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As the pharmaceutical and biotech industries increasingly shift attention to biologics, much more attention is being paid to the prospect of membrane-bound proteins as drug targets for antibodies and other protein scaffolds. For the large GPCR and ion channel target classes, biologics offer improved selectivity, an alternative for targets with known function that have not been amenable to small molecule drugs and the potential for using antibodies for the targeted delivery of therapeutics.

The first meeting in the set, Antigen Optimization; Generation and Selection of Antibodies and Protein Scaffolds, offers a comprehensive examination of the range of methods available for producing appropriate membrane protein antigens, selecting the best screening methods for a specific target or target classes and how to develop and optimize the discovery and screening campaigns to identify functional antibodies. Part One also reviews other scaffold options, including single domain antibodies, as alternative therapeutic modalities for these targets.

Final Agenda


Day 1 | Day 2 | Download Brochure 


Tuesday, September 22

7:00 am Registration and Morning Coffee

8:00 Chairperson’s Opening Remarks

Matt Holsti, Ph.D., Principal Scientist, Global BioTX Technologies, Pfizer

8:10 Keynote Presentation: Selection of Membrane Protein Targets: GPCRs as a Paradigm 

Paul Insel, M.D., Ph.D., Vice-Chair and Distinguished Professor, Pharmacology; University of California, San Diego

GPCRs are the largest superfamily of membrane signaling receptors and the largest group of targets of approved drugs, but are the optimal GPCRs being targeted? Using a GPCRomic approach to define the GPCRs expressed by individual cell types from healthy and diseased subjects, we have discovered “novel” GPCRs, including potential therapeutic targets for diseases that are unmet medical needs.


IMMUNIZATION AND DISPLAY STRATEGIES
FOR MEMBRANE PROTEINS

8:40 Computational Design of Epitope Scaffolds to Induce Antibodies against Membrane Proximal Epitopes

William R. Schief, Ph.D., Professor, Immunology & Microbial Science, Scripps Research Institute; Director, Vaccine Design, International AIDS Vaccine Initiative

Our HIV vaccine design work involves immunogen design projects aiming to induce antibodies against membrane proximal structural epitopes – with challenges including engineering membrane proteins, optimizing epitope conformation and designing antigens to select for specific H-CDR3 loops. This talk presents lessons that may assist induction of antibodies against other membrane targets.

9:10 Cell-Free Expression of G-Protein Coupled Receptors: New Pipelines for Challenging Targets

Frank Bernhard, Ph.D., Group Leader, Institute of Biophysical Chemistry, Goethe University, Germany

The unique variability of cell-free expression reactions allows systematic optimization screens to improve the quality of synthesized GPCRs. Preparative scale amounts of ligand binding active receptor can thus be obtained and structural approaches come into focus. Strategies for GPCR quality optimization will be exemplified and characteristic biochemical properties of the samples are presented.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

10:25 Immunization Strategies for Antibody Generation against Multi-Spanning Proteins

Jane Seagal, Ph.D., Senior Scientist, AbbVie Bioresearch Center

Hybridoma generation against multi-spanning proteins is challenging. Expression levels of proteins on the cell surface may not be sufficiently high, and peptides corresponding to extracellular loops do not have natural conformation. We utilized cDNA immunizations to elicit immune response against multi-spanning proteins, leading to successful generation of hybridomas producing functional mAbs.

10:55 Identification of Biased Antagonists by Screening Single Domain Antibodies against GPCRs in Lipoparticles

Mick Foley, Ph.D., CSO, AdAlta, Australia

i-bodies are human single domains with a long CDR3 that enables access to proteins such as GPCRs. High affinity i-bodies specific for CXCR4 were obtained by screening on lipoparticles and each of the i-bodies have different functional profiles. These blocked SDF-1-induced leukocyte recruitment in a mouse model of inflammation and did not mobilize stem cells from bone marrow.

11:25 VelocImmune Mice for Generation of Antibodies against Complex Membrane Protein Targets

Andrew Murphy, Ph.D., Vice President, Gene Discovery & Bioinformatics, Regeneron Pharmaceuticals

11:55 Discovery of MAbs against Difficult GPCRs, Ion Channels, and Transporters

Joseph Rucker, Ph.D., Vice President, Research and Development, Integral Molecular, Inc.

To enable the isolation, characterization, and engineering of MAbs against challenging membrane protein targets, Integral Molecular has developed the MPS Discovery Engine™ platform, encompassing lipoparticles for concentrating native membrane proteins and shotgun mutagenesis for membrane protein engineering and epitope mapping. Using MPS, we have generated functional MAbs against the ion channel P2X3 (neuropathic pain), GLUT transporter (diabetes), and CXCR4 (cancer), and have ongoing discovery programs against additional GPCR, ion channel, and transporter targets.

