protein purification technology



As more and more biological drugs are developed, an increasing demand falls on achieving pure protein, either for research or for therapeutic development. Achieving pure protein quicker and cheaper is essential, while also ensuring protein quality. Researchers must streamline the steps required to achieve purity, but protein’s intrinsic nature can cause headaches and frustrations. When faced with greater protein challenges, such as membrane proteins, expanding the purification toolbox becomes extremely helpful.

In addition, new technologies are continually emerging that offer support, and traditional techniques, such as chromatography and Protein A, are also being innovated. The “Protein Purification Technologies” conference explores current strategies that are proving successful, and looks at new ways to streamline techniques in the continual quest for purity.

Final Agenda

THURSDAY 21 NOVEMBER

13:00 Registration (Foyer A)

13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

CONTINUOUS PROCESSESING
Auditorium II

14:00 Chairperson’s Opening Remarks

Ana Correia, PhD, Scientist, Biologics Optimization, Amgen, Inc.


14:05 KEYNOTE PRESENTATION: Hot Topics in Continuous Chromatography for Protein Purification

Massimo Morbidelli, Professor, Chimica, Materiali e Ingegneria Chimica, Giulio Natta, Politecnico di MilanoMassimo Morbidelli, PhD, Professor, Chimica, Materiali e Ingegneria Chimica, Giulio Natta, Politecnico di Milano

Continuous countercurrent chromatography is recognized as the technology of choice for a number of instances in the area of protein purification. Approaching its maturity stage, this technology has to be reconsidered with respect to crucial aspects for its future development. In particular, we discuss issues related to scalability in the GMP environment, model-based process characterization and validation, as well as process automation, control and digitalization particularly in the context of continuous integrated manufacturing.

14:35 Continuous Chromatography Purification Process: From Small Peptides to Virus-Based Biologics

Silva_RicardoRicardo Silva, PhD, Scientist, Animal Cell Technology, Instituto de Biologia Experimental Tecnologica (iBET)

Alternative purification strategies that can improve the purification yield, such as continuous chromatography, are regarded nowadays as potential tools to overcome the capacity bottleneck in biomanufacturing. The current talk will focus on the development of continuous purification processes targeted at small peptides and novel biologics such as virus for vaccines and gene therapy applications.

IBA_no-tagline 15:05 Overcoming Limitations of Conventional Tag Systems – Strep-Tactin®XT Applications

Mike Rothe, PhD, CEO, IBA Lifesciences

The Strep-Tactin®XT:Twin-Strep-tag®-purification system enables protein purification at high yields and purity under physiological conditions. Providing the highest binding affinity among all affinity tag systems, the technology fulfills the demands of detections and monitoring of biomolecular interactions in real time and is available for applications like SPR and Octet®/BLItz®.

GenScript-CRO 15:20 Novel Solutions for HTP Antibody and Protein Purification Using Magnetic Beads

Roumen Bogoev, Marketing Director, Catalog Products, GenScript

GenScript has partnered with Amgen to design the AmMag SA, an automatic platform using magnetic beads for purifying antibodies and proteins. The system facilitates increased throughput for drug screening. It also eliminates the need for centrifugation and filtration of samples prior to processing, saving significant amount of time and labor. 

 

15:35 Networking Refreshment Break (Foyer D)

BREAKTHROUGH TECHNOLOGIES
Auditorium II

16:00 A Microfluidic Platform for Antibody Manufacturing Optimization

Aires_Barros_RaquelRaquel Aires Barros, PhD, Full Professor, Bioengineering, IBB – Institute for Bioengineering and Biosciences, Instituto Superior, Universidade de Lisboa

The number of biotechnology-based pharmaceuticals in the late-stage pipeline has been increasing more than ever in particular monoclonal antibodies (mAbs) representing a quarter of all biopharmaceuticals in clinical trials. As a result, there is an enhanced demand for more efficient and cost-effective processes for antibody manufacturing. Here, the potential of miniaturization as a high-throughput screening tool to speed up process development of antibodies is explored.

GE Healthcare

16:30 Taking Chromatography to the Next Level - A Novel Fiber Based Protein A Chromatography Platform

Troeng_LinneaLinnea Troeng, Product Manager, Protein Preparation and Purification, GE Healthcare Bio-Sciences AB

In this presentation we show the development of a novel cellulose fiber-based chromatography solution “Fibro”, that combines high binding capacity with high flowrates to enable increased productivity from industrial research, process development, to clinical & commercial mAb purification. The technology is scaleable and enables true single-use chromatography solutions. Here we will present data on binding capacity, purification performance and scalable performance.

