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Conference

Difficult to Express Proteins

03 - 04 Nov 2014  New Date Reminder
Lisbon Marriott Hotel, Lisbon, Portugal

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The Difficult to Express Proteins, organized by the Cambridge Healthtech Institute will take place from 3rd November to the 4th November 2014 at the Lisbon Marriott Hotel in Lisbon, Portugal. The conference will cover areas like Controlling glycosylation, folding, immunogenicity, stability, toxic proteins , Managing disulfide bonds, Inclusion bodies, Low yields, Non-active expression results.


Timings

12:00 PM - 07:05 PM (Nov 03) (General)
07:30 AM - 06:45 PM (Nov 04) (General)

Entry Fees

Paid Ticket Starts from 125 EUR View Details

Participants

upto 100
Delegates
Estimated Count

Category & Type

Conference
Medical & Pharma

Editions

03 - 04 Nov 2014


Frequency Not Available

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Organizer

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Cambridge Innovation Institute USA

500 Total Events / 153 Upcoming Events 80+ Followers

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Speakers

Speaker
Andreas Pahl

Andreas Pahl

Chief Scientific Officer at Heidelberg Pharma Germany
Speaker
Matthew Baker, Ph.D

Matthew Baker, Ph.D

Immunology | Therapeutic Antibodies & Proteins | Research Commercialization at... Cambridge, Canada
Speaker
Murali Bilikallahalli

Murali Bilikallahalli

Associate Director at MedImmune LLC (AstraZeneca) United States
Speaker
David Pearlman

David Pearlman

Product Manager at Schrodinger United States
Speaker
Rakesh Dixit

Rakesh Dixit

Vice President, R & D at MedImmune (AstraZeneca Biologics) Gaithersburg, United States
Speaker
William (Jonny) Finlay

