The First Protein Tomography™ Symposium
1 pm – 6 pm, Thursday, May 1, Boston InterContinental Hotel

The Executive Forum will focus on the unique biological information obtained in situ and in vitro by Protein Tomography to elucidate the
interaction of antibodies with drug targets at the molecular level. We will discuss the role of Protein Tomography to provide essential data for epitope mapping, IP, and how to resolve issues in the discovery phase. We will focus on how this insight impacts the decision-making process for the development of bio-therapeutics.  Watch the Sidec Webinar

Sidec’s Executive Forum will be held during the PEGS Summit on May 1 from 1-6pm with dinner to follow at 6:30pm. The audience will
be comprised of executive-level members of the therapeutic antibody discovery and development industry.

For more information about Sidec, visit www.sidec.com

Protein Tomography™ gives you a glimpse of biological secrets
Don’t miss the opportunity to see Sidec’s team demonstrate and guide you through two projects:

1. In a project with Genmab A/S, Protein Tomography™ has been used to study the molecular mode of action of a therapeutic antibody binding to its target, EGFr. 

2. In collaboration with Nobel laureate Prof. Roger Kornberg and his team at Stanford University, Protein Tomography™ is used to study the dynamics of RNA polymerase in solution.

The demonstrations take place Thursday, May 1 – Friday, May 2 in the Rose Kennedy foyer, just outside the Dartmouth/Eleanor room on 3rd floor, at the InterContinental Hotel.

The Secret Life of Therapeutic Antibodies
Molecular Mechanism of action to power discovery
The First Protein Tomography™ Symposium

Thursday, May 1, 1:00 pm – 6:00 pm
Dartmouth/Eleanor room, on 3rd floor at InterContinental Hotel

Chairperson: Fritz Frickel, PhD, Senior Pharma Advisor

1:00 pm Chairpersons Opening Remarks 

1:15 Using Protein Tomography™ to understand protein function
Ulf Skoglund, PhD, Cell & Molecular Biology, The Karolinska Institute
Three-dimensional (3D) visualization of individual protein conformations is a powerful way to understand protein function and large-scale molecular dynamics under various conditions. This can be realized by using the molecular electron tomography procedure. Using specimen recordings from a transmission electron microscope (TEM), a 3D reconstruction of the specimen can be calculated. Algorithms developed at CMB, Karolinska Institute, and Sidec, allow 3D reconstructions to be calculated at around 2 nm resolution for proteins in buffer solution and between 2 3 nm resolution for proteins in situ, e.g., in their membrane setting. Thus, several individual macromolecules in a biological specimen, e.g., a protein solution or a tissue section, can be examined for their conformational flexibility, subunit assembly and tendency to deviate from a perhaps known X-ray crystallographic structure. 

Dr. Skoglund, Professor in Molecular Genetics, pioneered the development of molecular electron tomography for 3D reconstruction of individual protein molecules. He is the co-founderof the company Sidec AB.

1:45 Antibody conformation and interactions studied by Protein Tomography™
José R. Casas-Finet, PhD, DSc, Fellow, R&D, MedImmune
Antibodies are not rigid bodies but instead consist of three domains connected by a flexible hinge that allows characteristic segmental motion and presentation of combining sites. This feature is critical to antibody function, but is difficult to model from X-ray crystallography results and Molecular Dynamics simulations. Protein Tomography affords direct visualization of conformations of individual MAb molecules and complexes.

Dr. Casas-Finet is a Scientific Advisor and R&D Fellow at MedImmune (Gaithersburg, MD) where 
he evaluates new technologies for the characterization of drug candidates. He was formerly Senior Scientist and Head of the AIDS Vaccine Program's Physical Chemistry Section in the Frederick campus of the National Cancer Institute.

2:15 Talk title to be announced later
William T. Loging, PhD, Director of Research, Pfizer 

2:45 Mechanisms of Therapeutic Antibodies for Cancer: Modes of Action of zalutumumab
Wim K. Bleeker, PhD, Director Translational Research & Pharmacology, Genmab 
Zalutumumab (HuMax-EGFr) is a human IgG1 antibody blocking the activation of the Epidermal Growth Factor receptor (EGFr) and efficiently recruiting effector cells for antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the interaction between HuMax-EGFr and EGFr on cells using protein tomography, in order to gain insight in the mechanism of receptor inhibition at molecular level. Furthermore, we compared EGFr antibodies with different characteristics in several in vitro and in vivo models to estimate the differential contributions of the different mechanisms of action to the anti-tumour effects of HuMax-EGFr in mouse models. 

