The idea that there was a form of RNA that carried genetic instructions from DNA to the protein-making machinery of cells was only conceived of in 1960. Sixty years later, messenger ribonucleic acid (mRNA) helped curb a global pandemic, and is now being used to develop personalised medicine, treatments for genetic disorders, and drugs to cure cancer.
This success has encouraged significant investment in mRNA vaccine technology. According to one recent study, the global mRNA vaccines and therapeutics market size reached USD 57.7 Billion in 2023, and was projected to reach USD 72.7 billion by 2032. With investment in technology comes a focus on patents. This Insight, adapted from our article published in Bio-Science Law Review, looks at the importance of patents in protecting investment in mRNA technology.
What is mRNA and what can it be used for?
mRNA is the intermediary (or messenger) in the flow of genetic information from DNA to protein synthesis.
In 1989, it was demonstrated that synthetic mRNA could be introduced into cells to produce specific proteins, paving the way for the use of mRNA technology in vaccine development. mRNA vaccines, such as Pfizer and BioNTech’s COMIRNATY® and Moderna’s SPIKEVAX®, work by using lipid nanoparticles (LNPs) to deliver mRNA that instructs cells to produce spike proteins. These proteins help the immune system recognise and respond to viruses like SARS-CoV-2 more effectively. COMIRNATY® was the first mRNA vaccine approved by a US Federal Drug Administration (FDA), receiving emergency authorisation in December 2020 and full approval in August 2021. SPIKEVAX® followed shortly after, also using synthetic mRNA to code for SARS-CoV-2 spike proteins.
The success of COVID-19 mRNA vaccines has encouraged research into other mRNA vaccines. In 2023, Moderna announced its Respiratory Syncytial Virus (RSV) mRNA vaccine showed 83.7% effectiveness in adults over 60. Additionally, the FDA granted ‘Breakthrough Therapy Designation’ for a personalised mRNA vaccine in combination with Merck’s KEYTRUDA® for high-risk melanoma patients.
Currently, over 300 mRNA-based therapies are in development for various diseases, including cancer, infectious diseases, and cardiovascular conditions.
The first mRNA patent controversy
The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), which is administered by the World Trade Organization (WTO), sets minimum standards for the protection of IP in the domestic markets of member states. In October 2020, India and South Africa requested the WTO waive the TRIPS requirements for patent protection for COVID-19 technology until global herd immunity was reached. The WTO approved the waiver in July 2022, allowing member states to suspend the enforcement of IP rights to allow for domestic production of vaccines for a limited period. Meanwhile, Moderna announced in 2020 it would not enforce its COVID-19 patents during the pandemic and later committed to licensing its technology for low and middle-income countries.
The patenting of mRNA technology
To be patentable in Australia, an invention must be a ‘manner of new manufacture’, that is, an ‘artificially created state of affairs of utility in a field of economic endeavour’. Since the 2015 High Court of Australia’s decision in D’Arcy v Myriad Genetics Inc it has been clear that while naturally occurring sequences (DNA or RNA) that are isolated from a naturally occurring organism are not patentable, modified genetic material (for example, synthetic sequences, sequences used in diagnostic tests and methods of using genetic material) may be the subject of a valid patent. This is consistent with the US and European positions.
The key players and the first shots fired in the mRNA patent wars
The first three key players have been the makers of the COMIRNATY® vaccine, the US pharmaceutical company Pfizer and the German biotechnology company BioNTech, and American pharmaceutical and biotechnology company Moderna, the manufacturer of the SPIKEVAX® vaccine. BioNTech has a portfolio of patents relating to methods of delivery of mRNA vaccines, including LNPs and lipid carriers.
Other key players include:
- The University of Pennsylvania (UPenn), whose research on mRNA technology has been critical for the development of mRNA-based therapies. UPenn sublicensed many of its patents to both Moderna and BioNTech.
- The Canadian biopharmaceutical company Arbutus Biopharma (Arbutus) and the University of British Columbia (UBC), who worked together on LNPs in the late 1990s. Patents that followed this work are owned solely by the UBC and licensed back to Arbutus.
- A fellow Canadian biotech, Acuitas Therapeutics (Acuitas), to which Arbutus licensed patents relating to the delivery of nucleic acids in 2012.
- The German biopharmaceutical company CureVac, that entered into a development and option agreement with Acuitas in 2016.
- Genevant Sciences (Genevant), a company created when Arbutus entered into an agreement with the biotech company Roivant. Genevant received a licence to exploit Arbutus’s patents relating to LNPs. Genevant then sublicensed those patents to BioNTech, who then entered into an agreement with Pfizer to develop the COMIRNATY® vaccine.
- Alnylam, an American biopharmaceutical company that invented a breakthrough class of cationic biodegradable lipids used to form LNPs that carry RNA-based vaccines. It claims its LNP technology is foundational to the success of the COVID-19 vaccines.
This complex web of players, patents, licences and sublicences has precipitated an equally complex web of patent disputes around the world.
