Personalized Medicine/ Diagnostics/ Chemical- Complex Ecosystems Produce Various Strategies Connecting IP with Products and Services AIPLA Mid-Winter Institute January 31, 2013 Natalie Wright Curley, JD Managing Director, Office of Technology Commercialization

MD ANDERSON BACKGROUND Established in 1941 by the Texas State Legislature and matching funds from Monroe Dunaway Anderson. One of the nation’s original three comprehensive cancer centers designated by the National Cancer Act of One of 41 National Cancer Institute-designated comprehensive cancer centers. In 2011, MD Anderson marked its 70-year anniversary and welcomed Ronald DePinho, M.D., as the fourth full-time president in the institution's history. Ranked as the best hospital in the nation for cancer care 8 out of the past 10 years by US News and World Report. Currently employs more than 19,000 people, including 1,600 faculty.

Our Mission To eliminate cancer in Texas, the nation and the world through outstanding programs that integrate patient care, research and prevention, and through education for undergraduate and graduate students, trainees, professionals, employees and the public.

Patient Care FY 2012 *115,000 patients seen, nearly 1/3 new patients Hospital admissions 26,726 Hospital patient days 191,735 Average number of operating beds 616 Outpatient clinic visits, treatments and procedures 1,281,489 Pathology and laboratory medicine procedures 11,619,591 Diagnostic imaging procedures 497,660 Surgery hours 66,241 Active clinical research protocols 1,078

MD Anderson Locations MD Anderson Radiation Treatment Center in Istanbul at American Hospital (Turkey) Centro Oncológico MD Anderson International España (Madrid, Spain) MD Anderson Radiation Treatment Center at Presbyterian Kaseman Hospital (Albuquerque, NM) MD Anderson Cancer Center-Orlando (FL) Banner MD Anderson Cancer Center (Gilbert, AZ) MD Anderson Cancer Center Main Campus, Houston, TX

TEXAS In addition to MD Anderson’s main campus in the Texas Medical Center in Houston, multiple regional care centers:  Regional Care Center in the Bay Area (Nassau Bay)  Regional Care Center in Katy  Regional Care Center in Sugar Land  Regional Care Center in The Woodlands Two research campuses in Bastrop County, Texas

Research funding FY 2011 Federal grants and contracts$196,753,104 Private industry grants and contracts$68,413,794 Philanthropy and foundations$100,794,491 Internal funding$241,560,330 State funding$40,019,178 Total research funding$647,540,897

Of MD Anderson’s total revenue of $3.7 billion in FY12, only 4.6% was general revenue appropriated by the State of Texas. Sources of Revenue (in millions)

Obtain invention disclosures from faculty; Evaluate for patentability and commercial potential; Oversee patent drafting and prosecution; Out license discoveries for commercial development and sale; Create new companies to commercialize university technologies; Goal: generate revenue to contribute back to mission! Office of Technology Commercialization

Patient demand; Shorter time to market (especially compared to those difficult therapeutic approvals!!!); Better technologies at cheaper costs; Money easy to get; Patient samples available.  Personalized Medicine! As a result, we saw a surge in “diagnostic discoveries.” Diagnostics on the Scene!

Before 2010After 2010 Invention Disclosures (average 134/year)

There is a need, BUT…. Markers are changing and under debate. If new/better biomarkers are identified, how can these be validated and included on an existing panel? Cost? Regulatory approval? Tests often stratified by disease type; diagnostic; prognostic; predictive…not a one size fits all market. Regulatory uncertainty—not clear what the FDA will require. Patentability issue…Supreme Court ruling on Prometheus has cast a cloud over the patentability of diagnostics in general; Myriad to be heard by SC. Potential infringement of previously issued patents/FTO. Reimbursement not certain. Indicated course of treatment may still not be clear. Funding is difficult. Hmmm….Diagnostic “Market” Issues

CURRENT PRACTICE Patient treated based on original biopsy CHALLENGE Patient outcome is determined by metastatic tumor Does the primary tumor represent metastatic or recurrent tumor? Are there subclones in the primary tumor? Are they selected by the metastatic process? Does it matter? Diagnostic “Technology” Issues

Assay Loss Gain Discordance PTEN10% (5/46)15% (8/46)25% PIK3CA 8% (4/21) 8% (4/21)16% marked change8% (4/21)12% (6/21)20% ER (38) 7% (4/38) 0% (0/38) 7% PR12% (7/38) 3% (2/38)15% HER22% (1/12) 2% (1/12) 4% *n=51 tumors and 56 metastases Ana Gonzalez; Funda Meric; Kat Hale Heterogeneity and Molecular Evolution PrimaryMetastasis

Breast Cancer PIK3CA (Exon 9/20 only) 48% discordance between primary and metastasis Example Primary WT Metastasis #1 H1047R Metastasis #2 E542K Deep sequencing of primary tumor may identify mutations HETEROGENEITY: DO DIFFERENT SUBLCONES METASTASIZE TO DIFFERENT SITES Jensen et al. 2011E542K

WHAT CLONE FREQUENCY MATTERS FOR PATIENT OUTCOMES???? Drivers and passengers: Specific mutation matters Functional genomics program How do we know which mutations are functional drivers and which ones are noise? (More of a problem as more genes are examined and we expand to whole exome sequencing.) Current offerings only tell us which genes are mutated, not which ones are functional. Functionality

HOW CAN WE DEVELOP A MODEL THAT ADDRESSES THESE ISSUES????? Panels; Functional information; Better biopsy technologies; Improved certainty from regulatory and legal/PTO landscape; Reimbursement criteria/economics. Opportunities