Sponsoring Society: Speakers From: Eisai Research Institute Eli Lilly and Company Genentech, Inc. Novartis Pharma AG Massachusetts Institute of Technology McGill University National Cancer Institute University of Manitoba University of New Hampshire Genzyme Corporation GlycoFi, Inc. Glycominds Ltd. Glygen Corporation Proteome Systems Ltd. Millennium Pharmaceuticals, Inc. Momenta Pharmaceuticals, Inc. Neose Technologies, Inc. Optimer Pharmaceuticals, Inc.
	Sponsoring Publications: Carbohydrate Research Glycoconjugate Journal High Content Screening Advances in Lead Optimization Web Partners: BioCompare GenomicsProteomics.net
Dr. Prabhat Arya, Chemical Biology Program, Steacie Institute for Molecular Sciences, National Research Council of Canada Dr. Tillman Gerngross, GlycoFi, Inc. Dr. Ram Sasisekharan, Massachusetts Institute of Technology Dr. Frank Schweizer, The University of Manitoba Dr. Peter H. Seeberger, Massachusetts Institute of Technology Dr. Ashok K. Shukla, Glygen Corporation Dr. Ganesh Venkataraman, Momenta Pharmaceuticals Inc.

Monday, May 5

8:00-9:00am
Registration and Light Continental Breakfast

9:00-12:00 Short Course Glycomics: Technological Breakthroughs Pave the Way to the Next Wave in Biotechnology Dr. Peter H. Seeberger, Firmenich Associate Professor of Chemistry, Massachusetts Institute of Technology New platform technologies offer unique opportunities to exploit carbohydrates and glycoconjugates for drug discovery. Automated synthesis of oligosaccharides allows for rapid access to structures for drug discovery and lead optimization as well as for the procurement of standards for sequencing. Carbohydrate sequencing has rapidly progressed in the past few years as well. Using synthesis and sequencing, a detailed picture of the structure-function relationship for carbohydrates is emerging. The functional biology of carbohydrates is better understood thanks to technological advances. Participants can expect to obtain information about the following: (1) technology platforms-automated synthesis of oligosaccharides and advances in carbohydrate sequencing, (2) carbohydrate arrays for high-throughput screening, and (3) examples for the use of glycomics in biotechnology.

12:00-1:25
Conference Registration/Lunch on your own
Technology workshop (sponsorship available)

 

High-Throughput Methods for Carbohydrate Synthesis and Analysis

1:25-1:35
Chairperson's Welcome and Opening Address
Dr. Craig Karr, High Throughput Biochemistry, Millennium Pharmaceuticals, Inc.

1:35-2:05
Sugar-Amino Acid Hybrids: A New Structural Motif for Presenting Drug Pharmacophores
Dr. Frank Schweizer, Assistant Professor of Chemistry, Department of Chemistry, University of Manitoba
Sugar-Amino Acid Hybrids (SAAHs) are a class of molecules that combine the structural features of carbohydrates and amino acids. Over the years, a variety of naturally occurring SAAHs have been found to display important biological activity. This presentation will describe our efforts in the design and synthesis of unnatural SAAHs by means of combinatorial synthesis.

2:05-2:35
Synthetic TLR-4 Agonists: Their Potential as Vaccine Adjuvants
Dr. Lynn Hawkins, Principal Scientist, Eisai Research Institute
This presentation will provide the history and current progress of Eisai's lipopolysaccharide- or LPS-like agonists that are being developed as vaccine adjuvants. These novel, synthetic phospholipid dimers have been shown to specifically activate human monocytes via the toll-like receptor-4 (TLR-4) causing the release of inflammatory mediators. Discussion of the physicochemical properties and biological impact of these agents will be included.

2:35-3:05
ABCs of Functional Glycomics: Abstruse, Bastardly, and Compelling
Dr. Vernon Reinhold, Center for Structural Biology, University of New Hampshire
Molecular glycosylation imparts profound biological activity to a host of platform structures involved in non-covalent, adhesive cell-cell, and matrix interactions. These surface structures vary in development, differentiation, cell activation and senescence. The pleiotrophic nature of glycosylation means that modulation at any point in its biosynthetic pathway imparts the outcome to a host of structures and ultimately tissues. The single gene product, target, and consequence of earlier metabolic thinking is now multiple glycomers, interactions, and targets in a cooperative outcome defined as systems biology. This basic reality imparts huge challenges in determining structure, synthesis, and eventually drug design. Recent structure-function findings will be presented.