12:25 pm Towards Native and Stable GPCRs for Conformational Antibody Development. Case Study with Native and Functional Adenosine Receptor A2A

Anass Jawhari, Ph.D., CSO, CALIXAR

Adenosine receptor A2A plays an essential role in the central nervous system. Thanks to CALIXAR patented technology based on new chemistry approach to safely isolate membrane proteins, functional A2A was solubilized and purified without any single mutation, truncation or fusion for antibody development purposes and crystallization.

12:40 Session Break

12:45 Luncheon Presentation to be Announced

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


DISCOVERY STRATEGIES FOR FUNCTIONAL ANTIBODIES AGAINST MEMBRANE
PROTEIN TARGETS

1:50 Chairperson’s Remarks

Barbara Swanson, Ph.D., Director, Research, Sorrento Therapeutics, Inc.

2:00 Selecting Antibodies Using a Combined in vitro and in vivo Approach

Andrew M. Bradbury, Ph.D., MB, BS, Staff Scientist, Biosciences, Los Alamos National Laboratory

The identification of antibodies suitable for in vivo use can be challenging. In this talk, we will present new data on the selection of antibodies against previously identified membrane protein targets using a combined in vitro/in vivo approach.

2:30 Protein Knockout Mice: A Novel in vivo Validation Approach for Membrane Targets

Stefan Dübel, Ph.D., Director, Institute of Biochemistry, Biotechnology and Bioinformatics, Technical University of Braunschweig, Germany

We present a novel drug discovery method which is applicable to all membrane and secretory proteins. We demonstrate that endoplasmatic reticulum retained antibodies (“intrabodies”) can induce a protein knockdown phenotype in transgenic mice. A single cloning step is needed from phage display selection of human antibodies to a target to induction of the mouse knockdown phenotype for this target.

3:00 Identifying Antibodies against Cell-Surface Receptors Using Live Cells within an Emulsion

Michael Weiner, Ph.D., CSO, AxioMx, Inc.

Our goal is to produce a fully recombinant IgG antibody within 3-4 weeks of receiving a suitable antigen. We will demonstrate the use of emulsion screening to identify affinity binders from a >1010 sized library against protein receptors displayed in situ on a living cell surface. Emulsion panning generates a greater number of unique clones by effectively eliminating the clonal expansion seen with traditional panning methods that use multiple rounds of enrichment.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Winner Announced

4:10 Engineering Conformation Selective Antibodies to Membrane Protein Complexes

Marcin Paduch, Ph.D., Technical Director, Synthetic Antibody & Crystallography Core Facility, Department of Biochemistry and Molecular Biology, Recombinant Antibody Network, The University of Chicago

To address the challenges of membrane protein complexes and their conformational states, we have developed a suite of high-throughput technologies exploiting multiple antigen presentation formats, novel phage display libraries and improved biopanning techniques networking them together on a modern automation system. This integrated pipeline generated antibodies to nuclear pore complex and several Get3-tail anchored protein complexes.

4:40 Going Native: Direct High-Throughput Screening of Soluble, Secreted mAbs against Intact Target Cells

Karl Griswold, Ph.D., Associate Professor, Thayer School of Engineering, Dartmouth University

We describe an ultra-high throughput screening platform that enables identification and isolation of soluble, secreted, monoclonal antibodies that bind membrane proteins in their native environment: on the cell surface. Using gel microdroplet encapsulation combined with high-speed flow cytometry, we demonstrate recovery of rare clones producing IgG binders to targets such as EGFR.

5:10 Interactive Breakout Discussion Groups

6:10 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 Close of Day

Day 1 | Day 2 | Download Brochure 


Wednesday, September 23

7:30 am Registration and Morning Coffee


BEYOND ANTIBODIES: OTHER STRATEGIES FOR TARGETING MEMBRANE PROTEINS
WITH BIOLOGICS

8:00 Chairperson’s Remarks

Matthew Gardener, Ph.D., Senior Scientist, Research, MedImmune, United Kingdom

8:10 Affimers – Novel Scaffolds for Molecular Recognition of Membrane Targets

Darren Tomlinson, Ph.D., University Academic Fellow, University of Leeds, United Kingdom

Novel scaffold proteins represent a promising alternative to antibodies in applications ranging from research reagents to therapeutics. Affimers are highly stable scaffold proteins that show great versatility. We describe the development of these scaffolds and give examples of generating highly specific reagents against membrane proteins that can inhibit function directly or through allosteric mechanisms.

8:40 Allosteric Nanobodies for Better Drug Discovery

Jan Steyaert, Ph.D., Director, Structural Biology Brussels Research Center, Vrije University Brussels, Belgium

By using Nanobodies that exhibit G protein-like behavior, we were able to lock GPCRs constitutively in their active conformation. These GPCR-Nanobody complexes have a unique pharmacological profile that is similar to the G protein bound receptor and allow screening of compounds that selectively bind the active conformation of these receptors.

