Creation and Implementation of New

Knowledge
In Technology and Medicine
James C. Willey, M.D.
Professor of Medicine and Pathology
George Isaac Professor for Cancer Research
University of Toledo Health Sciences Campus
Topics of Presentation
Importance of innovation and patent protection
Driver of Economic Growth
Must be fostered federally and regionally
Biotech innovation is a key driver of recent
innovation boom.

Development of Lung Cancer Screening Method
The debate over implementation (re-imbursement)
Possible way forward

Innovation and Individualized Medicine
Each cancer
has different genetic alterations
Responds to different gene specific treatment


University of Toledo College of Medicine
Mission Statement
The UT College of Medicine and Life Sciences is
here to improve the human condition.

We do this by providing a world-class education
for the next generation of physicians and
scientists, and by creating knowledge that is
translated into cutting edge clinical practice and
research.

United States Constitution
ARTICLE I, SECTION 8, CLAUSE 8
The Congress shall have Power To...promote the
Progress of Science and useful Arts, by securing for
limited Times to Authors and Inventors the
exclusive Right to their respective Writings and
Discoveries....
Patent Act of 1790. The first patent statute passed by the
federal government of the United States. Enacted on April
10, 1790. It granted the applicant the "sole and exclusive
right and liberty of making, constructing, using and vending
to others to be used" of his invention

Goal: Better management of inventions created
through $75 billion a year in R&D spending.
Government had accumulated 28,000 patents but
fewer than 5% commercially licensed.
Government had ramped up spending on R&D on the
basis of a key report stating importance of scientific
progress to security, better health, higher standard of
living, and cultural progress.
However, policy was government would retain title to
inventions and license them only nonexclusively.
BayhDole Act 1981
Brookings Institute: Metropolitan Policy Program, 2013 Report

Rate of patenting in US increasing recently and now at historically high levels
Patented inventions are a driver of long-term regional economic growth
Research universities play an important role in driving innovation.

Key conclusions:
The federal government should establish and maintain a sound platform for
innovative activity
Aim for federal R&D spending (e.g. grants) at 3% of GNP.
Increase tax reduction incentives for private industry R&D to 20% from current rate of 14%
Regions and their states must foster innovative activity
Target resources to address discrete gaps in regional innovation systems performance.
take steps to intensify workings of regional innovation clusters.
Headwall at
Tuckermans Ravine
circa 1937
Played a leading role in
formation of Medical
College of Ohio
Biomedicine & Health Care
Translational Health and Bioscience

Advanced Energy
Advanced Renewable Energy and the
Environment

Advanced Transportation & Aerospace
Transportation and Logistics
Ohio's Centers of Excellence
University of Toledo
U.S. Patents/Capita
Patents/capita directly related to productivity
Productivity directly related to wealth
Quality of patents is a key factor. Metrics:
How often cited
Number of claims/patent


Brookings Institute Patent Report
Rothwell et al, 2013
Patents/capita directly related to productivity
Productivity directly related to wealth
Patents/capita rising rapidly and near historic record high
Quality of patents is increasing
Patent quality metrics
Citations within 8 years
Number of claims

Technology Transfer
Willey patents licensed to two
companies
Gene Express, Inc.
Founded 1992, declared bankruptcy 2010
Toledo; 2001-2006
Accugenomics
Founded 2010
Wilmington, NC
Revenue now increasing
Brookings Institute Patent Report
Rothwell et al, 2013
Patent quality metrics
Citations with 8 years
Number of claims
Willey 5,639,606; granted 1997;
has been cited 82 times, 50 times in last two years.


Lung cancer remains the top killer according to 2013
American Cancer Society.
Kills more than Breast, Prostate, and colon cancer combined

The Lung Cancer Problem

Lung Cancer Death Rates
Ohio Among the Highest in US

Cancer is an Acquired Genetic Disease
Normally, each individual comprises trillions of
cells in a highly organized organ system.
A cancer is born when a certain set of genes
mutates in a single cell
That cell then replicates in uncontrolled fashion,
disrupts the organization and harms the host.
Cancer is not one disease
Each cancer started with mutations in a
certain set of genes from a group of known
candidates (a few hundred of the 20,000)
It is essential to determine which of these
genes is altered in each individual tumor

Recognition for
Developing Standards
for measuring gene
activity
CT scans before and after erlotinib therapy (targets EGFR gene).
Pan M et al. (2007) CNS response after erlotinib therapy in a patient with metastatic NSCLC with an EGFR mutation Nat Clin Pract
Oncol 4: 603607 doi:10.1038/ncponc0931
Why is it important to identify which
known cancer genes are altered in
each tumor?
Because there are effective gene targeting treatments
CT scans before and after crizotinib therapy
(targets RET, ALK, and ROS genes)
Eleanor Dana Cancer Research Center
Research that will improve future
Funded by >$500,000 from National Cancer Institute to develop
more sensitive and accurate tests for genetic biomarkers for
lung cancer individualized treatment
Advance in Diagnostics:
Less invasive diagnostic testing
Transthoracic fine needle aspirate
Endobronchial ultrasound (EBUS)
needle aspirate
Challenge in Diagnostics:
Fine needle aspirates yield
small samples
There is need for more sensitive
diagnostic methods
UTMC-IELCAP
Lung Cancer Screening Clinic
Establishment of Lung Cancer
Screening Clinic

Rationale: Lung cancer is fatal in 95% of cases because it is
advanced when diagnosed
Asymptomatic until it is too late
Annual CAT scan of chest reduces lung cancer mortality >20%
(New England Journal of Medicine, 2011)
By catching cancer early when surgically curable

Through support from George Isaac Cancer
Research Fund
UT has established an International
Early Lung Cancer Action Program
(I-ELCAP) site at the University of Toledo
This subsidizes CT scans to
affordable rate
We will enroll at least 500
subjects/year


Lung Cancer Alliance
Praise for UT Lung Cancer Screening Program
Letter to Representative Kaptur

Eleanor N. Dana CancerCenter
Research that will improve future
Development of test to identify who is at
greatest risk for lung cancer

This laboratory has identified a genetic test that is associated
with diagnosis of lung cancer (Blomquist et al, Cancer
Research, 2009).
This test
has potential to identify the 10% of heavy smokers who are at greatest
risk for developing lung cancer
Is now in an NIH-funded multi-site clinical validation trial
University of Toledo, Toledo Hospital/Promedica,
Mayo Clinic, Cleveland Clinic, Ohio State University, Vanderbilt
Results are expected in 2-3 years
If validated, the CT screening can be provided to those at greatest risk,thereby
Reducing cost from $5 billion/year to $0.5 Billion/year
Reducing risk from unnecessary procedures


George Isaac Cancer Research Laboratory:
J Willey, P.I.
Lab Personnel: Erin Crawford, M.S., Tom Blomquist, M.D./Ph.D., Lauren Stanoszik, M.D./Ph.D. candidate, Ji Yeo, Ph.D.
candidate, Xiaolu Zhang, Ph.D. candidate
Maumee Valley Interns (since 2010): Casey Spitzer, Paige Willey, Thad Woodard
College Intern (MV graduate): Karan Padda
Scientists of the future: Katie and Seth Crawford, Nolan and Cole Blomquist