2013 Archived Content
 

Expression Stream

3rd Annual
Optimizing Protein Expression

Enhancing Expression Systems

May 1-2, 2013

Day 1 | Day 2 | Download Brochure 


 Tuesday, April 30 from 4:15 - 5:30 PLENARY KEYNOTE PANEL 

Conventional vs. Non-Conventional Formats 

 Janice ReichertModerator: Janice Reichert, Ph.D., Editor-in-Chief, mAbs; Managing Director, Reichert Biotechnology Consulting LLC
With the explosion in the number of formats available, what are the potential benefits and risks to patients? This panel will discuss the realistic outlook and uncertainties with developing a diverse array of non-canonical antibodies in terms of immunogenicity, safety, competitive marketplace, commercial development, business strategies, regulatory approval, target validation and clinical development.
 

Panelists: 

David Meininger David Meininger, Ph.D., MBA, Executive Director, Molecular Discovery, Merck





 

Tillman GerngrossTillman Gerngross, Ph.D., CEO and Co-Founder, Adimab LLC; Professor, Bioengineering, Thayer School of Engineering, Dartmouth College




 

Trudi VeldmanTrudi Veldman, Ph.D., Senior Director, Biologics Generation, AbbVie





 


WEDNESDAY, MAY 1

7:00 am Conference Registration and Morning Coffee


Protein Expression Challenges and Regulation 

8:30 Chairperson's Opening Remarks

George W. Buchman, Ph.D., Vice President and CSO, Chesapeake PERL, Inc.


8:40  OPENING KEYNOTE PRESENTATION: 

Protein Expression: Past Achievements and Future Prospects

John BirchJohn Birch, Ph.D., Consultant, Henley-on-Thames (former CSO of Lonza Biopharmaceuticals)
The last three decades have seen remarkable progress in the development of recombinant biopharmaceutical proteins. Well over one hundred recombinant proteins are approved and many hundreds more are in development. This talk will review the key developments in protein production technology that have made this progress possible and will look at potential future trends.


9:10  Featured Presentation 

Regulatory Expectations for Expression Systems for Manufacturing Therapeutic Proteins

Baolin ZhangBaolin Zhang, Ph.D., Senior Investigator & Drug Quality Reviewer, Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA)

Most novel protein products are produced by recombinant DNA technology, which utilizes a cell-based expression system (e.g. E. coli, yeast and mammalian cells), or by transgenic animals. This presentation takes a close look at each of these expression systems, particularly glycosylation, as well as regulatory perspectives and quality control measures for production of recombinant therapeutic proteins. 


9:40  Featured Presentation 

Developing and Regulating Bioengineered Therapeutic Proteins: Synonymous Mutations Might Matter

Chava Kimchi-Sarfaty, Ph.D., Principal Investigator, Senior Staff Fellow, Hematology, Center for Biologics, Evaluation and Research (CBER) Food and Drug Administration (FDA)

Because of the redundancy in the human genetic code, many recombinant proteins produced in the pharmaceutical industry are introduced with synonymous mutations to optimize yield. The optimized and other unnatural sequences may have a significant impact on function of these therapeutic proteins. The presentation will discuss possible effects of mutations on a broad spectrum of recombinant therapeutic proteins.


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


Compare/Contrast Expression Systems 

11:10   Comparing Host Systems for Heterologous Protein Expression: Predicting a Likely Best Choice or Testing in Parallel

Dominic EspositoDominic Esposito, Ph.D., Director, Protein Expression Lab, Advanced Technology Program Directorate, SAIC Frederick

We will present data showing how the three main systems (E. coli, insect, and HEK293 cells) compare and differ for a variety of case study proteins, and offer suggestions on how to determine which host system is best for a given target protein or of proteins.  Microscale processes which allow parallel processing of samples will also be discussed.

11:40   Expression Optimization Strategy Guided by Russell Body-Inducing Propensity of Individual IgG Clones

Haruki HasegawaHaruki Hasegawa, Ph.D., Senior Scientist, Protein Science, Amgen, Inc.

Russell bodies (RBs) are intracellular aggregates of immunoglobulins that cannot be secreted or degraded. In this talk, I will highlight the impact of differential RB-inducing propensities on the outcomes of protein secretion output. I also explore the value of imaging-based RB detection assays to assess IgGs' over-expression fitness to guide protein engineering and cell phenotype engineering strategies.

Wacker Biotech 12:10pm  Secretory E. Coli Technology: An Innovative System for the Production of Novel Biopharmaceuticals

Silvana Di Cesare, Ph.D., Manager, Business Development, Wacker Biotech GmbH

Antibody fragments and protein scaffolds are the current trend in the biotechnology industry, as they are significantly less complex than antibodies yet still retain high target specificity. Selected case studies will be presented on the use of a unique secretory E. coli system for the production of these novel biopharmaceuticals and their easy recovery from the culture medium, thus reducing cost of goods.
 

