Universities role - global access to essential medicines UBC UAEM Introductory Seminars UBC Medical Student Alumni Centre October 13, 2007 Emma Preston

Access gap Ten million people die needlessly each year because they do not have access to existing medicines and vaccines Countless others suffer from neglected tropical diseases for which there is little financial incentive for drug development Quick, WHO, 2005 Research gap

Pecoul, PLoS Med Basic research published but preclinical research not considered worthwhile Validated candidate drugs don’t enter clinical development Drugs never reach patient: -registration problems, no production, high prices, drugs poorly adapted to local conditions

UBC Mission Statement “The University of British Columbia…will prepare students to become exceptional global citizens, promote the values of a civil and sustainable society, and conduct outstanding research to serve the people of British Columbia, Canada, and the world”.

The access and research gaps Comprehensive solutions are needed to increase both access to existing medicines and research on neglected diseases. Universities have an opportunity and a responsibility to take part in these solutions Universities are dedicated to the creation and dissemination of knowledge in the public interest. Global public health is a vital component of the public interest. Universities best realize their objectives when they promote innovation and access to essential medicines.

Universities are major contributors to “health-related innovations” Includes but not limited to: drugs vaccines diagnostics monitoring tools know-how and technical expertise

Universities are major contributors to drug development A recent report found that 15 of the 21 drugs with the most therapeutic impact were derived from federally funded projects at academic centres. Senate Joint Economic Committee 2000

Universities’ patent rights in key HIV/AIDS drugs on the market · Emtricitabine - Emory Emtriva ®, component of Truvada ® & Atripla ® · 3TC - Emory Epivir®, component of Combivir ®, Epzicom ® & Trizivir ® · Staduvine - Yale Zerit ® · Abacavir - Minnesota Ziagen ® component of Trizivir ® & Epzicom ® · T-20 - Duke Fuzeon ®

The landscape of R&D for neglected diseases Moran, PLoS Med, 2005 Universities are involved in 26/63 current ND drug projects (2005).

What do universities do with their research? Potential for commercialization? Decision to patent Usually just in high-income countries, given limited resources for tech transfer, but selection bias is important. Costs $12K-$15K to register a patent in a developing country (plus maintenance and lawyer’s fees) Followed by licensing to industry … often for further development (likely involving additional patents) and marketing of the invention “Upstream research”, improvement patents, exclusive deals Exclusive licenses generally used for products requiring additional development / deals with start-ups Universities receive royalties and/or other payments in exchange for the license.

University Industry Liaison Office “UBC's University-Industry Liaison Office (UILO) is a high performance team that guides breakthrough UBC research to market. UILO's services include facilitating collaborative research, protecting intellectual property, assisting in prototype development, licensing technology, creating spin- off companies, and providing educational programs.”

What do universities do with their research? Growth in patenting and commercialization:  1991 to 2004, ten-fold increase in number of U.S. patents applied for annually by U.S. academic institutions, more than two-fold increase in number of patents issued. AUTM U.S. Licensing Survey, FY 2004

Increase in U.S. Patenting and Commercialization: Bayh-Dole (1980) Goal: Increase technology transfer and utilization of federally- funded research What did it do? Universities given the right to OWN, LICENSE and MARKET the fruits of their research. Exclusive licensing permitted Special provision for the public domain (march-in rights) Growth in Patenting (faster than other patenting in the United States) Surge in Licensing Activity Increase in Royalties from Licensing

Increase in Canadian Patenting and Commercialization: Momentum Report. 2005, AUCC.

Increase in Canadian Patenting and Commercialization: Momentum Report. 2005, AUCC.

How can universities ensure that their innovations reach low and middle income populations?

The Case for University Action: A Brief History of UAEM Yale, MSF & d-4-t

In the mid-60s…

In the mid-80s…

In the mid 90s….

In 2001….