3:05-3:45
Refreshment Break (in the Exhibit Hall)

Emerging Company Showcase 3:45-4:10 OPopS™ for Drug Discovery Dr. Yoshi Ichikawa, Director of Chemistry Technology, Optimer Pharmaceuticals, Inc. PopS™ is Optimer's breakthrough glycosylation technology that enables efficient glyconjugation and oligosaccharide synthesis. Synthetic procedures are performed, in a one-pot manner, using preassembled sugar building blocks (BBs) that are algorithm-selected by OptiMer software based on structure and reactivity. Our wide selection of BBs is suitable for systematic sugar-based medicinal chemistry and creating carbohydrate diversity. Optimer's successful application of OPopS™ technology as a medicinal chemistry approach for antimicrobials, cancer vaccines, and glycoarrays will be described. 4:10-4:35 Sequencing and SAR of Complex Polysaccharides: Applications for Creation of Designer Molecules Dr. Ganesh Venkataraman, Vice President Technology, Momenta Pharmaceuticals Inc. Complex polysaccharides, along with DNA/RNA and proteins, are important biological information carriers , that coordinate processes at the cell, tissue, and organ level. Due to their functional and structural complexity (orders of magnitude greater than that of either DNA or proteins), underatnding structure/function relationships for complex polysaccharides has been challenging. Novel methods for sequencing and structural profiling of complex polysaccharides will be addressed in this talk. Furthermore, the use of bioinformatics based approaches to handle the microheterogeneity associated with sugar-based molecules will be addressed. Finally, examples of use of these analytical methods towards predictive modeling and design of novel molecules with attractive properties will be discussed. 4:35-5:00 Automated Analysis of Sugar Structures on Glycoproteins Dr. Nicolle Packer, Executive Vice President, Proteome Systems Ltd. The discovery of the significance of carbohydrate modifications is dependent upon being able to easily and routinely analyze the sugar structures on both naturally occurring and recombinant proteins. Using mass spectrometry coupled with our proprietary database of glycan structures we have developed techniques that enable the automated analysis of glycoprotein carbohydrate structures. These methodologies are applied to our discovery and diagnostic programs in respiratory disease, cancer, and aging. 5:00-5:25 Mucin : A Delivery Vector for Biomolecules Dr. Ashok K. Shukla, President, Glygen Corp. Glycoconjugates are essential components of cellular signaling, specificity and interaction and specific glycoconjugates are potentially optimal tools for gene delivery. Currently available gene delivery methods present significant shortcomings for successful gene therapy. For example, virus-based vectors introduce the risk of generating an immune response in a patient and cationic lipids present toxicity risks to the patient. In contrast, the Mucin-DNA or Mucin- Biomolecule complex, the first gene delivery tool of its kind, can be derived from natural sources and targeted to individual cell types with high specificity, thus posing no risk of side effects and maximizing the qualities desired in an optimal gene delivery vector.

5:25
Close of Day One

Tuesday, May 6

7:30-8:15am
Light Continental Breakfast
Technology workshop (sponsorship available)

Carbohydrate-Based Therapeutics

8:30-8:40
Chairperson's Remarks

8:40-9:10
Emerging Views of Heparan Sulfate Glycosaminoglycan Structure/Activity Relationships
Dr. Ram Sasisekharan, Associate Professor of Biological Engineering, Biological Engineering Division, Center for Biomedical Engineering, Center for Environmental Health Sciences, Massachusetts Institute of Technology
Heparin/Heparan sulfate glycosaminoglycans [HSGAGs] are an important subset of the family of complex polysaccharides that represent the third major class of biopolymer, along with polynucleic acids and polypeptides. However, the importance of HSGAGs in biological processes is under appreciated because of a lack of effective molecular tools to correlate structure with function. It is only recently that significant strides have been made in understanding HSGAG biosynthesis, structure and function. Such advances now create possibilities for intervening in numerous clinical situations, creating much needed novel therapies for a variety of pathophysiological conditions including atherosclerosis, thromboembolic disorders, unstable angina and cancer.

9:10-9:40
Drug Conjugates of Sodium Hyaluronan
Dr. Robert J. Miller, Senior Scientific Director, Biomaterials and Surgical Products, Genzyme Corporation
Sodium hyaluronan is a polyanionic polysaccharide found in the extracellular matrix, synovial fluid, and vitreous humor. HA binds to and transports into cells containing CD44. Drug conjugates to HA can serve as prodrugs for sustained release and targeting to CD44 containing cells.

