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While Protein Expression may be regarded as an established field, cell line development advances and reaching higher titers in cell culture are critical components that enable and support the next generation of Protein Science. These bedrocks of recombinant Protein Expression benefit from innovations in DNA engineering, such as new transfection modes, automation, robotics, high-throughput technologies, and rapid analysis. Newer technologies produce advances that lead to quickly identifying high expressing clones, and improving protein solubility and stability.

THURSDAY, MAY 7


The Big Picture of Protein Expression

12:00pm  Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

1:40 Chairperson’s Remarks

Susan Sharfstein, Ph.D., Associate Professor, NanoBioscience, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute


1:50 KEYNOTE PRESENTATION

Speed to Clinic and Cell Line Stability: How Do We Reconcile These Competing Requirements?

Interview
James Fandl
James P. Fandl, Ph.D., Senior Vice President, Protein Expression Sciences, Regeneron Pharmaceuticals, Inc.

Clonality and stability, both of which are fundamental to a robust therapeutic protein production process, should be the sole key drivers in cell line development. However, the pressure to quickly deliver novel protein therapeutics to the clinic, and the economic demand for high productivity, may at times be in conflict with assuring clonality and stability. Regeneron’s approach for harmonizing these seemingly disparate drivers of cell line development will be discussed.
(Please read the March 2015 Interview)

2:20 Bioreactor Process Improvements in a Legacy Perfusion-Based Process

Lada-Laenen-HorvatLada Ivana Laenen Horvat, Ph.D., Senior Director and Head, Allston Manufacturing Science & Technology, Genzyme, A Sanofi Company

 

2:50 Development of Next-Generation of Therapeutic Proteins 

Ingo Gorr, Ph.D., Senior Scientist, Roche Diagnostics GmbH

We present an integrated approach to CHO cell line selection, USP, DSP and analytics that enabled us to deliver high quality drug substance. Supported by this approach, this presentation demonstrates that expression titer is not the primary selection criterion for the best suited clone. In summary, we have succeeded in designing and developing complex protein-based therapeutics for clinical use enabled by a sophisticated integrative technical program to select the best clone.

3:20 Efficient Manufacture of Autologous Therapeutics: Automated Hollow-Fiber Bioreactors as a Key Enabling Technology

Waniger_ScottScott Waniger, Director, Cell Culture, Biovest International

Production demand for protein therapeutics ranges from large scale commercial batches to small, unique lots required for patient-specific applications. To accommodate these diverse needs, a novel, fully automated system was developed for high density cell culture and collection of concentrated proteins. More specifically, this novel platform technology allows for concurrent production of numerous proteins and addresses regulatory concerns associated with multi-product facilities. Through feedback control and minimal operator interaction, this closed system results in a more safe and cost effective method for autologous or heterologous therapeutic protein production.

3:35 Optimizing CHO Expression for Rapid Identification of Relevant Drug Candidates with Flow Electroporation

JamesBradyJames Brady, Ph.D., MBA, Director, Technical Applications, MaxCyte, Inc

When preclinical research is done in a cell line other than the manufacturing cell line, promising candidates are overlooked while irrelevant candidates are put forward. Flow electroporation, a universal means of fully scalable TGE capable of producing multiple grams of antibodies, bispecifics, and non-antibody like recombinant proteins, enables R&D with CHO cells for rapid clinical-grade biotherapeutics. Using this technology and optimizing cell culture and transfection variables to further increase the amount of antibody produced will be discussed.

4:05 Refreshment Break

4:30 Problem-Solving Breakout Discussions

Next Generation Sequencing and its Role in Regulatory

Moderator: Chapman M. Wright, Ph.D., Scientist II, Cell Culture Development, Biogen Idec, Inc.


