8 Biotechnology in the time of COVID-19

The arrival of COVID-19 in late 2019 brought biotechnology, specifically vaccine science, development, production and access, into the world’s spotlight in an unprecedented way. Once health officials began to understand the transmissibility and lethality of the virus and governments realized its potential to devastate economies, it became clear that the old way of doing business would not be effective in meeting the challenge. This spurred novel collaboration, with 170 countries actively engaging in developing hundreds of vaccines, antibody therapies and inhibitory small molecule drugs, diagnostic tests and specialized protective devices, all aimed at preventing transmission, identifying infected individuals and reducing suffering, morbidity and death from COVID-19 infection.

With respect to vaccines, three types were created: protein subunit vaccines, vector vaccines (DNA vaccines) and mRNA vaccines. The timing for mRNA vaccines was especially fortunate because several companies, in particular Pfizer (and its partner BioNTech) and Moderna, had already been looking at this innovative approach to stimulate a safe, effective immune response. Other companies like Merck had long experience with both traditional vaccines and antiviral medications (antivirals). The clinical effectiveness of different interventions has varied depending on the technology, company and government involved with development.

Funding to develop, manufacture and distribute COVID-19 therapies has come from corporate companies, governments, charities, non-governmental organizations (NGOs) and other sources. In some instances, the funding was used for R&D efforts or to underwrite manufacturing scale-up before completion of phase III clinical trials. The latter was to ensure the rapid deployment of therapeutics in the event of successful trials. In many cases, governments paid significant amounts to pre-purchase the drugs or vaccines. Although the benefits have not been evenly distributed within their borders, for developed and wealthier countries, the effort has been a remarkable success.

The need for developed innovation ecosystems

The same cannot be said for less-developed countries. There are many reasons for this, including financial and political reasons as well as lack of suitable infrastructure, manufacturing capability, raw materials for vaccine production, researchers and know-how, and ineffective distribution and delivery. However, some efforts have been made to address these deficiencies. To support equitable and humane medical intervention, a number of initiatives aimed to ensure universal access to COVID-19 therapies. Several for-profit companies signed an Open COVID Pledge in which they pledged to make their IP available free of charge. Other groups or companies pledged not to pursue infringers during the pandemic. Several companies engaged in broad sublicensing to facilitate production of less-expensive biologics or other drugs. Patent pools were established or broadened to make them relevant to COVID-19. Over 90 leading universities in the United States and other countries, led by the Association of University Technology Managers (AUTM), ⁽¹⁾AUTM is a nonprofit organization dedicated to bringing research to life by supporting and enhancing the global academic technology transfer profession through education, professional development, partnering and advocacy. agreed COVID-19 licensing guidelines ⁽²⁾https://autm.net/about-tech-transfer/covid19/covid-19-licensing-guidelines which were promoted to IP owners worldwide to facilitate the sharing of technology during the pandemic. For technology or products needing little investment to bring to market, for example, personal protective equipment or a standard diagnostic test, companies, universities and charities either gave the products or the specifications to make them for no cost.

Limited nonexclusive royalty-free license

TTOs realized that a paradigm shift was necessary to support efforts to bring a swift end to the crisis, especially in developing and least-developed countries. The COVID-19 licensing guidelines developed by the AUTM aimed to facilitate rapid pandemic responses by licensees and to make the execution of associated transactions a top priority. In its guidelines AUTM urged that, for most technologies, where legally possible, parties should consider time-limited, nonexclusive royalty-free licenses in exchange for the licensees’ commitment to rapidly make and broadly distribute products and services to prevent, diagnose, treat and contain COVID-19 and protect healthcare workers during the pandemic (that is, while COVID-19 was defined as a public health emergency of international concern by the World Health Organization (WHO)). These licenses could subsequently convert to a more typical commercial license as appropriate, and they also had to preserve the licensor’s freedom to publish and use the IP for teaching and research.

Licensing pools and patent pools to facilitate access to a suite of patented technologies

The COVID-19 pandemic also highlighted other existing technology transfer mechanisms, including licensing pools and patent pools. Licensing pools and patent pools can be an efficient means for licensors to out-license their technologies, as well as for potential licensees to in-license technologies from multiple entities in a single transaction, and can help to connect patent holders seeking to license their patented technology with candidate users seeking to use patented technology.

Patent pools

Patent pools are one approach to allowing licensors to combine self-selected patent assets, typically in a specifically defined technology, to facilitate licensing of the bundled patent assets to industry via a single license. ⁽³⁾Patent pools are often modeled on the “Sewing Machine Trust” of the mid-19th century, where a group of innovators agreed to pool their patents and agree to terms such that a consumer could buy a machine with features owned by different patentholders, and proceeds were distributed by the patent pool to the patentholders. Often, the patent pool is set up as a distinct entity from the licensors and serves as a liaison between the licensors and the licensee. This strategy can reduce the number of agreements and thus transaction costs (compared to licensing from each patent owner), enabling companies to obtain convenient, transparent and efficient access to technologies. Patent pools can be set up either as nonprofit entities (wherein the focus may be to improve access to technologies and/or drugs in underserved communities or low- and middle-income countries (LMICs)) or for-profit entities (wherein the goals often include increasing dissemination and monetization of IP assets). Given the significant effort and the many millions of dollars in investment required by companies, it is important to ensure that contributions to these pools remain voluntary. It is also important for patent pools and associated licensing programs to have a comprehensive portfolio of assets such that licensees have reasonable confidence that they can gain access to the technologies they need for a given use. Finally, there must be no restrictions of access to the patent pool for antitrust reasons.

