by in vitro engineering. Here, I will review the recent advances in our understanding of the normal physiological processes of antibody generation and maturation with a view to how these processes have or can be exploited for the generation of engineered antibodies. Michael S. Neuberger, Ph.D., Head, Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, United Kingdom |
| 9:30 | Audience Questions |
| 9:45 | Networking Refreshment Break |
| 10:15 | Keynote Introduction by Session Chair |
| Keynote Presentation | |
| 10:30 | Antibodies: Versatile Proteins for Multiple Applications Because of their unique properties, antibodies are ideal for many applications. They recognize their targets with exquisite specificity and high affinity. They are comprised of discrete functional domains. This domain structure of antibodies facilitates their genetic manipulation and makes it possible to produce diverse antibody-related proteins for many different applications. Antibodies exist as different isotypes with different properties. They bind Fc receptors and can activate the complement cascade, leading to important functional outcomes. They have a long half-life that can be manipulated. Antibodies are glycoproteins, with the structure of their attached carbohydrate making important contributions to their functional properties. Antibodies retain their essential characteristics when fused to a wide range of non-antibody proteins. Sherie Morrison, Ph.D., Chair, Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles |
| 11:30 | Audience Questions |
| 11:45 | Lunch on Your Own |
| 1:15 | Technology Workshops |
Using the ProteOn to Characterize Antigen/Antibody Interactions
The ProteOn is a parallel-processing surface plasmon resonance biosensor that can address 36 interactions per binding cycle in a 6 by 6 format through the use of its unique crisscrossing flow paths. In a single injection, it can measure the kinetics of an analyte binding to six different ligands on the chip, without the need for regeneration. Multiplexing assays in this way is particularly useful in other applications, such as blocking.Yasmina Abdiche, Ph.D., Senior Principal Scientist, Rinat Laboratories, Pfizer Inc. | |
Reconstituted Ribosome Display for Efficient Evolution of Antibody Affinity
We re-created a functional in vitro expression system based on purified E. coli proteins and translation factors. This tool was adapted to ribosome display demonstrating superior robustness and efficiency. We will show examples of selecting antibodies from naive libraries with similar ease to phage display, optimising antibody affinity and using reconsituted ribosome display to generate cyclic peptide libraries through the incorporation of non-natural amino acids.Lutz Jermutus, Ph.D., Senior Director of Technology, MedImmune, United Kingdom | |
| 1:45 | Technology Workshops |
Synthetic Biology and Secretion-Capture Display in Antibody Engineering
We will describe advances in construction of extremely high-fidelity synthetic libraries, and in display technologies for selection of antibodies from such libraries. These include large synthetic variant libraries with error rates lower than 1 in 3,000 base pairs, and a novel, secretion-and-capture display method, which allows in-vitro selection of even complex, disulfide-bonded proteins, such as full-length IgG. We will also describe an application of these technologies to affinity maturation of antibodies.Dasa Lipovsek, Ph.D., Director of Protein Engineering, Codon Devices, Inc. | |
A Custom Designed Approach to Antibody Discovery
Phage display libraries are powerful tools to generate human recombinant human antibodies with high specificity and high affinity. Through its scientific expertise and proprietary technologies, XOMA is in a unique position to construct custom phage display libraries. Multiple library types including naïve, immune or patient-derived phage display libraries can be constructed to increase the probability of success of isolating functional antibodies and high affinity antibodies. XOMA’s large Naïve Phage Display Library provides broad antibody diversity, represents the natural antibody repertoire, and contains functional antibodies to virtually all targets. XOMA’s Patient-derived Phage Libraries strategically position library design for a therapeutic area or disease focus and are powered to capture rare, disease-specific antibodies from patients who survived the disease (i.e infectious disease, oncology and autoimmune diseases).Nathalie Dubois-Stringfellow, Ph.D., Senior Director, Preclinical Research and Development, XOMA (US) LLC | |
| 2:15 | Announcements |
| Session II: The Single-Chain Fv and its Fusion Proteins: 20 Years Old and Coming of Age | |
| 2:20 | Chairperson's Opening Remarks James S. Huston, Ph.D., Vice President and Senior Research Fellow, EMD Serono Research Center |
| 2:30 | Engineered MFE-23 scFv Fusion Proteins for ADEPT Cancer Therapy and Systems Medicine Antibody-directed enzyme prodrug therapy (ADEPT) has been developed using a single chain Fv fused to carboxypeptidase G2 that is glycosylated in Pichya pastoris. Enzyme is targeted to tumor where it generates a cytotoxic drug through activation of a harmless prodrug. The approach to developing a complex therapy has been formalized in guidelines for information about antibody therapy. Richard H.J. Begent, M.D., Head of Oncology, Ronald Raven Professor of Oncology, University College London, United Kingdom |
