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Cambridge Healthtech Institute 第21回

Recombinant Protein Expression and Production
( 組み換えタンパク質の発現と製造 )

質と量の確保

2019年1月15日~16日

 

組み換えタンパク質の発現と製造をテーマにしたこのカンファレンスプログラムでは、宿主発現系の最良の選択肢に関連する最新のデータや新機軸などについてのセッションが予定されており、既存のシステムを「救出」し、効果的に機能させることで、必要な生物学的製剤の質と量を確保する方法なども議論されます。

Final Agenda

 

1月15日(火)

1:00 pm Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing

タンパク質発現から生物学的製剤製品へ

2:00 Chairperson’s Opening Remarks

Henry C. Chiou, PhD, Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific


KEYNOTE PRESENTATION

 2:05 Expression Systems for Various Biologics Modalities: Today and Tomorrow

Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck

Developing a robust expression system is the most critical step during biologics development for all modalities, including mAb, non-mAb complex molecules, and CAR-T, etc. A robust expression system can impact the productivity, also product qualities and process controls. In this presentation, we discuss the details of the major factors that need to be considered when developing the new expression system, and how to apply Quality-by-Design strategy at this stage.

2:45 Presentation to be Announced

3:15 ExpiSf, ExpiCHO and Expi293: Latest Developments in High-Titer Transient Protein Expression

Jonathan Zmuda, PhD, Director, Cell Biology, Thermo Fisher Scientific

The Expi Expression Systems comprise three different cell hosts to provide researchers with unprecedented access to high-titer recombinant proteins. Here, we highlight the latest data and recent additions to the Expi family of products, including the first ever chemically defined insect expression system, ExpiSf, a structural biology module for the Expi293 expression system, GMP-banked Expi293 and ExpiCHO-S cells and ExpiCHO Stable Production Media to support the transition from transient to stable protein expression.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

 

効果的な発現と製造:

VECTORS FOR GENE THERAPY

4:30 Optimizing Sf9-Based Stable Cell Lines for the Production of Highly Infectious rAAV Vectors

Sergei Zolotukhin, PhD, Professor, Department of Pediatrics, College of Medicine, University of Florida

We describe a new insect cell-based production platform utilizing attenuated Kozak sequence and a leaky ribosome scanning to achieve a serotype-specific modulation of AAV capsid proteins stoichiometry. By way of example, rAAV5 and rAAV9 were produced and comprehensively characterized side by side with HEK293-derived vectors. The data will be presented demonstrating a superior infectivity and higher genetic identity of OneBac-derived rAAV vectors providing a scalable platform for good manufacturing practice (GMP)-grade vector production.

5:00 LVV Production Process: Recent Advances and Opportunities for Innovation

Yogesh Waghmare, PhD, Associate Director, Vector Downstream Process Development, Bluebird Bio

LentiViral Vector (LVV)-based Cell and Gene Therapy products are steadily increasing in number. Industrial production of LVV poses significant challenges compared to AAV due to the large size, complexity, and labile nature of LVV. An overview of industrial LVV production process evolution, recent technological advances, and LVV specific challenges will be presented.

5:30 Close of Day

5:30 - 5:45 Short Course Registration


5:45 - 8:45 Recommended Dinner Short Courses*

SC5: Transient Protein Production in Mammalian Cells

Click here for more details.

*Separate registration required

1月16日(水)

7:45 am Registration and Morning Coffee

効果的な発現と製造:

ANTIBODIES

8:15 Chairperson’s Remarks

Jie Zhu, PhD, Associate Director, Cell Culture & Fermentation Sciences, MedImmune

FEATURED PRESENTATION

8:20 Controlling Protein Quality and Antibody Expression

Anne Skaja Robinson, PhD, Chair, Chemical and Biomolecular Engineering, Catherine and Henry Boh Professor of Engineering, Tulane Brain Institute Faculty Member, Tulane University

Monoclonal antibodies (mAbs) are a class of commercially valuable biopharmaceuticals that are used for treating diseases that are typically expressed in mammalian cell lines such as Chinese Hamster Ovary (CHO) cells to enable posttranslational modifications. One such posttranslational modification that results in structural and pharmacological changes in the protein is N-linked glycosylation. This talk addresses approaches to maintaining desired product quality of mAbs in the presence of process variations during manufacturing.

8:50 Therapeutic Antibody Fragments: Simplifying the Choice of the Expression Platform and Optimizing Protein L Capture

Philippe Billiald, PharmD, PhD, Professor, Biochemistry, University of Paris-Sud; Co-Founder, Acticor Biotech

Therapeutic antibody fragments are produced from various hosts, but no downstream process is well established. Here, we report a universal method to confer Protein L binding ability to any antibody fragment. In addition, based on a case study, we assess E. coli, P. pastoris and CHO expression systems in terms of cell line development, culture time, product quality and cost. We report differences to consider before pharmaceutical development and moving forward to the clinic.

9:20 Presentation to be Announced

9:35 Scaling Up and Scaling Out: Pushing the Boundaries of Transient Protein Production

Ian Wilkinson, PhD, CSO, Research & Development, Absolute Antibody Ltd.

