Open Science

Authors:
Pascale Boulet, ASAP IP Strategy Consultant, Intellectual Property & Access Leader, DNDi
Dr Ed Griffen, ASAP Lead Optimization Project Lead, MedChemica Consultancy Ltd

Our approach to open science and intellectual property is described in detail in our formal policy:

Griffen, E., & Boulet, P. (2024). ASAP Policy on Intellectual Property Management and Open Science Disclosure (1.0). Zenodo. https://doi.org/10.5281/zenodo.12191567

Below, we provide a brief summary of the main principles of our approach to open science:

Antivirals must be globally accessible to be effective against pandemics

ASAP accelerates open science antiviral drug discovery to deliver oral antivirals for pandemics with the goal of global, equitable, and affordable access.

Nobody is safe unless everybody is safe. Modern air travel means infectious agents can spread easily across the globe. An outbreak that begins in a low or middle income country (LMIC) can rapidly become a global problem. As climate change pushes different mosquito species to higher latitudes, diseases currently only considered a threat in LMICs, such as Dengue and Zika, will transition into high income countries (HICs). If we cannot ensure global, equitable, and affordable access to antivirals, we will not be able to contain future epidemics before they become global pandemics.

Drug discovery for pandemic preparedness requires a hybrid R&D model

The history of the SARS, MERS, and SARS-CoV-2 viral outbreaks has demonstrated that pure market solutions are not sufficient to respond to pandemic threats. Both drug discovery (finding new therapeutic molecules) and drug development (demonstrating they are safe and effective in the clinic) are expensive and risky undertakings. Philanthropic and government funding of drug discovery has led to the generation of potentially useful new agents via a variety of collaborative efforts. However, for the much more expensive and challenging clinical development process, it is essential to engage industrial partners either in large pharma or generic drug manufacturers while creating the framework to secure global equitable and affordable access to the resulting end-products.

Learning from the COVID Moonshot: to patent or not to patent?

During the COVID Moonshot project, we adopted a patent-free, open science direct-to-generic approach. This was highly effective in the research phase, enabling rapid recruitment of collaborators and remarkably fast transfer of ideas and data unencumbered by lengthy contract negotiations. However, it had several unforeseen consequences.

First, discussions with potential manufacturers were made more complex, as we could not guarantee that other parties would not develop production routes to the new antiviral in parallel, risking the recovery of their investment costs, and having the effect of dissuading manufacturers from agreeing to make the antiviral. While several manufacturers have expressed interest in downstream collaboration based on anticipated Phase 2(a) clinical efficacy results and the state of the COVID-19 pandemic, for them it was too risky to invest in the project before that point.

Second, and as a result, to provide comfort to downstream development partners, a counterintuitive outcome was that we could not publicly disclose the chemical structure of the antiviral we chose to take into the clinic until we had initiated clinical trials in order to prevent others from performing poorly controlled experiments or filing for regulatory approval in a manner that could significantly delay our effort. In other words, we had to replace patents with delayed data disclosure as a means to safeguard our ability to identify a partner for the clinic, which is not ideal from the perspective of enabling the scientific community to make progress based on our work.

Third, several philanthropic funders were uncomfortable with the patent free approach and declined to provide funding for the research phase of the project because there was no patent to control downstream licensing. This delayed the identification of a funder to finance our progress to a candidate drug. In the end, the international Access to COVID Tools Accelerator (ACT-A) through the Wellcome Trust funded the expensive preclinical development phase of COVID Moonshot antivirals to reach Phase I clinical safety readiness despite the lack of a patent.

Fourth, we underestimated how much impact our adoption of open science could have. In addition to numerous academic efforts around the world building on the data we released, a major pharmaceutical company demonstrated how they were able to build on our work to develop a new, effective antiviral that is now approved in Japan and fast-tracked by the FDA, providing an important new tool for treating COVID-19, though it is unclear if it will be globally available and affordable. With these lessons in mind, we have refined our strategy to secure control of the antivirals we develop to make them globally and equitably accessible and affordable while still making our data open as rapidly as possible.

Making the patent system work toward global equitable and affordable access

We next explored how the patent system can be used, as a tool, to enable our goals of both global equitable access and rapid development. It is important to understand key features of patents on novel chemical matter—chemical compounds that might be useful antiviral drugs. A patent is a time-limited legal monopoly where, in exchange for full public disclosure of exactly how to reproduce an invention, (in this case: how to make an antiviral drug), the state granting the patent enables the owner or licensee to prevent others from replicating the invention without permission. In commercial drug discovery, these patents are generally as broad as possible, with the goal of excluding competitors from making similar or second-generation molecules, even if they might be better, cheaper, or have fewer side effects without paying royalties to the broad patent holder. This is the opposite of what we aim to do in a pandemic, where we want second-generation antivirals that are more convenient to take, cheaper, or have different resistance profiles as they may be essential in saving lives.