The post-COVID mRNA patent wars
A detailed analysis of the patent litigation that started in 2022, when many countries began to treat COVID-19 as an endemic virus, can be found in our article, ‘The role of patents in protecting investment in mRNA technology’, that was just published in the Bio-Science Law Review. Below is a brief overview of the key disputes:
- Arbutus and Genevant v Moderna: In February 2022, Arbutus and Genevant filed a suit in a US Federal Court against Moderna seeking damages that flowed from the alleged infringement of six of Arbutus’s LNP technology patents by Moderna’s manufacture and sale of the SPIKEVAX® vaccine.
- Alnylam v Moderna; Alnylam v Pfizer and BioNTech (US): In March 2022, Alnylam filed two patent suits against Moderna and Pfizer and BioNTech. Over the following 18 months, Alynam filed four additional claims against Moderna and Pfizer relating to infringement of a number of other newly granted patents.
- CureVac v BioNTech (Germany): In July 2022, CureVac filed a suit in the German Regional Court in Düsseldorf against BioNTech (but not Pfizer) seeking compensation for infringement of one European patent and three German patents relating to features of the mRNA payload and lipid formulation. It later added a second European patent.
- Pfizer and BioNtech v CureVac (US): In July 2022, just weeks after CureVac filed its suit against BioNTech in Germany, Pfizer and BioNtech filed an action against CureVac in a US Federal Court for a declaration that the COMIRNATY® vaccine does not infringe CureVac’s three US patents that are in the same family as the European and German patents asserted in Germany.
- Moderna v Pfizer and BioNTech (US, Europe): In August 2022, Moderna filed a suit against its Pfizer and BioNTech in a US Federal Court. Moderna alleges that BioNTech infringed its patents relating to the use of LNPs to encapsulate mRNA, the replacement of uracil with 1-methylpseudouridine in the vaccine mRNA, and the use of mRNA that codes the SARS-CoV-2 spike protein. Moderna also filed a related action against Pfizer and BioNTech in the Düsseldorf Regional Court in Germany in August 2022, based on two of its European patents. Further actions then arose in the Netherlands and the UK.
- Arbutus and Genevant v Pfizer and BioNtech (US): In April 2023, Arbutus and Genevant filed a patent infringement claim in a US Federal Court against Pfizer and BioNTech. Arbutus claims that Pfizer and BioNTech’s COMIRNATY® vaccine and other COVID-19 mRNA LNP vaccine products infringe five of Arbutus’s LNP technology patents.
- Moderna v National Institutes of Health (NIH) (US): The parties have been in a long-running dispute over inventorship of technology that led to the creation of the SPIKEVAX®. Moderna filed a US patent application relating to the technology but did not name any NIH scientists as inventors that NIH alleges contributed to the invention.
- Acuitas v Alnylam (US): In July 2024, Acuitas filed a complaint against Alnylam in a US Federal Court relating to inventorship of seven US patents relating to LNP technology used in COVID-19 mRNA-LNP vaccines. Acuitas is seeking orders that two of its scientists are co-inventors of seven of Alnylam’s patents.
- UPenn v BioNTech (US): On 5 August 2024, UPenn filed a suit in a US Federal Court against BioNTech claiming unpaid royalties for the use of patented technology used in BioNTech and Pfizer’s COMIRNATY® vaccine.
We can also add one new player into this mix — GlaxoSmithKline (GSK) — that last week filed a claim against Moderna relating to the SPIKEVAX® vaccine in a US Federal Court. This followed GSK filing a similar suit in April this year against Pfizer and BioNTech relating to the COMIRNATY® vaccine.
Notably, no parties to these proceedings have sought an injunction to restrain exploitation of patented technology that may have an impact on the availability of COVID-19 vaccines.
Navigating the patent landscape
Patent conflict can be fatal to recovering expected returns on investment. Conflicts also present risk and uncertainty for patentees, investors and researchers in the field (and adjacent fields), as well as to the availability of resources to pursue new medical treatments.
Ownership and entitlement disputes often arise from unclear agreements among collaborators, particularly where contributions stray beyond that which was originally contemplated. They also become increasingly likely where multiple collaborators are contributing their existing intellectual property rights to joint ventures.
Designing research and development programmes around existing rights reduces infringement risk but can also present significant challenges. In the area of mRNA vaccines, we have seen innovators navigate existing patent rights by using different mRNA sequences, delivery systems, and manufacturing processes. For example, Novavax used a traditional protein-based vaccine technology to sidestep patent conflict.
Some experimental use exceptions exist to allow researchers to use patented inventions for experimentation without infringement risk. However, these exceptions are narrow and vary by jurisdiction, adding complexity for global entities with research teams in different jurisdictions.
The evolution of mRNA technology and the ability of researchers to develop new treatments will be shaped by the patents that are eventually granted, licensing arrangements, and the outcome of disputes that are currently being litigated. Investors in mRNA vaccines will need to implement future proof IP strategies to ensure a return on their investment.
You can read our full-length article in in Lawtext Publishing’s latest issue of the Bio-Science Law Review.
