Biophysical analysis is now playing a significant role in the research and early development for a new generation of complex protein therapeutics. The combination of improved understandings of the structure and function of proteins with advanced, higher resolution analytical methods helps researchers identify and fine-tune candidate molecules before advancing them into development. As protein engineers and analytical scientists increase their reliance on biophysical analysis, they are driving a move to instruments with higher throughput and resolution – and working to quantify analytical results previously used only for qualitative assessments. Biophysical Analysis of Biotherapeutics will bring together an international audience of protein scientists and analytical specialists to explore the latest technologies and techniques used for problem solving in this dynamic field.


7:00 am Registration and Morning Coffee

8:00 Chairperson’s Remarks

Hubert Kettenberger, Ph.D., Principal Scientist, Protein Analytics, Roche Pharma Research & Early Development, Roche Innovation Center Penzberg


Competing Effects for Optimizing Protein Behavior at Low and High Concentrations

Unpublished DataChristopher J. Roberts, Ph.D., Associate Professor, Chemical & Biomolecular Engineering, University of Delaware

Multiple factors are considered when selecting protein product formulation and manufacturing conditions, as there may be competing effects that require optimization. This presentation focuses on examples from therapeutic proteins and model proteins that highlight the balance between different behaviors (e.g., aggregation, solubility, viscosity) and how to reasonably account for or predict these in at least a semi-quantitative manner based on biophysical measurements.

Predictive Modeling of Biophysical Characteristics

8:40 Beauty or Beast? In Silico Molecule Assessment to Support Lead Selection

Case Study
Hubert Kettenberger, Ph.D., Principal Scientist, Protein Analytics, Roche Pharma Research & Early Development, Roche Innovation Center Penzberg

Successful new biotherapeutics should possess – besides the desired biological activity – high biochemical and biophysical stability. In silico prediction of chemical degradation “hotspots”, charge distribution, molecular dynamics and other features can support the lead selection and protein engineering process.

9:10 Structure-Based Predictive Tools for Engineering Biophysical Characteristics of Biotherapeutics

SidSridharanSudharsan (Sid) Sridharan, Ph.D., Scientist, Antibody Discovery and Protein Engineering, MedImmune

Structural data of antibodies and other biotherapeutics provide key knowledge for understanding their biophysical characteristics which impacts both research and development of these molecules. Predictive tools using structures complement experimental analyses and can enable rational engineering of biotherapeutics. In this talk examples of these tools and their applications in engineering favourable biophysical properties of biotherapeutics will be highlighted.

9:40 Structural Flexibility and Allosteric Responses are Widely Redistributed Within Antibody Fragments Upon Mutation

Unpublished Data
Dennis Livesay, Ph.D., Professor, Bioinformatics and Genomics, University of North Carolina

Recombinant antibody fragments have emerged as credible alternatives to full therapeutic antibodies. Unfortunately, reduced thermostability is frequently observed, limiting their broad utility. In response, screening for mutants that increase stability without compromising affinity is commonly employed. Little is known about how the uncovered mutations affect dynamical properties. In this talk, I will discuss the frequency and scale of changes in structural flexibility and allostery across a number of different antibody fragment systems.

10:10 Analyzing Varying Biochemical and Biophysical Data in Discovery Biologics

Unpublished Data
Timothy Fenn, Ph.D., Principal Scientist, Boehringer Ingelheim

In discovery biologics, simple and information rich biochemical/biophysical methods are required to provide the wide variety of information necessary to evaluate antigens, multispecifics, and potential antibody leads. This talk will focus on some common analytical methods and how the information derived from each can be used in a complementary manner. Examples will be provided in a variety of contexts, including bispecific scaffold selection, antibody purification and protein reagent analysis.

10:40 Coffee Break in the Exhibit Hall with Poster Viewing

11:25 Combining Biophysical Tools and Transgenic Mouse Models to Understand the Immunogenic Potential of Subvisible Particles

Unpublished Data
Emilien Folzer, Scientist, Pharma Technical Development Europe (Biologics) Analytics, Roche

Theoretical concerns regarding the potential immunogenicity of proteinaceous sub-visible particles in protein therapeutics have being widely debated in literature with very limited experimental data available to date. This talk will focus on describing two methods for particle fractionation that have been developed to isolate defined particle species, as well as the detailed physicochemical and biological characterization of these species.

