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WEDNESDAY, APRIL 8
7:30am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
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Keynote Presentation
8:40 Mechanisms of Action of Ofatumumab: A Novel Therapeutic Monoclonal Antibody against CD20
 Paul W.H.I. Parren, Senior Vice President, Research & Pre-Clinical Development, Genmab
CD20 monoclonal antibodies represent one of the flagships of immunotherapy as they continue to revolutionize the treatment of B cell cancers and inflammatory diseases. Their mechanisms of action have been investigated in detail and this knowledge has been at the basis of the development of ofatumumab. A key mechanism of CD20 antibodies is the killing of target cells via the recruitment and activation of complement. Ofatumumab is a unique human monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule and displays an exceptional efficacy in recruiting complement and inducing specific cell lysis. Novel insights into the mechanisms of tumor cell killing by ofatumumab and its efficacy in a pivotal clinical trial in B-CLL will be discussed.
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9:10 Constant Region Effects on Antibody Specificity and Affinity
Arturo Casadevall, M.D., Ph.D., Chair, Department of Microbiology & Immunology, Albert Einstein College of Medicine
Current dogma views immunoglobulins as bifunctional molecules where the variable and constant region function essentially independently. In recent years our laboratory has obtained evidence that variable region identical antibodies differing in constant region manifest different binding characteristics for univalent ligands indicating the existence of constant region effects on specificity and affinity. The results have important implications for our views of antibody function, variable region and isotype restriction, and idiotype responses.
9:40 Variable Lymphocyte Receptors as Natural Non-Ig Antigen-Binding Proteins
Roy A. Mariuzza, Ph.D., Center for Advanced Research in BioTechnology, University of Maryland BioTechnology Institute
To date, the search for alternatives to antibodies has focused on synthetic binding scaffolds. However, the only natural antigen receptors that are not Ig-based are the variable lymphocyte receptors (VLRs) of lamprey and hagfish. X-ray crystallographic analysis of the complex between an anti-protein VLR, isolated by yeast surface display, and its protein antigen has revealed the structural basis for recognition by these novel leucine-rich repeat-based receptors, and its relationship to recognition by conventional antibodies.
10:10 Coffee Break in the Exhibit Hall
11:10 The Human Autoantigenome and Predictive Autoantibodies
11:40 High Affinity Lamprey Antibodies
Zeev Pancer, Ph.D., Assistant Professor, UMD The antigen receptors of jawless vertebrates are called variable lymphocyte receptors (VLR), and consist of highly diverse leucine-rich repeats. The potential diversity of the sea lamprey VLR repertoire can exceed 1014 different receptors. Yeast surface displayed VLRs from naïve or immunized animals can be used to select high affinity and high avidity antigen-specific binders. VLRs that bind nanomolar concentrations of protein and carbohydrate ligands were isolated and characterized. VLRs are amenable to in vitro mutagenesis to increase affinity for the ligand. The evolutionary oldest antibodies will soon take a central place in the biotechnology arena.
Sponsored by
 12:10pm Luncheon Presentation I
Slonomics® – A Unique Technology for the Generation of Highly Designed Gene Libraries
Thomas Waldmann, Ph.D., Science and Technology Applications, Sloning BioTechnology
Sloning specializes in the synthesis of highly genetically diverse and precise customized gene libraries for protein engineering up to 1011 different variants. Unlike traditional methods that rely on single-stranded oligonucleotides, the patented Slonomics® technology uses a set of double-stranded DNA triplets as universal building blocks. Predefined triplets represent all possible sequence combinations required to synthesize any gene – ‘one codon at a time’. For library production, multiple codons can be introduced in parallel during the synthesis of a gene construct at any desired sequence position. The absence of functional bias and the ability to select and precisely control delivery up to 20 specific codons per sequence position and at any ratio results in exceptionally high quality libraries containing the complete set of desired mutants. In this talk, new technology advancements regarding the random integration of codons into gene sequences and practical examples for improved screening success with SlonoMax™ mutant libraries will be presented.
12:40 Luncheon Presentation II (Opportunity Available)
1:10 Break
1:30 pm Chairperson’s Remarks
Lutz Jermutus, Ph.D., MedImmune
1:35 VB6-845: An Immunotoxin Optimized for Clinical Development
Jeannick Cizeau, Ph.D., Director, Research, Viventia Biotech Inc.
Immunotoxins are comprised of a cell-targeting domain linked to a bacterial or plant-derived cytotoxic payload and represent a highly potent alternative to conventional anti-cancer agents. However, most cytotoxic payloads are inherently immunogenic and thus have limited use therapeutically. VB6-845 is a recombinant fusion protein consisting of a tumor-targeting Fab specific for epithelial cell adhesion molecule (EpCAM) linked to bouganin, a plant-derived ribosome-inactivating protein that prevents protein synthesis leading to cell death. The bouganin moiety was de-immunized through the identification and removal of T cell epitopes. The molecular design, purification strategy, biological characterization, and preclinical experience will be presented.
2:05 Engineering Antibody Species Cross-Reactivity
David Lowe, Ph.D., Head of Display
Technology, RI & A, Medimmune
The development of antibodies as therapeutics for human diseases involves pre-clinical testing in vivo for pharmacological and toxicological assessment. In order to expedite this process, cross-reactivity to non-human homologues of the target antigen is highly desirable. We report here a case-study exemplifying an antibody optimisation project which was designed to both improve affinity to the human antigen, and additionally to introduce high affinity binding to pre-clinical animal species.
Sponsored by
2:35
Using the Octet QK as a Rapid Screening Platform
Brian Miller, Ph.D., Biogen-Idec
In this presentation I will demonstrate how we’ve incorporated the ForteBio Octet QK into our protein engineering platform. We routinely screen protein libraries expressed in E. Coli for molecules displaying improved biophysical properties, and the Octet allows us to quickly triage based on affinity measurments on crude samples. This allows us to winnow out molecules which have reduced binding to their targets. In addition, we use the Octet in epitope mapping experiments where we can express large numbers of variant antigens in either E. Coli or yeast systems and determine which substitutions affect antibody affinity, again without having to scale-up or purify the antigens. In programs where we have multiple candidate Mab’s or Fab’s, the Octet allows us to rapidly preform cross blocking assays in order to group the antibodies in to similar bins. Finally, the Octet has become an indispensible tool for determinng antibody titer for research scale production.
2:50 Sponsored Presentation (Opportunity Available)
3:05 Refreshment Break in the Exhibit Hall
3:50 Problem Solving Breakout Sessions
Expression of Therapeutic Antibodies for Pre-Clinical Testing
Moderator: Gerard Casperson, Ph.D., Pfizer, Inc.
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Expression systems/cell lines
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Showing comparability from
different cell lines
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Dealing with difficult to
express/purify antibodies
4:50 Networking Cocktail Reception in the Exhibit Hall
6:00 Close of Day
For questions or suggestions about the meeting, please contact:
Elizabeth Lamb
Cambridge Healthtech Institute
Phone: 207-493-7874
email: elamb@healthtech.com
For sponsorship and exhibit information, contact:
Carol Dinerstein
Phone: 781-972-5471
email: dinerstein@healthtech.com
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