Since the 1990s, some companies have developed patent pools and licensing strategies for certain technologies and standards that are widely used in consumer electronics, video and information technologies, radio-frequency identification (RFID) and power management. MPEG LA, founded in 1997, developed a patent pool strategy to facilitate adoption of the MPEG-2 standard required for digital television applications (for example, DVDs) by offering a “one-stop” license for the required technologies. MPEG LA has continued to develop licensing programs for additional MPEG standards, and has also developed patent-pool-based licensing and standards programs for wireless power, electric vehicle charging, video coding and other technologies. MPEG LA now holds licensing-related rights to thousands of patents owned by hundreds of patent holders in 100 countries and has over 7,200 licensees.

Efforts to form centralized patent pools for the biotechnology sector have been less successful. In 2012, MPEG LA launched Librassay®, a one-stop patent licensing program in the field of molecular diagnostics, but that program is not currently offering licenses. Using a different model, MPEG LA recently began to offer a drug development and design program for cell-targeting oligonucleotides, which appears to be an internally developed set of technologies as opposed to an externally sourced pool of patented technologies. ⁽⁴⁾https://www.mpegla.com/wp-content/uploads/IAM-article-June-2-2020.pdf In 2017, MPEG LA proposed developing patent pools for CRISPR-Cas genome editing using the foundational techniques of CRISPR-Cas9 technology, ⁽⁵⁾https://www.via-la.com/mpeg-la-invites-crispr-cas9-patents-to-be-pooled-in-a-one-stop-license although ongoing patent disputes among potential contributors has delayed progress. The classic patent pool model may not prove useful for biotech innovations, due in part to the lack of modular standards and the often distinct needs of each user.

Licensing pools/licensing partnerships

Licensing pools or licensing partnerships are another approach allowing users access to a suite of separately owned patented innovations in order to accomplish a goal (say, to carry out a treatment campaign or a research program). This approach utilizes voluntary licensing and, if possible, voluntary patent pooling. When a need has been identified – for example, a treatment need that has been defined by a disease, a patient population, a proposed dosage amount/regimen and an intended geographical field of use – the licensing pool or partnership can negotiate with patent holders to license the medicines and technology needed to meet the need. The licensing pool or partnership can then sublicense the right to make any patented assets to meet the identified need. In some cases, a voluntary patent pool may have already put some country-specific patent assets at the disposal of the licensing pool or partnership. The Medicines Patent Pool (MPP) is an international organization that has pioneered this approach, and some of its successes are described in Box 8.1. ⁽⁶⁾https://medicinespatentpool.org

There are ways that companies can be encouraged to volunteer their technologies, especially in times of public health emergencies such as COVID-19. Such agreements can be beneficial for companies, allowing them to increase their knowledge of the effect of their product in LMICs where they have no, or limited, presence.

In short, the global health response to the COVID-19 pandemic has been inspiring, astonishing and hugely successful and, at the same time, an alarming wake-up call. On the one hand, extremely effective therapies were developed and approved in record times and widely, though unevenly, distributed, saving lives and protecting critical economic structures. On the other hand, from the point of view of governments, international organizations, the medical and research establishment, disadvantaged populations and even the average citizen, there have been multiple failures to ensure access to life-saving treatments for all those in need, many of which could have been prevented. Pandemic preparedness, despite warnings in recent decades, was inadequate. Investment in key areas of biotechnology as well as international cooperation has been lacking and must be increased. This concerns not only the development of biotechnological innovations but also the exchange of data, such as sequence information for viruses, to enable researchers to develop vaccines and medicinal products. There is no adequate framework for ensuring that a patient in a poor country receives, in a timely fashion, the same effective medical intervention as someone in, for example, the United States, Europe or Japan.

The necessary infrastructure of education, personnel, facilities and distribution does not exist in many countries, especially LMICs, and until it does, pandemic response in these countries will be ineffective. There is a lack of understanding on the part of key stakeholders concerning the science of biotechnology and how therapies are funded, developed and manufactured. In an interconnected world, future pandemics are likely. Hopefully, the biotechnology community and its myriad stakeholders will have learned from what went right or wrong with the response to COVID-19 and better confront the next threat. In the European Union, for example, the COVID-19 pandemic has led to the creation of the “European Health Union” with the objective to improve EU-level protection, prevention, preparedness and response against human health hazards and to collectively respond to cross-border health crises. ⁽⁸⁾EU Commission, European Health Union: Protecting the health of Europeans and collectively responding to cross-border health crises.https://commission.europa.eu/strategy-and-policy/priorities-2019-2024/promoting-our-european-way-life/european-health-union_enSimilarly, the mRNA Technology Transfer Hub, co-led by WHO and MPP, was established in July 2021 in response to the flagrant inequities in access to COVID-19 vaccines in LMICs. It is aimed at improving health and health security through sustainable mRNA manufacturing capabilities in and for LMICs. It is based around a technology transfer “hub” located in South Africa, which will provide technology development, training and transfer to “spokes” in LMICs across the world. Currently, there are spokes in 15 LMICs (Argentina, Bangladesh, Brazil, Egypt, India, Indonesia, Kenya, Nigeria, Pakistan, Senegal, Serbia, South Africa, Tunisia, Ukraine and Viet Nam). The program is focused on mRNA vaccines against COVID-19 at present, but it is also designed to stimulate the development of other mRNA vaccines against important diseases that threaten LMICs, thereby ensuring that the capacity built by the project is sustained and available to combat future pandemics.