2016 Archived Content

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Cambridge Healthtech Institute’s Inaugural
Emerging Technologies for Antibody Discovery and Engineering
Cutting-Edge Technologies to Enable the Discovery of Novel Biotherapeutic
Targets and Well-Behaved Biotherapeutics
January 21-22, 2016

As large pharma continues its integration of biologic drugs into its product portfolios and discovery operations, it is imperative that industry companies identify truly novel drug targets for unmet medical needs – and that the biotherapeutics against these are selected and engineered to minimize development risk. The Emerging Technologies for Antibody Discovery and Engineering conference offers a forum for showcasing the current state of the art for research methodologies that will support the discovery and development of next-generation biotherapeutics. The meeting explores the evolution of traditional library and display approaches, along with emerging technologies with the potential to have significant near-term impacts on the ability of scientists to develop unique, differentiated biologics.

Final Agenda

THURSDAY, JANUARY 21

7:45 am Conference Registration and Morning Coffee

8:15 Chairperson’s Opening Remarks

Randall Brezski, Ph.D., Scientist, Antibody Engineering, Genentech, Inc.

KEYNOTE PRESENTATION

8:20 Integrated Computational Design and High-Throughput Screening

Philip_Kim Philip M. Kim, Ph.D., Associate Professor, Computational and Integrative Biology, University of Toronto

I will present our advances in combining computational and experimental techniques to develop novel inhibitors. We have developed an integrated pipeline that first computationally designs large libraries of potential inhibitors and can then screen these for either cellular phenotype or high affinity binding. I will showcase this pipeline on two example applications, first for developing inhibitors to protein-protein interactions and second for developing novel high-affinity biologics.

9:00 Screening for Blood-Brain Barrier Targeting Antibodies

Eric_Shusta Eric Shusta, Ph.D., Professor, Chemical and Biological Engineering, University of Wisconsin

The blood-brain barrier presents a substantial obstacle to brain drug delivery. To help address this issue, we have recently developed a variety of antibody screening paradigms specifically designed with the blood-brain barrier in mind. New screening paradigms and resultant antibodies that have preference for the brain vasculature will be discussed.

9:30 Targeting Influenza A: Discovery and Structural Analysis of a Human-Derived Broadly Neutralizing Anti-HA Antibody

Patrick_Lupardus Patrick Lupardus, Ph.D., Scientist, Structural Biology, Genentech, Inc.

Influenza A results in millions of infections worldwide each year and represents a significant pandemic threat. Using a technique to enrich and isolate antigen-targeted plasmablasts from vaccinated healthy donors, we discovered an anti-hemagglutinin (HA) antibody that neutralizes all clinically relevant Influenza A strains and is efficacious in preclinical models of infection. Structural analysis identified the stalk region of HA as the epitope and provides a molecular mechanism for virus neutralization.

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

11:00 B Cell Selection for Antibody Discovery

Partha_Chowdhury Partha Chowdhury, Ph.D., Principal Scientist, MedImmune

Despite being a useful platform for antibody discovery, the main bottleneck of the hybridoma technology has been the low number of specific hits that are typically obtained. This necessitates large number of fusions and deep mining of clones for assuring success. This presentation will be about a new process improvement approach showcasing how B cell population can be fractionated to ensure a large increase in the quantity and quality of hybridoma generation.

11:30 Engineering a Protease Inhibitor Scaffold for Alternative Functions

Maun_Henry Henry Maun, Ph.D., Principal Scientific Researcher, Early Discovery Biochemistry, Genentech, Inc.

12:00 pm Rare but There: Accessing Natural Antibody Diversity by Deep Screening of the Plasma Cell Compartment

Lecault_Veronique Veronique Lecault, Ph.D., Co-Founder, AbCellera

AbCellera has developed a rapid and high-throughput antibody discovery platform that allows screening of over 1,000,000 single B cells per run from any species. This talk will highlight the advantages of looking into the plasma cell compartment to access greater diversity, and to select for antibodies with defined properties using a variety of single-cell multiplexed binding and specificity assays.

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

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

2:00 Chairperson’s Remarks

Partha Chowdhury, Ph.D., Principal Scientist, MedImmune

2:05 High-Throughput Sequencing of B Cell VH:VL Pairs and Proteomic Methods for the Discovery of Human mAbs in Serum

Gregory_Ippolito Gregory C. Ippolito, Ph.D., Research Assistant Professor, Molecular Biosciences, The University of Texas at Austin

The Georgiou Group has developed and patented technologies for the extensive molecular analysis of human antibody responses. These techniques allow for the direct comparison of protein-level serum antibody repertoires to DNA-level repertoires in circulating peripheral blood B cells. Their utility for the discovery of native serum antibodies shall be discussed.

2:35 Novel Phage Display Library from Naïve Rabbit Antibody Repertoires

Christoph_Rader Christoph Rader, Ph.D., Associate Professor, Cancer Biology and Molecular Therapeutics, The Scripps Research Institute

Owing to their high affinities and specificities, rabbit mAbs have demonstrated value and potential as basic, diagnostic, and therapeutic reagents. We generated and validated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies. Rabbit mAbs selected from this library against a panel of human antigens revealed high affinity, specificity, and diversity, as well as therapeutic utility as components of CAR-engineered T cells.

3:05 Creating Focused Mutant Libraries for Protein Engineering

Thorsteinson_Nels Nels Thorsteinson, Scientific Services Manager, Biologics, Chemical Computing Group

Protein engineering plays a pivotal role in modulating the function, activity and physical properties of biologics. However, the efficient search and evaluation of an excessively large sequence design space is challenging. Here we have developed a computational approach which predicts mutation probabilities for given residue sites in specified sequences. In assessing the probabilities at given residue sites, the sequence search space can be efficiently sampled to design and produce focused mutant libraries.