William (Jonny) Finlay

Director at Pfizer Ireland
Speaker
Melody Sauerborn

Melody Sauerborn

Senior expert immunogenicity TT/ Founder & CEO ADA InVivo at... Netherlands

Schedule & Agenda

Mon, 03 Nov 12:00 PM - 01:45 PMConference Registration
Mon, 03 Nov 01:45 PM - 01:50 PMPLENARY SESSION
PEGS Europe Team Welcome
Mon, 03 Nov 01:50 PM - 02:00 PMPLENARY SESSION
Chairpersonu2019s Opening Remarks William Finlay, Ph.D., Director, Global Biotherapeutic Technologies, Pfizer, Inc.
Mon, 03 Nov 02:00 PM - 02:45 PMPLENARY SESSION
The Impact of the New Regulatory Guidance Landscape on the Validation of the Manufacturing Process and the Characterisation of Starting Materials, Drug Substance and Drug Product Steffen GrossSteffen Gross, Ph.D., Head, Monoclonal and Polyclonal Antibodies, Paul-Ehrlich-Institut The regulatory guidance landscape regarding biological products changes rapidly. Documents overseeing process validation is currently facing major overhauls. New guidelines are published defining the requirements for starting materials and excipients. This might have a deep impact not only on the process development of traditional monoclonal antibody type products but also on new antibody formats such as conjugates as well as on new developed formulations.
Mon, 03 Nov 02:45 PM - 03:30 PMPLENARY SESSION
Current Progress with Armed Antibody Products Dario NeriDario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, ETH Zurich There is an emerging trend in Pharmaceutical Biotechnology to u201carmu201d antibodies, capable of selective localization at the site of disease, with suitable therapeutic payloads (e.g., drugs, cytokines, radionuclides, a second antibody moiety, hence producing a bispecific product). This strategy aims at concentrating therapeutic agents in diseased part of the body, while sparing normal tissues. In this lecture, I will present a comparative evaluation of different classes of armed antibody products, developed in my laboratory in collaboration with Philogen. In particular, I will present preclinical and clinical data of armed antibodies in the field of cancer, of chronic inflammation and of endometriosis.
Mon, 03 Nov 03:30 PM - 04:00 PMRefreshment Break
Mon, 03 Nov 04:00 PM - 04:05 PMENGINEERING BETTER HOSTS
Chairpersonu2019s Opening Remarks
Mon, 03 Nov 04:05 PM - 04:35 PMKEYNOTE PRESENTATION
Production of Protein Tools in Support of R&D Pharma ProjectsJacques DumasJacques Dumas, Ph.D., Head, Protein Production, Global Biotherapeutics, sanofiThe genomic era of the 90u2019s is culminating in the identification and production of novel protein targets for drug discovery. Increasing numbers of u201chigh valueu201d proteins are used for crystallography and High Throughput Screening (HTS). Proteins are produced by recombinant technology and purified to homogeneity using platform strategies. In the last 10 years, strategies have evolved to adapt to difficult to express proteins, such as kinases. In addition, the revival of biotherapeutic proteins has generated the need for new protein tools.
Mon, 03 Nov 04:35 PM - 05:05 PMHigh-Yield, Zero-Leakage Expression System in Escherichia coli
Yusuke Kato, Ph.D., Senior Researcher, Genetically Modified Organism Research Centre, National Institute of Agrobiological SciencesWe designed a high-yield, zero-leakage expression system using a transcriptional-translational double-regulation for toxic protein production in E. coli. u201cTranslational switchesu201d were constructed using site-specific unnatural amino acid incorporation at the amber stop codons that were inserted in target genes. Under repression conditions, leakage-expression was completely abolished by a synergistic repression both at the transcriptional and translational levels. In contrast, both transcription and translation were fully activated under induction conditions.
Mon, 03 Nov 05:05 PM - 05:35 PMAddressing Challenges for Production of Human Proteins and Multi-Protein Complexes Using the Baculovirus Expression System (BEVS)
Arnaud Poterzman, Research Director, Integrated Structural Biology, IGBMC/CNRSWe present here recent advances for the production of multi-subunit complexes in the baculovirus expression system using human multi-subunit transcription factors as model systems: Vector development for parallel expression/co-expression screening, use of Lambda red recombination in E. coli for manipulation and improvement of the baculoviral genome and assembly of multi-gene constructs from synthetic biology approaches. We will also discuss use of fluorescent proteins as infection makers and of baculovirus-infected insect cells (BIIC) for storage and standardization.
Mon, 03 Nov 05:35 PM - 06:05 PMSponsored Presentation (Opportunity Available)
Mon, 03 Nov 06:05 PM - 07:05 PMWelcome Reception in the Exhibit Hall with Poster Viewing