UAEM policy proposals Access Provisions in Licensing Agreements Neglected Disease Provisions Technology Transfer Metrics

Your handy dandy PCS…

What can universities do to promote access to essential medicines? Promote equal access to university research Require licensing terms in technology transfer agreements that ensure low-cost access to health-related innovations. Equitable Access License (EAL): allows generic companies to manufacture and export university innovations to developing countries. UAEM Policy Statement

Gener-X Patent The EAL

The Equitable Access License - Definitions Associated Licensee Rights: All rights in data, information, know-how, methods, procedures and processes, including patent and marketing rights, possessed by Licensee during the term of this Agreement that are necessary to make, use, sell, offer to sell, import or export an End Product or to perform Neglected Research, including but not limited to biological, chemical, biochemical, toxicological, pharmacological, metabolic, formulation, clinical, analytical and stability information and data. Associated Notifier Rights: All rights in data, information, know- how, methods, procedures and processes, including patent and marketing rights, possessed by a Notifier during the term of the Open License granted to such Notifier that are necessary to make, use, sell, offer to sell, import or export an End Product or to perform Neglected Research, including but not limited to biological, chemical, biochemical, toxicological, pharmacological, metabolic, formulation, clinical, analytical and stability information and data. Eligible Country: Any country classified by the World Bank as Low-income or Middle-income at the time a Notification is made. End Product: Any product whose manufacture or use relies upon or is covered by the Licensed Technology. Fair Royalty: i. For countries classified by the World Bank as Low-income at the time of the sales on which royalties are due, 2% of Notifier’s Net Sales of End Products in the Notified Country of Net Sales; ii. For countries classified by the World Bank as Middle- Income at the time of the sales on which royalties are due, 5% of Notifier’s the Net Sales of the End Products by the Notifier in the Notified Country in question. Licensed Technology: The rights licensed by the University to the Licensee pursuant to the Main Agreement. Neglected Disease: Any disease, condition, or affliction that, at the time Notification under Section 3.a. is made, either affects less than 200,000 persons in the United States or for which there is no reasonable expectation that the cost of developing and making available in the United States a treatment, prophylaxis, or device for such disease, condition, or affliction can be recovered from sales in the United States of such treatment, prophylaxis, or device. Neglected Research: Any use of the Licensed Technology or Associated Licensee Rights in an effort to develop treatments, prophylaxis, or devices for a Neglected Disease. Notification: A writing that announces the intention of a party to receive an Open License. Notification Fee: i. For Notification to receive an Open License to supply End Products to an Eligible Country that is classified by the World Bank as Low-income at the time of Notification, $5,000; ii. For Notification to receive an Open License to supply End Products to an Eligible Country that is classified by the World Bank as Middle- income at the time of Notification, $50,000; iii. For Notification to receive an Open License to perform Neglected Research, $500. Notified Country: An Eligible Country indicated by a Notifier in a Notification. Notifier: A party that has submitted a Notification to the University and Licensee along with an appropriate Notification Fee. Open License: A non-exclusive license to the Licensed Technology, Associated Licensee Rights, and Associated Notifier Rights granted by the University to a Notifier from University upon Notification. There are no limitations on the number of Open Licenses that may be received or the parties whom may receive an Open License..

