Advanced Biotechnology Industry and Research in the Czech Republic:



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Advanced Biotechnology Industry and Research in the Czech Republic: Peter Šebo Institute of Biotechnology Academy of Sciences of the Czech Republic Prague 1

Great past: Used to be extremely strong in tradional biotechnology: Crop and animal breeding fermentation industry Famous Brewery tradition Wine, ethanol, baker`s yeats production Fodder yeast (Biocel Paskov) Biotransformations: Aminoacid production, cyclosporin A, ergot alcaloids Vitamines, food additives etc. Among pioneers of antibiotics production (penicilin) World famous school of continous culture technology (at Institute of Microbiology of the Academy of Sciences) 2

modest present: somewhat behind in cutting edge biological research advanced biotech research is limited advanced biotech intellectual property limiting Small size of advanced biotech industry 6real biotech companies: Lonza, Baxter, Contipro, Exbio, BioVendor, Immunotech Low numbers of high tech biotech SME thus far 3

Selected biotech companies Prague Immunotech (Beckman Coulter) immunodiagnostics Ascoprot Biotech SME (5 p.) rec. proteins BIOPREPARÁTY biological plant protection GeneAge Technologies expression profiling Genomac International sequencing/genotyping LentiKat waste water treatment R&D Top Bio molecular biol. kits producer SME (<5)

Sel. biotech companies Central Bohemia Apronex SME, recombinant proteins (4 p) Baxter Czech flu vaccine production site Biologicals SME, forensics, HCV Y Screen EXBIO SME, Mab and reagent producer Lonza Biotec fermentation plant and R&D FDA registered pharma enzymes Proteix SME, recombinant proteins (3 p) recoli SME, recombinant proteins VIDIA SME, clinical diagnostic kits BioTest drug and biologicals testing

Sel. biotech companies South Moravia BioVendor SME, recombinant proteins, diagnostics Bioveta veterinary vaccines R&D and production Enantis SME, recombinant dehalogenases contract research in protein engineering EPS SME, bioremediation, biogas Moravian Biotechnology SME, custom antibody services TEST LINE SME, human and veterinary diagnostics

Sel. biotech companies remaining regions GENERI BIOTECH SME, oligonucleotides, DNA genotyping services Contipro Group world leader in hyaluronic acid GMP recombinant defensins, wound healing R&D B.P.Medical SME, bioactivity testing ENVISAN GEM bioremediation GEN TREND SME, diagnostics and proteins AgroBio agrochemicals and agrobiologicals Biocel pulp industry fodder yeast producer IVAX Teva Pharmaceuticals, generics OlChemIm SME, phytohormones, antibodies (5 p)

Promising future: Government recognizes the problem Advanced biotechnology and molecular biology among strategic longterm research orientations funding schemes Good culture, education, enough PhDs, qualified manpower National applied research support schemes (NPV ) Incentives for Academia collaborations with Industry 4. 5 bil. Euro from ERDF funds for OP R&D for Innovation and Enterprise for Innovation a fair portion of it going to biotech Institute of Biotechnology AS CR, v.v.i. founded on January 1, 2008 BIOCEV, CEITEC, BioMedReg and several other major projects in preparation 8

University students vs. life science students: geographical distribution

Academy of Sciences Basic Facts and Mission of the ASCR Leading basic research institution of CR Funded from state budget mainly ~6400 employees, >50% university graduates and PhDs Not a University Network of 60 institutes All transformed to Public Research Institutes by January 1, 2007 http://www.cas.cz/en 10

Flemingovo nám. 2 Prague 6, CZ-16637 Czech Republic Phone: +420 220 183 111 Fax: +420 224 310 955 E-mail: img@img.cas.cz http://www.img.cas.cz New Institute's building to completed in 2007

INSTITUTE OF MOLECULAR GENETICS AS CR Molecular & Cell Biology Molecular & Applied Immunology Recombinant proteins Monoclonal antibodies Cellular vaccines Monoclonal antibodies Molecular Genetics Unique mouse strains Developmental Biology Virology Unique chicken inbreds

