Infectiology
Models
Vaccine
Monoclonal antibodies New Therapeutic Antimicrobial & Vaccine Approaches in
THE BOOK Infectious Diseases
April 2nd 2008 The Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla, CA 92037
French American Biotechnology Symposium
French BIO Beach Preambule Diseases. In 2008, the symposium isfocused on the New therapeutic and Vaccine Approaches inInfectious •Favor the emergence of collaborative and innovative research projects. •Foster French-Californian cooperation between research laboratories and biotech companies •Promote research and innovation where California and France share acompetitive advantage The FABS event aims to : Embassy of France, aiming to be held yearly inCalifornia. The French American Biotech Symposium islaunched by the Office for Science and Technology of the 2 held onApril on “New Therapeutic & Vaccine Approaches in Infectious Diseases”, Welcome to the FABS, French American Biotech Symposium, French based firms. opportunities Targeted attendees areFrench and American scientists and biotech entrepreneurs. Networking Economy, (LR-PACA) and Medicen Paris Region. The event benefits from the support of the French Ministry of Competitiveness Clusters, Alsace Biovalley (Alsace), Cancer-Bio-Health Cluster (Toulouse), Orpheme Studies (La Jolla, and CA) French BIO Beach (La Jolla, and CA) with the presence of the French Bio Technology of the Embassy of France inLos Angeles, inpartnership with The SalkInstitute for Biological The symposium isorganized by Lyonbiopole (Rhône-Alpes, France) and The Office for Science and round antimicrobial treatments. Each session willpropose French &American presentations followed by a monoclonal antibodies, the advances of humanized animal models and the new perspectives for Bio Biz, FABZ April 3
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Antimicrobial PROGRAM
“Ne w Th e r a p e u t i c a n d Va c c i n e Ap p r o a c h e s in In f e c t i o u s Di s e a s e s ” Antimicrobial at The Salk Institute for Biological Studies
8.00 am...... Registration Opening Jacques Descotes, M.D., Pharm.D., Ph.D., Professor, Claude Bernard University and Head, Lyon Poison Center 8.30 to 9.00 am ...... Welcome Talks Title: Immunotoxicity evaluation of monoclonal antibodies: from Roger Guillemin, Distinguished Professor, Nobel Prize of Medicine, animal to man President by interim of The Salk Institute for Biological Studie Philippe Larrieu, Consul General of France in Los Angeles 1.00 to 2.30 pm...... Lunch – Posters Sessions
9.00 to 10.30 am...... Session 1: 2.30 to 4.00 pm...... Session 3: 1 Key Issues for Vaccine Development – Part I 3 Towards Humanized Animal Models Chairman : Jean-Yves Bonnefoy, Ph.D., VP, R&D, Transgene Chaiman: James P. Di Santo, M.D., Ph.D., Professor of Immunology, Institut Pasteur Keynote Speaker : Jacques Banchereau, Ph.D., Director, Baylor Institute for Immunology Research, Director, INSERM-U899, BIIR/ANRS/ Amine Abina, M.D., Ph.D., President & CEO, Nokad INSERM Center for Human Vaccines Title: Protein-functional-Knock-Out: a new approach in target Title: Humanized mice to understand the pathophysiology of human validation and models of pathology dendritic cells in vivo Jérôme Tiollier, Ph.D., EVP Development & Operations, Innate Pharma Greg Lemke, Professor & Director, Molecular Neurobiology Laboratory, Title: Limist & Merits of preclinical pharmacological assessment of The Salk Institute for Biological Studies immunotherapeutic drugs during development Title: New Adjuvant Approaches Kader Thiam, Ph.D., VP Transgenic Technologies, genOway Anette Schneemann, Ph.D., Associate Professor, Department Molecular Title: Use of genetically modified animal models aiming at increasing Biology, The Scripps Research Institute the predictability and the throughput of immune response analysis Title: Virus-like particles as platforms for vaccine development in vivo
Alain Rolland, Pharm.D., Ph.D., Senior Vice President, Product Develop- Erwan Corcuff, Axenis Project Leader, Technical Coordinator of ment and Corporate Officer, Vical Inc. « Human Vaccine Consortium» and Medicen/Modexa/Biotherapies, Title: DNA Vaccines : the end of the beginning Cytokines & Lymphoïd Development, Institut Pasteur Title: Novel humanized mouse model for Testing HIV and HCV Vaccine 10.30 to 10.45 am...... Coffee break Candidates
10.45 to 12.00 am...... Session 1: 4.00 to 4.15 pm...... Coffee break 1 Key Issues for Vaccine Development – Part II Chairman: Jean-Yves Bonnefoy, Ph.D., VP, R&D, Transgene 4.15 to 5.45 pm...... Session 4: 4 New Perspectives for Antimicrobial Treatments Marie Louise Michel, Ph.D., Department of Virology, Institut Pasteur, Chairman: John A. T. Young, Ph.D., Professor and faculty Director of Pathogenesis of hepatitis B virus laboratory Chair, The Salk Institute for Biological Studies Title: Therapeutic vaccination for chronic infection Keynote Speaker: Jean-Pierre Gorvel, Ph.D., Director of the Centre Phil Felgner, Professor, University of California at Irvine d’Immunologie de Marseille-Luminy, Executive Director of the Title: Profiling the Immune Response to Infections with Genome-Wide Foundation FINOVI, Innovation in Infectiology Proteome Arrays Title: Dr. Jekyll and Mr Hide : virulence factors as new antimicrobials
Philip R. Dormitzer, M.D., Ph.D., Sr. Director, Viral Vaccine Research, Erica Ollmann Saphire, Ph.D., Assistant Professor, Department of Novartis Vaccines and Diagnostics Immunology, The Scripps Research Institute Title: Structure based vaccine design Title: Crystal Structure of the Trimeric, Prefusion Ebola Virus Glycopro- tein in Complex with a Neutralizing Antibody from a Human Survivor 12.00 to 1.00 pm...... Session 2: 2 The Future of Therapeutic Monoclonals Antibodies Sonia Escaich, Ph.D., Vice-President, Chief Scientific Officer, Mutabilis SA Chairman: Shane Crotty, Ph.D., Assistant Professor, Division Title: New antibacterial approaches using new targets of Vaccine Discovery, La Jolla Institute for Allergy and Immunology Ludovic Tailleux, Ph.D., Mycobacterial Genetic Unit, Institut Pasteur Title: Challenges in Tuberculosis Therapies Ava Song, Ph.D., Scientist and Project Leader, Kirin Pharma USA, Inc., Shinichiro Kato, PhD, President and CSO, Kirin Pharma USA, Inc. 5.45 to 6.15 pm...... Closing Session Title: A fully human monoclonal antibody targeting influenza A virus M2 protein: Novel therapeutics for flu 6.15 to 7.00 pm...... Cocktail and Posters sessions TABLE OF CONTENTS p.6 p.80 p.80 p.74 p.62 p.54 Part 3 Part 2 Part 5 Part 1 Part 4 ...... Poster Abstracts Presentations Cluster French Talk Abstracts Contacts Partner Presentations
Bio Partners
Competitiveness
Infectiology
Antimicrobial Part Part 1
Part 1 • Talk Abstracts
6 Part 1 • Talk Abstracts
7 Notes Welcome Talks
Pr. Roger Guillemin
Distinguished Professor, Nobel Prize of Medecine President by interim of The Salk Institute for Biological studies, La Jolla, CA, USA bstracts bstracts
A Roger Guillemin, born in Dijon, France,1924. M.D. Faculty of Medicine, Lyon, 1949, Ph.D., University of Montreal, 1952. Professor of Physiology, Baylor College of Medicine, Houston, Texas 1953-1970. Founding Director, Laboratories for Neuroendocrinology, The Salk Institute, La Jolla CA, 1970-1990, Distinguished Professor, The Salk Institute, current. Numerous degrees honoris causa. National Academy of Sciences, Washington, D.C., Académie des Sciences, Paris, Académie nationale de Médecine, Paris. National Medal of Sciences, USA, 1976. Nobel Prize in Physiology & Medicine, 1977. Officer, Légion d’Honneur, 1984. Since October 1st., 2007,
Part 1 : Talk 1 : Talk Part interim President, The Salk Institute.
8 Notes Welcome Talks
Philippe Larrieu
Consul General of France in Los Angeles, USA
Born on October 27, 1953, Mr. Philippe Larrieu holds a law degree and is a gradutated of the Institut d’Etudes Politiques and the Ecole Nationale d’Administration (the school for future leaders in the French civil service). A career diplomat, Mr. Larrieu joined the French Ministry of Foreign Affairs on June 1, 1980 and served as First Secretary at the French Embassy in Brasilia until 1982. He was then assigned to Djeddah, Saudi Arabia, as Counsellor for Development and Cultural Cooperation. In 1985, he returned to the Ministry’s headquarters and was appointed to the Department for Cooperation, Cultural, Scientific and Technological Relations. From 1987 to 1989, he served at the French Embassy in Singapore as Deputy Head of Mission, prior to becoming Under-Secretary for North Africa at the Ministry of Foreign Affairs. Subsequently, Mr. Larrieu held the position of Counsellor at the French Embassy in Ankara (1992-1993) and at the French Embassy in Warsaw (1994-1998). He was Consul General of France in Algiers from 1998 until 2002 when he was assigned to the Inspection Corps of the Ministry. In September 2004, he took up his current post of Consul General of France in Los Angeles, with jurisdiction over Southern California, Arizona, Colorado, New Mexico and Southern Nevada. A knight in the French National Order of Merit, Mr. Larrieu is married and has two children.
9 Session 1: Key Issues for Vaccine Development – Part I
Dr. Jean-Yves Bonnefoy Vice President, Research and Development Transgene, Strasbourg, Lyon, France
Dr Jean-Yves Bonnefoy, VP, Research and Development was appointed Vice President, Research in February 2005 and Vice President, Research and Development in March 2006 in charge of Research, Clinical Development, Regulatory Affairs and Intellectual Property. Prior to joining Transgene, he was Head of the Canceropôle Lyon Rhônes-Alpes. From 1997 to 2002, he was Director of the Immunology Center of the Pierre Fabre Group in Saint-Julien en Genevois, France. He previously
C hairman was responsible for the Immunology Department of the Biomedical Research Institute of the Glaxo-Wellcome Group in Geneva, Switzerland. Jean-Yves Bonnefoy holds a PhD in immunology from the Lyons Claude Bernard University and has completed the Senior Management Program of the London Business School. bstracts bstracts A KEYNote SPEAKERS
> Humanized mice to understand the Notes pathophysiology of human dendritic cells in vivo Part 1 : Talk 1 : Talk Part
Dr. Jacques Banchereau Director, Baylor Institute for Immunology Research, Dallas, USA Director, INSERM-U899, BIIR/ANRS/INSERM Center for Human Vaccines
Dr. Jacques Banchereau is the director of Baylor Institute for Immunology Research (BIIR) in Dallas and holds the W.W. Caruth, Jr. Chair in Organ Transplantation Immunology. He received his Ph.D. in biochemistry from the University of Paris in 1980 and later served as director of the Schering Plough Laboratory for Immunological Research near Lyon, France, where he was among the first to discover how to grow human dendritic cells. Dr. Banchereau came to Baylor in 1996 to develop the BIIR. He is the director of INSERM Unit 899 at BIIR, entitled “Center for Human Vaccines”. Dr. Banchereau is an Adjunct Professor of Microbiology and a Member of the Cancer Immunobiology Center at The University of Texas Southwestern Medical Center. Dr. Banchereau also holds an Adjunct Professorship in Biomedical Studies at Baylor University Medical Center in Waco, TX. He has published more than 275 papers and 170 book chapters and reviews in major international journals.
10 Notes Presentation abstract
A. Karolina Palucka, Chun Yu, Caroline Aspord, Alexander Pedroza, Mike Gallegos, Florentina Marches & Jacques Banchereau Baylor NIAID Center for Translational Research on Human Immunology and Biodefense, Baylor Institute for Immunology Research, Dallas, TX
The paucity of in vivo models of human disease represents a major drawback in translational research. Results obtained in mice cannot always be directly extrapolated to humans because of differences between the species. These include, among others, CD1 antigen presenting system on dendritic cells (DCs) and differential expression of TLRs by DCs.
We have used humanized mice to study the human DCs in vivo. There, nonobese diabetic/LtSz-scid/scid (NOD/SCID) 2m-/- mice engrafted with human CD34+ hematopoietic progenitors develop all subsets of human DCs, B cells and other cells but T cells need to be adoptively transferred. NOD/ SCID chain-/- mice develop both B and T cells. Thus, we can analyze T cell dependent and independent events.
We have now used humanized mice to study human cancer, infectious diseases and vaccination with ex vivo generated DCs. When applied to cancer this model permitted us to establish a novel pathway through which breast cancer might escape immune surveillance. There, breast cancer instructs DCs to prime IL-13 secreting CD4+ T cells that promote tumor development. When applied to infectious diseases, we developed a model of natural infection with H1 Influenza viruses. We demonstrated induction of Influenza-specific immunity upon vaccination with ex vivo generated DCs. Most particularly, Influenza-specific Igs are generated that are protective and can inhibit Influenza–virus induced hemagglutination. Humice vaccinated with ex vivo generated antigen-loaded DCs mount antigen-specific CD8+T cell immunity including primary responses to HIV derived peptides. Thus, this model will be useful in i) modeling human disease such as cancer and autoimmunity to unravel pathogenic pathways and ii) testing novel vaccines, particularly vaccines based on in vivo targeting of human DCs.