17:00 Protein Separation by Magnetic Particles at the Technical Scale

Fraga_García_PaulaPaula Fraga Garcia, PhD, Scientist, Mechanical Engineering, Bioseparation Engineering, Technical University of Munich

Biocompatible magnetic nanoparticles are a promising material that has shown applicability in a wide range of areas. This work paves the way for an innovative, economical purification process for biotechnologically produced proteins and contributes to a deeper understanding of bio-nano interactions

17:30 End of Day

17:00 Dinner Short Course Registration*

17:3020:30 Dinner Short Courses


Recommended Short Course*

SC7: Protein Aggregation: Mechanism, Characterization and Consequences - LEARN MORE

*Separate registration required.

FRIDAY 22 NOVEMBER

08:00 Registration (Foyer A) and Morning Coffee (Foyer D)

MEMBRANE PROTEIN PURIFICATION
Auditorium II

08:30 Chairperson’s Remarks

Dirk Linke, PhD, Professor, Molecular Microbiology, Biosciences, University of Oslo

08:35 The Gram-Negative Bacterial Cell Surface: How to Study Its Protein Components and How to Remove Endotoxin

Linke_Dirk Dirk Linke, PhD, Professor, Molecular Microbiology, Biosciences, University of Oslo

In our recent work, we have developed methods to express bacterial outer membrane proteins in ways that allow direct NMR studies in the native environment. As experts in membrane protein purification, we constantly develop expression strains and methods for quality control. In that regard, we recently found a small protein with high affinity for bacterial endotoxin, that we hope can be used for endotoxin detection and removal.

09:05 Sane in the Membrane – Salipro One-Step Reconstitution of Membrane Proteins

Frauenfeld_Jens Jens Frauenfeld, PhD, CEO, Salipro Biotech AB

Membrane proteins are important drug targets (GPCRs, ion channels), yet are notoriously difficult to work with. We have developed a novel one-step approach for the incorporation of membrane proteins directly from crude cell membranes into lipid Salipro particles. This direct approach presents new opportunities for the analysis of novel drug targets. Furthermore, we present how the Salipro system can be used to generate antibodies against important membrane proteins.

09:35 A Tricky Endeavour: Production of Membrane-Bound P450s

Spadiut_Oliver Oliver Spadiut, PhD, Associate Professor, Chemical, Environmental and Bioscience Engineering, Integrated Bioprocess Development, Vienna University of Technology (TU Wien)

Cytochrome P450s (P450s) comprise one of the largest known protein families. They occur in every kingdom of life and catalyze essential reactions, such as carbon source assimilation, synthesis of hormones and secondary metabolites, or degradation of xenobiotics. Due to their outstanding ability of specifically hydroxylating complex hydrocarbons, there is a great demand to use these enzymes for biocatalysis. However, this requires a great understanding of these enzymes – thus we need to know their protein crystal structure. In this talk I will present how we recombinantly produced and purified a plant cytochrome P450.

10:05 Networking Coffee Break (Foyer D)

PURIFYING BISPECIFIC ANTIBODIES
Auditorium II

10:35 Overcoming Some Challenges in the Purification of Bispecific Antibodies

Correia_Ana Ana Correia, PhD, Scientist, Biologics Optimization, Amgen, Inc.

Bispecific antibodies are an emerging class of therapeutics which are engineered to simultaneously bind two distinct targets. Production and purification of these molecules is challenging due to the presence of byproducts such as aggregates and half-antibodies, which are difficult to eliminate by conventional chromatographic techniques. Here I show results from a novel Protein A chromatography strategy that removes these impurities, thereby reducing processing cycle-time and improving product quality.

11:05 Novel Protein A Small and Large-Scale Purification Platforms for Bispecific Antibodies

Mahmoudi_Afshin Afshin Mahmoudi, MS, Scientist II, Biotherapeutics, Celgene Corp.

Our goal was to develop a robust 1-2 step process that can be applied for the purification of most bispecific antibodies (BsAbs). In this study, we present a BsAb purification process consisting of affinity capture using a novel Protein A chromatography resin, and subsequent screening of chromatography resins (ion exchangers, HIC or multimodal resins) for additional polishing. Recovery and purity indicate a robust purification platform for BsAb programs. This novel platform simplifies process development, reduces time and expense, and ultimately time to market.

