First published in our Biotech Review of the Year publication (Issue 10).
The “updating” of that pledge in March 2022, limiting it to low-income countries, foreshadowed a new era in patent litigation. In this article we provide an overview of ongoing patent litigation relating to mRNA technology and discuss what the future might hold in this fertile new battleground for licensing disputes.
In Issue 9 of the Bristows Biotech Review of the Year, we took a closer look at mRNA, what it is and what it could potentially be used for. We discussed its transformational potential, not only as a vaccine platform but also for use as a therapy against genetic diseases, in cancer immunotherapy, and in regenerative medicine. This potential has led to staggering levels of growth and investment in mRNA companies. As expected, this has also led to companies jostling for position in the market.
Pfizer made $37.8bn in revenue from Covid vaccine sales alone in 2022, while Moderna made $18.4bn. This year, with hundreds of millions of dollars in royalties at stake, we examine the uglier and sometimes inevitable outcome of revolutionary technologies such as this – patent litigation.
A detailed overview of mRNA technology can be found in a previous Bristows article here. However, in short, mRNA technology can essentially be viewed in two parts: (1) the delivery system and (2) the coded mRNA itself. The delivery system ensures the mRNA gets into the intended cells in the body effectively and safely. The most used delivery system is lipid nanoparticles (LNPs). The mRNA component corresponds to the specific genetic sequence of the protein or antigen you want the cells to produce. Broadly, patents protecting mRNA technology fall within one of these two categories.
As discussed in another previous article by Bristows, the web of intellectual property that protects mRNA technology is complex and overlaid by a large network of partnerships and licensing arrangements. However, there are a few key companies leading the way in the field, each with a market capitalisation in the multiple billion dollars. Moderna, BioNTech and CureVac are the largest of these and each have numerous mRNA products in their pipelines as well as large mRNA patent portfolios, valuable know-how and key patent licences and partnerships in place. Companies such as Arcturus and Translate Bio also have significant presences in the market, along with market capitalisations over a billion dollars and multiple products in their pipelines.
Early work on LNPs was carried out by Canadian biotech Arbutus Biopharma Corporation (Arbutus) in collaboration with the University of British Columbia. Several companies have since taken licences of LNP patents owned by Arbutus. In 2018, Arbutus spun out rights to its LNP technology (excluding rights to hepatitis B) into a company called Genevant Sciences GmBH (Genevant) as part of a joint venture with Roivant Sciences Ltd. The Arbutus patents have been the subject of some litigation, discussed below.
Moderna has been focused on the potential of mRNA since it was founded in 2010 and has invested heavily in delivery science. Moderna has indicated that it has an extensive portfolio of patents relating to its mRNA platform, including novel lipid components designed for optimal expression of both therapeutic and vaccine mRNAs. The Moderna patents have been the subject of some of the highest profile litigation in this space and Moderna’s own Covid-19 vaccine is also accused of patent infringement.
BioNTech uses several delivery formulations for its products, including LNPs and its own proprietary lipoplex (lipid carriers) formulations for which it has several patent filings. Again reflecting the importance of delivery systems to the success of an mRNA product, BioNTech also has several active third-party partnerships focussed on this area, including a partnership with Genevant and a non-exclusive licence from Acuitas Therapeutics, Inc (Acuitas) for LNP formulations used in the Pfizer/BioNTech Covid-19 vaccine. BioNTech has also indicated it has a broad patent estate comprising over 100 patent families. BioNTech’s patent estate includes patent filings directed to features of therapeutic mRNA structures, mRNA formulations (including its lipoplex formulations and lipid nanoparticles), mRNA manufacturing, and uses of mRNA therapeutics. Whilst BioNTech is not yet asserting its own patents, the Pfizer/BioNTech vaccine is accused of patent infringement.
CureVac is in the process of developing its own proprietary LNP system, however it currently relies on third party LNP delivery systems for its clinical assets. CureVac is also party to a Development and Option Agreement with Acuitas that provides CureVac with access to Acuitas’ LNP technology and has entered into a development and option agreement with Arcturus Therapeutics (Arcturus) to access Arcturus’ lipid-mediated delivery IP. CureVac similarly has a large patent portfolio relating to mRNA products. These include patents relating to CureVac’s mRNA technology platform, its delivery system and its product candidates (which include oncology candidates and rabies vaccines). CureVac is actively asserting some of these patents already.
Unsurprisingly, almost all the ongoing patent litigation relates to these key players. The outcomes of these early battles could cement the parties as market leaders in the mRNA field. For the purpose of this article, we will therefore focus on these companies. However, this is by no means an exhaustive review and we expect more disputes focussed on mRNA to emerge in the future. Furthermore, there are ongoing invalidity proceedings in many jurisdictions, for example EPO oppositions, that we will not cover here.
Arbutus and Genevant v Moderna
In the first major patent infringement lawsuit in the mRNA space, on 28 February 2022, Arbutus and Genevant filed a claim for patent infringement by Moderna in the US District Court of Delaware.
Arbutus alleges that Moderna infringes the claims of 6 US patents through sales of its Spikevax (Covid-19) vaccine and booster products. The patents relate to LNP technology, specifically lipid vesicles and nucleic acid-lipid particles. Moderna had previously sublicensed some of Arbutus’ LNP delivery technology. However, following the limitation of these rights in 2018, Moderna attempted to invalidate three of Arbutus’ patents in proceedings before the USPTO’s Patent Trial and Appeal Board (PTAB). These had mixed results and Moderna appealed the ruling on one patent that was later upheld by the Court of Appeals for the Federal Circuit, paving the way for the patent infringement claim by Arbutus and Genevant.
