Lead Author: Andrea Lucard
Additional Author: Sylvie Fonteilles-Drabek
Organization: Medicines for Malaria Venture
Country: Switzerland
Abstract
Medicines for Malaria Venture (MMV) is a not-for-profit Swiss foundation that discovers, develops and delivers high-quality, low-cost anti-malarial medicines for the endemic world. Since inception in 1999, MMV and its partners have developed six new antimalarials; together with two drugs taken into our portfolio from DNDi, our drugs have enabled over 500 million courses of affordable, quality treatments for the world’s most vulnerable people.
We have developed and delivered these medicines within the current frameworks of intellectual property, and do not find that the current policy environment hinders creation and delivery of affordable products for neglected diseases. Instead, we have used the global policy environment—particularly patent protection—to
• Ensure appropriate freedom-to-operate in the development of these products
• Incentivize commercial partners to contribute resources and know-how
• Safeguard the quality of those products and,
• Stipulate co-investment, access and affordability of the products, using a strong contractual framework with our partners.
To make major changes in our operating model at this time could threaten our ability to help attain SDG3: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases . Given the on-going financial commitments made to us by public and private donors to attain this goal, changes of this sort would be of questionable value for money and, moreover, harmful to public health in developing countries.
MMV is one of a group of similar not-for-profit organizations focused on products for neglected populations known as product development partnerships (PDPs). These organizations have been responsible for many of the 485 products that are currently in the pipeline for diseases of poverty. Many of those products have intellectual property (IP) protection that is used creatively to guarantee quality, pricing and access.
Discussions with PDPs in other fields of poverty-related and neglected diseases indicate that experience from similar organizations can be used to compliment and strengthen these findings, should the panel choose this submission.
Submission
The Sustainable Development Goal 3b spells out clearly the requirement for the development of new health technologies:
“Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries, provide access to affordable essential medicines and vaccines, in accordance with the Doha Declaration on the TRIPS Agreement and Public Health”
Engaging in the complex, technical, expensive, and time-consuming process of product development requires actors from many sectors including researchers, academic institutions, biotech firms, pharmaceutical companies, NGOs, product regulators, international bodies and health ministries. This is particularly true for products for diseases of poverty, where market returns are very small or non-existent, and thus where a clear market incentive is insufficient to attract the major pharmaceutical players. In this arena, therefore, a set of processes has been built into the product development partnerships (PDPs), which use existing structures to fill the gaps in medical needs for diseases of poverty, and rely - and will need to continue to do so - on significant grant contributions. The lack of private sector investment is not a result of IP, but from so-called market failures, and IP is used proactively to unblock scientific bottlenecks or address other access concerns along the drug development and delivery continuum. This highlights the need for ongoing public investment to the most vulnerable people in societies around the world who get disproportionally by affected these diseases.
MMV’s IP management strategy for developing antimalarials
MMV was established as a foundation in Switzerland in 1999 with the mission to reduce the burden of malaria in disease-endemic countries by discovering, developing and delivering new, effective and affordable anti-malarial drugs. MMV's partners include academia and research institutes, the pharmaceuticals industry, country partners and not-for-profit organisations. Together, MMV and its partners have brought six new medicines to market, all of which are already being used to treat people across the globe and saving lives.
Developed and refined over the past 15 years, MMV’s IP management policy provides “freedom to operate” to MMV whilst also increasing the attractiveness of projects to future pharmaceutical company partners, whose skills and experience to develop, register and market drugs, especially in the complex clinical phases, is essential. Within a clearly defined ownership framework an Open Innovation model has also been evolved, to stimulate the discovery of hits and leads in the pre-competitive stages of R&D. Appropriate use of IP may also provide a mechanism to challenge the production of poor quality medicines, providing a parallel potential health benefit. This is laid out sequentially below.
Early stage R&D
MMV collaborations in early discovery work are very open and follow an ‘open source’ or ‘open science’ model. That is, very early stage R&D supported by MMV is open, with no assignment or ownership of Intellectual Property Rights (IPRs).
For subsequent development steps, a model of open innovation is employed, in which all IP is shared among partners within a circumscribed ‘closed’ framework whereby information circulates freely within the partnership, but is limited to the partnership. The 'Malaria Box' [Spangenberg, 2013 ] is a good example of an open access initiative operating as part of MMV’s wider IP strategy which can improve efficiencies in early stage R&D [Dimitri, 2011 ].
The Malaria Box’s open model facilitates access to large (industrial) chemical libraries so that scientists are not prevented from moving ahead in translating assays into new and exciting hits due to a priori IP considerations. A condition for access to the compound set is that data obtained with it are shared in the public domain; this ensures there are no obstacles to the rapid publication and use of results, which can happen in a more closed and traditional R&D model. MMV strongly encourages (mandates in the case of the ‘Malaria Box’) that results are published within a reasonable timeframe. This is therefore a situation in which 'Open Innovation' is the most productive model.
Mid-stage and later development
A protected compound is a valuable asset and therefore patent protection is often sought before entering the translation phase of development. Thus, as projects progress, the partnerships and related IP ownership structures become clearly defined among a unique combination of expert partners (Holmes, 2013) . IP ownership is usually shared if academia is involved (often with an assignment of the IP to MMV in order to facilitate future company engagement for the development phases), but if a pharmaceutical company partner is involved, it will tend to assume ownership.
Having clearly defined patent rights at this stage is critical to engage pharmaceutical partners or sustain company interest to develop the drug. In return, a sine qua non condition for pharmaceutical partners is an agreement to specific access terms for the developed products. In its agreements, MMV (akin to most other PDPs) defines the geographic scope, pricing scales and in which sectors a country will have preferential access to the technology (along with any other access issues pertaining to the eventual marketing of the drug) [Grace 2010 ]. In order to ensure that promising projects do not wither if a company partner walks away, MMV ensures that the IP rights are either transferred to MMV or licensed to MMV on an exclusive, worldwide (malaria), paid-up, royalty-free and sub-licensable basis.
In addition to guaranteeing access at the end point of drug development, this IP protection also helps to safeguard the pathway to regulatory approval, by guaranteeing that the data sets submitted to regulators are clear and not confused by parallel but not necessarily comparable clinical trial data sets that conform to Good Clinical Practice.
Enforcing patents
For each of the seven drugs supported by MMV currently in the market, patents have never been used to block the development of generics, and there are several generic versions currently on – or soon to enter - the market. However, if a sub-par generic copy were to be on the market, MMV would be able to invoke patent infringement against the unlicensed generic company in order to block the distribution of the unsafe medicine.
Simplified overview of the MMV IP strategy
For MMV (and other similar PDPs), patent protection has never driven prices up as clear affordability and accessibility principles are embedded in the development and commercialization agreements between MMV and its pharmaceutical partners.
In summary, the MMV IP management policy is modular: each development stage requires a different approach as different partners are involved. MMV works to open up early stage knowledge beyond specific organizational boundaries to enable scientific progress in the field of malaria research, while using patents as a driver of subsequent drug development to bring innovative treatments to malaria patients worldwide. It is an example of how ‘open’ models work in the pre-competitive R&D phase, whilst clear IP ownership models work in subsequent phases (Massum and Harris, 2011 ). In this context, IP is not at all inconsistent with a rights based approach to public health.
Conclusions regarding access to medicines and the PDP model of IP management
For many PDPs, although imperfect, the current IP framework is appropriate, giving certainty to patent owners but allowing rights to be waived or not asserted when desirable. This model respects the notion of health as human right for all and takes a pragmatic approach to solving innovation bottlenecks, providing the incentives, including patents, to partners when needed, whilst giving control to the PDP to achieve their ultimate objectives – the right medicines/technologies, delivered at the right time and at the right price to the people who need them most. Contractual agreements are used to ensure affordable access.
