Crossing Boundaries
The Do's and Don'ts of a Med School Professor
Starting a Business
• Traditional Academic World
– Goal: Understand and Communicate Something That Other People Can Learn
– Propose and Prove Hypotheses; Publications (Scientists)
– Inventions seem to appear “out of the blue” in this setting
• The Corporate World
– Goal: Make Something That Other People Can Use
– Deliverables and Applications Oriented; Products (Entrepreneurs)
– Innovations occur by collaboration and networking in this setting
• The New Translational Science
– Teach and Encourage Innovation
– Promote an Entrepreneurial Spirit
Invention
(Patent)
Innovator Steve Jobs
“Stay hungry. Stay foolish.”
Innovation
Henry Ford was an Innovator
Antigen Discovery Inc.
Antigen Discovery
Xiaowu Liang
Angela Yee
Doug Molina
Gary Hemanson
Andy Teng
Vu Huynh
Scott Weiss
Jiin Felgner
Pierre Baldi, UCI
Matt Kayala
Michael Zeller
Arlo Randall
Abe Lee, UCI
Armando Tovar
Arlene Doria
Maulik Patel
Peter Crompton, NIAID
Joe Vinetz, UCSD
Denise Doolan, QIMR
Angela Trieu
Robert Sauerwein, Nijmegen
Rob Hermsen
Carlota Dobano, Barcelona
Joe Campo
P. falciparum protein microarray
containing 4,528 proteins
USA Malaria
Naïve Adult
Naturally Exposed Resident of
Mali West Africa
Inventory of Cloned Genes, Proteins & Microarrays
Category
Retroviruses
Papilloma
Orthopoxviruses
Herpes Viruses
Flaviviruses
Alphaviruses
Bacteria
35,000
Arrays
Printed
25,000
Sera
Probed
Parasites
Human
Total # of
HIV 1&2 (5 clades)
HPV viruses (11 types)
3 types
HSV 1&2, VZV, EBV
WNV, Dengue, YF, SLE, JE
Chikungunya
Brucella melitensis
Chlamydia trachomatis
Chlamydia muridarum
Mycobacterium tuberculosis
Francisella tularensis
Coxiella burnetii
Borrelia burgdorferi
Burkholderia pseudomallei
Leptospira interrogans
Salmonella enterica thyphi
Orientia tsutsugamushi
Rickettsia ricketsii
Bartonella henselae
Clostridium difficile
Staphylococcus aureus (MRSA)
Streptococcus pneumoniae
Enteric toxogenic E. coli
Plasmodium falciparum
Plasmodium vivax
Schistosoma mansoni
Toxoplasma gondii
Cytauxzoon felis
Necator americanus
Trypanosoma cruzi
Trypanosoma brucei
Autoimmune array
Ovarian, Breast & Pancreas Cancer
A
C
B
C
A
B
B
B
C
B
B
Total #
proteins # cloned %proteome
100%
83
83
100%
88
88
100%
260
260
100%
300
300
100%
50
50
100%
10
10
100%
3,194
3,190
99%
911
900
99%
911
900
98%
3,990
3,899
97%
1,933
1,874
97%
2,065
2,000
97%
1,600
1,540
24%
5,728
1,400
100%
3,658
3,658
99%
4,318
4,300
100%
1,400
1,400
100%
900
900
100%
1,400
1,400
3,747
100%
3,747
95%
2,628
2,509
100%
2,200
2,200
100%
9,000
9,000
97%
5,643
5,400
60%
5,300
3,200
10%
9,000
900
30%
12,000
4,000
20%
4,300
850
5%
12,000
600
2%
15,099
240
3%
8,529
214
9%
21,000
1,800
"
"
62,812
$>18 MM STTR/SBIR Awards
STTR
1.
Vaccinia Proteome Affinity Reagents From Phage Display (NIH-NIAID, $1 million
/ 2y)
2.
Scanning Chlamydia Proteome for Vaccine Antigens (NICHD-NIAID, $600K / 2y)
3.
Scanning Chlamydia Proteome for Vaccine Antigens (NICHD-NIAID, $1.8 million/
2y)
SBIR
1.
Phage Display for antigen discovery (NIH-NIAID, $1 million / 2yr)
2.
Scanning the P. falciparum Proteome for Vaccine Antigens (NIH-NIAID, $600K /
2y)
3.
Adjuvants for Agile Vaccine Development (NIH-NIAID, $1 million / 2y)
4.
Multiplex Serodiagnostic Test for Lyme Disease (NIH-NIAID, $534K / 1y)
5.
Antibody profiles in single and mixed-species malaria infections (NIH-NIAID,
$600K / 2y)
6.
Serodiagnostics Chips for Biodefense and Emerging Inf. Dis. (NIAID-NCRR,
$3Million/3y)
7.
Protective Biomarkers for the development of vaccines against malaria (NIAID,
$2.3 Million/3y)
What are the tools of successful
Entrepreneurship? (Wollaeger)
Technology
Sustaining vs. Disruptive
Patents – a vocation, not inspiration
don’t have to appear out of the blue
Scientists and engineers can learn to invent
Capitol
Grants – SBIR/STTR
Contracts – NIH, Industry
Angels – ~$1M; 10X return in 10 yrs
Venture – ~$10M; 5X return in 5 yrs
People
Teamwork
Difference in Orientation & Scope
Between R01 and SBIR Grants
 R01 Grant