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

4:15 Antibodies from Immunotherapy Treated Cancer Patients

Mark Branum, Ph.D., Director, Theraclone Sciences

Theraclone utilizes its proprietary I-STAR human B-cell technology platform to discover novel targets and antibodies. The memory B cell repertoires of several cancer patients with clinical responses immunotherapy were interrogated. Antibodies from these patients were sequenced, expressed and and characterized for tumor reactivity.

4:45 Next Generation Sequencing (NGS) in mRNA Display Selections

Ginger_Rakestraw Ginger Chao Rakestraw, Ph.D., Senior Research Investigator II, Bristol-Myers Squibb

Applications of NGS with mRNA display selection will be discussed. This will include methods to recover low-abundance sequences from a diverse population and additional methods for rapid optimization of antibodies and other polypeptides.

5:15 A Pipeline to Select Human Antibodies in vivo Against Defined Cancer Targets

Fortunado_Ferrara Fortunato Ferrara, Ph.D., Research Assistant Professor, Experimental Therapeutics, University of New Mexico

We have developed an in vitro approach that combines the advantage of phage display selection with yeast display cell sorting, to discover hundreds of recombinant human antibodies against different targets, including cancer biomarkers. For immune-based cancer detection and treatment, antibodies recognizing targets in their native state are required. For this reason, we have introduced in vivo screening to our pipeline to isolate effective candidates for cancer detection.
> View recent Interview with Dr. Ferrara

5:45 Close of Day

6:00-7:00 Reception in the Tiki Pavilion

FRIDAY, JANUARY 22

8:00 am Conference Registration and Morning Coffee

8:30 Chairperson’s Remarks

Vaishnavi Ganti, Senior Scientist, PKPD, Biologics, Discovery, Merck Research Laboratory-Palo Alto

8:35 Screening Antibodies for Conformational and Colloidal Stability

Mark_Brader Mark Brader, Ph.D., Biopharmaceutical Industry Consultant, Formulation Development; Former Principal Scientist, Bioge n

A major challenge to more efficient mAb developability engineering and formulation optimization is decision-making and risk assessment from accelerated stability data and measurements of physicochemical properties. The design of optimally stable protein pharmaceuticals must take into account degradation via conformational and colloidal mechanisms, recognizing that in high concentration formulations colloidal effects become more pronounced. Insights into conformational and colloidal stability aspects from rapid screening and stability data are presented.

9:05 Translational Research Models for Improved Antibody Discovery

Vaishnavi_Ganti Vaishnavi Ganti, Senior Scientist, PKPD, Biologics, Discovery, Merck Research Laboratory-Palo Alto

The effective information flow and translation of accumulated knowledge across various antibody development stages remain a major challenge. Successful strategies for development of monoclonal antibodies require integration of relevant knowledge with respect to target antigen properties, antibody design criteria such as affinity, isotype selection, pharmacokinetic (PK)-pharmacodynamic (PD) properties, and antibody cross-reactivity across species from the early stages of antibody development. Incorporation of effective translational strategies from the early stages of the antibody development process is a necessity; when considered it not only reduces development time and cost, but also fosters implementation of rational decision making throughout all phases of antibody development.

9:35 Regulation of Antibody Class Switch Recombination

Ali_Zarrin Ali Zarrin, Ph.D., Scientist, Immunology, Genentech, Inc.

Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, Sε, is replaced with prominent recombination hotspot Sμ. Our studies provide novel insights into the regulation and genetic manipulation of antibody isotype switching.

10:05 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.

11:00 A Computational-Experimental Pipeline for Biologic Design

Samuel_Flores Samuel Coulbourn Flores, Ph.D., Assistant Professor, Cell and Molecular Biology, Uppsala University

Predicting the effect of substitution mutations on affinity and specificity is key to designing biologics in silico. I present ZEMu, a novel multiscale method which focuses computer resources on the region around the mutation site. With ZEMu, we produce a short list of mutations with high probability of substantially improving affinity, leading to a considerable reduction in the experimental effort. I discuss ongoing development of cancer and autoimmune disease therapies.

11:30 A Comprehensive System to Manage GSK’s Antibody Discovery Processes

Trevor_Wattam Trevor Wattam, Ph.D., Manager, Biopharm Discovery Group, Biopharm Discovery Group, GlaxoSmithKline

GSK’s large-molecule research programs are based on a unique platform of antibody discovery technologies. To support and integrate the different screening, engineering and production processes, we have implemented a comprehensive R&D workflow system called the GSK’s Antibody Discovery Database (ADD). We will present how the ADD makes GSK’s lead discovery process more efficient, with use cases from GSK’s yeast and phage display as well as hybridoma and humanization processes.

IT’S A WRAP:
PEPTALK 2016 CLOSING PLENARY PANEL DISCUSSION
Friday, January 22, 12:00 pm

Protein therapeutics is one of the fastest-growing global markets, driven by increasing adoption of protein- over non-protein drugs, growing funding for protein engineering and reduced drug discovery timelines and costs. As the science improves, so does the complexity of the R&D organization: it really does “take a village” to bring nextgeneration therapies to market and patients who need them. Ensuring product quality plus speed to market requires collective insights from experts working across the stages of protein science R&D – as embodied by panelists representing each PepTalk Pipeline topic.

They discuss: