The year 2019 exposed humankind to an unprecedented situation. While preparing to welcome the New Year, the world was unaware of the devastating condition lurking around the corner. A viral infection caused by the Novel strain COVID-19, engulfed all the continents in the blink of an eye. Covid-19 had severe, devasting effects in all spheres that were initially not envisaged causing irreversible damage. The global medical community was shaken by this phenonmena. The world was in lockdown situation for almost a year. The economy of most countries was impacted and the public was grappling with critical financial problems and commodity crises. To curb this devasting situation, efforts to produce a vaccine were initiated.

This article at the beginning focuses on a brief description of vaccine technology, followed by detailed information regarding the COVID-19 mRNA vaccine and the patent infringement suit filed by Moderna.

Vaccine Technology

Numerous approaches have been attempted to manufacture viable vaccines ever since the first vaccine was created in 1796 to treat smallpox. These techniques are getting more sophisticated and make use of cutting-edge technology to help safeguard the world from diseases that can be prevented.

Different technologies are applied to produce an efficient vaccine, depending on the pathogen (a bacteria or a virus) that is being targeted. There are mainly six types of vaccines.

Live-attenuated vaccine:

Live pathogens from bacteria or viruses that have been "attenuated," or weakened, are included in live-attenuated vaccines. In order to create live-attenuated vaccines, bacteria or viruses that nevertheless elicit a strong immune response but do not propagate disease or attenuated or modified form are chosen. Because these vaccines include a live attenuated pathogen, the immune system responds to them quite favourably and frequently retains the attenuated form of pathogen for a very long period. Example of these type of vaccine includes Measles, mumps, and rubella (MMR) vaccine, varicella (chickenpox) vaccine.  The mechanism behind the vaccine includes the administration of live attenuated pathogens (virus or bacteria) by syringe or mouth, followed by replication of weakened viral elements in the host cells. These replicated viral elements are taken up by Antigen-presenting immune cells (APCs), which ultimately trigger helper cells due to the immune response. As a result, the body creates B- cells to produce antibodies against the viruses. These antibodies bind with the virus and prevent it from entering the host cell and also destroy the infected cell. Apart from this, B-cells create memory cells to avoid attack when encountering the same virus in the future.

Inactivated vaccine

Inactivated vaccines generally use a dead pathogen i.e. a dead virus-like Polio mosaic virus. The inactivated or killed pathogen is potent enough to elicit an immune response when the vaccine is administered to a human, for example, but it is unable to spread illness. It frequently takes several doses to fully protect a person and develops immunity. These vaccines can be mass-produced and less expensive. The commonest examples include Polio vaccine and influenza vaccine. The inactivated vaccine is delivered by syringe or mouth, which is then taken up by antigen-presenting cells. The vaccine is cut into pieces called antigen which is recognized by the immune system and consequently triggered the immune helper cell. B-cells thus triggered produce antibodies destroying viruses or bacteria. The antibodies level generally fades away with time, due to which additional shots are needed. This type of vaccine precedes all others and may be considered a conventional vaccine. Covaxin from Bharat Biotech, Sinovac, and Sinofam from China, are amongst this category of vaccines developed recently.

Subunit (polysaccharides, recombinant, and conjugate) Vaccine

Subunit vaccinations do not contain the entire pathogen but only a piece of the pathogen, thus they cannot cause infection. They are therefore appropriate for those who cannot receive "live" vaccines, including small children, the elderly, and those with impaired immune systems.

Protein vaccine: In this case, protein from the virus is isolated and mixed with an adjuvant immune-system stimulator. Once the vaccine is administered in the body, the target protein is taken up by the APCs and triggers the immune system, which ultimately destroys the pathogen.

Polysaccharides and conjugate vaccines: Bacteria camouflaged themselves in their polysaccharides layer which is not detectable by the immune system. In this case, a conjugate protein is attached to the polysaccharides and injected into the host body. The polysaccharides are taken up by the APCs and triggered the immune system destroying the pathogen.

