The “RNAissance”

Before 2020, medicines based on mRNA technology were far from the public consciousness and may have seemed the preserve of academics and young biotech companies. But in just a few years, mRNA vaccine technology has been heralded as “revolutionary” in the pages of international news publications; the “RNAissance of life science” in world-leading journals; and has attracted the most prestigious prize in all of science.

Propelled to cultural fame, mRNA vaccines are also the subject of an increasing number of patent applications. A recent Insight Report by the European Patent Office (EPO) highlights that the number of patent families published in the mRNA vaccines field more than doubled in 2021 – a rate which outpaces the increase in patent family publications averaged across all other technical fields.

Figure 1 Number of International Patent Families for mRNA-based vaccines per earliest publication. Figure from EPO’s Insight Report: mRNA Technologies (accessed April 2024).

The above pace of patent activity mirrors the scientific complexity of this nascent technology. mRNA vaccines generally come in two parts, both of which are the subject of ongoing innovation and optimisation. First is the mRNA itself, which must express its encoded protein in adequate quantities to trigger a sufficient immune response, while avoiding undesired immunogenicity. Second is the delivery vehicle, which protects a large, negatively charged mRNA payload against degradation in blood plasma, and ensures efficient delivery across the cell membrane to the cytoplasm. One of the most popular delivery vehicles is the lipid nanoparticle (LNP), the miniscule oil droplets that envelop mRNA vaccines as used in two successful COVID-19 vaccines: Spikevax® (Moderna) and Comirnaty® (BioNTech/Pfizer).

In addition to new innovations in the mRNA and the delivery vehicle, we can expect innovations in the manufacturing and formulation options that ensure mass availability of quality vaccine.

Filing trends

The modular construction of mRNA vaccines and their production methods leads to a complex network of IP rights protecting commercial products and platform technologies.

The EPO Insight Report indicates that there has been a remarkable acceleration in patent filings relating to the mRNA-based vaccines between 2019 and 2021. The filings are not limited to anti-viral vaccines. An almost equal number of patent families are filed to anti-viral vaccines and general mRNA vaccine technology, with smaller numbers to anti-bacterial vaccines and anti-malaria vaccines.

Figure 2 International Patent Families in the field of mRNA-based vaccines according to important groups of vaccines per earliest publication year. Figure from EPO’s Insight Report: mRNA Technologies.

The broad potential of mRNA vaccines is illustrated by the sheer number of viral targets for which companies have filed international patent families, including: pneumovirus (7 applicants, 52 patent families); influenza virus (15 applicants, 44 patent families); cytomegalovirus (7 applicants, 29 patent families); HIV (11 applicants, 21 patent families); flavivirus (9 applicants, 21 patent families); papillomavirus (5 applicants, 7 patent families); rabiesvirus (2 applicants, 10 patent families); and ebolavirus (4 applicants, 5 patent families).

Beyond communicable diseases, anti-cancer mRNA vaccines also make up an appreciable number of filings. The principle of mRNA vaccination against cancer mirrors the approach for infectious diseases: a tumour antigen is encoded in mRNA, which is delivered and expressed in patients to stimulate the immune system against cancer. Although a breakdown of mRNA cancer vaccine targets is not included in the EPO Insight Report, to date clinical trials for mRNA vaccines have been announced for cancers as diverse as melanoma, non-small cell lung cancer, pancreatic cancer, glioblastoma, and prostate cancer.

One notable aspect of the EPO Insight Report is that it does not appear to account for patent filings for technologies adjacent to mRNA vaccines, including patent filings to specific delivery vehicles and lipids, as well as nucleic acid modifications and delivery techniques that may be applicable to various RNA medicines including mRNA vaccines. It is therefore likely that the EPO Insight Report tangibly underestimates the total number of patent filings that are relevant to commercial mRNA vaccines.

Litigation trends

Given the complicated network of IP rights and the value of mRNA-based vaccines, it is not surprising that multiple infringement lawsuits have been launched in the wake of the COVID-19 pandemic. Most of the lawsuits involve the companies that rose to prominence with their successful mRNA-based COVID-19 vaccines. Somewhat foreseeably, these same companies are at the top of the EPO’s list of most active applicants in the field of mRNA-based vaccines. The litigation is mostly taking place in the US, the UK and Germany, accompanied by related patent challenges at the EPO and the USPTO.

CureVac v BioNTech

CureVac has filed two patent infringement lawsuits against BioNTech in the Dusseldorf Regional Court, Germany. CureVac alleges that BioNTech infringes two of its European patents (EP1857122 and EP3708668) and three German utility models (DE202015009961U1 (4c O 38/22), DE202015009974U1 (4c O 46-48/22) and DE202021003575U1 (4c O 51/22)). The European patents and the first two German utility models are directed to artificial nucleic acid molecules comprising specific features, while the third German utility model is directed to a composition which comprises an mRNA encoding a specific sequence for the SARS‑CoV-2 spike protein. In both lawsuits, CureVac is seeking fair monetary compensation, and not an injunction.

