Patent Pools As Public Health Meta Collaborations: the Experience of NIH and the Medicines Patent Pool

Steven M. Ferguson, CLP

Email: sf8h@nih.gov Deputy Director, Licensing & Entrepreneurship

NIH Office of Technology Transfer

Today’s Topic: Is There An Additional Way to Stimulate Innovation & Improve Access to HIV

Therapeutics?

‘3D’ INNOVATION

CYCLE

DISCOVERY • Lead identification / optimization • Basic research • Patents

DEVELOPMENT • Lead identification / optimization • Basic research & more patents

DELIVERY • Getting products to patients • Markets

Translational research

Market approval and manufacture

Demand for new / improved tools and post marketing research

Source: MPP & Public Health, Innovation and intellectual property rights (WHO)

But First A Word From Our Sponsor:

• Annual budget of $ 30.9 billion (FY12)

• ~10% of funding for intramural research

• 6,000 intramural scientists / 18,000 staff

• Basic & clinical research discoveries

• Partners commercialize into products !

• But what are “partners”?

What Exactly Do We Mean By “Partners” Anyway?

• Traditionally, this has been companies who have used licenses & other T2 mechanisms to help launch new products

• However, these “partners” are no longer exclusively companies!

• Example: PATH Meningitis Vaccine Project product launch – December 2010

Companies Have Launched A Number of Innovative HIV Products

Based Upon NIH Research • Videx® (ddI) – BMS & generics • Hivid® (ddC) – Roche • Prezista® (Protease Inhibitor)– Tibotec • HIV Test Kit – Abbott & many others • HIV Protease – genotyping assay; drug

target

• And hopefully future products via other non-company organizations --

Why Might A Patent Pool Be

Useful For HIV Therapeutics?

Source: MPP

Despite Progress There Are Still Significant Treatment Needs

Source: World Health Organization. Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector. http://www.who.int/hiv/pub/2010progressreport/summary_en.pdf and MPP

• > 6 million people in developing countries on ART by end of 2009

• But further 10 million people are in urgent need of treatment as per WHO guidelines

• An additional 18 million people are HIV positive and will need treatment

• 1.2 million new people on treatment in 2009, but 2.6 million new infections

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2009

Peop

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Will Need TreatmentIn Need of TreatmentTreated

• Generic competition central to treatment scale-up of past decade

Price of 1st line drug therapies down to under 1% of original price • Widespread patenting of newer drugs in developing countries

Limited generic availability and limited price reductions Differential pricing: not same impact on pricing as robust generic

competition • Promising fixed-dose combinations (FDCs) / formulations

often not developed WHO Committee on Essential Medicines has identified opportunities

• Financial crisis budgets for purchase of HIV medicines not growing

• Treatment Needs

WHO Treatment Guidelines (earlier start; drugs with less side effects) People in developing countries developing resistance to 1st line Special (unmet) needs of children with HIV

New evidence: HIV treatment prevents transmission of HIV

MPP’s Rationale Back For Establishing A Patent Pool

Source: MPP

Origins of Medicines Patent Pool: Integral Part of UNITAID's Strategy

A common goal : " improving access to quality, affordable, effective, well-

adapted HIV medicines in developing countries " A common market based approach:

Converging goals through a focus on market impact to lower the prices of medicines

Influence of global patenting on the medicines' market dynamics

Market incentives to channel the demand Bridging the gap between accessible and affordable Strategic use of intellectual property (changing

international rules that limit competition and lower cost production)

Source: UNITIAID

The UNITIAD Story Begins: The Air Ticket Levy

Contributions from 11+ countries 80% of UNITAID funds from air ticket tax 20% multi budgetary contributions

Applied to all fights departing from countries Amount can vary and decided by government

Around $US 1 domestic economy Over $US 40 business international Predictable, sustainable funding

UNITAID hosted & administered by WHO

Over US$ 2 billion raised since 2006 Source: UNITAID

94 Countries Receive UNITAID support Through Partnerships: WHO, UNICEF, STOP

TB, UNAIDS & Others

HIV / AIDS 49 recipient countries

Malaria 29 recipient countries

Tuberculosis 72 recipient countries

- Pediatric ARV - Second line ARV -PMTCT

US$592 m

- LLIN - ACT - AMFm

US$318 m

- First line TB - Pediatric TB - MDR-TB - Diagnostics

US$211 m Cross cutting programs: US$109 m for PQ of drugs & diagnostics and transversal programs

Source: UNITAID

MPP Public Health Vision

Medicines Patent Pool Mission

To improve access to appropriate affordable HIV treatments in developing countries

The patent pool will bring down the prices of HIV drugs, facilitate the development and production of improved

formulations (e.g., fixed dose combinations and pediatric and heat-stable formulations) by providing access to

intellectual property relating to these products

Why Would NIH Want to Work With The Medicines Patent Pool?

