Development of the scientific-technical platforms in a
field of biomedicine
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Author:
Academician Genrikh Sofronov
Speakers:
Prof. Anton Orlov
Prof. Youry Scherbuk
• Single product development
• Complex vehicle
Ideology:
Development of founded platforms will lead to wide-front breakthrough in
technologies creation and implementation
Scientific-technical platforms as mainstream approach for effective
innovative development
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Developing Platforms:
Nosological
group
Technological
group
Oncology
Autoimmune diseases
Recombinant
vaccines
Scientific-research centers
Clinical centers
Healthcare system - Implementation
- Clinical studies
- Invention & development
Ap
pro
ac
hes
alt
ern
ati
ve
Experimental-industrial
production
Education centers - Education
- Test output
Institute of Experimental Medicine (IEM)
of the North-West Branch
of Russian Academy of the Medical Sciences
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• 7 academicians, members of RAMS;
• 24 professors;
• 53 doctors of sciences (Dr.Sc);
• 102 PhDs.
An investigation of molecular mechanisms of
dysfunctions of the human organs and systems
and search of the ways for their correction
Major goal of the studies
conducted in IEM:
Over 120-years history (since 1890)
The most authoritative center of the biomedical science in Russian Federation
•
•
Staff: more than 600 employees, including:
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- diagnosis, study, treatment and prophylaxis of human diseases
• Mass-spectrometers,
• Real time PCR equipment,
• Confocal microscopy,
• Microarray systems,
• Sequencers,
• Cytofluorymeters, etc.
International cooperation:
USA, Sweden, Slovakia, Vietnam, Germany, Australia, Italy, Poland, Hungary,
China, Czech Republic, Japan and others
Research
facilities
Institute of Experimental Medicine (IEM)
of the North-West Branch
of Russian Academy of the Medical Sciences
11 research
departments
Clinic
Structure include:
Educational
unit
Scientific-
practical centers
Sustainable development of new clinical capacities
Unique facilities for initial founding of scientific-technological platforms of a
State/Federal value
Modern Clinical facilities of Saint-Petersburg
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Saint-Petersburg State Healthcare complex
RAMS
Scientific
capacity
•
International
Scientific
capacity
Outstandingly equipped
clinical complexes• oncology;
• cardiology;
• infections;
• multi profile;
• others
Sustainable city Expenses on top-class equipment
•
•
Bases to implement
breakthrough technologies and methodics
Launched – feb 2010
Clinical complex of a top level in Russia relevant to a worldwide level
Modern Clinical facilities of Saint-Petersburg
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Saint-Petersburg clinical scientific & practical center (oncological)
Technical capacity:
• Multispiral computed tomography 128
• combined PET-CT,
• MRT 3Tesla,
• Intraoperational MRT,
• Dual-head CT gamma camera,
• Dual-source CT angiograph,
• US complexes of expert and premium class,
• Digital X-Ray complexes.
14 beam therapy complexes, including:
• LEA 20 MeV complexes,
• Brahitherapy complexes,
• Intraoperational X-Ray complexes.
Properties:78 000 sq.m. area
23 units
14 surgeries GMP laminar coatings
Diagnostics Beam therapy
Bright example of one of nosological
platform Participant
Personnel – 1 200 employees.
Clinical capacity – 600 beds
Research & Development of the facilities for
personified diagnostics and treatment of
oncological diseases
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Scientific-technical platform #1
Project Participants
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Saint-Petersburg State University
Institute of Experimental Medicine of the North - West
Branch of the Russian Academy of the Medical Sciences
Saint-Petersburg clinical scientific & practical center (oncological)
IEM
SPbSU
CSPC
• The risk group identification, via genetic diagnostics of the oncology
predisposition
• General diagnostics of oncology
• Noninvasive extracting of tumor cells
• Differential diagnostics with optimal for therapy tumor cell surface
antigens recognizing
• R&D and production of medicines made of genetically engineered
complexes
• Target therapy of multiple origin tumors
Project structure:
First case in Russia of full-stages united system to be created: from diagnostics to
personified therapy
Research & Development tools for personified diagnostics and
treatment of oncological diseases
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1
2
2,5 mln
patients
490 000 new
cases
290 000
patients
Under monitoringAnnually
detected new casesAnnual
deaths
29 % growth
in 10 years
11 % growth
in 5 years
0 % growth
Russia: the disease rate increase
• Cancer– the second in value cause of country population mortality
• While peoples life length is growing the following growth of disease rate is estimated
Medicine therapy
required
Medicine
therapy
provided
Deathes due to the
absence of medicine
therapy
Lung tumor 65% 10% >50%
Breast tumor 95% >50% >30%
Ovary tumor 95% >50% >30%
Low medicine consumption rate in Russia
65-70% of cancer patients need to be treated with medicines on multiple desease stages
• Indexes show medicines demand unavoidable growth in close future
Ве
стн
ик
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им
. Н
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9 г
.
Ста
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ка о
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аб
ол
ева
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Project actuality
10
• The risk of hereditary cancer development is near 90%.
• The hereditary breast cancer occurs mostly due to genes BRCA1 and BRCA2 mutations.
• Most frequently noted is the 5382 ins C mutation, which is responsible for breast cancer cases and 40% ovary
cancer cases. Also were found some other mutations associated with tumors of several types development.
• The risk of cancer development in young aged mutations holders is 10 times higher.
• It is reasonable to run tests on mutations presence (PCR, sequenation, restriction analysis) firstly for women of
families with breast or ovary cancer, and for all women from 20 to 50 years old, as routine healthcare campaign.
Over 90% of patients with determined tumors of breast in due time are able to run a valid life.
