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From fundamental research to
structured technology transfer –
the VUB model
Prof. Jan Cornelis
Vicerector Research
Presentation outline
IP ownership regulation in 1991 and now
Fundamental research in the Lab of Raymond
Hamers leads to a break-through technology
What did we learn?
Where VUB stands today in technology and
knowledge management
Dubrovnik-UNICA 2008
| pag. 2
Bayh-Dole act in US
Situation in Belgium (Flanders)
Bayh-Dole Act of 1980 requires U.S. universities
to put into use the intellectual property rights
generated from their federally funded research
No equivalent in Belgium / Flanders until 1998
Dubrovnik-UNICA 2008
| pag. 3
Presentation outline
IP ownership regulation in 1991 and now
Fundamental research in the Lab of
Raymond Hamers leads to a break-through
technology
What did we learn?
Where VUB stands today in technology and
knowledge management
Dubrovnik-UNICA 2008
| pag. 4
1991: getting the
environment right
VUB professor Raymond Hamers and the “wild west” of
biotechnology
Generator of diversity...
Fundamental Research:
Molecular immunology
DNA-protein interactions:
antibodies against DNA
Parasitology: sleeping disease, malaria…
cloning and cristallisation of antibodies against
carbohydrates (very important in the interaction
processes between cells)
-> ?monoclonal antibodies, but this seemed
impossible in practice
Dubrovnik-UNICA 2008
| pag. 5
Our attitude in fundamental
research
No thematic steering – initiative of individuals and research
groups
Internal quality control based on peers and correlated with
bibliometry
Depth of the project reviewing process depending on the
level of research:
- Seed level: quality of proposal; starters investement
- Incubation level: matching of externally acquired
funds
- Excellence level: external peer review
Dubrovnik-UNICA 2008
| pag. 6
The students !
Student ‘practicum’ immunology:
? blood of the teaching assistant to isolate antibodies
-> ‘80s: students refuse out of fear for hiv contamination
? collect blood from a mouse
-> experiment already done several times, no useless killing
The research group ‘sleeping disease’
received blood samples from camels from
Mali:
Dubrovnik-UNICA 2008
| pag. 7
use of some camel blood for the experiment
Investment in talent &
technology
Investment in new talent –
important motivation of R&D
Research in university context
ensures crossfertilisation
education/research
Dubrovnik-UNICA 2008
| pag. 8
The discovery !
Results: not as expected
•possible reasons:
•the
students have done something wrong
•there’s something wrong with the blood samples
•there’s something else going on
•possible solution:
•ignore
these results
conduct
further research on fresh camel blood
•the results:
cameloïds posses a different kind of antibodies
Dubrovnik-UNICA 2008
| pag. 9
What they found: nanobodies®
Fv
CH2
Fc
conventional antibody
CH3
CH2
Fc
camel heavy-chain
antibody
single domain
antigen binding
NANOBODY®
fragment (15 kDa)
CH3
Dubrovnik-UNICA 2008
| pag. 10
Hamers et al., Nature, 1993
Spotting the value
Laboratory:
: constant shortage of cash
Not
yet in an era where ‘publications’ were an
absolute must for researchers
Seeing
the possibilities of the camel
antibodies:
file a patent, before publication!
Dubrovnik-UNICA 2008
| pag. 11
Patent and publication
‘Hamers1’ patent was
filed
(Hamers, Casterman)
Immunoglobulins devoid of light
chains (priority date 21/8/1992)
Publication in Nature.
1993 Jun 3;363(6428):446-8
Luckily, in this order !
Dubrovnik-UNICA 2008
| pag. 12
Patent portfolio: valorisation @ vub
Patent costs soon became considerable:
inventors turned to the VUB
•
•
•
•
21/8/1992 ep19920402326 immunoglobulins devoid of light chains
29/4/1993 ep19930201239 production of antibodies or (functionalized) fragments
thereof derived from heavy chain immunoglobulins of camelidae
2/8/1993: fr19930009511 recombinant vector containing a lipoprotein gene sequence
for expressing nucleotide sequences
25/4/1995: ep19950400932 variable fragments of immunoglobulins - use for
therapeutic or veterinary purposes + ......
