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Cambridge Healthtech Institute’s Ninth Annual
Optimising Expression Platforms

Meeting the Demand for Recombinant Antibodies

2-3 November 2016 | EPIC SANA Lisboa Hotel | Lisboa PORTUGAL

The utilisation of recombinant antibodies for basic research, clinical diagnostics and therapy continues to expand. Consequently, the efficient expression and production of these valuable biomolecules face challenges in improving their quantity and quality while minimising time and cost. To meet these demands, an increasing variety of recombinant production platforms are being developed. Unfortunately, there is no “universal” production system which can guarantee high yields of recombinant antibody, particularly as every antibody-based molecule itself causes its own issues in terms of expression.

The Optimising Expression Platforms conference offers comparisons, evaluations and solutions that enable researchers to efficiently express the recombinant antibody of their choice.

Final Agenda

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07:45 Registration and Morning Coffee

Engineering Expression Platforms to Meet the Demand

08:30 Chairperson’s Remarks

Bjørn Voldborg, MSc, Director, CHO Cell Line Development, Novo Nordisk Foundation Center for Biosustainability (CFB), DTU Biosustain, Technical University of Denmark

Animal Cells in Bioreactors for Production of High-Value Biologics – From Vaccines to Therapeutic Proteins, Lessons of the Past Applied Today and Tomorrow

Florian M. Wurm, Dr. rer. nat., Honorary Professor, Swiss Federal Institute of Technology Lausanne (EPFL); CEO, ExcellGene SA

The talk reviews the dramatic history of our industry -- 100 years -- towards high-value biologicals whose manufacturing requires a huge range of knowledge of fundamental and applied sciences in fields as diverse as molecular biology to fluid dynamics of water and gas. Reflecting and analysing the involved technologies in production provide excellent leads and opportunities for the future. CHO cells in bioreactors will be a central part of this discussion.

09:20 The Effect of Vector Design on the Expression of Bispecific Antibodies

Jason Saunders, MSc, Senior Scientist, Biologics Expression and Technology, Merck & Co., Inc.

09:50 Complementary Approaches for Protein Production in Insect and Mammalian Cell Lines

Konrad Buessow, Ph.D., Scientist, Helmholtz Centre for Infection Research

10:20 Strep-Tactin XT - A Superior Next-Generation System for Purification of Proteins, Isolation of Cells & Assay Development

Uwe Carl, Ph.D., Head, Protein Production, Strep-tag Products and Proteins, IBA GmbH

The new third-generation Strep-tag® system is based on recently engineered Strep-Tactin®XT and Twin-Strep-tag®. Due to the affinity improved but still reversible binding of Strep-Tactin®XT to Twin-Strep-tag® in the low pM range, the system is superior to other affinity purification systems and now also suitable for assay development.

10:35 Sponsored Presentation (Opportunity Available)

10:50 Coffee Break in the Exhibit Hall with Poster Viewing


11:30 Development of a CRISPR/Cas9 System for Engineering the Trichoplusia ni Genome for Improved Protein Production

Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.

We describe the complete sequencing of a Trichoplusia ni insect cell line, and the development of CRISPR/Cas9 reagents which permit modification of the genome of this line. We also show how this system can be used to engineer pathways for post-translation modification of proteins and also to enhance other aspects of the system to improve protein production yields and protein quality.

12:00 SINEUPs: A New Class of Antisense Long Non-Coding RNAs that Specifically Activate Translation of Targeted Proteins

Silvia Zucchelli, Ph.D., Assistant Professor, Health Sciences, University of Eastern Piedmont; CSO, TransSINE Technologies Inc.

SINEUPs represent a new functional class of natural and synthetic antisense long non-coding RNAs that upregulate translation of partially overlapping sense mRNAs through the activity of an inverted SINEB2 element. Given their modular structure, SINEUPs can be designed to increase protein synthesis of potentially any gene of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies.

12:30 Engineering of CHO Cell Lines for Enhanced Process Robustness

Pierre-Alain Girod, Ph.D., CSO, Selexis

High-quality production cell lines secreting maximal levels of recombinant proteins require stable integration of the recombinant DNA, elevated gene transcription, optimized secretion machinery to handle increased protein secretion and folding loads and, ideally, being easily tracked during manufacturing. Using the data from our CHO-K1 genome and transcriptome, we have engineered our CHO-K1 to address these issues, particularly for difficult-to-express proteins, as well as to provide detailed genomic analysis packages for manufacturing cell lines.

13:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:30 Session Break


14:00 Chairperson’s Remarks

Nicola Burgess-Brown, Ph.D., Principal Investigator, Biotechnology, Structural Genomics Consortium (SGC), University of Oxford

14:05 CHO Cell Energetics: Understanding the Powerhouse of the Cell through Mitochondrial Deep Sequencing

Paul S. Kelly, Ph.D., Senior Postdoctoral Researcher, School of Biotechnology, National Institute for Cellular Biotechnology, Dublin City University

The predominant metabolic pathways, glycolysis and oxidative phosphorylation, have been linked to critical bioprocess relevant CHO cell phenotypes, growth and productivity. We have shown SEAP producing CHO cells engineered to be depleted of microRNA-23b exhibited a 3-fold increase in product yield associated with elevated mitochondrial activity. Given CHO cells’ genetic instability, we sought to compare the mitochondrial genomic sequence of 22 CHO cell lines and provide a mitochondrial genome reference sequence from the hamster.

