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Cambridge Healthtech Institute’s Sixth Annual
Higher-Throughput Protein Production and Characterization
Innovating Processes
January 12-13, 2017 | Hilton San Diego Bayfront | San Diego, CA

High-throughput processes have transformed the traditional protein-by-protein trial-and-error approach for testing criteria and scaling up. In this leading conference on Higher-Throughput Protein Production and Characterization, HTP will be explored in the quest to develop methods that ensure quality and translate to large scale. Automation, robotics and liquid handlers will be discussed, along with developing small-scale models that shed light on bioproduction. Case studies will be presented that illustrate how leaders in the field are integrating HTP approaches in order to reduce the time and effort needed to successfully analyze proteins, fine tune processes, and achieve well-folded, pure protein.


7:45 am Conference Registration and Morning Coffee


8:15 Chairperson’s Opening Remarks

William Clay Brown, Ph.D., Associate Research Scientist and Scientific Director, High-Throughput Protein Lab, Center for Structural Biology/Life Sciences Institute, University of Michigan

Keynote Presentation

8:20 Scale-Down Models for High-Throughput Chromatography of Proteins

Alois JungbauerAlois Jungbauer, Ph.D., Professor, Laboratory of Protein Technology and Downstream Processing, Austrian Center of Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU)

To get reliable data from high throughput methods used for development and optimization of protein chromatography the measured parameters must allow prediction to pilot and large-scale operation. Microtiter plates are used to estimate equilibrium data. Models to predict the power input and stirring efficiency will be shown, and for kinetic data, scale-down models using mini chromatography columns will be discussed and methodology, how to scale it will be shown.

9:00 Automation Solutions for Different Stages of Protein Purification Process Development

Jean AucampJean Aucamp, Ph.D., Principal Scientist, Technology Development, Novel Biological Entities, Novartis Pharma AG

Advances in biotechnology significantly decreased timelines required for lead development while simultaneously increasing the number of leads of interest. These technology and cost drivers demand increased efficiencies in purification operations. Examples are presented demonstrating how automation supports protein purification and various stages of process development. Emphasis will be on approaches for combinatorial process synthesis, process robustness evaluation, scaled process confirmation and process characterization studies.

9:30 Enabling High Throughput Antibody Purification: Achieving mg Scale Antibody Production with Throughput and Quality

Jiyoung Hwang, MSc, Associate Scientist, Biology, Gilead Sciences

High-throughput antibody purification has become a growing area of focus. We have implemented a HTP purification platform that can process culture volumes ranging from 500uL up to 30mL, with elution products showing high purity. Coupling our HTP transient transfection of Expi293F and ExpiCHO cultures with our HTP purification platform has allowed us to produce milligram-scale titers of many antibodies, which has expanded our capability in supporting Gilead’s large molecule programs.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Multistage Purification of Human Antibodies for Candidate Selection Using an Automated Liquid Handler Platform That Enables High Throughput and High Recovery

Louis FabriLouis Fabri, Director, Protein Technologies, Research, CSL Limited

The selection of lead antibodies in pharmaceutical drug development programs initially involves generating a diverse repertoire of proteins using optimized transient mammalian expression systems. This presentation will describe the rapid purification of proteins, through multiple stages of chromatography, that have been generated via commercially available high titre transient mammalian expression systems such as Expi293F™ or ExpiCHO™, using our recently described Janus platform system coupled to a robotic arm.

11:30 Tackling Development Challenges of Non-MAb Biotherapeutics in Microbial Systems using HTPD
Georg_KilmaGeorg Klima, Dipl. Ing., Executive Director, Process Science, Boehringer Ingelheim RCV GmbH & Co KG
Increasing requirements for process and product understanding as well as process robustness together with decreasing timelines make alternative process development strategies a prerequisite for successful manufacturing development of new biotherapeutic drugs. This is particularly true for non-platform proteins like classical non-antibody proteins novel formats. To lever this complexity, Boehringer-Ingelheim Biopharma Austria has established a holistic approach based on a HTPD toolbox that integrates the whole process chain. Case studies using our flexible HTPD platform and its diverse applications ranging from early stage process development to late stage optimization and characterization studies for commercial processes will be highlighted.

12:00 pm Session Break

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Ice Cream Break in the Exhibit Hall with Poster Viewing


2:00 Chairperson’s Remarks

Louis Fabri, Director, Protein Technologies, Research, CSL Limited

2:05 Applying Synthetic Biochemistry and High-Throughput Processes to Enable Bugs to Make Drugs

Andrew_FosberryAndrew Fosberry, Ph.D., Senior Scientific Investigator, Protein and Cellular Sciences, GlaxoSmithKline plc

Chemical bio-transformations using enzymes and microbes to make small molecule drugs were a thing of the past, but not now! The realisation that bacteria make pretty good medicinal chemists and can actually do things that chemists cannot, along with other pressures such as cost of goods, and sustainability of our processes triggered a route change. I will give examples on how Synthetic Biochemistry is bringing chemistry and biology closer together to discover drugs.

2:35 Using High-Throughput Techniques to Produce Difficult Targets: Flavivirus NS1, an Updated Case Study

William Clay BrownWilliam Clay Brown, Ph.D., Associate Research Scientist and Scientific Director, High-Throughput Protein Lab, Center for Structural Biology/Life Sciences Institute, University of Michigan

Flavivirus, such as West Nile, Dengue and Zika, represent a serious global threat to human health. We applied high-throughput cloning and expression evaluation techniques and a matrix buffer screen to develop a robust production pipeline for NS1 protein, a multi-functional virulence factor, from several different Flavivirus, which resulted in the determination of crystal structures of full-length, glycosylated NS1.