Recombinant vaccine: In this case, DNA coding for the surface protein of virus or bacteria is engineered into a vector (bacterium plasmid) and this hybrid is injected into the body. The vaccine is taken up by the APCs and triggered the immune system to destroy the pathogen.  

Toxoid Vaccine:

Instead of attacking the bacteria themselves, toxoid vaccinations target the harmful activity produced by the bacteria using inactivated toxins. The purpose of toxoid vaccinations is to provide individuals with a method to produce antibodies that can neutralize these toxins. Tetanus, diphtheria, and pertussis are a few of the toxoid-mediated illnesses that can be prevented using toxoid vaccines. Typically, booster shots are advised every 10 years or so.

Viral Vector Vaccine

Viral vector vaccines transmit the genetic code of the antigen to the immune system to fight the hosts' cells through a harmless virus. They essentially function as gene delivery devices. By doing this, information about the antigen is sent, causing the body to produce an immunological response. The immune system typically responds strongly to vector vaccinations. Usually, immunity can be built up with just one dose of the shot. Boosters could be required to keep immunity strong. The most recent example includes the Ebola vaccine, and COVID-19 vaccines Sputnik as well as from AstraZeneca,  Johnson & Johnson.

Messenger RNA (mRNA) Vaccine

The use of mRNA vaccines is one of the most recent and intriguing developments in vaccine technology. mRNA vaccines can be created fast utilizing the pathogen's genetic code, as opposed to traditional vaccinations, which can take several months or even years to culture.

When an mRNA vaccine is administered, the RNA material instructs the body to produce a particular kind of protein that is particular to the virus but does not harm the recipient. An immunological reaction to the protein results in the production of antibodies that can detect it. In this manner, if a person were to come into contact with that virus in the future, the body would be equipped (through antibodies) to combat it. This is the most recent technology, and examples include the Moderna’s COVID-19 vaccine and the Pfizer-BioNTech’s COVID-19 vaccine.

Moderna: mRNA Vaccine Technology Journey

Moderna was founded in 2010 in Cambridge, Massachusetts, and ever since, the company has dedicated all of its efforts and financial resources to the development of mRNA therapies.

One of the major problems with mRNA is that the body's immune system can mistake it for foreign material and fight it. Moderna's foundational research in this field advanced the solution to this issue. To better avoid triggering an immunological response, Moderna scientists started researching novel chemical changes to the mRNA in 2010. Through that effort, it was discovered that mRNA molecules with a particular modification, in which uridine is switched out for 1-methylpseudouridine, were surprisingly better than other chemically modified mRNAs. Then, Moderna researchers looked into ways to get the chemically altered mRNA to cells. They investigated if lipid nanoparticle-formulated chemically altered mRNAs might be delivered to cells in 2011. These tests demonstrated that cells could successfully express the protein that was encoded by modified 1-methylpseudouridine mRNA for the first time if they are contained in lipid nanoparticle capsules. Following those productive tests, Moderna built their mRNA platform on 1-methylpseudouridine-modified mRNA in a lipid nanoparticle capsule.

Around the time a coronavirus known as "Middle East Respiratory Syndrome" or "MERS" initially appeared in 2014, Moderna established a division dedicated solely to the creation of mRNA vaccines for infectious diseases. A lipid nanoparticle encoding the full-length spike protein of the MERS coronavirus was created by Company scientists in 2015 as a MERS mRNA vaccine. Animal challenge trials demonstrated that the novel vaccine successfully produced antibodies that blocked the MERS virus and avoided infection. These experimental outcomes offered proof of the concept that coronavirus infection may be successfully avoided by using mRNA encoding the full-length spike protein in a lipid nanoparticle.

Moderna was granted patents covering the inventions underpinning its mRNA platform and disease-specific vaccine designs, including those for coronaviruses, to safeguard its significant time and resource investments in creating its technologies. These patent applications were made from 2011 to 2016.

Moderna was in a unique position to respond to the COVID-19 pandemic since it had already carried out ten years of fundamental research in the field of mRNA drugs, specifically on coronaviruses.

