DISCOVERY STREAM

14th Annual

Phage and Yeast Display of Antibodies
and Proteins April 30 - May 1

The methods for using phage and yeast display are constantly being improved and modified for the purpose of isolating high affinity protein ligands against nearly any receptor through directed evolution. The use of display techniques generate high quality antibody libraries to screen against disease targets. This meeting will look at the use of high throughput gene sequencing for improving library diversity and depth. It will also look at using criteria early in selections for developability. The use of available crystal structures is now guiding engineering approaches for biologics. Plan to take in the latest developments in this important sector of protein engineering to see where the field is headed.

Day 1 | Day 2

SUNDAY, APRIL 29

4:00 - 6:00 pm Main Conference Registration

MONDAY, APRIL 30

7:00 am Registration and Morning Coffee

B CELL CLONING

9:40 B Cell Display: Screening the Native Human B Cell Repertoire for Broadly Crossreactive Antibodies against the Influenza A Virus

Minha Park, Ph.D., Scientist, Antibody Discovery & B Cell Immunology, Trellis Bioscience

The human B cell repertoire represents a rich library of antibodies that have been naturally selected for high affinity, stability, and lack of off-target reactivity against human antigens, and therefore, less likely to cause immunogenicity when used as therapeutic agents. However, the low frequency of B cells expressing high quality antigen-specific antibodies has posed a barrier to discovery. Here, we show successful application of the Trellis Cellspot platform of single cell phenotyping to recover rare human B cells expressing high affinity and broadly crossreactive antibodies against the influenza A virus.

10:10 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

IN VIVO HALF-LIFE EXTENSION

11:10 Engineering Super Albumin for Improving Serum Half-Life

Chaity Chaudhury, Ph.D., Scientist, Antibody Discovery & Protein Engineering, MedImmune LLC

FcRn binds both IgG and albumin and diverts them from the lysosomal degredation pathway thus enhancing their lifespan. While FcRn mediated half-life extension through Fc has been engineered extensively, pH dependent affinity maturation of albumin to improve serum half-life remains laregely unexplored. We have engineered human albumin to improve its affinity for FcRn while retaining the pH dependence of binding through off rate engineering to extend lifespan of non-antibody therapeutics.

11:40 Use of pH Dependent Binding of Engineered Antibodies with Improved in vivo Half-Life Extension

E. Sally Ward, Ph.D., Paul and Betty Meek-FINA Professorship, Molecular Immunology, Cancer Immunobiology Center, University of Texas Southwestern

FcRn plays a central role in regulating the transport and distribution of IgG in the body. The presentation will cover recent developments in understanding FcRn function, combined with engineering FcRn-Fc interactions to generate therapies for autoimmune disease.

Sponsored by
12:10 pm Advances in Albumin Half-Life Extension Platform Translates to Positive Pharmacokinetic Studies

Mark Perkins, Ph.D., Technical Solution Specialist, Novozymes Biopharma

The ability to enhance the therapeutic half-life of drugs by conjugation or fusion to albumin is now well established. We have shown that albumin can be further enhanced for uses in drug delivery by manipulating its interaction with the neonatal Fc receptor (FcRn) via the introduction of specific amino acid changes in the albumin sequence. This talk will highlight a novel albumin platform and will include new pharmacokinetic data demonstrating the extended circulatory half-life of the albumin variants and protein drugs linked to such variants.

12:40 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

EPITOPE MAPPING WITH CRYSTALLIZATION AND DISPLAY

2:00 Chairperson's Remarks

David Lowe, Ph.D., Fellow, R&D, MedImmune UK

2:05 Phage Selection of Bicyclic Peptides

Christian Heinis, Ph.D., Laboratory of Therapeutic Peptides and Proteins, Ecole Polytechnique Federal de Lausanne (EPFL)

My laboratory is generating bicyclic peptide ligands with high affinity and specificity for disease targets using a phage display-based approach that I had developed with Sir Greg Winter at the Laboratory of Molecular Biology (LMB) in Cambridge, UK (1). I will present the structure of a target-bound bicyclic peptide, new bicyclic peptide formats as well as first in vivo data.

2:35 Synthetic Antibodies: Structure and Function

Sachdev Sidhu, Ph.D., Associate Professor, Medical Research, University of Toronto

Synthetic antibody libraries have simplified the discovery of antibodies for structural studies. Synthetic antibody libraries are highly versatile for generating antibodies against diverse antigens. Moreover, synthetic antibodies exhibit superior performance in crystallization studies due to their stable nature.

3:05 Optimizing Functional Modules of Bispecific Antibodies Using Yeast Display Platform

Lihui Xu, Ph.D., Principal Scientist, Merrimack Pharmaceuticals

We developed a yeast display platform that combines the features of surface display and soluble expression within the single system, in conjunction with small structure-guided antibody library and innovative screening strategy, we are able to discover optimal functional modules in single campaign for a bispecific antibody that targets two Growth Factor Receptors.

3:35 State of the Art Epitope Mapping and Insights Gained from mAb-Target Co-Crystal Structures

Andrew Buchanan, Ph.D., Senior Scientist, Protein Engineering, MedImmune Ltd.

Examples of co-crystal structures will be used to provide insight into the antibody mechanism of action, species cross reactivity and the characteristics of the antibody paratope. In addition, alternative methods of epitope mapping will be illustrated.

4:05 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem Solving Breakout Discussions

5:45-6:45 Welcome Reception in the Exhibit Hall with Poster Viewing

Day 1 | Day 2