2014 Archived Content
Facilitated, small-group discussions. Interactive participation leads to problem-solving solutions and future collaborations around focused topics.
To see BuzZ Session A discussion table topics (2:00-3:00 pm), please click here.
TABLE 41B What Factors Will Drive HLE Technology Selection in the Future?
Mark Perkins, Ph.D., Customer Technical Solutions Manager, Novozymes Biopharma Ltd.
- As the application of HLE technologies to peptides and proteins becomes more widespread, what are the factors that will drive companies to adopt new technologies for achieving these therapeutic impacts by comparison to some of the more established routes such as PEGylation and Fc fusion?
- Are ambitions such as monthly dosing and enhanced differentiation likely to become the targets that drug developers are using to design their drugs and select technologies to achieve these aims? Are other factors likely to be equally or more relevant?
- How important will the ability to target specific tissues/organs (for example tumours) be in the selection of an HLE technology?
TABLE 42B Bispecific Antibodies vs. Oligoclonal Antibodies
Greg Adams, Ph.D., Co-Leader, Developmental Therapeutics Program, Fox Chase Cancer Center
- Are there clear advantages and disadvantages of each approach in terms of efficacy, safety or developmental costs?
- Does one face greater developmental or regulatory hurdles?
- Are there specific clinical indications or therapeutic strategies where one approach has a clear advantage over the other?
TABLE 43B Exploring the Use of Purified Membrane Proteins as Antigens for mAb Development
Jian Payandeh, Ph.D., Scientist, Structural Biology, Genentech, Inc.
- At what point should you consider using purified membrane protein as antigen? Are DNA injections or cell-based immunizations always tried first or in parallel?
- What detergent or reconstitution systems are the most or least productive? What are the best adjuvants and protocols for immunization? Are there target- or class-specific trends for what works or what doesn’t?
- What platforms are best for phaging against membrane proteins?
- What are the novel technologies worth considering? And what are your experiences with CROs?
TABLE 44B The Role of Fc Receptors in Immunomodulatory mAb Function
Ann White, Ph.D., Senior Research Fellow, University of Southampton, United Kingdom
- Activatory versus inhibitory FcgR engagement
- Optimizing immunomodulatory versus therapeutic function
- Requirements for agents targeting receptors on T cells versus APC
- Treatment of cancer versus infectious disease
- Can efficacy and toxicity be uncoupled?
TABLE 45B Translation Strategies to Develop Next-Generation mAbs
Randall Brezski, Ph.D., Senior Scientist, Biotechnology Center of Excellence, Janssen R&D
- What animal models are required for Fc-engineered mAbs? Transgenic mice? Humanized mice?
- How important is it to define in vivo mechanism of action in preclinical studies?
- How will the success (or failure) impact early stage next-generation mAbs?
TABLE 46B Antibody Combinations in Discovery and Development
David Buckler, Ph.D., Director, Therapeutic Proteins, Regeneron Pharmaceuticals
- Is it too soon to focus resources on combinations, given current opportunities to tackle single targets?
- What informatic tools have been helpful in identifying relevant target combinations?
- Compare bispecifics vs. two-component antibody combinations, both from discovery and development perspectives
- What are the biggest hurdles regarding formulation and regulatory approval of antibody combinations?
TABLE 47B Half-Life Extension of Biopharmaceuticals
Volker Schellenberger, Ph.D., CEO and President, Amunix
- Overview of available technologies
- Applicability to multispecific products
- Recombinant and/or synthetic payloads
- Manufacturing and analytics
TABLE 48B Mass Spectrometric Techniques for Protein Therapeutic Analysis
Jennifer Nemeth, Ph.D., Principal Research Scientist and Head, Biologics Mass Spectrometry & Allied Technologies, Janssen R&D LLC
- What MS platforms are being used in biopharma today?
- What is the required resolving power needed to address most intact mass questions?
- When can you use intact mass profiling vs. employing a peptide map?
- What are the critical assays for biotherapeutic development?
TABLE 49B Clinical Aspects of ADCs
Robert S. Kahn, M.D., CPI, Safety Science Leader, Early Clinical Development, Global Safety Risk Management, Genentech, Inc.
