Cambridge Healthtech Institute's 6th Annual

Biophysical Analysis of Biotherapeutics

( 生物学的治療薬の生物物理学的分析 )

次世代生物製剤の研究開発におけるタンパク質の物理的な特性の評価と最適化

2018年5月2-3日 | World Trade Center | マサチューセッツ州ボストン

 

Biophysical analysis is now playing a significant role in the research and early development for a new generation of complex protein therapeutics. 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 PEGS Biophysical Analysis meeting brings 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.

Final Agenda

Recommended Short Course(s)*

SC8: Introduction to Biophysical Analysis for Biotherapeutics: Discovery & Development Applications

Christine P. Chan, PhD, Principal Scientist, Global Manufacturing Science & Technology, Sanofi


*Separate registration required.

5月2日 (水)

7:30 am Registration and Morning Coffee

手法と手段

8:30 Chairperson's Remarks

George Bou-AssafGeorge Bou-Assaf, PhD, Scientist, Technical Development, Biogen


8:40 Integrating Biophysical Analyses Earlier in the Discovery Process to Improve Final Lead Selection

Jennifer F. NemethJennifer F. Nemeth, PhD, SCPM, Director, Biophysics, Structural Characterization, Biologics Discovery Sciences, Janssen Research & Development

Biophysical characterization has a critical role in drug discovery from target identification, to early hit lead screening, to intensive structural characterization at the pre-NME stage. Historically, biophysics has been applied heavily in the late discovery phases as a drug candidate approaches the NME declaration. I will examine what assays are having the greatest impact in our workflows across the discovery space, and where we are looking to make in-roads into new functional areas.

9:10 Alternatives to SEC for Measuring Aggregates and Fragments

David HayesDavid Hayes, PhD, Principal Scientist, Boehringer Ingelheim Pharmaceuticals, Inc.

It is known that some aggregates cause immunogenicity and therefore it is important for analytical scientists to use multiple techniques to robustly monitor and control aggregate levels. Analytical Ultracentrifugation (AUC) is the gold standard technique orthogonal to SEC for aggregate quantification. This talk will outline best practices for using AUC and also discuss limitations of AUC in terms of precision and repeatability illustrated with examples using synthetic data.


9:40 KEYNOTE PRESENTATION: Capturing, Identifying and Visualizing Preaggregate Transients Using Chaperonin-Based Biolayer Interferometry Platforms

Mark T. FisherMark T. Fisher, PhD, Professor, Biochemistry and Molecular Biology, University of Kansas Medical Center

We can detect the presence of transient preaggregates within protein solutions using Chaperonin (GroEL) Biolayer interferometry (BLI) biosensors. ATP binding to GroEL Biosensors can specifically release captured proteins from the biosensor into microvolume aliquots. These released proteins are easily visualized by electron microscopy and evaluated using mass spectroscopy analysis. In some instances, we can even obtain low resolution 3D structures of released proteins released into these microvolumes using Electron Tomography.

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

10:55 AUC for the Biophysical Characterization of Gene Therapy Products

George Bou-AssafGeorge Bou-Assaf, PhD, Scientist, Technical Development, Biogen

During production of AAV-based therapeutics, some viral particles remain empty while others incorporate a partial gene of interest. Both species constitute impurities. Hence, accurate separation and quantitation from the main product, the full particle, is indispensable for the characterization of AAV-based therapeutics. We developed two AUC-based methods for the quantitation of aggregates and empty versus full particle ratios in gene therapy products to enable process development and drug product characterization.

11:25 Concentration Dependent ∆G Measurements Reveal the Mechanism of Aggregation for mAbs and Bispecifics

Ralf Joe CarrilloRalf Joe Carrillo, PhD, Senior Scientist, Physical Chemistry, AbbVie Bioresearch Center

ICD (Isothermal Chemical Denaturation) has been performed to characterize and predict aggregation for both mAb (monoclonal) and DVDs (dual variable domain) antibodies. ICD determines ∆G the Gibbs free energy of unfolding and concentration dependent measurements of ∆G elucidates the mechanism of aggregation revealing either native or partially unfolded propensities to aggregate. Determining the mechanism of aggregation aids greatly in rationally designing formulations and cuts down on the number and types of excipients utilized in formulations screens.

11:55 Labeling Methods for Understanding Protein-Protein Interactions

Michael B. Goshe, PhD, Associate Professor, Molecular and Structural Biochemistry, North Carolina State University

Alterations in the meta-stable three-dimensional structure of large protein therapeutics can lead to aggregation, decreased efficacy, unwanted side effects, and/or immunological responses and therefore must be reliably detected. We are developing a mass spectrometry-based platform that combines chemical crosslinking, hydrogen exchange, and customized software for assessing protein structure based on the identification of crosslinked peptide fragments. The presentation describes development of a toolbox of crosslinking technologies to characterize the structural integrity of mAbs.

