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Cambridge Healthtech Institute’s 3rd Annual
Enhancing Antibody Binding and Specificity
Scientific Strategies for Measuring and Engineering Target-Specific Binding and Specificity
for Next-Generation Antibody Therapeutics

January 19-20, 2016

As the industry expands its repertoire of antibody-drug products into new therapeutic areas, product formats and protein constructs, the control of antibody/antigen targeting, binding and specificity will take on a new level of importance for researchers in this field. The Enhancing Antibody Binding and Specificity conference presents innovative approaches to the modulation of binding activity, mechanism of action and difficult target challenges such as transmembrane proteins and intracellular targeting.

Final Agenda


1:00 pm Conference Registration

2:00 Chairperson’s Opening Remarks

Yasmina Abdiche, Ph.D., Research Fellow; Head, Bioanalytics Group, Rinat-Pfizer


2:05 New Methods and Antibody Formats for Achieving Exceptional Specificity

Shohei_KoideShohei Koide, Ph.D., Professor, Biochemistry and Molecular Biology, University of Chicago

Creating affinity reagents that discriminate subtle chemical differences, such as post-translational modifications, remains a major challenge, although the problem of achieving high affinity is essentially solved. We have engineered antibody and non-antibody reagents with high specificity, including those that cleanly discriminate the difference of a methyl group, arguably the smallest difference in protein antigens. A surprising mechanism underlying their exquisite specificity led to new antibody formats suitable for achieving exceptional specificity.


2:45 Strategies and Applications for Epitope Mapping

Caroline_ColleyCaroline Colley, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune

There are a variety of epitope mapping methods with a range of different applications in antibody discovery. These range from low-resolution approaches, such as competition assays, which enable selection of antibodies recognizing different regions of the target, through to high-resolution X-ray crystallography, which can contribute to defining mechanism of action. This talk outlines epitope mapping approaches at MedImmune, and using case studies, highlights their application for drug discovery.

3:15 Refreshment Break in the Exhibit Hall with Poster Awards

Assisted Design of Antibody and Protein Therapeutics (ADAPT): Recent Advances in the Antibody Affinity Maturation Platform

Jason_BaardsnesJason Baardsnes, Ph.D., Research Officer, National Research Council Canada

To assist affinity maturation of therapeutic antibodies we have developed a platform combining binding affinity predictions with stepwise experimental validation. Starting from the crystal structure of an antibody-antigen complex, an efficient workflow interleaves computational predictions with experimental validation from single-point to quadruple mutants. Examples of employing ADAPT to optimize antibodies against VEGF and HER2 are presented.


Direct Proteomic Sequencing of Monoclonal Antibodies

Stefano Bonissone, Ph.D., Chief Technology Officer, Digital Proteomics LLC


4:30 Advances in the Analytical Methods Used to Characterize the Epitopes of Monoclonal Antibodies

Yasmina_AbdicheYasmina Abdiche, Ph.D., Research Fellow; Head, Bioanalytics Group, Rinat-Pfizer

This talk will focus on high throughput biosensor methods aimed at characterizing epitopes of monoclonal antibodies in the context of drug discovery. Data will be corroborated by orthogonal analytical techniques.

5:00 Epitope Diversity Evaluation in the Early Screening Funnel

Alexander Ivanov, Ph.D., Senior Scientist, Head, Biomolecular Interaction Group, AbbVie Bioresearch Center

Generation of large and diverse pools of biologic molecules may be critical to improve success in Biologic drug discovery. Properly designed high throughput screening at a very early stage could be important to secure competitive advantage. The talk will provide case study examples and review of the role and use of emerging and existing technologies for early epitope diversity screening that could help in selecting a drug candidate, save time and resources on assay development, enrich institutional knowledge and potentially inform intellectual property considerations.


8:00 am Conference Registration and Morning Coffee


8:30 Chairperson’s Remarks

Tilman Schlothauer, Ph.D., Senior Scientist, Biochemical and Analytical Research, Large Molecule Research, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg

8:35 Biologic and Antibody Approaches to Undruggable Intracellular Targets

David_ScheinbergDavid A. Scheinberg, M.D., Ph.D., Vincent Astor Chair, and Chairman, Molecular Pharmacology Program, Sloan Kettering Institute

Most proteins and oncogenic drivers are not druggable currently with small molecules. MHC presentation of peptide fragments of these critical proteins on the cell surface allows recognition and killing of target cells by TCR’s on T cells after vaccination or by use of TCR mimic antibodies. Several examples with multiple formats showing selectivity and cytotoxicity to several cancer cell types will be demonstrated.

9:05 Targeting Cell Surface Antigens with a Novel Therapeutic Antibody Concept

Paul_ParrenPaul W.H.I. Parren, Ph.D., Senior Vice President and Scientific Director, Genmab

IgG molecules can form ordered hexamers upon binding to membrane-bound antigens. We developed a novel therapeutic antibody platform inspired by this natural mechanism. By introducing specific mutations in the Fc domain, we developed the HexaBody technology, a novel antibody format that shows enhanced hexamerization upon target binding on a cell surface, while remaining fully monomeric in solution. This presentation describes therapeutic applications of HexaBody for the treatment of cancer.

Schrodinger Biologics9:35 Computational Advances in Antibody Design: Toward Improved Optimization and Selection

Pearlman_DavidDavid Pearlman, Ph.D., Senior Principal Scientist, Schrödinger

Recent computational advances hold significant promise both for improved prediction of antibody structure from sequence, and for the ability to precisely calculate physically relevant properties such as affinity and stability. When combined with additional theoretical approaches to identify liabilities, we can use these tools to variously optimize a lead antibody candidate and triage among multiple potential leads.