- Novel dosing mechanisms
- Safety of ADCs observed in current clinical trials
- Risk mitigation of ADC toxicities
- The current roles of ADCs in oncology
TABLE 50B Epitope Binning and Its Importance
Benjamin Brooks, Ph.D., VP, R&D, Wasatch Microfluidics
- The financial importance of epitope binning early in the drug discovery cycle
- The importance of throughput in EB. How much throughput is necessary?
- What are the disadvantages of EB early?
- What other epitopic techniques are important?
TABLE 51B Can Antibodies with Exquisite Specificity and High Affinity Binding to an Antigen be Developed from Synthetic Antibody Libraries?
An-Suei Yang, Ph.D., Research Fellow, Genomics Research Center, Academia Sinica
- Expression of synthetic antibody libraries – phage display, yeast display or other systems?
- Antibody format for synthetic antibody libraries – scFv or Fab?
- Antibody fragment stability – how to maximize complexity and functional size of the antibody libraries?
- The origin of antibody affinity towards protein antigens – can antibody affinity be engineered onto the antibody variants in an antibody library?
- The origin of antibody specificity towards protein antigens – can antibody specificity be engineered onto the antibody variants in an antibody library?
- Target-specific antibody libraries – can antibody libraries be specifically engineered to target a specific site on a protein antigen?
- Comparison of synthetic antibody libraries and natural antibody libraries – which and for what application?
TABLE 52B High-Throughput Formulation Screening in Early Process Development
Nicolas Moniotte, Ph.D., Technology Development Leader, R&D Formulation Development, GlaxoSmithKline Vaccines
- Screening for many conditions while dealing with limited amount of material
- Minimal candidate features to start screening (purity, protease, concentration)
- Selection of container for screening (microplates, glass vials)
- Biophysical characterization in multiwell plates (conformation, physico-chemical analysis, bioassays, etc.)
TABLE 53B Particulate Formation in Protein Drug Products
Meera Agarkhed, Principal Associate, Formulation Development, ImClone Systems, a Wholly-Owned Subsidiary of Eli Lilly & Co.
- Different methods used for particulate analysis
- Impact of particulates on safety and stability
- How to control particulates
TABLE 54B Kinetics and Thermodynamics Controls of Protein Aggregation
Murali Bilikallahalli, Ph.D., Associate Director, Formulation Sciences, Proteins, Vaccines & Oligos, MedImmune
- What dictates the shelf life of a therapeutic protein?
- How and why excipients interplay?
- Why my protein folds faster but is less stable than yours?
TABLE 55B Design on Experiments in Biologics Drug Product Development
Vishal C. Nashine, Ph. D., Senior Research Investigator, Bristol-Myers Squibb
- Is DoE an overkill during early formulation development?
- When and how to implement DoE in formulation and process development
- Design space, CQAs and CPPs in drug product formulation and processes
- When to expect interactions between parameters and how to derive mechanistic information
- What processes can truly benefit from implementation of DoE? Is lyo the only process that benefits from DoE studies?
TABLE 56B Improving Protein Solubility
Thomas Laue, Ph.D., Professor, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire
- What features of a protein influence solubility?
- How much can the solvent mitigate poor solubility?
- How solubility should be checked at the Discovery/Development interface
TABLE 57B Implications of Controlled Ice Nucleation in Freeze-Drying
Vamsi Mudhivarthi, Ph.D., Postdoctoral Fellow, Pharmaceutical Sciences, University of Connecticut
- Process Development
- Buffer Crystallization
- Protein Stability
TABLE 58B Confinement of Biologics in Nanopores: Mimicking Nature or Improving Upon Nature for Enhanced Stability, Delivery and Activity?
Pankaj Karande, Ph.D., Assistant Professor, Department of Chemical & Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute
- What keeps proteins stable under high crowding and packing inside cells?
- Are there advantages offered by physical confinement in nanopores for protein formulation and stabilization?
- Can confining proteins in nanomaterials offer desired combination of targeting, delivery and activity?
TABLE 59B Reactive Leachables in Biopharmaceuticals
John Iannone, Program Manager and Technical Specialist, Toxikon Corporation
- Examples of reactive leachables
- Observed reactions of leachables with functional groups of a peptide/protein
- Correlation between Genotoxicity, Cramer Class III compounds and observed reactivity
- Control strategies for (reactive) leachables
TABLE 60B Hetero/Homodimeric Proteins
Lawrence J. Tartaglia, Ph.D., Researcsh Scientist, Biochemistry and Molecular Biology, Center for Structural Biology, University of Florida
- Vector design and development
- Protein expression and purification
- Downstream applications
TABLE 61B Protein Complexes and Multi-Gene Constructs Generation
Wassim Abdulrahman, Ph.D., Research Scientist, Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research and CPC Novartis
- How frequent co-expression is required?