11:35 SELECTED POSTER PRESENTATION:
Isolation and Characterization of Light Chain Misassembled Bispecific Antibody Variants by Hydrophobic Interaction Chromatography and Knowledge Use for Production Cell Line Optimization 

Thomas von Hirschheydt, Dr. rer. nat., Principal Scientist and Technical Development Leader, Roche Diagnostics GmbH

 

12:05 Problem-Solving Breakout Discussions with a Light Snack

 

TABLE 34: Inclusion Bodies – Curse or Blessing?

Moderator:  Oliver Spadiut, PhD, Associate Professor, Chemical, Environmental and Bioscience Engineering, Integrated Bioprocess Development, Vienna University of Technology (TU Wien)

  • Can IB processes oucompete mammalian production processes?
  • What do we miss to make IBs competitive?
  • How can we use IBs directly?
  • Shedding light onto the black box refolding.

 

TABLE 35: Fiber vs Resin Based Chromatography – Strategies for Intensifed Chromatography
Moderator: Linnea Troeng, Product Manager, Protein Preparation and Purification, GE Healthcare Bio-Sciences AB

  • Recent development in chromatography technologies
  • Strategies for effective process development and scale-up
  • Parameters determining best technology choice

INNOVATING PURIFICATION STRATEGIES
Auditorium II

13:00 Chairperson’s Remarks

Oliver Spadiut, PhD, Associate Professor, Chemical, Environmental and Bioscience Engineering, Integrated Bioprocess Development, Vienna University of Technology (TU Wien)

13:05 A Development and Manufacturing Platform for Non-Platform Proteins

Berkemeyer_Matthias Matthias Berkemeyer, PhD, Associate Director, Downstream Development, NBE and Biosimilars, Biopharma Process Science Austria, Boehringer Ingelheim RCV GmbH & Co KG


13:35 Advanced Chromatography-Free Protein Purification Strategies Enabling High-Resolution Structure Determination of Large, Labile Multi-Subunit Biological Assemblies and Drug Discovery

Chari_Ashwin Ashwin Chari, PhD, Project Group Leader, Structural Dynamics, Max Planck Institute for Biophysical Chemistry

Biochemical purification of large, labile assemblies remains a formidable challenge and often fails when strategies suitable for single biomolecules are adapted to larger complexes. Here, I will present the development of chromatography-free purification strategies, which enable the purification of large biological assemblies in high yield and high quality. The strategies reported here have enabled the structure determination of proteasomes and fatty acid synthases at unprecedented resolution and opened up new venues for drug discovery.

14:05 Improved Downstream Processing of Recombinant Proteins Using Aqueous Two-Phase Systems Composed of Ionic Liquids

Pedro_Augusto Augusto Pedro, PhD, Postdoctoral Fellow, Chemistry, CICECO – Aveiro Institute of Materials, University of Aveiro

Previous studies have shown that ionic liquids display highly interesting features concerning protein stabilization, and by properly tailoring their anion/cation pairs, increased selectivity towards the target protein can be achieved in IL-ATPS. Process intensification and scale-up of IL-ATPS for the purification of recombinant proteins can be achieved by centrifugal partition chromatography (CPC), in which the stationary phase is also liquid and kept by centrifugal force.

14:35 Purification of Viruses and Virus-Like Particles for Structural Studies

Stehle_Thilo Thilo Stehle, PhD, Professor, Interfaculty Institute of Biochemistry, University of Tübingen

Structure-function studies of viruses require large amounts of intact particles of either complete, infectious virus or infection-deficient virus-like particles. I will report on strategies that we use in my group to express and purify such particles, and I will present data on the structural analysis of these particles.

15:05 NEW -- Talk Cancelled:  Bioconjugates: Development of an Efficient and Scalable Maleimide Linker Stabilization Method

Saremirad_Pegah Pegah Saremirad, PhD, Scientist, Process Development, AstraZeneca

Conjugation of Active Pharmaceutical Ingredients (APIs) to macromolecules via Maleimide (Mal) conjugation to a sulfhydryl is used for generating medicines with selective delivery and prolonged half-life. However, deconjugation often occurs for Mal linkers, resulting in product heterogeneity and decreased shelf-life. De-conjugation can be mitigated via the hydrolysis of the Mal-linker. Here we report development of a controlled and scalable process for Mal linker hydrolysis. Process efficiency, scale up suitability and impact on the molecule was investigated, followed by demonstration of linker stabilization under different storage conditions.


15:05 End of Protein Purification Technologies