* Supported by U19 AIO57234, RO-1 CA89440, CA78846 and CA85540
Antimicrobial
11 Session 1: Key Issues for Vaccine Development – Part I
Notes > New Adjuvant Approaches
Pr. Greg Lemke Professor & Director Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, la Jolla, CA, USA
Greg Lemke is Professor of Molecular Neurobiology at the Salk Institute. Research in his laboratory is focused on the roles that receptor tyrosine bstracts bstracts kinases play in mammalian development and mature organ function. A Part 1 : Talk 1 : Talk Part
Antimicrobial
12 Notes Presentation abstract
The activation of Toll-like receptors (TLRs) in dendritic cells (DCs) triggers a rapid inflammatory response to pathogens. However, this response must be tightly regulated since unrestrained TLR signaling generates a chronic inflammatory milieu that often leads to autoimmunity. We have found that the TAM receptor tyrosine kinases—Tyro3, Axl, and Mer—broadlyinhibit both TLR and TLR-induced cytokinereceptor cascades. Remarkably, TAM inhibition of inflammation is transduced through an essential stimulator of inflammation—the type I interferon receptor (IFNAR)—and its associated transcription factor STAT1. TLR induction of IFNAR-STAT1 signaling upregulates the TAM system, which in turn usurps the IFNAR-STAT1 cassette to induce the cytokine and TLR suppressors SOCS1 and SOCS3. These results illuminate a self-regulating cycle of inflammation, in which the obligatory, cytokine-dependent activation of TAM signaling hijacks a proinflammatory pathway to provide an intrinsic feedback inhibitor of both TLR- and cytokine-driven immune responses. Inhibitors of the TAMs may therefore function as powerful new adjuvant technolies.
13 Session 1: Key Issues for Vaccine Development – Part I
Notes > Virus-like particles as platforms for vaccine development
Dr. Anette Schneemann Associate Professor The Scripps Research Institute, La Jola, CA, La Jolla
bstracts bstracts Dr. Schneemann received her PhD from the University of Wisconsin, Madison,
A where she studied assembly and morphogenesis of nodaviruses, a family of viruses pathogenic to insects and fish. She pursued postdoctoral work at the University of California-Irvine, investigating transcription and replication of Borna disease virus, a mammalian neurotropic virus. In 1995, Dr. Schneemann joined the faculty of The Scripps Research Insitute. Research in her laboratory focuses on structure-function relationships of non-enveloped, icosahedral viruses, particularly nodaviruses and development of nodaviruses for applications in nanotechnology and biotechnology. Most recently, Dr. Schneemann and collaborators employed virus-like particles of the Part 1 : Talk 1 : Talk Part nodavirus Flock House virus to develop a novel anthrax antitoxin and vaccine. Additional research in the laboratory focuses on RNA silencing and its suppression by nodaviral proteins.
Antimicrobial
14 Notes Presentation abstract
Background: Virus-like particles (VLPs) are attracting increasing attention as platforms for multivalent presentation of foreign antigens. We have used a nodaviral VLP to display a receptor ligand complex that is normally formed during cell entry of anthrax toxins. B. anthracis produces two bipartite toxins composed of the receptor-binding moiety protective antigen (PA) and one of two enzymatic moieties: edema factor (EF) and lethal factor (LF). Binding of PA to a cellular receptor permits entry of EF and LF into the cell. Two receptors have been identified: anthrax toxin receptor/tumor endothelial marker 8 (ANTXR1) and capillary morphogenesis protein 2 (ANTXR2). The portion of ANTXR2 that is involved in binding to PA is represented by a 200 amino acid von Willebrand factor A domain. A soluble form of ANTXR2 was previously shown to function as an efficient receptor decoy for PA.
Methods: We have used the T=3 icosahedral insect virus Flock House virus as a platform to display the PA binding domain of ANTXR2 in a multivalent fashion. Electron cryomicroscopy and image reconstruction of the recombinant particles combined with pseudoatomic modeling provided insights into the surface arrangement of the 180 ANTXR2 domains and their capacity to bind PA.
Results: The chimeric particles functioned as a potent antitoxin in cell-based assays and in vivo experiments. In addition, recombinant particles complexed with PA induced a rapid and strong immune response that protected rats from lethal toxin challenge four weeks after a single immunization in the absence of adjuvant. Monomeric recombinant PA did not confer protection under identical conditions.
Conclusions: These results suggest that the chimeric particles could be useful as a therapeutic compound to treat B. anthracis infection and form the basis for the development of an improved anthrax vaccine.
15 Session 1: Key Issues for Vaccine Development – Part I
Notes > DNA Vaccines : the end of the beginning
Dr. Alain Rolland, Senior Vice President, Product Development, Vical Inc.
bstracts bstracts Alain Rolland is Senior Vice President, Product Development and Corporate
A Officer at Vical. Until 2002, he was Senior VP, Preclinical R&D, and Head of The Woodlands Center at Valentis. From 1993 to 1999 he was Director of Gene Delivery, then Vice President of Research at Ge n e Me d i c i n e . From 1989 to 1993, he was Head, Formulation Research at Galderma International in France. From 1987 to 1988, he was a scientist at the Advanced Drug Delivery Research Center of Ciba Geigy Pharmaceuticals in the UK.
Dr. Rolland received his Pharm.D. (1981) and D.E.A. degree in Pharmacokinetics and Biopharmaceutics (1983) from Rennes University (France). He obtained Part 1 : Talk 1 : Talk Part his Ph.D. in Pharmaceutical Sciences in 1987 from Rennes University after inventing and developing a novel nanotechnology for targeting anticancer drugs to the liver that was evaluated in a Phase 1-2 clinical trial for the treatment of hepatocellular carcinoma. He has published over 70 scientific articles and book chapters, edited three scientific books and he is the recipient of several awards. He is also the Editor-in-Chief of Current Pharmaceutical Biotechnology and an Editorial Board member of the Journal of Controlled Release. He is a member of scientific societies, including the American Controlled Release Society, the American Association of Pharmaceutical Scientists, and the American Society of Gene Therapy. He holds more than 20 patents in the field of advanced drug delivery systems, drug/gene targeting and formulation.
16 Notes Presentation abstract
Over the past few years, plasmid DNA vaccines have reached licensure against infectious hematopoietic necrosis virus in farmed salmon (Canada), West Nile virus in horses (United States) and a canine melanoma DNA vaccine has received conditional approval in the US. A number of approaches are currently evaluated in clinical trials to enhance the potency of DNA vaccines in humans, including formulation of DNA with adjuvants and administration of DNA with devices.
A novel cationic lipid-based adjuvant, Vaxfectin®, has been shown to enhance immune responses in several animal models and the development of DNA vaccines formulated with that adjuvant will be presented. In particular, a pandemic influenza DNA vaccine encoding conserved antigens and formulated with Vaxfectin® is currently being evaluated in two clinical trials and may represent an alternative approach to conventional vaccines. The application of Vaxfectin® as an adjuvant to enhance the immunogenicity and provide a dose-sparing effect of protein-based vaccines will also be discussed.
17 Session 1: Key Issues for Vaccine Development – Part I
Notes bstracts bstracts A Part 1 : Talk 1 : Talk Part
18 Notes
19 Session 1: Key Issues for Vaccine Development – Part II
Notes > Therapeutic vaccination for chronic infection
Dr Marie-Louise MICHEL Institut Pasteur and INSERM, Paris, France
bstracts bstracts Marie Louise Michel is the Head of the Laboratory “Pathogenesis of hepatitis
A B virus” at Institut Pasteur, Paris France. She is Director of Research at INSERM, National Institute for Health and Medical Research. She received her PhD degree in Microbiology from the University of Paris VII (France) in 1985. From 1985-2000 she worked in the laboratory of Pr Pierre Tiollais at Institut Pasteur on hepatitis B vaccine and is co-inventor of a recombinant hepatitis B vaccine produced in CHO cells (GenHevac B, Aventis Pasteur). For her work on the hepatitis B vaccine, she received awards from the National Academy of Medicine (Novartis-Pharma Award in 1997 and Gallet- Breton Award in 2000). Since 1993, ML Michel performed pioneering Part 1 : Talk 1 : Talk Part studies on DNA vaccines for hepatitis B, first in animal models and then during clinical trials. For this work she received the Saul Krugman Award on Viral Hepatitis, in 1996. She moved then to the laboratory directed by Pr C. Bréchot at Necker Hospital to join efforts in designing novel therapeutic vaccines for patients with chronic active hepatitis B.
20 Notes Presentation abstract
Hepatitis B virus (HBV) cause chronic infections worldwide that are associated with development of liver diseases ranking from mild liver inflammation to hepatocellular carcinomas. Despite effective prophylactic vaccines against hepatitis B exist since more than 20 years, more than 2,5 billion people worldwide have been exposed to HBV and around 370 million people are chronically infected with HBV. Currently available therapies fail to allow a complete control of viral replication in most patients. Viral persistence has been associated with a defect in the development of HBV-specific cellular immunity. Thus, novel immune- based therapies are actively being developed to complement or replace standard antiviral treatments. Among those, development of therapeutic vaccines represents a major effort. Peptide-, recombinant protein-, DNA- or viral vector-based vaccines have been engineered and tested at pre- clinical and clinical levels. Means to adjuvant these vaccines are being pursued as well as approaches based on combining vaccines of different nature.
• the key issue for chronic infections remains the fact that a chronic carrier immune system is impaired (eg impairment of CD4 + and CD8+ mediated response, narrow T cell repertoire, presence of regulatory T cells…). Clearly, efficacy of therapeutic vaccines would be enhanced if functionality of T-cells is restored prior to vaccination. • reasons for development of chronic carrier state versus protective immunity are not well known. Studies on the interactions between the virus and the innate immune system are just at the beginning. • Not all patients with chronic hepatitis B will benefit from immunotherapy. Adequate characterization and selection of patients for therapeutic immunization, according to HBV replication and virus-specific T-cell reactivity prior to therapy would be necessary for the efficacy of this strategy. • More information is needed regarding the nature of the HBV antigens to be included in a therapeutic vaccine. In particular it will be necessary to determine which antigens or epitopes are best candidates to stimulate immune response and to avoid functional impairment of the vaccine-induced responses.
Pol S, Michel ML. Therapeutic vaccination in chronic hepatitis B virus carriers. Expert Rev Vaccines. 2006. 5(5):707-16.
21 Session 1: Key Issues for Vaccine Development – Part II
Notes > Profiling the Immune Response to Infections with Genome-Wide Proteome Arrays
Dr. Philip L. Felgner, Professor University of California, Irvine, CA, USA bstracts bstracts A Dr. Felgner received his graduate degrees in Biochemistry & Neurosciences in 1978 from Michigan State University and completed his Post Doctorate training in Biophysics in 1982 from the University of Virginia. His work has emphasized aspects of drug delivery, gene therapy, and high throughput proteomics for serodiagnostic and vaccine antigen discovery. He was Staff Scientist at Syntex Research where he discovered the first cationic lipid reagents (LipofectinTM; Gibco, BRL) for gene transfer. Lipofectin, LipofectAMINE, and many other similar reagents are now in widespread use for molecular biology and gene Part 1 : Talk 1 : Talk Part therapy applications. He made a landmark discovery in 1989 showing that functional reporter gene sequences could be administered directly by injection into skeletal muscle without the use of viral vectors leading to the acceptance of a new class of infectious disease vaccines referred to as “DNA vaccines”. This discovery led to the founding of a San Diego gene therapy business in 1990 called Vical. He has 32 issued United States patents in areas related to synthetic gene transfer vectors, and high throughput proteomics.
22 Notes Presentation abstract
We have developed technology that enables rapid, comprehensive and high- throughput analysis of humoral immune responses to infectious disease antigens that is being used for subunit vaccine antigen discovery and to develop serodiagnostic tests. The method is based on printing microarray chips with proteins encoded by infectious microorganisms which cause medically important diseases in humans. Currently, we have expressed and printed more than 16,000 individual proteins from 8 bacteria, 17 viruses, and 2 parasites. The chips are probed with serum from infected patients and healthy controls to identify the dominant antibody responses, to determine the serodominant antigen profile and to identify a set of 10-20 serodiagnostic antigens for each infectious agent. By using a multiplicity of antigens for each infectious agent, serodiagnostic tests with statistically improved sensitivity and specificity can be configured.
In malaria endemic regions resistance to malaria disease and the ability to control parasitemia develops steadily throughout childhood and into adulthood. Protein microarrays can be used to characterize the differences between susceptible young children and adults that are resistant to disease. A protein microarray containing 2,320 proteins from P. falciparum has been fabricated and probed with 2,000 serum samples from 300 infected Ghanaian children ages 1-5 years. Sera were taken at 2 month intervals from each patient during 1 year. The immune response strengthens during the high transmission period and weakens thereafter, and the immunoreactivity profiles between the youngest and oldest children differ. The subset of serodominant antigens that are associated with protection will be particularly interesting to evaluate as subunit vaccines.
A microarray containing 4,000 M. tuberculosis proteins was fabricated and probed with hundreds of sera from patients with clinical tuberculosis, and a profile of immunoreactive antigens was determined. TB infected subjects react against many antigens and there is no single serodiagnostic antigen that can be used to produce an accurate diagnostic test. However, a multiplex test using 25 serodiagnostic antigens produces a result with high sensitivity and specificity.
This platform is being applied to other targets for vaccine and serodiagnostic antigen discover including, human papilloma, hepatitis, and polio viruses, with future plans to investigate schistosomiasis, trypanosomiasis, Leptospira and leishmania.
23 Session 1: Key Issues for Vaccine Development – Part II
Notes >Structure based vaccine design Dr. Philip R. Dormitzer Sr. Director, Viral Vaccine Research Novartis Vaccines and Diagnostics, Cambridge, MA, USA
Philip Dormitzer, MD, PhD, is Senior Director for Viral Vaccine Research at Novartis Vaccines and Diagnostics. Dr. Dormitzer joined Novartis in 2007 from
bstracts bstracts Harvard Medical School, where he was an Assistant Professor of Pediatrics. At
A Harvard, Dr. Dormitzer led a structural virology research laboratory that focused on the structural basis for rotavirus entry into cells. His educational background includes undergraduate studies in anthropology at Harvard College, MD-PhD training at the Stanford University School of Medicine, housestaff training in internal medicine at Massachusetts General Hospital, and an infectious diseases fellowship at Brigham and Women’s Hospital. Part 1 : Talk 1 : Talk Part
24 Notes Presentation abstract
Vaccine design is progressing from empiricism towards an increasingly rational presentation of the targets of protective immunity. Nevertheless, current vaccine antigens remain essentially the native surface molecules of pathogens. These molecules are adapted to evade, not induce, immunity. High resolution structures reveal the electrostatic surfaces recognized by neutralizing antibodies and the architecture that underlies these surfaces. Structures reveal which parts of an antigen must be left intact and which can be changed to optimize biochemical and immunologic performance. Thus, we can engineer optimized antigens that are more stable, homogeneous, and efficiently produced, making immunization more practical and affordable. Understanding the structural basis for immunogenicity and immunodominance will allow us to improve vaccine efficacy and broaden the range of preventable diseases.
25 Session 1: Key Issues for Vaccine Development – Part II
Notes bstracts bstracts A Part 1 : Talk 1 : Talk Part
26 Notes
27 Session 2: The Future of Therapeutic Monoclonals Antibodies
Dr. Shane Crotty Assistant Professor La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA
Shane Crotty, Ph.D., and his team study immunity against infectious diseases. They investigate how the immune system remembers infections and vaccines. Dr. Crotty’s team has discovered that anti-smallpox B cells—white blood cells responsible for producing antibodies against smallpox virus—remain present and active in the human body for up to 60 years after immunization with the smallpox vaccine. By analyzing the similarities and differences between the smallpox vaccine and less effective vaccines, they want to decipher the secrets of generating lifelong immune memory. Dr. Crotty’s team studies immune memory by C hairman understanding the function of a gene called SH2D1A or SAP. Dr. Crotty has discovered that the SAP gene plays a central role in generation of immune memory. Understanding the role of SAP in greater detail may help XLP patients and may, more broadly, allow for the design of better human vaccines that take advantage of SAP’s important role in the process of generating immune memory. bstracts bstracts A
> A fully human monoclonal antibody Notes targeting influenza A virus M2 protein: Novel therapeutics for flu Part 1 : Talk 1 : Talk Part Dr. Ava Song Ph.D., Scientist and Project Leader, Kirin Pharma USA, Inc.
Education: M.D., Beijing Medical University, Beijing, China ((1993),M.Sc., University of New South Wales, Sydney, NSW, Australia (1996), Ph.D., University of Toronto, Toronto, ON, Canada (2002) Professional Experience: Postdoctoral fellow, La Jolla Institute for Allergy and Immunology, La Jolla, CA (2002-2006), Scientist, Kirin Pharma USA, Inc, La Jolla, CA (2006-present) C. Publications: 1. Song A, Song J, Tang X and Croft M (2007) Cooperation between CD4 and CD8 T cells for anti-tumor activity is enhanced by OX40 signals. Eur. J. Immunol. 37: 1224-1232; 2. Lee SW, Park Y, Song A, Cheroutre H, Kwon BS, Croft M (2006) Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell responses. J. Immunol. 177: 4464-4472; 3. Song A, Tang X, Harms K. M. and Croft M. (2005) OX40 and Bcl-xL Promote the Persistence of CD8 T Cells to Recall Tumor- Associated Antigen. J. Immunol. 175: 3534-3541; 4. Song A, Winer S, Tsui H, Sampson A, Pascari P, Ellis J, Elliott JF, Dosch H-M (2003) Deviation of Islet Autoreactivity to Cryptic Epitopes Protects NOD Mice from Diabetes. Eur. J. Immunol. 33 (2): 546-55; 5. Winer S, Tsui H, Lau A, Song A, Li X, Cheung RK, Sampson A, Afifiyan F, Elford A, Jackowski G, Becker DJ, Santamaria P, Ohashi P, Dosch H-M (2003) Autoimmune islet destruction in spontaneous Type 1 Diabetes is not b cell exclusive. Nature Medicine 9 (2): 198-205
28 Notes Presentation abstract
Influenza is one of the most prevalent viral diseases in humans. For some high-risk human populations, including the infant, the elderly, and the immunocompromised, who may not benefit from active immunization, passive immunotherapy with antibodies reactive with all influenza A strains may be an alternative. In this study, we characterized several fully human monoclonal antibodies (MAb) reactive with M2e, which were generated from transchromosomic mice engineered to produce fully human antibodies following immunization with a consensus-sequence M2e peptide. The MAbs showed strong binding to M2e peptide and to virus infected MDCK cells. One MAb recognizing the highly conserved N-terminal portion of consensus M2e displayed high binding to the majority of M2e variants from natural viral isolates, including highly pathogenic avian strains, which were recently reported to infect humans. Passive immunotherapy with this MAb in mice resulted in significant reduction in virus replication in the lung and protection from lethal infection when administered either prophylactically or therapeutically. These results suggest the potential of the anti-M2e human MAb with broad binding spectrum as a universal passive immunotherapeutic agent to infection by influenza A virus.
This work was performed by Kirin Pharma USA in collaboration with Kirin Pharma and LIAI. This work was sponsored by Kirin Pharma Co., Ltd., Japan.
29 Session 2: The Future of Therapeutic Monoclonals Antibodies
Notes > Immunotoxicity evaluation of monoclonal antibodies: from animal to man
Pr. Jacques Descotes M.D., Pharm.D., Ph.D., Professor, Claude Bernard University and Head, Lyon Poison Center, Lyon, France
bstracts bstracts Dr Descotes is professor of pharmacology at the Laennec school of A medicine, Claude Bernard University, and head of the Poison Center and Pharmacovigilance Department at Lyon University Hospitals, France. He is a fellow of the US Academy of Toxicological Sciences. Over the past 30 years, Dr Descotes has been actively involved in non clinical as well as clinical toxicology. His leading area of expertise is immunotoxicological evaluation. He is the author or editor of 10 books on the immunotoxicity of drugs and chemicals. Part 1 : Talk 1 : Talk Part
30 Notes Presentation abstract
Two issues of major concern can be identified regarding the immunological safety of monoclonal antibodies intended for therapeutic use. One issue is related to potential immunogenicity, and the second to possible adverse consequences of immunopharmacological properties. Despite significant progress in the humanization of monoclonal antibodies, immunogenicity can still result in the production of specific antibodies either neutralizing therapeutic efficacy or causing hypersensitivity reactions. Depending on the immunopharmacological profile, immunosuppression resulting in infectious complications and virus-associated neoplasia, immunoactivation leading to cytokine release syndromes, and an increased incidence of autoimmune diseases as well hypersensitivity reactions to unrelated allergens have been described. Immunogenicity in human beings cannot be reliably predicted in non clinical studies with currently available models and assays. The risk of adverse events related to immunopharmacological effects can be assessed non clinically, but the need for dedicated safety immunopharmacology studies should be emphasized. While current in vitro and animal models can be refined, there is a need for novel assays and animal models to be developed. A major pitfall is the lack of human biomarkers of immunotoxicity applicable to the clinical safety evaluation of monoclonal antibodies. There is an urgent need to design biomarkers useful to assess any of the risks mentioned above. These could be clinical immunology endpoints already in use for other purposes, e.g. diagnosis, or novel biomarkers derived from omics, for instance. In any case, careful qualification and validation will be absolutely essential.
31 Session 2: The Future of Therapeutic Monoclonals Antibodies
Notes bstracts bstracts A Part 1 : Talk 1 : Talk Part
32 Notes
33 Session 3: Towards Humanized Animal Models
Pr. James P. Di Santo Professor of Immunology, Institut Pasteur, Paris, France
After receiving combined M.D./Ph.D. in 1989/1991 from Cornell University Medical College and the Memorial Sloan– Kettering Cancer Center, I completed post-doctoral training with Alain Fischer in Paris, where I characterized several genes responsible for primary human immunodeficiency syndromes. In 1994, I became a permanent staff scientist with the Institut National de la Santé et de la Recherche Médicale (Inserm). Since 1999, I direct a laboratory in the Immunology Department of the Institut
C hairman Pasteur, where my research interests include the role of cytokines in lymphoid development, natural killer cell differentiation and animal models of immunodeficiency. bstracts bstracts A
> Protein-functional-Knock-Out: a new Notes approach in target validation and models of pathology Part 1 : Talk 1 : Talk Part
Dr. Amine M. Abina President & CEO NOKAD, Paris, France
Amine Abina, M.D, PhD, is the President and Chief Executive Officer of NOKAD. He did his medical and research training in different hospitals in Paris, the Gustave Roussy Institute (IGR) in Paris (from 1986 to 1997) and at the Clinical Research Institute of Montréal (Canada) from 1998 to 2000.
Dr ABINA studied different applications in gene therapy using adenovirus vectors, and characterized the importance of the immune response against transgene-encoded proteins and vectors.
He patented in 2001 the vaccination strategy for induction of protein- functional-Knock-Out in mammals. He is the founder of NOKAD in 2004. Dr ABINA held a senior position in the French regulatory authority for health products, where he set up the new regulation for cell and gene therapy products.
34 Presentation abstract Notes
Nokad develops protein inactivation models leading to functional protein- Knock-Out (KO) in different mammalian species (mouse, rats…) within about 6 months. The established method allows the specific induction of cross-reactive immune responses using optimized vaccination strategies and designed mutant proteins. The mutants predicted in silico allow to bypass the natural self tolerance encountered with endogenous proteins. This approach helps to break through some limits inherent to the genetic- KO technology, i.e. mice only, embryonic or neonatal lethality for some gene products, time-consuming process and lack of reversibility of the phenotype.
This technology, applicable for secreted and receptor proteins, accelerates in vivo target validation and functional discoveries by applying it directly to the most relevant animal model or species. In this way it becomes possible to combine differently protein-KO with, genetic-KO, transgenic animals, spontaneous mutant mice, in parallel.
This tool already allows the discovery of a new therapeutic application by combining the different advantages offered by the technology.
35 Session 3: Towards Humanized Animal Models
Notes > Limits & Merits of preclinical pharmacological assessment of immunotherapeutic drugs during development
Dr. Jérôme TIOLLIER EVP Development & Operations Innate Pharma, Marseille, Lyon, France bstracts bstracts A
Jérôme TIOLLIER, PhD, 49 years old, joined the company Innate Pharma as Progam Director on September 2001. He holds the position of EVP Development and Operations in charge of pre-clinical and product development operations. He graduated from C.Bernard University-Lyon as PhD and has a scientific background in cell biology and immunology. He has been previously with IMEDEX SA (1986- 1997) French biotech spin off from Institut Mérieux (now Sanofi Pasteur) at different position. He managed the development of different Part 1 : Talk 1 : Talk Part products from preclinical to early clinical stage (phase I/II) with the collaboration of internal groups and CRO. Then he moves to Pasteur Mérieux IMTIX Transplant business unit (then acquired by US-based SANGSTAT (now part of Genzyme) in 1998) as Preclinical Director (1997-1999) and European R&D Director (1999-2001). In this latter position, he managed different pharmaceutical product license building (Thymoglobuline & Antilfa) as well as new molecule research projects within the Corporate Activity.
36 Presentation abstract Notes
Innate Pharma is a clinical-stage biopharmaceutical company developing first- in-class drug candidates targeting innate immunity, with a primary focus in oncology, infectious diseases and inflammation. Innate Pharma is developing drug candidates on three pharmacological platforms, each targeting a type of innate immunity cell: gamma delta T cells, NK cells and TLR. During these developments, pharmacological and pre-clinical in vivo steps have been a challenge on species relevance. Indeed most of the biopharmaceuticals products based on human epitope or receptor recognition have no counterpart in most animal species except some times non-human primate. When available such relevance should be thoroughly investigated. Three examples will be developed based on different situations: 1) NK cell and anti-KIR mAb development: To explore the feasibility of achieving NK-mediated anti-kir anti-leukemia activity by a pharmacological approach, we generated with our partner Novo Nordisk, fully human anti- KIR mAbs that block the interactions of inhibitory KIR2DL receptors with their HLA-C ligands, thereby enhancing NK activity (therapeutic candidate anti-KIR IgG4mAb, designated 1-7F9). As KIR are not found in mice, in vivo activity was tested in a NOD-SCID mouse model where inoculation of human in vitro-expanded NK cells (80% of NK cells KIR2D-positive) and autologous human B-EBV cells (E:T=1:3) resulted in death of all mice by day 26. A single injection of 1-7F9 (125 µg/mouse) resulted in long-term survival, with 100% of treated mice alive beyond day 60; in contrast, 60 µg/ mouse of the mAb was ineffective. These data show that 1-7F9 augments NK-mediated tumor killing in vivo, and that it exhibits long-lived KIR binding in vivo, providing a preclinical basis for initiating phase 1 clinical trials with the mAb. 2) TLR3 and dsRNA poluApolyU drug development: PIC (polyIpoly C) has been used since in a long time as a “TLR3” agonist in most experimental development. Rodent are relevant for TLR3 pharmacological characterization, however some pharmacological elements show that transduction pathways could be differently activated between rodent and primate with different ds-RNA questioning the relevance of rodent for providing a preclinical basis for initiating phase 1 clinical trials with such compounds. 3) Gamma9 delta2 T cells: human Vgamma9Vdelta2 subset of T lymphocytes has functional equivalent only in primate species. Thus, pre-clinical studies preceding the first administration to patients of IPH 1101 &1201, our lead phosphoantigen designed to modulate gd T cell activity, were all performed in cynomolgus monkeys. In this model, we dissected the features of in vivo activation of gd cells, from early systemic cytokine release to proliferation in response to successive administrations over several months, as well as more fundamental phenotypical and functional changes induced by the treatment. The model allowed us to establish the scheme of administration applied to still ongoing clinical trials (dosing, route and schedule of samplings for pharmacological survey of the patients). It also provided the primary elements of practical and relevant skills for therapeutic potential in pathological situations (infectious diseases, immune disorders…). 37 Session 3: Towards Humanized Animal Models
Notes > Use of genetically modified animal models aiming at increasing the predictability and the throughput of immune response analysis in vivo
Dr. Kader, Thiam Vice President Transgenic Technologies genOway, Lyon, France bstracts bstracts A
Dr. Kader Thiam received a Ph.D. for his work at the department of Cellular Immunology of the Pasteur Institute, Lille. Then he was a fellow at The Pasteur Institute, Lille, Department of Peptide Chemistry. His work was focused on the regulation of the immune response by the use of recombinant viruses or synthetic agonist of cytokine and on the cytoplasm delivery of lipopeptides to modulate pharmacological targets.