In further developments, Moderna countered with a motion to dismiss in May 2022, arguing that the US government should defend against the patent infringement because Moderna was simply providing vaccines under a federal contract. However, US District Judge Mitchell Goldberg was not convinced and dismissed the motion. Modena will therefore have to fight this battle on its own.
Alnylam v Moderna and Alnylam v Pfizer
Less than two weeks after the Arbutus and Genevant claim, on 17 March 2022, Alnylam Pharmaceuticals (Alnylam), an American biopharmaceutical company, also filed a claim against Moderna, and separately Pfizer, in the US District Court of Delaware. Alnylam alleges that both Moderna and Pfizer infringe its patent relating to LNP technology, specifically covering one of the four lipid components encapsulating the mRNA payload. Alnylam filed the claims on the same day the USPTO granted the patent in question.
On 12 July 2022, Alnylam added fuel to the fire and again separately sued Moderna and Pfizer for infringement of a second newly-granted patent, this time for the entire LNP and its method of production.
In both cases Alnylam is seeking royalties from the sales of vaccines and boosters, but no injunction.
CureVac v BioNTech
On 7 July 2022, CureVac filed a patent infringement claim against fellow German company BioNTech in the Dusseldorf Regional Court in Germany, alleging infringement of four CureVac patent claims concerning the features of the mRNA payload and lipid formulation used to make the BioNTech coronavirus vaccine.
CureVac said it has no intention to seek an injunction, but it does seek recognition and royalties from past and future sales. CureVac CEO Franz-Werner Haas stated “There’s a piece of IP which we think has been used. That’s OK. We’re not against using it, especially in a pandemic… We just want to have this piece of contribution recognized.”
If CureVac were to win, it is estimated by Berenberg Capital Markets, assuming $20bn of Pfizer and BioNTech’s Covid-19 vaccine revenue could be in question, that there is a $500m “potential upside” for CureVac based on a royalty rate of 2% to 3% in an “optimistic scenario.”
BioNTech maintains that its vaccines and boosters do not infringe the CureVac patents. In retaliation on 26 July 2022, BioNTech filed complaints in the US District Court of Massachusetts, seeking non-infringement judgments in relation to the equivalent US patents to those being asserted in the German case.
Moderna v Pfizer and BioNTech
In the most high-profile patent litigation case relating to mRNA, after more than a year of dominating the Covid-19 vaccine market between them, Moderna made patent infringement claims against Pfizer and BioNTech. After Moderna filed claims in August 2022 in the US and Germany, Pfizer and BioNTech countered with invalidity proceedings in the UK. Moderna alleges that Pfizer and BioNTech’s vaccine infringes patents it holds.
Moderna is asserting patent rights filed between 2011 and 2016, relating to three elements of Pfizer/BioNTech vaccine:
- Use of lipid nanoparticles to encapsulate mRNA;
- Replacement of uracil with N1-methylpseudouridine in the vaccine mRNA; and
- Use of mRNA which codes for the SARS-CoV-2 spike (S) protein.
CEO Stéphane Bance said Moderna is seeking to “protect the innovative mRNA technology that we pioneered, invested billions of dollars into creating, and patented during the decade preceding the Covid-19 pandemic”.
A company spokesperson for Pfizer stated that it is “surprised by the litigation given the Pfizer/BioNTech Covid-19 vaccine was based on BioNTech’s proprietary mRNA technology and developed by both BioNTech and Pfizer” and will “vigorously defend against the allegations of the lawsuit.”
Moderna is not seeking to remove the Pfizer/BioNTech vaccine from any market. It also is not targeting vaccine sales in lower income countries covered by the global COVAX initiative, instead focussing only on developed markets.
In recent developments in the US, Pfizer/ BioNTech argue that their vaccine does not infringe the patents, that Moderna’s patents are invalid, and that Moderna waived its rights to bring the claim when it pledged not to sue other Covid-19 vaccine producers during the pandemic.
It is important to note that none of the claimants in the above cases are seeking an injunction to remove vaccines from the market, in any jurisdiction. This is probably due to the very low chance of obtaining such an injunction owing to the public interest in allowing the vaccines to remain on the market. Furthermore, any claimant seeking an injunction would likely face significant public backlash. Therefore, the primary motivation in these cases is damages, normally calculated as a ‘reasonable royalty’ applied to infringing sales. With vaccine products having collectively achieved tens of billions of dollars in revenue in recent years, such damages awards could be quite significant.
All these cases are in their very early stages and anyone operating in the mRNA field should keep up to date with their outcomes. For example, if any of the early LNP patents are invalidated, other mRNA competitors could have more flexibility in the use of delivery formulations without having to take a licence. Alternatively, if patents survive validity challenges during litigation, then surviving patents would effectively be strengthened, having been battle-tested, and rights holders may be more likely to utilise them to force competitors to take a licence to the technology covered by those patents in the future.
As already mentioned, we expect many more disputes to arise in this area. It is expected that defendants in these cases will begin to weaponise and deploy their own patent portfolios in retaliation. These disputes may therefore take years to play out in full.
In conclusion, companies working in the mRNA space should monitor this ongoing litigation carefully and work with their IP lawyers to set appropriate strategies to traverse this complex space based on the outcomes.