Institute of Experimental Medicine (IEM) Prof. Eva Sykova, D.Sc. phone: +420 296 442 230 fax: +420 296 442 782 sykova@biomed.cas.cz http://uemweb.biomed.cas.cz

Stem cell research at IEM iron nanoparticles for in vivo NMR imaging of stem cells Biodegradable hydrogels for stem cell ingrowth into hydrogel implants in spinal cord lesion reparation Growth of olfactory glial ensheathing cells Establishing and characterizing human embryonic stem cells (Dr. P. Dvorak in Brno among the world`s leaders) sykova@biomed.cas.cz http://uemweb.biomed.cas.cz

Institute of Physiology Neurophysiology & Centre of Cardiovascular Research Videnska 1083, 142 20 Prague 4-Krc, Czech Republic Phone: +420 2 9644 1111 Fax: +420 2 4106 2488 E-mail: fgu@biomed.cas.cz http://www.biomed.cas.cz/fgu/en/index.php - Bioartificial vascular tissue prostheses - Regionally-selective cell adhesion on micropatterned surface - Bone tissue engineering on nanostructured materials

Innovation of clinically used vascular prostheses: coating with extracellular matrix (ECM) molecules and endothelialization Inner surface On the inner surface, laminin or fibrin were immobilized Endothelial cells grow and differentiate fgu@biomed.cas.cz

Institute of Microbiology Videnska 1083 CZ-142 20 Prague 4 Czech Republic phone: +420 296 442 341 fax: +420 296 442 201 e-mail: mbu@biomed.cas.cz http://www.biomed.cas.cz/mbu/en/

Institute of Microbiology microalgae cultivation biotechnology Biotechnological pilot plant Targeted polymeric drugs Biotransformation of glycans Antigen delivery tools for immunotherapy and diagnostics http://www.biomed.cas.cz/mbu/en/

Current status of antigen delivery technology 1997 - Protective immunity against a virus (LCMV) 1999 - Immunotherapy of transplanted tumors in mice 2004 - Enhanced detection of latent tuberculosis 2005 - Protective immunity against Plasmodium (mouse malaria model) 2005 - immunotherapy of experimental tumors (such as HPV16 induced) (US Patent No. 5,503,829, No. 5,679,784, No. 5,935,580, EU Patent application No. 03291486.3, US Prov 03495, 6094 (2003) ) preclinical data in vivo toxicological studies Phase I&II clinical trial in preparation for: melanoma (EU FP consortium THERAVAC) HPV16-induced cervical carcinoma (BT Pharm,a S.A. Toulouse France) http://l125lsx.mbu.cas.cz/lab125/ sebo@biomed.cas.cz

INSTITUTE OF EXPERIMENTAL BOTANY Cytokinins as cell-division-inhibiting substances for cancer treatment Sorted chromosomes for plant genomics Edible vaccines in plants Institute of Experimental Botany Rozvojová 135 165 00 Prague 6 - Lysolaje Czech Republic Phone: +420 220 390 453 Fax: +420 220 390 456 E-mail: machackova@ueb.cas.cz www.ueb.cas.cz

Inhibitors of cyclin-dependent kinases (CDK) R-Roscovitine - (Seliciclib) R phase II of clinical trials for cancer CDK2 / roscovitine co-crystal -Multiple myeloma -B-cell Chronic Lymphocytic Leukemia - Mantle Cell Lymphoma. Phase II clinical trial for Non-Small Cell Lung Cancer treatment M. Strnad et.al. http://rustreg.upol.cz/

Institute of Biotechnology Founded by Academy of Sciences January 1, 2008 22

IBT seeding groups 2007 2010 2008: IBT M. Kubista Single cell expression profiling J. Neužil Molecular and recombinant therapeutics J. Pěknicová Diagnostics for reproductive medicine R. Sedláček Transgenic Animals Š. Růžičková Diagnostics of autoimmune diseases P. Šebo Recombinant binding proteins (ligands) syructural bioinformatics 2009: G. Pavlinkova gene expression regulation in diabetic embryopathy C. Barinka structural biology 20010 / 2011 Evaluation/new recruitements 2012 Recruitement of new groupleaders 2013 New BIOCEV center opens 23

