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.

Bayh–Dole 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 Tuckerman’s 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: 603–607 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