Catalent 12:40 Luncheon Presentation I: Cell Line Engineering Case Studies Using Multiple Human and CHO Cell Lines in Combination with GPEx®

Gregory Bleck, Ph.D., Research & Development Platform Lead, Biologics, Catalent Pharma Solutions

Case studies examining the use of GPEx in 293 HEK cells and multiple CHO cell lineages to express various antibodies and other recombinant proteins will be outlined.  The presentation will discuss clonal cell line growth characteristics, protein expression and specific productivity data demonstrating the ability of the GPEx process to yield consistent results in many different cell lines.  Process development results for these cell lines will also be shown.

ProteoNic1:10 Luncheon Presentation II: Novel UNic™ Vectors Boosting Recombinant Protein Production

Maurice van der Heijden, Ph.D., Research Manager, ProteoNic

ProteoNic's UNic™ Translation Enhancing Elements (TEEs) improve translation in a recombinant protein expression vector. The TEE-s have been tailored for major eukaryotic production platforms, including mammalian cells, yeast, and baculovirus. The TEEs are compatible with existing transcriptional enhancer technologies. ProteoNic recently developed mammalian expression vectors comprising optimized transcription and translation enhancing elements. Here we present examples of boosted antibody and non-antibody expression in CHO-S cells.


Expression in Chinese Hamster Ovary Cells (CHO)  

2:00 Chairperson's Remarks

Sebastien Ribault, Ph.D., Director, Development and BioProduction, Merck Biodevelopment

2:05 Early Prediction of Instability of CHO Cell Lines

Subinay GangulySubinay Ganguly, Ph.D., Scientific Director, CMC Team Lead, Centyrex, Janssen R&D, Johnson & Johnson

One of the most important criteria for the successful manufacture of a therapeutic protein, e.g., an antibody) is to develop a mammalian cell line that maintains stability of production. In the absence of that, problems with process yield, lack of effective use of costly resources, and a possible delay in obtaining regulatory approval of the product can occur. This presentation will highlight investigation of expression stability in a number of Chinese Hamster Ovary (CHO) derived production cell lines and development of a screening protocol that identifies unstable CHO production cell lines at an early stage of the cell line development process.

2:35  Can Modification of Untranslated and Signal Sequences Improve Recombinant Protein Expression from CHO Cells?

John HeskethJohn E. Hesketh, Ph.D., Professor, Mammalian Molecular Biology, Institute for Cell and Molecular Biosciences, University of Newcastle Medical School

Mammalian cell factories using Chinese hamster ovary (CHO) cells are used frequently for recombinant protein production but there is considerable scope to increase expression levels. We have used a secreted luciferase model in CHO cells to investigate the extent to which modification of key elements within the expression vector (signal sequence or 3'untranslated region) can improve expression.

MaxCyte 3:05  Streamlining Antibody Development Using Large Scale, CHO Transient Gene Expression (TGE) followed by Rapid Production of CHO Stable Clones

James Brady, Ph.D., Director, Technical Applications, MaxCyte Inc. 

Flow electroporation greatly shortens the timeline of antibody development by enabling large scale transient gene expression (TGE) directly within CHO cells and eliminating the need to change cell backgrounds during scale up to biomanufacturing. Using the MaxCyte STX® Scalable Transfection System, antibody titers greater than 400 mg/L allow for production of over a gram of antibody from <3L culture volume following a single CHO transfection.  A simple selection protocol enables production of stable CHO clones generating titers >1g/L in 6 weeks.

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


Baculovirus & Recombinant Vaccine Expression Challenges 

4:20 Expression of Human Major Vault Protein in Whole Insects Using Baculovirus: Formulation of a Vault-CCL21 Nanocapsule as a Lung Cancer Treatment

George BuchmanGeorge W. Buchman, Ph.D., Vice President and CSO, Chesapeake PERL, Inc.

"Vaults" are naturally-occurring protein particles found in all higher eukaryotes, formed from self-assembly of the Major Vault Protein (MVP).  C-PERL has produced vaults at very high levels by infection of whole insect larvae with recombinant baculovirus expressing MVP.  Current progress in the preparation and evaluation of a CCL21-vault "nanocapsule" as a candidate lung cancer therapeutic will be discussed.

4:50 Tackling Recombinant Vaccine Expression Challenges: Screening and Optimization of Platforms

Shyamsundar Subramanian, Ph.D., Principal Scientist and Head, Expression Systems Group, Vaccine R&D, Merck & Co.

Vaccine products have very long lifecycles and therefore early irreversible decisions, such as the choice of expression system can have profound impact on manufacturing and supply. To make the right decisions, early investments of resources to screen expression systems and optimize their performance is needed, especially so for recombinant products. Case studies on multiple recombinant vaccine candidates will be presented on executing this strategy, paving the way for uninterrupted future vaccine supply.

Blue Sky Bioservices5:20 - 6:30 Networking Reception in the Exhibit Hall with Poster Viewing



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