Taken together, our findings indicate that HuMax-EGFr has two therapeutic mechanisms. First, it blocks EGFR signalling by preventing receptor dimerization. This mechanism was found to be effective in established tumours, at doses giving full receptor occupancy. Second, induction of ADCC represents an additional effector mechanism, which is in vivo already active at a very low dose and is likely to be important for preventing metastases. 

Dr. Bleeker was involved in the preclinical in vitro and in vivo evaluation of zalutumumab. Currently, he is responsible for translational research at Genmab and especially for the evaluation of various antibodies in animal models

3:15-3:45 pm Coffee break in the Rose Kennedy Foyer, just outside the Dartmouth/Eleanor Room 
Take the opportunity during the Coffee Break to see Sidec’s team demonstrate and guide you through two Protein Tomography projects: One in collaboration with Nobel laureate Prof. Roger Kornberg and his team and one project with Genmab A/S. The demos take place Thursday, May 1 – Friday, May 2 in the Rose Kennedy Foyer, just outside the Dartmouth/Eleanor Room.

3:45 Use of Protein Tomography to Image in situ the Synaptic Vesicle Protein 2A
Berkley Lynch, PhD, Senior Director, Discovery Research, Link Medicine 
The antiepileptic drug (AED) levetiracetam (LEV, Keppra®) binds to a unique site in the brain: the synaptic vesicle protein 2A (SV2A), a member, by sequence homology, of the major facilitator superfamily (MFS) of transporter proteins (Lynch et al, 2004). Despite evidence that LEV acts at least partly via its binding to SV2A, very little is known about the molecular and cellular functions of SV2A, and there is no current understanding of the possible effects of LEV binding to SV2A. In order to advance our understanding of SV2A, we undertook a project to image the protein through the use of advanced methods of tomographic analysis of electron microscopy (EM) images of presynaptic terminals. This study was undertaken to determine if SV2A might take conformations consistent with its having a transporter function, as predicted by its sequence homology, and with the alternating-access model of MFS proposed by Kaback et al (2007). 

Dr. Lynch previously worked at UCB Pharma on the mechanism of action of levetiracetam. Currently, he heads the Discovery Research department at Link Medicine, a biotechnology company developing therapeutics targeting neurodegenerative diseases. 

4:15 Protein Tomography: Enabling Technology for Therapeutic Antibody Development
Fritz Frickel, PhD, Senior Pharma Advisor
Despite the wealth of information and strategies arising from in silico molecular modeling and screening, there is still a glaring lack of information on the molecular mechanisms of action between drug and target. I will illustrate the potential of deeper molecular insight and indicate where, when and how I envisage its impact in the drug discovery process. 

Dr. Frickel is an independent advisor to biopharmaceutical companies.He held various management positions at BASF Pharma, Abbott and Alantos in Research,Development and Strategic Marketing in the US and Europe.He played a leading role in the development of the first (murine) antibody against TNF and Humira. He is chairman of Sidec and a director of RespiVert

4:45 Does Unambiguous Proof of a Drug Epitope Permit Enhanced IP Protection?
Kathleen Madden Williams, PhD, JD Edwards Agnell Palmer & Dodge LLP

Present day patent protection on antibodies has entered an ever-narrowing tunnel, and many current patents are limited to a specific antibody sequence or a set of CDR sequences. This level of protection most often does not prevent competition by slightly different CDR or antibody sequences. The ideal antibody patent protection is limited to the antigen specificity, but rarely do we see such patents issuing now. How can one  narrow the legal void between protection of an antibody specific for an antigen and an antibody having a specific sequence? Is there a gold standard by which to distinguish an antibody and thereby obtain meaningful patent protection?

Dr. Williams is an intellectual property attorney specializing in life sciences IP and a partner at Edwards, Angell Palmer & Dodge LLP. She advises as to the strategic use of IP to obtain patent protection, as well as positioning research and commercial activities with respect to third party patents.

5:15 Chairpersons Remarks

6:00 pm End of Sidec Executive Forum

6:30 pm Dinner in the Hutchinson Room