CzechBiotech-Petr_Sebo.ppt - Gate2Biotech

mutebabiesBiotechnology

Dec 6, 2012 (4 years and 8 months ago)

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Advanced Czech
B
iotech
:

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



L
imited

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

limite
d 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


*
-

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**

1800
-
2200

Combined yearly
turnover**

4
-
5
bil CZK

(
160
-
200
mil Euro)

Average yearly
growth rate**

12
-
16
%

Czech
advanced

biotech


overall description

Biotech companies


geographical distribution

Selected b
iotech companies

-

Prague

Ascoprot

Biotech

SME (5 p.)
rec
.
proteins

BIOPREPARÁTY

biological

plant

protection

GeneAge

Technologies

expression

profiling

Genomac

International

sequencing
/
genotyping

LentiKat


waste

water

tr
eatment

R
&D


Top
-
Bio

molecular

biol
.

kits

producer

SME (
<5)

Sel
.

b
iotech companies



Central Bohemia

AppGenics


SME , transgenic rabbits,
hEPO




recombinant proteins

Apronex

SME, recombinant proteins


(4 p)


Baxter

Czech


flu

vaccine

production

site


B
iologicals


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

V
IDIA


SME,
clinical

diagnostic

kits

Sel
.

b
iotech 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
.

b
iotech companies



remaining regions

GENERI BIOTECH


SME,
oligonucleotides
,




DNA genotyping services

Contipro

Group


world
l
eader

in
hyaluronic

acid

GMP recombinant
defensins
, wound healing R&D

AgroBio

agrochemicals and
agrobiologicals

Biocel

pulp industry


fodder yeast producer


IVAX Pharmaceuticals , generics, ergot
alcaloids

OlChemIm

SME,
phytohormones
, antibodies (5 p)

B.P.Medical


SME,

bioactivity testing


ENVISAN
-
GEM

bioremediation


GEN
-
TREND

SME, diagnostics and proteins

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

b
iotech

research

at Universities


Centre

of

I
ntegrated

G
enomics
:

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

Proteomic
s

:

Military

Academy

in

Hradec

Kr
álové



Centre

for

Biocatalysis

and

B
iotran
s
formation
:

AS

CR
,

Masaryk

University
,

South

Bohemian

University



enzyme

engineering





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

substance
s



Medicinal

and

pharmaceutical

chemistry
:

Palacky

University

Olomouc



biologically

active

plant

substances


Centers

of b
iotech
research
at Universities

Since 2005


major

investments

at Masaryk University

ILBIT

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



N
etwork of 60 institutes


All transformed to Public Research Institutes
by

January 1, 2007

http://www.cas.cz/en

Basic Facts and Mission of the ASCR









Welcome

Institute of Molecular Genetics, Academy of Sciences of the Czech Republic




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

Developmental Biology

Virology

Molecular Genetics

Recombinant proteins

Monoclonal antibodies

Cellular vaccines

Monoclonal antibodies

Unique mouse strains

Unique chicken inbreds


Inhibition of HIV Protease by Bizarre Compounds

„WIDE
-
OPEN“ PROTEASE IN THE COMPLEX

HIV PR dimer + 2 carborane molecules + tetrapeptide


Co

=
BH

=
CH

Carboranes:
Boron
-
containing polyhedral

compounds

previously
used
i
n boron neutron capture therapy

Ki = 66 nM



X
-
ray structure


Cigler
et al.

(2005) PNAS 102, 15394
-
9

Dr. Ladislav Andera


http://www.img.cas.cz/csa

andera
@
biomed.cas.cz




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


A
poptosis
-
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

sykova
@biomed.cas.cz

http://uemweb.biomed.cas.cz

Stem cell research at IEM


iron nanoparticles for in vivo
N
MR imaging

of stem cells


Biodegradable h
ydrogel
s

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)




sykova
@biomed.cas.cz

http://uemweb.biomed.cas.cz

Invasion of axons into the hydrogel implanted

into the spinal cord injury

Institute of Experimental Medicine ASCR

E. Sykova sykova
@
biomed.cas.cz

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: fgu@biomed.cas.cz



-

B
ioartificial vascular tissue prostheses



-

Regionally
-
selective cell adhesion on micropatterned

s
urface



-

Bone tissue engineering on nanostructured materials

Innovation of clinically used vascular prostheses
:

coating with extracellular matrix (ECM) molecules and endothelialization

Endothelial cells grow and differentiate

On the inner surface,
l
aminin

or
fibrin

were i
mmobilized

Inner surface

fgu@biomed.cas.cz

Bone tissue engineering


Human osteoblast
-
like MG 63 cells

in “three
-
dimensional“ porous scaffolds

Cells in depth of
:


