Cambridge Healthtech Institute’s 9th Annual
Higher-Throughput Protein Production and Characterization
Analyzing & Improving Processes
January 23-24, 2020
Part of the Process Technologies & Purification pipeline
In Cambridge Healthtech Institute’s Higher-Throughput Protein Production and Characterization conference, HTP is explored in the quest to develop methods that ensure quality and translate to large scale much more quickly and efficiently than in
the past. Automation, robotics, and liquid handlers will be discussed, along with developing small-scale models and multi-scale models that shed light on bioproduction, particularly for continuous processing. Case studies will be presented that illustrate
how leaders in the field are integrating HTP approaches to reduce the time and effort needed to successfully analyze proteins, fine tune processes, and develop new classes of biological products.
Final Agenda
THURSDAY, JANUARY 23
7:45 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
8:10 Organizer’s Welcome Remarks
Mary Ruberry, MA, Senior Conference Director, Cambridge Healthtech Institute
8:15 Chairperson’s Opening Remarks
Christopher Bahl, PhD, Head, Protein Design, Protein Design Laboratory, Institute for Protein Innovation
KEYNOTE PRESENTATION
8:20 High-Throughput Generation of Protein Libraries for Early-Stage Development of Novel Therapeutics
Renaud Vincentelli, PhD, Head, High-Throughput Protein Production, Structural Biology Core, Architecture et Fonction des Macromolécules
Biologiques (AFMB), UMR, CNRS – Aix-Marseille University
This presentation details the high-throughput E. coli protein production pipeline at the AFMB and its streamlining to generate exhaustive libraries of various protein families, including animal toxins and PDZ domains. The
pipeline facilitates rapid expression screening, protein production, and sample quality control; thereby harnessing the potential of these large protein families for the development of novel therapeutics.
9:00 Platformization of Multi-Specific Protein Engineering III: Generating Large, Multiparametric Data Sets for Data Mining through End-to-End Automated High-Throughput
Engineering Workflows
Jörg
Birkenfeld, PhD, Section Head, High-Throughput Biologics, R&D Biologics Research/Protein Therapeutics, Sanofi-Aventis Deutschland GmbH
We recently established a novel, end-to-end automated process for the fast generation and characterization of very large panels of multi-specific variants (up to 10.000). Here we report on how we apply this high-throughput engineering platform for
multiparametric optimization of next-generation protein therapeutics.
9:30 Extended Horizons of LabChip™ Microfluidic Characterization Platform for Biotherapeutic Screening and Quality Control
Guangnan Meng, Product Manager, Microfluidics, PerkinElmer
The LabChip™ GXII Touch protein characterization system from PerkinElmer is a smart microfluidic platform for high throughput quantification and quality screening of protein molecules. With simple sample preparation setup, minimal sample volume
consummation, and accurate and reliable measurements, it has been widely adopted into modern biotherapeutic screening and quality control processes. We will present our latest development of protein characterization assays, and discuss the new
range and capabilities of the LabChip™ GXII Touch platform.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
FEATURED PRESENTATION
11:00 PEPP: An Automated High-Throughput Protein Production Platform
Sarah Rue, PhD, Associate
Director, Advanced Automation Technologies, Genomics Institute of the Novartis Research Foundation (GNF)
Recombinant protein expression and purification is critical to support biomedical research. Chinese hamster ovary (CHO) cells and Human Embryonic Kidney (HEK) cells are workhorse cell lines for protein production from mammalian cells. GNF
has developed a suite of automation and custom software to support transient protein production in CHO or HEK cells, stable pool establishment in CHO cells, the archive of cell banks, and protein purification. Cells are handled in AutoFlasks™
on the system, and cell growth is monitored in a non-invasive manner daily using a custom Flask Density Reader. An innovative new software Dashboard to help the operator manage projects and execute processes will be described, as will
new hardware to enable a magnetic bead-based purification workflow. This platform enables cost-effective, facile production of proteins at quantities and of quality useful for early stage drug discovery tasks such as screening and even
in vivo studies.
