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Cambridge Healthtech Institute’s 18th Annual
Recombinant Protein Expression
Achieving Quality and Quantity
January 19-20, 2016

Biopharmaceuticals currently represent the fastest-growing sector of the pharmaceutical industry, driven by a rapid expansion in the manufacture of recombinant protein-based drugs. To meet the demand, it is crucial to increase the throughput of expression, production and purification processes and systems.

Cambridge Healthtech Institute’s Recombinant Protein Expression conference explores the newest data and innovations relating to the best choices in hosts / systems, as well as ways to “rescue” existing systems and make them work more effectively to produce the quality and quantity of the desired biotherapeutic.

Final Agenda


1:00 pm Conference Registration


2:00 Chairperson’s Opening Remarks

Lars Keld Nielsen, Ph.D., Chair & Professor, Biological Engineering, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland


2:05 Expressing Human Intracellular and Integral Membrane Proteins for Structural and Functional Studies

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

Production of human integral membrane proteins (IMPs) for structural studies, although still challenging, has advanced significantly over the past couple of years. Since 2004, the Structural Genomics Consortium (SGC) globally has solved more than 1700 soluble human protein structures in addition to five novel IMPs. These recombinant proteins have provided a rich resource for functional genomics, small molecule inhibitor screens and generation of antibodies. Our established expression systems will be presented as well as some new technologies to tackle challenging proteins.

2:45 Production of Human Lysosomal Enzymes in Microorganism: Achievements and Challenges

Carlos_Almeciga-DiazCarlos J. Alméciga-Díaz, Ph.D., BPharm, Associate Professor, Institute for the Study of Inborn Errors of Metabolism (IEIM), School of Sciences, Pontificia Universidad Javeriana

Lysosomal storage diseases are produced by the deficiency of an enzyme associated with the lysosomal catabolism of several substrates. Currently, the main treatment alternative is the use of recombinant enzymes produced in mammalian cells. As an alternative, microorganisms have been used as a host, showing the production of active and even therapeutic enzymes. Meanwhile, challenges involve the tailoring of N-glycosylation and the impact of O-glycosylations on protein production and efficacy.

3:15 Refreshment Break in the Exhibit Hall with Poster Awards

4:00 Selexis SUREscan™: De-Risking Research Cell Bank Generation with Comprehensive Genomic Analysis

Girod_Pierre-AlainPierre-Alain Girod, Ph.D., CSO, Selexis

RCBs are cell populations with neither identical genomes nor single integration sites even when selected from single isolated clones. The inherent genomic instability of CHO-K1 leads to the appearance of mixed populations that can result in decreased manufacturability. Selexis’s proprietary SUREscan™ bioinformatics, based on Next Generation Sequencing of entire genomes, provides unique and detailed genomic maps of cell populations. It is used to fully characterize integration sites and transgene sequences as well as provide detailed genomic information that reduces and mitigates risk while manufacturing recombinant protein drugs.

4:30 High-Titer Production of Knob-into-Hole Bispecific Antibodies in E. coli

James_GiulianottiJames Giulianotti, Senior Research Associate, Early Stage Cell Culture, Genentech, Inc.

Bispecific antibodies (bisAbs) are being developed by companies attempting to address complex disease states. Production of bisAbs in E. coli requires optimization of cellular processes within two distinct compartments (cytoplasm and periplasm) and across a single membrane (inner membrane). Over the past decade, technologies have been tested and implemented at Genentech that aid the production of bisAbs in E. coli. This talk discusses some recent work in this area.

5:00 Production of Complex Protein Therapeutics in the Chloroplast of the Green Algae Chlamydomonas reinhardtii

Miller_TranMiller Tran, Ph.D., Senior Scientist, Lead Discovery, Verdant Therapeutics, Inc.

Chlamydomonas reinhardtii chloroplasts have a unique biochemical environment that allows production of complex therapeutic proteins, including recombinant immunotoxins. Recent improvements in biomass and protein production in C. reinhardtii strains have been achieved through optimized fed-batch protocols and vector design. These improvements have made our system a potential platform for unique and complex protein products.