Part 1 : Talk 1 : Talk Part Dr Thiam joined genOway in 1999 as Scientific Consultant and Head of the Immunology Department. Today, Dr Thiam served the company as Vice President of Transgenic Technologies, driving the R&D programs aiming at developing new alternatives to overcome transgenesis limitations.
38 Notes Presentation abstract
genOway is dedicated to the development of tailor-made genetically modified rat and mouse models for target validation and drug development programs. genOway has developed a complete range of innovative technological solutions to create a new generation of improved models. genOway’s expertise combines technologies classically used in transgenesis and several cutting-edge proprietary technologies (humanization, RNAi, inducible system) aiming at enhancing the efficiency, security and relevance of the animal model ultimately developed.
Based on these technologies, genOway also develops animal models as ready-to-use tools aiming at increasing the predictability of in vivo analysis and permitting in vivo medium throughput of pre-clinical studies. For the immune system analysis, the use of genOway humanized mouse models enables more relevant physiopathological studies compared to human physiology and increases the relevance of candidate molecules selection.
39 Session 3: Towards Humanized Animal Models
Notes > Novel humanized mouse model for Testing HIV and HCV Vaccine Candidates
Erwan Corcuff Axenis Project Leader, Technical Coordinator of “Human Vaccine Consortium” and Medicen/ Modexa/Biotherapies, Cytokines & Lymphoïd bstracts bstracts Development, Institut Pasteur, Paris, France A
Erwan Corcuff, Project Leader at Pasteur Institut, is in charge of the « Axenis » project since 2007. This project will give rise in 2008 to Axenis, a Start Up dedicated to preclinical trials using humanized mouse models. Erwan Corcuff will be Chief Executive Officer of Axenis.
In 1997, Erwan Corcuff starts his career as a technician, under the direction of Dr Lantz (France) and Dr Matzinger (USA), he collaborates with James Di
Part 1 : Talk 1 : Talk Part Santo on research project using immunodeficient mice. In 1999, he was Ingenior Assistant, responsible for the human in vitro study of: “Multiple sclerosis and Hepatitis B vaccination”, financed by SmithKline and Beecham and the French Government.
In 2000, he finally joins Pasteur Institut, in the unit of James Di Santo. He is responsible of the technical coordination between mice, men and consortiums (Human Vaccine Consortium and Medicen). Erwan Corcuff holds two Master degrees in Science and Technology, and HEC challenge + training (Business School of Paris).
40 Notes Presentation abstract Novel Humanized Mouse Models for Testing HIV and HCV Vaccine Candidates James P. Di Santo & Erwan Corcuff,
Institut Pasteur, Paris France (for the BMGF-sponsored “Human Vaccine Consortium”)
Infection by hepatitis C virus (HCV) is a major health problem. Millions of individuals are affected by HCV worldwide, leading to chronic infections that result in significant morbidity and mortality. Thus far, vaccine development to combat HCV infection has been hampered by the lack of a suitable animal model that allows for efficient screening and prioritizing of vaccine candidates.
The mouse constitutes a well-established and cost-efficient model system to develop vaccines in part due to the similarity between human and murine innate and acquired immune systems. However, mouse hepatocytes cannot be productively infected with HCV, which severely limits the use of mice for HCV vaccine development.
The goal of this project is to develop a mouse model harboring both a human immune system and human liver cells (HIS/HuHEP mice). These mice should be permissive for HCV infection and may develop a virus- specific immune response after HCV infection. This presentation will provide an update on the progress of HIS/HuHEP mouse development that may ultimately allow screening of immunogenicity and efficacy of vaccine candidates against HCV and other important human pathogens.
41 Session 3: Towards Humanized Animal Models
Notes bstracts bstracts A Part 1 : Talk 1 : Talk Part
42 Notes
43 Session 4: New Perspectives for Antimicrobial Treatments
Pr. John A.T. Young Ph.D., Professor and Faculty Chair, The Salk Institute for Biological Studies, La Jolla, CA, USA
John A. T. Young is a Professor in the Infectious Disease Laboratory of the Salk Institute for Biological Studies. Dr. Young previously served on the faculty of several US institutions-UCSF, and Harvard, Medical Schools, and the University of Wisconsin-Madison. The Young laboratory studies mechanisms of retrovirus, influenza, filovirus, and anthrax toxin entry into cells. C hairman bstracts bstracts A KEYNote SPEAKERS
Notes > Dr. Jekyll and Mr Hide : virulence factors as new antimicrobials Part 1 : Talk 1 : Talk Part Dr. Jean-Pierre Gorvel Director of the Centre d’Immunologie de Marseille-Luminy, France Executive Director of the Foundation FINOVI, Innovation in Infectiology, Lyon, France
1982 Award from The Société française de chimie biologique (Dina-Surdin’s prize). 1987 Award from The Fondation pour la recherche médicale (Cell Biology). 1983-1989 Research scientist (CNRS) at the Centre de Biochimie et de Biologie Moléculaire, Marseille. 1992-now Group Leader, Immunology and cell biology of bacteria-host cell interactions. Director of CIML since January 2006.
2002: Member of the Biodefence committee at Aventis Pasteur, Ltd., Toronto, Canada. 2003 President of the Scientific Council of Institutional research grants (Ministry of Research, France), in Microbiology. Member of the NIH evaluation panel (2004-2006) roster N°ZRG1 IDM-A 90. Member of the R&D Expert group on Countering the Effects of Biological and Chemical Terrorism at European Union. Member of the Directorate of Emerging Diseases, Ministry of Health and Ministry of Research, France. Charles-Louis de Saulces de Freycinet Award from the French Academy of Science, 2007. Executive director of the FINOVI foundation sine 2007
44 Notes Presentation abstract
Human brucellosis is a zoonotic disease that results from direct contact with infected animals or ingestion of contaminated food products. It is usually presented as a debilitating febrile illness that can progress into a chronic disease with severe complications such as infection of the heart and bones. It has been previously shown that B. abortus infection in calves using an intestinal loop model occurred via Peyer’s patches. Several studies using animal models have established macrophages and placental trophoblasts as two key targets of Brucella infection but a more recent study has shown that Brucella can replicate in vitro within human monocyte-derived DCs. DCs may therefore constitute an important cellular niche to promote infection and nothing is yet known regarding the consequences of Brucella infection on the immune function of DCs.
Although there is increased knowledge about the virulence factors that enable Brucella to survive inside host cells, it is still unclear how Brucella is able to remain hidden from the immune system and cause chronic disease. The escape from the lysosomal pathway and fusion with the ER may interfere with the ability of host cells to mount an efficient immune response against Brucella. B. abortus replicates within BMDCs and inhibits the process of maturation, ultimately leading to a reduction of cytokine secretion and antigen presentation. We have identified two Brucella proteins, Btp1 and Btp2, which modulate the process of inflammation during late stages of disease in a mouse model of chronic brucellosis. In addition, these Brucella proteins contribute to inhibiting maturation of infected DCs in vitro by targeting different TLR signalling pathways, highlighting a new mechanism to control the immune response of the host. In addition, we discovered that changes in LPS structure and the presence of a new virulence factor called cyclic glucan are also able to modulate the immune response mediated by DCs and might be considered as new tools to fight pathogenic bacteria.
45 Session 4: New Perspectives for Antimicrobial Treatments
Notes > Crystal Structure of the Trimeric, Prefusion Ebola Virus Glycoprotein in Complex with a Neutralizing Antibody from a Human Survivor
Dr. Erica Ollmann Saphire Assistant Professor
bstracts bstracts The Scripps Research Institute,
A La Jolla, CA, USA
2003- Assistant Professor, Dept. of Immunology, TSRI: Structural Analysis of the Host-Pathogen Interface. 2002-2003 Senior Research Associate, Dept. of Immunology, TSRI : Structural analysis of key determinants of Ebola viral pathogenesis. 2000-2001 Research Associate, Dept. of Molecular Biology, TSRI : Structure-based design of HIV-1 vaccines and complement activation by IgG. 1994-2000 Graduate Student, Dept. of Molecular Biology, Part 1 : Talk 1 : Talk Part TSRI: Crystal Structure of an Intact Human IgG:Implications for HIV-1 Vaccine Design & Effector Function.
Awards and Honors: ICAAC Young Investigator Award, American Society for Microbiology (2006), Burroughs Wellcome Career Award in the Biomedical Sciences (2003-2008); Ellison Medical Foundation New Initiatives Award in Global Infectious Disease (2003), Sidhu Award, for the most outstanding contribution to the field of crystallography or diffraction by a person within 5 years of the Ph.D. (2003). Given by the Pittsburgh Diffraction Society. Fellowship, Universitywide AIDS Research Program, state of California, (2001-2003).
46 Notes Presentation abstract
Ebola virus (EBOV) belongs to the filoviridae family and causes severe hemorrhagic fever with 50-90% human mortality. EBOV entry requires the surface glycoprotein, GP, to initiate attachment and fusion of viral and host membranes. Here, we report the crystal structure at 3.4 Å resolution of a trimeric and prefusion conformation of GP (GP1+GP2) in complex with a neutralizing antibody Fab , KZ52, derived from a human survivor of a 1995 outbreak in Kikwit, the Congo. Three GP1 subunits assemble as a trimer to form a chalice-like structure for the receptor binding site, that is cradled in a pedestal comprised of the GP2 fusion subunits, while a novel glycan cap and mucin-like domain restricts access to the receptor-binding site. The glycocalyx surrounding Ebola virus GP points to the strategies of immune evasion that explain why patients that survive have low to insignificant antibody titres. The KZ52 antibody recognizes a protein epitope at the chalice base where it clamps several regions of the prefusion GP2 to the N terminus of GP1, which preclude rearrangements required for fusion. This structure now provides a template for unraveling the mechanism of Ebola virus infection and for future immunotherapeutic development.
47 Session 4: New Perspectives for Antimicrobial Treatments
Notes > New antibacterial approaches using new targets
Dr. Sonia Escaich Vice President and Chief Scientific Officer MUTABILIS SA, Romainville, France bstracts bstracts
A Sonia Escaich, vice President and Chief Scientific Officer, holds a PhD in microbiology and has 16 years of experience in the R&D divisions of pharmaceutical companies. Focusing on the fields of microbiology and molecular biology, she led several drug discovery projects in the antiviral and antibacterial fields. At first, she worked at the Sandoz research centre in Vienna working on HIV gene therapy. Then in Palo Alto CA, she was head of the virology/assays unit in the Sandoz/Systemix Inc. joint venture. She later led research studies for drug discovery in the field of HIV and bacterial virulence and managed different laboratory units in the anti-infective Part 1 : Talk 1 : Talk Part research department at Rhone-Poulenc, then Aventis, France. In 2001 she cofounded Mutabilis to develop new antibacterial therapies.
48 Notes Presentation abstract
MUTABILIS novel approach is called Antivirulence, and is based on the understanding that within microbes’ genes lie the keys to developing entirely new classes of anti-infective agents that selectively cripple pathogenic microbes without killing bacteria which under normal circumstances colonize various human body sites. Pathogenic bacteria, capable of multiplying in extra cellular fluids, have developed specific virulence factors that block the efficacy of the host’s innate immune system.
Using genomic analysis MUTABILIS has identified biological virulence targets which promote bacteria growth in extra cellular fluids, belonging to and conserved through all gram negative bacteria. The same genomics approach was used for a model gram positive bacterium, and several virulence factors common to gram positive were discovered and validated as new targets.
Compounds inhibiting one or several of these virulence factors will prevent the growth, multiplication and dissemination of bacteria through extra cellular fluids, allowing the host’s innate immune system to destroy the invading bacteria, and thereby preventing bacteremia, septicemia and sepsis. The prevention and treatment of severe nosocomial infections will be the medical indications for these new drugs.
49 Session 4: New Perspectives for Antimicrobial Treatments
Notes > Challenges in Tuberculosis Therapies
Dr. Ludovic Tailleux Unité de Génétique Mycobactérienne Institut Pasteur, Paris, France
L. Tailleux, Ph.D., has worked for several years in immunology and in cell
bstracts bstracts biology of mycobacterial infection. He has contributed to the identification
A of DC-SIGN/CD209 as the major M. tuberculosis receptor in human dendritic cells and in alveolar macrophages from patients with tuberculosis.
Re l e v a n t publications - Tailleux L. et al. Probing Host Pathogen Cross-Talk by Transcriptional Profiling of Both Mycobacterium tuberculosis and Infected Human Dendritic Cells and Macrophages. PLoS ONE. 2008 Jan 2;3(1):e1403. - Tailleux L. et al. DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis. PLoS Med.
Part 1 : Talk 1 : Talk Part 2005 Dec;2(12):e381. - Tailleux L. et al. Constrained intracellular survival of Mycobacterium tuberculosis in human dendritic cells. J. Immunol. 2003 Feb 15;170(4):1939-48. - Tailleux L. et al DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J. Exp. Med. 2003 Jan 6;197(1):121-7.
50 Notes Presentation abstract
Despite important efforts to fight tuberculosis (TB), this disease remains a major public health problem. TB is still responsible for 1.7 million deaths annually in the world, and up to one third of the global population is estimated to carry latent Mycobacterium tuberculosis infection. TB incidence varies from 7 per 100,000 in Northern Europe to up to 300 per 100,000 in some parts of Africa. In 2003, the incidence of TB was around 10 per 100,000 in France and 800 deaths due to TB were recorded in 2005. Chemotherapy (combined with DOTS strategy) has clearly helped to decrease the incidence of TB in countries with effective public health systems, but vaccination remains the most cost-effective intervention in most countries. However the BCG vaccine in current use, although effective against severe forms of TB in children, is of minimal and inconsistent efficacy against the much more common pulmonary forms of TB in adults. Multi-drug resistant (MDR) and extensively drug resistant (XDR) TB strains has emerged worldwide as a threat to public health and TB control, raising concerns about a possible future epidemic of virtually untreatable TB. An ineffective vaccine and the alarming appearance of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains underline the need to urgently find novel control measures and therapies.
The development of knowledge-based and adapted interventions strategies, including prognostic tools, new drugs and more effective vaccines, to combat TB would benefit considerably from improvements in our understanding of host - M. tuberculosis interactions.
51 Session 4: New Perspectives for Antimicrobial Treatments
Notes bstracts bstracts A Part 1 : Talk 1 : Talk Part
52 Notes
53 Part Part 2
Part 2 • Poster Abstracts
54 Part 2 • Poster Abstracts
55 Title of the Vaccination without adjuvants : Poster two “proof of concept” studies with murine malaria
Jean-Baptiste Marchand; Contact Head of Immunology; Imaxio SA 181-203 avenue Jean Jaurès 69007 Lyon, France
Tel: +33 (0) 437 655 496 - Fax: +33 (0) 437 650 617 [email protected] - www.imaxio.com bstracts bstracts A
Imaxio’s aXent™ technology increases the immunogenicity of antigens by Abstract of fusing them to a small oligomerisation domain derived from the complement the Poster inhibitor C4bp (C4 binding protein). In proof of concept studies using the murine C4bp oligomerization domain and the MSP1-19 antigen of Plasmodi- um yoelii, mice have been successfully vaccinated against otherwise lethal challenges using either recombinant proteins or by prime-boosting with different viral vectors. Protein engineering techniques have been used to
Part 2 : Poster 2 : Poster Part reduce (to 20% identity) the similarity to mammalian C4bp sequences, while simultaneously improving the “adjuvant-like” effect. The current version is more effective than complete Freund’s adjuvant in mice.
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56 Title of the Computational modeling of the immunologic response to both natural Poster HPV infection and vaccination with Gardasil®
Mr. Gustavo OLIVERA / Chemical Engineer, MSc., Doctoral Candidate. Institute Contact for Theoretical Medicine (IMTh) & Claude Bernard University. IMTh / EZUS Lyon 1 / Laënnec. Rue Guillaume Paradin. 69376 Lyon 08. +33.6.99.30.67.01 +33.4.78.78.57.68 +33.4.78.77.69.17 [email protected] - [email protected] www.gustavoolivera.com - imth.univ-lyon1.fr
Although a major breakthrough, the licensing of HPV vaccines does not Abstract of imply that the end of the battle against HPV is close. Therefore, therapeutic the Poster (prophylactic) innovation is still a need in HPV research. The main purpose of this project is to develop, implement and exploit a com- putational model for screening novel therapeutic (prophylactic) approaches in HPV research. Recurrent Respiratory Papillomatosis (RRP) is a chronic disabling disease for which no therapeutic procedure has been proven efficient in reducing the risk of relapse. A VLP-based therapeutic agent might dampen the reactiva- tion (and the progression) of the disease by inhibiting the reinfection of target cells (hampering this way the completion of the viral life cycle). The quest of the optimal VLP-based therapeutic agent demands the simultane- ous analysis of several variables such as which viral protein(s) (e.g. L1, E2, etc.) to mimic with the VLPs, which adjuvant to use (if any), what comple- mentary drug(s) to use (if any) (e.g. artemisinin, cidofovir, etc.), over what schedule (number of doses, frequency, etc) and through which mode of administration (intramuscular, mucosal, etc.). The computational simulation of these multiple scenarios emerge as a response to: i) the limitations of both in vitro and animal models in the study of RRP, and ii) to the difficulties for conducting clinical trials, mainly due to the lack of standardized clinical registries of the disease. While this work is still in progress, we have already succeeded in developing a completely original simulation platform (based on a multi-agent system), which permits us to recreate in-silico the dynamics of a population of epithe- lial cells. Additionally, we have succeeded in complementing our simulator through the adaptation and implementation of an already-published math- ematical model of the immune system.
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57 Title of the Development of HIV Vaccine Poster
Dr Nicolas Mouz, Chief Scientific Officer Contact Protein’eXpert 7 Parvis Louis Néel – BP 50 Minatec BHT 52B 38040 Grenoble Cedex 9 France Tel: +33 438 023 650 +33 476 961 038 bstracts bstracts [email protected] - www.proteinexpert.com A
Protein’eXpert will present the project aiming at developing a HIV Abstract of vaccine inducing broadly reactive neutralising antibodies. This project the Poster is conducted by scientists with diverse expertise as protein engineering and characterization, formulation for intramuscular and mucosal delivery, evaluation of functional antibody response and efficacy testing in animal models. The first results obtained with the gp41-based antigens will be presented.
Part 2 : Poster 2 : Poster Part Funded in 2000 in Grenoble, France, Protein’eXpert is an expanding Contract Research/Manufacturing Organisation devoted to recombinant protein engineering, development and cGMP manufacturing for biomedical research and clinical applications. We differentiate from other protein CMOs by our integrated way of working from early stage research to phases I & II clinical production of therapeutic proteins and recombinant vaccines. Over the seven past years, the company has demonstrated its capability to tackle highly complex and recalcitrant protein projects and take them to production stages. Protein’eXpert has indeed been working on more than 500 protein related projects, gathering expertise on various target and therapeutic proteins.
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58 Title of the Biotherapic: therapeutic solutions against hepatitis C virus Poster
Dr Jean-Yves Bonnefoy Contact Vice President, Research and Development Transgene SA – France 11 rue de Molsheim F – 67000 Strasbourg +33 388 27 91 50 +33 620 88 50 92 [email protected] - www.transgene.fr
This program is in its second year of realization. It is aiming at structuring a Abstract of network of partners working in the development, production and testing of the Poster novel therapies to fight chronic infectious diseases. Because of its worldwide dramatic impact on human health as well as because of the strong expertise existing in Rhône-Alpes (unique in France and in Europe), the pilot model used by the consortium today is hepatitis C virus (HCV) related infections. Biotherapic currently supports the realization of a phase I/II clinical trial with a prototype therapeutic vaccine, the development of second generation candidate vaccines, the development of novel pre-clinical in vitro and in vivo models for vaccine evaluation, the optimization and development of novel immunological and virological assays for assessment of vaccine or therapy efficacies.
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59 Title of the From infectious mononucléoses to viral persistence and cancer : The structure bases of the interactions between the pro teins of Epstein- Poster Barr virus and the host cell : Diagnosis and therapy
Dr. Tadamasa OOKA Contact Research director of CNRS Molecular virology laboratory, FRE3011, CNRS, Faculté de Médecine Laennec, Université Claude Bernard Lyon-1, Rue G. Paradin, 69372, Lyon Cedex 08 France Tel: 33-0478771078 - Mobile: 06 20 55 79 17 Fax: 33-0478771079
bstracts bstracts [email protected] A
Our objective is to study the interactions between Epstein-Barr virus Abstract of proteins and cellular proteins in latency (LMP-1) and lytic cycle (Zta and Rta) the Poster as well as in nasopharyngeal carcinoma (BARF1 oncogene, discovered by OOKA’s group in 1989). We study the interactions by biophysical techniques on one hand with the ultimate goal of a co-crystallization and structure determination by X-ray crystallography. On the other hand new interactions are identified by immunoprecipitation and mass spectrometry and the role of interaction is studied using cellular models. The network covers groups which are complementary concerning their Part 2 : Poster 2 : Poster Part techniques: biophysics and structural biology (Wim BURMEISTER, EMBL, Grenoble, France), and biological and virological questions of the protein- protein interactions (Tadamasa OOKA and Evelyne MANET, Lyon and Dr. Pierre BUSSON, Paris). Our collaborative study permitted us to demonstrate crystalographical image of BARF1 protein (N. Tarbouriech, F. Guggiero, M. de Turenne-Tessier, T. Ooka and W. P. Burmeister, 2006. J. Mol. Biol . 359(3):667-78) and its post- translational modification (M. de Turenne-Tessier and T. Ooka 2007, J. Gen. Virol ; 88 : 2656-2661) Lyon’s group (Tadamasa OOKA) in collaboration with Algerian group has recently demonstrated the presence of secreted two EBV oncoproteins, BARF1 and LMP1 in serum of Nasopharyngeal carcinoma’s patient (NPC). Moreover purified oncoproteins from NPC patient’s serum had a powerful mitogenic activity in vitro, suggesting their important role in tumor development (Houali et al., 2007, Clin. Cancer Res. 13 :4993-5000). Most of secreted LMP1 molecule was associated with exosome-like vesicle. Taking all together, The inhibition of action of two oncoprotein secreted in serum would become a good tool for therapy of EBV-associated cancers.
This work was supported by ANR-MIME and Lyonbiopole.
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60 Notes
61 AR T 3 P
Part 3 • French Bio Competitiveness Cluster Partners Presentations
62 Part 3 • French Bio Competitiveness Cluster Partners Presentations
• LYONBIOPOLE
• ALSACE BIOVALLEY
• CANCER-BIO-HEALTH CLUSTER
• MEDICEN
• ORPHEME
63 Lyonbiopôle Building a healthcare shield to fight infectious diseases Lyonbiopôle’s strength is its focus on infectious diseases, meeting healthcare and economic challenges, on dynamic markets. The cluster is led by firms with active involvement of all critical stakeholders in Lyonbiopôle’s fields of activity. It receives strong support from the French Government and local authorities. From the very beginning, Lyonbiopôle is designed by its founders as a means to bring together firms and academic researchers. It is drawn as a “factory” to generate multi-partner R&D projects to launch new
LE products more quickly and safely in order to create added value and jobs.
IOPO Lyonbiopôle, a World Center of Excellence in Lyonbiopôle: a booster for an Innovation and
B Diagnostics and vaccines Knowledge based Economy Lyonbiopôle is one of France’s 7 world-class competitiveness Lyonbiopôle has an unique mission: creating economic value clusters since November 2005. Its and developing R&D partnerships by:
YON President is Philippe Archinard, CEO of Transgene, • Helping public research organizations to understand L supported by a ten current members board which includes industry needs in the field of infectious diseases, world’s premier firms such as sanofi pasteur, bioMérieux, • Boosting the quantity and the quality of partnerships, Merial, BD, high potential SMEs (EUSA Pharma formerly OPi, • Improving the international visibility of the pole. Protein’eXpert) and centers of excellence (CEA, Inserm, CNRS and the Mérieux Foundation). The Infectiology Center: a cornerstone of
Part 3 : Part Lyonbiopôle’s action plan Lyonbiopôle aims to manage human and animal infectious Public and private research groups have expressed their diseases in a global approach in order to meet public needs, which include hosting mixed research teams, sharing healthcare needs by : activities and equipment, maintaining dialog and organizing research networks. • Building a “healthcare shield” to fight human and animal In response, the Infectiology Center, located on the Charles infectious diseases and viralinduced Cancers Mérieux Campus, will offer joint organization of R&D activities • Developing innovative diagnostic, preventive and and shared services for the cluster’s partner research teams. therapeutic solutions and delivery systems for more The real estate development program will be carried out in 2 responsive, personalized medicine. steps: • Opening of the Domilyon building in 2008 Lyonbiopôle is built on the distinctive know-how of Lyon and • Extension in 2012/2013 (with a new building) Grenoble in the Rhône-Alpes region, an alliance between industrial biology, structural biology and micro and nano- Charles Mérieux Campus: key figures technology. • 16,000 sq. m. (172,000 sq. ft) of high-level laboratories It promotes a major R&D network of 2500 researchers and facilities, in infectious diseases (half in the private sector, half • 1,000 researchers and related staff in the field of infectious in public research) and 4000 researchers in micro and diseases, nanotechnologies including 300 specialized in healthcare • 50.25 million in overall real estate investment for the years applications. 2007-2013, financed by the French State and local authori- ties, including the Rhône-Alpes Region, the Rhône County Council and Greater Lyon.