Agreement on transfer of the patent to the VUB
(1995):
no framework or ruling existed regarding IP
a deal was set up to distribute possible income from
the patents
Dubrovnik-UNICA 2008
| pag. 13
Opportunity vs risk
The university was unexperienced
• no specialised technology transfer cell
The researchers were unexperienced
• starting negotiations without a non-disclosure
agreement
• company starts filing patents around the nanobody
technology
-> licence-agreement VUB - Unilever (1997) on
‘non-healthcare’ applications
Dubrovnik-UNICA 2008
| pag. 14
Flemish Institute of
Biotechnology
Start of the VIB (Vlaams
Instituut Biotechnologie): 1997
www.vib.be
Raymond Hamers’ lab becomes
a VIB-department
Agreement VUB-VIB
• VIB takes the lead in commercialisation
• Income distribution system
Dubrovnik-UNICA 2008
| pag. 15
VIB-Virtual research institute
•
Virtual institutes, cherishing the best talents without fragmentizing or
duplicating efforts and investments
•
Advantages
•
- light weight central administration dedicated to specific R&D theme
•
- research is done by university partners, residing in their local labs talent creation for the sector
•
•
•
- the best from each research domain are involved
•
- balanced/mixed leadership between industry and university
•
- Coherence of action
•
- Very high R&D performance
- bridging gaps between different monodisciplinary research domains
Dangers
•
- Unique entry point for all R&D rules for new entries and exits of research groups
•
- Balance between internal competition and collaboration
1
Creation in 2001 of the
spin-off Ablynx
• Licence to Ablynx: diagnostics & therapeutics
• 5 mio € capital
www.Ablynx.com
• External CEO (Mark Vaeck) + 4 researchers VIB/VUB
• Start of several government-funded research projects
with VUB/ VIB department
• Ablynx becomes a biopharmaceutical company that
further develops the Nanobody ® Technology
Dubrovnik-UNICA 2008
| pag. 17
Company history and
milestones
Ablynx established by VIB and
GIMV
Hennie
Hoogenboom joins
as CSO
Mark Vaeck joins as CEO
Grant by VIB of rights to the
Nanobody technology and
patent portfolio for all human
and animal healthcare
applications
Collaboration with
Novartis
2002
2003
2004
Collaboration with P&GP
Raised €25mm from Alta
Partners and existing
shareholders
Edwin Moses joins as Chairman
of the Board
Dubrovnik-UNICA 2008
| pag. 18
Josefin-Beate Holz joins as CMO
Awarded €1.9mm grant to develop new
therapeutic applications of Nanobodies
2005
2006
2007
Achieved first milestone and extended scope of
P&GP collaboration
Began research operations
€3mm from Sofinnova and
Gilde
€206mm collaborative agreement with
Boehringer Ingelheim for AD
€1.3bn collaborative agreement with
Boehringer Ingelheim
€2mm seed money
2001
First clinical trial of Nanobody (ALX0081)
Edwin Moses becomes CEO, Wim Ottevaere
joins as CFO, Eva-Lotta Allan joins as CBO
Raised €40mm from KBC Private Equity,
SROne and existing shareholders
Collaboration with Wyeth—$212.5mm
licensing agreement on TNFα
Moved into new facilities (Ghent)
Ablynx history
Currently over 160 employees
Successful IPO on Euronext Brussels (ABLX)
Nov 7th 2007
Extensive and actively managed IP portfolio: over 200
patent applications and patents in more than 50
patent families worldwide
Active protection of know-how and trade secrets
Trademarks: nanobody™ and nanoclone™
Dubrovnik-UNICA 2008
| pag. 19
Ablynx business model
Pipeline development strategy
•
•
•
internal programs focused primarily on clinically
validated targets
target selection based on commercial opportunity,
nanobody competitive advantage and freedom to
operate
opportunistic therapeutic area focus
Partnering strategy
Dubrovnik-UNICA 2008
| pag. 20
•
Collaborate selectively on the development and
commercialization of certain Nanobodies
•
Provide exclusivity on targets rather than
indications or therapeutic area
Established partnerships with industry leaders
Partnering rationale: Exploit the
platform’s full capabilities across
multiple therapeutic areas (restricted to
just 10 different Nanobody therapeutics)
Deal value: €1.3bn; €75mm during the
research term. Development milestones
of €125mm per therapeutic program,
and royalties
Type: Worldwide research and licensing
agreement
Field: Human therapeutics
Ablynx product rights: Certain European
co-promotion rights
Year: 2H 2007
Partnering rationale: Specialist in
Alzheimer’s disease, strong biological
manufacturing expertise
Deal value: €206 million (excluding
royalties). Upfront, development and
commercial milestones, FTE funding
and royalties
Type: Worldwide research and
licensing agreement
Field: Target in Alzheimer’s disease
and all other human therapeutics
Ablynx product rights: None retained
Year: 1H 2007
Partnering rationale: External validation of the
technology platform
Deal value: Not disclosed. R&D funding, R&D
milestones and royalties
Type: Worldwide research and development agreement
Field: Targets in musculoskeletal indications and all
other human therapeutics
Ablynx product rights: None retained
Year: 2004 & 2006
Dubrovnik-UNICA 2008
| pag. 21
Partnering rationale: Partner has
specific TNFα expertise (Enbrel®), and
broad therapeutic area expertise.