8:00 am Conference Registration and Morning Coffee


8:30 Chairperson’s Remarks

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

8:35 Light-Controlled Intracellular Delivery of Native Peptides and Proteins

Norbert_ReichNorbert O. Reich, Ph.D., Professor, Chemistry & Biochemistry, University of California, Santa Barbara

We have developed a nanoparticle-based platform to deliver proteins into specific cells with spatiotemporal control achieved through the use of highly penetrating near-infrared light. The delivery of therapeutic peptides as well as transcription factors provides a means to control the timing and amount of release for synthetic biology and translational applications.

9:05 Cell-Free Expression of High-Quality GPCRs in Eukaryotic and Prokaryotic Lysates

Ralf-Bernhardt Rues, Research Fellow, Institute of Biophysical Chemistry, Goethe University Frankfurt

GPCRs are crucial regulators of cellular physiology and play central roles in medical research. The development of efficient GPCR production pipelines based on synthetic biology is discussed. Key issues will be systems adaption to individual GPCRs, folding optimization with defined nanodisc and lysate combinations and directed engineering for sample stabilization. Presented examples are human endothelin as well as catecholamine binding receptors. GPCR sample properties obtained from either bacterial or insect cell lysates will be compared.

9:35 Automated Transient Transfection for High Throughput Protein Production

Suh_ChrisChris Suh, Ph.D., Business Development, PhyNexus, Inc.

Transient transfection of mammalian cell lines is being implemented by the pharmaceutical industry to produce the therapeutic protein candidates very rapidly compared to previous technology thus allowing large numbers of drug candidates to be screened and studied. However, high throughput automated transient transfection is required to cope with the dramatically increased sample load. Here we describe the integration, implementation and validation of different robotic platforms for automated transient transfection of mammalian cells.

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

10:50 Nanodisc in Drug Discovery: Assembly, Characterization and Application

Han_XuHan Xu, Ph.D., Principal Scientist, Amgen, Inc.

Integral membrane proteins (IMPs) are of therapeutic interest and are targeted by a majority of approved drugs. It’s difficult to express, purify and maintain the functional conformation of IMPs. Nanodisc presents a reliable method to solubilize and stabilize IMPs in detergent-free condition. In this presentation, I detail assembly and characterization of KcsA-Kv1.3 Nanodisc and demonstrate applications of Nanodisc in drug discovery.

11:20 Developing a Targeted Integration CHO Host for Clinical & Commercial Cell Line Development

Yongping_CrawfordYongping Crawford, Ph.D., Scientist, Early Stage Cell Culture, Genentech, Inc., a member of the Roche Group

11:50 Expression of Membrane Recombinant Hemagglutinins, Components of Influenza Vaccine Flublok®, Using Baculovirus Expression System

Nikolai_KhramstovNikolai Khramtsov, Ph.D., Associate Director, Upstream Development, Process Development, Protein Sciences Corp.

We developed a universal process for the GMP production of influenza recombinant hemagglutinins (rHAs), components of seasonal influenza vaccine Flublok®. The GMP manufacture in BEVS (baculovirus expression vector system) begins in less than two months from the FDA announcement of vaccine composition for a new flu season (in February of each year). Our results suggest that BEVS is a highly efficient system for expression of membrane-bound biologically active HAs.

12:20 pm ExpiCHO Transient Expression System: Comparative Data, New Applications and Tips for Maximal Performance

Zmuda_JonathanJonathan Zmuda, Ph.D., Associate Director, Cell Biology, Thermo Fisher Scientific

The ability to produce transient CHO-derived proteins early on during the drug development process is highly advantageous to minimize changes in critical quality attributes observed when progressing from discovery to bioproduction. Previous CHO-based transient systems have been hampered by low levels of protein production compared to HEK293 systems, in some instances 50-100 times less than the best 293-based systems. With the introduction of the ExpiCHO transient expression system, researchers have a flexible new tool to express proteins at significantly higher levels than in 293 cells, up to 3 grams per liter, while benefitting from the relevance of CHO cells. In this session we will present data comparing the ExpiCHO and Expi293 transient expression systems, newly-developed ExpiCHO applications notes as well as tips for ensuring easy set-up and maximal performance from the ExpiCHO transient expression system.

