In 2005, a scientist working at the University of Pennsylvania filed a patent describing a novel method of inducing mammalian cells to produce any given protein using artificially synthesized mRNAs [1]. That scientist, Dr. Katalin Kariko, had made the crucial discovery that incorporation of a uridine isomer called pseudouridine into synthetic mRNA not only increases the production of a target protein by 10-fold, but also avoids triggering a strong immune response – a characteristic property of unmodified mRNAs that limits their potential therapeutic efficacy [1]. Dr. Kariko’s method of using modified mRNA to make cells in a living system manufacture a specific protein, without activating the immune response, would soon lay the groundwork for the breakneck development and approval of the first ever mRNA-based vaccines amidst the global coronavirus pandemic.
By translating her discoveries into a patent, Dr. Kariko secured the legal rights to the mRNA technologies she had long worked on in the lab. Contrary to popular belief, a patent does not explicitly grant patent-holders the right to an invention’s production, but rather provides a legal mechanism to prevent others from producing whatever is defined in the patent [2]. In the United States, this right is typically granted for a period of 20 years, and is bestowed upon the patent-holder in exchange for public disclosure of the invention [2]. For inventors, an alternative method of protecting one’s ideas is known as a trade secret, granting the inventor exclusive access to those ideas by virtue of them not being publicly disclosed [3]. While this protection lasts only as long as secrecy can be maintained, some of the world’s most successful products are to this day protected as trade secrets - including the recipe for Coca-Cola as well as WD-40 [4].
In theory, the use of patents as an alternative to trade secrets serves two main purposes, with the ultimate goal being to promote technological progress: first, it allows individuals to secure the exclusive legal rights of protecting their inventions for a non-trivial period of time, providing a financial incentive for the creation of new technologies; and second, it opens the door for other individuals to build on the concepts described by the patent and create new inventions of their own [1].
Patents contain detailed technical depictions of protected technology. This example shows a unique bicycle described in a patent from 1894. "'Monocycle' patent, 1894" by Michael Neubert is licensed under CC BY 2.0
While patents are an integral feature of most countries' legal systems, it remains controversial whether they always encourage the creation of new technologies and serve the greater good in society. In practice, the legal and industrial landscape of intellectual property is multi-faceted and extremely complex, which at times raises questions as to how such legal protections should be best applied. For example, it is perfectly legal for an individual to obtain the rights to a patent solely for the purposes of bringing lawsuits and obtaining financial settlements, regardless of whether they ever intend to use the technology described in the patent [5]. In the medical sphere, patents may sometimes make it difficult for patients to obtain access to needed therapeutics, as is the case with some cancer drugs such as Herceptin, costing up to $150,000 per year of treatment due to the monopoly on production secured via patent protections [6].
Under certain conditions, such as public health emergencies, the World Trade Organization (WTO) permits governments to authorize the production or import of a product that is under patent protection without the permission of the patent-holder in a process called compulsory licensing [7]. The rationale for compulsory licensing is that, in dire circumstances, upholding a legal barrier that hinders access to a critical technology can result in significant harm to vulnerable populations. Critics argue, however, that granting such licenses only serves to circumvent the financial incentives patents are designed to provide in the first place, ultimately hampering the invention of new technologies or drugs [8].
The global COVID-19 pandemic, which has lasted for more than a year and had seismic effects on daily life, is a textbook example of such a circumstance where compulsory licensing is justified – particularly considering every new infection has the potential to generate a mutant strain that could worsen the pandemic. To date, 58 countries at the WTO have publicly called for compulsory licensing to be used to expand vaccine and other therapeutic access related to the coronavirus in an effort to curb its spread as soon as possible [9].
Stories of human suffering permeate the history and present of the pandemic, yet there has been at least one silver lining – namely, the awe-inspiring speed at which numerous vaccines providing effective protection against the coronavirus have been developed, including two vaccines based largely on the mRNA technology first described in Dr. Kariko’s 2005 patent [10]. Though the potential for her discoveries to be used therapeutically has existed for some time, the technology initially struggled to attract private-sector interest [10]. That changed when Moderna and BioNTech, two pharmaceutical companies interested in mRNA-based therapeutics, negotiated license agreements with the patent-holders, granting these companies the right to use the underlying technology in their development pipelines [10]. Both companies began to invest heavily in the development of mRNA-based therapeutics to target a variety of infectious diseases and cancers by combining the modified mRNAs with lipid-based delivery systems necessary for ferrying the mRNA into living cells [11, 12, 13]. The expanding efforts by the two companies would eventually become hyper-focused on development of a vaccine against the novel coronavirus at the outset of the pandemic, culminating in the creation of the world’s first mRNA-based vaccines [14]. These two vaccines are now responsible for the vast majority of vaccinations against COVID-19 in the United States [15].