MPP Is Attractive To NIH Because of Public Health Vision & Mission:

Source: MPP

MPP Guiding Principles

1

2

3

4

5

6

7

8

9

10

11

12

13

Public health driven

Focus on HIV

Voluntary

Developing country focus (low & middle income)

Price reductions

Enable product development

Flexible

Quality assurance

Standardised licenses

Non discriminatory licenses

Additional / complementary to existing mechanisms

Operate within current intellectual property framework

Independent entity

Source: MPP

• Enable the development of fixed dose combinations (FDCs) of which the patents are held by different entities

• Enable the development of adapted formulations for children or for specific developing country needs (e.g., heat stable)

• Accelerate the availability of generic versions of new ARVs in developing countries

Three Main Objectives For MPP

Source: MPP

MPP Context: HIV/AIDS Market

• Low and middle income countries represent a small proportion of current global sales for HIV/AIDS (a fraction of 6%) and highly concentrated in a handful of countries.

• For 2nd and 3rd line drugs: less than 3%

• But over 90% of the disease burden

6%

94%

Global ARV Sales

Rest of theWorld

US + Europe

3%

97%

Global Sales 2nd and 3rd Line ARVs

Rest of theWorld

US + Europe

Source: MPP

Context: Patents on some new ARVs Product +/- Expiry date

Atazanavir (Novartis) 2017

Cobicistat (Gilead) 2027

Darunavir (J&J/Tibotec) 2023

Etravirine (J&J/Tibotec) 2019

Fosamprenavir (ViiV) 2018

GSK 572 –Dolutegravir (ViiV)

2026

Raltegravir (MSD) 2025

Rilpivirine (J&J/Tibotec) 2022

Ritonavir hs (Abbott) 2024

Tenofovir DF (Gilead) 2018

Maraviroc (Pfizer) 2019 Source: MPP

Pool

Sub-Licensee

Sub-Licensee

Sub-Licensee

Sub-Licensee

Sub-Licensee

Sub-Licensee

Sub-Licensee

Royalties

Royalties

Patents

Patents

Patents

Licensor

Licensor

Licensor

Licensor

Licensor

How the MPP Pool Works

Source: MPP

Patent Pool Partnerships • UNITAID:

– Initiated the Medicines Patent Pool project ’08 – Funds operations of Pool under a 5-year MOU

• WHO: – Medicines quality assurance (WHO PQ Department) – Identification of priority medicines (HIV/AIDS Dept.

and Expert Committee on Essential Medicines) • WIPO

– Licensing terms and conditions (co-organization of expert workshop in 2010)

– Arbitration – Patent status information

• Many others (WTO, Global Fund, UNAIDS, ANRS, EPO, MSF etc.)

Source: MPP

HIV Medicines Patent Status Database

• The WIPO and the National Patent Offices have provided/verified the patent status information

• Public resource for HIV drug development

Source: MPP

Medicines Patent Pool: Progress to Date • The Medicines Patent Pool opened in 2010, and a dialogue

has been opened with all known patent holders • The NIH became the first to license patents to the Pool • Negotiations on terms and conditions are on-going with

other potential licensors • Consultations have also been held with generic

manufacturers • External legal / licensing experts in collaboration with WIPO • Prioritisation based on latest scientific evidence in

collaboration with the WHO and UNITAID • Continued engagement with governments in developing and

developed countries • Information about and produced by the Pool made available

on the website

Source: MPP

MPP: Recent Developments Gilead Sciences: tenofovir (TDF), emtricitabine (FTC), cobicistat (COBI), elvitegravir (EVG) & Quad [a combination of TDF, FTC, COBI, and EVG].

MPP secured its second license agreement from Gilead Sciences in July 2011. It was the first agreement the Pool has made with a pharmaceutical company patent holder.

MedChem: tenofovir (TDF), emtricitabine (FTC), cobicistat (COBI), elvitegravir (EVG) & Quad [a combination of TDF, FTC, COBI, and EVG].

In July 2011, MedChem became the Pool's first generic company sublicensee. MedChem is a new player in the HIV field. Attracting generic producers will help increase production capacity.

Aurobindo Pharma Limited: emtricitabine (FTC), cobicistat (COBI), elvitegravir (EVG) & Quad [a combination of TDF, FTC, COBI, and EVG].

In October 2011, the Pool signed a sublicensing agreement with key generics manufacturer Aurobindo.

MPP: Recent Developments Larus Laboratories: tenofovir (TDF), emtricitabine (FTC), cobicistat (COBI), elvitegravir (EVG) & Quad [a combination of TDF, FTC, COBI, and EVG].

In November 2012, MPP signed a sublicensing agreement with another key generics manufacturer Larus Laboratories.

ViiV Healthcare: abacavir for pediatric AIDS.

In February 2013, Viiv Healthcare -- a joint venture of GlaxoSmithKline, Pfizer, and Shionogi –- agreed to facilitate greater availability of critically needed medicines by MPP for children living with HIV. Abacarvir included now -- new pipeline products in the future.

Shashun Pharmacueticals: emtricitabine (FTC), cobicistat (COBI), elvitegravir (EVG) & Quad [a combination of TDF, FTC, COBI, and EVG].

In March 2013, the Pool signed a sublicensing agreement with another key generics manufacturer Shashun Pharmaceuticals.