Understand and Communicate Something
That Other People Can Learn
 Small Business (SBIR) Grant

Make Something That Other People Can Use
SBIR Advanced Technology Grants
The SBIR Funding Opportunity
http://grants1.nih.gov/grants/funding/sbir.htm
Standard Funding Distribution
 Phase I - $100,000 for 6 months

Proof of Concept
 Phase II - $750,000 for 2 years

Commercial/Preclinical Development
Advanced Technology SBIR/STTR Grants
The SBIR Funding Opportunity (Expired Jan 8, 2014)
http://grants2.nih.gov/grants/guide/notice-files/NOT-AI-03-049.html
Vaccine and Diagnostic Discovery and
Development
Phase I - $600,000 for 2 years
Phase II - $3,000,000 for 3 years
Replaced with: Direct Phase II SBIR Grants to
Support Biomedical Technology Development
New SBIR Funding Opportunity
Must use a Small Business with prior SBIR experience
Vaccine and Diagnostic Discovery and
Development
Phase I - $600,000 for 2 years
Phase II - $3,000,000 for 3 years
Requirments to Qualify for SBIR/STTR Funding
 Small business <500 people
 <50% Venture Capital Equity Support
 SBIR: PI retains >50% employment in the small
business

60% $$ to small business / 40% $$ to UCI
 STTR: PI can be 100% with UCI

60% $$ to UCI / 40% $$ to small business
Accessing Small Business Grants &
Contracts at UCI
Commercial Distribution
& Licensing Agreements
New
Products
&
Services
UCI Lab
Technology, Staff
& Resources
Research and Development Supported by Small Grants
(SBIR & STTR) and by Government and Commercial
Contracts
An Active Example:
Davies/Guan/ImmPORT SBIR
Adjuvants for improved vaccines
Commercial Distribution
Contracts & Licensing
$550,000 / 2 yr
New
Products
& Services
$450,000 / 2 yr
UCI
Novel chemistry
Animal studies
Does & Don’ts
• Talk with the Office of Technology Alliances
• File a provisional patent application
• Start a small business
– Come up with a name and an aim
• Apply for SBIR grants
– Partner with an established small business
• Disclose everything on your Conflict of Interest
Forms
– Don’t try to keep secrets from the COI committee
Synthetic Gene Delivery Systems
Discovery of Lipofection: A highly efficient, lipid-mediated DNAtransfection procedure. (Felgner et al. PNAS 1987)
Nonviral Strategies for Gene
Therapy. (Felgner, Scientific
American, 1997)
Synthetic Gene Delivery Systems
Discovery of Lipofection: A highly efficient, lipid-mediated DNAtransfection procedure. (Felgner et al. PNAS 1987)
Nonviral Strategies for Gene
Therapy. (Felgner, Scientific
American, 1997)
From Invention to Innovation
Lipofectin & Lipofectamne
2013
2005
1991-2000
1988
1987
1985
• Discovery
• Draft Patent
application
• Publish in
PNAS
• Patent
issued
• BRL license
• Start Vical
Invitrogen $250 Million Annual Sales
of Lipofectin & Lipofectamine
Invitrogen is supporting 2,000 families
with income on sales of these
reagents
• Life Tech.
buys BRL
• In vitrogen
buys Life
Tech.
• Patent
expires
Naked DNA Gene Delivery
(Wolff et al. Science 1990)
Influenza Naked DNA
Vaccine
Protection against influenza by injection of
DNA encoding a viral protein
(Ulmer et. al. Science 1993)
100
% Survival
80
60
40
Control
Treated
20
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Days Post Challenge
From Invention to Innovation
Vical – The Naked DNA Company
2013
1998 - 2002
1996
1993
1990 - 91
1988
• Discovery
• Draft Patent
application
• Published in
Nature
• Merck
License
• Initial Public
Offering
IPO
• $350 million
• Patent
issued
• Move to
UCI
200 employees
Numerous clinical trials underway