Nearly all of Moderna's workers were involved in research and development before COVID-19. To meet the challenge posed by COVID-19, Moderna moved resources away from other initiatives and hired and developed new teams. To raise the money required to produce the vaccine, Moderna also issued additional stock. Because Moderna had done the study and was confident that its mRNA platform could combat this novel coronavirus, the Company performed all of these activities.

As a result, Moderna was able to quickly use its current mRNA technology to address the situation in the early 2020s. In a couple of weeks, the Company was able to create a COVID-19 vaccine that was ready for testing in clinical trials thanks to its collaboration with the U.S. government, particularly the National Institute of Health (NIH).

The NIH began using Moderna's COVID-19 vaccine in human trials on March 16, 2020, just two months after the genetic sequence for the virus that causes COVID-19 was disclosed, contrary to prior predictions that vaccine development could take years.

On December 18, 2020, the FDA granted an emergency use permission allowing Moderna's COVID-19 vaccine, now known as Spikevax®, to be used in people 18 years of age and older. On January 31, 2022, the FDA granted Spikevax® full approval for use in that demographic.

Pfizer-BioNTech: mRNA Vaccine Technology Journey

The much-discussed Pfizer-BioNTech m-RNA vaccine was actually developed by BioNTech, a German immunotherapy company. This was further assigned to Pfizer, an American Multinational Pharma and Biotech company, for further upscaling before manufacturing, marketing, and distribution.

On 17^th March 2020  BioNTeh and Pfizer announced that the companies developed a possible mRNA-based coronavirus vaccine to prevent COVID-19 infection has been developed, and it has been stated that the businesses have signed a letter of intent about its co-development and distribution. Combating this spreading pandemic as soon as feasible by combining Pfizer's development, regulatory, and commercial skills with BioNTech's mRNA vaccine technology and knowledge as a leader in the field. To enable the parties to collaborate right away, the companies signed a Material Transfer and Collaboration Agreement.

BioNTech and Pfizer collaborated on a project called “Project Light Speed” to develop an mRNA COVID-19 vaccine in record time.  Pfizer and BioNTech would eventually complete one of the most ambitious vaccine development programs in history over nine months, breaking the previous record of four years set by the creation of a mumps vaccine in the 1960s. A COVID-19 mRNA vaccine created by Pfizer and BioNTech is sold under the trade name Comirnaty®. The US Patent No. 10,960,070 has been granted to Pfizer for Comirnaty®. 

More than 20 vaccination candidates representing various mRNA constructions and target antigens were the initial Project Lightspeed vaccine candidates that BioNTech put through preclinical testing. On April 23, 2020, Pfizer and BioNTech have chosen to move on with clinical testing of four of the remaining vaccine candidates. Not every COVID-19 vaccine candidate developed by Pfizer and BioNTech made advantage of Moderna's proprietary innovations. For instance, based on information and conviction, Pfizer and BioNTech looked into the "BNT162a1" vaccine candidate, which used mRNA containing unmodified uridine. Additionally, BNT162c2, a vaccine candidate that made use of self-amplifying mRNA technology, was investigated by Pfizer and BioNTech. Both BNT162a1 and BNT162c2 do not utilize Moderna's patented mRNA platform, which consists of modified mRNA with 1-methylpsuedouridine in a lipid nanoparticle formulation.

Nevertheless, as Pfizer and BioNTech advanced in their clinical development, they primarily concentrated on vaccine designs that made use of Moderna's unique technologies. The FDA authorized the use of BNT162b2 for emergency use in people older than sixteen (16) on December 11, 2020. The FDA authorized Comirnaty® (BNT162b2BLA)'s for use in people older than 16 on August 23, 2021.

The Patent Infringement suit

On August 26, 2022, Moderna sued Pfizer and BioNTech for patent infringement, claiming they duplicated technology that Moderna developed years before the pandemic. The case was filed in the United States District Court in Massachusetts and the Regional Court of Dusseldorf in Germany for monetary damage.