- Improving targets expression and solubility: robotized screening for protein interactions
- The choice between co-infection (BV)/co-transfection (mammalian) heterogeneity and the limits of large DNA constructs: low transfection efficiency, stability issues, etc.
- The future of gene synthesis in multi-gene constructs generation, time and cost considerations
TABLE 62B Monoclonal Antibodies that Selectively Detect Nerve Agent Biomarkers
John Cashman, Ph.D., President and Founder, Human BioMolecular Research Institute
- Can phosphonylated peptides that correspond to the region of human serum albumin that is adducted by nerve agents be chemically synthesized, conjugated to a carrier protein and used to procure monoclonal antibodies from mice?
- Can biomarkers from blood samples of animals exposed to actual nerve agents be recognized by the monoclonal antibodies?
- Can the monoclonal antibody be combined with a handheld flow device useful in detecting nerve agent biomarkers in a convenient, portable biosensor?
TABLE 63B How to Control Product Quality without Sacrificing Productivity
Zhimei Du, Ph.D., Senior Scientist, Cell Sciences & Technology, Amgen, Inc.
- Which process conditions impact product quality?
- Which process conditions can increase specific productivity?
- How should we consider both attributes during process development?
TABLE 64B Increasing Transient Expression Titers
Bernie Sweeney, Ph.D., Senior Group Leader, Mammalian Expression, UCB
- What are the maximum titers achievable with current transient expression platforms?
- What criteria are required to achieve this: host cell line, transfection reagents, media?
- How good are the reagents that are already on the market?
- Are current platforms suitable for new novel formats (bispecifics, tribodies, etc.)?
TABLE 65B Managing Your “Crown Jewels”: Internally Produced Protein-Related Information
Peter Nollert, Ph.D., Vice President, Technology and Client Solutions and Head, Membrane Protein Practice, Emerald Bio
- Why is it so difficult to keep track of protein data?
- Commonly used practices for protein data capture and dissemination
- Dream scenario for protein data and sample management
TABLE 66B Using Mammalian Expression Systems to Express Drug Targets
Jiansheng Wu, Ph.D., Scientist, Protein Chemistry, Genentech, Inc.
- What host systems to use? CHO, 293 or others?
- What are the popular expression systems?
- What are the yields of these drug targets?
- What are the limitations to the mammalian system? What can be expressed, what cannot?
- What are your success stories?
TABLE 67B Advances in Protein Purification by Chromatography and Market Adaptation
Yamuna Dasarathy, Ph.D., MBA, Director, Marketing, Chromatography, Pall Life Sciences
- Have purification needs caught up with high-titer production upstream? If not, future needs
- Single-use options and their adaptations in chromatographic purification of proteins
- High-throughput screening for process development – manual or automated? User acceptance
TABLE 68B Protein Melting as a Tool for Buffer Optimization and Protein Characterization
Bill Gillette, Ph.D., Senior Scientist, Group Leader, Protein Purification, Protein Expression Laboratory, Advanced Technology Program SAIC-Frederick, Inc.
- Measuring thermal stability as a proxy for protein stability
- Monitoring ligand binding
- Onset of aggregation
TABLE 69B Solving the Problems of Protein Expression
Andrew Fosberry, Ph.D., Manager, Expression & Fermentation Sciences, Biological Reagents and Assay Development, PTS, GlaxoSmithKline Research & Development Limited
- Do we take a multiconstruct approach?
- Do we look at different expression parameters?
- Move to an alternative host such as baculovirus/yeast?
- Try something new?
- Or all of the above?
TABLE 70B Bringing Single-Use to Fill/Finish
Jessica Frantz, Field Marketing Manager, Aseptic Transfer Systems, Fluid Management Technologies, Sartorius Stedim Biotech North America
- Particulates – what is acceptable?