| 3:00 | Visualization of Tumor Targeting at High Resolution Solid tumors possess a spatially and temporally heterogeneous pathophysiology, which has a major impact on both the distribution and efficacy of systemically delivered therapies. The use of novel high-resolution microscopy, to investigate the effect of the tumor microenvironment on antibody-targeted therapies, will be discussed for both subcutaneous and liver metastatic models of colorectal cancer. This work illustrates the importance of studying intratumor antibody distribution for the optimization of therapies. R. Barbara Pedley, Ph.D., Reader in Tumor Biology, UCL Cancer Institute, United Kingdom |
| 3:30 | Vascular Targeting with Recombinant Antibody Derivatives: From the Bench to the Clinic The formation of new blood vessels is a relatively rare event in the adult, but these structures can serve as excellent targets for the antibody-based delivery of therapeutic agents. Our laboratory, in collaboration with Luciano Zardi and with Philogen, has brought six vascular targeting antibody derivatives into clinical development programs. Dario Neri, Ph.D., Professor, Department of Chemistry and Applied Biosciences, ETH Zürich, Switzerland |
| 4:00 | Networking Refreshment Break |
| 4:30 | Array-Based Oncoproteomics using scFv Microarrays - A Tool for Clinical Diagnostics? We have developed a high-performing, human antibody microarray technology platform, based on designed scFvt antibody fragments. This microarray platform has now been applied in more than ten different clinical studies, including analysis of serum/plasma proteomes from patients suffering from e.g. metastatic breast carcinoma, glioblastoma multiforme, pancreatic carcinoma, gastric adenocarcinoma, chronic lymphocytic leukemia etc. Data demonstrating the accuracy and predictability of array-based proteomics in oncoproteomics will be discussed. Carl A.K. Borrebaeck, Ph.D., Program Director, Department of Immunotechnology, Create Health - The Strategic Center for Translational Cancer Research, Lund University, Sweden |
| 5:00 | Applications of rPEG to dAbs, scFvs and Diabodies rPEG is Amunix' recombinant, unstructured amino acid polymer of 25-50kD that is genetically fused to proteins to increase their serum halflife. Whereas PEG is not biodegradable and accumulates to form vacuoles in kidney cells, rPEG is biodegradable. A benefit of rPEG fusions to eukaryotic proteins, including antibody fragments, is the increased solubility of the proteins in the cytoplasm, preventing inclusion body formation. By adding rPEG, we have been able to express a variety of antibody fragments in soluble, active form in the E. coli cytoplasm. Willem 'Pim' Stemmer, Ph.D., Chief Executive Officer and Founder, Amunix Inc. |
| 5:30 | scFv Derived by Nanoselection and their Application to Parkinson's Disease and Huntington's Disease Protein misfolding and assembly into toxic aggregates is a shared feature in numerous neurodegenerative diseases including Parkinson's and Huntington's Diseases. By combining the diversity of surface display antibody libraries with the imaging capabilities of Atomic Force Microscopy, we developed biopanning protocols that enable isolation of antibody fragments to specific protein morphologies. The antibody fragments can be used either extracellularly or intracellularly to target specific toxic species involved in disease progression. Michael Sierks, Ph.D., Professor, Chemical Engineering, Arizona State University |
| 6:00 | Networking Cocktail Reception; Opening of Poster and Exhibit Hall Sponsored by: 
|
|
Main Conference - Day Two Tuesday, December 9, 2008 | PRE-CONFERENCE WORKSHOP | SPECIAL EVENING MEETING | DAY ONE | DAY THREE | DAY FOUR | | |
| 7:00 | Registration, Networking Coffee |
| 7:45 | Announcements |
| Session III: The Theory, Practice and Use of Libraries Based on Restricted Amino Acid Sets | |
| 7:50 | Chairperson's Opening Remarks Andrew Bradbury, M.B., B.S., Ph.D., Research Scientist, Los Alamos National Laboratories |
| 8:00 | The Antibody Combining Site and Tools to Link Antibody Sequence and Structure We have analyzed characteristics of the 6 "complementarity determining regions" (CDRs) which encode antibody variability and specificity with regard to the general class of antigen with which they interact. These results may help guide antibody library generation. More recently we have developed a number of tools for working with antibody sequence and structure including a measure of "humanness", analysis of VH/VL packing and an integrated database of antibody sequence and structure known as Abysis. These tools and their applications will be presented. Andrew C.R. Martin, D.Phil., Senior Lecturer in Bioinformatics, Institute of Structural and Molecular Biology, Division of Biosciences, University College London, United Kingdom |
