2014 Archived Content

Biophysical Analysis of Biotherapeutics

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.  The Biophysical Analysis meeting at PEGS 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. 

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Recommended Tuesday Dinner Short Course* 

Overcoming the Challenges of Immunogenicity Assessment - View Detailed Agenda 

*Separate registration required. 



7:00 am Registration and Morning Coffee

8:00 Chairperson's Opening Remarks

JenniferNemethJennifer Nemeth, Ph.D., Program Leader, Biologics Research, Janssen R&D

Subvisible Particulate Matter in Therapeutic Protein Injections: USP<787> and Extended Characterization Using Orthogonal Methods 

SatishSinghSatish Singh, Ph.D., Research Fellow and Group Leader, Pfizer; Member, 787 Expert Panel, U.S. Pharmacopeial Convention (USP)

USP<787> is a new chapter that addresses the limitations of USP<788> for therapeutic proteins. This talk will cover the key aspects of USP<787> and discuss the orthogonal methods for characterization of these proteinaceous aggregates in the context of risk assessments during product development. (March 2014 Interview) 

High-Throughput and High Resolution Analysis  

8:40 Automation, Acceleration and Enhancement of Analytical Assays for Biotherapeutics

MarkusHaindlMarkus Haindl, Ph.D., Group Leader, Research & Development, Roche Diagnostics GmbH, Germany

Conventional methods for characterization of therapeutic proteins show limitations with respect to speed and compatibility with the growing demand for high-throughput formats. We developed improved and rapid analytical assays for bioprocess development and characterization of biotherapeutics. In combination with an enhancement of assay automation we are able to significantly accelerate process development and PC/PV studies. (March 2014 Interview) 

9:10 Utility of Hydrogen/Deuterium Exchange Mass Spectrometry for Probing Higher Order Structure of Biotherapeutics

GuadongChenGuodong Chen, Ph.D., Principal Scientist, Bioanalytical and Discovery Analytical Sciences, Bristol-Myers Squibb

One of the key challenges in biotherapeutics characterization is how to define the higher order structures that often dictate their biochemical functions. Classical biophysical methods do not provide detailed conformational information. HDX-MS has emerged as a powerful technology for probing higher order structure of biotherapeutics. This presentation highlights recent developments and applications of HDX-MS in higher order structure analysis.

9:40 High-Throughput Solution-Based Measurement of Antibody-Antigen Affinity and Epitope Binning

YingdaXuYingda Xu, Ph.D., Group Leader, Protein Analytics, Adimab

Advances in antibody discovery have allowed for the selection of hundreds of high affinity antibodies against many therapeutically relevant targets. This has necessitated the development of reproducible, HT analytical techniques to characterize the output from these selections. Here we report the use of FortéBio for rapid kinetic profile screening and epitope binning, while using MSD for fast and accurate solution phase based KD measurement.

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


11:10 Application of Ultrahigh-Resolution Mass Spectrometry to the Characterization of Antibody Biotherapeutics

HeatherDeGruttolaHeather DeGruttola, Scientist, Mass Spectrometry and Biophysical Characterization, Pfizer

The presentation will discuss the application of an LC/MS characterization method for mAbs that demonstrates rapid, definitive detection of modifications at the subunit/domain level, including deamidation and oxidation. In addition, rapid confirmation of the amino acid sequence and the detection of potential sequence variants at the subunit/domain level during early stages of process development will be addressed.

11:40 Developing Automated Ribosome Display Selections and Various High-Throughput Screenings

JonasSchaeferJonas Schaefer, Ph.D., Head, High-Throughput Laboratory, Biochemistry, University of Zurich, Switzerland

Reliable methods for the selection and screening of affinity reagents in parallel are key to cover today’s demand of specific binders. Our laboratory has developed a semi-automated high-throughput pipeline, aiming at an improved robustness of the overall process, while decreasing its time and cost requirements. This approach has generated binders that specifically recognize different, non-overlapping epitopes at their targets with high affinities.

12:10 pm Molar Mass, Size, Conjugation and Interactions: Light Scattering Tools for Biophysical Characterization 

DanSomeDan Some, Ph.D., Principal Scientist, Wyatt Technology Corporation

Biophysical techniques based on static and dynamic light scattering address many of the key analytical challenges in biotherapeutic R&D, from early candidate selection through scale-up, formulation, characterization and comparability studies. This seminar will review light scattering technology and instrumentation, then present select examples illustrating how Wyatt’s light scattering solutions facilitate rapid and effective development of biologics including mAbs, ADCs, PEGylated and other proteins.