 

12:25 pm Presentation to be Announced

12:40 Sponsored Presentation (Opportunity Available)

 

12:55 Luncheon Presentation I to be Announced

 

1:25 Luncheon Presentation II to be Announced

1:55 Session Break

粘度の測定

2:10 Chairperson's Remarks

Deniz B. TemelDeniz B. Temel, PhD, Scientist, Amgen


2:15 Predicting Viscosity of Therapeutic Antibodies: A Systematic Study Involving Small-Scale in vitro and in silico Methods

Hubert KettenbergerHubert Kettenberger, PhD, Senior Principal Scientist, Protein Engineering, Roche Innovation Center Munich, Germany

Subcutaneous or intravitreal administration of antibodies often requires a high protein concentration as well as a low viscosity. Viscosity measurement is low-throughput, cumbersome and demands comparatively high sample amounts. Using a set of approximately 30 therapeutic antibodies, we aim at identifying small-scale in vitro and in silico methods to predict viscosity.

2:45 Emerging Automated Viscosity Measurements with Small Sample Size: An Evaluation of Multiple Methods and Technologies

Deniz B. TemelDeniz B. Temel, PhD, Scientist, Amgen

It is crucial to optimize the usage of available samples and time for candidate differentiation, especially in terms of developability. There are many emerging methods and technologies with the promise to measure biophysical properties in a high throughput fashion with small sample consumption. In this talk, a number of instruments and methods, based on various physical principals, are evaluated and compared to measure (or predict) viscosity of biologics at high concentrations.

 

3:15 Talk Title to be Announced

John Champagne, Northeast Regional Manager, Wyatt Technology

A smorgasbord of biophysical screening capabilities for development and formulation of biologics: light scattering does it in plates.

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

4:45 Problem-Solving Breakout Discussions

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

7:00 End of Day

5月3日 (木)

8:00 am Morning Coffee

分光法の進歩

8:30 Chairperson's Remarks

Guodong ChenGuodong Chen, PhD, Research Fellow, Bioanalytical and Discovery Analytical Sciences, Bristol-Myers Squibb


8:35 Development and Implementation of a Component-Based Hydrogen-Deuterium Exchange MS System

Kristopher TruncaliKristopher Truncali, Scientist, Biophysics, Structural Characterization, Biologics Discovery Sciences, Janssen Research & Development

Hydrogen-Deuterium Exchange (HDX) mass spectrometry can provide critical insights into protein binding interactions. However, the technique's complexity has raised confusion around its routine utility and application. Here, we present an advanced HDX platform for early biophysical characterization of protein therapeutics. The workflow employs a LEAP H/D-X PAL, Thermo Orbitrap Fusion Lumos, Vanquish UHPLC, HDExaminer software, and in-house built automation software. The platform setup, applications, and limitations will be discussed.

9:05 Novel Mass Spectrometry-Based Strategies to Study Biomolecular Structure, Dynamics and Interactions in Complex Systems

Igor KaltashovIgor Kaltashov, PhD, Associate Professor, Chemistry, University of Massachusetts, Amherst

LC/MS is now routinely used in characterization of biopharmaceuticals, with reversed phase HPLC being the preferred separation method. In this presentation, we will discuss the advantages of using MS and MS/MS in combination with non-denaturing separation methods (ion exchange and size exclusion) to characterize complex therapeutic proteins. We will also present examples of using native LC/MS for characterization of other extremely heterogeneous macromolecular therapeutics, such as heparin and heparin-based medicines.

 

9:35 Presentation to be Announced

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

高次構造の特性評価

11:05 Higher Order Structure Determination: Strategy and Case Study

Guodong ChenGuodong Chen, PhD, Research Fellow, Bioanalytical and Discovery Analytical Sciences, Bristol-Myers Squibb

The higher order structure (HOS) of biologics plays an important role in stability, biophysical attributes, biological potency, and may have impact on safety and efficacy of biologics. Determining the HOS of biologics is a critical aspect of biologics discovery and development in the biopharmaceutical industry. This presentation will describe HOS determination strategy and methodology including case studies.

11:35 Novel Benchtop Method of Oxidative Footprinting for HOS Determination

Michael BrenowitzMichael Brenowitz, PhD, Professor, Biochemistry and Molecular Pharmacology, Albert Einstein College of Medicine

Controlled oxidation is an insightful method of protein structure determination well-suited to mapping protein-protein interfaces such as those between antibodies and epitopes. We present a robust method of quantitative hydroxyl radical generation based on Fenton chemistry that is readily implemented on the benchtop using common laboratory tools and scalable to robotic sample handling. Example maps of protein surface accessibility and binding interfaces will be presented.

12:05 pm The Role of Biophysical Tools in Understanding Comparability and Biosimilarity

William WeissWilliam Weiss, PhD, Principal Research Scientist and Group Leader, Biophysical Characterization, Eli Lilly and Company

Higher order structure (HOS) characterization is an important component of the broader analytical data package required to provide a comprehensive understanding of comparability/biosimilarity. This presentation will include an overview of established and emerging biophysical techniques for HOS characterization as well as discussion of important considerations for establishing comparability/biosimilarity of processes/products including selecting HOS techniques, developing and controlling methods based on these techniques, and comparing the resulting data.

12:35 End of Biophysical Analysis of Biotherapeutics

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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