Mon, 03 Nov 07:05 PM - 07:05 PMEnd of Day One
Tue, 04 Nov 07:30 AM - 07:45 AMRegistration
Tue, 04 Nov 07:45 AM - 08:30 AMBreakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
Tue, 04 Nov 08:30 AM - 08:40 AMNOVEL STRATEGIES
Chairpersonu2019s Remarks
Tue, 04 Nov 08:40 AM - 09:10 AMHigher Yield u2013 An Ultimate Goal for Biological Product Development: A Case Study about Use of Process Intensification Technology for a Difficult to Express Glycoprotein
Mallika Singh, Ph.D., Associate Director, Upstream Development & Manufacturing, Teva Biopharmaceuticals USA, Inc.The case study will show the use of an emerging technology (process intensification technology using Alternating Tangential Flow, ATF) which will perhaps be the direction of cell culture manufacturing process for biologics in near future.
Tue, 04 Nov 09:10 AM - 09:40 AMExploring Codon Optimisation Strategies for Production of Membrane Proteins
Morten Nu00f8rholm, Ph.D., Academic Entrepreneurial Research Group Leader, DTU Biosustain; Technical University of Denmark, Novo Nordisk Foundation Center for BiosustainabilityUsing a library of GFP-tagged membrane proteins, we have compared different codon optimisation strategies including synonymous mutations in the 5u00b4end, complete re-coding using multiparameter optimisation algorithms and complementing rare codon usage with additional copies of the corresponding low-concentration tRNAs.
Tue, 04 Nov 09:40 AM - 10:10 AMChaperones Enable Native Folding of a Disulfide-rich Scorpion Toxin in the E.coli Periplasm
Andrias Ou2019Reilley, Ph.D., Researcher, Department of Physiology and Pathophysiology, Friedrich-Alexander Universitu00e4t Erlangen-Nu00fcrnbergAnimal neurotoxin peptides are valuable probes for studying ion channel pharmacology. Misfolding through formation of incorrect disulfide isomers has hindered recombinant toxin expression in E.coli. We report that co-secretion of a suite of protein disulphideisomerases and peptidyl-prolylcis/trans-isomerases into the E.coli periplasm boosts expression and produces correct folding of an insecticidal scorpion toxin, as validated by X-ray crystallography.
Tue, 04 Nov 10:10 AM - 10:50 AMCoffee Break in the Exhibit Hall with Poster Viewing
Tue, 04 Nov 10:50 AM - 11:20 AMcerevisiae-Based High Yield Expression System for Efficient Purification of High Quality Human/Eukaryotic Membrane Proteins for Structural Studies
Per Armstrup Pedersen, Ph.D., Professor, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Center for Microbial Biotechnology, Department of Systems Biology, Technical University of DenmarkWe have managed to develop a S. cerevisiae-based platform with the capacity to deposit eukaryotic membrane proteins to a density of up till 8% of total membrane protein content and identified conditions that allow efficient purification of high quality eukaryotic membrane proteins. We believe that our expression platform is of relevance for any membrane protein as we have managed to express and purify, 7TM receptors, P-type ATPases, K-channels, amino acid/hexose transporters/tranceptors.
Tue, 04 Nov 11:20 AM - 11:50 AMSponsored Presentation (Opportunity Available)
Tue, 04 Nov 11:50 AM - 12:50 PMProblem Solving Roundtable Discussions
Using Codon Optimisation to Facilitate Expression of Membrane ProteinsMortenNorholmModerator(s): Morton Nu00f8rholm, Ph.D., Academic Entrepreneurial Research Group Leader, DTU Biosustain; Technical University of Denmark, Novo Nordisk Foundation Center for BiosustainabilityCodon optimization choicesHost-related decisionsWhat to expectRecombinant Expression of Toxins and PeptidesJacques DumasModerator: Jacques Dumas, Ph.D., Head, Protein Production Vitry, Biologics SCP, Vitry Research Center, sanofiExpression systemsPeptide size limitationsMammalian vs microbialIs recombinant expression competitive to synthesis?Overcoming Challenges in Protein Expression with BaculovirusModerator: Arnaud Poterzman, Research Director, Integrated Structural Biology, IGBMC/CNRSWhen is baculovirus better?Tools for improving expressionTweaking the system
Tue, 04 Nov 12:50 PM - 02:00 PMLuncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
Tue, 04 Nov 02:00 PM - 02:30 PMDessert Break in the Exhibit Hall with Poster Viewing
Tue, 04 Nov 02:30 PM - 02:35 PMMODULAR APPROACHES, CO-EXPRESSION AND PARTNERS
Chairpersonu2019s RemarksStefanSchmidtStefan Schmidt, Ph.D., Vice President, Downstream Processing, Rentschler Biotechnology
Tue, 04 Nov 02:35 PM - 03:05 PMModular Approaches to Express Complex Therapeutic Proteins