11:55 Biophysical Tools for Molecular Assessment of mAbs

Unpublished Data
Arun Alphonse Ignatius, Ph.D., Principal Scientist, Biotherapeutics Pharmaceutical Science, Pfizer, Inc.

Molecular assessment is a key component of the candidate selection process. Previously, candidate selection has focused mainly on the biological properties of the protein and developability/manufacturability aspects were not considered. Many programs required additional resources and non-platform approaches during development due to lack of early developability assessment data. In this presentation, biophysical characterization tools optimized to probe into the conformational and colloidal stability of mAbs will be used on a set of Pfizer candidates to enable de-selection of risky candidates and ranking during molecular assessment stages.

12:25 pm Molar Mass, Size, Charge and Conformation: Light Scattering
Tools for Biophysical Characterization of Macromolecules

John Champagne, Ph.D., Senior Applications Scientist & Northeast Regional Manager, Wyatt Technology Corporation

This seminar describes a comprehensive suite of characterization tools based on static and dynamic light scattering, which work together with size-based separation, to provide first principles biophysical characterization of macromolecules. Some of the key applications of the light scattering toolbox include analyses of molar mass and size distributions, aggregation, branching and other measures of conformation, and the composition of complex protein systems and other conjugated macromolecules.

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:55 Session Break

Novel Biophysical Analytical Methods

2:10 Chairperson’s Remarks

Sudharsan (Sid) Sridharan, Ph.D., Scientist, Antibody Discovery and Protein Engineering, MedImmune

2:15 Optimizing Selection of Aggregation-Resistant Antibodies Using Self-Interaction Nanoparticle Spectroscopy

Unpublished Data
Jiemin (Jimmie) Wu, Research Associate, Chemical and Biological Engineering, Rensselaer Polytechnic Institute

Conventional methods of measuring mAb self-association are difficult to employ during antibody discovery due to the low purities, limited quantities, and large numbers of mAb candidates. To address this challenge, we are developing a robust method (affinity-capture self-interaction nanoparticle spectroscopy, AC-SINS) capable of identifying mAbs with low self-association propensity at extremely low antibody concentrations and in the presence of contaminants.

2:45 Catching the Seeds of Destruction: Probing Structurally Altered and Aggregated States of Therapeutically Relevant Proteins Using GroEL Coupled to Bio-Layer Interferometry

Unpublished Data
Mark T. Fisher, Ph.D., Professor, Biochemistry and Molecular Biology, University of Kansas Medical School

Nature employs a wide array of chaperone proteins to prevent large scale aggregation in vivo by interacting with partially folded protein species. This chaperone network actively or passively reverses misfolding to prevent and/or reverse the accumulation of aggregation prone species. Taking this tact, we demonstrate that a GroEL chaperonin-based biolayer interferometry platform can successfully detect initial “seed” preaggregate species in therapeutic protein formulations prior to large aggregate formation in vitro.

 3:15 Simple Approaches to Monitoring Bio Pharmaceutical Purification with Flow Imaging

Noyes_AaronAaron Noyes, Ph.D., Process Engineer, Purification Process Development, Pfizer

Sub-visible particle analysis using micro-flow imaging is critical to monitor biopharmaceutical product quality and safety. Compared to older techniques which only provide particle size and count and can undercount, MFI also provides particle morphology. As a result, MFI can resolve complex particle types such as protein aggregates from silicone oil and other contaminants. During purification of biologicals, complex particle environments are common. In this webinar, Aaron Noyes, Scientist at Pfizer, will show how MFI presents a fresh approach for characterizing biopharmaceutical production processes of mAbs and vaccines. Case studies focused on flocculation, precipitation, and filtration will demonstrate how measuring particle size, count and morphology can enhance process understanding, improve productivity, and ultimately, increase the robustness, of biopharmaceutical production processes.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Microspectroscopic Analysis of Free Fatty Acid Particles in Protein Formulations

Case Study
Xiaolin Cao, Ph.D., Principal Scientist, Amgen

Free fatty acid particles were identified in a number of protein formulations containing the surfactant polysorbate 20 using multiple microspectroscopic methods. These fatty acid particles were numerous in number, granular or sand-like in morphology and were several microns in size. In addition, protein particles and particles containing a mixture of protein and fatty acids were also identified. The techniques and observations described in this case study will be useful for the identification of microparticles in pharmaceutical products.

5:15 HELM: Setting the Standard for Biomolecular Data Exchange

Case Study
Sergio Rotstein, Ph.D., Director, Research Business Technology, Pfizer, Inc.