| 8:30 | Defined-Sequence Libraries in Antibody Engineering Our library-construction method relies on complex mixtures of defined-sequence oligonucleotides as the source of diversity. This allows the diversity at each position to be restricted to a defined subset of amino acids, with a particular probability of occurrence assigned to each amino acid. In addition, such libraries can incorporate higher-order design rules, such as diversity correlated between up to twenty adjacent amino-acid residues. This allows the user control over properties encoded by linear oligopeptide sequence. Dasa Lipovsek, Ph.D., Director of Protein Engineering, Codon Devices, Inc. |
| 9:00 | Slonomics - A Novel Technology for the Generation of Highly Designed Gene Libraries We have developed a novel mutagenesis technology based on the iterative assembly of base triplets. This technology is especially suited to generate highly designed gene libraries for the use in e.g. antibody display experiments. The high degree of control over type, number and proportion of codons within variable regions and its impact on screening success will be demonstrated. Jan Van den Brulle, Ph.D., Head of Research and Development, Sloning BioTechnology GmbH, Germany |
| 9:30 | Networking Refreshment Break, Exhibit and Poster Viewing |
| 10:15 | Highly Functional Minimalist Antibodies Highly functional antibodies can be designed with combining sites composed of just two amino acids (tyrosine and serine). In this minimalist background, we have explored fundamental aspects of molecular recognition and evolution by systematically replacing or adding to the binary code. We find that antigen recognition is simpler than previously believed and we can design simple, synthetic antibodies with properties beyond those of natural antibodies. Sachdev Sidhu, Ph.D., Associate Professor, University of Toronto, Canada |
| 10:45 | Minimalist Design of Synthetic Binding Proteins using Non-Antibody Scaffolds Generating novel functions using simple scaffolds has become a major branch of protein engineering. Restricted diversity libraries of the fibronectin type III scaffold produce high-performance binding proteins, overcoming the combinatorial challenge. In these minimalist interfaces, tyrosines and conformational diversity play dominant roles in forming productive interactions. By expanding this minimalist approach we have developed "affinity clamps", a new class of synthetic binding proteins targeted to short peptide motifs. Shohei Koide, Ph.D., Associate Professor, Biochemistry & Molecular Biology, University of Chicago |
| 11:15 | The Path to Platinum: The Evolution of Human Combinatorial Antibody Libraries (HuCAL®) Trinucleotides (TRIMs) have been used as core technology for diversification of CDRs in all HuCAL Libraries. TRIM synthesis guarantees a high quality and sequence diversity can be restricted to the set of amino acid found in nature. In HuCAL Gold® six CDRs have been diversified in up to 61 positions. The CDR design in HuCAL PlatinumTM, presented here the first time, was refined to obtain a higher number of functional CDR3 sequences. Josef Prassler, Ph.D., Associate Director, Research & Development, MorphoSys AG, Germany |
| 11:45 | Technology Workshops |
Therapeutic Antibodies without Helper T Cell Epitopes
Data will be presented demonstrating enhancements in the in vitro detection of T cell epitopes within therapeutic antibodies. This enhanced method has been applied to screen lead therapeutic antibodies during preclinical development, and provides an assessment for the relative risk of immunogenicity. Furthermore, data will be presented in which a refinement of this process has been applied to enable the selection of fully human sequence segments that are devoid of T cell epitopes.Frank J. Carr Ph.D., Director for Biologics Research, Antitope, United Kingdom | |
PER.C6® Cells: A Highly Efficient Production Platform for Antibodies
Yields of 8 g/L in fed-batch and 27 g/L using DSM's XD™ for IgGs and over 1.5 g/L in fed-batch for IgMs are now possible due to the ability to obtain stable clones producing 50 picograms of IgG per cell per day and 20 pcds of IgM, reliably, using the PER.C6® cell line. The workshop will focus on key aspects of the technology and economic impact relative to current approaches in manufacturing of protein therapeutics.Marco A. Cacciuttolo, Ph.D., President & Chief Executive Officer, Percivia LLC | |
The Versatile Role of Bio-Layer Interferometry in Therapeutic Antibody Discovery and Development
Bio-Layer Inteferometry is a label free, real time technology to analyze molecular interactions from small molecules to proteins. In this presentation, we will discuss several applications of the Octet(R) system within antibody discovery and development processes. Applications used in tool generation, early discovery, characterization and cell line development will be shown. Furthermore comparison between standard technologies and Bio-Layer Interferometry (BLI) will be discussed.Arnout F. Gerritsen, Associate Director, Lead Discovery, Genmab bv, The Netherlands | |
| 12:15 | Networking Luncheon, Exhibit and Poster Viewing |
| 1:45 | Technology Workshops |
Balancing Power and Simplicity in Real Time, Label-Free Characterization/Selection of Antibodies and Development of Biopharmaceuticals: The Added Value of Biosensors
This presentation will discuss the applications of Attana's label-free, real time analysis technology to address the current market needs for high quality and cost-efficient analysis of molecular interactions. The presentation will also highlight different applications focusing on biopharmaceutical developments. How can biosensors provide added value?Johan Lindberg, Vice President, Sales & Marketing, Attana AB, Sweden | |