Promoting Czech biotech Catalyzed establishement of a Czech biotech company cluster CzechBio national association of advanced biotech industry Initiating a project of a Czech Biomanufacturing Centre (National center for GMP manufacturing of biological drugs for early stage clinical testing)

Establishing a CzechBio cluster AppGenics s.r.o. Central Europian Biosystem s.r.o. Jihomoravské inovační centrum BVT Technologies, a.s. Apronex s.r.o. Contipro CPN Group, a.s. LentiKat s a.s. BTÚ Ascoprot Biotech, s.r.o. Dyntec s.r.o. Lonza Biotec, s.r.o. Zentiva a.s. B.P.Medical spol. s.r.o. Enantis s.r.o. Protean s.r.o. Klastr NATURPOL Baxter Czech spol. s r.o. ENVISAN GEM, a. s. Proteix s.r.o. MERCI Biocel Paskov a.s. Exbio Praha a.s. SEVAPHARMA a.s. BIO SKIN, a.s. Biologicals s.r.o GEN TREND s.r.o. TATAA molecular diagnostics Bionext Energy Europe s.r.o. GENERI BIOTECH s.r.o. Technologický park Hořátev BIOPHARM VÚ biofarmacie a veterinárních léčiv a.s. Genomac International, s.r.o. TEST LINE, Clinical Diagnostics, spol. s r.o. IVAX Pharmaceuticals s.r.o. GeneAge Technologies, a.s. ADW BIO, a.s. Biotest s.r.o. GENZYME EUROPE BV, organizační složka Top Bio, s.r.o. Biocel paskov a.s. BioVendor Laboratorní medicína a.s. IMMUNOTECH, a.s. VIDIA spol. s r.o. VUAB a.s. Bioveta, a.s. 25

Establishing a CzechBio cluster About 60 companies targeted, 3 AS CR institutes, ICT Prague All major players responded On December 18th 2008 founded 20 members, more joining Specifying tasks and objectives Analysing case studies of successful clusters Appling for spport to OP EI Mingling session program for 2009 26

Biotech & Biomed Research Center of Academy of Sciences and Charles University Vestec at Prague Regional development and competitiveness through promotion of cutting-edge biotechnology and biomedical R&D in Czech Republic Shortlisted for funding from European Regional Development Fund Operational Program R&D for Innovation 2007-2013

Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy On December 20. 2007 the prime minister of CR assisted the signature of BIOCEV z.s.p.o. consortium agreement IBT AV ČR CU IEM IMIC IMG biocev-office@img.cas.cz

Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy Academy of Sciences of CR Public research institutes: Charles University: Institute of Biotechnology (established on 1.1.2008) Přírodovědecká fakulta Institute of Physiology Institute of Microbiology 1. Lékařská fakulta Institute of Experimental Medicine Institute of Macromolecular chemistry Institute of Molecular Genetics Joint International Graduate School of molecular and cellular biotechnology biocev-office@img.cas.cz

