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Advanced Czech Biotech: Great past Sad present Promising future Peter Šebo Institute of Biotechnology Academy of Sciences of the Czech Republic Prague.

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Presentation on theme: "Advanced Czech Biotech: Great past Sad present Promising future Peter Šebo Institute of Biotechnology Academy of Sciences of the Czech Republic Prague."— Presentation transcript:

1 Advanced Czech Biotech: Great past Sad present Promising future Peter Šebo Institute of Biotechnology Academy of Sciences of the Czech Republic Prague

2 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

3 Sad present: Lagging behind in cutting-edge biological research Lagging behind in cutting-edge biological research Limited and noncompetitive advanced biotech research Limited and noncompetitive advanced biotech research Almost inextisting advanced biotech intellectual property Almost inextisting advanced biotech intellectual property Absence and poor interest of venture capital Absence and poor interest of venture capital Minimal size of advanced biotech industry Minimal size of advanced biotech industry 4 real companies: Lonza, Baxter, Contipro, Exbio Extremely limited R&D in advanced biotech Extremely limited R&D in advanced biotech Low numbers of high-tech biotech SME Low numbers of high-tech biotech SME 3

4 Czech advanced biotech – overall description 43 biotech companies* Most companies located in Prague and Brno metropolitan areas Directly employed ** : people Combined yearly turnover**: 4-5 bil CZK ( mil Euro) Average yearly growth rate**: 12-16% * - traditional biotech and foreign trade representations excluded **- estimation based on a incomplete dataset source of data: Czech Biotech Report 2008, Ernst&Young presentation at G2B conference 2006, company data in public domain

5 * - traditional biotech and foreign trade representations excluded **- estimation based on a incomplete dataset source of data: Czech Biotech Report 2008, Ernst&Young presentation at G2B conference 2006, company data in public domain No of biotech companies* 43 Directly employed** Combined yearly turnover** 4-5 bil CZK ( mil Euro) Average yearly growth rate** 12-16% Czech advanced biotech – overall description

6 Biotech companies – geographical distribution

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

8 Sel. biotech companies – Central Bohemia SME, transgenic rabbits, hEPO recombinant proteins AppGenics SME, transgenic rabbits, hEPO recombinant proteins SME, recombinant proteins(4 p) Apronex SME, recombinant proteins (4 p) flu vaccine production site Baxter Czech flu vaccine production site SME, forensics, HCV-Y-Screen Biologicals SME, forensics, HCV-Y-Screen SME, Mab and reagent producer EXBIO SME, Mab and reagent producer fermentation plant and R&D Lonza Biotec fermentation plant and R&D FDA-registered pharma enzymes FDA-registered pharma enzymes SME, recombinant proteins (3 p) Proteix SME, recombinant proteins (3 p) SME,recombinant proteins rEcoli SME, recombinant proteins SME, clinical diagnostic kits VIDIA SME, clinical diagnostic kits SME, transgenic rabbits, hEPO recombinant proteins AppGenics SME, transgenic rabbits, hEPO recombinant proteins SME, recombinant proteins(4 p) Apronex SME, recombinant proteins (4 p) flu vaccine production site Baxter Czech flu vaccine production site SME, forensics, HCV-Y-Screen Biologicals SME, forensics, HCV-Y-Screen SME, Mab and reagent producer EXBIO SME, Mab and reagent producer fermentation plant and R&D Lonza Biotec fermentation plant and R&D FDA-registered pharma enzymes FDA-registered pharma enzymes SME, recombinant proteins (3 p) Proteix SME, recombinant proteins (3 p) SME,recombinant proteins rEcoli SME, recombinant proteins SME, clinical diagnostic kits VIDIA SME, clinical diagnostic kits

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

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

11 Promising future: Government recognizes the problem Government recognizes the problem Advanced biotechnology and molecular biology among strategic longterm research orientations - funding schemes More funds than competent individuals and teams available… Good culture, education, enough PhDs, qualified manpower Good culture, education, enough PhDs, qualified manpower National applied research support schemes (NPV ) National applied research support schemes (NPV ) Incentives for Academia collaborations with Industry Incentives for Academia collaborations with Industry ERDF funds for OP R&D for Innovation and Enterprise for Innovation / pert of going to biotech ERDF funds for OP R&D for Innovation and Enterprise for Innovation / pert of going to biotech Institute of Biotechnology AS CR, v.v.i. founded on January 1, 2008 Institute of Biotechnology AS CR, v.v.i. founded on January 1, 2008 BIOCEV, CEITEC and several other major projects in preparation BIOCEV, CEITEC and several other major projects in preparation 11