A Combination of Gene Evolution Technologies for Protein Improvement
We will present a collection of versatile technologies for the improvement and targeted modification of protein properties. The sequential permutation technology - either alone or in succession with other high-fidelity library technologies - allows for the systematic and optimal adaption of pharmaceutical proteins and industry enzymes to comply with specific demands, and to meet a wide range of different technical requirements.Christian Kranz, Ph.D., Product Manager. Directed Evolution, GENEART AG, Germany | |
Development of MOR103, a GM-CSF Specific Human Antibody for the Treatment of Inflammatory Diseases Currently Tested in a Phase I Clinical Trial
MOR103 targets GM-CSF, a pro-inflammatory cytokine implicated in the pathogenesis of several auto-immune diseases e.g. rheumatoid arthritis. Utilizing the modular design of the human combinatorial antibody library (HuCAL®) enabled antibody optimization via targeted CDR diversification. Preclinical data demonstrating the mode of action of MOR103 will be presented. Currently MOR103 is tested in a Phase I clinical trial to assess safety, tolerability and the pharmacokinetics of this fully human high affinity anti-GM-CSF HuCAL antibody.Stefan Steidl, Ph.D., Associate Director, MorphoSys AG, Germany | |
| Session IV: Are Non-Antibody Scaffolds Really any Better than Antibody Fragments? | |
| 2:15 | Announcements and Chairperson's Opening Remarks Ian M. Tomlinson, Ph.D., Vice President, GSK-Domantis Group, United Kingdom |
| 2:30 | Immunogenicity Problems: A Paradigm Shift? Tools designed by expert immunoinformaticians have enabled the prediction of immunogenicity and the prospective identification of subjects who may be at increased risk of developing adverse immune responses. These same techniques can also be used to elucidate the dynamic balance between T effector and T regulatory cells in the development and treatment of autoimmune diseases. This presentation illustrates the use of these tools to predetermine immunogenicity. Techniques for salvaging immunogenic therapeutics are also addressed. Anne S. De Groot, M.D., Associate Professor of Pediatric Infectious Disease (adjunct), Brown University Medical School; Director, Institute for Immunology and Informatics, University of Rhode Island; Chief Executive Officer, EpiVax |
| 3:00 | DARPins, the Next Generation Protein Drugs DARPins are a novel class of binding molecules combining the advantages of antibodies with the ones of small molecule drugs. The unreached high affinity target binding is combined with exceptional stability, cost effective production and low immunogenic potential. DARPins have been validated in several different disease models. The DARPin scaffold allows for a whole range of format choices, allowing tailored drug design for improved therapies. An example of how this can translate into patient benefit will be discussed. Christian Zahnd, Ph.D., Chief Executive Officer, Molecular Partners, Switzerland |
| 3:30 | Single Variable Antibody Domains from Camelids - Pros and Cons of Being Camelid Camelids have unique homodimeric heavy chain antibodies with an antigen-binding site comprised in one single domain, known as Nanobody. After a short immunization, high affinity, antigen-specific Nbs are retrieved by various display and selection techniques. The stable, soluble and strict monomeric Nbs are easily humanized or tailored into pluripotent constructs, employed as research tool in immuno-precipitations, to localize antigen in living cells, or to diagnose and treat infections and diseases. Serge Muyldermans, Ph.D., VIB Department of Molecular and Cellular Interactions, Vrije University, Belgium |
| 4:00 | Networking Refreshment Break, Exhibit and Poster Viewing |
| 4:45 | Human Domain Antibodies: From Selection to Innovative Products Human Domain Antibodies (dAbs) offer innovative therapeutic opportunities such as pulmonary delivery and dual targeting thanks to their thermodynamic stability, intrinsic solubility and tolerance to engineering for potency and formatting. The first dAb products are now in the clinic and several late stage preclinical assets are following close behind. Case studies will illustrate how desired functionality and manufacturability have been achieved by process optimization right from phage library selection. Laurent S. Jespers, Ph.D., Director of Protein Engineering, Domantis Limited, United Kingdom |
| 5:15 | Anticalins®, a Novel Class of Binding Proteins, and their use as Therapeutics Anticalins®, which are derived from human lipocalins, are small 20kDa proteins with highly selective binding properties. The use of Anticalins has already been validated in vivo for oncology, inflammation, ophthalmology and molecular imaging. Recent data for the clinical candidate PRS-050 (VEGF antagonist) will be presented. Moreover, unique features such as dual targeting and pulmonary delivery that come along with the compact structure, intrinsic stability and broad formulation flexibility of Anticalins will also be discussed. Evert J. J. Kueppers, Chief Executive Officer, Pieris AG, Germany |