Two (2) essential components of Moderna's unique mRNA technology platform were duplicated by Pfizer and BioNTech. First, they chose to apply the same chemical alteration to their mRNA that Moderna scientists had first created years earlier, patented, and used in Spikevax®. Secondly, the coronavirus vaccine design that Moderna had pioneered based on its prior work on coronaviruses and which the business copyrighted and employs in Spikevax®, the Pfizer and BioNTech vaccine encoded for the same sort of coronavirus protein (i.e., the full-length spike protein). The success of Pfizer and BioNTech's vaccine was largely due to the Moderna technologies they decided to imitate.

The infringement case is based on three patents that cover the core intellectual property of Moderna and which claim priority to applications submitted between 2011 and 2016. The three patents which are collectively known as Asserted Patents are U.S. Patent Nos. 10898574,10702600 and 10933127.

Moderna is suing for the loss of the revenue Pfizer and BioNTech derived from sales in the United States as well as from its domestic manufacturing for export to non-AMC 92 countries. Any patent rights created as a result of the cooperation between Moderna and the NIH to fight COVID-19 are unrelated to this lawsuit. In addition, the scope of the remedy requested in this complaint is limited in recognition of the importance of providing access to these essential vaccines. Moderna is not asking for an injunction because it does not want Comirnaty® to be taken off the market or sold in the future. Moderna is not requesting damages for actions taken before March 8, 2022, under its patent agreement. Furthermore, Moderna is not requesting compensation for the sales made by Pfizer and BioNTech to the 92 low- and middle-income nations covered by the Gavi COVAX Advance Market Commitment.

Moderna voluntarily agreed on October 8, 2020, that "while the pandemic continues, Moderna will not enforce our COVID-19 related patents against those manufacturing vaccines designed to battle the pandemic." This was due to the unusual difficulties posed by the COVID-19 pandemic. To avoid detracting from efforts to terminate the pandemic as soon as feasible, Moderna refrained from asserting its patents earlier.

Case Analysis

Moderna's patent no.  US 10,898,574 titled "Delivery and formulation of engineered nucleic acids" teaches Moderna's mRNA platform technology, which uses mRNA to encode a polypeptide that includes modified uracil, including 1-methylpseudouridine, in a formulation of lipid nanoparticles capsule. This patent claims pharmaceutical formulations as well as processes for making polypeptides of interest.

Claim 2 of patent no.: US 10,898,574 is recited as:

"A pharmaceutical composition comprising:

a plurality of lipid nanoparticles comprising a cationic lipid, a sterol, and a PEG-lipid,

wherein the lipid nanoparticles comprise an mRNA encoding a polypeptide,

wherein the mRNA comprises one or more uridines, one or more cytidines, one or more adenosines, and one or more guanosines and wherein substantially all uridines are modified uridines."

Comirnaty® is a pharmaceutical composition comprising a plurality of lipid nanoparticles comprising a cationic lipid, a sterol, and a PEG-lipid, wherein the lipid nanoparticles comprise an mRNA encoding a polypeptide, wherein the mRNA comprises one or more uridines, one or more cytidines, one or more adenosines, and one or more guanosines, and wherein substantially all uridines are modified uridines.

Claim 9 of patent no.: US 10,898,574 is recited as:

"The pharmaceutical composition of claim 2, wherein the modified uridine is 1-methyl-pseudouridine."

Pfizer confirmed in its publication that the uridines in Comirnaty® are modified uridines—namely, 1-methylpseudouridine.

Another Moderna's patent no.: US 10,702,600 titled “Betacoronavirus mRNA vaccine" claims a composition comprising mRNA comprising an open reading frame encoding a betacoronavirus S protein or S protein subunit formulated in a lipid nanoparticle.

Claim 1 of patent no.: US 10,702,600 is recited as:

"A composition, comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle."

Comirnaty® is a composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle."