64 Lyonbiopôle offered R&D and funding services more HYPERBAR: Development of a new industrial physical pro- precisely: cess for the inactivation of bacteria and viruses in Vaccine • Project support and setup, coordination of public funding production. providers, Participants: Merial, Top Industries, the High Pressure Network • Leadership of an expertise network, (CNRS) and IMVS. • Developing market opportunities for the cluster’s know- how. COLLECTAIR: Development of an air sampling device dedi- cated to bioaerosol analysis for healthcare center. In 2008, development of a new Program of Participants: CIAT, Faure Ingénierie, CEA Leti, CSTB, ELYO Cylergie and International Technological Partnerships ENS Lyon. In December 2007, Lyonbiopole with two other French Bio- clusters, Cancer-Bio-Health (Toulouse) and Alsace BioValley HU’S MAP: Development of technologies for monoclonal (Strasbourg), has set up a strategic alliance, positioning antibody humanization. itself as a mega-cluster called Lifescience Corridor France. Participants: PX’Monoclonals, genOway and Inserm U851. It will aim to support SMBs in their development by setting up technology cooperation with foreign partners. THYMO 2010: Lymphocytes Monoclonals Antibodies. Participants: Genzyme Polyclonals SAS, IBCP, Indicia Biotechnology, February 4, 2008 marked the signature in Osaka (Japan) Novotec, Texcell and the French of the first international partnership agreement between Blood Agency. the Lifescience Corridor France and the Kansai Biomedical *The Rhône-Alpes Region, Greater Lyon, Grenoble Alpes Métro and the Cluster to carry out international collaborative projects. county Councils of Rhône, Isère and Ain. The purpose of this partnership is to build the foundations for future collaborative projects involving business parks, Funding and accredited R&D projects research laboratories, pharmaceutical and biotechnology Since 2005, 38 R&D projects accredited by Lyonbiopôle, companies, and for the organisation of joint missions and representing a total investment of €128 M, obtained €40 M seminars or exchanges of experience between bio-clusters. in funding from the State, local authorities (Rhône-Alpes Region, Greater Lyon, Grenoble Alpes Metropole, Grenoble For the next months, Lyonbiopôle will carry on its develop- and Isère Country Councils), Oséo and the European ment to Canada, Quebec in May and United States, San Diego Community. and Boston in June.
Projects selected by the Single Inter-Ministry Fund, local authorities* and Oséo un 2007: ALPHA VAC: New therapeutic approach for the treatment of hepatitis C virus infection. Participants: Flamel Technologies, Transgene, Inserm U823, Lyon Civil Hospitals (HCL), Grenoble, University Hospital, the Geneva Canton Hospital and Lausanne CHUV.
CARBINFEC: Identification and development of oligosaccha- rides molecules, from biomass, inhibiting virus attachment CONTACT LYONBIOPOLE and stopping their entry into target cells. Isabelle Scarabin Barbelet Immeuble Domilyon, Participants: Elicityl, Kalys, Cermav-CNRS, UMR CNRS/CEA/UJF and Development & International Director 321 avenue Jean-Jaurès the Lyon Human Virology Laboratory Inserm U758. [email protected] F – 69007 Lyon Mob: + 33 (0)6 32 57 92 87
65 Alsace BioValley Therapeutic innovations to develop and bring to market new therapeutic innovations through a unique synergy of three fields of excellence: chemical sciences, biology and medical technology. y
Facing the challenges of tomorrow’s healthcare Part of BioValley, a leading tri-national industrial cluster in life sciences Thanks to the Alsace BioValley cluster all the Alsatian players
valle in the medical field from both the private and public sectors The Alsatian healthcare and biotech industry is the only one are united around shared objectives: innovating to face in France which fully integrates a tri-national geographical io the major challenges that healthcare will have to address reality, as the BioValley network brings together companies over the next 30 years and speeding up the economic established in France, Switzerland and Germany. This
e e b development process of this technological field of activity. biocluster includes over 300 companies and 40,000 jobs
c This cluster is based, not only on the excellence of Alsace directly involved in the domains of biotechnologies and
a in all the scientific domains on which tomorrow’s medicine healthcare (including pharmaceuticals giants as Novartis s and drug sciences will be based (life sciences, chemical and Roche), as well as over 200 interface companies sciences, information and communication sciences, involved in sectors such as precision mechanics, al robotics), but also on a strong tradition of interactions engineering, optics or electronics, which are also concerned between all these disciplines. by the Alsace BioValley cluster.
Such multidisciplinary and scientific excellence are elements The Alsace BioValley cluster federates about 200 of the conferring Alsace the competitiveness necessary to become 500 companies of this sector set in Alsace, representing
Part Part 3 : a cluster of international rank in the field of «Therapeutic more than 14, 000 employees; its 49 research laboratories Innovations». involve 2, 200 researchers in public research organizations.
Because medicine in the 21st century will result from The integration of Alsatian businesses in this tri-national the cross-fertilization between medical technologies and biocluster facilitates collaborative work between these biotechnologies, the Alsatian cluster spans two main companies and allows the development of transborder domains: activities with major players of the pharmaceutical industry • Bio Pharmaceuticals: from chemistry and genes toward – such as Novartis, which has a presence on both sides of new drugs the French and Swiss border. • Medical Technologies: Medical and surgical devices, This tri-national synergy also translates into direct benefits imaging and robotics in terms of creating employment and foreign investments in Alsace.
66 An outstanding service and business Environment A personal Business Liaison Officer to support you throughout the process: Speed up development thanks to a world class services offer throughout the value chain To make it as simple as possible for you, you will be assigned a personal Business Liaison Officer to support The major characteristic of this cluster is its ability to you throughout our process and to provide answers to any provide all the components of the value chain in close questions that might arise. proximity; from initial research to product development, each component is able to provide service complying with the highest international standards. This includes: world-class public and private research laboratories; multi-disciplinary research programs and approaches; scientific platforms providing state-of-the- art scientific services to industry and academics alike (including chemical libraries, screening an target production, phenotyping and animal imaging, preclinical drug technology and clinical trials). facilities for preclinical and CONTACT clinical studies; a dynamic network of innovation-oriented companies. Alsace BioValley Tel: + 33 (0)3 90 40 30 00 And also... [email protected] www.alsace-biovalley.com • One of Europe’s most competitive set of financial www.innovations-therapeutiques.fr Incentives • A Comprehensive Property solutions (several science parks in Strasbourg, Colmar and Mulhouse dedicated to life sciences) • A qualified knowledge work force due to the leading universities in Alsace (Université Louis Pasteur, member of the League of European Research Universities, LERU, an association bringing together 12 of the most prestigious European universities)
67 CANCER-BIO-HEALT CLUSTER
Joining the fight © Pic du Midi ER In 2000, 5.3 million men and 4.7 million women throughout the world developed cancer and 6.2 million ST people died from this disease. According to the World Cancer
LU Report, the incidence of cancer could increase by 50% over the next 20 years, resulting in 20 million new cases per year in 2020 and 10 million deaths. To overcome this major T C T threat to public heath, the French President launched a major Cancer Plan in 2003 which led to the creation of a network of
EAL interregional cancer research centers. The Midi-Pyrénées Region benefits from all the resources In the context of French government initiatives to create necessary to treat cancer (fundamental research, techno- logical research, clinical research and industry).
IO-H competitiveness clusters, the Cancer-Bio-Health Cluster was
B formally approved on July 12, 2005. The principal mission of
- the Cancer-Bio-Health Cluster to improve management of the This continuity between fundamental science and practical continuum of cancer care by adopting an unique and wide- application will contribute to improving cancer prevention,
ER ranging approach: and the diagnosis, treatment and rehabilitation of patients. NC A Part 3 : C : 3 Part
68 © Corbis A strategic regional convergence of stakeholders
The area covered by the cluster includes major cities such as Toulouse, Albi, Castres, Mazamet and Limoges. The Toulouse- Langlade Cancéropôle, a 220 ha campus, will be dedicated to the fight against cancer, combining and integrating both research institutions and industry:
• A comprehensive cancer research consortium: at the University Cancer Hospital, priority shall be given to research and innovation in the fight against cancer by grouping patient care, fundamental research, technology transfer and innovation on the same site. This dynamic is supported by highly federative structures • A public research institute which aims to become a leading such as Midi Pyrénées expansion, Limousin expansion and international authority on cancer research, Ariège expansion (the economic Development agencies), • The ITAV, a multidisciplinary life sciences research institute, Midi-Biotech and the SISMIP (two regional Biotech and and a business incubator dedicated to life science start- Pharmaceutical industries associations), incubators such ups, as Prologue Biotech, Incubateur Midi Pyrénées and CAP • Major pharma companies such as Laboratoires Pierre Delta as well as the Communities of towns such as SICOVAL, Fabre, sanofi-aventis ,GlaxoSmithKline. la Communauté d’agglomération du Grand Toulouse and la communauté d’agglomération de Castres-Mazamet.
Top-level research
Midi-Pyrénées is one of the leading regions in Europe for Research and Development. Two thousand people are involved in R&D in the public sector and 1,650 in the private sector. They work for three public sector scientific and technical institutions (CNRS, INSERM and INRA), four Universities (Toulouse I, II and III, plus the INPT), several advanced specialized schools (INSA, Ecole des Mines d’Albi-Carmaux, ENVT, ESAP, ESCT etc.), science complexes (EFS, CRT-CRITT Bio-industries, Génopole, IPBS, IMRCP, RMN etc.), the University Teaching Hospitals of Toulouse and Limoges, and the Claudius Regaud Institute CONTACT etc... Jean Pierre Saintouil Chief Executive Officer CANCER BIO HEALTH CLUSTER A dense industrial network Immeuble Le Caffarelli 9 place Alfonse Jourdain 31000 Toulouse France Midi-Pyrénées encourages innovative and start-up Tel: + 33 (0)5 34 25 50 43 - Fax: + 33 (0)5 34 25 50 41 companies, particularly in the sectors of health (130 [email protected] companies, 9,000 jobs), biotechnology (63 companies including 36 start-ups), pharmaceuticals (8,000 jobs), health foods (30 companies, 1,100 jobs) and information technology (2,100 companies, 14,000 jobs).
69 MEDICEN PARIS REGION Innovative therapies and advanced technologies in healthcare Medicen Paris Region is a cluster which unites all key life science and healthcare players in the Paris metropolitan area. Located at the heart of Europe’s leading regional economy, the cluster brings together the highest concentration of healthcare expertise and resources in Europe. It also leverages the assets to be found in of the world’s leading metropolises
N including financial infrastructure, real estate and transportation networks. E
3 Strategic Pillars DIC With strong support from the State, the Paris Region (Ile-de- © Paris Tourist Office / Stephane Querbes France) Regional Council, local authorities and economic ME development organizations, Medicen Paris Region is committed to reinforcing the international competitiveness, visibility and attractiveness of the Paris region in life sciences and make it one of the world’s major metropolitan areas for therapeutic innovation. Part 3 : Part Medicen Paris Region‘s ambition is based on three strategic pillars: • Excellence in university education and research (including clinical research) • Attractive synergy between public and private players • Financing for life science innovation and entrepreneurial businesses. There are also public and private-sector research Medicen Paris Region’s top priority is to bring up the region’s organizations (Inserm-the National Institute for Health and competitiveness and international attractiveness, in terms of Medical Research, CNRS-the National Center for Scientific high-level therapeutic innovations, to best-in-class level. We Research, CEA-the Atomic Energy Commission, the Pasteur, seek to create high added-value jobs in life sciences. Curie and Gustave Roussy Institutes, INRIA-the National Institute for Research in Computer Science and Control), Europe’s leading hospital network (AP-HP) and the region’s Key Stakeholders universities (P.R.E.S. Paris Sud, Paris V René Descartes, To achieve its objectives, Medicen Paris Region relies on a Paris VI Pierre & Marie Curie, Paris VII Denis Diderot, Paris synergy between the cluster’s various stakeholders. Sud XI Orsay, Paris XII Val-de-Marne, Paris XIII Nord, Cergy- Pontoise, Versailles) and “Grandes (Écoles”École Normale Active members include major pharmaceutical and Supérieure-Cachan as well as École Centrale de Paris, École healthcare companies (Sanofi-Aventis, Servier, Ipsen, Glaxo- Polytechnique, ENSCP, ENSMP, ESPCI and HEC). SmithKline, the LFB, Pierre Fabre, Siemens Medical Solutions France, Guerbet, Philips France et GE Healthcare) and biotech These stakeholders are developing close partnerships and & medtech entrepreneurs. active collaborations around innovative projects, company start-ups and business creation.