0


60

洠⡢汵攠獩杮g氩

㠰8


160

洠⡧r敥温e


180


220

洠m祥汬潷)

㈴〠


300

洠m潲o湧攩


㌲〠


400

洠mr敤e

㐲〠


480

洠m癩v汥琩

400

m

______



Scaffolds made of lactide and glycolide

a
copolymer



Average pore size and depth ~400 µm

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
@biome
d
.cas.cz

http://www.biomed.cas.cz/mbu/en/


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

Institute
of

Microbiology


http://www.biomed.cas.cz/mbu/en/

Laboratory of
Algae

Biotechnology


I
sotopically labelled chemicals (
13
C,
15
N,
2
H)


B
ioactive

compounds

for pharmac
euticals
,
cosmetics and nutrition



S
olar bioreactors

http://www.alga.cz/en/


masojidek@alga.cz

Pilot plant for microalgal
biomass

www.greentech.cz

Plasma
membrane

Extracellular

matrix

Endosome

Intracellular

fluid

Lysosome

Targeted cancerostatic drug action

rihova
@
biomed.cas.cz


Targeted therapy = Reduced side effects


Stimulation of anti
-
cancer immunity


Improved efficiency


Much better survival of treated animals


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

AC

Ca

+

AC

Repeats

Translocation

into

cytosol

Inserted

a
ntigen

CD8+


T cell

Repeats

?

?


M

2

integrin receptor

CD11b/

CD18

Ag

Ag

Ag

Ag

Ag

Ag

Antigen
-
specific T cells:

P. Sebo
http://l125lsx.mbu.cas.cz/Lab125/


sebo
@
biomed.cas.cz


Current

status
of

antigen ACT
delivery

technology

I
mmunity

against

virus
es

Immunotherapy

of

transplanted

tumors


Protective

immunity

against

Plasmodium
(
mouse

malaria

model)

Immunotherapy of
experimental

tumors

(HPV16


induced
)


Improvement

of

latent

tuberculosis

diagnosing



P
hase

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/


sebo
@
biomed.cas.cz

INSTITUTE OF EXPERIMENTAL BOTANY


C
ytokinins

as

c
ell
-
division
-
inhibiting substances for cancer
treatmen
t


S
orted chromosomes for plant genomics



E
dible vaccines in plants

Phone:

+
420 220 390 453



Fax:

+
420 220 390 456



E
-
mail:
machackova@ueb.cas.cz


www.ueb.cas.cz

Institute of Experimental Botany



Rozvojová 135



165 00 Prague 6
-

Lysolaje



Czech Republic



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.

http://rustreg.upol.cz/

I
nhibitor
s

of cyclin
-
dependent kinases (CDK)


R
-
Roscovitine
-

(
S
eliciclib)
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

38

IBT

seeding

groups

2007
-
2010


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:


G. Pavlinkova


-

gene expression regulation in diabetic embryopathy


New recruitments



200
10

/ 201
1


Evaluation/new recruitements


201
2


Recruitement of new groupleaders

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

Vestec
at

Pra
gue


Regional development and competitiveness

t
hrough

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 Research Center


of Academy of Sciences and Charles University

Biotech
&Biomed

Res. Center of

Academy of Sciences and Charles University


20 000 m
2
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


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

A
dvanced cell culture techniques

Advanced biomacromolecule (protein)
separation and purification

Cutting
-
edge biomacromolecule analysis and
characterization methods

S
tructural biology and protein engineering

B
ioinformatics and modeling

Nanobiotechnologies


molecular motors

Biosensors


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
M
edicine

biocev
-
office@
img.cas.cz

Academy of Sciences

Public research institutes
:

Charles University

B
institute

of

Biotechnology


(
founded

1
.
1
.
2008
)

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

Pros and cons for the future

Strong points


Weak 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


Summary of p
ros 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


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 p
ros 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 p
ros 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 p
ros 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 p
ros and cons for the future

Special

Thanks
:


Jiří
Damborský


Michal Kostka


Contact:

sebo@biomed.cas.cz



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/