Whilst transient yields have improved drastically in the last decade, scalable systems are time-consuming and costly to implement. Absolute Antibody has developed systems which scale up and scale out protein expression and purification, enabling the rapid and cost-effective production of milligram-to-gram quantities of large panels of proteins.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

10:35 Multi-Specificity of a Recombinant Monoclonal Antibody

Gary McLean, PhD, Reader in Molecular Immunology, Cellular and Molecular Immunology Research Centre, London Metropolitan University; Honorary Senior Research Fellow, National Heart and Lung Institute, Imperial College London

Whilst studying the cellular molecular switch protein m-ras, a recombinant monoclonal antibody was generated to an m-ras-specific peptide sequence. The recombinant antibody was expressed in mammalian cells and interestingly the IgG bound to both recombinant full-length m-ras and h-ras proteins. The cross-reactive binding of the monoclonal Ab to h-ras revealed that the Ab showed preference for peptide sequences containing multiple positively charged amino acid residues. These data reinforce the concept of antibody multi-specificity through multiple interactions of the Ab paratope with diverse polypeptides and emphasize the importance of immunogen and Ab selection processes when generating recombinant monoclonal Abs.

11:05 Mammalian Display Platform for Facile, FACS-Based Engineering of Antibodies and Other Receptors

Jennifer Maynard, PhD, Associate Professor, Chemical Engineering, University of Texas at Austin

Discovery of new antibodies is most commonly performed using phage or yeast display, but mammalian cells are used for large-scale production because of the complex antibody structure, including multiple disulfide bonds and a key glycosylation required for function. To circumvent problems associated with changing hosts, we developed a screening platform on CHO cells which allows for antibody selection in the same host used for manufacturing. We have used this approach to affinity mature an antibody Fab, a human T cell receptor and modulate binding of human IgG1 Fc to the FcgRIIIa receptor. Finally, modifications of the approach allow us to select for receptors that activate T cells in the presence of ligand as opposed to just binding the ligand.

11:35 Understanding and Engineering Fc Glycans in CHO Cells for the Production of Therapeutic Proteins

Jie Zhu, PhD, Associate Director, Cell Culture & Fermentation Sciences, MedImmune

Glycosylation of monoclonal antibody and derivatives plays an important role for complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) functions. Case studies are presented here on the generation of stable CHO cells cell line to produce recombinant proteins with desirable and consistent glycosylation patterns in Fc domain using both vector and host engineering approaches.

12:05 pm Session Break

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

2:00 PLENARY KEYNOTE PANEL

Click here for more details.

PepTalk Perspectives: Point-Counterpoint Discussions

Moderator:
Howard Levine, PhD, President and CEO, BioProcess Technology Consultants






Panelists:
Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck






Lorenz Mayr, PhD, CTO, GE Healthcare Life Sciences




 

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

 

効果的な発現と製造:

RECOMBINANT PROTEINS

4:00 Chairperson’s Remarks

Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

4:05 Implementing Next-Generation Sequencing for DNA-Based Sequence Variant Analysis of Recombinant Proteins

Ulrich Goepfert, PhD, Principal Scientist, Large Molecule Research, Roche Pharma Research & Early Development, Roche Innovation Center Munich

Sequence variants are unintended amino acid substitutions in biopharmaceuticals, which can either be due to the manufacturing process or mutations of the transgene. Transgene mutations are permanent properties of affected cell lines and may give rise to critical quality attributes. Therefore, mutated cell lines need to be identified and excluded from development. We share our experience with Next-Generation Sequencing as an efficient and highly sensitive method to detect DNA-based sequence variants.

4:35 The BEST of Both Worlds – Targeted Integration and Multiple Copies: How Can These Go Together for Improved Cell Line Development?

Anton Bauer, PhD, MBA, COO, R&D, The Antibody Lab GmbH

Targeted Hot Spot integration and multiplication of independent expression units – can this go together and even speed up cell line development? Targeted integration of the gene-of-interest in an expression hot spot is contributing to high protein expression yields as well as to epigenetic stability of selected clones. This increases the probability of identifying promising clones and lowers the attrition rate during process development. By targeting the Rosa26 Hot Spot in vitro we generated BAC-based expression vectors, which integrated in multiple copies into the CHO host cell chromatin and acted as independent expression units. This allowed us to adapt the selection process and developed long-term stable high-yield production cell lines at an unprecedented speed. New data from case studies and further improved vector versions demonstrate the capability of the technology.

5:05 Optimizing Productivity and Product Quality of Difficult-to-Express Biosimilars with a Novel NS0 Platform

Darryl Sampey, PhD, President & CEO, Research & Development, BioFactura, Inc.

Biosimilar cell lines that produce complex glycoproteins such as monoclonal antibodies must be both highly productive and express a product with critical quality attributes closely matching those of the innovator references. In this presentation, a novel biomanufacturing platform and case studies are described that harness the commercially established NS0 host cell in new ways to create stable, productive cell lines with product characteristics meeting biosimilar technical and regulatory demands.

5:35 Engineering CHO Cell Lines for the Production of Hard-to-Produce Proteins

Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

Using our high-throughput cell line engineering platform, we have engineered CHO cells able to produce a therapeutic protein that has previously not been possible to produce in CHO cells. This approach may result in improved therapeutic proteins, with better biological properties, such as increased half-life, improved activity, etc.

6:05 - 7:00 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Recombinant Protein Expression and Production Conference

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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