Cambridge Healthtech Institute’s Seventh Annual

Higher-Throughput Protein Production and Characterization

Innovating Processes

January 11-12, 2018


High-throughput processes have come of age by transforming the traditional protein-by-protein trial-and-error approach for testing criteria and scaling up. In this leading conference, HTP will be explored in the quest to develop methods that ensure quality and translate to large scale. Automation, robotics and liquid handlers will be discussed, along with developing small-scale models that shed light on bioproduction. Case studies will be presented that illustrate how leaders in the field are integrating HTP approaches to reduce the time and effort needed to successfully analyze proteins, fine tune processes, and achieve well-folded, pure protein.

Final Agenda


7:45 am Registration and Morning Coffee

Next-Gen HTP Tools and Technologies

8:15 Chairperson’s Opening Remarks

Allan Matte, Ph.D., Senior Research Officer, Downstream Processing & Analytics, Human Health Therapeutics, National Research Council Canada (NRC-CNRC)


8:20 High-Throughput de novo Computational Protein Design and Its Applications

Gabriel_RocklinGabriel Rocklin, Ph.D., Senior Fellow, Biochemistry & Bioengineering, University of Washington

Advances in computational protein design and DNA synthesis technology have made it possible to design and recombinantly express tens of thousands of small designer proteins (40-80 amino acids) at once, each with a novel de novo fold and unique functional possibilities. These proteins can be engineered to bind to targets and to resist thermal denaturation and aggregation, and we can iteratively improve these properties through cycles of large-scale design and efficient, massively parallel experimental testing.

9:00 Mitigating Developability Risks by Application of Affinity-Capture Self-Interaction Nanoparticle Spectroscopy (AC-SINS)

Craig_DickinsonCraig D. Dickinson, Ph.D., Senior Research Advisor, AME, Eli Lilly and Company

9:30 Flow Cytometry – An Old Dog with New Tricks for Ultra-High Throughput Screening of Recombinant Protein Libraries

Karl_GriswoldKarl E. Griswold, Ph.D., Associate Professor, Thayer School of Engineering, Dartmouth College

Flow cytometry (FC) is a powerful tool for screening recombinant protein libraries via cell surface display. However, functional screening of soluble, secreted proteins that act in-trans upon heterologous target cells is more challenging, since the genotype-phenotype link is inherently lost for such trans-interactions. Here, we describe integrated gel microdroplet-FC (GMD-FC) screens in which recombinant expression hosts are co-encapsulated with heterologous target cells in micron scale hydrogel droplets, thereby re-establishing the genotype-phenotype link and enabling FC screening of soluble, secreted protein libraries.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 High-Throughput Protein Production within the Swedish Human Protein Atlas Project

Hanna_TegelHanna Tegel, Ph.D., Scientist and Group Leader, Biotechnology, Proteomics and Nanobiotechnology, KTH Royal Institute of Technology

Within the Swedish Human Protein Atlas project, an antibody-based proteomics effort with focus on protein profiling in human tissues and cells, a protein production pipeline has been set up to handle hundreds of proteins per week. The challenges we met when setting up this pipeline and the solutions we have chosen will be discussed and presented.

11:30 Enjoy Lunch on Your Own

1:15 Ice Cream Break in the Exhibit Hall with Poster Viewing

HTP Purification

2:00 Chairperson’s Remarks

Nigel F. Reuel, Ph.D., Assistant Professor, Chemical and Biological Engineering, Iowa State University

2:05 Integrated High-Throughput Purification Platforms for Bio-Therapeutics R&D

Allan_MatteAllan Matte, Ph.D., Senior Research Officer, Downstream Processing & Analytics, Human Health Therapeutics, National Research Council Canada (NRC-CNRC)

Early-stage screening campaigns for therapeutic antibody development involve the purification of hundreds of antibody samples, often produced in CHO or HEK transient expression systems with a range of titers and volumes. To meet this challenge, we have implemented a number of high-throughput purification platforms capable of rapidly generating sub-milligram to hundreds of milligrams of purified products. Redundancies in purification platforms and integration with in-process analytics is required to achieve this outcome.

2:35 Development of an Automated Mid-Scale Parallel Protein Purification System for Antibody Purification and Affinity Chromatography

Brian_HallBrian Hall, Ph.D., Principal Scientist, Biologics, Merck & Co.

To address the need for higher throughput affinity purification of samples 20ml-100ml we modified a 4 channel SPE system with switching valves and holding loops to perform affinity purification using commercially available columns and micro-titer deep well blocks. The system has the capacity to purify 24 samples using a single-step affinity purification protocol or a two-step protocol consisting of affinity chromatography followed by desalting/buffer exchange.

Automated Procedures for Large-Scale Purification of Human GTPase KRas and Raf1 Cystine Rich Domain (CRD)

Simon_MessingSimon Messing, Ph.D., Scientist II, Leidos Biomedical Research/RAS initiative

Here, we show a fully automated protein purification strategy for the large-scale production of the G domain of KRas, and one of its effectors, the cysteine rich domain of RAF1. This strategy includes five purification steps, which includes TEV protease-mediated affinity tag cleavage, Ni2+ affinity, ion exchange, and size exclusion chromatography. This automated approach provides distinct advantages to previous manual workflows, by reducing typical large-scale purification from 3-4 days down to 1.5 days. This saving in run time and workload significantly reduces protein production as a rate-limiting step in the processes of drug discovery.