14:35 Harmonization of Transient CHO and Stable CHO Expression Platforms for Early Phase Drug Discovery

Gavin Barnard, Ph.D., Group Leader, Eli Lilly and Company

We describe the development of a transient CHO system capable of generating high titers, currently scalable to 6L. Additionally, we describe the generation of high titer stable CHO bulk pools (instead of clones) for the expression of gram quantities of therapeutic protein. Using the same plasmid DNA, CHO cell line and media for both platforms streamlines expression during early phase drug discovery.

15:05 Inactivation of GDP-Fucose Transporter in CHO Cells: A New Strategy for Producing Fucose-Free Biobetter Antibody Therapeutics

Zhiwei Song, Ph.D., Principal Scientist, Expression Engineering Group, Lead PI for GlycoSing Programme, Bioprocessing Technology Institute, A*STAR

Removal of core fucose from IgG1 has been shown to significantly enhance its affinity to FcgRIII and thereby dramatically improves its antibody-dependent cellular cytotoxicity (ADCC). To address these industry-specific needs, we have inactivated the GDP-fucose transporter in CHO cells. The DHFR and GS genes have also been inactivated in these cells as selection markers. Using these cells, stable lines have been developed to produce fucose-free rituximab and fucose-free obinutuzumab (Gazyva).

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing


16:15 A Big Step Forward for Next-Generation CHO Clone Characterization and Selection

Oliver Popp, Ph.D., Pharma Research and Early Development, Cell Culture Research, Roche Innovation Center Munich, Roche Diagnostics GmbH

In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. For that, we established a novel hybrid approach for supporting comprehensive characterization of metabolic CHO clone performance. The proposed approach also provides a mechanistic link between observed clone phenotype, process setup, and feeding regimes, and thereby offers concrete starting points for subsequent process optimization.

16:45 FEATURED PRESENTATION: Engineering the CHO Cell

Bjørn Voldborg, MSc, Director, CHO Cell Line Development, Novo Nordisk Foundation Center for Biosustainability (CFB), DTU Biosustain, Technical University of Denmark

Using high-throughput (HT) technologies, the CHO Cell Line Engineering project at the Center for Biosustainability is genetically modifying CHO cells based on experimental and in silico generated data, to engineer CHO cell lines optimised for the production of therapeutic proteins. The HT cell line engineering pipeline as well as examples of the engineered improved cell lines will be described.

17:15 Problem-Solving Breakout Discussions

18:15 Networking Reception in the Exhibit Hall with Poster Viewing

19:15 End of Day

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08:00 Registration and Morning Coffee


08:30 Chairperson’s Remarks

Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific

08:35 Expression of IgG in Genetically Engineered E. coli

Na Ke, Ph.D., Research Scientist, Protein Expression and Modification Division, New England Biolabs

We have expressed for the first time in the cytoplasm of E. coli full-length human, rabbit and mouse antibodies, along with chimeric versions, including the commercial blockbuster Humira. The expression is further improved by the co-expression of a series of protein-folding helpers. Microbial expression of IgG offers an expanded potential for rapid screening, engineering and expression antibodies.

09:05 Meeting Demand: Optimisation of Our Transient Expression Platforms to Increase Throughput and Titre

Christina Gordon, Scientist, New Meds, UCB Pharma

Development of antibody therapeutics, from early stage research to preclinical and clinical development, requires ever-increasing amounts of reagents. To meet the challenge of furnishing a diverse and full pipeline, we utilise several different transient platforms. Through continuous optimisation, streamlining and automation of component parts of our panel of platforms (utilising both HEK293 and CHO host cells with a variety of transfection methods), we now have the capability to produce microgram-to-gram quantities of panels of purified antibodies and antibody fragments in as few as four weeks from receipt of plasmid DNA.

09:35 Server of Many Masters: The Challenges of a Slim Protein Expression Core Facility

Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, Protein Expression Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem

Running a small core facility that serves multiple academic groups with a wide range of disciplines is extremely challenging. Trying to do it with one technician, two postdocs and no automated platforms sounds like mission impossible. However, it is all about the surrounding! An academic environment and supporting ecosystem allowed our facility to turn the challenge into a new model that successfully accommodates not only academic groups but also early stage biotech startups.

10:05 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing


11:15 Efficient Production of Recombinant Human Monoclonal Antibodies from Single B Cells

Hugo Mouquet, Ph.D., Head, Laboratory of Humoral Response to Pathogens, Immunology, Institut Pasteur

The molecular dissection of anti-pathogen B-cell responses using modern technologies to efficiently generate and characterize antigen-specific human monoclonal antibodies has allowed breakthrough discoveries in antiviral responses to viruses such as Influenza virus and HIV-1. These recombinant antibodies represent unique “fingerprints” for each B-cell clone and when characterized at a molecular and functional level, provide crucial information to help developing therapeutic and vaccine strategies against a given pathogen.

11:45 FEATURED PRESENTATION: Expressing Challenging Proteins at the SGC

Nicola Burgess-Brown, Ph.D., Principal Investigator, Biotechnology, Structural Genomics Consortium (SGC), University of Oxford

The SGC has solved >1700 human protein structures and 6 novel integral membrane proteins. Although we have significantly contributed to structural biology and protein production for functional studies, there are many highly desired targets including protein-protein complexes and known drug targets that remain a challenge to obtain. We present our established expression systems using E. coli and BEVS, and new processes (BacMam and mutagenesis) to generate the most difficult-to-produce proteins.

12:15 Enjoy Lunch on Your Own

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

13:30 End of Optimising Expression Platforms

Day 1 | Day 2 | Download Brochure