9:40-10:10
Glyconanotechnology: Construction and Properties of Sugar/Peptide-Bearing Nanoparticles
Dr. Joseph Barchi Jr., Senior Scientist, Medicinal Chemistry, National Cancer Institute
One consequence of the aberrant expression of tumor cell surface glycans is a non-self-immune response to these truncated (O-linked) or elongated (N-linked) structures. This response may be directed to the carbohydrate alone, the underlying peptide sequence, or a combination of the two (glycopeptide). We are synthesizing various multivalent carbohydrate and glycopeptide nanoparticles containing immunologically relevant tumor-associated antigens to define the precise structures needed to elicit powerful immune responses and use these as potential leads in the development of tumor vaccines.

10:10-10:40
Refreshment Break (in the Exhibit Hall)

10:40-11:10
Novel Glycodendrimers Self-Assemble to Nanoparticles That Function as Polyvalent Ligands in Vitro and in Vivo
Dr. Gebhard Thoma, Scientific Expert, Novartis Pharma AG
A novel aspect of supramolecular chemistry is the formation of non-covalent nanoparticles by small molecules comprising both a ligand and a self-assembling moiety. These particles-but not the individual molecules-function as highly potent polyvalent receptor blockers allowing for the control of physiologically relevant polyvalent interactions. Synthesis, characterization, and biological evaluation will be discussed.

11:10-11:40
Neoglycopeptides by High-Throughput Approaches: Small-Molecule Probes for Chemical Glycobiology
Dr. Prabhat Arya, National Research Council of Canada; and Adjunct Professor, Department of Chemistry, University of Ottawa, and Biochemistry Department, McGill University
Due to the involvement of carbohydrates and carbohydrate conjugates in several disease states-i.e., inflammation, microbial infections, cancer, etc.-there is a growing demand for understanding their functions at the molecular level. This could then further lead into the design and synthesis of small-molecule carbohydrate mimics as a starting point in developing new therapeutics. One of the major limitations is the rapid access to relevant small molecules that could play critical roles in understanding carbohydrate/carbohydrate conjugate mediated biological processes. This talk will feature our efforts on several fronts in developing high-throughput synthesis of artificial glycopeptides. In few cases these derivatives have been synthesized in a fully automated manner.

11:40-12:10
Synthetic and Biotechnology Derived Glycomimetics: Impact on Antithrombotic Drug Development
Dr. Jawed Fareed, Professor of Pathology and Pharmacology, Director, Hemostasis & Thrombosis Research Laboratories' Loyola University Medical Center
During the past 50 years heparins have made a major impact on the management of thrombotic disorders. Chemically modified heparins and heparin- related glycosaminoglycans such as the Dermatan, heparans, and chondroitin sulfate derivatives have also been used in the overall measurement of thrombotic and vascular disorders. More recently synthetic and biotechnology-based approaches have been used to design and produce glycomimetics. These agents are free of viral contaminants and can be molecularly modified to develop agents with predictable actions. This presentation will review the conventional and newer approaches in the design and development of various glycomimetics with particular reference to their use of antithrombotic agents. Specific examples will include heparin-derived oligosaccharides, pentosann polysulfate, K5 derivatives, and sulfated pentomannan.

12:10-12:40 Antiglycan Antibodies as Biomarkers Dr. Nir Dotan, President and Chief Technical Officer, Glycominds Ltd. Glycominds has developed the GlycoChip®, a unique complex carbohydrate microarray technology. This technology is being utilized to profile antiglycan antibodies from population sera. In the presentation we will demonstrate the suitability of this approach for finding antiglycan antibodies as biomarkers to differentiate between patient populations.

12:40-1:40
Luncheon (sponsored by Cambridge Healthtech Institute)

1:40-2:00
Dessert (in the Exhibit Hall)

 

Glycosylation of Recombinant Proteins

2:00-2:10 Chairperson's Remarks

2:10-2:40
N-linked Glycosylation: Friend or Foe
Dr. Tim Edmunds, Vice President, Therapeutic Protein Research, Genzyme
N-linked glycans are essential for stabilizing and maintaining the activity of many recombinant proteins. The type of glycan structures present can affect plasma half life as well as receptor binding properties. The oligosaccharide profile can make the difference between a highly successful product and an ineffective molecule. Therefore, it is not surprising that a significant amount of effort is put into obtaining the "optimal" glycosylation of recombinant proteins. This can be achieved by choosing the appropriate expression system or by modification of the expressed protein by either chemical or enzymatic means. With the tools and techniques that are now available it is possible to engineer the "optimal" glycoprotein. However the major challenge of defining what is optimal glycosylation still remains. I will review what we have learnt about optimizing glycosylation in the 10 years since the approval of Cerezyme, the first recombinant protein with engineered glycosylation approved for therapeutic use.