Baculovirus Insect Cell Expression System for Protein Production

Moderator: Nikolai Khramtsov, Ph.D., Associate Director, Upstream Development, Product Realization, Protein Sciences Corporation

  • Different baculovirus expression systems
  • Glycosylation in insect and mammalian cells
  • Generation of baculovirus stock with high titer
  • Storage of baculovirus stocks
  • Reduction of defective genomes during baculovirus amplification

5:20 End of Day

5:15 Registration for Dinner Short Courses


FRIDAY, MAY 8

8:00am  Morning Coffee


Synthetic Biology & Omics Technologies

8:30 Chairperson’s Remarks

Patrick Hossler, Ph.D., Senior Scientist III, Process Sciences, AbbVie Bioresearch Center

8:35 FEATURED PRESENTATION:
Mammalian Synthetic Biology: From Parts to Modules to Therapeutic Systems

Unpublished Data
RonWeiss
Ron Weiss, Ph.D., Professor, Biological Engineering, MIT

Synthetic biology is revolutionizing how we conceptualize and approach the engineering of biological systems. In this talk, we will discuss the creation of foundational elements for mammalian synthetic biology, including genetically encoded cellular sensors, information processing, and actuation. These genetic devices enable us to implement precise control over gene expression and other cellular behaviors. We will also briefly discuss applications that are uniquely enabled by genetically encoded programs, including cancer therapy, programmable organoids, and vaccination.

9:05 Next Generation Bioprocess: How the ‘Omics’ Era will Affect Future Biotherapeutic Development

Chapman M. Wright, Ph.D., Scientist II, Cell Culture Development, Biogen Idec, Inc.

The Next-Generation Sequencing (NGS) and Omics revolution has had a profound effect on the manner in which we approach the study of biology and medicine, but these effects are not limited to these fields alone. With the process of collecting and analyzing large datasets becoming more seamless, a growing number of disciplines are incorporating these techniques into their workflow. In this presentation, I will highlight areas of interest in which NGS and Omics could guide changes to current biotherapeutic development and lead us into the ‘next generation of bioprocess.’

9:35 Omics Meets Process Science: From Marker Discovery to Application

Sohye Kang, Ph.D., Senior Scientist, Amgen, Inc.

Omics technology allows integration of powerful analytical and computational tools to identify predictive markers associated with various phenotypes exhibited by different cell lines. Moreover, omics evaluations reveal mechanism of action associated with phenotypic changes induced by process or raw material alterations. Examining both intrinsic and external factors at the systems level using multi-omics approach could enable us to develop effective application strategies to improve recombinant protein production with desired product quality.

10:05 Coffee Break


Quality & Bioprocessing

10:35 Expression of Monoclonal Antibody Variants in Transient and Stable Cultures, the Effects of Sequence and Culture Temperature on Stability and Expression Level

SusanSharfsteinSusan Sharfstein, Ph.D., Associate Professor, NanoBioscience, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute

We examined the effects of protein sequence on expression level for two monoclonal antibodies with a single amino acid difference. The change in sequence altered the expression level more than ten-fold and significantly changed the protein stability. We found that reducing the culture temperature improved the expression of the lower productivity variant, but not the higher producing variant. Biophysical analysis suggested that lower culture temperatures improved the folding and stability of the lower productivity variant.

11:05 Quantification of Cytosolic Plasmid DNA Degradation Using High-Throughput Sequencing

MarkBanaszakHollMark M. Banaszak Holl, Ph.D., Professor, Chemistry and Biomedical Engineering, University of Michigan

Cytosolic DNA degradation plays an important role in decreasing transgene expression; however, the cleavage locations remain largely unexplored. High-throughput sequence mapping of cytosolic nuclease cleavage sites for Luciferase plasmid in HeLa cells revealed the following most common cut sites: the poly(A) region between the β-lactamase gene and the cytomegalovirus promoter, the 5’ end of the β-lactamase gene, the OriC region, the SV40/poly(A) region, the luciferase gene, and the CMV promoter.