70 6 Areas of Excellence © P. Stroppa / CEA Medicen Paris Region has a strategy focusing on six scientific and therapeutic fields in which the region’s players are recognized as world-level leaders:
• nervous system diseases, • oncology, • infectious diseases, • molecular & cell therapies, • biomedical imaging, SME’s at the core of Medicen Paris Region • drug design science & technology Most of the Paris region’s 150 biotech companies are located on technology parks or business incubators that are cluster Interaction between these therapeutic and technological members: Agoranov, Biocitech, Genopole®, Incuballiance, areas of excellence constitutes the very essence of the Paris Biopark, PARIS BIOTECH SANTE, Pasteur BioTop. cluster and is a key driver for innovation. From September 2005 to November 2007, 57 biotech companies were part of the 23 collaborative R&D projects Collaborative R&D Projects accredited by Medicen Paris Region: AbCell, AgileBio, Medicen Paris Region accredits and supports collaborative Amcor Flexibles, Anaconda Pharma, Apcis, Ariana Pharma, R&D projects, allowing a large number of companies and Armines, ATL, Axinoe, Biocortech, Biojectis, Biométhodes, institutions to be granted public funding. Biospace Lab, Cellectis, Celogos, CIRA, Cytomic Systems, Dosisoft, Drugabilis, EchoSens, Eucodis, Fluigent, Fovea From September 2005 to November 2007, Medicen Paris Pharma, Genewave, Genomic Vision, GenoSafe, Hutchinson Region accredited 23 collaborative R&D projects of which Santé, Hybrigenics, Imagine Eyes, Immuno-Designed 19 received public funding through the Fund for Corporate Molecules, Imstar, Kenium, Mauna Kea Technologies, Effectiveness (FCE), from the Ministry of Economy, Finance Medasys, MEDIT, Mutabilis, Myosix, New Phenix, Noveron, and Industry, Oseo Innovation, and local community Novexel, Obetherapy, Oncodesign, Oroxcell, PartnerChip, administrations. Total subsidies amounted to €42,3 million. Sepal Pharma, Seppic, Serial Genetics, ShigaMediX, Sibio, sponsored by Medicen Paris Region members during the Steris, SuperSonic Imagine, Techniz, TexCell, Theraclion, TIGA period 2005-2007. Technologies, VigiCell.
In addition, the National Research Agency (ANR) allocated a total of €42 million to 80 projects sponsored by Medicen Paris Region members during the period 2005-2007.
Cohesion-promoting projects CONTACT Medicen Paris Region also supports the development of Jean Pierre Saintouil several cohesion-promoting projects aimed at facilitating the MEDICEN PARIS REGION development of new R&D activities in the Paris Region, at the Isabelle BOYER DE LA GIRODAY-Agnès de SIMONE best world level, consistent with the cluster’s focus areas. 6 rue Alexandre Cabanel, F - 75015 Paris Tel: + 33 (0)1 44 49 30 00 - Fax: + 33 (0)1 44 49 30 05 Eurocord and the Institut de la Vision are two such projects [email protected] - www.medicen.org accredited by Medicen.
71 ORPHEME
The Competitiveness Cluster ORPHEME concerns Orphan Diseases and Emerging Pathologies. This cluster joins 2 Regional Councils : Languedoc Roussillon and Provence Alpes Côte d’Azur and gathers consequently the Health players along the French Mediterranean border.
EME ORPHEME concerns Orphan Diseases and Emerging Pathologies The Orphan Drug Status is given in order to promote PH Research, Development and Marketing of new drugs for rare R diseases. The main criteria for the European Union (1999), so as to get this status, is a disease affecting less than 5 patients for 10.000 people ORPHEME includes 5 cities along the Neglected Diseases such as Malaria, Trypanosomiasis,... are Mediterranean sea: also included. Montpellier, Nîmes, Marseille Toulon and Nice Part 3 : O Part The objectives of ORPHEME are: Emerging Pathologies • to develop the health business in the south of France A pathology could be emerging for different reasons: through innovative projects done in partnership • evolution of science, • and in particular to facilitate the establishement of young • appareance of a disease on a specific territory innovative companies, (international travels, ...) • to help small companies in their development. • increase of incidence such as: ageing, obesity,...
ORPHEME has 4 themes: Companies • Diagnosis & treatment of infectious and tropical diseases • Big groups: Allergan, Arkopharma, Bausch & Lomb, Beck- • Medical equipment & Bio-ingeniery man Coulter, Bio-Rad, Galderma, Genévrier, Horiba ABX, • Treatment & Care of ageing, neurological diseases and PCAS, sanofi-aventis, Virbac, etc… handicap • Small companies and start ups: Bio Veto Test, Cezanne, Cis- • Diagnosis & Immunotherapy of rare and emerging cancers Bio International, IDM, Idenix, Innate Pharma, Intrasense, Ipsogen, Ivagen, Proteus, Phylogene, Neureva, Nicox, Pharmaxon, Skuld-Tech, Trophos, Tx Cell, …
More than 160 companies with 10.000 direct jobs in Health, 3000 of them are in R & D.
72 Breakdown of staff in companies involved > 5 by National Agency for Research in Health (LR / PACA) • “NK Tolerance” • “Microstroke” • “DimHer” • “PrP Depletion” • “Assist”
> 2 by Oseo • “Vaccine against Bilharziosis” • “Syncontraints” synthesis of proteins Education Universities of Montpellier, Nîmes, Marseille, Aix-en-Provence and Nice. “Ecole des Mines” Alès, ESIL, EGIM, “Ecole de Chimie” Montpellier…
39 000 students graduated every year including 14 000 PhD in life sciences. Montpellier launched the first university of Medicine of the occidental world in 1220 A.C.
CONTACT Projects Jacquie Berthe - President Since its launch in March 06, ORPHEME got a financing for Tel: + 33 (0)4 99 77 64 65 12 projects. [email protected] Alain Yvorra - General Director The total amount is 31 M€ and 15 M€ of financing Tel: +33 (0)4 91 13 74 67 [email protected] > 5 from the Competitiveness Fund of Entreprise • “NivaChick” Nivaquin in Chickungunya • “VaxiLeish” Vaccine against Leishmaniosis • “Cell Arthrix” treatment of Juvenile Rheumatoid Arthritis with autologus cells • “Neurocom” Cochlear Implant • “Newsolife” bone ingeniery
73 Part Part 4
Part 4 • Partner Presentations
74 Part 4 • Partner Presentations
75 The Office for Science and Technology of the Embassy of France
Contact : Office for Science and Technology The Office for Science and technology of the Embassy of The Embassy of France in the United States of America France is a multidisciplinary team of 35 faculty members, 4101 Reservoir Road, NW senior researchers and staff scientists under the leadership of Washington, DC 20007 a science counselor who reports directly to the Ambassador. Tel: (202) 944 6249 The Office is distributed between headquarters at the French Fax: (202) 944 6219 Embassy in Washington, DC, and 5 satellites offices in the www.ambafrance-us.org - www.france-science.org Boston (MA), Chicago (IL), Houston (TX), San Francisco (CA) and Los Angeles (CA) consulates. Mireille Guyader, Ph.D Attaché for Science & Technology The role of the Office incorporates three strategic missions: Tel: (310) 235-3248 • To monitor advances in science and technology to attache-sdv.mst@consulfrance- stakeholders, decision makers and scientists. losangeles.org • To establish and/or strengthen partnerships in science and technology. • To promote exchanges of students, researchers and Mireille Guyader joined the Office for Science and Tech- entrepreneurs. nology at the French Embassy in December 2006, as Scientific Attache in Life Sciences domain. Her office is Every year, the Office for Science and Technology based at the French consulate in Los Angeles. She was develops programs in the following areas: life sciences, research scientist at INSERM (National Institute for Health
Part Part 4 : Partner Presentations nanotechnologies, agronomy, environment, information and Medical Research) for 18 years and has been working technology, innovation and entrepreneurship. The Office on molecular biology of retroviruses, molecular imaging organizes major bilateral events such as an innovation day and vaccine approaches to HIV. She has been developing (FAID) and several events dedicated to science as a basis of research projects at Pasteur Institute in Paris, Columbia mutual understanding. University in New York, Centre Medical Universitaire in Geneva, and more recently at the Center for Immunology The action of the Office for Science and Technology is strongly of Marseille-Luminy. In 2003, she was a visiting scientist coordinated with other diplomatic offices, such as the Trade at the Scripps Research Institute in La Jolla. She owns a Department or the Cultural Services. This situation allows PhD in Biochemistry from the University of Paris VII. the Office of Science and Technology to efficiently handle the many economic and social implications of today’s science and technology.
76 The Salk Institute for Biological Studies
Dr. Jonas Salk, developer of the polio vaccine, established the Salk Institute for Biological Studies more than 40 years ago. His goal was to create an institute that would serve as a «crucible for creativity» to pursue questions about the basic principles of life. Today, the Salk Institute conducts its biological research under the guidance of 59 faculty investigators. It employs a scientific staff of more than 850, including visiting scientists, postdoctoral fellows, and graduate students. Recruited throughout the world, this group receives advice from nine distinguished nonresident fellows—influential scientists at similar institutions throughout the world.
The major areas of study are: Molecular Biology and Genetics; Neurosciences; and Plant Biology. Knowledge acquired in Salk laboratories provides new understanding and potential new therapies and treatments for a range of diseases—from cancer, AIDS and Alzheimer’s disease, to cardiovascular disorders, anomalies of the brain and birth defects. Studies in plant biology at the Salk may one day help improve the quality and quantity of the world’s food supply.
The Salk Institute consistently ranks among the leading research institutions in the world for its faculty’s contributions and the impact of their findings. The Institute has trained more than 2,000 scientists, many of whom have gone on to positions of leadership in other prominent research centers worldwide. Five scientists trained at the Institute have won Nobel prizes, and three current resident faculty members are Nobel Laureates.
Contact : The Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla, CA 92037 Tel: 858.453.4100 www.salk.edu
77 French BIO Beach
Stéphane B. Richard, Ph.D., French BIO Beach was created in 2006 by Stephane B Richard, Staff scientist, Salk Institute for Biological PhD, Staff Scientist at the Salk Institute for Biological Studies Studies (La Jolla) and owner of GEN2X LLC, as a combined effort with the Founder, Gen2X LLC, and Founder, French Bio Economic Department of the French Embassy. Beach
Since its creation, French BIO Beach as organized a number of Dr Richard graduated from the University Joseph Fourier networking events with scientific content and French-American (Grenoble, France). He then joined the team of Prof. Joseph P. social warmth, in order to gather together the local French- Noel in the Structural Biology Laboratory of the Salk Institute American BIO community at large, and establish itself as a valid to study the biosynthesis of terpenoid natural products. Now local partner for any French delegation related to business in life part of the Jack Skirball Chemical Biology and Proteomics sciences in search for a local network in the San Diego area. Center of the Salk Institute, Dr Richard is now interested in the chemo-enzymatic derivatization of natural products So far, French BIO Beach had the opportunity to work with the to develop novel therapeutically relevant compounds. Dr Economic Department of the French Embassy, the French Office Richard is also the founder Gen2X LLC (www.gen2x.com), a of Sciences and Technology, the French General Direction of San Diego based contract research organization specializing Enterprises (DGE), the Invest in France Agency (AFI), the Young in structural biology. Pursuant to the signature of an agree- Entrepreneur Initiative (YEi), the San Diego French-American ment with the French Ministry of the Economy, Finance and Chamber of Commerce, and Lyon Bio pole, among others. Industry, Dr Richard created French BIO Beach (http://www. frenchBIOBeach.com), in collaboration with the Economy A complete list of our previous events with press kits and videos Part Part 4 : Partner Presentations Department of the French Embassy in San Francisco, in order are available on our web site at www.frenchbiobeach.com to foster academic and business partnerships between San Diego’s entrepreneurial spirit and France’s expertise in life Contact : sciences. French BIO Beach Stéphane B. Richard, PhD P.O. Box 910483, San Diego, CA 92121-0483, USA Mobile : 1(858) 342.6807 Tel: 1(858) 342.6807 Fax: 1(336) 868.7241 [email protected] - www.frenchbiobeach.com
78 The General Directorate for Enterprises