MPP Open Letter: Key Elements of Licenses

. • Licenses will be for products needed for the treatment & prevention of

HIV/AIDS. • Licenses will be available on a non-exclusive and non-discriminatory basis to

qualified entities to enable the production and development of HIV medicines, including adapted formulations and fixed dose combinations, for use in developing countries.

• Licensors will be compensated through royalties. Reasonable rates of remuneration that take into account different countries' ability to pay, disease burden, and other relevant factors, will be considered in an effort to expand the benefits of the licenses to as many low- and middle-income countries as possible.

• Licenses will include quality assurance provisions leveraging existing mechanisms (e.g. World Health Organization Prequalification Program, United States Food and Drug Administration tentative approval and European Medicines Agency).

• The Pool will operate in a transparent manner, in recognition of the critical nature of the public health issues at stake and the widespread public interest in its work. Therefore, the terms and conditions of the licenses will be made public.

Focus of MPP License Negotiations: NIH Patents Concerning Darunavir

NIH Patent: Methods of Use For Darunavir & Similar Compounds • Method claims only • Important for treating drug-resistant HIV • Joint invention with University of Illinois

– Chicago • Managed under NIH-lead Inter-

Institutional Agreement • Previously licensed non-exclusively:

Tibotec, Sequoia

Inventors For NIH Patent Rights

• John W. Erickson (NCI) • Sergei V. Gulnik (NCI) • Hiroaki Mitsuya (NCI) • Arun K. Ghosh (UIC)

NIH Licensed Patent Rights • US Application 09/720,226 – issued (7,470,506) • US Application 11/870,931 (pending) • Canada Application 2336160 (pending) • Australia Application 48280/99 – issued (7717880) • Australia Application 2004200629 (issued) • Australia Application 2007203321 (issued) • Japan Application 556057/2000 (issued) • Japan Application 266865/2009 (allowed) • EPO Application 99931861.1 (issued)

NIH License: Licensed Territory

• United States, Canada, Australia, Japan Austria, Belgium, Switzerland, Cyprus,

Germany, Denmark, Spain, Finland, France, Great Britain, Greece, Ireland, Italy, Liechtenstein, Luxembourg, Monaco, Netherlands, Portugal, and Sweden.

Licensed Fields of Use

• Treatment and prevention of medical

conditions affecting humans

NIH License: Term & Termination

This Agreement shall expire, on a country-by-country basis within the Licensed Territory, on the last to expire patent containing a valid claim, unless previously terminated under Article 7.

NIH License: Grant Of Rights

PHS hereby grants and Licensee accepts, subject to the terms and conditions of this Agreement,

a royalty-free nonexclusive license under the

Licensed Patent Rights in the Licensed Territory to make, have made, and to use, but not to sell the Licensed Products and Licensed Processes in

the Licensed Fields of Use for the purposes of supplying the Licensed Products in low and

middle-income countries, as defined by the World Bank.

NIH License: Right To Sublicense

Licensee may enter into sublicensing agreements under the Licensed Patent Rights, provided

that such sublicenses do not have a further right of sublicense and are granted in accordance with

the Development Plan as described in Appendix C. Sublicenses shall be issued without

discrimination to any sublicensee with the demonstrated commitment, ability and readiness to use the sub-license.

Support for the Medicines Patent Pool “We think that the Medicines Patent Pool is an important initiative towards achieving universal access to the newer HIV medicines….At WHO we will be pleased to give priority to any of the newly developed FDCs for assessment by our WHO/ UN Prequalification Programme in order to facilitate its rapid uptake by the funding agencies and national governments.”

Dr. Hans Hogerzeil, Director Essential Medicines and Pharmaceutical policies (October 2010)

“This license underlines the U.S. Government’s commitment to the Medicines Patent Pool and its goal to increase the availability of HIV medicines in developing countries. We are now discussing licensing to the Medicines Patent Pool other patents that could have a positive impact on the treatment of HIV/AIDS.” NIH Director Francis S. Collins, M.D., Ph.D.

“We urge all public institutions and pharmaceutical companies to follow the measures taken by the NIH, and to share without delay their patents on this and other antiretrovirals with the Medicines Patent Pool, in order to facilitate access to these treatments at the lowest possible price for countries in need

Prof. Kazatchkine, Executive Director Global Fund

"A successful patent pool will help in accelerating the scaling up of access to care and treatment and will reduce the risk of stock out of medicines in the developing world"

Michel Sidibe, UNAIDS Executive Director (July 2010)

"One promising initiative that can help decrease the cost of patents for the Index Countries is the patent pool initiative of UNITAID"

ATM Index 2010 (Engagement with PP included as one of the issues measured in the Index)

Source: MPP

Award Recognition: 2012 “Deals of Distinction™”

• One of the top national awards given for technology transfer activities • Citations for “an innovative endeavor in facilitating access to HIV treatment in developing countries“

• And “showcases the success of public-private partnerships to improve availability of medicine”

NIH and MPP: Lessons To Date

• Too early to tell if MPP will ultimately be successful – good start is continuing

• NIH license jump started the MPP to give credibility to effort

• Not a vehicle for major financial returns, but • NIH and MPP share key public health goals • Non-traditional partners important means

for NIH technology to developing countries