Advanced Czech Biotech:

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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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Great past

• Used to be extremely strong in tradional
  biotechnology
• Crop and animal breeding
• fermentation industry
• Famous Brewery tradition
• Wine, ethanol, bakers 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)

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Sad present

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

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Czech advanced biotech overall description

• 43 biotech companies
• Most companies located in Prague and Brno
  metropolitan areas
• Directly employed 1800 -2200 people
• Combined yearly turnover 4-5 bil CZK (160-200
  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, ErnstYoung presentation at
G2B conference 2006, company data in public domain
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Czech advanced biotech overall description
No of biotech companies 43
Directly employed 1800-2200
Combined yearly turnover 4-5 bil CZK (160-200 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, ErnstYoung presentation at
G2B conference 2006, company data in public domain
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Biotech companies geographical distribution
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Selected biotech companies - Prague
Ascoprot Biotech SME (5 p.) rec.
proteins BIOPREPARÁTY biological plant
protection GeneAge Technologies expression
profiling Genomac International
sequencing/genotyping LentiKat waste water
treatment RD Top-Bio molecular biol. kits
producer SME (lt5)
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Sel. biotech companies Central Bohemia
AppGenics SME , transgenic rabbits, hEPO
recombinant proteins 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 RD
FDA-registered pharma enzymes Proteix
SME, recombinant proteins (3 p) rEcoli
SME, recombinant proteins VIDIA SME,
clinical diagnostic kits
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Sel. biotech companies South Moravia
BioVendor SME, recombinant proteins,
diagnostics Bioveta veterinary vaccines
RD and production Enantis SME,
recombinant dehalogenases contract
research in protein engineering EPS
SME, bioremediation, biogas Moravian-Biotechno
logy SME, custom antibody services TEST-LINE
SME, human and veterinary diagnostics
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Sel. biotech companies remaining regions
GENERI BIOTECH SME, oligonucleotides,
DNA genotyping
services Contipro Group world leader in
hyaluronic acid GMP recombinant defensins,
wound healing RD
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
Pharmaceuticals , generics, ergot
alcaloids OlChemIm SME, phytohormones, antibodies
(5 p)
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Promising future

• 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
• National applied research support schemes (NPV )
• Incentives for Academia collaborations with
  Industry
• ERDF funds for OP RD for Innovation and
  Enterprise for Innovation / pert of going to
  biotech
• Institute of Biotechnology AS CR, v.v.i. founded
  on January 1, 2008
• BIOCEV, CEITEC and several other major projects
  in preparation

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Biotech research - geographical distribution
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University students vs. life science
studentsgeographical distribution
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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

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Centers of biotech research at Universities

• 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

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Since 2005 major investments at Masaryk
University ILBIT
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Academy of Sciences

• Leading basic research institution of CR
• Funded from state budget mainly
• 6400 employees, gt50 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

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Welcome Institute of Molecular Genetics, Academy
of Sciences of the Czech Republic
Flemingovo nám. 2Prague 6, CZ-16637Czech
RepublicPhone 420 220 183 111Fax 420 224
310 955E-mail img_at_img.cas.czhttp//www.img.cas.
cz

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INSTITUTE OF MOLECULAR GENETICS AS CR
Recombinant proteins
Molecular Cell Biology
Monoclonal antibodies
Cellular vaccines
Molecular Applied Immunology
Monoclonal antibodies
Molecular Genetics
Developmental Biology
Virology
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Inhibition of HIV Protease by Bizarre Compounds

Carboranes Boron-containing polyhedral compounds
previously used in boron neutron capture therapy
Ki 66 nM
X-ray structure
WIDE-OPEN PROTEASE IN THE COMPLEX HIV PR dimer
2 carborane molecules tetrapeptide
Cigler et al. (2005) PNAS 102, 15394-9
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Cell signalling and apoptosis
Dr. Ladislav Andera http//www.img.cas.cz/csa and
era_at_biomed.cas.cz

• 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

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Institute of Experimental Medicine (IEM)
Prof. Eva Sykova, D.Sc.phone [phone]
230fax [phone] sykova_at_biomed.cas.cz htt
p//uemweb.biomed.cas.cz
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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 worlds leaders)

sykova_at_biomed.cas.cz http//uemweb.biomed.cas.cz
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Institute of Experimental Medicine ASCR
Invasion of axons into the hydrogel
implanted into the spinal cord injury
E. Sykova
sykova_at_biomed.cas.cz
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Institute of Physiology Centre of
Cardiovascular ResearchVidenska 1083, 142 20
Prague 4-Krc, Czech RepublicPhone 420 2 9644
1111Fax [phone]E-mail
fgu_at_biomed.cas.cz

• - Bioartificial vascular tissue prostheses
• - Regionally-selective cell adhesion on
  micropatterned surface
• - Bone tissue engineering on nanostructured
  materials

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Innovation of clinically used vascular
prostheses coating with extracellular matrix
(ECM) molecules and endothelialization
Endothelial cells grow and differentiate
fgu_at_biomed.cas.cz
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Bone tissue engineering Human osteoblast-like MG
63 cells in three-dimensional porous scaffolds