| 5:45 | Adnectins: Realizing the Promise of a Novel Class of Targeted Biologics Adnectins, a novel, proprietary class of targeted biologics, are derived from a human, extracellular protein, fibronectin. Adnectin-based products offer potential advantages compared to traditional biologics, including speed of discovery, ease of manufacturing, and the ability to create multi-functional targeted antagonists and agonists. CT-322, an Adnectin inhibitor of VEGFR-2, had potent activity in a Phase 1 study, based on changes in biological and pharmacodynamic markers. Data for the next generation of Adnectins will also be presented. Eric Furfine, Ph.D., Senior Vice President, Research and Preclinical Development, Adnexus |
| 6:15 | Networking Cocktail Reception, Exhibit and Poster Viewing |
|
Main Conference - Day Three Wednesday, December 10, 2008 | PRE-CONFERENCE WORKSHOP | SPECIAL EVENING MEETING | DAY ONE | DAY TWO | DAY FOUR | | |
| 7:30 | Registration, Networking Coffee |
| Session V: Intrabodies Revisited | |
| 8:00 | Announcements and Chairperson's Opening Remarks Andreas Plückthun, Ph.D., Professor of Biochemistry, Department of Biochemistry, University of Zürich, Switzerland |
| 8:15 | Interfering with RAS-Effector Protein Interactions Inside Cells RAS mutations occur in many human cancers but attempts to develop drugs blocking protein interactions between RAS and effectors have been ineffective. We have developed methods, including intracellular antibody capture (IAC), to select single domain interfering antibodies that block protein-protein interactions. This is exemplified with interfering antibodies that bind activated RAS, prevent it binding its effectors and inhibiting tumourigenesis in mouse models. Our findings have implications for drugging "undruggable" protein-protein interactions in disease. Terence H. Rabbitts Ph.D., FRS, FMedSci, Director, Leeds Institute of Molecular Medicine, United Kingdom |
| 8:45 | Protein Silencing: Engineering Intrabodies for Targeted Protein Degradation Strategies to confer protein neutralizing properties to Intrabodies include 3-SPLINT, a technology for the selection of antibody domains that are intrinsically endowed with the ability to interfere with target protein-protein interaction domains, and a protein silencing switch made by engineering ligand-induced proteasome-targeting intrabodies. Silencing intrabodies are able to rapidly and effectively redirect intracellular target proteins for degradation in a catalytic fashion. Applications of intrabodies against Alzheimer's amyloid Aβ oligomers are presented. Antonino Cattaneo, Ph.D., Professor of Biophysics, European Brain Research Institute and International School for Advanced Studies, Italy |
| 9:15 | Facts and Fairy Tales about Tat-Mediated Uptake of Peptides, Proteins and Antibodies During the last decade, the potential of cell-penetrating peptides (CPPs) for cellular drug delivery has been highlighted by the discovery of the Tat- and the Antennapedia-derived peptides. These CPPs are actually very efficient in delivering their "cargo" molecules into various cell types. "Cargoes" include peptides, proteins, antibodies, oligonucleotides, drugs, or even bigger entities such as liposomes or nanoparticles. In this presentation, the "pros" and "cons" of using CPPs as a tool for drug delivery will be discussed. Eric Vives, Ph.D., Assistant Professor, University of Montpellier, France |
| 9:45 | Networking Refreshment Break, Exhibit and Poster Viewing |
| 10:30 | Small Molecule Mimics of an Alpha-Helix for Efficient Transport of Proteins into Cells We have designed and synthesized small-molecule mimics of an alpha-helical peptide protein transduction domain (a). These small-molecule carriers, which we termed SMoCs, are easily coupled to biomolecules, and efficiently deliver dye molecules and recombinant proteins into a variety of cell types. As an example of a protein cargo, we applied this new technology to the internalization of the DNA replication licensing repressor geminin, in vitro, providing evidence that extracellularly delivered SMoC-geminin can have an anti-proliferative effect on human cancer cells. David L. Selwood, BSc CSci FRSC CChem, Head of Biological Chemistry, Wolfson Institute for Biomedical Research, University College London, United Kingdom |
| 11:00 | The Human TOPONOME Project: Translating the Cellular Protein Network Code into Efficient Therapies A technology termed MELC/TIS enables researchers for the first time to address the hierarchical properties of protein networks directly in any cell or tissue section by colocalizing hundreds of proteins simultaneously using large tag libraries, e.g. antibodies (Nat. Biotechnology 24, 1270-1278, 2006). Clinical proofs of concept lay the ground for a human toponome project deciphering the protein network code (toponome) of human diseases for immediate pharmacological and clinical applications. Walter Schubert, M.D., Professor for Toponomics, International Faculty, Max Planck-CAS Partner Institute for Computational Biology, China; Head Molecular Pattern Recognition Research Group, University of Magdeburg, Germany |
