mRNA Patent Litigation: The ‘Sport of Kings’

Battle lines are being drawn in the fight over the lucrative mRNA vaccine technology used in certain Covid 19 vaccines. Moderna recently sued Pfizer alleging patent infringement of three out of eight patents that cover its Covid 19 vaccine (Spikevax).

Moderna has supplied over 299 million doses of its Covid 19 vaccine to the United States and has, reportedly, lined up supply deals worth USD 35 billion through the end of 2022.

Pfizer and BioNTech have supplied over 472 million doses of their COVID-19 vaccine (Comirnaty) for use in the United States. Pfizer recently announced that it expects an additional USD 32 billion in global revenues from Comirnaty.

As reported, Moderna earned revenue of around USD 10 billion for its vaccine, and Pfizer earned around USD 22 billion, in just a year. Both companies have enjoyed windfall financial gain from the sale of their respective vaccines. The sales of these vaccines are likely to rank among the highest in a single year for any medical product in history.

The sheer size of sales and revenue coupled with patent monopolies and the immense potential of the mRNA technology, makes both these entities King-like – rich, supreme and sometimes hypocritical.

The tale of two kings

Moderna

Strikingly, the portrait that Moderna paints of itself is not one of a King but of a small, research-driven start-up in need of funding. Moderna’s patent infringement lawsuit is a revenue seeking activity since Moderna wants fair compensation but does not want to remove Comirnaty from the market.

As claimed, fair compensation will allow it to invest in its leading mRNA platform. Moderna believes that this case will also ensure that next generation biotech startups don’t lose their ability to rely on the patent system.

This David v. Goliath narrative is probably drawn up since Moderna has requested a jury trial. Some studies have shown that juries favour independent inventors / start-ups over bigger corporate defendants (e.g. Judge Kimberly Moore, Populism and Patents, NYU L.Rev).

Moderna was set up in 2010 with its sole focus being mRNA technology. Moderna claims to be at the forefront of this technology having begun its research before the pandemic and before anyone had figured out how to make or use mRNA medicines successfully. And along the way it encountered several technical challenges which it successfully overcame.

Moderna’s Spikevax is covered by eight patents, three of which have allegedly been infringed by Pfizer and BioNTech. The three patents cover novels ways through which Moderna stabilized the mRNA by modifying its chemical structure (to reduce immune response against mRNA itself); identified ways to optimise its mRNA platform; and developed new techniques for manufacturing on a large scale.

These efforts include – replacing uridine in the mRNA molecule with 1-methylpseudouridine to reduce immune response against mRNA itself; and discovering that encoding a full-length coronavirus spike protein in a lipid nanoparticle formulation was highly effective at producing neutralizing antibodies to the coronavirus.

Due to its focus on mRNA technology and research in this field, once the genomic sequence for SAR-CoV-2 was published, Moderna was able to produce its vaccine at a lightning-fast pace. Moderna had six mRNA candidates for infectious diseases in clinical trials by the time COVID-19 arrived.

However, it must be kept in mind that Moderna was able to get the vaccine out so fast because of several other factors. As disclosed by KEI and The Intercept, the US government gave companies special authority to use another person’s technology, without permission, to produce Covid 19 vaccines. Moderna was one such company that was granted a compulsory license. Such relaxations were specifically aimed at speeding up the process of vaccine production. Easy for Moderna to now push for ‘licensing and not abrogating patents’. This issue is the center of controversy in two lawsuits filed against Moderna by Arbutus Biopharma Corp. and Alnylam Pharmaceuticals Inc. over the use of lipid nanoparticle technology in the mRNA vaccines.

Its partnership with the NIH is also alluded to. However, patent ownership controversy with the NIH is a separate story (here and here).

Pfizer and BioNTech

Unlike Moderna, Pfizer and BioNTech started with as many as 20 vaccine candidates representing different mRNA constructs. Moderna claims that not all 20 infringed its patents but ultimately Pfizer and BioNTech decided to go ahead with the one that uses Moderna’s patented technology i.e. uses the same 1-methylpseudouridine chemical modification in a lipid nanoparticle formulation and contains mRNA encoding for the same full-length spike protein for SARS-CoV-2.

It appears that BioNTech (another start-up founded by Dr. Sahin and Dr. Tureci) was focused on cancer treatments prior to the pandemic but was also looking into mRNA for cancer treatment.

Further, Katalin Karikó whose scientific research has been acknowledged as foundational in RNA mediated immune activation research is associated with BioNTech. Together with Drew Weissman, she holds U.S. patents for the application of non-immunogenic, nucleoside-modified RNA.

As reported, these patents have been licensed to both Moderna and BioNTech. BioNTech entered into a partnership with 173 year old Pfizer to commercialise its mRNA technology.

Pfize and BioNTech also have patent infringement cases filed against them for their vaccine e.g. by CureVac, Alnylam Pharmaceuticals and Allele Biotechnology and Pharmaceuticals.

The world their battlefield

While this patent battle is technically being fought in court rooms in Cambridge, MA and Düsseldorf, Germany, it could have worldwide implications.

Moderna has pledged (again but this time it appears to be a pledge forever) never to “enforce 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 (AMC), provided that the manufactured vaccines are solely for use in the AMC 92 countries.” This pledge becomes relevant for initiatives such as the WHO’s mRNA tech-transfer hub in South Africa. It appears that WHO asked Moderna and Pfizer and BioNTech to help teach researchers in low-and middle-income countries how to make their COVID-19 vaccines. However, neither of the companies responded so the WHO decided to go ahead anyway and replicated Moderna’s vaccine (relying on its older pledge). See here for implications on reneging on pledges in the patent context.

Added to this, the fact remains that mRNA vaccine technology is a new era in vaccine science, one with immense potential even beyond Covid 19. Due to its effectiveness, potential for low-cost manufacturing, capacity for speedy development and safe administration, mRNA vaccines have been prophesied to be a promising alternative to conventional vaccine approaches. The facility to make mRNA can also be used for vaccines for different diseases making manufacturing flexible. See here for a brief overview of the science behind mRNA vaccines.

The surest and easiest way for countries and companies to access this technology is to obtain a license from the technology owner. However, as is evident, ownership over this technology and its component parts is extremely fuzzy.

When ownership is itself in dispute, the process of obtaining a license from either entity becomes a risky and expensive exercise.

Some argue that neither Moderna nor BioNTech-Pfizer nor Curevac and others who are litigating this tech own the technology – it belongs to the world and is in public domain (here). Others argue that some of Moderna’s patent claims are over-broad and may be weakened due to prior art.

Given the potential of this technology, it is hoped that this battle gets over sooner rather than later. Some suggest that a simplified inter partes review (before the USPTO rather than courts) is all that it would take which could result in a quick decision. However, given that this is a sport of kings, history shows that when billion-dollar biomedical inventions are involved, disputes drag on in courts for years.

Thank you to Swaraj for his inputs!