Building on decades of research, the COVID-19 pandemic brought messenger RNA (mRNA) technologies to the forefront, with hundreds of millions of people receiving mRNA vaccines against SARS-CoV-2.
Although the value of the mRNA COVID-19 vaccine market is decreasing, the future potential of mRNA technologies is widely acknowledged. In recent years key players in this field have sought to assert their Intellectual Property rights to mRNA platform technologies, with number of infringement lawsuits playing out in Europe and the US.
The mRNA vaccine technology
mRNA is a single stranded nucleic acid composed of four different nucleosides adenosine, guanosine, cytidine and uridine. It is the intermediary in the production of proteins from DNA. mRNA is transcribed in the nucleus of a cell from DNA and is subsequently translated in the cytoplasm to produce proteins. mRNA vaccines introduce synthetic mRNA encoding a protein into the cytoplasm of cells to induce the production of the encoded protein in the cell. An immune response may subsequently be initiated against the protein, such that immunological memory to the protein is generated.
The COVID-19 mRNA vaccines developed by Moderna and Pfizer/BioNTech both comprise features which overcome two key hurdles associated with the use of mRNA as a drug platform. The first is innate immune receptors recognise synthetic mRNA, resulting in the initiation of an innate immune response. In both vaccines uridine nucleosides are replaced with a pseudouridine, a chemically modified uridine which is believed to prevent the innate immune system reacting to the introduced mRNA. Secondly the synthetic mRNA must be delivered to the cytosol of cells so it may be transcribed. The mRNA vaccines use lipid-based nanoparticles to encapsulate the mRNA, allowing for the delivery of the mRNA to the cytosol of cells.
However, mRNA technologies have applications beyond vaccines against SARS-CoV-2. The growth of mRNA technologies has rapidly increased in recent years. Momentum in this field and increased commercialisation is illustrated by the number of patents and patent applications for mRNA technologies. A 2023 report by the European Patent Office showed an increase of around 400% in the number of international patent families relating to mRNA vaccine technologies between 2015 and 2021. Both Moderna and BioNTech, as well as others in the field, are developing mRNA vaccines to target a wide range of infectious diseases and cancers. For example, in 2023 Moderna and Merck launched a Phase III clinical trial of their personalised mRNA vaccine, mRNA-4157, against melanoma. Additionally, in February 2024 the first UK patients received Moderna’s mRNA immunotherapy, mRNA-4359, in a Phase I/II trial, assessing its safety and potential for the treatment of melanoma, lung cancer and other solid tumour cancers. The current commercial importance of COVID-19 mRNA vaccines and the predicted future importance of mRNA technologies has resulted in several IP disputes.
Intellectual Property Disputes
In 2020 Moderna pledged not to enforce COVID-19 related patents during the COVID-19 pandemic. They updated their pledge in 2022 highlighting, although they would not enforce their IP rights in low- and middle-income countries in the GAVI COVAX Advance Market Commitment, they expected their IP rights to be respected elsewhere. Moderna subsequently filed for patent infringement against Pfizer and BioNTech in the US and Germany in August 2022 and later in further European countries, including the UK. Moderna are requesting damages for acts of infringement occurring after 8 March 2022 but are not seeking a court order to remove Pfizer/BioNTech’s Comirnaty vaccine from the market.
In Europe, Moderna is claiming the Comirnaty vaccine infringes European Patent Nos. 3590949 and 3718565. The ‘949 patent claims an mRNA where uracil nucleotides are replaced with N1-methyl-pseudouridine. The ‘565 patent claims a betacoronavirus mRNA vaccine encoding a spike protein, which is formulated in lipid nanoparticle comprising four different types of lipids. Moderna claims the Comirnaty vaccine infringes these patents due to the formulation of the lipid nanoparticle used, the replacement of uracil with 1-methylpseudouridine and as the mRNA encodes an entire SARS-CoV-2 Spike protein. The defendants have counterclaimed for invalidity of Moderna’s patents.
Additionally, Pfizer, BioNTech, and others filed notices of opposition at the EPO against both the ‘949 and ‘565 patents. In a decision in November 2023, the Opposition Division of the EPO revoked Moderna's ‘565 patent on the grounds that certain combinations of features as claimed in claim 1 of the patent cannot be directly derived from the originally filed patent. Moderna have indicated they will appeal this decision. Additionally, in their preliminary opinion, the Opposition Division have suggested there are also doubts as to the validity of the ‘949 patent. This has led to suspension of the infringement proceedings in Germany in respect of these patents.
Several other infringement disputes relating to mRNA technologies have arisen in the US and Europe. In one example CureVac, a German Pharmaceutical company specialising in mRNA technologies, but who’s mRNA COVID-19 vaccine was abandoned after Phase III clinical trials, brought action against BioNTech in Germany. CureVac claimed BioNTech infringed several of their patents and utility models relating to mRNA technologies. However, in a decision by the German Federal Patent Court, one of CureVac’s patents was ruled invalid. It is unlikely the dispute between CureVac and BioNTech will be concluded swiftly, with CureVac indicating they will appeal this decision and BioNTech filing an opposition at the EPO against a further one of CureVac’s patents.
Conclusion
The present commercial importance, and perceived future importance of mRNA technologies in drug development can be shown by the increase in patent applications in this space, as well has the recent web of infringement proceedings in the US and Europe in respect of patents to mRNA technologies. With sales of mRNA COVID-19 vaccines still generating billions of dollars, and pharmaceutical compositions which use mRNA technologies in the pipelines of a number of parties, it will be important to establish the validity of intellectual property rights to different mRNA platforms and delivery formulations. However, certainty regarding freedom to operate in this space is unlikely to be soon.
Preparation and filing of oppositions at the EPO, which allows the validity of granted European patents to be challenged, can be complex. The attorneys at Secerna have expertise in this area and can assist in navigating the opposition process and advise on strategies for achieving a successful outcome.