Enabling equitable and affordable access to novel therapeutics for pandemic preparedness and response via creative intellectual property agreements.

The COVID-19 pandemic demonstrated that the current purely market-driven approaches to drug discovery and development alone are insufficient to drive equitable access to new therapies either in preparation for, or in response to, pandemics. A new global framework driven by equity is under negotiation at the World Health Organization to support pandemic preparedness and response. Some believe that the global intellectual property (IP) system itself is part of the problem and propose a purely Open Science approach. In this article, we discuss how existing IP frameworks and contractual agreements may be used to create rights and obligations to generate a more effective global response in future, drawing on experience gained in the COVID Moonshot program, a purely Open Science collaboration, and the ASAP AViDD drug discovery consortium, which uses a hybrid, phased model of Open Science, patent filing and contractual agreements. We conclude that 'straight to generic' drug discovery is appropriate in some domains, and that targeted patent protection, coupled with open licensing, can offer a route to generating affordable and equitable access for therapy areas where market forces have failed. The Extended Data contains a copy of our model IP policy, which can be used as a template by other discovery efforts seeking to ensure their drug candidates can be developed for globally equitable and affordable access.

Drug discovery and development organizations usually recoup their investment in this risky and expensive process by filing patents on drug candidates which, if granted, give them a time-limited monopoly on the manufacture, sale or licensing of the drug. This means they can negotiate its price and terms of distribution, which creates distortions in access globally. In an alternative 'Open Science' approach, R&D organizations publish all the information about a prospective drug without applying for patents, meaning that anyone can use this knowledge to make and sell the drug, while the R&D organizations have no control over how it is priced or distributed. In a pandemic, fast-spreading viruses must be rapidly contained by delivering drugs to where they are most needed. This requires innovation and global access, but this is stifled in both models ­ in the first because of patent abuses, in the second because the lack of control may jeopardize the most efficient development. The authors share a model that prioritizes globally fair and affordable pricing by creating 'maximally permissive licenses' based on 'minimally defensive patents'. They explain the practical and bioethical background to their proposals and share an example of collective management of intellectual property and licensing agreement that is being used in the AI-driven Structure-enabled Antiviral Platform (ASAP) Center's Pandemic Preparedness work.

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery.

Supplementary protection certificates and their impact on access to medicines in Europe: case studies of sofosbuvir, trastuzumab and imatinib.

In recent years, there has been increasing pressure on public health systems in high-income countries due to high medicines prices, one of the underlying causes of which are the market monopolies granted to pharmaceutical undertakings. These monopolies have been facilitated by expanded forms of intellectual property protections, including the extension of the exclusivity period after the expiration of the patent term concerning medicinal products. In the European Union such an approach lies in the Supplementary Protection Certificate, a mechanism formally introduced under Regulation 1768/92/EEC (now: Regulation 469/2009/EC, amended). After more than 20 years of implementation since it was first introduced, the common justifications for SPCs are being challenged by recent findings as to their functioning and impact. Similarly, legitimate questions have been voiced as to the negative impact of SPCs on timely access to affordable medicines. On the basis of an analysis of three medicines for hepatitis C and cancer treatments, the present article critically engages with the policy justifications underlying SPCs. It then analyses access challenges to a hepatitis C medicine and an HIV treatment in Europe, highlighting the social cost of the introduction of SPCs. Both the normative and empirical analyses have demonstrated that the common justifications supporting the SPC regime are deeply questionable. The addition of SPC exclusivity has also heavily delayed competition and maintained high medicines prices in European countries. Ultimately, the granting of such extended exclusive private rights on medicines may result in unnecessary suffering and be a factor in the erosion of access to medicines for all.

Does the political will exist to bring quality-assured and affordable drugs to low- and middle-income countries?