12 Biotech research - geographical distribution

13 University students vs. life science students: geographical distribution

14 Centers of biotech research at Universities Centre of Integrated Genomics: AS CR, Charles University Institute of Chemical Technology – genomes, gene expression Genomics of animals: Veterinary and Pharmaceutical University Brno, South Bohemian - genomics of farm animals Centre of Proteomics : Military Academy in Hradec Králové Centre for Biocatalysis and Biotransformation: AS CR, Masaryk University, South Bohemian University – enzyme engineering

15 Centre for Molecular and Gene Biotechnology: AS CR, ICT, 5 companies – biosynthesis, biotranformation proteins Centre for Research of Structure and Mechanism of Action of Potential Drugs: School of Pharmacy, Hradec Králové + companies – gene therapies, biologically active substances Medicinal and pharmaceutical chemistry: Palacky University Olomouc – biologically active plant substances Centers of biotech research at Universities

16 Since 2005 – major investments at Masaryk University ILBIT

17 Academy of Sciences 17 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, Basic Facts and Mission of the ASCR

18 Welcome Institute of Molecular Genetics, Academy of Sciences of the Czech Republic Flemingovo nám. 2 Prague 6, CZ Czech Republic Phone: Fax: New Institute's building to completed in 2007

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

20 Inhibition of HIV Protease by Bizarre Compounds Inhibition of HIV Protease by Bizarre Compounds „WIDE-OPEN“ PROTEASE IN THE COMPLEX HIV PR dimer + 2 carborane molecules + tetrapeptide Carboranes: Boron-containing polyhedral compounds previously used in boron neutron capture therapy Ki = 66 nM X-ray structure Cigler et al. (2005) PNAS 102,

21 Dr. Ladislav Andera Cell signalling and apoptosis  TRAIL induces death of tumor cells  TRAIL is produced as soluble trimer  TRAIL-based drugs in combination with other cancer therapies  Apoptosis-inducing humanized monoclonal antibodies against TRAIL receptors DR4 and DR5

22 Institute of Experimental Medicine (IEM) Prof. Eva Sykova, D.Sc. phone: fax:

23 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 – among the world`s leaders)

24 Invasion of axons into the hydrogel implanted into the spinal cord injury Institute of Experimental Medicine ASCR E. Sykova

25 Institute of Physiology & Centre of Cardiovascular Research Videnska 1083, Prague 4-Krc, Czech Republic Phone: Fax: Bioartificial vascular tissue prostheses - Regionally-selective cell adhesion on micropatterned surface - Bone tissue engineering on nanostructured materials

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

27 Bone tissue engineering Human osteoblast-like MG 63 cells in “three-dimensional“ porous scaffolds Cells in depth of: 0 – 60  m (blue signal)80 – 160  m (green) 180 – 220  m (yellow)240 – 300  m (orange) 320 – 400  m (red)420 – 480  m (violet) 400  m ______  Scaffolds made of lactide and glycolide a copolymer  Average pore size and depth ~400 µm

28 Institute of Microbiology Videnska 1083 CZ Prague 4 Czech Republic phone: fax:

29 Pioneered continous culture research in 60`s…Pioneered continous culture research in 60`s… microalgae cultivation biotechnologymicroalgae cultivation biotechnology Biotechnological pilot plantBiotechnological pilot plant Targeted polymeric drugsTargeted polymeric drugs Biotransformation of glycansBiotransformation of glycans Antigen delivery tools for immunotherapy and diagnosticsAntigen delivery tools for immunotherapy and diagnostics Institute of Microbiology

30 Laboratory of Algae Biotechnology Isotopically labelled chemicals ( 13 C, 15 N, 2 H) Bioactive compounds for pharmaceuticals, cosmetics and nutrition Solar bioreactors Pilot plant for microalgal biomass