We therefore propose the concept of a “minimally defensive patent”: a precise, focused patent, only specifying the exact molecules we will be studying clinically. This enables us to prevent others working only on the exact molecules we aim to take all the way through the clinic to manufacture, avoiding the issues of either ‘rogue synthesis for profit’ or uncontrolled experimentation leading to clinical development delays, while still allowing others to work on better, cheaper, or differentiated antivirals that build on our work. It also provides ASAP with critical negotiating rights with development partners to ensure global, equitable, and affordable access during clinical development, manufacture, distribution and commercialization.

As an open science program, we are still putting a wealth of data into the public domain immediately—antiviral targets, structures, protocols, plasmids, mutational data, molecules, and data up through early lead compounds. During the final stage of drug discovery—lead optimization—our unsuccessful early discoveries (chemical structures and measured data) are rapidly disclosed into the public domain, while the release of the rest of the data is delayed. This will provide contemporaneous researchers with indications of areas that we have demonstrated to be unproductive therefore saving time and avoiding duplication of work. By requesting our patents be published at the earliest possible date after filing, rather than the standard 18 months, we will be able to share all of our remaining data once the patent publishes, avoiding the need to hide which antivirals we are carrying into the clinic. All our data will end up in the open where others can exploit it for global benefit.

We believe our policy of late patenting only the compounds we aim to take into the clinic and publishing the areas we are not interested in until the patent posts will support rapid development of our own molecules while supporting others who aim to build on our work to discover differentiated antivirals that serve the public good. The combination of these two approaches maximizes our ability to deliver on our primary goal of generating new antivirals for pandemic use which will be available globally on an affordable and equitable basis while being as open as possible as quickly as possible.

The ASAP licensing strategy focuses on ensuring global benefit

Owning a patent for the compound we aim to take into the clinic gives us the ability to control the terms and conditions under which it is licensed to downstream development partners who are essential in the manufacture of our future antivirals and will conduct the clinical trials. Under ASAP IP policy, all ASAP members undertake to only license ASAP patent(s) on terms ensuring global equitable and affordable access. ASAP as a patent owner undertakes to license its patent rights under global non-exclusive licenses as the preferred licensing strategy to ensure affordable competitive pricing and enough supplies globally, if needed, through multiple manufacturers. By controlling the licencing of patent rights, ASAP can provide the first developer(s) (which will necessarily invest more than generics followers), with the comfort that competition is not left to the market (as in Moonshot if we had published the molecule) but will be managed to ensure both a fair return on private investments and global equitable and affordable access. Building in licensing terms that avoid the generation of monopolies is a key tactic in ensuring affordable antiviral production. The assumption is that significant public funding will be made available by the global donor community to incentivize and support the downstream development of new antivirals for pandemic use, which ought to be affordable and equitably available to serve the common public interest. Therefore exclusivity would not be necessary to recoup significant investments in downstream development. Further, developers would still be able to claim IP on specific formulations or manufacturing processes to distinguish their products from competitors, though access to the molecule itself would remain free to anyone interested. The policy also foresees that licensing of new IP generated in the downstream development of ASAP antivirals could be subject to the payment of tiered and capped royalties to the developer, but only with regard to sales in High-Income and/or Upper-Middle Income Countries.

In case of demonstrated inability to engage with a development partner on global non-exclusive licensing terms, ASAP IP policy provides that ASAP institutions may decide, by vote, to license ASAP patent(s) on an exclusive basis to a development partner. However, such exclusive rights would be limited to sales in high-income countries and subject to additional conditions. First, global non-exclusive licenses would remain available to interested companies for development and/or sale in low and middle income countries (LMICs) to secure the lowest sustainable prices based on generic competition. Second, the exclusive licensee would be obligated to sell ASAP antivirals at transparent and affordable prices in high-income countries, and to reserve half of the production for sale to LMICs on a no-profit-no-loss basis, allocated equitably according to WHO guidelines, to avoid sales being prioritized in high-income countries, as happened with first commercialized COVID-19 vaccines. Lastly, in case of an international pandemic declared by the World Health Organization, ASAP IP policy requires any developer of ASAP antiviral to sub-license its rights to interested generic manufacturers, including through international patent pools, to ensure enough supplies globally.

Our intent is to publish both the ASAP IP policy with the background and rationale for its development, so others can use it as a model and further develop contractual tools for equitable access to antiviral treatments.

Conclusion

ASAP IP policy aims to use patents rights as a tool to avoid some of the short-comings of a pure open-science approach tested by the Moonshot consortium, while contractually conditioning the use of patent rights to the ASAP fundamental goal of global equitable access.

Our Intellectual Property Management and Open Science Disclosure Policy is here:

Griffen, E., & Boulet, P. (2024). ASAP Policy on Intellectual Property Management and Open Science Disclosure (1.0). Zenodo. https://doi.org/10.5281/zenodo.12191567