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Cambridge Healthtech Institute’s 2nd Annual
Enhancing Antibody Binding and Specificity
Emerging Science and New Technologies to Fine-
Tune Antibody-Antigen Binding and Target Specificity

January 21-22, 2015


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 take on a new level of importance for researchers in this field. The second component of the PepTalk Protein Engineering & Development pipeline, Enhancing Antibody Binding and Specificity, presents innovative approaches to the modulation of binding activity, mechanism of action and difficult target challenges such as transmembrane proteins.

Day 1 | Day 2 | Download Brochure | Speaker Biographies 

Final Agenda 


TUESDAY, JANUARY 20

1:30 pm Conference Registration


BUZZ Sessions png

2:00 BuzZ Session A

3:00 Refreshment Break in the Exhibit Hall with Poster Awards

3:45 BuzZ Session B
(More Details >>)


4:30-5:00 Short Course Registration

5:00-8:00 Dinner Short Courses More Details >> 


WEDNESDAY, JANUARY 21

7:30 am Conference Registration and Morning Coffee


Specificity Engineering

8:15 Chairperson’s Opening Remarks

Jonas V. Schaefer, Ph.D., Head, High-Throughput Laboratory, Department of Biochemistry, University of Zurich


Keynote Presentation

8:20 The Impact of Anti-IgG Hinge Antibodies in Protease-Enriched Diseases

RobertJordanRobert E. Jordan, Ph.D., Senior Director and Senior Research Fellow (retired), Janssen Pharmaceuticals

Anti-IgG hinge antibodies display fine specificity for proteolytically-cleaved IgGs but are not cross-reactive with the intact IgG counterpart. Engagement of anti-hinge antibodies with cell-bound cleaved IgGs restores antibody effector function in vitro and in vivo either when elicited by vaccination or as a mAb. The findings presented here suggest a novel mechanism for enhancing antibody-mediated cell-killing effector functions with application in pathological settings where protease activity is abundant.


9:00 Engineering of High-Affinity Two-in-One Antibodies Using Phage Display Coupled to Deep Sequencing

SarahSanowarSarah Sanowar, Ph.D. Senior Research Associate, Antibody Engineering, Genentech, Inc. – A Member of the Roche Group

To improve antibody affinity, we sought to develop a robust strategy to identify improved affinity variants beyond traditional phage-based screening. We turned to an approach, which combines affinity-based selection on phage with deep sequencing. Phage libraries with various diversity designs were combined to maximize the searched sequence space. This strategy gave us a comprehensive set of information on the effect of mutations in the antigen-binding site for a two-in-one antibody with dual action Fab for both of its antigens.


STRATEGIES FOR SCREENING LARGE ANTIBODY LIBRARIES

9:30 The Antibiome: Toward Renewable Antibodies to the Proteome

MichaelHowleyMichael Hornsby, Ph.D. Researcher, Pharmaceutical Chemistry, University of California, San Francisco

We have developed a robust high-throughput robotic pipeline for the generation and validation of renewable recombinant antibodies utilizing antibody phage-display. In order to match the capacity of the antibody generation to the availability of input antigens, we have developed several robust antigen production pipelines. Both pipelines working together in concert will allow the Recombinant Antibody Network (RAN) to develop quality renewable antibody reagents to the proteome.

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

10:50 Pipeline 2.0: Integrating All Aspects from Target Acquisition through Binder Validation for Optimized Binder Generation

JonasSchaeferJonas V. Schaefer, Ph.D., Head, High-Throughput Laboratory, Department of Biochemistry, University of Zurich

A robust pipeline for the high-throughput generation of affinity reagents enables many scientific projects and novel applications. To optimize the pipeline’s throughput, our laboratory developed a streamlined process, consisting of parallel Ribosome Display selections and various semi-automated high-throughput screenings. Also including aspects of target acquisition to binder validation while decreasing its time and cost requirements, we perform simultaneous selections against 94 targets and screen and validate several thousand binders in parallel for their characteristics.


Screening for Rare Antibodies

11:20 An in vivo Human-Plasmablast Enrichment Technique Allows Rapid Identification of Therapeutic Influenza A Antibodies

GeraldNakamuraGerald Nakamura, Ph.D., Scientific Manager, Antibody Engineering, Genentech, Inc. – A Member of the Roche Group

Recent advances enabling the cloning of human immunoglobulin-G genes have proven effective for discovering monoclonal antibodies with therapeutic potential. However, these antibody-discovery methods are often arduous and identify only a few candidates from numerous antibody-secreting cells. We describe an in vivo enrichment technique that identified broadly influenza neutralizing human antibodies with high frequency. Using this technology, we identified four broadly neutralizing influenza A antibodies by screening only 840 human antibodies.