31 Plasma membrane Extracellular matrix Endosome Intracellular fluid Lysosome Targeted cancerostatic drug action Targeted therapy = Reduced side effects Stimulation of anti-cancer immunity Improved efficiency Much better survival of treated animals

32 Antigen delivery tools inducing cellular immune response in vaccination, immunotherapy and diagnostics Proteasome Endosome MHC II peptide CD4+ T cell Transporter associated with antigen procesing MHC I MHC II Golgi Endoplasmatic reticulum MHC I peptide AC Ca + AC Repeats AC Translocation intocytosol Inserted antigen CD8+ T cell Repeats ? ?  M  2 integrin receptor CD11b/ CD18 Ag Antigen-specific T cells: P. Sebo

33 Current status of antigen ACT delivery technology Immunity against viruses Immunotherapy of transplanted tumors Protective immunity against Plasmodium (mouse malaria model) Immunotherapy of experimental tumors (HPV16 – induced) Improvement of latent tuberculosis diagnosing Phase I&II clinical trial in preparation for:Phase I&II clinical trial in preparation for: –melanoma treatement –HPV16-induced cervical carcinoma (US Patent No. 5,503,829, No. 5,679,784, No. 5,935,580, EU Patent application No , US Prov 03495, 6094 (2003) )

34 INSTITUTE OF EXPERIMENTAL BOTANY Cytokinins as cell-division-inhibiting substances for cancer treatment Sorted chromosomes for plant genomics Edible vaccines in plants Phone: Fax: Institute of Experimental Botany Rozvojová Prague 6 - Lysolaje Czech Republic Institute of Experimental Botany Rozvojová Prague 6 - Lysolaje Czech Republic

35 Senescent human fibroblasts treated (A) and untreated (B) with a cytokinin. Blue-green color is indicates ageing marker Cytokinins Prevent Aging of Human and Plant Cells: Synthesis and use of cytokinins and their synthetic analogs M. Strnad et.al.

36 Inhibitors of cyclin-dependent kinases (CDK) R-Roscovitine - (Seliciclib) R – phase II of clinical trials for cancer -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.

37 Institute of Biotechnology Founded by Academy of Sciences January 1,

38 38 IBT seeding groups : IBT/Sebo 2008: IBT/Sebo P. Bartůněk- Chemical genetics 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) 2009: 2009: G. Pavlinkova - gene expression regulation in diabetic embryopathy G. Pavlinkova - gene expression regulation in diabetic embryopathy New recruitments New recruitments / 2011 Evaluation/new recruitements 2012Recruitement of new groupleaders

39 39 S78E or S78A or S78G A186F or A186Y or A186W I166E or I166Q or I166N or I166D Setting-up the ribosome display technology on the model of Improvement of IFN  receptor binding site Calculations and rational design: J. Vondrášek

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

41 Biotech&Biomed Res. Center of Academy of Sciences and Charles University m 2 of R&D facilities 450 researchers 150 students and postdocs ~100 M€ 2012 – the true START!

42 Biotech&Biomed Res. Center of Academy of Sciences and Charles University Center of Molecular Biotechnologies Emphasis on: Emphasis on: protein research and engineering - Structural Biology protein research and engineering - Structural Biology Openings for discovering new interesting molecules for therapy and diagnostics Openings for discovering new interesting molecules for therapy and diagnostics Processes for producing recombinant therapeutic and diagnostic proteins of extremely high added value Processes for producing recombinant therapeutic and diagnostic proteins of extremely high added value qRT/PCR for clinical and research applications qRT/PCR for clinical and research applications Licensing to biotech companies Licensing to biotech companies Start-up and spin-off biotechs Start-up and spin-off biotechs Transgenic cells, animals and plants Genetic manipulation of producing cells Culture techniques for bacteria and yeasts Advanced cell culture techniques Advanced biomacromolecule (protein) separation and purification Cutting-edge biomacromolecule analysis and characterization methods Structural biology and protein engineering Bioinformatics and modeling Nanobiotechnologies – molecular motors Biosensors