| 11:30 | DARPins Inside Designed Ankyrin Repeat Proteins (DARPins), besides having shown excellent promise for in vivo applications on extracellular targets, can also be used as a tool to study cytoplasmic targets. Since all members of the library are stable to the reducing environment and fold well without aggregation even as fusion proteins, the full diversity can be exploited. Progress on observing and inhibiting a variety of intracellular events will be discussed. Andreas Plückthun, Ph.D., Professor of Biochemistry, Department of Biochemistry, University of Zürich, Switzerland |
| Technology Workshops | |
| 12:00 | Clinical Trials Using Potelligent® Mabs
Depletion of the target cell population expressing a specific antigen is one of the therapeutic concepts of antibody drugs. Potelligent® technology enhances the ADCC activity of therapeutic antibodies, which is the key mechanism of action of those depleting antibodies. In this presentation, clinical studies using Potelligent® antibodies in the oncology and inflammatory areas will be discussed.Masamichi Koike, Ph.D., President and Chief Executive Officer, BioWa, Inc. |
The ADLib® System: The Most Flexible Technology with Alternative Diversity
Chiome's ADLib® System is the only avian cellular antibody-library technology based on a completely proprietary mechanism of antibody diversification. The system provides many different approaches for generating highly specific antibodies against difficult antigens such as trans-membrane and highly homologous proteins. A unique approach for addressing different epitopes on the same target is also available. Chiome is very flexible in structuring partnerships with companies seeking alternative diversity and having complementary technologies and/or novel targets.Hidetaka Seo, Ph.D., Director, Research and Development, Chiome Bioscience, Inc., Japan | |
Differentiating your Antibody using Xencor's Antibody Platforms for Enhanced Pharmacokinetics and Cytotoxicity
Xencor has created and validated a suite of antibody Fc variants that enhance in vivo pharmacokinetics or cytotoxicity of targeted antibodies. Xtend™ variants increase affinity for FcRn and increase in vivo half-life by 3-fold in monkey studies, creating potential for less frequent dosing and reduced cost of goods. XmAb® variants increase affinity for Fc g receptors and enhance anti-tumor activity in mouse and monkey models, and are expected to increase clinical efficacy of targeted antibodies.
John R. Desjarlais, Ph.D., Vice President, Research, Xencor, Inc.
| |
| 12:30 | Networking Luncheon; Last Chance for Exhibit and Poster Viewing |
| Session VI: Novel Antibody Targets and Applications | |
| 2:00 | Announcements and Chairperson's Opening Remarks Dennis R. Burton, Ph.D., Professor, Immunology Department, The Scripps Research Institute |
| 2:15 | Bacterial Quorum Sensing as a Target for Anti-Infective immunopharmacotherapy Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. This lecture will detail an immunopharmacotherapeuctic strategy for the prevention or treatment of infections in which QS signaling contributes to bacterial pathogenesis. Kim D. Janda, Ph.D., Professor, Departments of Chemistry and Immunology, Ely R. Callaway, Jr. Chair in Chemistry, Director, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute |
| 2:45 | Molecular Mechanisms of the Anti-Inflammatory Activity Of IVIG Monomeric IgG, when administered at very high concentrations, is a well-established therapeutic for the treatment of autoimmune inflammatory disorders. A fully recombinant preparation was developed in which a 2,6 sialylated IgG1 Fc can recapitulate the biological activities of IVIG with a potency 30 fold greater than IVIG. The consequences of 2,6 sialylated Fc binding to this lectin initiates an anti-inflammatory cascade, ultimately resulting in enhanced expression of the inhibitory Fc receptor, FcRIIB, on effector macrophages. Jeffrey Ravetch, Ph.D., Professor, Laboratory of Molecular Genetics and Immunology, Rockefeller University |
| 3:15 | New Approaches to Discovery of Effective Prophylactic and Therapeutic Antibodies to Influenza, Including Avian Viruses New ways to protect groups most vulnerable to influenza are needed, since Oseltamivir resistance is on the rise and influenza vaccines have been shown to be less effective in the elderly. There is preliminary and anecdotal evidence that immunoglobulins from survivors of the 1918 H1N1 pandemic and from individuals surviving H5N1 avian influenza may be therapeutically effective. We report the discovery of influenza virus neutralizing human monoclonal antibodies effective against a broad range of avian and human influenza strains. Jaap Goudsmit, M.D., Ph.D., Chief Scientific Officer, Member of the Management Board, Crucell NV, The Netherlands |
| 3:45 | Networking Refreshment Break |
| 4:15 | Neutralizing Antibody Solutions from H5N1 Avian Influenza Survivor Combinatorial Antibody Libraries We have generated combinatorial antibody libraries from the bone marrow of convalescent H5N1 Avian influenza survivors that have yielded >300 unique antibodies against H5N1 viral antigens. Amongst these antibodies, we have identified several broadly neutralizing, anti-hemagglutinin antibodies for use as passive immunization against H5N1 viral infection. Remarkably three such antibodies neutralize a broad range of present and past H5 clades, as well as several relevant H1 subtype influenza viruses. Ramesh R. Bhatt, Ph.D., Vice President, Research, Sea Lane Biotechnologies |