• Scaffolds made of lactide and glycolide a
  copolymer
• Average pore size and depth 400 µm

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 ______
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Institute of Microbiology
Videnska 1083CZ-142 20  Prague 4Czech Republic
phone [phone] fax [phone]e-
mail mbu_at_biomed.cas.cz
http//www.biomed.cas.cz/mbu/en/
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Institute of Microbiology

• Pioneered continous culture research in 60s
• 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/
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Laboratory of Algae Biotechnology

• Isotopically labelled chemicals (13C, 15N, 2H)
• Bioactive compounds for pharmaceuticals,
  cosmetics and nutrition
• Solar bioreactors

http//www.alga.cz/en/
masojidek_at_alga.cz
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Targeted cancerostatic drug action

• Targeted therapy Reduced side effects
• Stimulation of anti-cancer immunity
• Improved efficiency
• Much better survival of treated animals

rihova_at_biomed.cas.cz
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Antigen delivery tools inducing cellular immune
response in vaccination, immunotherapy and
diagnostics
Ag
AC
Repeats
AC
Inserted antigen
Repeats
Ag

Ca
?M?2 integrin receptor
CD11b/ CD18
Ag
Ag
Ag
AC
AC
AC
AC
Ag
AC
?
Endosome
Proteasome
?
Transporter associated with antigen procesing
MHC II peptide
Endoplasmatic reticulum
MHC II
MHC I peptide
MHC I
Golgi
Antigen-specific T cells
CD4 T cell
CD8 T cell
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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 III 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. 03291486.3,
  US Prov 03495, 6094 (2003) )

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INSTITUTE OF EXPERIMENTAL BOTANY

• Cytokinins as cell-division-inhibiting substances
  for cancer treatment
• Sorted chromosomes for plant genomics
• Edible vaccines in plants

Phone [phone]  Fax [phone] 
E-mail machackova_at_ueb.cas.cz www.ueb.cas.cz
Institute of Experimental Botany  Rozvojová 135 
165 00 Prague 6 - Lysolaje  Czech Republic 
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Cytokinins Prevent Aging of Human and Plant Cells
Senescent human fibroblasts treated (A) and
untreated (B) with a cytokinin. Blue-green color
is indicates ageing marker

http//rustreg.upol.cz/
Synthesis and use of cytokinins and their
synthetic analogs M. Strnad et.al.
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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

http//rustreg.upol.cz/
M. Strnad et.al.
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Institute of Biotechnology

• Founded by Academy of Sciences January 1, 2008

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IBT seeding groups 2007-2010

• 2008 IBT/Sebo
• P. Bartunek - Chemical genetics
• M. Kubista - Single cell expression profiling
• J. Neužil - Molecular and recombinant
  therapeutics
• J. Peknicová - Diagnostics for reproductive
  medicine
• R. Sedlácek - Transgenic Animals
• Š. Ružicková - Diagnostics of autoimmune
  diseases
• P. Šebo - Recombinant binding proteins
  (ligands)
• 2009
• G. Pavlinkova - gene expression regulation in
  diabetic embryopathy
• New recruitments
• 20010 / 2011 Evaluation/new recruitements
• 2012 Recruitement of new groupleaders

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Setting-up the ribosome display technology on the
model of Improvement of IFN? receptor binding site
S78E or S78A or S78G
A186F or A186Y or A186W
I166E or I166Q or I166N or I166D
Calculations and rational design J. Vondrášek
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(No Transcript)
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20 000 m2 of RD facilities450
researchers150 students and postdocs100
M2012 the true START!
BiotechBiomed Res. Center of Academy of Sciences
and Charles University
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BiotechBiomed Res. Center of Academy of Sciences
and Charles University
Center of Molecular Biotechnologies

• Emphasis on
• protein research and engineering - Structural
  Biology
• Openings for discovering new interesting
  molecules for therapy and diagnostics
• Processes for producing recombinant therapeutic
  and diagnostic proteins of extremely high added
  value
• qRT/PCR for clinical and research applications
• Licensing to biotech companies
• 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







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BiotechBiomed Res. Center of Academy of Sciences
and Charles University
Center of Regenerative Medicine

• 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

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BiotechBiomed Res. Center of Academy of Sciences
and Charles University
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Pros and cons for the future
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Summary of pros and cons for the future
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Summary of pros and cons for the future
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Summary of pros and cons for the future
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Summary of pros and cons for the future
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Summary of pros and cons for the future
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Special Thanks

• Jirí Damborský
• Michal Kostka

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Contact

• sebo_at_biomed.cas.cz
• Peter Sebo, PhD.
• BIOCEV coordinator
• Institute of Biotechnology AS CR, v.v.i.
• Academy of Sciences of the Czech
  RepublicVidenska 1083142 20 Prague 4Czech
  Republic
• GSM (420) 774 798 121office (420) 241 062
  762
• http//www.ibt.cas.cz
• http//125lsx.mbu.cas.cz/Lab125/