11:50 Towards a Quantum Leap in the Utility of Combinatorial Libraries for Drug Hunters by Placing New Functional Screening Options Up Front

RonaldLindsayRonald M. Lindsay, Ph.D., CEO, Zebra Biologics

Whereas the relative merits of deriving therapeutic antibody candidates via humanized mouse or phage display approaches are still debated, both approaches yield an over abundance of initial ‘hits’ as defined by binding to a desired target. Selecting “winners” from these initial hit binders remains a bottleneck. I will discuss new screening approaches that allow more direct high throughput selection of functional antibodies for known targets and the discovery of new targets.

12:20 pm Recent Advances and Successes in Structure-Based Protein Design Using BioLuminate

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

We describe several recent studies demonstrating the power of theoretical structure-based protein design tools as applied to antibodies, enzymes, and other proteins. We demonstrate how these tools can be applied to critical issues in design such as improved affinity and stability, as well as the elucidation of hot spots in an attempt to triage research efforts toward residues where modifications are more likely to be successful.


12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own


Rational Approaches to Antibody Engineering

2:00 Chairperson’s Remarks

Michael Drummond, Ph.D., Applications Scientist, Chemical Computing Group 

2:05 ADAPT – A Platform for Antibody Affinity Maturation

TraianSuleaTraian Sulea, Ph.D., Senior Research Officer, Human Health Therapeutics, National Research Council Canada

To assist affinity maturation of therapeutic antibodies we have implemented a platform combining binding affinity predictions with stepwise experimental verification. Starting from the crystal structure of an antibody-antigen complex, an efficient workflow based on mutation additivity interleaves ADAPT predictions with experimental validation from single-point mutations up to typically quadruple mutants. In this talk we will present prospective examples of employing ADAPT to affinity mature antibodies against VEGF and HER2.

2:35 Extracting Life’s Operating Manual – Comprehensive Ruleset Discovery and Bioengineering Applications

JacobGlanvilleJacob Glanville, Ph.D., CSO, Distributed Bio

Without comprehensive rulesets to guide rational design, most antibody bioengineering efforts are iterative process of applying and testing small changes. The combination of high-throughput sequencing, combinatorial gene synthesis and selection pressures provides a unique opportunity to enumerate the ruleset space that governs a molecule or entire repertoire. We’ll review the last 6 years of theory and practical application, then transition to highlight some of the startling novel technological applications such rule-based design can enable.

3:05 Precise and Efficient Antibody Epitope Determination Through Library Design, Yeast Surface Display and Next- Generation Sequencing

ThomasVanBlarcomThomas Van Blarcom, Ph.D., Principal Scientist, Protein Engineering, Pfizer, Inc.

Here we describe a method to precisely and efficiently map the epitopes of small panels of antibodies in parallel over the course of several weeks. This method relies on the nexus of rational library design, quantitative yeast surface display and next generation DNA sequencing and was demonstrated by mapping the epitopes of several antibodies that neutralize the alpha toxin from Staphylococcus aureus.

Chemical Computing GroupNEW logo3:35 Creating Focused Mutant Libraries for Protein Engineering

Michael Drummond, Ph.D., Applications Scientist, Chemical Computing Group 

Protein engineering plays a pivotal role in modulating the function, activity and physical properties of biologics. Representative strategies employed in protein engineering include directed evolution and rational protein design. Although both approaches are effective at identifying and optimizing protein therapeutic candidates, efficient search and evaluation of an excessively large sequence design space becomes challenging and requires multiple experimental rounds to reasonably assess the sequence space. 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.

4:05 Refreshment Break


4:30 Plenary Keynote Session

From Yeast to the Brain: Advances in Proteomics (More Details >>

John YatesJohn R. Yates, Ph.D., Ernest W. Hahn Professor, Chemical Physiology and Molecular and Cellular Neurobiology, The Scripps Research Institute

 

5:30-7:00 Reception in the Exhibit Hall with Poster Viewing



Day 1 | Day 2 | Download Brochure | Speaker Biographies