Biophysical & Biochemical Characterization of Biotherapeutics April 30 - May 1
Many recent pharmaceutical advances are based on detailed knowledge and characterization of the underlying proteins involved. Many companies are working to meet those demands through new tools, technologies, and assays. More important than the tools themselves is the hard work of applying the technologies appropriately to each situation and evolving a true analytical strategy.
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SUNDAY, APRIL 29
2:00-5:00 pm Recommended Short Course*
SC5 - Translational Strategies for Development of Monoclonal Antibodies: Focus on Early Discovery
*Separate registration required.
4:00 - 6:00 pm Main Conference Registration
MONDAY, APRIL 30
7:00 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Micah Lieberman, Executive Director, Conferences, Cambridge Healthtech Institute (CHI)
Jennifer Nemeth, Ph.D., Principal Research Scientist, Biologics Mass Spectrometry & Allied Technologies, Janssen R&D
8:40 Tissue Imaging and its Applicability in the Development of Therapeutics
Jennifer Nemeth, Ph.D., Principal Research Scientist, Biologics Mass Spectrometry & Allied Technologies, Janssen R&D (biography)
The direct imaging for tissues using MALDI-TOF MS has been an emerging field over the past twelve years. This technology has opened up the possibility of tracking drugs and/or drug metabolites, within tissues for the purpose of localization and PK studies. Presented will be a historical perspective on the field and highlight possibilities for drug discovery.
9:10 Imaging Drug Distribution with Mass Spectrometry
Stacey Oppenheimer, Ph.D., Principal Scientist, World Wide Medicinal Chemistry, Pfizer (biography)
Mass spectrometry imaging is a useful tool for drug discovery studies due to its ability to elucidate the spatial distribution of non-labeled therapeutics. This technology offers a unique compliment to conventional LC-MS analysis of drugs in tissues, which requires sample homogenization, because it maintains the spatial localization of drugs and their metabolites and enables correlation with histochemistry techniques. This talk will highlight some impacts mass spectrometry imaging has had in pharmaceutical research ranging from oncology and neuroscience to environmental safety.
9:40 Towards Implementation of MALDI IMS into the Drug Development Workflow: Bridging Histology and Drug Tissue Distributions
Reid Groseclose, Ph.D., Investigator, DMPK, GlaxoSmithKline (biography)
We will present data that demonstrates the ability of IMA to link chemistry and biology and provide examples of how this is permitting us to examine the basis of drug toxicity and pharmacology and refine our understanding of pharmacokinetics and drug transport. Examples will include distribution analysis of a drug and its metabolites in liver tissue and the correlation with observed hepatotoxicity, assessment PK/PD relationship for a drug and key metabolites in tissues, and comparative CNS penetration and metabolism of a compound and its metabolites in different pre-clinical models.
10:10 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
11:10 Use of Proteomics in Advancing Drug Discovery Programs
Steve Pomerantz, Senior Research Scientist, Biologics Mass Spectrometry & Allied Technologies, Janssen R&D (biography)
Mass spectrometry-based proteomics has tremendous potential to impact the entire product life cycle through commercial release. Pertinent proteomic techniques, interspersed with case histories, to support target discovery and target validation studies will be presented. Particular emphasis will be placed on the utility of multiple reaction monitoring (MRM) assays to drive drug development.
11:40 Successful Mass Spectrometry Strategies for Biomarker and Target Discovery and Verification
Daniel Chelsky, Ph.D., Chief Scientific Officer, Caprion (biography)
Two mass spectrometry methods have been applied for the rapid discovery of biomarker and target candidates. A non-hypothesis driven strategy is used to identify and compare proteins in samples from multiple cohorts when no candidates exist. Alternatively, an MRM assay can compare hundreds of specific proteins with known biological associations. Successful examples of both approaches will be presented.
12:10 pm Antibody Screening and Characterization Using Multiplexed SPR
Kevin Lindquist, Sr Principal Scientist, Rinat Pfizer
Measure 36 label free interactions simultaneously and with greater experimental design flexibility utilizing the 6 x 6 fluidics array of the ProteOn XPR 36 biosensor. Antibody characterization and epitope binning are completed in a fraction of the time as compared to serial flow biosensors.
12:25 Sponsored Presentation (Opportunity Available)
12:40 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own
2:00 Chairperson’s Remarks
Steven Berkowitz, Ph.D., Principal Investigator, Analytical Development, Biogen Idec, Inc.
» 2:05 Featured Presentation
Unformed Disulfide Bonds in Antibodies
Yung-Hsiang Kao, Ph.D., Principal Scientist and Senior Group Leader, Protein Analytical Chemistry, Genentech (biography)
We found several recombinant mAbs that contain unusually high amounts of variants missing one specific intra-chain disulfide bond (i.e. the cysteines remained in the reduced form) in the variable heavy or light chain domain. The characterization, impact and causes of these buried and unpaired cysteines will be discussed.
