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7:00 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
George Georgiou, Ph.D., Professor, Chemical Engineering, University of Texas, Austin
8:40 Unique Combination of Computational Modeling, Antibody Engineering and Cell Biology
Birgit Schoeberl, Ph.D., Vice President, Discovery, Merrimack Pharmaceuticals
We will discuss the importance of disease context with respect to the design of monoclonal or bispecific antibodies. In addition, we will address the importance of growth factor receptor signaling crosstalk and how these insights drive the antibody design and engineering.
9:10 Importance of Early and Complete Characterization of Antibodies in the Lead Selection Process
Shrikant Deshpande, Ph.D., Senior Director, Protein Chemistry, Medarex, a wholly owned subsidiary of Bristol-Myers Squibb Co.
Selection of a lead candidate from a pool of antibodies is a critical step in product development. A wrong lead selected will result in major development issues. Understanding the biophysical and analytical characteristics of a pool of antibodies using a variety of tests will not only help select ideal leads, but also reduce or eliminate development issues.
9:40 Case Study: Engineered Human Antibody CH2 Constant Domains (Nanoantibodies) as Novel Candidate Therapeutics
Rui Gong, Ph.D., Postdoctoral Visiting Fellow, Protein Interaction Group, CCRNP, CCR, NCI-Frederick
Isolated immunoglobulin constant CH2 domains (nanoantibodies) are promising as scaffolds for selection of binders with potential effector functions. The binders against HIV-1 were selected and identified from several large libraries based on CH2 scaffold. However, CH2 domain is relatively unstable to thermally induced unfolding, which limits the use of CH2 as scaffold. A stabilized CH2 mutant (m01) with an additional disulfide bond was engineered and characterized, which can be used for the development of candidate therapeutic antibodies with increased stability.
10:10 Coffee Break, Poster and Exhibit Viewing
11:10 A Computational-Experimental Strategy for the Isolation of Antigen-Specific Antibodies from Immunized Animals
George Georgiou, Ph.D., Professor, Chemical Engineering, University of Texas, Austin
We have developed a computational-experimental strategy for the isolation of antigen-specific antibodies from immunized animals. This methodology is simple, fast and requires neither cloning nor screening. In addition, and to complement Ab isolation from immunized animals we have developed an improved bacterial display system for affinity maturation, for Fc engineering and de novo antibody discovery.
11:40 Analytical Methods to Characterize and Evaluate the Mode of Action of Antibody Drug Conjugates
Vangipuram Rangan, Ph.D., Director, Protein Chemistry, Medarex, a wholly owned subsidiary of Bristol-Myers Squibb Co.
Antibody drug conjugates (ADC) are emerging platform technology where antibodies are used as targeting agents to deliver payloads to the tumor site. In order to characterize ADCs as well as to understand their mechanism of action, one has to develop various analytical methods and assays that are unique to ADCs. This presentation describes several analytical methods that are employed to characterize ADCs being developed at Medarex, a wholly owned subsidiary of BMS.
Sponsored by
12:10 pm Luncheon Presentation I
Slonomics® - An Innovative Toolbox for the Precise Engineering of Immunoglobulin Repertoires
Thomas Waldmann, Ph.D., Director, Science & Technology Support, Sloning BioTechnology GmbH
Slonomics®, a proprietary genetic engineering platform, uses standardized DNA triplets as building blocks. It allows for introducing multiple codons in parallel at any desired sequence position. The ability to precisely control the individual frequency of up to 20 specific codons per position results in genetically diverse libraries with unique molecular profiles. The technology easily allows for combining complex positional mutation strategies with diversifying the length of randomized regions. Therefore, synthetic antibody libraries of highest quality can be created that mimic the design of naturally occurring immunoglobulin repertoires.
12:40 Luncheon Presentation II (Opportunity Available)
1:30 Chairperson’s Remarks
1:35 Application of H/D-Exchange for Epitope Screening to Assist with Candidate mAb Selection
Jennifer Nemeth, Ph.D., Principal Research Scientist, Biologics Research, Centocor Research and Development
Hydrogen/deuterium-exchange (H/D-Ex) coupled with mass spectrometry is having an impact in the biopharmaceutical arena in the area of epitope mapping and lead selection. As the use of the technology is still quite novel for biopharmaceutical applications, this talk is timely and relevant in this era of intelligent drug design. An example of the utility of this technology is highlighted during lead selection in a monoclonal antibody (mAb) drug program. As the timelines and sample amounts were limited, hydrogen/deuterium-exchange (H/D-Ex) was chosen for mapping out the epitopes on the target antigen, as opposed to more traditional techniques. Based on the results, lead and back-up mAbs were selected that had desirable epitopes for further product development.
2:05 A Multi-Fc-Species System for Recombinant Antibody Production
Stefan Dübel, Ph.D., Professor, Technical Institute of Braunsweig
Sponsored by
2:35 Talk Title to be Announced
Arnout Gerritsen, Genmab, Netherlands
Sponsored by
2:50 Deriving and Epitope Mapping
Antibodies Targeting Membrane Proteins
Benjamin Doranz, Ph.D., President and CSO, Integral Molecular
Integral Molecular’s Lipoparticle technology provides an innovative solution for presenting structurally intact membrane protein antigens, including GPCRs and ion channels, at concentrations 10-100x higher (50-200pmol/mg) than in cells or membrane preparations. This enabled us to derive high titer serum responses (>1:500) against membrane proteins of interest and to characterize resulting antibodies using techniques such as biosensor analysis. Once MAbs are isolated, our Shotgun Mutagenesis Mapping technology enabled us to rapidly identify both linear and conformationally complex epitopes that distinguish MAb binding sites.
3:15 Networking Refreshment Break, Poster and Exhibit Viewing
3:50 Problem Solving Break-Out Sessions
In vitro screening or immunization? Isolating biologically active antibodies
Host: George Georgiou, Ph.D., Professor, Department of Biomedical Engineering, University of Texas at Austin
CMC issues with ADCs
Host: Vangipuram S. Rangan, Ph.D., Director, Protein Chemistry, Medarax Inc. a subsidiary of Bristol-Myers Squibb
- Importance of identification of site of conjugation in current ADC platforms
- Random conjugation versus site-specific conjugation
- Importance of analytical methods
Engineered Antibody Domains
Host: Rui Gong, Ph.D., Postdoctoral Visiting Fellow, Protein Interaction Group, CCRNP, CCR, NCI-Frederick
Increasing Efficiency of Phage Display Libraries and Selection
Host: Prof. Dr. Stefan Dübel, Technische Universität Braunschweig, Institute of Biochemistry and Biotechnology
- Pitfalls in library making
- Controlling display valency
- QC of libraries
- Tuning of panning conditions to get what you want
Stability prediction parameters: How well they perform in the real world?
Host: Shrikant Deshpande, Ph.D., Medarex Inc, a subsidiary of Bristol-Myers Squibb
- How can we predict the stability of the antibodies in the real world based on early screening techniques such as DSC, aggregation propensity
- Acclerated deamidation studies: How well they correlate with the in vivo situation?
4:50 Networking Cocktail Reception in the Exhibit Hall
6:00 End of Day
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