- Extractables & Leachables – impact of brief contact times
- Dosing accuracy – system design and testing
- System integrity – quality by design vs. point-of-use testing
TABLE 71B Optimizing Continuous Downstream Processing
SeongKyu Yoon, Ph.D., Assistant Professor & Director, Department of Chemical Engineering, Massachusetts Bio Manufacturing Center, University of Massachusetts
- Technical hurdles
- Regulatory aspects
- Tangible and intangible benefits
- Implementation strategy
TABLE 72B Single-Use Supply Chain Risk
Leslie Cianella, EMBA, CPIM, CQA, Senior Sourcing and Procurement Manager, Supply Chain Operations, MedImmune, Inc.
- Supply chain transparency
- Supplier-initiated change risks
- Supplier customization risks
- Lagging supplier capacity
TABLE 73B Regulatory Considerations for Multiproduct Facilities
John Godshalk, Senior Consultant, GMP, CMC, Biologics Consulting Group, Inc. and former Review/Inspector, Division of Manufacturing and Product Quality, CBER, U.S. FDA
- Modular/Hybrid models
- Process consistency/validation
- Design space
- Closed systems
TABLE 74B Technologies and Process Integration in Modular Facilities
Par Almhem, President, ModWave
Modular process facilities are an extension of the process itself. By starting with a well-defined and, to the extent possible, modularized process and designing process modules, suites and facilities around this process, we can develop building blocks that are more or less standardized. These building blocks can then be used to design and build a wide range of processes and facilities in a much more efficient way than using traditional methods.
- How does modularization affect cost, timing and flexibility of a process facility?
- We are mostly discussing biotech and aseptic processing – is this also applicable to small molecules?
- Will it really be possible to have standard design that can be used by many owners/operators?
- What are the main challenges in integrating processes in modular facilities?
- How do you see the near- to mid-term development and acceptance of modular processing facilities?
TABLE 75B Protein Sequences and Structural Elements of Therapeutic Antibodies Modulating Protein Production Levels in Mammalian Cells
Xiaotian Zhong, Ph.D., Principal Scientist & Lab Head, GBT, Pfizer Global BioTherapeutic R&D
- Why are some antibodies well expressed in mammalian cells while some aren’t?
- Why do some amino acid changes severely diminish protein production but some don’t?
- What are the structural motifs and primary sequences crucial for protein production?
- Can we predict a good expresser or a bad one? What can we do about them?
TABLE 76B Expression of Recombinant Kinases
Alexei Degterev, Ph.D., Associate Professor, Tufts University
- What are the best strategies to improve baculoviral expression of recombinant kinases, i.e., yields, activity?
- Which recent advances in baculoviral and non-baculoviral expression of recombinant kinases offer maximal benefits (e.g., in vitro or mammalian expression systems, use of chaperones, etc.)?
- What is the optimal size of the expressed proteins?
- How closely recombinant kinase domains reflect activity and regulation of endogenous proteins? What does this mean for analysis of Type I and Type II inhibitors?
- Are there general kinase domain modifications that could improve yields and activity of recombinant kinases?
TABLE 77B Challenges and Opportunities in Membrane Protein Research
Qinghai Zhang, Ph.D., Associate Professor, Integral Structural and Computational Biology, The Scripps Research Institute
- Name your most challenging target and topic in this area for the discussion
- Cell-free expression – challenges and solutions?
- How to best stabilize membrane proteins during and after purification?
- Unidentified and under-developed therapeutic targets?
TABLE 78B Strategies to Tackle Difficult Preparative Protein Purification Challenges
Thomas Müller-Späth, Ph.D., CSO, ChromaCon AG
- What makes a purification operation difficult?
- Removing product-related impurities: Evade or engage?
- Opportunities through multicolumn chromatography
TABLE 79B Protein-Ligand Interactions
Andrew Stephen, Ph.D., Acting Director, Protein Chemistry Laboratory, Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
- Protein characterization prior to binding assay
- Thermal-shift assays
- Surface Plasmon Resonance Spectroscopy
- Fluorescence based approaches
TABLE 80B Production Challenges for Fc-Fusion Proteins
Steven Chamow, Ph.D., Principal Consultant, Chamow & Associates, Inc.
- Product heterogeneity and control of glycosylation
- Process productivity compared to mAbs
- Differences with Protein A compared to mAbs
- How easily can mAb platform processes be adapted?