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4:00 – 6:00 Main Conference Pre-Registration
Monday, APRIL 6
7:00am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Gregory A. Weiss, Ph.D., Associate Professor, Department
of Chemistry, Molecular Biology & Biochemistry, University of California, Irvine
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Keynote Presentations
8:40 Phage-Antibodies for the Masses
George
Smith, Ph.D., Curators Professor of Biological Sciences, University of Missouri
9:10 Healthcare and Biopharmaceuticals: A Patient-
Focused Partnership
 Mark Levick, M.D., Ph.D., Global Head, Biologics Unit, Novartis Institutes for BioMedical Research (NIBR)
Advances in the discovery and development of monoclonal
antibodies and recombinant proteins has resulted in better therapeutic options
for difficult-to-treat diseases. Newer approaches in molecular medicine are
creating novel opportunities for highly targeted therapies, as well as
challenging the more traditional notions of drug development. Successful
biological medicines of the future are likely to be those that deliver better
outcomes for patients.
9:40 Target Validation via VelociGene, Fully HumanAntibody
via VelocImmune
Andrew Murphy, Vice President, Target Discovery, Regeneron Pharmaceuticals Inc.
VelociGene technology has revolutionized our ability to
manipulate the mouse genome allowing for single base pair resolution combined
with mega base capability. We have exploited VelociGene technology to
improve upon earlier generation human antibody mice (“HumAb mice”), by precisely
exchanging 6 mega bases of mouse immune genes with their human immune gene
counter parts. This (VelocImmune) mouse is perhaps the new standard for
generating fully human antibodies against targets of interest, and when combined
with VelociMab technologies provides perhaps the fastest approach for going from
target to fully human antibody in the clinic. The VelocImmune mouse is
part of a technology platform that will generate well over half a billion
dollars in combined licensing and collaboration revenues.
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10:10 Grand Opening Coffee Break in the Exhibit Hall
11:10 Phylomers:
Peptides Derived from Biodiverse Genomes, as Blockers for Intracellular as Well
as Extracellular Targets
Richard Hopkins, Ph.D., Research Manager, Phylogica
Phylomers are a new class of peptide derived from genomic
fragments of biodiverse archael and bacterial species. These peptides can
have high affinities and high specificity for targets, even before affinity
maturation or optimisation which can further increase affinity to the low
nanomolar-picomolar range. Phylomer peptides can also exhibit superior
functional hit-rates, when compared to randomly derived peptides, possibly due
to an evolutionary selection for structure and stability. The majority of
Phylomer peptides are not significantly immunogenic, since their small
size reduces the likelihood of containing MHC epitopes. Synthesised
Phylomers directed against intracellular targets have been shown to function in
animal models of ischemia and wound healing of severe burns, when fused to a
protein transduction domain. Inhaled Phylomers have also shown in vivo
efficacy. Phylomers can block both extracellular and intracellular
targets, which are challenging to block with small molecules or to access with
larger proteins such as antibodies or protein-based scaffolds. Watt PM (2006)
Nature Biotechnology 24 (2):177-83.
11:40 Use of Phage Display to Develop Therapeutic Antibodies for the Treatment of TTP, a Potentially Fatal Autoimmune Thrombotic Disorder
Don Siegel, M.D., Ph.D., Professor and Vice-Chair,
Department of Pathology & Laboratory Medicine, University of Pennsylvania School
of Medicine
Thrombotic thrombocytopenic purpura (TTP) is a potentially
fatal clotting disorder caused by autoantibody inhibition of ADAMTS13, a von
Willebrand Factor-cleaving metalloprotease. Antibody phage display was
used to dissect the pathogenic autoimmune response responsible for this
disorder. Over 100 human anti-ADAMTS13 inhibitory scFv’s have been
isolated from multiple TTP patients and have led to the development of
crossreactive anti-idiotypic reagents and a novel mouse model system in which to
test their potential therapeutic efficacy.
12:10pm Engineering the Filamentous Phage Surface to Alter
its Immunogenicity
Jamie Kathleen Scott, M.D., Ph.D., Professor and Canada
Research Chair in Molecular Immunity, Department of Molecular Biology &
Biochemistry and Faculty of Health Sciences, Simon Fraser University
Our lab has altered the immunogenic properties of the
filamentous phage by altering the biochemical properties of its surface.