| 4:45 | Domain Exchanged Antibodies to Glycans Although antibody responses to glycans, such as those present on the surface of invading microorganisms, are well documented, the quality and quantity of the antibodies ordinarily elicited clearly identify carbohydrates as a hypoimmunogenic antigenic class. To overcome this limitation, we are using domain-exchanged antibodies, in which the VH domains of the molecule are swapped, as a unique structural template for generation of high affinity antibodies binding specifically to glycan targets. Anthony Williamson, Ph.D., President and Chief Executive Officer, Calmune |
| 5:15 | A Unique Class of Protective Human Anti-M2 mAbs for Pandemic Influenza M2, is a highly conserved, virally encoded transmembrane protein present on the surface of influenza A virus and infected cells. We have isolated mAbs directly from human B cells that recognize an unanticipated, conformational epitope within M2 using a novel antibody discovery platform. This unique class of human anti-M2 mAbs could be useful as therapeutic agents for protection from and treatment for pandemic influenza, and also as a tool for the design of a universal influenza vaccine. Matthew Moyle, Ph.D., Senior Vice President, Research and Development, Chief Scientific Officer, Spaltudaq Corporation |
| 5:45 | Close of Session |
|
Main Conference - Day Four Thursday, December 11, 2008 | PRE-CONFERENCE WORKSHOP | SPECIAL EVENING MEETING | DAY ONE | DAY TWO | DAY THREE | | |
| 7:30 | Networking Coffee |
| Session VII: Antibodies in a Complex Environment: Target Selection in Relation to Efficacy | |
| 8:05 | Announcements and Chairperson's Opening Remarks Richard H.J. Begent, M.D., Head of Oncology, Ronald Raven Professor of Oncology, University College London, United Kingdom |
| 8:15 | B7-H1 Pathway as a Therapeutic Target of Antibody in Cancer and Autoimmune Diseases Upon engaging its receptor(s) on T and B cells, B7-H1 induces T cell to undergo apoptosis, exhaustion and anergy, therefore, downregulating immune and inflammatory responses. In addition to be a ligand, tumor-associated B7-H1 could also serve as a receptor to receive signal from PD-1, one of B7-H1 receptor on T and B cells. Antibody blockade of B7-H1 or its receptor represents a new approach to enhance immune responses against cancer and viral infection. Lieping Chen, M.D., Ph.D., Professor, Dermatology, Oncology and Immunology, Johns Hopkins University School of Medicine |
| 8:45 | Blocking Inhibitory Self-Recognition to Promote ADCC To improve the magnitude of ADCC, we have previously manipulated antibody structures and cytokine milieus. Here we show that the ADCC-based effector cell responses can be amplified by blocking inhibitory self-recognition in a human model, applying an autologous system in which physiologic checkpoints are in place. This method provides an alternative approach to potentiate the therapeutic benefit of antitumor antibodies that mediate ADCC. Louis M. Weiner, M.D., Director, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center |
| 9:15 | Systems Optimization of ErbB-Targeted Therapeutics: Development of an Anti-ErbB3 Monoclonal Antibody Computational biology is improving our understanding of complex biological systems. Using very large biological datasets of cell signaling, we have constructed detailed, mechanistic models. These may be used to predict network responses to targeted therapeutics such as monoclonal antibodies and small molecule inhibitors. Using the ErbB signaling network as an example, we will present how simulation proposed MM-121, a monoclonal anti-ErbB3 antibody, as a potentially superior approach current therapies. Ulrik B. Nielsen, Ph.D., Senior Vice President, Research, Merrimack Pharmaceuticals |
| 9:45 | Networking Refreshment Break |
| 10:15 | Adapting Antibodies According to Target Diversity in Viral Diseases and Cancer Antigenic variability of circulating viral strains and neutralization escape have been longstanding barriers to commercial development of human(ized) Mabs for prophylaxis and treatment of viral infections. Similar evasion mechanism(s) can exist with human cancers where Mab refractory disease can arise due to downregulation and/or modulation of target epitopes. Our studies on different types of combination immunotherapies will be discussed with emphasis on target diseases, epitope selection, escape mechanisms, and Mab based strategies to prevent escape. Wayne A. Marasco, M.D., Ph.D., Associate Professor of Medicine, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School; Scientific Director, National Foundation for Cancer Research (NFCR) - Center for Therapeutic Antibody Engineering (CTAE) |
| 10:45 | Anti-Human Transferrin Receptor Avidin Fusion Protein: A Molecule Capable of a Two-Pronged Attack Against Malignant Cells through Toxin Delivery and Direct Induction of Apoptosis We have demonstrated that fusing avidin to a mouse/human chimeric IgG3 specific for the human transferrin receptor results in a novel molecule (anti-hTfR IgG3-Av) with intrinsic pro-apoptotic activity against hematopoietic malignant cells. In addition, conjugation of anti-hTfR IgG3-Av with biotinylated toxins significantly enhances the cytotoxic effect of the fusion protein and overcomes resistance. Therefore, the anti-hTfR IgG3-Av is a molecule capable of a two-pronged attack against malignant cells through toxin delivery and direct induction of apoptosis. Manuel L. Penichet, M.D., Ph.D., Assistant Professor, Assistant Professor of Surgery and Immunology, Division of Surgical Oncology, University of California, Los Angeles |