1 Risk groups identification
Genetical diagnostics of hereditary cancer predisposition
The predisposition to breast and ovary cancer was explored
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IEM
re
se
arc
hes
Researches held
Original Methodics
2012-2013 г.
• PCR with reverse transcription
(cDNA, detection on transcriptase level);
• ELISA
(detection on proteomics level).
2 General diagnostics via tumor markers
Universal tumor genes are found which are proposed as base for
diagnostics.
Reverse transcription PCR analysis of these markers (cDNA)
shows sensibility up to 95% and specificity – 95%.
ELISA with purified proteins for antibodies used in blood
detection shows sensibility up to 94%, specificity – 98%
Methods
Base
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Start-up №1original methodics
2012-2013
Registration of medicines,
certification of methodics,
launch on market
• The fraction of tumor cells in blood determination via stream cytologic fluorimetry
• Concentration of tumor cells via monoclonal antibodies based sorter
• Test of tumor cells RNA function of specific surface antigen encoding
3 Extraction of tumor cells via non-invasive technique
Method
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Advantages:
• Biopsy avoidance
• High promptnessOriginal methodic
2012-2013
• for monoclonal antibodies (МАb) and target-medicines created on their base
• for medicine resistance determination and its neutralization vehicles switching on
• for immunotherapy efficiency increasing
4 Differential diagnostics
Method: Reverse transcription – real time PCR
Antigens specification – as targets for each individual case
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Start-up №2original methodics
2012-2013
Medicines registration,
Methodics sertification,
Product launch
• Specified linking to the transmembrane antigenes, expressed on the surfaces of tumor cells (onco-markers)
• Initiate a cascade of immunological reactions of the humans organism which leads to a lysis of onco-markers
expressing cells
• Fundamental difference of MAb opposite to chemo-medicines is its specificity of damage action on target-cells causing
minimal harmful influence on normal tissues and organs of host
• Nowadays in Russia some of himeric and humanized monoclonal antibodies (MAb) medicines which are totally foreign
made are approved for clinical implementation
- Monoclonal antibodies (MAb)
5 Developing of biotechnological medicines based on genetically
engineered complexes
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receptor
MAb
Invention 2 original MAb worldwide exclusive
Particularly based on stage №4 achievements
(Definition of universal tumor markers)
Therapeutic efficiency studies using cell-models and
clinical samples
Methodics of application studies
IEM
Conventional MAb
action illustration:
Start-up №3MAb pharmaceuticals
2013 г.
Clinical studies,
Pharmaceuticals registration,
Methodics certification,
Product launch
- Single-chain antibodies (mini-MAb)
• Single-chains are genetically engineered atnibodies consisting of only
Fv and Sc fragments of ordinary monoclonal antibodies.
Their size is 5 times less than that of ordinary antibodies (up to 20nm).
• Action mechanism is equivalent to one of ordinary MAb
• Small size allows it to penetrate the areas unreachable for МАb
5 Developing of biotechnological medicines based on genetically
engineered complexes
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Start-up №3single-chain MAb
pharmaceuticals
2013
Clinical studies, Pharmaceutical registration,
Methodics certification,
Product launch
- MAb conjugated with cytostatic agents (A-MAb)
• Complexes of MAb molecules (as nano carrier) conjugated with chemotherapy cytostatic molecules
• Action principles based on MAb’s ability to specifically conjugate with onco-markers expressed on tumor cells
surface
• Due to implementation of MAb as nano-carrier it allows to deliver cytostatic agents directly to cells expressing
onco-markers.
Nucleus
Clathrine
Clathrine-banded
vesicle
5 Developing of biotechnological medicines based on genetically
engineered complexes
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Start-up №3conjugated MAb
pharmaceuticals
2013
Clinical studies, Pharmaceutical registration,
Methodics certification,
Product launch
1. Risk groups identification
4. Differential diagnostics
2. General diagnostics
6. Developed pharmaceuticals
appliance to cancer therapy
Targeted R&D achievements
5. Development of genetically-
egineered pharmaceuticals
Field
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3. Non-invasive tumor cells
extraction
Investigation of additional reasonable
mutations;
Population studies
Original methodics;
Base for diagnosticums development
and commercialization
Extended studies of proposed
tumor-specified genes
Studies of additional reliable tumor-
specified genes
Extended studies and proving the
precision of proposed method ,
relevant to all types of tumors
Original methodics;
Matter Target
Base for unified diagnosticums
development and
commercialization/
Original methodics
In framework of following start-up
development
Technologies of synthesis
of 4 original pharmaceuticals.
Lab Protocols of
efficiency studies
Base for unified diagnosticums for
onco-markers development and
commercialization.
Original methodics
Developing new 4 genetically-
engineered medicines: technology
of synthesis, therapeutic efficiency
studies
Start-
up
Start-
up
Start-
upExtended studies and proving the
precision of proposed method
relevant to all types of tumors
Project result
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Creation of technologies and tools for Russia’s first united full-stage
system in treatment of oncological diseases: from risk groups
identification to personified diagnostics and therapy, relevant to top
worldwide class
Creation of technologies for national innovative pharmindustry of
general and differential diagnostics facilities and target-therapy
pharmaceuticals for treatment of oncological diseases. Creation of
original treatment methodics.
This will lead to competence for developing start-ups purchased with
more than 7 original oncologic medicines of top worldwide level
Creation of scientific-technological platform aimed to facilitate quick
spinoff of start-ups for development and to put into healthcare
practice a new highly innovative pharmaceuticals and treatment
methodics in a field of oncology
Within 5 years following aims will be reached: