PepTalk 2017
PepTalk 2017
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Cambridge Healthtech Institute’s Nineteenth Annual
Recombinant Protein Expression and Production
Achieving Quality and Quantity
January 10-11, 2017 | Hilton San Diego Bayfront | San Diego, CA


Biopharmaceuticals currently represent the fastest-growing sector of the pharmaceutical industry, driven by a rapid expansion in the manufacture of recombinant protein-based drugs. Consequently, the efficient expression and production of these valuable biomolecules face challenges in improving their quantity and quality while minimizing 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 protein, particularly as every biomolecule itself causes its own issues in terms of expression. 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 and Production 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.

TUESDAY, JANUARY 10

1:00 pm Conference Registration

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

BIOTHERAPEUTIC EXPRESSION AND PRODUCTION

2:00 Chairperson’s Opening Remarks

Donald L. Jarvis, Ph.D., Professor, Molecular Biology, University of Wyoming; President, GlycoBac, LLC


Keynote Presentation

2:05 High-Throughput Screening and Selection of Mammalian Cells for Enhanced Protein Production

Michael Betenbaugh, Ph.D., Professor, Chemical & Biomolecular Engineering, Johns Hopkins University

 


VACCINES

2:45 The Beginning of the End: HIV-1 Vaccine Design and Production

Jiang Zhu, Ph.D., Assistant Professor, Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, Scripps Research Institute

3:15 ExpiCHO: Latest Developments in High-Titer Transient Protein Expression in CHO Cells

Jonathan Zmuda, Director, Cell Biology, Thermo Fisher Scientific

The ExpiCHO™ transient expression system offers a turnkey solution for generating high-titer recombinant proteins for therapeutic drug development, reagent generation and hard-to-express proteins and has become an integral part of the transient expression workflow in companies around the world. Here, we share the latest data on the ExpiCHO expression system, tips for obtaining maximal performance and applications data supporting protein purification and characterization as well as protein production up to the multi-liter scale.

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

 

MEMBRANE PROTEINS

4:30 Strategies for Optimizing GPCR Expression and Production: Multi-Milligram Quantities of Functional Cannabinoid Receptor Isolated by Tandem Affinity Chromatography

Alexei_YeliseevAlexei Yeliseev, Ph.D., Staff Scientist, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, NIH

Human cannabinoid receptor CB2, a GPCR, is an important target for pharmaceutical drug development. We expressed the functional CB2 receptor and optimized its purification using novel affinity resins StrepTactin XT and EF2 Ca-calbindin-based resins. Applications of the CDFast chromatographic technique and the results of the SPR binding analysis will be presented as well as examples of selectively stable isotope-labeled CB2 and NMR studies on the agonist- and inverse agonist-bound receptor.

5:00 Production of Chemokine/Chemokine Receptor Complexes for Structural Studies

Martin_Gustavsson_BengtMartin Gustavsson, Ph.D., Staff Scientist, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego

Chemokine receptors are seven-transmembrane proteins that interact with chemokine ligands to drive cell migration. Despite the development of new methods for expression and purification of seven-transmembrane receptors, production of stable complexes between chemokine receptors and chemokines remains a challenging task. We present methods for producing purified complexes by co-expression in Sf9 cells. These methods have been successfully used for crystallization and biophysical experiments of CC as well as CXC receptor/chemokine complexes.

5:30 Close of Day


5:30 - 5:45 Short Course Registration

5:45 - 8:45 Dinner Short Courses*

* Separate registration required

WEDNESDAY, JANUARY 11

8:00 am Conference Registration and Morning Coffee

BIOTHERAPEUTIC EXPRESSION AND PRODUCTION (CONT.)

ANTIBODIES

8:30 Chairperson’s Remarks

Ashok D. Bandaranayake, Ph.D., Director, Bioprocess Development, Peptide Drug Discovery Initiative, Fred Hutchinson Cancer Research Center

8:35 Optimizing Antibody Expression by Using Natural Framework Diversity and Host Engineering in a Live Bacterial Antibody Display System

Noelle_LombanaNoelle Lombana, Ph.D., Senior Scientific Researcher, Antibody Engineering, Genentech

We present insights into a novel bacterial display system using full-length formats for antibody and antigen in a live cell setting. We discuss ways to improve expression and stability of antibodies in vitro by mimicking the natural antibody selection process, which translates to a mammalian host, as well as ways to improve antibody expression in host expression strains. We also cover novel use of high-throughput screening to study translocation, stability and protein folding in E. coli.

9:05 Rapid Production of Biologics with Pichia pastoris

Kerry_Routenberg_LoveKerry Routenberg Love, Ph.D., Research Associate & Technical Program Manager, InSCyT Program, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

Pichia pastoris has demonstrated utility as a host organism, yet relatively little strain engineering has been performed. Here, we present recent results using our genomic and transcriptomic insights to improve cultivation conditions and strain performance during heterologous protein expression. These upstream process developments have enabled the deployment of Pichia as the production host in a portable and distributed platform for real-time manufacturing of biologic drugs.