11:35 High-Throughput Automation Solutions in Bioprocess Development

Unpublished Data
GregKeil
Gregory Keil, MS, Senior Scientist, Merck

Within Merck’s Bioprocess Development organization we have implemented a fully automated approach to cell line development involving multiple automation systems designed to streamline many of the activities involved in cell line development, characterization, and process development. Here we will demonstrate how a modular approach to automation allows for increased functionality, flexibility, and overall throughput. With these automation solutions in place bioprocess development has observed both increased efficiency and productivity across the entire the platform.

12:05pm Integrated Continuous Bioprocessing: A Bench-Top Factory Framework for Production of Complex Recombinant Proteins

MatsAkessonMats Åkesson, Ph.D., Principal Scientist, Cell Culture Technology, Novo Nordisk A/S

We have developed an integrated continuous framework for end-to-end production of complex recombinant proteins based on perfusion cultivation and automated multi-step purification. The integrated set-up employs standard laboratory equipment, and it enables compact automated bench-top factories converting cell culture media to purified protein without intermediate storage. Examples from production of complex recombinant proteins for preclinical supply will be presented.

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Refreshment Break


Optimizing Process Development

1:35 Chairperson’s Remarks

Mark M. Banaszak Holl, Ph.D., Professor, Chemistry and Biomedical Engineering, University of Michigan

1:40 Expansion of the Genetic Alphabet

FloydRomesbergFloyd Romesberg, Ph.D., Professor, Chemistry, The Scripps Research Institute

Expansion of the genetic alphabet to include a third base pair would be a fundamental accomplishment that would not only have immediate utility for a number of applications, but would also lay the foundation for a semi-synthetic organism. We have developed an unnatural base pair, d5SICS-dNaM, that forms based on packing and hydrophobic interactions rather than complementary H-bonding. Structural studies, as well as several applications, including ongoing selections for unnatural DNAzymes will be discussed.

2:10 Fast Early Development of a Complex Novel IL2-Based Immunocytokine

Ingo GorrIngo Gorr, Ph.D., Senior Scientist, Roche Diagnostics GmbH

We present a fast and elegant strategy for cell line selection and development of a manufacturing process for IL2 fusion proteins. Here, only cell line development (CLD), upstream processing (USP) and downstream processing (DSP) together were capable of reducing critical impurities and producing the molecule in high amount with high quality. Intriguing tricks to achieve a high quality therapeutic protein in combination with accelerated timelines are highlighted.

2:40 Cell Culture Media Supplementation of Uncommonly Used Sugars Sucrose and Tagatose for the Targeted Shifting of Protein Glycosylation Profiles of Recombinant Protein Therapeutics

Case Study
PatrickHossler
Patrick Hossler, Ph.D., Senior Scientist III, Process Sciences, AbbVie Bioresearch Center

Protein glycosylation is an important post-translational modification towards the structure & function of recombinant therapeutics. In this presentation we highlight a series of studies utilizing the uncommonly used sugars sucrose & tagatose for the targeted shifting of protein glycosylation profiles on recombinant glycoproteins. Both sugars were found to significantly increase the levels of high mannose N-glycans, and reduce fucosylation. Structure/function studies, as well as potential bioprocessing implications will be discussed.

3:10  Rapid Generation of Recombinant Baculoviruses for GMP Production of Recombinant Hemagglutinins, Components of Influenza Vaccine Flublok

Nikolai KhramtsovNikolai Khramtsov, Ph.D., Associate Director, Upstream Development, Product Realization, Protein Sciences Corp.

We developed universal process for the GMP production of influenza recombinant hemagglutinins (rHAs), components of seasonal influenza vaccine Flublok®. The GMP manufacture of drug substances in BEVS (baculovirus expression vector system) begins in less than two months from FDA announcement vaccine composition for new flu season (in February of each year). The rapid generation of recombinant baculoviruses containing rHA genes is completed within 25 days that allowed producing and delivering vaccine to the users on time.

3:40 End of Conference

 


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