43 Biotech&Biomed Res. Center of Academy of Sciences and Charles University Tissue engineering and therapies Cellular therapies using stem cells Immunobiology of stem cells Application of stem cells in: neurology, cardiology, diabetology and hepatology ophthalmology, stomatology a otolaryngology Stem cell use on scaffolds for bone and cartilage reconstruction Biomaterials Nanotechnologies for cell and tissue imaging Nanotechnologies for therapy and diagnostics Center of Regenerative Medicine

44 Academy of Sciences Public research institutes : Charles University Binstitute of Biotechnology (founded ) Institute of Physiology Institute of Microbiology Institute of Experimental Medicine Institute of macromolecular Chemistry Institute of Molecular Genetics Faculty of Science 1 st Medical School Biotech&Biomed Res. Center of Academy of Sciences and Charles University

45 Pros and cons for the future Strong pointsWeak points long tradition in classic biotechnology lag in cutting-edge molecular biotechnology established education system; well qualified and cheap manpower insufficient interaction of academia with industry; brain-drain improved infrastructure in R&D; restructuring research organizations missing tradition of spin-offs; lack of managers trained in science growing awareness on intellectual property protection in academia lack of funding for patenting in academia; lack of venture capital increasing funding to R&D; long-term funding growing bureaucracy; complex rules for the use of funding

46 Summary of pros and cons for the future Strong pointsWeak points long tradition in classic biotechnologyLagging behind in cutting-edge molecular biotechnologies established education system; well qualified and cheap manpower insufficient interaction of academia with industry; brain-drain improved infrastructure in R&D; restructuring research organizations missing tradition of spin-offs; lack of managers trained in science growing awareness on intellectual property protection in academia lack of funding for patenting in academia; lack of venture capital increasing funding to R&D; long-term funding growing bureaucracy; complex rules for the use of funding

47 Strong pointsWeak points long tradition in classic biotechnologyLagging behind in cutting-edge molecular biotechnologies established education system; well qualified and affordable manpower insufficient interaction of academia with industry; past brain-drain improved infrastructure in R&D; restructuring research organizations missing tradition of spin-offs; lack of managers trained in science growing awareness on intellectual property protection in academia lack of funding for patenting in academia; lack of venture capital increasing funding to R&D; long-term funding growing bureaucracy; complex rules for the use of funding Summary of pros and cons for the future

48 Strong pointsWeak points long tradition in classic biotechnologyLagging behind in cutting-edge molecular biotechnologies established education system; well qualified and affordable manpower insufficient interaction of academia with industry; past brain-drain improved infrastructure in R&D; restructuring research organizations missing tradition of spin-offs; lack of managers trained in science growing awareness on intellectual property protection in academia lack of funding for patenting in academia; lack of venture capital increasing funding to R&D; long-term funding growing bureaucracy; complex rules for the use of funding Summary of pros and cons for the future

49 Strong pointsWeak points long tradition in classic biotechnologyLagging behind in cutting-edge molecular biotechnologies established education system; well qualified and affordable manpower insufficient interaction of academia with industry; past brain-drain improved infrastructure in R&D; restructuring research organizations missing tradition of spin-offs; lack of managers trained in science growing awareness on intellectual property protection in academia lack of funding for patenting in academia; lack of venture capital increasing funding to R&D; long-term funding growing bureaucracy; complex rules for the use of funding Summary of pros and cons for the future

50 Strong pointsWeak points long tradition in classic biotechnologyLagging behind in cutting-edge molecular biotechnologies established education system; well qualified and affordable manpower insufficient interaction of academia with industry; past brain-drain improved infrastructure in R&D; restructuring research organizations missing tradition of spin-offs; lack of managers trained in science growing awareness on intellectual property protection in academia lack of funding for patenting in academia; lack of venture capital increasing funding to R&D; long-term funding growing bureaucracy; complex rules for the use of funding Summary of pros and cons for the future

51 Special Thanks: Jiří Damborský Michal Kostka

52 Contact: Peter Sebo, PhD. BIOCEV coordinator Institute of Biotechnology AS CR, v.v.i. Academy of Sciences of the Czech Republic Videnska Prague 4 Czech Republic GSM: (+420) office: (+420)


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