 9:35 Sponsored Presentation (Opportunity Available) 

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

 

PEPTIDE AND PROTEIN THERAPEUTICS

10:50 Characteristics and Utility of an Sf-Rhabdovirus-Negative Insect Cell Line for Baculovirus-Mediated Recombinant Protein Production

Donald_JarvisDonald L. Jarvis, Ph.D., Professor, Molecular Biology, University of Wyoming; President, GlycoBac, LLC

Recent work suggests all Spodoptera frugiperda-derived insect cell lines are contaminated with an adventitious viral agent, now known as Sf-rhabdovirus. This talk focuses on the characteristics of a novel, Sf-rhabdovirus-negative Sf cell line and its utility as an improved host for recombinant protein production in the baculovirus system.

11:20 A Cell-Free Expression and Purification Platform for Rapid and Flexible Production of Protein Biologics

John_DresiosJohn Dresios, Ph.D., Chief Scientist and Technical Fellow, Leidos, Inc.

We report on the development of a fluidic process for rapid end-to-end production of recombinant proteins. This process incorporates a bioreactor hosting a cell-free system programmed for transcription/translation of engineered DNA integrated with a series of configurable downstream purification/formulation modules for process-specific isolation of protein targets. Using this approach, we demonstrate production of two bioactive protein therapeutics, each within 24 hours. This process is flexible, scalable and amenable to automation.

11:50 Optides: A Novel Mid-Size Medicine Drug Discovery Platform Based on Knotted Proteins

Ashok_BandaranayakeAshok D. Bandaranayake, Ph.D., Director, Bioprocess Development, Peptide Drug Discovery Initiative, Fred Hutchinson Cancer Research Center

Knottins are highly disulfide crosslinked peptides associated with the venoms of insects. They inhabit a unique space between antibodies and small molecules but are difficult to make synthetically. We have developed a fully automated mammalian expression platform to generate these molecules as therapeutic leads. We call these optimized peptides Optides, and our first dye-peptide conjugate, Tumor Paint (Blaze Biosciences), is now in multiple clinical trials as a surgical aid for resecting tumors.

12:20 pm Presentation to be Announced

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

ENGINEERING AND SELECTING HIGH(ER) PRODUCERS

2:00 Chairperson’s Remarks

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

2:05 A Predictable, Plug-and-Play Cell Culture Platform Process

James_LambropoulosJames Lambropoulos, MS, Engineer III, Cell Culture Development, Biogen

We have implemented a defined workflow for early stage clinical cell line development. A meta-analysis of several monoclonal antibody products, in multiple host cell lines, demonstrates predictable trends and correlations amongst growth, metabolite, productivity, and quality attributes. This analysis confirms that our development platform is a robust and reliable workflow for generating representative, high-quality protein material for clinical use, and offers interesting avenues for further refinement of the process.

2:35 In the Pursuit of High Producers: Use of the Sony SH800 Cell Sorter for the Selection of Cell Lines with Superior Productivity Characteristics

Nadia Amharref, Ph.D., Scientist, Cell Line Development, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH

Shortening the process of developing and isolating high-producing cell lines remains a challenge. Our study focuses on the development of a simple and rapid method using Fluorescence-Activated Cell Sorting (FACS) for the screening of high-producing recombinant CHO cell lines. In this method, flow cytometry was partnered with a reporter protein for rapid, early stage identification of clones producing high levels of a therapeutic protein. A cell surface protein not normally expressed on CHO cells is co-expressed, as a reporter, with the therapeutic protein and detected using a fluorescently labeled antibody. The reporter protein’s expression level accurately predicts the relative expression level of the therapeutic protein for each clone.

3:05 Fast Cell Line Development for CHO Clones with High-Yield Protein Production Using Euchromatin-Containing BAC Expression Vectors

Anton_BauerAnton Bauer, Ph.D., COO, The Antibody Lab GmbH

Upon stable cell line generation, chromosomal integration site of the vector DNA has a major impact on transgene expression. By using chromosomal loci in BACs and random integration into host cell chromosomes, we developed stable high-yield production cell lines at an unprecedented speed. We performed several case studies for CHO production clones, and we established for antibodies and even difficult-to-express proteins generation of production clones within three weeks from transfection.

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

4:30 A Method for Specifically Targeting Two Independent Genomic Integration Sites for Co-Expression of Genes in CHO Cells

Joop van den Heuvel, Ph.D., Research Group Leader, Recombinant Protein Expression, Helmholtz Centre for Infection Research

5:00 Engineering Protein Production Hosts

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

We are using the combined competencies of scientific groups working within the areas of metabolic modelling, glycobiology, cell line engineering, high-throughput methodology and genome editing tool development to design and engineer the next generation of recombinant protein production hosts. The most recent results from high-throughput targeted genomic manipulations to engineer cells for tailored and homogenous glycosylation, increased productivity, improved product quality and more robust bioprocesses will be presented.

Buzz Sessions5:35 BuzZ Session B

Join your peers and colleagues for interactive roundtable discussions.

6:20-7:20 Reception in the Exhibit Hall with Poster Viewing

7:20 Close of Conference