Vials similar to the ones shown here are used to store and distribute the mRNA vaccines against the novel coronavirus manufactured by Moderna. Covid-19 vaccine from Moderna Inc. by Marco Verch under Creative Commons 2.0
In a move sure to be praised by those advocating for increased worldwide access to vaccines over the financial considerations of patent-holders, Moderna recently made a public pledge to not enforce patent rights related to their vaccines for the duration of the pandemic [16]. However, in this specific case, it is not entirely clear what effect this move would have on expanding vaccine access. In reality, the intention behind patent pledges and compulsory licenses for technologies like Moderna’s mRNA vaccine may ultimately be hamstrung by the fact that, even with free access to the required intellectual property, producing the vaccines safely and on a large scale requires industrial infrastructure, technical expertise, and potentially the wet lab reagents and protocols used by the original manufacturer [17]. Many of these resources are less likely to be shared with a competitor, making it unrealistic that access to the underlying intellectual property alone will result in increased production and access to vaccines [17]. Alternatively, it may be more beneficial for both activists and governments to encourage voluntary licensing and joint manufacturing agreements, under which a company such as Moderna would be actively involved in helping to set up production of their vaccine at an offsite facility. There are already several examples of such agreements related to the pandemic, including the recent use of the Defense Production Act by the United States to secure a joint vaccine manufacturing partnership between Johnson & Johnson and Merck, as well as a similar international agreement between the United States, India, Japan, and Australia [17].
Regardless of where one stands on the issue of patent protections, the COVID-19 pandemic is a unique lens through which one can newly examine the question of how to best balance incentives for investment in medical research with ease of access to the underlying technologies for the global community. Beyond this, the incredible speed at which the mRNA vaccines were developed serves as a critical proof-of-principal exercise in the use of mRNA-based vaccines to respond to inevitable future pandemics. Notably, investments into RNA-based therapeutics have skyrocketed in the past decade, and encompass projects targeting not only infectious diseases, but a litany of other ailments, including cancers and autoimmune disorders. It remains to be seen what effect the mainstreaming of mRNA-based therapies via the coronavirus vaccines will have on bolstering public interest and investment in these related technologies, but one can imagine the exciting new therapeutics this may one day lead to.
Edited by Allen Zinkle
References
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What Is Intellectual Property? World Intellectual Property Organization (WIPO), 2020.
Kasden, Michael J, et al. “Trade Secrets: What You Need to Know.” The National Law Review, 12 Dec. 2019, www.natlawreview.com/article/trade-secrets-what-you-need-to-know.
“Trade secrets: 10 of the most famous examples.” Vethan Law Firm, 08 Nov. 2016, https://info.vethanlaw.com/blog/trade-secrets-10-of-the-most-famous-examples
Stoll, Robert L. Patent Trolls: Friend or Foe?, World Intellectual Property Organization, Apr. 2014, www.wipo.int/wipo_magazine/en/2014/02/article_0007.html.
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“Countries Obstructing COVID-19 Patent Waiver Must Allow Negotiations: MSF.” Médecins Sans Frontières (MSF) International, 9 Mar. 2021, www.msf.org/countries-obstructing-covid-19-patent-waiver-must-allow-negotiations.
Kolata, Gina. Kati Kariko Helped Shield the World From the Coronavirus. The New York Times, 8 Apr. 2021, www.nytimes.com/2021/04/08/health/coronavirus-mrna-kariko.html.
“Moderna's Pipeline.” Moderna, www.modernatx.com/pipeline.
“BioNTech Pipeline.” BioNTech, biontech.de/science/pipeline.
Cross, Ryan. “Without These Lipid Shells, There Would Be No MRNA Vaccines for COVID-19.” C&EN, 6 Mar. 2021, cen.acs.org/pharmaceuticals/drug-delivery/Without-lipid-shells-mRNA-vaccines/99/i8.
Understanding MRNA COVID-19 Vaccines. Centers for Disease Control and Prevention, 4 Mar. 2021, www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html.
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“Statement by Moderna on Intellectual Property Matters during the COVID-19 Pandemic.” Moderna, Inc., 8 Oct. 2020, investors.modernatx.com/news-releases/news-release-details/statement-moderna-intellectual-property-matters-during-covid-19.
Silverman, Rachel. “Perspective | Waiving Vaccine Patents Won't Help Inoculate Poorer Nations.” The Washington Post, WP Company, 15 Mar. 2021, www.washingtonpost.com/outlook/2021/03/15/vaccine-coronavirus-patents-waive-global-equity/.