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


4:15 Medium-Scale Higher Throughput Purification and Characterization of Antibody Therapeutics and Bispecific Antibodies

Haiyan Jiang, Ph.D., Principal Scientist, Biologics Research, Janssen BioTherapeutics, Janssen R&D

4:45 High-Throughput Production of Antibodies Using Yeast and Mammalian Cells

Juergen_NettJuergen Nett, Ph.D., Director, High Throughput Expression, Adimab, LLC

High-throughput, small-scale production of antibodies is an essential part of a discovery workflow. After isolation from a large yeast-based antibody library, Adimab directly expresses large panels of full-length IgGs in 96-well and 24-well format. Protein purification is accomplished in a plate-based format using liquid handling platforms. The same semi-automated process is also compatible with IgGs expressed in mammalian hosts. Process setup, attributes, and output will be reviewed.

5:15 High-Quality Antibodies Targeting Protein Post-Translational Modification Sites through Affinity and Specificity Engineering

Yongku_ChoYongku Cho, Ph.D., Assistant Professor, Chemical and Biomolecular Engineering, University of Connecticut

Developing high affinity and specificity antibodies targeting protein post-translational modification sites remains a challenge. Using human tau as a model protein, we show that antibodies engineered for high affinity alone often lose their specificity. Using a novel approach to screen for improved specificity, we engineered picomolar affinity clones with no detectable off target binding. The new methods developed may be useful for setting a quantitative standard for characterizing antibody specificity.

5:45 Close of Day


8:00 am Registration

8:00 BuzZ Sessions with Continental Breakfast

Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across the stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies and strategies, challenges, and future trends.

Table Moderator: Haiyan Jiang, Ph.D., Principal Scientist, Biologics Research, Janssen BioTherapeutics, Janssen R&D


Assessing and Ensuring Developability

9:00 Chairperson’s Remarks

Gabriel Rocklin, Ph.D., Senior Fellow, Biochemistry & Bioengineering, University of Washington

9:05 Platformization of Multi-Specific Protein Engineering I: From in silico Design and Bulk Modular Cloning to Automated Deconvolution of Variant Libraries

Joerg Birkenfeld, Ph.D., Section Head, High Throughput Biologics, R&D Biologics Research/Protein Therapeutics, Sanofi-Aventis Deutschland GmbH

The success rate to identify a multi-specific lead molecule with favorable drug-like properties increases with the number of variants tested. We report here the establishment of a novel, automated platform process for the fast generation of large panels of multi-specific variants (up to 10,000). Our high-throughput process integrates emerging cloning technologies with state-of-the-art automation and workflow supporting bioinformatics based on Genedata Biologics Database.

9:35 High-Throughput Methods for Protein Stability Prediction and Formulation Challenges Identification

Smita_RaghavaSmita Raghava, Ph.D., Senior Scientist, Sterile Formulation Sciences, Merck & Co.

Successful development of biologics requires development of orthogonal tools to meet the challenge of rapidly and accurately assessing protein solution stability using limited material. This presentation will focus on combination of high-throughput technologies and assays for formulation and drug product development of biologics, such as monoclonal antibodies (mAbs) and mAb-based modalities. The overview of tools, their novel implementation, and relationship to commonly conducted “stability studies” will be further discussed using examples of high-throughput workflows, pre-formulation screening, and formulation development/optimization.

10:05 HTP Method for Affinity Determination in Complex Matrices by Solution Equilibrium Analysis Using Meso Scale Discovery Technology

Eilyn R. Lacy, Ph.D., Principal Scientist, Janssen BioTherapeutics (JBIO), Janssen Research & Development, LLC
The determination of antigen-antibody affinity is essential in the development of biotherapeutics and high throughput methods for affinity analysis in physiologically relevant and complex matrices are needed. We developed a high throughput method for affinity determination in neat serum by solution equilibrium analysis using Meso Scale Discovery technology (MSD-SEA). The results highlight the potential of the MSD-technology for HTP analysis of high affinity therapeutic candidates using physiologically relevant matrices.

10:35 Coffee Break with a Poster Pavilion

PepTalk is proud to support and recognize the protein scientists of tomorrow during the Poster Pavilion. This time has been set aside to view the Student Fellowship posters and interact with presenters one on one. This opportunity gives job seekers the chance to share their expertise with future/potential employers or develop contacts to further their research.

11:15 High-Throughput Automations and Optimizations for Improved Binder Generation and Validation

Jonas_SchaeferJonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich

While recombinant binder selection pipelines by now work in rather high-throughput, the screening of suitable affinity reagents and especially the validation of their essential features for the final applications is still laborious and time-intensive. To optimize the efficiency of these processes, we have improved already existing and developed novel methods to efficiently test candidates for their suitability, e.g., regarding their specificity.

11:45 High-Throughput Characterization of Hydrolytic Enzymes in Low Volume and Closed Systems

Nigel_ReuelNigel F. Reuel, Ph.D., Assistant Professor, Chemical and Biological Engineering, Iowa State University

Hydrolytic enzymes play a significant role in biologic and synthetic processes. The ability to better characterize these enzymes would enable shorter development times and better products. This talk will detail two recent developments for hydrolytic enzyme characterization: 1) a carbon nanotube-based optical sensor that allows for quantitative measurement in <20ul volumes and 2) a resonant antenna sensor that passively transmits its response in the 1-100MHz range, enabling detection within closed, opaque systems.

12:15 pm Conference Wrap-Up

Richard Altman, MS, Scientist, Protein Technologies, Amgen

Haiyan Jiang, Ph.D., Principal Scientist, Biologics Research, Janssen BioTherapeutics, Janssen R&D

Diane Paskiet, MS, Director of Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical Services

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

Moritz von Stosch, Ph.D., Senior Manager, Fermentation, Technical R&D, GSK Vaccines


12:45 Close of Conference


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