• Produce industrial statistics and economic analyses on French industry, • Roll out technological and economic prospective The General Directorate for Enterprises, known in France as analysis. DGE, is part of the French Ministry of the Economy, Finance and Employment. Its role is to prepare and implement Within this framework, the competitiveness clusters French policy, to enhance business competitiveness, stimu- foster links between academia and industrial research, late innovation, and develop the information society within a between SMEs and large companies. Biotechnology and European and international framework. health occupy an important place with 8 clusters, 3 of DGE’s Missions them being already global clusters with a strong inter- national visibility. The DGE supervises the installation of • to improve the competitive edge of French companies in an these 8 clusters and accompanies them in their develop- international environment, ment especially by supporting their R&D programs. The • to promote and implement an environment that fosters financial support covers all partners involved in the R&D enterprises and employment as well as France’s attractive- projects whatever their size and/or origin. ness, • to promote entrepreneurship and creativity and to support innovation and industrial research Contacts: General Directorate for Enterprises DGE’s Spheres of Action David SENET – health and biotechnology department • Support industrial R&D cooperative projects via the Fund Le Bervil – 12, rue Villiot – 75572 Paris cedex 12 for Enterprises Competitiveness (FCE), Tel: 00 33 1 53 44 92 59 • Provide support to industrial R&D via the National Agency Fax: 00 33 1 53 44 91 73 for Research (ANR) and to innovative SMEs projects via [email protected] Oséo-Innovation, www.industrie.gouv.fr - www.competitivite.gouv.fr • Promote and enforce European and national laws and regulations,
79 Part Part 5
Part 5 • Contacts
80 Part 5 • Contacts
81 ORGANISATION AND INFORMATION CHAIRMANS
Isabelle Scarabin Barbelet Dr. Jean-Yves Bonnefoy Development & International Director Vice President, Research and Development LYONBIOPOLE Transgene SA – France Immeuble Domilyon, 321 avenue Jean-Jaurès 11 rue de Molsheim F – 69007 Lyon F – 67000 Strasbourg Mob: + 33 (0)6 32 57 92 87 Mobile: +33 (0)6 20 88 50 92 - Tel: +33 (0)3 88 27 91 50 [email protected] -www.lyonbiopole.com [email protected] - www.transgene.fr
Mireille Guyader, Ph.D Dr. Shane Crotty Attaché for Science & Technology Assistant Professor Office for Science and Technology La Jolla Institute for Allergy and Immunology The Embassy of France in the United States of America 9420 Athena Circle 4101 Reservoir Road, NW La Jolla, CA 92037-1387 Washington, DC 20007 Tel: (858) 353 2139 Tel: (310) 235-3248 - Tel: (202) 944 6249 [email protected] - www.liai.org Part Part 5 : Contacts [email protected] Fax: (202) 944 6219 Pr. James P. Di Santo www.ambafrance-us.org - www.france-science.org Professor of Immunology Institut Pasteur WELCOME ADDRESS Department of Immunology 25 rue du Docteur Roux, F - 75724 Paris cedex15 Tel: + 33 (0)1 45 68 86 96 Pr. Roger Guillemin [email protected] - www.pasteur.fr Distinguished Professor, Nobel Prize of Medecine President by interim of The Salk Institute for Biological studies Pr. John A.T. Young The Salk Institute for Biological Studies Ph.D., Professor and Faculty Chair 10010 North Torrey Pines Road The Salk Institute for Biological Studies La Jolla, CA 92037 10010 North Torrey Pines Road Tel: (858).453.4100 - www.salk.edu La Jolla, CA 92037 Tel: 858.366.3181 Philippe Larrieu [email protected] - www.salk.edu Consul General of France in Los Angeles Embassy of France in the United States of America 4101 Reservoir Road, NW Washington, DC 20007 Tel: (202) 944 6249 - Fax: (202) 944 6219 www.ambafrance-us.org - www.france-science.org
82 KEYNOTE SPEAKERS SPEAKERS
Dr. Jacques Banchereau Dr. Amine M. Abina Director, Baylor Institute for Immunology Research, Dallas, USA President & CEO Director, INSERM-U899, BIIR/ANRS/INSERM Center for Human NOKAD Vaccines 4 rue Pierre Fontaine The Baylor Institute for Immunology Research F - 91000 Evry 3434 Live Oak Tel : +33(1) 60 87 89 86 Dallas, TX 75204 [email protected] - www.nokad-technology.com Tel: 214.820.7450 - Mob: 469.877.7416 [email protected] Erwan Corcuff www.baylorhealth.com - www.inserm.fr Axenis Project Leader, Technical Coordinator of «Human Vaccine Consortium» and Medicen/Modexa/Biotherapies Dr. Jean-Pierre Gorvel Institut Pasteur Director of the Centre d’Immunologie de Marseille-Luminy Unité des cytokines et développement lymphoïde Executive Director of the Foundation FINOVI, Innovation in Unité INSERM U668, Physiopathologie du système Infectiology immunitaire Centre d’Immunologie de Marseille-Luminy 25 Rue du Dr ROUX - F - 75724 Paris cedex15 Parc scientifique de Luminy Tel laboratory: + 33 (0)1 45 68 86 13 Case 906, F - 13288 Marseille cedex 9 Tel incubator: + 33 (0)1 44 38 95 11 - Mob: + 33 (0)6 81 33 49 03 Tel: +33491269418 [email protected] - www.pasteur.fr [email protected] - www.ciml.univ-mrs.fr FINOVI Pr. Jacques Descotes Christelle Bidaud, General Secretary M.D., Pharm.D., Ph.D., 50 avenue Tony Garnier Professor, Claude Bernard University and Head, F - 69007 Lyon Lyon Poison Center Tel: +33 (04) 37 28 76 41 Poison Center and Pharmacovigilance Department [email protected] - www.finovi.eu Lyon University Hospitals, 162 avenue Lacassagne - F - 69424 Lyon cedex 03 Tel: +33 (0)4 72 11 94 10 [email protected] www.centres-antipoison.net/lyon - www.chu-lyon.fr
Dr. Philip R. Dormitzer Sr. Director, Viral Vaccine Research Novartis Vaccines and Diagnostics 500 Technology Square, Rm. 918-10 Cambridge, MA 02139 Tel: 617-230-2459 [email protected] - www.novartisvaccines.com
Dr. Sonia Escaich Vice President and Chief Scientific Officer Mutabilis SA 102 RAv Gaston Roussel - F - 93230 Romainville France Tel: + 33 (0)1 57 14 05 21 - Mob: +33 (0)6 18 63 38 90 [email protected] - www.mutabilis.fr
83 Dr. Philip L. Felgner, Dr. Anette Schneemann Professor Associate Professor University of California at Irvine The Scripps Research Institute 3052 Hewitt Hall Department of Molecular Biology, CB262 Irvine, CA 92067 10550 N. Torrey Pines Rd - La Jolla, CA 92037 Tel: (949) 824 1407 - Mob: 858 735 6259 Tel: (858)-784-8643 [email protected] - www.uci.edu [email protected] - www.scripps.edu
Pr. Greg Lemke Dr. Ava Song Professor & Director Ph.D., Scientist and Project Leader Molecular Neurobiology Laboratory, Kirin Pharma USA, Inc. The Salk Institute for Biological Studies 9420 Athena Circle, La Jolla, CA 92037 10010 North Torrey Pines Road - La Jolla, CA 92037 Tel: (858)-952-7035 Tel: (858).453.4100 [email protected] - www.kirinpharma.co.jp/english [email protected] -- www.salk.edu Dr. Ludovic Tailleux Dr Marie-Louise MICHEL Unité de Génétique Mycobactérienne Part Part 5 : Contacts Institut Pasteur and INSERM Institut Pasteur Laboratory of Pathogenesis of hepatitis B virus 25-28, rue du Dr. Roux Department of Virology F - 75724 Paris Cedex 15 Institut Pasteur, 28 rue du Dr. Roux, F - 75724 Paris cedex15 Tel: +33 (0)1 45 68 88 77 - Mob: +33 (0)6 10 58 88 78 Tel: + 33 (0)1 45 68 88 49 [email protected] - www.pasteur.fr [email protected] www.pasteur.fr - www.inserm.fr Dr. Kader, Thiam Vice President Transgenic Technologies Dr. Alain Rolland, genOway Senior Vice President, Product Development 181 ave Jean Jaurès Vical Inc. F - 69 362 Lyon cedex 07 10390 Pacific center court - San Diego, CA 92121-4340 Tel: +33 (0) 4 37 65 41 00 Tel: (858)-775-9805 [email protected] - www.genoway.com [email protected] - www.vical.com Dr. Jérôme TIOLLIER Dr. Erica Ollmann Saphire EVP Development & Operations Assistant Professor Innate Pharma The Scripps Research Institute Dept. of Immunology 121 Ancien Chemin de cassis 10550 North Torrey Pines Rd, IMM-2 - La Jolla, CA 92037 F – 13008 Marseille Tel: (858)784-8602 Mob: + 33 (0)6 16 72 17 95 [email protected] - www.scripps.edu [email protected] - www.innate-pharma.fr
84 FRENCH BIO COMPETITIVENESS CLUSTERS PARTNERS
Lyonbiopôle, Building a healthcare shield to fight infectious Office for Science and Technology diseases The Embassy of France in the United States of America www.lyonbiopole.com 4101 Reservoir Road, NW Yves Laurent, General Director Washington, DC 20007 Bernard Mandrand, Scientific Director Mireille Guyader, Ph.D Isabelle Scarabin Barbelet, Development & International Director Attaché for Science & Technology Immeuble Domilyon, 321 avenue Jean-Jaurès Tel: (310) 235-3248 - Tel: (202) 944 6249 F – 69007 Lyon [email protected] Mob: + 33 (0)6 32 57 92 87 Fax: (202) 944 6219 [email protected] www.ambafrance-us.org - www.france-science.org
Alsace Biovalley, Facing the challenges of tomorrow’s healthcare French BIO Beach www.alsace-biovalley.com - www.innovations-therapeutiques.fr Stéphane B. Richard, PhD, Staff scientist, Salk Institute for Nicolas Carboni, General Manager Biological Studies 9, Bd Gonthier d’Andernach Founder, Gen2X LLC, and Founder, French Bio Beach F - 67400 Illkirch P.O. Box 910483, San Diego, CA 92121-0483, USA Tel: + 33 (0)3 90 40 30 00 - [email protected] Mobile : 1(858) 342.6807 Tel: 1(858) 342.6807 - Fax: 1(336) 868.7241 Cancer-Bio-health Cluster, A unique and broad approach [email protected] - www.frenchbiobeach.com throughout the continuum of Cancer www.cancerbiosante.com The Salk Institute for Biological Studies Jean Pierre Saintouil, Chief Executive Officer 10010 North Torrey Pines Road Immeuble Le Caffarelli, 9 place Alfonse Jourdain, La Jolla, CA 92037 F-31000 Toulouse Tel: (858).453.4100 Tel: + 33 (0)6 87 61 83 12 - [email protected] www.salk.edu
Medicen Paris Region, A cluster for innovative therapies and The French Ministry of Economy, Finance and Employment advanced technologies in healthcare General Directorate for Enterprises (DGE) www.medicen.org David SENET – health and biotechnology department Isabelle Boyer de la Giroday - Agnès de Simone 12 rue Villiot, F-75012 Paris, 6 rue Alexandre Cabanel, F-75015 Paris Tel: + 33 (0)1 53 44 92 59 Tel: + 33 (0)1 44 49 30 00 - Fax: + 33 (0)1 44 49 30 05 [email protected] [email protected] www.industrie.gouv.fr – www.competitivite.gouv.fr
Orpheme, Emerging Pathologies and Orphan Diseases 2 rue Henri Barbusse, F-13001 Marseille www.orpheme.org Jacquie Berthe - President Tel: + 33 (0)4 99 77 64 65 - [email protected] Alain Yvorra - General Director Tel: +33 (0)4 91 13 74 67 - [email protected]
85 Thanks to:
The French Ministry of the Economy, Finance and Employment, especially Luc Rousseau, Alain Griot and David Senet from the General Directorate for enterprises (DGE) and the French Ministry of Foreign Affairs, especially Michel Israël, for their support and funding
Lyonbiopôle,French world-class Bio Cluster, especially Isabelle Scarabin Barbelet and Valérie Four, appointed by the General Directorate for enterprises (DGE) and the Office for Science and Technology of the Embassy of France in Los Angeles, to coordinate this event
The Office for Science and Technology of theE mbassy of France in Los Angeles, especially Mireille Guyader and Camille Arnaud, for their support and their involvement for the organization of the seminar
The Salk Institute for Biological Studies, especially John A. T. Young and Greg Lemke, for their support and advices to organize the symposium and for hosting the symposium
French BIO Beach, especially Stéphane Richard, for his organization and mobilization of the French BIO Beach network
Pr. Roger Guillemin, Distinguished Professor, Nobel Prize of Medecine and President by interim of The Salk Institute for Biological studies and Philippe Larrieu, Consul General of France in Los Angeles to welcome the attendees of the symposium
The chairmans : Dr. Jean-Yves Bonnefoy, Vice President, Research and Development, Transgene • Dr. Shane Crotty, Assistant Professor, La Jolla Institute for Allergy and Immunology • Pr. James P. Di Santo, Professor of Immunology, Institut Pasteur • Pr. John A.T. Young, Ph.D., Professor and Faculty Chair, The Salk Institute for Biological Studies
The keynote speakers: Dr. Jacques Banchereau, Director, Baylor Institute for Immunology Research, Director, INSERM-U899, BIIR/ANRS/INSERM Center for Human Vaccines • Dr. Jean-Pierre Gorvel, Director of the Centre d’Immunologie de Marseille-Luminy, Executive Director of the Foundation FINOVI, Innovation in Infectiology in Lyon
The speakers : Dr. Amine M. Abina, President & CEO, NOKAD • Erwan Corcuff, Axenis Project Leader, Technical Coordinator of «Human Vaccine Consortium» and Medicen/Modexa/Biotherapies, Cytokines & Lymphoïd Development, Institut Pasteur • Pr. Jacques Descotes, M.D., Pharm.D., Ph.D., Professor, Claude Bernard University and Head, Lyon Poison Center • Dr. Philip R. Dormitzer, Sr. Director, Viral Vaccine Research, Novartis Vaccines and Diagnostics • Dr. Sonia Escaich, Vice President and Chief Scientific Officer, Mutabilis sa • Dr. Philip L. Felgner, Professor, University of California at Irvine • Pr. Greg Lemke, Professor & Director, Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies • Dr Marie-Louise MICHEL, Institut Pasteur and Inserm • Dr. Alain Rolland, Senior Vice President, Product Development, Vical Inc. • Dr. Erica Ollmann Saphire, Assistant Professor, The Scripps Research Institute • Dr. Anette Schneemann, Associate Professor, The Scripps Research Institute • Dr. Ava Song, Ph.D., Scientist and Project Leader, Kirin Pharma USA, Inc. • Dr. Ludovic Tailleux, Unité de Génétique Mycobactérienne, Institut Pasteur • Dr. Kader Thiam, Vice President Transgenic Technologies, genOway • Dr. Jérôme TIOLLIER, EVP Development & Operations, Innate Pharma
The 4 others French Bio Competitiveness Clusters involved in the symposium : Alsace Biovalley, Cancer- Bio-Health Cluster, Medicen Paris Region and Orpheme
The others following actors : the French Economic Mission in San Francisco and AFII, the Invest in France Agency in San Francisco 86 SPONSORS
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87 CONTACTS [email protected] Mob: +33 (0)632 57 92 87 F –69007 Lyon Immeuble Domilyon, 321 avenue Jean-Jaurès LYONBIOPOLE Development &International Director Isabelle Scarabin Barbelet
Mireille Guyader, Ph.D [email protected] Tel: (310) 235-3248 Los Angeles, 90025 CA 10390 Santa Monica Blvd, Suite 410 French Consulate and Science of The Office Technology Attaché for Science &Technology
© Photothèque Sanofi Pasteur - Photothèque Inserm M.Depardieu