2:40-3:10
Recombinant Protein Pharmaceuticals: Glycosylation Issues
Dr. Andrew J.S. Jones, Staff Scientist, Analytical Chemistry Department, Genentech, Inc.
The talk will cover some of the key issues for the manufacture and testing of recombinant glycoprotein pharmaceuticals and some of the experimental approaches we employ. It will be illustrated with some examples from "case histories.

3:10-3:40
Characterization Strategy for Glycoprotein Biopharmaceuticals During Development
Dr. Ralph M. Riggin, Research Advisor, Manufacturing Science and Technology, Eli Lilly and Company
This presentation will present an overview of the most relevant techniques for glycan characterization. Strategies for application of these techniques to address relevant questions during each phase of development of biopharmaceutical products and recent case studies will be discussed.

3:40-4:10
Refreshment Break

4:10-4:40
In Vitro Enzymatic Modification of Glycan Structures to Optimize Pharmacological Performance of Glycoprotein Drugs
Dr. David A. Zopf, Executive Vice President, Neose Technologies, Inc.
With increased understanding of the functional roles of specific glycan structures there emerges a need for economical and scalable technologies to synthesize carbohydrates as critical components of drug substances. Remodeling of the glycan chains of glycoprotein drugs by serial addition of simple sugar units can be achieved using appropriately selected recombinant glycosyltransferases. These reagents can be overexpressed in organisms that require only simple, inexpensive growth media and can be purified as cGMP reagents for use in drug manufacturing processes. Data will be presented to illustrate the use of in vitro enzymatic glycan remodeling of glycoprotein drugs to improve circulatory half-life, product uniformity, glycoprotein drug performance, and manufacturing efficiency. Besides adding simple sugar subunits of glycan structures, glycosyltransferases can be employed to add sugars that have other substituents covalently attached. For example, sialic acid with covalently attached polyethylene glycol (SA-PEG) can be transferred by a sialyltransferase from a sugar nucleotide construct, CMP-SA-PEG, to a terminal galactosyl residue of a suitable glycan chain. Enzymatic attachment of PEG to glycan chains leaves intact the biological activity of many glycoprotein drugs as it avoids random chemical modification of the polypeptide backbone in the vicinity of the active site. Addition of PEG to existing glycans confers significantly increased molecular size and brings associated improvements in plasma half-life. The benefits of this technique, termed GlycoPEGylation™, will be illustrated with several examples.

4:40-5:10
Engineered Fungal Strains for the Production of Fully Humanized Glycoproteins: Progress in Addressing the Glycosylation Problem
Dr. Tillman Gerngross, Chief Scientific Officer, GlycoFi, Inc.
Several fungal protein expression systems are ideal for the production of therapeutic glycoproteins because they are nonpathogenic, do not promote human pathogens, do not rely on any animal derived growth factors, and are able to produce large amounts of properly folded proteins on an industrial scale. However, the aberrant, nonhuman glycosylation associated with these expression systems has prevented them from becoming a major production platform for human therapeutic proteins. GlycoFi's technology harnesses the inherent advantages of fungal-based protein expression by engineering these systems to perform humanlike glycosylation.

5:10-5:40
Panel Discussion

5:40
Close of Conference

Cambridge Healthtech Institute's Inaugural Glycomics: Carbohydrates in Drug Development conference provides an excellent venue for companies wishing to target the leading glycobiology and carbohydrate chemistry researchers. There are an array of sponsorship packages and exhibit opportunities for you to reach this targeted audience, which include overall event sponsorship, technology workshops, networking receptions, delegate bags, etc. We are ready to work with you in customizing a solution to meet your specific marketing objectives. Make a lasting impression as a thought leader by taking advantage of these marketing tools.  For additional information, please contact: Angela Parsons at 781-972-5467 or aparsons@healthtech.com.

Hotel Information
University Park Hotel @ MIT
20 Sidney Street
Cambridge, MA 02139
T: 617-577-0200
F: 617-494-8366
Room Rate: $139.00 S/D
Cut-off Date: April 13, 2003

Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive the reduced room rate. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.

Travel Information
Special Airline Discounts Available
Special Zone and Discount Fares have been established for this conference with United Airlines. Please call United Airlines Meeting Reservation Desk at 800-521-4041 and reference ID#579YS.

Call for Posters
Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference CD, a one-page summary must be submitted and registration must be paid in full by March 28, 2003.   Click here for poster instructions