BACKGROUND: Increased coverage with antiretroviral therapy for people living with HIV in low- and middle-income countries has increased their life expectancy associated with non-HIV comorbidities and the need for quality-assured and affordable non-communicable diseases drugs . Funders are leaving many middle-income countries that will have to pay and provide quality-assured and affordable HIV and non-HIV drugs, including for non-communicable diseases. OBJECTIVE: To estimate costs for originator and generic antiretroviral therapy as the number of people living with HIV are projected to increase between 2016 and 2026, and discuss country, regional and global factors associated with increased access to generic drugs. METHODS: Based on estimates of annual demand and prices, annual cost estimates were produced for generic and originator antiretroviral drug prices in low- and middle-income countries and projected for 2016-2026. RESULTS: Drug costs varied between US$1.5 billion and US$4.8 billion for generic drugs and US$ 8.2 billion and US$16.5 billion for originator drugs between 2016 and 2026. DISCUSSION: The global HIV response increased access to affordable generic drugs in low- and middle-income countries. Cheaper active pharmaceutical ingredients and market competition were responsible for reduced drug costs. The development and implementation of regulatory changes at country, regional and global levels, covering intellectual property rights and public health, and flexibilities in patent laws enabled prices to be reduced. These changes have not yet been applied in many low- and middle-income countries for HIV, nor for other infectious and non-communicable diseases, that lack the profile and political attention of HIV. Licensing backed up with Trade-Related Aspects of Intellectual Property Rights safeguards should become the norm to provide quality-assured and affordable drugs within competitive generic markets. CONCLUSION: Does the political will exist among policymakers and other stakeholders to develop and implement these country, regional and global frameworks for non-HIV drugs as they did for antiretroviral drugs?

Patent challenges in the procurement and supply of generic new essential medicines and lessons from HIV in the southern African development community (SADC) region.

High medicines prices increasingly pose challenges for universal access to treatments of communicable and non-communicable diseases. New essential medicines are often patent-protected which sustains high prices in many countries, including in low- and middle-income countries. To respond to the HIV/AIDS crisis of the late nineties and to increase access to antiretroviral treatment, certain flexibilities contained in the Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS flexibilities) have been clarified and in some respects strengthened at the global level. They have been applied by a number of countries to ensure access to lower-priced generic medicines to treat HIV/AIDS. Governments in the South African Development Community (SADC) have also used TRIPS flexibilities to gain access to lower-priced generic medicines. This paper documents 15 instances of the use of TRIPS flexibilities by eight SADC Member States during the period 2001-2016. Of those, six concerned least developed countries (LDCs) that declared non-enforcement of pharmaceutical patents pursuant to a new LDC transition provision. All instances occurred in the context of medicines procurement for HIV treatment. Such flexibilities can, however, also be used to overcome patent barriers to gain access to generic medicines for other diseases, including NCDs. The SADC, being a regional bloc with over 50% least developed country Members, can make use of the regional exception, a TRIPS flexibility that facilitates the production or procurement of generic medicines to the benefit of the entire region. SADC's Pharmaceutical Business Plan proposes strategies for increased collaboration and pooled procurement of medicines.

Data exclusivity exceptions and compulsory licensing to promote generic medicines in the European Union: A proposal for greater coherence in European pharmaceutical legislation.

The challenge of providing access to high-priced patented medicines is a global problem affecting all countries. A decade and a half ago the use of flexibilities contained in the World Trade Organization Agreement on Trade Related Aspects of Intellectual Property Rights, in particular compulsory licensing, was seen as a mechanism to respond to high-price medicines for the treatment of HIV/AIDS in low- and middle-income countries. Today a number of upper-income European Union (EU) Member States are contemplating the use of compulsory licensing in their efforts to reduce expenditure on pharmaceutical products. EU regulation of clinical test data protection and the granting of market exclusivity interfere with the effective use of compulsory licensing by EU Member States and can even prevent access to off-patent medicines because they prohibit registration of generic equivalents. EU pharmaceutical legislation should be amended to allow waivers to data and market exclusivity in cases of public health need and when a compulsory or government use license has been issued. Such an amendment can be modelled after existing waivers in the EU Regulation on compulsory licensing of patents for the manufacture of pharmaceutical products for export to countries with public health problems outside the EU. Allowing a public health/compulsory license exception to data and market exclusivity would bring greater coherence between EC regulation of medicinal products and national provisions on compulsory licensing and ensure that Member States can take measures to protect public health and promote access to medicines for all.

Patentes de medicamentos em evidência: compartilhando experiência prática sobre patentes de produtos farmacêuticos / Medicine patents in evidence: sharing practical experience on patents of pharmaceutical products

Apresenta informações técnicas sobre patentes de produtos farmacêuticos. Discute o Acordo sobre Aspectos de Direitos de Propriedade Intelectual Relacionadas ao comércio - TRIPS, estabelecido em 1994. Traz quatro conceitos chave para entender as patentes de medicamento. Mostra a razão pela qual o sistema de patente deveria responder aos interesses públicos dos países. Orienta como ler e usar uma tabela de patente