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

10:50 Novel Insights of Engineering Non-Antigen Contact Regions of Factor VIII Mimetic Bispecific Anti-Factor IXa/Factor X IgG Antibody

Yuri_TeranishiYuri Teranishi, M.E., Research Scientist, Antibody Engineering Group, Discovery Research, Chugai Pharmaceutical Co., Ltd.

ACE910 is a humanized anti-factors IXa and X bispecific IgG4 antibody that places two factors into proximity and mimics factor VIII function for the treatment of hemophilia A. We have evaluated the effect of modification of non-antigen contacting regions on the biological activity of FVIII mimetic bispecific antibody. Some novel insights from this study unique to our bispecific antibody will be presented.

11:20 Antibody Engineering for Enhanced Ph-Dependent FcRn Interaction

Tilman_SchlothauerTilman Schlothauer, Ph.D., Senior Scientist, Biochemical and Analytical Research, Large Molecule Research, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg

The human Fc receptor neonatal (FcRn) is responsible for endosomal antibody transport and mediation of antibody half-life. Many approaches of IgG engineering have been tested in the past to increase the binding affinity to FcRn. A possible pitfall of such approaches is the isolated view only at the Fc domain. We observed by the application of several FcRn interaction analyses and antibody engineerings that an antibody needs to be considered as a whole molecule for appropriate pH dependent FcRn engineering.

11:50 Insights into the Molecular Basis of a Bispecific Antibody’s Target Selectivity

Yariv_MazorYariv Mazor, Ph.D., Scientist, Antibody Discovery and Protein Engineering, MedImmune, LLC

Dual targeting is thought to enhance biological efficacy, limit escape mechanisms, and increase target selectivity via a strong avidity effect mediated by concurrent binding to both antigens on the surface of the same cell. However, factors that regulate the extent of target selectivity are not well understood. We show that dual targeting alone is not sufficient to promote efficient target selectivity, and report the substantial roles played by the affinity of the individual arms, overall avidity and valence.

12:20 pm HIV Envelope Glycoprotein Binding and Neutralizing Antibodies

Richard T. Wyatt, Ph.D., Professor, Immunology; Senior Director, IAVI Neutralizing Antibody Center, The Scripps Research Institute

12:50 Session Break

GE Healthcare_new1:00 Luncheon Presentations: Affinity Platforms for the Purification of Antibody Fragments

Pierre Tremblay, Ph.D., BioProcess Specialist, GE Healthcare

The last decade’s success of monoclonal antibodies has triggered the need for efficient purification platforms to ensure maximum time savings and optimized process economy at small & large scale. Currently, the industry is looking toward antibody fragments to find next-generation drugs. Mabs are typically purified using a platform approach with an initial protein A capture step. However, for antibody fragments there is not yet a corresponding solution. We will discuss purification challenges for antibody fragments and present examples of purification of antibody fragments of different subclasses, size, and structure.


2:00 Chairperson’s Remarks

Caroline Colley, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune

2:05 Antibodies Against Difficult to Express Membrane Protein Targets

Yelena_BisharyanYelena Bisharyan, Ph.D., Director of External Alliances, Tetragenetics, Inc.

Bill_HarrimanBill Harriman, Ph.D., CSO, Crystal Bioscience

Ion channels such as Kv1.3 have been historically difficult to raise antibodies against due to sequence conservation, paucity of cell surface epitopes, and poor expression levels in heterologous systems. Tetragenetics Inc. and Crystal Bioscience are addressing these issues by combining their unique technologies for membrane protein expression in Tetrahymena thermophila, and antibody generation in chickens, to develop therapeutic antibodies against a range of ion channel targets including Kv1.3, a voltage-dependent channel produced by effector memory T-cells implicated in certain autoimmune disorders.

2:35 Engineering Ion Channels for Structural Studies and Ligand Discovery

Susmith Mukund, Senior Associate Scientist, Molecular Engineering, Amgen Inc.

3:05 Antibody-Mediated Blockade of Human Orai1 Inhibits T Cell Activation in vitro and in vivo

Stefan Zahn, Ph.D., Principal Scientist, Antibody Technology, Novo Nordisk A/S

Ion channels are widely expressed on cells and tightly regulate the flow of ions between the extracellular and the intracellular environment. Dysregulation has been linked to pain, epilepsy and even autoimmune inflammatory diseases. We will present our recent work on targeting T cell-specific ion channels like CRAC by antibodies inhibiting T cell activation in vivo and in vitro.

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

4:30 Targeting Tumor Selective Cell Surface Antigens Using Designer Antibodies

Madan_KatragaddaMadan Katragadda, Ph.D., Senior Principal Scientist, Pfizer, Inc.

Potent novel means of therapeutic intervention utilizing immune cell retargeting and antibody-drug conjugates necessitates tumor selective targets owing to their extremely high potent nature. Several strategies have evolved in the past decade to selectively target tumors by either exploiting antigens, antigen complexes and glycoepitopes that are selectively overexpressed on tumor cells relative to the normal cells or simultaneously targeting two or more antigens using antibody engineering techniques. Examples describing these strategies are presented.

5:00 Challenges in Generating Antibodies to Integral Membrane Proteins

Ramu_SadhukhanRamkrishna (Ramu) Sadhukhan, Senior Group Leader, AbbVie Bioresearch Center Center

Developing therapeutic antibodies against integral membrane proteins is difficult, as GPCRs and ion channels are often expressed at low levels on cell surface and are unstable when purified. Poor quality membrane protein immunogens has led to limited success in generating antibodies that bind native cell surface molecules and remains a bottleneck for membrane protein target validation and monoclonal antibody-based therapeutics. Here, we present antigen preparation and antibody generation against multispanner proteins.

6:30-7:30 Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Conference