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| 7:30-8:15
Breakfast Workshop |
Sponsored by
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| The Expanding Role of Protein
Interaction Analysis in Biotherapeutic Development - from Discovery to
GxP-Regulated Environments Including Quality Control |
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Fredrik Sundberg,
Director Global Pharmaceutical Market Development, Biacore AB, Uppsala,
Sweden
This presentation reviews the role of protein interaction analysis
at key stages throughout pharmaceutical development and production - from
discovery to final product quality control. Examples include:
• Reducing
costs in biotherapeutic development by early kinetic screening for confident
selection of the best antibodies
• Improving safety and efficacy by reliable
detection and characterization of immunogenic responses during clinical
trials
• Efficient process control by monitoring fermentation and downstream
protein purification
• Rapid drug substance characterization and product
release testing Biacore systems provide unique, comprehensive protein
interaction analysis based on a well-established technology platform. Highest
quality data on specificity, affinity and kinetics, as well as concentration
measurements, support critical decisions at every stage from candidate selection
to product release. Cost-efficient strategies for meeting current GLP/GCP/GMP
requirements will also be discussed. |
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Drug Delivery
8:15 Comments by Session
Chairperson
Dr. Christine Mahoney, Surface and Microanalysis Science
Division, NIST
8:20 The Future of Protein and Peptide Drug
Delivery
Dr. John S. Patton, Founder and CSO, Nektar
Therapeutics
8:50 3-D Characterization of Polymeric
Biomaterials and Model Drug Delivery Systems with Cluster Secondary Ion Mass
Spectrometry (SIMS)
Dr. Christine Mahoney, Surface and Microanalysis
Science Division, NIST
Secondary Ion Mass Spectrometry (SIMS) has proven
to be a useful tool in the analysis of polymeric biomaterials and drug delivery
systems, where the distribution of both drugs and excipients within a drug
delivery system can be determined with a high degree of spatial resolution
(<1mm) and sensitivity (as low as ppm (mg/g)) when compared to other
analytical methods such as Raman and IR spectroscopies. With the advent of
cluster primary ion sources in SIMS (using molecular beams such SF5+ as opposed
to monatomic beams such as Ar+) significant improvements in molecular signals
have resulted. In addition, depth profiling through organic and polymeric
materials is now achievable with depth resolutions on the order of 1-10 nm. Here
we report the ongoing research efforts at NIST to further develop cluster SIMS
as a tool for biomaterial and drug delivery characterization. We have already
illustrated the ability to depth profile in model polylactic acid (PLA) based
drug delivery systems using cluster SIMS. More recently, we have been able to
successfully quantify the preferential segregation in polylactic acid /
polyethylene glycol (PLA/PEG) blends as well as determine the in-depth
distribution of acetamidophenol doped PLA films as a function of increasing
degradation time. It is our goal to continue to develop this technique as a tool
for quality control and drug development purposes.
9:20 Bifunctional Chelants for Protein-Based
Therapeutic Radiopharmaceuticals
Dr. Keith Frank, Development Leader,
Dowpharma, The Dow Chemical Company
Proteins can be used to target
therapeutic radiopharmaceuticals to particular sites in the body. Metallic
radioisotopes have many advantages in these applications, but require the use of
a bifunctional chelating agent to attach the metal ion to the protein. The
ability of chelants to form stable metal complexes in vivo is critical to their
role in delivering the radiometal safely and effectively to the
target.
9:50 The Plexis™ Drug Delivery System: Potential
for Sustained Release of Proteins and Peptides
Dr. Thomas J. Smith,
Chairman & Chief Scientific Officer, Auritec Pharmaceuticals
Inc.
Historically, there have been two successful approaches to
polymer-based sustained release parenteral drug delivery: implantable membrane
systems such as the Norplant® or Vitrasert®’ and injectable biodegradable
systems such as for Eligard®. However, each approach has its limitations, which
keep it from being more broadly useful. We have combined the best features of
each of these approaches and eliminated the major problems in our Plexis™
delivery platform, which is membrane-based, biodegradable and injectable.
Features of the platform such as particle production and polymer lamination that
make it suitable for the delivery of peptides and proteins will be
described.
10:20 Coffee Break, Poster and Exhibit
Viewing
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12:30 Luncheon
Technology Workshop
(Limited Seating)
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Sponsored by
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Improving the Delivery and
Pharmacokinetics of Therapeutic Proteins by Increased Resistance to
Proteolysis
Dr. Manuel Vega, CEO Nautilus Biotech
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| A short half-life in serum,
in tissues or, most strikingly, in the intestine, is a common trait of most
proteins being used or developed to become therapeutic products. Proteolysis is
increasingly seen as playing a significant role in the clearance of therapeutic
proteins. Specific single point mutations can render proteins highly resistant
to proteolysis and as a consequence, lead to extended survival in blood, tissues
and the intestine. Design of novel molecules resistant to proteolysis as a
strategy to create next-generation protein products with improved
pharmacological profiles and suitability for oral delivery will be
discussed. |
Engineering Enhanced
Delivery
2:00 Comments by Session
Chairperson
2:05 Keynote
Introduction
Dr. Stefan Löfås, Vice President and Chief Scientific
Officer, Biacore AB
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| 2:15
Keynote Presentation |
 |
"Optimizing" the Future For
Biotechnology Therapies: The Key Role of Protein Engineering
Dr.
Thomas F. Bumol, Vice President, Biotechnology Discovery Research, Lilly
Research Laboratories & Applied Molecular Evolution, a Subsidiary of
Eli Lilly and Company |
| Biotechnology is playing an
increasing role in truly innovative therapeutics across many diseases. Peptides,
proteins and monoclonal antibodies provide the basis of substantial
opportunities for lead discovery in physiological/disease pathways at the
ligand-cell surface receptor interface and other specific protein-protein
interactions. These leads however need substantial optimization to achieve the
ideal therapeutic index (maximum efficacy with minimal toxicity),
pharmacokinetic /pharmacodynamic performance, low immunogenicity and
compatibility with a commercially viable development path which could include
novel formulations or alternative delivery strategies for patient convenience.
Our group is extensively using protein engineering to address these challenges
in building a pipeline of first and second generation therapeutics. Examples
will be discussed regarding lead discovery and lead optimization with protein
engineering, along with strategies for the rapid evaluation of these constructs
in clinical
trials. | |
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3:05 Fc Fusion Proteins with Enhanced
Pharmacokinetics and Biological Activity
Dr. Alan Bitonti, Vice
President, Research & Development, Syntonix Pharmaceuticals
Syntonix
has explored the use of Fc fusion proteins to improve pharmacokinetics and to
enable pulmonary delivery of a broad range of therapeutic proteins and peptides.
We created a new class of "monomeric" Fc fusion proteins to increase the
pulmonary absorption, circulating half-life and biological potency compared to
the traditional dimeric Fc fusion proteins. Several examples of these enhanced
"monomeric" Fc fusions will be presented.
3:35 Refreshment Break, Poster and
Exhibit Viewing
5:00 PROMAXX Protein and Peptide
Microsphere Drug Delivery Technology
Dr. Terrence L. Scott, Senior
Director, Scientific Affairs, Epic Therapeutics, Inc., A Wholly-Owned Subsidiary
of Baxter Healthcare Corporation
PROMAXX technology is a novel method for
the fabrication of microspheres for drug delivery. The method has been applied
to labile proteins and peptides and demonstrated to produce microspheres of
0.2-3 microns with narrow particle size distributions. The microsphere
fabrication technology is performed under conditions that maintain the stability
of labile therapeutic molecules. The microspheres may be delivered by various
routes of administration and also be used as a platform material for the
subsequent application of secondary processes. These additional processes are
focused on providing targeting, altered release kinetics or other
therapeutically useful attributes to the microspheres. This technology provides
significant new opportunities for fabrication of unique product formulations
with engineered enhanced delivery of therapeutic proteins and
peptides.
5:30 Developing Novel Therapeutics by Targeting Protein-Protein
Interactions
Dr. A. Donny Strosberg, Professor, Department of
Infectology, The Scripps Research Institute-Florida
Protein-protein
interactions constitute a largely untapped source of targets for developing
novel therapeutics. Increasingly reliable technologies for identifying the
actual protein domains involved in these interactions have started to yield
considerable information useful for deriving peptides that may serve as
proof-of-principle dominant-negative antagonists of the interacting pair of
proteins or one of the two partners. Use of cargo peptides or appropriate vector
systems facilitate intracellular delivery. Small molecular weight functional
mimics of these peptides can be obtained by high-throughput screening or
rational design and display agonist or antagonist activity on the interacting
proteins in solution, on solid surfaces and finally in cells.
6:00 Close of Day |
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