Stefan Schmidt, Ph.D., Vice President, Downstream Processing, Rentschler BiotechnologyDifficult to express proteins represent an increasing amount of therapeutic molecules. This causes bioprocessing challenges such as controlling glycosylation, increasing titers and yields, suppressing aggregation and purification without specific affinity resins. Here we demonstrate how to develop modular quasi-platform processes solving these issues. The case studies with examples from various molecule classes highlight successful process design, optimisation strategies and critical manufacturing parameters. Additionally practical advice will be given what to consider when designing a novel molecule.
Tue, 04 Nov 03:05 PM - 03:35 PMEnhancing Protein Secretion of Clinically-Important Proteins
Tsafi Danieli, Ph.D., Head of Protein Expression Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life SciencesThe ability to improve recombinant protein secretion has significant biological and commercial benefits; Based on high throughput screening experiments, followed by bioinformatics analysis of protein databases of secreted vs. non-secreted proteins, we have developed an algorithm that can predict whether a protein will be poorly or efficiently secreted. We have tested our algorithm on several poorly secreted proteins, and found they all contained specific motifs that we predicted to impair translocation. We then demonstrated that disruption of these motifs by conserved replacement of a few amino acids resulted in a dramatic (up to 15 fold) enhancement of protein secretion in E.coli, insect cells and mammalian cells.
Tue, 04 Nov 03:35 PM - 04:05 PMHeterologous Expression and Purification of an Active Human TRPV3 Ion Channel
Stefan Kol, Ph.D., Protein Biochemist, Novo Nordisk Foundation Centre for Biosustainability, Danish Technical UniversityIn spite of great progress in the TRP-channel characterization, very little is known about their structure and interactions with other proteins at the atomic level. This is mainly caused by difficulties in obtaining functionally active samples of high homogeneity. I will present here the high-level Escherichia coli expression of the human TRPV3 channel, which retains its current inducing activity.
Tue, 04 Nov 04:05 PM - 04:35 PMSponsored Presentation (Opportunity Available)
Tue, 04 Nov 04:35 PM - 05:15 PMRefreshment Break in the Exhibit Hall with Poster Viewing
Tue, 04 Nov 05:15 PM - 05:45 PMExpression of Soluble and Active Interferon Consensus in SUMO Fusion Expression System in E. coli
Emmanuelle Laurine, Ph.D., PolyTherics Ltd.; The London Bioscience Innovation CentreInterferon consensus (IFN-con) is a non-natural recombinant interferon alpha displaying superior activity compared to most clinically used IFNu03b1-2a. However, production of this therapeutically promising protein remains challenging. Herein, we describe the optimisation of the production of IFN-con in E.coli as a soluble IFN-con. The recoded IFN-con gene was cloned into the Championu2122 pET SUMO expression vector downstream of the SUMO fusion protein under T7lac promoter and expressed in E.coli SHuffleuf7c5 strain. The fusion protein was efficiently expressed in soluble form and IFN-con remained stable following removal of the SUMO fusion partner. In addition, antiviral activity of the produced IFN-con was proven to be greater than activity of IFN u03b1-2a.
Tue, 04 Nov 05:45 PM - 06:15 PMTechnology for the Consistent Generation of Functional Antibody-Drug Candidates to Membrane Proteins
. Davis Farmer, Jr., Chairman, MSM Protein TechnologiesMSM Protein Technologies has developed proprietary methods for generating cell lines that over-express complex membrane proteins. We also have displays to present these proteins in their native conformation, highly purified for use in antibody discovery. To date we have generated fully human antibodies to several GPCRs that have met very stringent criteria as drug candidates. We will present an overview of the platforms and examples of antibodies that we have generated.
Tue, 04 Nov 06:15 PM - 06:45 PMExpression of USP18 (UBP43) for Enzymatic and Structural Analysis using a Trigger Factor Fusion System in E.Coli and Baculovirus Expression
Klaus Peter Knobeloch, Ph.D., Head, Liebniz Institute for Molecular PharmacologyProtein modification by ISG15 represents an interferon effector system counteracted by USP18. In mice, we selectively inactivated USP18 protease activity. Enhanced ISGylation increased resistance against influenza-virus infections qualifying USP18 inhibition as a potential antiviral strategy. Using a trigger factor fusion system in E.Coli and baculovirus expression we overcame poor USP18 expression yields, weak enzymatic activity and limited solubility, enabling us to perform inhibitor screens and solve the USP18/ISG15 complex crystal structure.
Tue, 04 Nov 06:45 PM - 06:45 PMEnd of Difficult to Express Proteins

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