9:10 Rational Design of Humanized Agonist Antibodies

Yong (Tiger) Zhang, Ph.D., Assistant Professor, Pharmacology & Pharmaceutical Sciences, University of Southern California

Inspired by antibodies with an ultralong heavy chain CDR3H that exhibits a unique architecture, functional polypeptides were genetically fused into the CDR regions of a humanized antibody. The resulting chimeric antibodies show excellent physical, biological, and pharmacological properties, and support the use of this approach for the generation of innovative antibody therapeutics for the treatment of human diseases.

9:40 Coffee Break in the Exhibit Hall with Poster Viewing

10:25 Novel Long VH CDR3 Antibodies Targeting the FPR Receptor

Matthew Gardener, Ph.D., Senior Scientist, Research, MedImmune, United Kingdom

Using an immunization approach and subsequent phage display-based engineering, Fpro0165 was generated which completely neutralizes the formyl peptide-mediated activation of human neutrophils. This antibody contains a long, protruding VH CDR3 of 24 amino acids and the critical requirement for this long VH CDR3 in determining the antibodies binding profile will be discussed.

10:55 Identification of Potent Nanobodies® against Ion Channels and GPCRs

Marie-Ange Buyse, Ph.D., Director, Discovery, Ablynx, Belgium

Nanobodies® are therapeutic proteins based on single-domain antibody fragments derived from naturally occurring heavy-chain only antibodies. They can be easily engineered via genetic fusion into multivalent and multispecific molecules. Case studies on the identification of potent Nanobodies with superior target-selective ion channel binding as well as potent GPCR Nanobodies will be presented.

11:25 Enjoy Lunch on Your Own

12:55 pm Plenary Keynote Program 

2:40 Refreshment Break in the Exhibit Hall with Poster Viewing

3:25 Close of Conference



Day 1 | Day 2 | Download Brochure 


Suggested Event Package: 

September 21 Short Course: GPCR Structure-Based Drug Discovery 

September 21 Short Course: Targeting of GPCRs with Monoclonal Antibodies 

September 22-23 Conference: Antibodies Against Membrane Protein Targets Part 1 

September 23-24 Conference: Antibodies Against Membrane Protein Targets Part 2 

September 23 Short Course: Introduction to Allosteric Modulators and Biased Ligands of GPCRs 

 

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2015 Discovery on Target Brochure  

2015 BROCHURE 


 PREMIER SPONSORS 

Cellecta 

Domainex

Molecular Sensing 

Rosa Drug Development Advisors

Sigma_NEW

 

VIEW ALL SPONSORS 

VIEW MEDIA PARTNERS 


IPR_Micrombiome 


SPONSORSHIPS & EXHIBITS 

The exhibit hall was sold out in 2014, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2015, contact:

Jon Stroup
Sr. Business Development Manager
781-972-5483
jstroup@healthtech.com 


 

September 21 

Next-Generation Histone Deacetylase Inhibitors Symposia 

Strategies for Rare Diseases Symposia 

September 22 

Developing CRISPR-Based Therapies Symposia 

September 22 - 23 

Targeting Epigenetic Readers and Chromatin Remodelers 

Targeting the Ubiquitin Proteasome System 

Targeting the Microbiome 

GPCR - Based Drug Discovery - Part 1 

Antibodies Against Membrane Protein Targets - Part 1 

RNAi for Functional Genomics Screening 

Gene Therapy Breakthroughs 

Targeting Ocular Disorders 

September 23 - 24 

Targeting Histone Methyltransferases and Demethylases 

Targeting the Unfolded Protein Response 

Kinase Inhibitor Discovery 

GPCR-Based Drug Discovery - Part 2 

Antibodies Against Membrane Protein Targets - Part 2 

New Frontiers in Gene Editing 

Quantitative Systems Pharmacology 

Short Courses 

SC1: Cancer Metabolism: Pathways, Targets and Clinical Updates 

SC2: Leveraging Data and Analytics for Drug DiSCovery 

SC3: Setting Up Effective Rnai SCreens: From Design to Data to Validation 

SC4: Phenotypic SCreening and Chemical Probe Development 

SC5: GPCR Structure-based Drug Discovery 

SC6: Targeting of GPCRs with Monoclonal Antibodies 

SC7: Setting Up Effective Functional SCreens Using 3D Cell Cultures 

SC8: Targeting Protein-protein Interactions: Biophysical Approaches 

SC9: Preclinical Animal Models for Ocular Indications 

SC10: Introduction to Allosteric Modulators and Biased Ligands of GPCRs 

SC11: Introduction to Targeted Covalent Inhibitors 

SC12: Assays and High-throughput SCreening for Novel Epigenetic Inhibitors 

SC13: Gamification and Drug Target Challenges 

SC14: A Primer to Gene Editing: Tools and Applications 

SC15: Using Mechanistic Physiological Models In Drug Development