To sum up, “IP and open innovation are […] often complementary” : patents and other IPRs enable knowledge transfer and protection that stimulate innovation (The World Intellectual Property Report, WIPO, 2011 ). In the context of NTDs, while not a panacea, PDPs are an adept and proven approach to addressing the policy incoherence of concern to the High Level Panel on Access to Medicines. Through their IP strategies, PDPs can offer a safe-house for patents and the sharing of knowledge, stimulating efforts in identification of hits in early research phases and catalysing non-commercial but socially valuable projects through the R&D life cycle.
IMPACT ON POLICY COHERENCE: For the PDP model, there is no incoherence in rules between rights of inventors, international human rights laws, trade rules, and public health objectives. PDPs specifically address gaps in R&D for NTDs and ensure equitable pricing and access terms. For this subset of global health issues, they demonstrate that the policy incoherence identified by some commentators does not apply, as long as public funding is forthcoming and the IP framework is applied strategically. As Hotez et al (2013 ) note: “IP rights can also be used in nontraditional ways, for example, to maximize positive social impact of research results and encourage follow-on research without direct monetary returns to the owner (although they are not always mutually exclusive). IP rights are intangible; they can bring additional intangible benefits such as affiliation, reputation, and good will, and other valuable outcomes such as collaboration, diversification of research funding sources, and access to networks and tools. Importantly, IP rights can be used to create industry standards, including more-open standards.”
IMPACT ON PUBLIC HEALTH: Already, PDPs have been responsible for developing more than three quarters of the approximately 380 new products for NTDs that have reached the market since 2000 (Policy Cures, 2015 ). Strategic ownership of IP by MMV and its partners incentivizes innovation to address the diseases of poverty in at least two ways: i) by stimulating the free flow of knowledge in the earliest stages of R&D, where it is most necessary, enabling the basic scientific knowledge to be developed, and ii) ensuring private sector partners join partnerships (during and after translational research phases) to ensure that their resources and know-how are utilized. Furthermore, access provisions are built into all agreements, ensuring that affordability, availability and quality are standard outcomes. In this way, PDPs can address public health needs and achieve impressive results, such as the introduction of more than 43 new products for neglected tropical diseases by 2013 (GHTC 2013 ).
ADVANCING HUMAN RIGHTS: The PDPs’ primary mission is to advance global public health goals as a fundamental human right and pursue the attainment of SDG 3. Access to safe, effective and affordable medicines is a critical pillar of effective health systems. IP is an important incentive to engage private partners in PDPs to take candidates through the critical phases of product development that will ensure that new products become available. Without clear ownership rights, it is unlikely that private sector skills and know-how will be available to PDPs. With this commitment of private partners, the PDP is able to secure commitments to access to ensure that products will be affordable to those who need them most and produced to a high quality. Invoking patent infringement against low quality generic manufacturers also ensures people will have access to safe medicines. Use of the IP system in a strategic and access-oriented way enables the PDP model to advance the human right to health.
IMPLEMENTATION: PDPs have already secured large scale public financing and are a tried and tested model that has been yielding tangible results over the last 20 years (as noted earlier). Securing ongoing commitment to this approach is likely to be much easier than for completely new mechanisms for which the return on public funds may be uncertain. The Wellcome Trust showed that PDPs “have been responsible for increased neglected disease R&D activity and are proving superior in terms of time to market, cost-efficiency, health value and innovative level of the products, when compared with industry working alone and public groups working alone in neglected disease technology development” (cited in Grace 2010).
EVIDENCE: This submission has been based on evidence generated since the establishment of the PDPs. Although the PDPs do receive ongoing funds from a variety of public and not-for-profit sources, the model proposed is limited by the political will and economic feasibility of continuing to fund them.
Recommendations to the High level Panel
1. Recognise that there is currently a functional IP system for the research and development of diseases of poverty, provided that government and private donors continue to focus on entities that focus on diseases with little or no market value.