In response, BioNTech launched invalidity proceedings against EP’122 and cancellation proceedings against the utility models in Germany, as well as an opposition against EP’668 at the EPO. The invalidity hearing for the EP’122 patent took place in December 2023. The German Federal Patent Court confirmed the validity of the patent in its preliminary option, but then changed its mind at the hearing and nullified the patent instead. It is expected that CureVac will appeal this decision.

The rest of the infringement proceedings have been stayed pending the cancellation actions against the utility models and the opposition proceedings at the EPO.

In addition, BioNTech and Pfizer have initiated invalidation proceedings against CureVac in the UK (HP-2022-000023). The proceedings seek the revocation of EP’122, EP’668 and EP4023755. EP’755 is directed to an artificial nucleic acid molecule comprising specific features. BioNTech and Pfizer allege that the patents are invalid on the grounds of novelty, inventive step and sufficiency. EP’688 and EP’755 have also been challenged on added matter. EP’755 is also currently being opposed by BioNTech and Pfizer at the EPO.

Conversely, CureVac has claimed that BioNTech infringes these patents. The trial on the UK patent is expected to take place at the beginning of July 2024.

Moderna v Pfizer

Moderna launched proceedings against Pfizer in the Patents Court in London (HP-2022-000022) in 2022, asserting two of its European patents. Both patents are also under opposition at the EPO by multiple parties, including Pfizer and BioNTech. EP3718565, directed to an mRNA vaccine comprising the spike protein and an LNP, was revoked by an EPO Opposition Division in December 2023, but Moderna is appealing this decision. The oral proceedings against EP3590949, directed to a method of synthesising an mRNA comprising a chemically modified nucleotide, are scheduled for later this year.

In the Patents Court in London, Moderna seeks a declaration that the two EP patents have been infringed by Pfizer/BioNTech and monetary compensation in lieu of an injunction. Since Moderna made a pledge in October 2020 not to sue any other COVID-19 vaccine producers during the pandemic, it has proposed to limit the relief sought to infringing products manufactured after 7th March 2022. On that date, Moderna updated its pledge to instead “never enforce [its] patents for COVID-19 vaccines against companies manufacturing in or for the 92 low- and middle-income countries in the Gavi COVAX Advance Market Commitment”.

Pfizer and BioNTech have denied the infringement allegations and argued that Moderna waived its rights to bring any infringement claim with its 2020 pledge not to sue other COVID-19 vaccine producers during the pandemic. The pledge issue will likely be heard during the main trial which is scheduled to take place towards the end of April 2024.

Pfizer and BioNTech have also counterclaimed for a declaration of invalidity (HP-2022-000027), seeking to revoke the two European patents in question on the grounds of lack of novelty, lack of inventive step and insufficiency. Moderna, in turn, has denied all grounds of invalidity.

Moderna has also sued Pfizer and BioNTech for infringement of EP’565 and EP’949 in Germany (4b O 62/22), Ireland, Belgium and the Netherlands (C/09/643000). In these cases, Moderna is also seeking damages, not injunctive relief.

License agreement disputes

In addition to the infringement actions, there are ongoing disputes over license agreements involving BioNTech. Reports indicate that the US National Institute of Health (NIH) recently sent BioNTech a “notice of default” alleging that the company breached a license agreement and owes the NIH royalties and “other related amounts” on the sales of the Pfizer/BioNTech COVID-19 vaccine. NIH has previously reported that it holds a non-exclusive license with BioNTech, relating to an engineered version of the COVID-19 spike protein developed by government and academic researchers.

BioNTech has indicated that it is also engaged in discussions over royalty payments with the University of Pennsylvania. Both Moderna and BioNTech hold a series of sublicenses to mRNA‑related patents belonging to the University of Pennsylvania.

Outlook

As evidenced by the EPO’s analysis, the field of mRNA technology is highly dynamic with an accelerated number of patent families being filed. The steady increase in the numbers of patent applications indicates not only constant technological innovation, but also the high economic expectations associated with mRNA-based vaccines.

The commercial importance of these products is reflected in the profits generated by the COVID-19 vaccines, as well as the estimations for the financial remedies that may be awarded in the ongoing infringement proceedings. For instance, Pfizer/BioNTech generated a revenue of $36.8 billion in 2021 and $37.8 billion in 2022 from sales of their vaccine Comirnaty®. It is estimated that if Moderna wins the lawsuits against Pfizer/BioNTech, it could be awarded damages up to 10% of sales which amounts to $7.46 billion from 2021 and 2022 sales alone.

As the number of granted patents in the mRNA field increases, and as new valuable technologies enter the market, we would expect to see more litigation in the future. Unusually, mRNA vaccines moved rapidly from being an experimental platform technology to being widely used commercially, meaning that many of the patents dating from early research on the platform are still in force. It will be interesting to observe how the court proceedings noted above shape the IP landscape for mRNA technology more generally and how those patentees with broad protection seek to enforce or license their rights as new mRNA vaccines reach the market over the next few years.

At Carpmaels & Ransford, our patent attorneys regularly handle cases across vaccine technologies. We are particularly familiar with the subject area of this brief note, working regularly at the forefront of mRNA vaccine technology. We are well-equipped to handle any complexities that this exciting field generates during patent drafting, prosecution, opposition, and litigation.