We removed the outer domains of the pIII protein of filamentous phage, and also
altered the amino acid sequence of the N-terminal 10 residues of pVIII, thus
changing the surface properties of the phage. Antibodies against wild-type
phage did not cross react with the altered phage, and vice versa. In
addition, for two different peptides, we prepared phage-immunogens that either
display a peptide-target as a recombinant fusion to pVIII, or that comprise a
synthetic version of the peptide chemically conjugated to the phage surface.
These immunogens were compared for their ability to elicit anti-peptide
antibodies, and to “focus” the antibody response against the displayed or
conjugated peptide. The results of these experiments and use of phage as
model immunogens will be discussed.
12:40 Luncheon
Presentation I (Opportunity Available)
1:10
Luncheon Presentation II (Opportunity
Available)
1:40 Break
2:00
Chairperson’s Remarks
K. Dane Wittrup, Ph.D., J.R. Mares Professor, Chemical
Engineering & Bioengineering, Massachusetts Institute of Technology
2:05
Modeling Effector Function
Rene Ott, Ph.D., Lab of Molecular Genetics & Immunology, Rockefeller University
2:35
Complement Proteins And Pathways
Michael C. Carroll, Professor, Pediatrics Pathology,
Harvard Medical School
3:05
Refreshment Break in the Exhibit Hall
3:45 The
Design and Engineering of Fc Heterodimers for the Production of Bispecific
Antibodies
Wei Yan, Ph.D., Principal Scientist, Protein Science,
Amgen Inc.
We have modified the CH3 domain of the Fc interface with a
few selected mutations so the engineered Fc proteins preferentially form
heterodimers. Our engineering approach takes advantage of electrostatic
interactions in promoting Fc heterodimer formation and discouraging Fc
homodimers and does not directly affect the hydrophobic core of the CH3 domain
interface. The successful production of heterodimeric Fc molecules facilitates
the construction of bispecific antibodies and various heterodimeric Fc fusion
proteins.
4:15
Selection of Internalizing Antibodies on Cells for Targeted Drug and Nucleic
Acid Delivery
James D. Marks, M.D., Ph.D., Professor of Anesthesia and
Pharmaceutical Chemistry, Chief of Anesthesia, San Francisco General Hospital,
Vice Chairman, Department of Anesthesia and Perioperative Care, University of
California, San Francisco
We have developed methodologies which allow direct selection
of phage antibody libraries on cells to either known or unknown surface
receptors. The resulting antibodies bind to cell surface receptors and are
internalized, providing a targeting moiety for the intracellular delivery of
drugs or nucleic acids.
4:45
Problem Solving Break-Out Sessions
Selection of Phage Libraries on Cells
Moderator: Don L. Siegel, Ph.D., M.D., Vice-Chair and Professor of Pathology & Laboratory Medicine, Chief, Division of Transfusion Medicine, University of Pennsylvania Medical Center
• Overview of panning methods
• Pros and cons of screening libraries on cells
• Cell-surface panning strategies
Engineering Bi-Specific Antibodies
Moderator: Aaron K. Sato, Ph.D., Senior Director, OncoMed Pharmaceuticals, Inc.
• Overview of different approaches
• Discussion of strengths and weaknesses
• Stability, expression and purification challenges
Expanding Library Diversity
Moderator: Richard W. Wagner, Ph.D., President and Chief Executive Officer, SRU Biosystems, Inc.
• Novel display methods
• Mutagenic strategies
• Big libraries versus iterative affinity maturation
Engineering Approaches to Minimize Aggregation and/or Immunogenicity
Moderator: Gregory A. Weiss, Ph.D., Associate Professor, Department of Chemistry, Molecular Biology & Biochemistry, University of California, Irvine and Jamie Kathleen Scott, M.D., Ph.D., Professor and Canada Research Chair in Molecular Immunity, Department of Molecular Biology & Biochemistry and Faculty of Health Sciences, Simon Fraser University
• Selections for solubility
• Selections for thermostability
• Designing libraries for solubilization
• Screens for thermostability and solubility
Designing Effector Function
Moderator: John R. Desjarlais, Ph.D., Vice President, Research, Xencor, Inc.
• Role of effector function in antibody activity
• Roles of effector cell types
• Technologies for designing effector function
• In vivo and clinical studies
5:45
Networking Cocktail Reception in the Exhibit Hall
6:45 Close
of Day
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