2. Recognise that PDPs using patents, co-investment and contractual agreements with commercial partners are currently working effectively to ensure attainment of SDG 3 by developing essential new products for NTDs.
3. Maintain a patents system that gives both flexibility and certainty for neglected disease research: IPR and global health policies need to be responsive and decision-oriented, yet predictable.
4. Recognise the value of a ‘sliding scale’ IP model, which can be applied by intermediaries such as PDPs and their partners on a case-by-case basis to guide R&D partners in deciding the strength of IPRs along the R&D pipeline, depending on the types of collaboration needed for particular tasks (and other criteria pertaining to the project). An example of this can be seen in the Lambert Agreements in the UK, which could potentially be adapted for global health purposes.
5. Promote non-exclusive voluntary licensing and other non-IP means to stimulate generic competition and increase efficiencies in medicines markets, with a clear role for not-for-profit and public sector third parties. This can include public funders globally, both bilateral and multilateral, to include more contractual safeguards on access, affordability and adoptability in science and innovation (grant) funding.
6. Review the case for some amendments to the patent framework - including patent quality and patentability criteria. More rigour is needed to prevent poor practices that may hinder innovation and access (Saha 2011) . These issues apply in other complex technology sectors and are not limited to global health (WIPO 2011), although they clearly have serious implications given that lives are at stake. Provisions outlined within the TRIPs agreement provide options to address access issues that may be created by IP.
7. Ensure that the pharmaceutical industry continues to play its role in conducting leading edge R&D, and accelerating access to medicines through:
- Tiered pricing policies which are based on affordability criteria
- Developing socially-responsible intellectual property management strategies
- Non-assertion of patents in LDCs and
- Working through public-private partnerships to help ensure sustainable improvements in healthcare delivery in poor countries.
Our submission clearly shows that with the right motives and with the right incentives the patent framework can be applied for the public good in an efficient and effective way. We nevertheless recognise that there are various examples where development of promising new health innovations has been held up for long periods of time or made impossible because patents made scientific and/or product development impossible and that additional measures may be needed to address delays in innovations for disease of poverty.
Bibliography and References
Dimitri, N. (2011). An assessment of R&D productivity in the pharmaceutical industry. Trends Pharmacol Sci, 32(12), 683-685
G-FINDER: Global Funding of Innovation for Neglected Disease, 2015 http://policycures.org/g-finder2015.html
Grace, C. (2010) Product Development Partnerships (PDPs): Lessons from PDPs established to develop new health technologies for neglected diseases
Holmes, D. (2013). The GHIT fund shows its cards. Nat Rev Drug Discov, 12(12), 894
Hotez, J, R. Cohen, C. Mimura, T. Yamada, and S. L.. Hoffman. 2013. Strengthening mechanisms to prioritize, coordinate, finance, and execute R&D to meet health needs in developing countries. Discussion Paper, Institute of Medicine, Washington, DC. http://www.iom.edu/StrengtheningMechanismsRD.
Massum H. and Harris R. (2011), Open Source for Neglected Diseases Magic Bullet or Mirage?, Center for Global Health R&D Policy Assessment, Research 4 Development, http://healthresearchpolicy.org/sites/healthresearchpolicy.org/files/assessments/files/Open%20source%20high%20res.pdf
Saha, C. N., & Bhattacharya, S. (2011). Intellectual property rights: An overview and implications in pharmaceutical industry. J Adv Pharm Technol Res, 2(2), 88-93.
Spangenberg, T., Burrows, J. N., et al. (2013). The open access malaria box: a drug discovery catalyst for neglected diseases. PLoS One, 8(6), e62906.
The Global Health Technologies Coalition website: Heath technologies. Available at: http://
www.ghtcoalition.org/files/NPPDnewproductslist_10.21.13.pdf
The World Intellectual property report 2011, available at : http://www.wipo.int/edocs/pubdocs/en/intproperty/944/wipo_pub_944_2011.pdf
United Nations Sustainable Development Information Platform accessible at:
https://sustainabledevelopment.un.org/sdgs