| 11:15 | An Integrated System for Tumor Detection and Targeted Drug Therapy using ADEPT: Preclinical, Clinical Testing and Mathematical Modeling Surgery is the most common treatment for cancers. However, the threat of unrecognized occult disease remains a major challenge for the surgeons. For patients with unresectable and advanced cancer, the standard chemotherapy yields poor response. We intend to develop a system using ADEPT for intraoperative real-time detection of occult tumors and abnormal lymph nodes, as well as to provide a therapeutic regimen for unresectable and advanced cancers in preclinical models, clinical patients, and mathematical modeling. Duxin Sun, Ph.D., Associate Professor, Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan |
| 11:45 | Lunch on Your Own |
| 1:15 | Announcements |
| Session VIII: Mechanism of Antibody Action Revisited | |
| 1:20 | Chairperson's Opening Remarks James D. Marks M.D., Ph.D., Department of Anesthesia and Pharmaceutical Chemistry, Member, Comprehensive Cancer Center, University of California, San Francisco |
| 1:30 | How Antibody Combinations Synergize to Potently Neutralize Botulinum Neurotoxins We have been generating antibodies to botulinum neurotoxin types A, B, and E (BoNTs) as treatments for botulism. Single antibodies do not neutralize BoNTs with the required potency, however combining antibodies leads to extremely potent BoNT neutralization. Using molecular evolution, we have determined the impact of epitope, affinity, and clearance mechanisms on BoNT neutralization for single mAbs and mAb combinations. The results identify the major mechanisms by which antibodies synergize to neutralize toxin and provide a path for development of highly potent recombinant BoNT antitoxin. James D. Marks M.D., Ph.D., Professor of Anesthesia and Pharmaceutical Chemistry, University of California, San Francisco |
| 2:00 | Antibody Mixture Regresses Tumors by a Novel Mechanism Data will be presented on the potent anti-tumor effect exerted by antibody mixture targeting a tumor-associated antigen. In vitro and in vivo experiments have shown a unique mechanism of action leading to sustained growth inhibition of cancer cells and potent efficacy in an aggressive xenograft tumor model. Also, data has been obtained from a tolerability study in Cynomolgus monkeys showing that the antibody mixture is well tolerated. John Haurum M.D, Chief Scientific Officer, Symphogen A/S, Denmark |
| 2:30 | Selection of Anti-CD22 Antibodies Based on Physiology and Epitope A panel of anti-CD22 mAbs were developed and tested. Anti-CD22 mAbs that bind the two NH2-terminal immunoglobulin domains of CD22 and specifically block the interaction of CD22 with its ligand were identified. Our studies have determined that the epitope bound by an anti-CD22 mAb, the interval between doses, target receptor resurfacing, and initial tumor size are critical factors that can predict preclinical efficacy. Joseph M. Tuscano, M.D., Associate Professor of Medicine, University of California Davis Cancer Center |
| 3:00 | Networking Refreshment Break |
| 3:15 | k-ras Mutations and Response to Cetuximab Treatment Abstract to come. David J. Mauro, M.D., Ph.D., Bristol Myers Squibb |
| 3:45 | Fc- and Fcγ Receptor-Dependent Mechanisms in Cell-Targeted Monoclonal Antibody Immunotherapy Evidence supports a role for Fc interactions with low-affinity Fc receptors (FcRs) in the mechanism of action of cell-targeted therapeutic monoclonal antibodies (mAbs). The function of both activating (CD16, CD32A) and inhibitory (CD32B) FcRs can be exploited to modify antibody potency. We have developed strategies that modulate Fc interactions with these receptors or selectively target individual receptors; results from these FcR-targeted interventions are presented that address the role of these receptors in mAb function in vitro and in vivo. Ezio Bonvini, M.D., Senior Vice President, Research, MacroGenics, Inc. |
| 4:15 | Enhancement of Effector Function for Small Modular ImmmunoPharmaceutical (SMIP™) Compounds and Other Protein Therapeutics SMIP™ proteins are single-chain polypeptides manufactured as dimeric products that are approximately one-half the size of monoclonal antibodies. Three SMIP candidates are currently in clinical trials and, as a class, are capable of utilizing effector functions. Given the association between clinical response and ADCC activity, we have developed a technology that allows for significant increases in ADCC activity irrespective of CD16 allelotype via addition of small molecule inhibitors of glycosylation during the bioreactor production process. This technology is applicable to SMIPs and other protein therapeutics. Kendall M. Mohler, Ph.D., Senior Vice President, Research & Development, Trubion Pharmaceuticals |
| 4:45 | Close of Meeting |
footer
Copyright IBC Life Sciences, a part of Informa Life Sciences Group