mRNA-Based Vaccine and Other Therapeutics

mRNA-based vaccines have become one of the most discussed technologies both inside and outside of the patent world since the pandemic. In a nutshell, mRNA-based COVID-19 vaccines comprise two main components: a modified mRNA that expresses a desired protein without setting off inflammatory responses in the cells, and a lipid delivery system made of lipid nanoparticles ("LNPs") that protects and transports the mRNA into the body so it will express the desired protein and elicit intended immune responses.  

The ability to deliver mRNAs into cells offers great potential and flexibility to develop not only vaccines against infectious pathogens, but also treatments for other diseases, such as cancer and genetic metabolic diseases. Indeed, both Moderna and Pfizer/BioNTech were able to develop COVID-19 mRNA vaccines, the first ever mRNA vaccines, at a record speed. They were also able to update their vaccines as new variants of the coronavirus emerged.  

GSK Sues Pfizer and BioNTech

On April 25, 2024, GSK became the latest player to join the crowded patent battlefield concerning COVID-19 mRNA vaccine, suing Pfizer and BioNTech for infringing five mRNA vaccine patents it owns. See GlaxoSmithKline Biologicals SA v. Pfizer Inc., Case No. 24-cv-00512 (D. Del).  

According to the complaint, GSK owns, through acquisition from Novartis, a patented platform "to formulate and administer mRNA encoding a wide range of immunogens." Id. dkt. 1, at 1-2, 10. The asserted claims recite formulations comprising a RNA and lipids, or methods of eliciting immune response by administering a formulation comprising a RNA and lipids. All asserted patents claim priority to two provisional applications filed in 2010, and are issued from applications that are either a continuation or a division of U.S. Patent Application No. 13/808,080.

The complaint identifies several monovalent and bivalent COVID-19 vaccine products by Pfizer/BioNTech that infringe. Id. at 3. The complaint alleges infringement under 35 U.S.C. § 271(a), (b) and (c) as well as willful infringement, and seeks monetary relief.  

It's unclear whether GSK will go after other mRNA vaccine manufacturers, e.g., Moderna. GSK has at least nine patents issued from the '080 application family and may continue prosecution to get more patents. 

The COVID-19 mRNA Vaccine Patent War: Where Things Stand Now

The technical and commercial success of COVID-19 mRNA vaccines led to a slew of patent infringement lawsuits against Moderna and Pfizer/BioNTech, alleging, inter alia,  their COVID-19 mRNA vaccines infringe various patents that are directed to modified mRNA, LNPs, and/or mRNA vaccines, as well as the disputes between Modern and Pfizer/BioNTech. The diagram below illustrates pending and completed patent disputes concerning COVID-19 mRNA vaccines.  

Direct Disputes Between Moderna and Pfizer/BioNTech 

In August 2022, Moderna sued Pfizer/BioNTech in the District of Massachusetts, alleging that Pfizer’s COVID-19 vaccine infringes three patents that are directed to modified mRNA or mRNA vaccine. See ModernaTX, Inc. v. Pfizer Inc., No. 1-22-cv-11378 (D. Mass.). Pfizer and BioNTech counterclaimed, and asserted several defenses, including license and waiver defenses stemmed from Moderna’s patent pledge. Claim construction is completed.  

In August 2023, right before the one-year bar, Pfizer filed a pair of IPRs challenging the validity of two out of the three patents that are asserted in the district court litigation. See Pfizer Inc. v. ModernaTX, Inc., No. IPR2023-01358 (P.T.A.B.); Pfizer Inc. v. ModernaTX, Inc., No. IPR2023-01359 (P.T.A.B.). On March 6, 2024, the PTAB instituted both IPRs. Oral argument is scheduled in December 2024 and the final written decision is expected by March 2025.

After institution, Pfizer quickly moved to stay the district court proceeding pending resolution of the IPRs. On April 12, 2024, the district court granted Pfizer's motion. The court reasoned that although substantial work has been completed in the case, IPRs could simplify the issues and a stay would not cause Moderna any harm because it only seeks monetary damages.  

Unless the parties settle, the district court proceeding will likely resume sometime in 2025 regardless of the outcome in the IPRs since one asserted patent is not challenged in IPR. 

Alnylam

In March 2022, Alnylam separately sued Moderna and Pfizer/BioNTech in the district court of Delaware, alleging that their COVID-19 mRNA vaccines infringe an LNP patent. See Alnylam Pharm., Inc. v. Moderna, Inc., No. 22-cv-00335 (D. Del.); Alnylam Pharm., Inc. v. Pfizer Inc., No. 22-cv-00336 (D. Del.). Subsequently, Alnylam filed two rounds of lawsuits on several newly issued patents. See Alnylam Pharm., Inc. v. Moderna, Inc., No. 22-cv-00925 (D. Del.); Alnylam Pharm., Inc. v. Pfizer Inc., No. 22-cv-00924 (D. Del.); Alnylam Phar., Inc. v. Moderna, Inc., No. 23-cv-00580 (D. Del.); Alnylam Pharm., Inc. v. Pfizer Inc., No. 23-cv-00578 (D. Del.). All the asserted patents are directed to a class of cationic biodegradable lipids used to form LNPs that deliver an active agent to body.