12:50 Session Break

Aragen horizontal1:00 Luncheon Presentation I: Development of an Extended Half-Life Erythropoietin for Treating Feline Anemia

Zhan_HangjunHangjun Zhan, Ph.D., Vice President and Head, Biologics Research, Kindred Bio

Due to various market pressures that are unique from human therapeutics, cost effective manufacturing of recombinant biologics is essential for veterinary applications. Here we present the development of high titer engineered feline EPO cell line for clinical trial and commercial manufacturing. In addition, product quality characterization including biophysical properties, in vitro activities and pharmacokinetics will also be discussed.

1:30 Luncheon Presentation II (Sponsorship Opportunity Available)


2:00 Chairperson’s Remarks

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

⊲ Featured Presentation
2:05 Multi-Omics Approach for Comparative Studies of Monoclonal Antibody-Producing CHO Cells

Lars_NielsenLars Keld Nielsen, Ph.D., Chair & Professor, Biological Engineering, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland

The availability of the CHO genome has renewed interest in using systems biology to guide rational strain design. Using optimized extraction, RNAseq and SWATH protocols for CHO, we here compared low- and high-producer clones from a single transfection pool. CVs of less than 5% were achieved for full biological triplicates and 55% of all identified proteins were differentially expressed. Targets for increased mAb production were identified and validated.

2:35 Designing CHO Cell Factories Using System Biology Models

Nathan_LewisNathan E. Lewis, Ph.D., Assistant Professor, Department of Pediatrics, University of California, San Diego

Cell line selection and development is becoming increasingly important for controlling critical quality attributes of recombinant therapeutic proteins. To guide the rational engineering of CHO cell lines, we are developing computational models of cell processes that influence product quality and using these models for data interpretation and predictive modeling, thus enabling the development of enhanced protein production hosts.

3:05 High-Throughput Stable Cell Line Platform

Sarah_RueSarah Rue, Ph.D., Senior Research Investigator, Genomics Institute of the Novartis Research Foundation

We have developed methods to establish antibody-expressing stable cell lines in a fully automated and high-throughput platform. This platform is integrated with GNF’s Protein Expression and Purification Platform (PEPP). This workstream is combined with different downstream expression workflows to enable fit-for-purpose use.

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

4:30 Speed-to-Clinic Cell Line Development without Compromising on Cell Line Stability

Gang_ChenGang Chen, Ph.D., Executive Director, Protein Expression Sciences, Regeneron Pharmaceuticals, Inc.

A key component of Regeneron’s rapid response platform for emerging infectious diseases is our speed-to-clinic cell line technology. Manufacturing-ready cell lines producing antibody-drug candidates are constructed in as short as 18 days. These speed-to-clinic cell lines have several design features that ensure exceptional genetic stability in the absence of prior single-cell cloning and stability screen. The quality attributes of the speed-to-clinic cell lines will be presented.

5:00 PANEL DISCUSSION: Considerations for CHO Cell Line Production and Recombinant Protein Expression

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



Gang Chen, Ph.D., Executive Director, Protein Expression Sciences, Regeneron Pharmaceuticals, Inc.

Nathan E. Lewis, Ph.D., Assistant Professor, Department of Pediatrics, University of California, San Diego

Lars Keld Nielsen, Ph.D., Chair & Professor, Biological Engineering, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland

Sarah Rue, Ph.D., Senior Research Investigator, Genomics Institute of the Novartis Research Foundation


6:30-7:30 Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Conference