Deal value: $212.5 million (excluding
royalties) Upfront, development and
commercial milestones, FTE funding
and royalties
Type: Worldwide licensing agreement
Field: Exclusive rights to TNFα
Nanobodies for all human therapeutics
Ablynx product rights: None retained
Year: 2006
Partnering rationale: External validation and
evaluation of platform across a range of targets
Deal value: Not disclosed. Deal includes up-front
payments, R&D payments, license fees, milestones
and royalties.
Type: Collaborative research program, exclusive
license agreement on a target-by-target basis
Field: Multi-target
Ablynx product rights: None retained
Year: 2005
The learning process...
Learning curve
– for the university
– for the scientists ....
... has lead to a valorization policy at the
university, a regulation comprising IP
management and income distribution
and ... professionalization of the
technology transfer interface cell
Dubrovnik-UNICA 2008
| pag. 22
Knowledge management
Technology transfer Interface
Multidisciplinairy team
(3FTE in 1999 -> 10 FTE + 4 consultants today)
Legal support contract research
Patent management & info-source (Patlib)
IP and contract managment
Creation of an entrepreneurial spirit (researchers, students...)
Spin-off creation
BI3 Fund (seed capital fund)
Research parks
Incubators IICB– ICAB
Industrial Network- Crosstalks
Dubrovnik-UNICA 2008
| pag. 23
Patent portfolio of the
Vrije Universiteit Brussel
www.vub.ac.be
> 50 patent families (application) VUB
> 20 patent families (application) with IMEC
(Interuniversity institute for Micro-electronics)
> 10 patent families (application) with VIB
(Flemish Interuniversity institute Biotechnology)
•Several patent families (application) with
other research institutions and industry
More information on technology offers: www.vub.ac.be/valorisatie
or contact
Dubrovnik-UNICA 2008
| pag. 24
[email protected]
Output indicators
Patents per FTE-professor: VUB ranks 3rd in Flanders
0.25
IOF parameter 5 (2001-2005) / # VTE ZAP 2005
0.2
0.15
0.1
0.05
0
KUL
Dubrovnik-UNICA 2008
| pag. 25
UH
UA
UG
VUB
BI3 Fund
Imagination- Incubation- Innovation
Aim:
Provide seed capital for VUB spin-off
companies
Partners:
Fortis Private Equity, KBC Private
Equity, Ethias Leven, GIMB, VUB
Value:
6 mio Euro (extendable to 12 mio Euro)
Obtained in 2006 VINNOF recognition
Participations:
Dubrovnik-UNICA 2008
| pag. 26
Elsyca, BruCells, Symbion, Eggcentris
21 spin-offs of the
21 spin-offs
Vrije Universiteit Brussel
Dubrovnik-UNICA 2008
| pag. 27
Output indicators
Spin-offs per FTE-professor: VUB ranks 1st in Flanders
aantal opgerichte spin-offs (2001-2005) / # VTE ZAP in 2005
0.03
0.025
0.02
0.015
0.01
0.005
0
KUL
Dubrovnik-UNICA 2008
| pag. 28
UH
UA
UG
VUB
Incubators of the
Vrije Universiteit Brussel
Brussels: ICAB
Incubator Arsenaal Brussel
Near campus Etterbeek
Operational in 2008
Flanders: IICB
Innovation & Incubation center Zellik
Near campus Jette
www.iicb.be
www.vub.ac.be
Dubrovnik-UNICA 2008
| pag. 29
Research at of the
Vrije Universiteit Brussel
www.vub.ac.be
Partner for industry:
* Medium to long term
research projects
* Contract research
* Consultancy and testing
facilities
* Training & industrial
residents
Contact the technology transfer interface
[email protected]
Dubrovnik-UNICA 2008
| pag. 30
Crosstalks
the VUB industry- university network
Creating an exchange dynamics
Encouraging cross-talking and stimulating innovation
Through different formats
And international publications
Conferences, science & industry lunches, workshops...
•Windows by Day, Linux by Night: open source paradigma
•The Future of Technology
•The Future of our Digital Commons
•Early Warning Signals
•Grenzen van de Geneeskunst
•Early Warning Information Systems
•The Future of Medication in a Patient-Centered Health Care
•.........
http://crosstalks.vub.ac.be
Dubrovnik-UNICA 2008
| pag. 31
Technological entrepreneurship
education program
Introduce technological entrepreneurship in the Masters
Engineer
<->
Business engineer
Courses
Business administration
Entrepreneurship
<->
<->
Technology
Entrepreneurship
for Bus.engineers
Writing of a business plan
Start up of a student business
via ETC (Entrepreneurial Talent Corporation)
Partners
PMV, Yakult, Ethias, WTCM, IBM, Fundus, Bank De Groof,
Solvay, Bekaert, Tyco Electronics Raychem,...
Dubrovnik-UNICA 2008
| pag. 32
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
Sketchy Technology Life Cycle
Program driven
Joint
research
Generic
technology
Embryonic
3
Project
driven
Proprietary
Industrial
Product
Potential
growth
Growth
Mature
Aging