11:30 High-Throughput Production of Human Proteins for Structure/Function Analyses
Nicola Burgess-Brown, PhD, Principal Investigator, Nuffield Department of Medicine, SGC, University of Oxford
The SGC promotes research advancement through our open access policy. Globally, we have solved more than 2000 human protein structures and 12 novel integral membrane proteins (IMPs). Our well-established high-throughput processes for production
and validation of intracellular and membrane proteins will be presented with their success rates. In addition, optimization strategies employed over the past 15 years to tackle the most recalcitrant proteins; including mutagenesis, mammalian
(BacMam) expression, FSEC, and twin-step purification will be discussed.
12:00 pm Rapid Development of Soluble, Highly Productive, Scalable Biomanufacturing Solutions for Complex Biologics in E. coli SoluPro®
Matthew Weinstock, PhD, Group Leader, Molecular Sciences
12:30 Session Break
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
2:15 Chairperson’s Remarks
Sarah Rue, PhD, Associate Director, Advanced Automation Technologies, Genomics Institute of the Novartis Research Foundation (GNF)
2:20 NEW -- SPEAKER CANCELLED -- DNA-Encoded Glycan Libraries as a Next-Generation Tool for Screening and Measuring Sugar Binding
Peng George Wang, PhD, Professor, Pharmacology and Chemical Biology, Baylor College of Medicine
Screening, detecting, and measuring carbohydrate-protein or carbohydrate-cell interaction/recognition is crucial to the understanding of glycan involving physiological and pathogenic processes, intervention, and regulation. Adopting DNA next-gene
sequencing, we used DNA-encoded glycan library (DEGL) for high-content, high-throughput study of glycan-protein interaction. Here we will discuss novel methods designed specifically for the high-content synthesis of DNA-encoded glycans,
encoding and decoding principles, selection, and sequencing approaches for the easy and universal application of DEGL for screening and measuring sugar binding.
2:50 A High-Throughput Approach for Screening Protein-Protein Interactions in Complex Biofluids Using Protein Engineering
Liviu Movileanu, PhD, Professor, Physics, Biomedical and Chemical Engineering, Syracuse University
Protein-protein interactions (PPIs) are at the heart of cell signaling. Yet, we have very limited ways to quantitate them, especially in a heterogeneous solution, such as blood serum. We have manufactured a single-polypeptide chain protein
sensor capable of detecting transient PPIs, one interaction at a time. In this talk, I will show how a parallel electrical recording technology can be used for assessing this protein sensor in a scalable fashion.
3:20 Networking Refreshment Break (Sapphire West & Aqua West Foyer)
3:45 Application of a High-Throughput Antibody Optimization Platform: From NGS-Supported Library Generation to High-Throughput Antibody Expression and Multi-Parameter
Characterization of Large Variant Libraries
Ernst Weber,
PhD, Laboratory Head, Biologics Lead Optimization and Project Leader, Ophthalmology, Bayer Healthcare AG
The presentation will focus on the set-up of an HT antibody optimization platform capable of improving multiple parameters in parallel. It will cover the NGS-supported generation of 1-10k variants, their HT expression and testing in parallel
for multiple parameters, including stability, x-reactivity, affinity, potency, immunogenicity potential, etc., and will also include the IT infrastructure assembling and compiling the data. Case studies showing the capabilities and
flexibility of such platform success, including the optimization of antibodies targeting GPCRs, will be presented.
4:15 Characterization of Novel and Complex Antibody Formats
Markus Haberger, Group Leader, Development Characterization Analytics, Roche Diagnostics GmbH
The number of novel biotherapeutic antibody-based formats in drug development is continuously increasing. Characterization of these formats is challenging. Since established physiochemical and mass spectrometric methods show limited capabilities
for characterization of product-related impurities, new analytical strategies have to be developed. Here, we present a native MS-based HT analytical approach which successfully assisted in the elucidation of size and charge variants
of complex antibody formats, such as bispecific antibodies or antibody fusion proteins.
4:45 High-Throughput Production of Antibodies Using Yeast and Mammalian Cells
Jürgen
Nett, PhD, Director, High-Throughput Expression, Adimab, LLC
High-throughput, small-scale protein production is an essential part of the antibody discovery workflow. After isolation from a large yeast-based antibody library, we directly express large panels of full-length IgGs in 96-well and 24-well
formats. Protein purification is accomplished in a plate-based format using liquid handling platforms. The same semi-automated process is also compatible with IgGs expressed in mammalian hosts. Process setup, attributes, and output
will be reviewed.
5:15 Close of Day
FRIDAY, JANUARY 24
8:00 am Registration (Sapphire West Foyer)
8:00 BuzZ Sessions with Continental Breakfast
Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across the stages
of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies and strategies,
challenges, and future trends.
Click here for more details
9:00 Chairperson’s Remarks
Nicola Burgess-Brown, PhD, Principal Investigator, Nuffield Department of Medicine, SGC, University of Oxford
9:05 From DNA to Protein in Under 24 Hours; A Rapid and High-Throughput Method to Produce Native Protein
Christopher Bahl, PhD, Head, Protein Design, Protein Design Laboratory, Institute for Protein Innovation
We have optimized a protein production pipeline that enables the automatic expression and purification of proteins in 96-well plate format. Starting from plasmid DNA, the process can be performed in under 24 hours. Our method leverages
transformation and expression in Escherichia coli, autoinduction media, affinity purification using paramagnetic beads, on-bead post-translational modification and elution; and it enables proteins to
be produced in user-defined buffers.
9:35 Automated Formulation Development Using a High-Throughput Approach
Sabine Eichling, PhD, Head, Advanced Formulation Development, NBE Formulation Sciences, AbbVie Deutschland GmbH & Co KG
10:05 High-Throughput Cloning and IVTT Expression for Biomarker Discovery and Functional Genomics
Vel
Murugan, PhD, MBA, Research Scientist, Virginia G. Piper Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University
DNASU is a central repository for plasmid clones and collections. Currently, we store and distribute over 300,000 plasmids, including 75,000 human and mouse plasmids, full genome collections, the protein expression plasmids from the
Protein Structure Initiative as the PSI: Biology Material Repository, and both small and large collections from individual researchers. We currently possess the largest collection of human full-length clones in multiple expression-ready
plasmids. I will discuss HT cloning methods that we employ for generating expression clones.
10:35 Networking Coffee Break (Sapphire West & Aqua West Foyer)
11:00 Implementing High-Throughput Purification and Analytics Processes to Accelerate Identification of Promising Biologics Therapeutics
Daniel Yoo, Scientist, Therapeutic Discovery, Biologics Optimization, Amgen, Inc.
As new and emerging biologic therapeutics rapidly increase in complexity, there is a significant need for high throughput (HT) purification and analytics processes. Here, I present our implementation of rapid processes for screening
panels, advancements to our higher-throughput platforms to enable automated complex chromatography, and tools for robust, rapid protein characterization. These enhancements enable more comprehensive screening and informed lead
selection decisions.
11:30 Antibody Specificity Measurement and Scoring for Targeting Protein Post-Translational Modification Sites
Yongku
Cho, PhD, Assistant Professor, Chemical and Biomolecular Engineering, University of Connecticut
Antibodies targeting site-specific protein post-translational modification (PTM) is an emerging category of biotherapeutics. Many antibodies claim PTM-specificity, but users have no means of comparing their specificity. Here we
report a robust flow cytometry assay that enables the determination of a specificity parameter termed Φ, which measures the fraction of non-specific signal in antibody binding.
12:00 pm Conference Wrap-Up
Renaud Vincentelli, PhD, Head, High-Throughput Protein Production, Structural Biology Core, Architecture et Fonction des Macromolécules Biologiques
(AFMB), UMR, CNRS – Aix-Marseille University
12:30 Close of Conference