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Overview | Short
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7:00am – 6:00pm Registration Open
7:30 Breakfast Workshop (Sponsorship Available)
DELIVERY INNOVATIONS
8:15 Chairperson’s Remarks
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Featured Speaker
8:20 Transepithelial Delivery of Peptide and Protein Therapeutics
Henry “Rick” Costantino, Ph.D., Founder, Costantino Consulting
Transepithelial administration as a non-invasive delivery route continues to generate interest. For instance, the nasal mucosal epithelium offers advantages for delivery such as a large surface and rapid drug onset. Extent of transepithelial permeation depends on drug properties, and high-molecular-weight peptides and proteins have relatively poor inherent permeation characteristics. To overcome the challenge, various permeation enhancers are being explored to achieve safe systemic delivery of peptides and proteins via the intranasal route.
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8:50 Clinical Development of an Oral Calcitonin Tablet for Osteoporosis
Nozer M. Mehta, Ph.D., Vice President, Biological Research and Development, Unigene Labs Inc.
We have developed an oral tablet formulation with excipients that overcome many of the physiological barriers to peptide oral delivery. The enteric coating permits passage of the tablet through the stomach into the small intestine. The oral delivery of several intact, biologically active peptides has been confirmed by measuring pharmacodynamic markers and/or blood levels using a dual antibody sandwich ELISA. Recent improvements in the oral delivery technology have significantly reduced the variability in the amount of peptide absorbed. Results from an exploratory clinical study with an oral formulation of salmon calcitonin showed a consistent pharmacodynamic response in all subjects as measured by a decrease in CTX-1, a marker for bone resorption.
9:20 Human Bak Proteoliposome as a Magic Bullet for Treating Glioblastoma
Jean-Luc Lenormand, Ph.D., Team Leader, HumProTher Laboratory, Equipe TheREx, University Joseph Fourier
Recombinant proteoliposomes containing proapoptotic Bak protein have been produced using an optimized cell-free expression system. We developed a one-step production and purification protocol for the Bak-proteoliposomes. These proteoliposomes have been used as delivery systems for the transfer of Bak membrane protein into different cancer cell lines and in vivo in mice bearing glioblastoma tumors. We demonstrate that these proapoptotic proteoliposomes are capable to specifically induce apoptosis in transduced cells and induce tumor regression and survival in mice. The recombinant proapoptotic proteoliposome is a totally new approach to achieving delivery of therapeutic membrane proteins.
9:50 Coffee Break in the Exhibit Hall
INNOVATING SPECIFICITY
10:45 Vascular Targeting of Therapeutic Prodrug Fusion Proteins
Vladimir Muzykantov, Ph.D., Associate Professor, Pharmacology, University of Pennsylvania
We have identified a series of target determinants on vascular endothelium and blood cells, useful for anchoring recombinant protein pro-drugs fused with scFv of monoclonal antibodies safely binding to these determinants. Animal studies show superior therapeutic and profilactic profile of these fusions in models of inflammation, thrombosis and ischemia.
11:15 Probodies: Site-Activated Antibody Therapeutics
Nancy Stagliano, Ph.D., Chief Executive Officer, CytomX
Antibody-based therapies have proven to be effective treatments for some cancers and inflammatory conditions. However, in some cases, toxicities due to broad target expression have limited their therapeutic effectiveness. Increased targeting of antibody to the disease site would reduce systemic mechanism-based toxicities and lead to broader therapeutic utility. Here we describe a method for producing a "ProBody," in which specificity is achieved by masking its antibody function until it is activated by tumor or inflammatory site-specific enzymes. This method is generally applicable to all antibodies to increase target specificity and therapeutic potential.
11:45 Spatially Addressed Combinatorial Protein Libraries for Antibody Drug Discovery
Vaughn Smider, M.D., Ph.D., Assistant Professor, Molecular Biology, The Scripps Research Institute
Antibody discovery is typically accomplished using a display technology (phage, yeast, ribosome, etc.) whereby the gene encoding the antibody fragment and the fragment itself is physically linked. Large pools of displayed antibody fragments are then selected to identify those with the highest affinity to a target of interest. These methods contrast with small-molecule discovery, for which combinatorial chemistry libraries are produced in a spatially addressed format, then screened on targets or even in functional cell-based assays. We have developed a high-throughput scalable methodology to produce highly pure proteins in a spatially addressed format. Libraries of recombinant antibodies have been produced and screened in unique assays not amenable to traditional biologic discovery technology. This paradigm shift in discovery format for biologic discovery could enable identification of unique molecules against new targets, opening certain target classes to antibody therapeutics.
12:15pm Close of Morning Session
12:30 Luncheon Workshop (Sponsorship Available)
or Lunch on your Own
CREATING THE FUTURE OF PROTEIN THERAPEUTICS
2:00 Chairperson’s Remarks
2:05 Improving Antibody Half-life Through Fc Engineering
Aaron Chamberlain, Ph.D., Lead Scientist, Protein Engineering, Xencor Inc.
The antibody Fc domain interacts with a variety of cell surface receptors, including Fc gamma receptors and the neonatal Fc receptor (FcRn), which mediates the long in vivo half-life of antibodies by protecting them from lysosomal degradation. Here, we demonstrate that engineering the Fc domain for higher FcRn affinity can enhance the half-lives of human antibodies in mice and nonhuman primates. Extended half-life affords a range of appealing features, such as less frequent dosing, improved cost of goods, better control over peak-to-trough concentrations, and alternative formulations.
2:35 The Antigenic Wall and a New Technology for Deriving New Therapeutic Monoclonal Antibodies
Peter L. Nara, D.V.M., Ph.D., President & CEO, Biological Mimetics, Inc.
Deriving new monoclonal antibodies for therapeutics and diagnostics to important human cancer and infectious disease targets requires some knowledge about the identification of the protective antigen(s). Most importantly however, is once this target is identified the process of inducing and selecting monoclonal antibodies against it are in general a completely uncontrolled process and dependent on the natural immunogenicity and immunodominance of the molecule. Developing and applying new technologies such as “Immune Refocusing” to specifically control and reverse the natural antigenic hierarchy of the molecule greatly enhances both the rational approach, efficiency and cost of deriving antibodies to new epitopes that would have under natural circumstances been unavailable to the process.
3:05 Novel
Approaches for Affecting Transcriptional Regulators for Therapeutic
Purposes
William Garland, Ph.D., CEO, Angiogenex Inc.
Robert Benezra, Ph.D., Member, Cancer Biology & Genetics Program,
Memorial Sloan Kettering Cancer Center
Cancer is a disease of gene Dysregulation. For this
reason, modulation of transcriptional regulators is a very active area of
cancer research. However, affecting transcriptional regulators for
therapeutic purposes at either the gene or protein level is a very
challenging goal requiring novel approaches, e.g., see Henke E. et al.,
Peptide-conjugated antisense oligonucleotides for targeted inhibition of a
transcriptional regulator in vivo, Nature Biotechnology 2008; 26: 91-100.
Several novel approaches will be provided and discussed in this
presentation.
3:35 Measuring
the Bioprocess : From Cloning to Product QA/QC in a Single System
Stuart Hassard, Ph.D., Co-Founder
and Head Biologist, deltaDOT Ltd. |
Sponsored by |
Label
Free Intrinsic Imaging (LFII™) is a combination of multi-pixel
detection, advanced signal processing and high performance capillary
electrophoresis. This combination removes the need for any labelling
step in the analysis, relying instead on of the absorption of energy
at specific wavelenghts, by a range of biological and chemical
analytes. This means there is no dependence of analysis on a
specific label/detector technology and the system can analyse
nucleic acids, proteins, viruses and small molecules, including
amino acids. The linear detectors are configured so that separating
molecules traverse the 512 pixels of the multipixel detector in a
time dependent fashion allowing a unique space-time correlation to
be acquired. Each pixel is also set to acquire data at 10-20 Hertz,
meaning thousands of data points are acquired for each analysis.
This combination allows a dramatic decrease in noise, increased
resolution and reproducibility as well as inherent quantification.
The LFII ™ instrument PEREGRINE can operate in a wide variety of
capillary electrophoresis modes, such as CZE and CGE. This, coupled
with the universal analysis afforded by our Label Free Intrinsic
Imaging technology, allows a very wide variety of analyses to be
performed on the same instrument. This same LFII ™ instrument can
be used to analyse; cloning steps in the genetic engineering of gene
into vectors, the titre of e.g. Baculoviral expression systems, the
condition and components of the bioreactor media, the expression
level of the target protein and the purification stages to the final
QA/QC steps. the system is small and adaptable enough to be sited
proximal to the bioreactor and allow point of operation analysis.
The data acquisition and handling for all these molecule analyses
follows the same format and workflow allowing the modelling of a
fully integrated and common data format. Use of the same data format
allows the projection of a bias free system for scoping a workflow,
real-time analysis and control of a manufacturing process through on
demand measurements (i.e., during processing) of essential quality
and performance parameters in-process components and processes with
the goal of ensuring final product quality. |
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3:50 Refreshment Break in the Exhibit Hall
4:30 BuzZ Sessions -
Moderated Small-group Breakout Discussions
Have a topic idea? Please send all topic suggestions to mabrown@healthtech.com
Click
here for a listing of BuzZ Session topics
5:30 Close of Day
Overview | Short
Courses | Day 1 | Day
2 | Day 3 (Joint Session) | Download
Brochure
For more information, please contact:
Mary Ruberry, Conference Director
Phone: 781-972-5421
E-mail: mruberry@healthtech.com
For exhibit and sponsorship information, please contact:
Suzanne Carroll, Manager-Business
Development
Phone: 781-972-5452
E-mail: scarroll@healthtech.com
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