12:40 Luncheon Presentation I: Biomolecular Binding Kinetics Assays Using Different Label-Free Platforms: Discriminating Sense From Non-Sense
Kamat_VishalVishal Kamat, Ph.D., Scientist, Biomolecular HTS Center, Therapeutic Proteins, Regeneron Pharmaceuticals 
The study of protein-protein interaction has always been in the forefront of drug discovery. Different real-time label-free biosensors are currently available to study various aspects of protein binding. Kinetics profile of monoclonal antibodies binding to their target is one of the key factors that guide the selection of lead therapeutic antibodies. So, accurate measurement of antibody binding kinetics is important. Various factors that could influence binding kinetics measurements and optimization of these parameters for accurate kinetics and affinity characterization of monoclonal antibodies will be presented. Comparison of binding kinetics profile for monoclonal antibodies against multiple targets measured using Surface Plasmon Resonance (SPR) and Biolayer Interferometry (BLI) will be also be presented

1:10 Luncheon Presentation II: Surface Plasmon Resonance (SPR) & Differential Scanning Calorimetry (DSC) for Analysis of Critical Quality Attributes

Belcher_Paul2Paul E. Belcher, Ph.D., Development Leader, GE Healthcare, Life Sciences

A range of analytical techniques are used to characterize and monitor CQAs in various stages of drug development and in comparability studies. Through case studies attendees will gain understanding of how SPR (Biacore™) and DSC (MicroCal™) can be used for analysis of binding activity and higher order structure. Case studies include characterization of IgG/Fc receptor interactions, active concentration measurements, and the use of specific epitope characterizing reagents for detection of changes in antibody higher order structure.


1:40 Session Break 


Molecular Assessment 

2:00 Chairperson's Remarks

Jonas Schaefer, Ph.D., Head, High-Throughput Laboratory, Biochemistry, University of Zurich, Switzerland

2:05 “Hammerhug” Selection Strategy Incorporating Thermal Challenge, Functional and Biophysical Screening

WilliamFinlayWilliam“Jonny” Finlay, Ph.D., Director, Pfizer, Ireland

We generated a tetravalent bispecific molecule targeting two inflammatory mediators for synergistic immune modulation. Phage-displayed 3B4 CDR-mutant libraries were used in an aggressive “hammer-hug” selection strategy that incorporated thermal challenge, functional, and biophysical screening. This approach identified leads with improved stability and > 18-fold, and 4,100-fold higher affinity for both human and cynomolgus CXCL13, respectively.

2:35 Developability Assessment through Molecular Modeling and Small-Scale High-Throughput Experiments

NareshChennamsettyNaresh Chennamsetty, Ph.D., Research Investigator, Bristol-Myers Squibb

Early assessment of developability is beneficial in selecting an optimal protein candidate in discovery and in guiding formulation approaches. We discuss modeling and high throughput experimental tools to address the developability issues of aggregation and oxidation. Aggregation is assessed using Spatial-Aggregation-Propensity (SAP) model along with kosmotrope-based solubility assay. The oxidation of methionine residues is assessed using molecular simulation models based on solvent assessable area and 2-shell water coordination number.

3:05 Applications of Surface Plasmon Resonance for Studying Amyloidogenic Peptides/Proteins 

Gobbi_MarcoMarco Gobbi, Head, Laboratory Pharmacodynamics & Pharmacokinetics, IRCCS, “Mario Negri” Institute for Pharmacological Research

A growing number of important human diseases are associated with the aggregation of amyloidogenic peptide/proteins. Surface Plasmon Resonance allows to obtain information hardly accessible with other approaches, regarding the binding events underlying assemblies growth, the recognition and characterization of the toxic aggregates, and the screening and identification of potential inhibitors.

3:20 Sponsored Presentation (Opportunity Available)

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:20 Use of Developability Data to Help Drive Lead Selection of a Bispecific Therapeutic

JenniferNemethJennifer Nemeth, Ph.D., Program Leader, Biologics Research, Janssen R&D

Two lead bispecific antibodies were recently assessed using developability assays for differentiation and lead selection. Assays included analytical structural assessments, amino acid risk assessments, molecule interaction and concentratability assessments, and large-scale expression in proposed manufacturing cell lines. The resultant data package allowed for a clear decision on candidate selection and proposed back-up molecules. A lead was recommended for advancement into product development and is currently under review by the therapeutic area for declaration as a New Molecular Entity.

4:40 High-Throughput Heterogeneity Analysis of Antibodies and Antibody-Like Molecules

Melissa GeddieMelissa Geddie, Ph.D., Senior Scientist, Merrimack Pharmaceuticals

Multispecific antibodies and antibody-like molecules broaden the therapeutic application of IgGs, but they can be challenging to engineer and manufacture. To address this we first use a network biology approach to identify key design parameters followed by iterative rational engineering, rapid design cycles and high-throughput screening assays to reduce heterogeneity. Our approach selects for potential therapeutic candidates with robust pharmaceutical properties.

5:20 Networking Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day


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