2:35 Rapid Profiling of N-linked Glycans from Monoclonal Antibodies Using Microfluidic-Based Chip NanoLC-MS
Niclas Tan, Ph.D., Scientist, Analytical Development, Biologics, Millennium: The Takeda Oncology Co. (biography)
Characterization of glycan post-translational modifications of therapeutic antibodies is of utmost importance due to their impact on efficacy, half-life, stability and mechanism of action. Traditional assays involving fluorophore-labeled glycans are tedious and typically require days to complete. Here we present a novel integrated microfluidic-based LC-MS chip for rapid online cleavage, purification, separation, identification and quantitation of label-free N-linked glycans from monoclonal antibodies based on accurate mass.
3:05 Improved Quantitation of Glycans Released from Biotherapeutics
Ron Orlando, Ph.D., Professor, Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia (biography)
Glycosylation is one of the most common post-translational modifications encountered in eukaryotic systems. One of the analytical challenges facing scientists in the characterization of glycoproteins involves the ability to identify and quantify changes in the attached glycans. This topic is of importance to a variety of researchers that ranges from those involved in the batch to batch analysis of recombinant glycoproteins to those involved in glycomics.
3:35 Epitope Mapping by Amide Hydrogen/Deuterium Exchange Mass Spectrometry
Yoshitomo Hamuro, Ph.D., Senior Director, ExSAR Corporation (biography)
Mapping of antigen-antibody interface is a critical step for scientific, regulatory and intellectual property reasons, especially with increasing demand for monoclonal antibody therapeutic agents. Principle and examples of epitope mapping for therapeutic antibodies by protein backbone amide hydrogen/deuterium exchange coupled with proteolysis and mass spectrometry (HDX-MS) are described. The epitopes identified for IL-13, IL-17A, and cytochrome c by HDX-MS are in good agreement with the epitopes identified by X-ray co-crystal structures.
4:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem Solving Breakout Discussions
Concurrent problem solving breakout discussions, open to all attendees, speakers, sponsors, and exhibitors, provide a forum for discussing key issues and meeting potential collaborators. Plan to take part and explore these topics in-depth. Please pick a topic of your choice, find your table and join in.
Tissue Imaging in Pharmaceutical Development
Moderators: Jennifer Nemeth, Ph.D., Principal Research Scientist & Head, Discovery Mass Spectrometry, Janssen R&D
Reid Groseclose, Ph.D., Investigator, DMPK, GlaxoSmithKline
• Areas of opportunity for large molecule development
• Issues and hurdles in implementation
• Methods and technologies for driving the field
Antibody Drug Conjugates (ADCs)
Moderator: Gadi Bornstein, Ph.D., Research Fellow, Centers for Therapeutic Innovation, Pfizer Inc.
• What market potential do antibody drug conjugates hold?
• What are the most significant challenges facing development and FDA approval of antibody drug conjugates?
• Which linker-payload combinations are the most effective for cancer therapy?
Characterization and Comparability of Biologicals: Analytical and Regulatory Aspects
Moderator: Marina Kirkitadze, Ph.D., MBA, Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D, Biochemistry Platform, sanofi pasteur
• Method comparability - Which samples to use to determine method comparability?
• Product comparability - What is a comparable product? Biological characteristics versus biochemical ones
• Standard reference material - How to qualify new reference standard with the methods used for older process?
Assessing 'High Order Structure' of Protein Therapeutics
Moderator: E. Neil Lewis, Ph.D., Chief Technology Officer, Malvern Instruments
• What role do changes/modifications of higher order (secondary, tertiary) protein structure play in aggregation?
• Can monitoring relative changes in higher order protein structure in-vitro using optical spectroscopy (CD, FTIR, Raman, etc.) provide rapid insight into optimal formulation conditions and predict long-term product stability?
• Can monitoring relative differences in protein higher order structure in-vitro using optical spectroscopy (CD, FTIR, Raman) provide useful comparative data for assessing biosimilarity?
Potential Damages to Protein Biotherapeutics During Bioprocessing: How to Monitor and Minimize
Moderator: Christine Chan, Ph.D., Senior Manager, Technology Development, Genzyme
• Characterization of bioprocessing stress on proteins: value of early lab scale stress studies, qualifying scale-down models based on manufacturing process, how best to delineate sequential effects
• Assay sets: selection of analytical tools, level of discriminating capability needed, criteria of comparability
• Mitigation strategies: share your experience in problems encountered and practical solutions
Analytical Challenges of Glycoprotein Therapeutic Characterization
Moderator: Ron Orlando, Ph.D., Professor, Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia
• Current best practices and areas where improvements are needed
• What challenges remain
• Negative proofs: how does one demonstrate that potentially immunogenic glycans are not present?
Protein Characterization by Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS)
Moderator: Yoshitomo Hamuro, Ph.D., Senior Director, ExSAR Corporation
• Characterization of higher order structure of therapeutic proteins by HDX-MS
• Mapping of conformational epitopes by HDX-MS
• Regulatory requirements for the characterization of higher order structure
• IP implications
5:45-6:45 Welcome Reception in the Exhibit Hall with Poster Viewing
Poster Awards Sponsored by
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