Transcript Document 7272842

Advanced Czech Biotech:
Great past
Sad present
Promising future
Peter Šebo
Institute of Biotechnology
Academy of Sciences of the Czech Republic
Prague
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
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 R&D in advanced biotech
• Low numbers of high-tech biotech SME
3
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, Ernst&Young presentation at G2B conference 2006, company data in public domain
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, Ernst&Young presentation at G2B conference 2006, company data in public domain
Biotech companies – geographical distribution
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 R&D
Top-Bio molecular biol. kits producer SME (<5)
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 R&D
FDA-registered pharma enzymes
Proteix
SME, recombinant proteins (3 p)
rEcoli
SME, recombinant proteins
VIDIA
SME, clinical diagnostic kits
Sel. biotech companies – South Moravia
BioVendor
Bioveta
Enantis
SME, recombinant proteins, diagnostics
veterinary vaccines R&D and production
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 Pharmaceuticals , generics, ergot alcaloids
OlChemIm SME, phytohormones, antibodies (5 p)
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 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
• BIOCEV, CEITEC and several other major projects in preparation
11
Biotech research - geographical distribution
University students vs. life science students:
geographical distribution
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
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
Since 2005 – major investments at Masaryk University
ILBIT
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
17
Flemingovo nám. 2
Prague 6, CZ-16637
Czech Republic
Phone: +420 220 183 111
Fax: +420 224 310 955
E-mail: [email protected]
http://www.img.cas.cz
New Institute's building to completed in 2007
INSTITUTE OF MOLECULAR GENETICS AS CR
Recombinant proteins
Molecular & Cell Biology
Monoclonal antibodies
Molecular & Applied Immunology
Cellular vaccines
Monoclonal antibodies
Molecular Genetics
Unique mouse strains
Developmental Biology
Virology
Unique chicken inbreds
Inhibition of HIV Protease by Bizarre Compounds
Ki = 66 nM
Carboranes: Boron-containing
X-ray structure
polyhedral compounds
previously used in boron neutron capture therapy
Co
„WIDE-OPEN“ PROTEASE IN THE COMPLEX
=
BH
=
CH
HIV PR dimer + 2 carborane molecules + tetrapeptide
Cigler et al. (2005) PNAS 102, 15394-9
Cell signalling and apoptosis
Dr. Ladislav Andera
http://www.img.cas.cz/csa
[email protected]

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
Institute of Experimental Medicine (IEM)
Prof. Eva Sykova, D.Sc.
phone: +420 296 442 230
fax:
+420 296 442 782
[email protected]
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 – among the world`s leaders)
[email protected]
http://uemweb.biomed.cas.cz
Institute of Experimental Medicine ASCR
Invasion of axons into the hydrogel implanted
into the spinal cord injury
E. Sykova
[email protected]
Institute of Physiology
& 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: [email protected]
- 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
[email protected]
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)
180 – 220 m (yellow)
320 – 400 m (red)
80 – 160 m (green)
240400
– 300
m (orange)
m
420______
– 480 m (violet)
Institute of Microbiology
Videnska 1083
CZ-142 20 Prague 4
Czech Republic
phone: +420 296 442 341
fax: +420 296 442 201
e-mail: [email protected]
http://www.biomed.cas.cz/mbu/en/
Institute of Microbiology
• Pioneered continous culture research in 60`s…
• 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/
Laboratory of Algae Biotechnology
• Isotopically labelled chemicals (13C, 15N, 2H)
• Bioactive compounds for pharmaceuticals,
cosmetics and nutrition
Pilot plant for microalgal
biomass
• Solar bioreactors
http://www.alga.cz/en/
[email protected]
www.greentech.cz
Targeted cancerostatic drug action
Extracellular
matrix
Intracellular
fluid
Plasma
membrane
Endosome
Lysosome
•
•
•
•
Targeted therapy = Reduced side effects
Stimulation of anti-cancer immunity
Improved efficiency
Much better survival of treated animals
[email protected]
AC
Antigen delivery tools inducing cellular immune response
in vaccination, immunotherapy and diagnostics
Inserted
antigen
Repeats
Ag
Ca+
M2 integrin receptor
CD11b/
Ag
CD18
AC
Ag
AC Ag
Ag
Repeats
Ag
?
Translocation
into cytosol
Endosome
Proteasome
?
Transporter associated
with antigen procesing
MHC II
peptide
Endoplasmatic
reticulum
MHC I peptide
MHC I
MHC II
Golgi
Antigen-specific T cells:
CD4+
T cell
CD8+
T cell
P. Sebo http://l125lsx.mbu.cas.cz/Lab125/
[email protected]
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:
– 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) )
http://l125lsx.mbu.cas.cz/Lab125/
[email protected]
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: [email protected]
www.ueb.cas.cz
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
Synthesis and use of cytokinins and their synthetic analogs M. Strnad et.al.
http://rustreg.upol.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
37
IBT seeding groups 2007-2010
•
2008: IBT/Sebo
P. Bartůněk
M. Kubista
J. Neužil
J. Pěknicová
R. Sedláček
Š. Růžičková
P. Šebo
•
2009:
•
•
•
•
- Chemical genetics
- Single cell expression profiling
- Molecular and recombinant therapeutics
- Diagnostics for reproductive medicine
- Transgenic Animals
- Diagnostics of autoimmune diseases
- Recombinant binding proteins (ligands)
G. Pavlinkova - gene expression regulation in diabetic embryopathy
New recruitments
20010 / 2011
2012
Evaluation/new recruitements
Recruitement of new groupleaders
38
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
39
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
European Regional Development Fund
Operational Program R&D for Innovation
2007 - 2013
Biotech&Biomed Res. Center of Academy of Sciences and Charles University
20 000 m2 of R&D facilities
450 researchers
150 students and postdocs
~100 M€
2012 – the true START!
Biotech&Biomed 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
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

Licensing to biotech companies
Nanobiotechnologies – molecular motors

Start-up and spin-off biotechs
Biosensors
Biotech&Biomed 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
Biotech&Biomed Res. Center of Academy of Sciences and Charles University
Academy of Sciences
Public research institutes:
Charles University
Binstitute of Biotechnology
(founded 1.1.2008)
Faculty of Science
Institute of Physiology
Institute of Microbiology
1st Medical School
Institute of Experimental Medicine
Institute of macromolecular Chemistry
Institute of Molecular Genetics
[email protected]
Pros and cons for the future
Strong points
Weak points
long tradition in classic
biotechnology
established education system;
well qualified and cheap
manpower
improved infrastructure in
R&D; restructuring research
organizations
growing awareness on
intellectual property
protection in academia
increasing funding to R&D;
long-term funding
lag in cutting-edge molecular
biotechnology
insufficient interaction of
academia with industry;
brain-drain
missing tradition of spin-offs;
lack of managers trained in
science
lack of funding for patenting
in academia; lack of venture
capital
growing bureaucracy;
complex rules for the use of
funding
Summary of pros and cons for the future
Strong points
Weak points
long tradition in classic biotechnology
Lagging 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
Summary of pros and cons for the future
Strong points
Weak points
long tradition in classic biotechnology
Lagging 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
Strong points
Weak points
long tradition in classic biotechnology
Lagging 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
Strong points
Weak points
long tradition in classic biotechnology
Lagging 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
Strong points
Weak points
long tradition in classic biotechnology
Lagging 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
Special Thanks:
Jiří Damborský
Michal Kostka
Contact:
[email protected]
Peter Sebo, PhD.
BIOCEV coordinator
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
http://125lsx.mbu.cas.cz/Lab125/