The Hierarchical Editing Language for Macromolecules (HELM) enables the representation of complex biologic entities such as oligonucleotides, peptides, proteins, antibodies and bioconjugates in a flexible and compact fashion. The technology, originally developed at Pfizer Incorporated, was released into the public domain through the Pistoia Alliance and is well on its way to becoming the industry standard for the exchange and manipulation of complex biomolecule structures and their associated data.

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day


8:00 am Morning Coffee

Spectroscopic Methods for Biophysical Analysis

8:30 Chairperson’s Remarks

Wim Jiskoot, Ph.D., Professor of Drug Delivery Technology, Leiden University, The Netherlands

8:35 Leveraging the Power of Mass Spectrometry to Study ADME Properties of Therapeutic Biologics

Unpublished Data and Case Study
Ji Ma, Ph.D., Principal Scientist, Amgen

Benefiting from rapid advances in protein engineering field, discovery of therapeutic biologics has evolved from primarily monoclonal antibodies to different molecular types, e.g. ADCs, huFc and HSA fusions. Using several case studies, cutting edge mass spectroscopic technologies have been applied to understand ADME properties of therapeutic biologics in discovery stage.

9:05 Using Hydrogen-Deuterium Exchange Mass Spectrometry to Characterize Protein Higher-Order Structure and Dynamics

Unpublished Data
George Bou-Assaf, Ph.D., Scientist, Biogen Idec

Hydrogen/Deuterium exchange mass spectrometry provides superior assessment of protein higher-order structure. Here, we discuss the applications of HDX-MS in various aspects of drug discovery and development. We showcase how its use in comparability and biosimilarity studies enables stronger regulatory filings. We discuss how the technique has been instrumental for epitope mapping and in characterizing protein-protein or protein-ligand interactions. Finally, we explore how it could be used in protein formulation development.

9:35 Terahertz Spectroscopy of mAb Formulations

Unpublished Data
Christopher van der Walle, Ph.D., Principal Scientist, Development, MedImmune

Terahertz time domain spectroscopy (THz-TDS) provides insight into the interaction between proteins and water, or ‘hydration shell’, by analyzing the nonlinear relationship between protein concentration and THz absorption. Distinct changes in THz absorption were observed for mAbs formulated up to 150 mg/ml in different excipients: NaCl, sucrose, proline and arginine. Relating these changes to key formulation parameters such as viscosity will improve our understanding of mAb behavior at high concentrations.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

Biophysical Analysis of High Concentration Proteins

11:05 Light Obscuration Measurements of Highly Viscous Solutions: Sample Pressurization Overcomes Underestimation of Subvisible Particle Counts

Case Study
Wim Jiskoot, Ph.D., Professor of Drug Delivery Technology, Leiden University

Light obscuration (LO) is a standard technique for subvisible particle analysis of therapeutic protein products. Some of those, however, exhibit high viscosities, which can lead to an underestimation of subvisible particle concentrations. To solve this problem, we evaluated the application of sample pressurization during analysis, which turned out to be an elegant way to restore the reliability of LO analysis of highly viscous products without the need for dilution.

11:35 Protein Intermolecular Organization within Clusters in High Concentration Solutions Effectively Differentiates Crystallization, Liquid-Liquid Phase Separation, Gelation and Viscous Rheology Processes

Unpublished Data
Wenhua Wang, Ph.D., Postdoctoral Fellow, Late Stage Pharmaceutical Development Department, Genentech, Inc.

Protein self-association, particularly at high concentrations, often leads to manufacturing and administration problems such as aggregation, high viscosity, opalescence, and liquid-liquid phase separation (LLPS). Here, the physical nature of phase behavior in concentrated monoclonal antibody solutions is addressed by characterizing protein interactions and cluster structures. A molecular-level understanding of protein self-assembly of different high concentration phase behaviors helps to control opalescence/LLPS and mitigate viscosities in drug product formulations.

12:05 pm Adopting Imaging and Other Analytical Techniques to Better Characterize and Study Novel Therapeutic Modes Such As the DVD-IgTM Molecule

Ivan-CorreiaIvan Correia, MBA, Ph.D.,Senior Principal Research Scientist,cHead, Global Protein Sciences, AbbVie Bioresearch Center (ABC)

12:35 End of Conference

5:15 Registration for Dinner Short Courses

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