OPERATIONAL PROGRAM RESEARCH AND DEVELOPMENT FOR INNOVATION PRIORITY AXIS 1:EUROPEAN CENTERS OF EXCELLENCE LOCATION: REGION OF CENTRAL BOHEMIA VESTEC TO BEBUILT 2010 2012 BUDGET : 114 MIL. WITHOUT START UP GRANT 131 MIL. WITH START UP GRANT Roadmap of BIOCEV March 2006 Department of Biotechnology of the Institute of Molecular Genetics AS CR formed to lead the preparatory work of the BIOCEV project August 2007 5,5 ha of constructible land purchased by the Academy of Sciences for construction of BIOCEV in the industrial zone at Vestec December 2007 Consortium agreement of BIOCEV z.s.p.o. signed in the presence of the prime minister of the Czech Republic January 2008 February 2008 March 2009 Institute of Biotechnology established by the Academy of Sciences on January 1, 2008 as a new public research institution legal entity, to serve for nucleation center of BIOCEV BIOCEV z.s.p.o. registered as a legal entity, Board leads project preparation BIOCEV project officially submitted for evaluation to the Ministry of Education, Youth and Sport of the Czech Republic October 2010 Start of BIOCEV infrastructure construction November 2010 October 2012 January 2013 Basic parameters of BIOCEV recruiting and international call for applications for BIOCEV groupleader positions under auspices of the International scientific advisory board of BIOCEV Heavy equipment technologies installation at the new BIOCEV campus, research groups moving into new BIOCEV buildings BIOCEV full operation

Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy Phase I 50 employees 2007-2011 at Prague-Krc - Lb Bldg. Phase II 2012 new BIOCEV Bldg. at Vestci near Prague AS CR purchased 55 000 m 2 of constructible land 400 450 employees and postdocs 30 45 research groups + 150 visiting researchers, students = 600 people biocev-office@img.cas.cz

Why at Vestec? BIOCEV Czech advanced Biotech research and industry hub Biotech park

A possible look of BIOCEV

Activities of BIOCEV v.v.i. National Biotech&Biomed Research Infrastructure MOUSE CLINIC INFRAFRONTIER National mammalian model phenotyping, genome mining & archiving infrastructure STRUCTURAL BIOLOGY INSTRUCT National Structural Biology Infrastructure & OMICS Infrastructure GRADUATE EDUCATION International School of advanced studies in biotechnology and biomedicine BASIC RESEARCH Molecular Genetics & Cell Biology & Immunology & Tumor Biology & Eukaryotic Microbiology Protein and Cell & Biomaterials and Tissue Engineering & Methods development ORIENTED RESEARCH Protection of Intellectual property Technology transfer & Business development IMAGING National Biological Imaging Core facility CELL CULTURE National Protein Expression and Purification facility & Cryotechnologies & Biobanking facility

Aim: integration into European Research Area European strategic research infrastructures ESFRI INFRAFRONTIERS Czech Mouse Clinic - Center of knock-in/knock-out mouse phenotyping ESFRI EuroBioImaging Optical and electron imaging Open-access equipments of BIOCEV Cutting-edge mass spectrometry for top-down protein modification analysis (FT-MS ion cyclotron 15T) Animal transgenesis unit mammalian cell culture facility Recombinant protein purification facility IT and data storage Biobank? and cryo repository? biocev-office@img.cas.cz

Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy Czech Center for Phenogenomics Man and mouse share 95% of highly similar genes 30 000 knock-out mouse strains in preparation - gene after gene What does which gene do Mouse clinic examinations: - pathologies - imunology resistance to infection - clinical biochemistry - metabolism - cardiology - neurology - behaviour - growth defects - perception vision, hearing, smell - genome expression biocev-office@img.cas.cz

Planing for transgenic animal disease models biocev-office@img.cas.cz

Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy Protein and cell engineering Targeted biological - protein drugs against cancer, pain, arthritis, osteoporosis biocev-office@img.cas.cz

Engineering tissue prostheses Artifical bones from cells grown on porous scaffolds Vascular prostheses colonized by endothelial cells biocev-office@img.cas.cz

Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy Biomaterials for tissue engineering biocev-office@img.cas.cz

Biology of tumor cells Tumor cell penetrating bone marrow Breast carcinoma cell How to defeat them biocev-office@img.cas.cz

Contact: sebo@biomed.cas.cz Peter Sebo, PhD. Institute of Biotechnology AS CR, v.v.i. Academy of Sciences of the Czech Republic Videnska 1083 142 20 Prague 4 Czech Republic GSM: (+420) 774 798 121 office: (+420) 241 062 762 http://www.ibt.cas.cz