2. Licensee Grant: The Licensee hereby grants the University a license to the Associated Licensee Rights for the sole purpose of granting Open Licenses either to Supply in accordance with Section 3.a. or for Neglected Research in accordance with Section 4.a.. The Licensee also agrees to include, in any patent application for a Licensee Improvement, a sentence reading: “This patent is subject to the provisions of the Equitable Access and Neglected Disease License.” 3. Notification to Supply a. Grant of Open License to Supply: Upon providing to University and Licensee Notification to receive an Open License to supply End Products to an Eligible Country, a Notifier automatically receives an Open License from the University permitting the making, using, selling, offering to sell, importing, and exporting of End Products in the Notified Country and the making and exporting of End Products in any country other than the Notified Country for the sole purpose of supplying End Products to the Notified Country. If Notifier exercises its right to make and export an End Product in any country other than a Notified Country for the sole purpose of export to a Notified Country, then Notifier shall use reasonable efforts to visibly distinguish the End Product it manufactures from the End Product sold distributed by the Licensee in the country of manufacture, but such reasonable efforts do not require Notifier to expend significant expense. b. Fair Royalties: The Open License to supply End Products received by Notifier shall be irrevocable and perpetual so long as Notifier submits to University and Licensee payment of a Fair Royalty on sales of End Products covered by the Licensed Technology or Associated Licensee Rights within 90 days of such sales, such Fair Royalty to be divided equally between University and Licensee. Failure or refusal of University or Licensee to accept the Fair Royalty shall not terminate or affect in any way the Open License. 3c. Notifier Grant: In exchange for receipt of an Open License to Supply, Notifier grants University a license to its Associated Notifier Rights for the sole purpose of granting Open Licenses either to Supply in accordance with Section 3.a. or for Neglected Research in accordance with Section 4.a.. 4. Notification for Neglected Research a. Grant of Open License for Neglected Research: Upon providing to University and Licensee Notification to receive an Open License to perform Neglected Research, a Notifier automatically receives a worldwide, irrevocable, and perpetual Open License from the University to perform Neglected Research. b. No Royalty: No royalty shall be payable to either the University or the Licensee for the Open License for Neglected Research. c. Notifier Grant: In exchange for receipt of an Open License for Neglected Research, Notifier grants University a license to its Associated Notifier Rights for the sole purpose of granting Open Licenses either to Supply in accordance with Section 3.a. or for Neglected Research in accordance with Section 4.a.. 5. Assurance of Freedom to Operate: No license or other transfer of the Licensed Technology or Associated Licensee Rights by the University or Licensee shall be valid unless the terms of this Equitable Access and Neglected Disease License are incorporated therein. 6. Transparency: Notwithstanding any other agreement or provision between the parties, either party may publicize the fact that the Licensed Technology and Associated Licensee Rights are subject to a license that includes this Equitable Access License. The Equitable Access License - Terms

Are you still following me?

Common Concerns about the EAL Hurts pharmaceutical companies: Black market Lost profit Industry won ’ t work with Universities, which hurts research

Importance of giving generic manufacturers the right to enter the market at the “source” TRIPS, The Doha Declaration & the WTO Aug 30th Decision Canadian implementation of the WTO Aug 30th Decision to allow compulsory licensing NOT EFFECTIVE. Pharmaceutical companies not registering drugs, like tenofovir, in developing countries. The enforcement of patents globally thereby blocking generic production (Abbott and Kaletra). Concern over the price of second-line ARVs and the limited mechanisms to lower the costs due to: India becoming TRIPS compliant Compulsory licensing not working There generally being fewer generic manufacturing options

What can universities do to promote access to essential medicines? Promote research & development for neglected diseases Promote in-house ND research; Engage with nontraditional partner to create new opportunities for ND drug development; Carve out an ND research exemption for any patents held or licenses executed. UAEM Policy Statement

What can universities do to promote access to essential medicines? Measure research and technology transfer success according to impact on human welfare. UAEM Policy Statement

How have universities tried to address the access and research gaps? Yale, d4t, and access-minded licensing Emory and Gilead Access Program for the HIV drug emtricitabine SLU Global Access Program Berkeley ‘Socially Responsible Licensing Initiative’ and Center for Neglected Diseases

Philadelphia Consensus Statement Stephen Lewis, UN Special Envoy for HIV/AIDS in Africa Paul Farmer, famous for his path-breaking work in Haiti Jeffrey Sachs, Earth Institute at Columbia University and Director, UN Millennium Project, “ The End of Poverty ” Edwin Cameron, South African Supreme Court Justice James Orbinski, Former President MSF Nobel Laureates (Dr. John Polanyi, Sir John Sulston, and Dr. Harold Varmus) Elizabeth May (Leader of the Green Party of Canada)

Philadelphia Consensus Statement Dr. Julio Montaner, Acting Director and Director of Clinical Activities of the BC Centre for Excellence in HIV/AIDS and Co-Director of the Canadian HIV Trials Network, recent President-elect of the International AIDS Society Dr. Bob Hogg, Director, HIV/AIDS Drug Treatment Program at the Center for Excellence in HIV/AIDS Dr. Bob Hancock, UBC infectious disease researcher, “ Gates Grand Challenges in Global Health ” funding Dr. Tom Perry, internist and clinical pharmacologist, MLA of British Columbia from 1989/96, Minister of Advanced Education, Training and Technology from 1991/93 Dr. David Ng, Advanced Molecular Biology Laboratory (AMBL),Michael Smith Laboratories, Director of Terry Project- UBC