3:05Calcium Dependent Fragment Immobilisation Technology (CD-FIT) - Highly Stable, Easily Regenerable Immobilisation for High-Throughput Kinetics Analysis of Binders to Targets

David_OConnellDavid O’Connell, Ph.D., Lecturer & Director, Biomolecular & Biomedical Science, University College Dublin, and Founder, YourProteome

To accurately rank binders to protein targets, a system that stably immobilises proteins on surface plasmon resonance surfaces is described. Using the complementation between two protein fragments proteins are immobilised in a directional manner at an optimal distance from the sensor chip surface to facilitate very accurate measurement of on and off rates with complete regeneration of the immobilised protein in 60 seconds facilitating high-throughput screening of very high affinity antibody fragments, peptides and small molecules.

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

4:15 HTP Production of the Human PDZ Repertoire, Identification and Ranking of the PDZ Interacting with the Human Papillomavirus E6 Oncoprotein

Renaud VincentelliRenaud Vincentelli, Ph.D., Head, Protein Production, Structural Biology Facility, CNRS Univ Aix Marseille I & II

Using our custom E. coli HTP protein production pipeline (Saez et al, JOVE 2014), we could produce the 266 human single PDZ domains. To characterize and quantify the HPV E6 - PDZome binding interactions, we automated the hold-up assay (Vincentelli et al, Nature Methods 2015), a quantitative and versatile in vitro protein-protein interaction assay. The protocol and some new results on this application will be exposed during the seminar.

4:45 A Fluorescent Protein Toolbox for Visualizing Protein Trafficking, Protein Interactions, and Membrane Protein Biogenesis  

Geoffrey WaldoGeoffrey Waldo, Ph.D., Team Leader, Los Alamos National Laboratory

We describe the split fluorescent protein toolbox we have developed for studying protein trafficking and protein-protein interactions. The system differs from others by the use of small peptide tags rather than large protein fragments. We describe case studies of its application in our lab and elsewhere to host-pathogen protein-protein interactions, trafficking of effectors, and protein-RNA interactions. We also cover recent applications for experimental elucidation of membrane protein topology and compare capturing the split GFP tag on nascent protein with detection after the membrane protein has been folded into the membrane.  

5:15 A Miniaturized Process Chain Representing the Entire Downstream Process for Inclusion Bodies

Cornelia Walther, Ph.D., Scientist, Biotechnology, University of Natural Resources and Life Sciences Vienna (BOKU)

We present a miniaturized high-throughput purification process representing the entire downstream purification for inclusion bodies from mechanical cell disruption to chromatographic purification. This downstream process chain connects extensive DoE setups in upstream development with the recovery of the active protein from inclusion bodies at a very early stage of process development. This fast and material saving platform method reduces the initial barrier for IB processes thus opening potential for new products.

5:45 Close of Day


8:00 am Conference Registration and Morning Coffee


8:30 Chairperson’s Remarks

Jonas V. Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich

8:35 High-Throughput Methods for the Characterization of Relevant Protein Features

Jonas SchaeferJonas V. Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich

To optimize the efficiency of the laborious process of generating specific affinity reagents, we established a streamlined pipeline consisting of simultaneous selections against 94 targets and subsequent high-throughput screenings and validations. This fast and efficient platform allowing the reliable discovery of recombinant binders requires the improvement of existing and the development of novel high-throughput methods which will be presented.

9:05 High-Throughput Biophysical and Biochemical Stability Screening for Early Stage Antibody Discovery

Yingda XuYingda Xu, Ph.D., Associate Director, Protein Analytics, Adimab LLC

Problems in the development of antibodies can often be traced back to their intrinsic poor biophysical and biochemical stabilities. High-throughput screening assays are developed or adapted to fit in the scope of early discovery stage to filter out candidates with poor properties.

9:35 High-Throughput Manufacturability Assessment of Complex Biologics

Zhenyu Gu, Ph.D., Development Scientist III, Early Assay Development, Alexion Pharmaceuticals

Bispecific/biparatopic antibodies, modified enzymes and fusion proteins have gained increasing popularity due to their unique therapeutic profiles. However, these molecules often pose significant challenges to manufacture as a result of their complex designs. In this study, high-throughput mechanical/chemical stress relevant to manufacture process was coupled with high-throughput orthogonal characterization methods to screen these early stage molecules for their manufacturability, focusing on solubility, aggregation, colloidal and thermal stability.

10:05 Coffee Break with a Poster Pavilion


11:00 Sequential Injection Capillary Electrophoresis for Bioprocess Monitoring

Rosanne_GuijtRosanne Guijt, Ph.D., Alexander von Humboldt Fellow and Senior Lecturer, Australian Centre for Research on Separation Science (ACROSS), University of Tasmania

Biological processes are naturally susceptible to variability because living cells consume substrates and produce metabolites and products in a dynamic way with variations in metabolic rate across short time intervals. This presentation explores the potential of capillary electrophoresis (CE) for bioprocess monitoring. Using a novel injection strategy, this fully automated system offers high sample throughput, good temporal resolution and low sample consumption combined with robustness, sensitivity and flexibility which provides a promising new platform for pharmacological and biotechnological studies.

11:30 High-Throughput Protein Analysis and Engineering Using Microcapillary Arrays

Spencer_AlfordSpencer Alford, Ph.D., Protein Engineer, xCella Biosciences, Inc.

We developed a high-throughput screening platform that allows researchers to assay the functional activity of millions of protein variants, displayed on or secreted from cells. This talk describes several protein analysis and engineering applications performed with this new technology platform.


1:15 Close of Conference


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