Moderna's patent no.: US 10,933,127. titled “Betacoronavirus mRNA vaccine" claims methods of administering to a subject mRNA comprising

an open reading frame encoding a betacoronavirus S protein or S protein subunit formulated in a lipid nanoparticle to induce in the subject an immune response to the S protein or S protein subunit,

wherein the lipid nanoparticle comprises certain specified percentages of ionizable cationic lipid, neutral lipid, cholesterol, and PEG-modified lipid.

Claim 1 of patent no.: US 10,933,127 is recited as:

"A method comprising administering to a subject a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S-protein or S protein subunit formulated in a lipid nanoparticle in an effective amount to induce in the subject an immune response to the BetaCoV S protein or S protein subunit wherein the lipid nanoparticle comprises 20-60 mol% ionisable cationic lipid, 5-25 mol% neutral lipid, 25-55 mol% cholesterol, and 0.5-15 mol% PEG-modified lipid.”

The use of Comirnaty®  is a method comprising administering to a subject a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle in an effective amount to induce in the subject an immune response to the BetaCoV S protein or S protein subunit wherein the lipid nanoparticle comprises 20-60 mol% ionizable cationic lipid, 5-25 mol% neutral lipid, 25-55 mol% cholesterol, and 0.5-15 mol% PEG-modified lipid.

While the '600 and '127 patents recite mRNAs encoding a b-coronavirus Spike protein, these claims would encompass vaccines to SARS-CoV-1. Of the three (3) asserted patents, the '574 patent offers the widest claims, not being confined to a particular virus or antigenic protein thereof. According to numerous paragraphs of the complaint, Moderna's accusations of infringement against the Pfizer/BioNTech Comirnaty® vaccine are based in part on these grounds.

The complaint has two noteworthy elements, which may be a reflection of the post-pandemic patent mood. The first is a lengthy explanatory part that outlines the long history of the technology that Moderna was able to use to create their Spike mRNA. vaccination for SARS-CoV-2. The background of Moderna's creation of the underlying mRNA technology and its efforts to create a vaccine during the epidemic are both included in this section of the complaint. Additionally, the complaint argues that the firm's intellectual property (IP) served as both the technological basis for its successful and quick development of the COVID vaccine and as protection against the considerable financial and investment risk caused by Moderna's development of its vaccine. The Prayer for Relief is the second noteworthy aspect of the case and Moderna's legal strategy.

In fact, at least one University of Pennsylvania-owned patent, U.S. Patent No. 8,691,966, which is in the name of the BioNTech Principal Katalin Kariko as an inventor,  discloses and claims mRNA modifications containing 1-methylpseudouridine; this patent has the earliest priority date about 4 years earlier than Moderna's patents asserted in the litigation. As a result, it is not unlikely that Pfizer/BioNTech will petition for inter partes review.

These factors combine to create a compelling story for this litigation procedure.

Conclusion

While observing the case and the history associated, first of all, an existing trend is visible wherein a small company or even a start-up with specific R&D expertise is developing a novel product, in this case, a vaccine, which was taken over by a much larger entity for upscaling, manufacturing and marketing purposes. A similar trend is visible in the technology sector. Region-wise, it is an observation that Europe is home to such smaller entities working on innovations, whereas the larger entities are mostly US based.

Coming to the vaccination drive, in the US, 229 million doses of Moderna and 360 million doses of Pfizer's Covid-19 vaccine have been administrated this year. It has been a calm reign for both businesses as both Moderna and Pfizer dominated the COVID-19 vaccination market for more than a year until Moderna started the patent war of the pandemic era.

Moderna reiterated its promise to never pursue its COVID-19 patents in 92 low- and middle-income countries, claiming that its litigation was not intended to prevent people from receiving vaccinations. However, Moderna asserted that it did anticipate that businesses like Pfizer and BioNTech would uphold its intellectual property rights. As a result, Moderna is asking for royalties based on sales made after March 8, 2022, but excluding sales to the U.S. government or low-income nations.

According to Jacob Sherkow, a professor at the University of Illinois College of Law who specializes in biotech intellectual property concerns, if Moderna prevails, the royalty in such cases is typically a "high single-digit" percentage of sales.