The first two cases against Moderna were consolidated, and Alnylam stipulated to non-infringement based on the claim construction and appealed that construction to the Federal Circuit (Fed. Cir. No. 23-2357). That appeal is currently pending oral argument. The third case against Moderna is currently in discovery with a jury trial set for December 15, 2025.

Meanwhile, Alnylam’s three cases against Pfizer/BioNTech have been consolidated for all purposes. The court set a jury trial for July 7, 2025.

Arbutus/Genevant and Acuitas

Both Arbutus and Acuitas are Canadian biotech companies that develop LNPs for use in RNA/DNA-based therapeutics and have a tangled history with each other. According to Acuitas, three doctors founded Inex, the predecessor of Arbutus, in the early 1990s to develop therapeutics incorporating lipid-based nanomaterials. Then, they left Arbutus and formed Acuitas in 2009 to focus on the development of LNP technology for the delivery of mRNA. Acuitas licensed Arbutus’s LNP patents in 2012, and sublicensed those patents to Moderna in 2015. That sublicense was limited to four specific targets, which did not include COVID-19. Arbutus disputed that Acuitas had the right to sublicense. Arbutus and Acuitas litigated their contractual disputes and settled in 2018. The settlement agreement terminated Acuitas’s licenses but left Moderna’s sublicense intact.

In 2018, Moderna filed IPRs challenging the validity of three LNP patents owned by Arbutus or its subsidiary Protiva. See Moderna, Inc. v. Arbutus Biopharma Corp., No. IPR2018-00680 (P.T.A.B.); Moderna, Inc.. v. Arbutus Biopharma Corp., No. IPR2018-00739 (P.T.A.B.); and Moderna, Inc. v. Arbutus Biopharma Corp.., No. IPR2019-00554 (P.T.A.B.). The PTAB found one challenged patent unpatentable, one not unpatentable, and the third with a mixed result. All PTAB’s invalidity determinations were affirmed on appeal. 

In 2022, Arbutus and Genevant (who is the exclusive licensee of the Arbutus LNP patents for vaccine uses) sued Moderna for infringing six LNP patents, including the two that survived IPRs. See Arbutus Biopharma Corp. v. Moderna, Inc., No. 22-cv-00252 (D. Del.). Moderna moved to transfer a portion of the case to the Court of Federal Claims pursuant to 28 U.S.C. § 1498(a), but the district court denied that motion as premature because Moderna failed to establish that the sales were “for the government” and fact discovery is required. The case is currently pending with a trial date set in April 2025. 

In 2018, BioNTech licensed Arbutus/Genevant’s LNP technology for certain non-covid vaccine uses. In November 2020 and October 2021, Genevant and Arbutus sent demand letters to Pfizer/BioNTech, identifying nine patents that were allegedly infringed by Pfizer/BioNTech’s COVID-19 mRNA vaccine. Thereafter, Genevant and Arbutus noticed two additional patents in June 2022. But Pfizer/BioNTech did not take a license.  

Complicating issues, Pfizer/BioNTech had licensed the LNP technology from Acuitas for Pfizer/BioNTech’s COVID-19 mRNA vaccine. In March 2022, after Pfizer received the demand letters from Arbutus/Genevant, Acuitas filed a declaratory judgment action against Arbutus/Genevant, seeking a declaratory judgment that nine Arbutus patents are invalid and not infringed by the Pfizer/BioNTech COVID-19 mRNA vaccine. See Acuitas Therapeutics Inc. v. Genevant Sciences GmbH, No. 22-cv-02229 (S.D.N.Y.)

In April 2023, Arbutus sued Pfizer/BioNTech in New Jersey, asserting five patents. See Arbutus Pharm. Corp. v. Pfizer Inc., No. 23-cv-01876  (D.N.J.). The parties are currently conducting discovery and no trial date has been set.

A few months after Arbutus’s action against Pfizer/BioNTech, Acuitas dismissed its first declaratory judgment action pending in the New York and filed a second action against Arbutus/Genevant in New Jersey, seeking declaratory judgment of non-infringement and invalidity of all of the nine patents asserted in the first declaratory judgment action plus two new patents that Arbutus had asserted against Pfizer/BioNTech. See Acuitas Therapeutics Inc. v. Genevant Sciences, GmbH, No. 23-cv-04200 (D.N.J.)  Arbutus moved to dismiss for lack of subject matter jurisdiction. That motion is fully briefed and pending before the judge. 

CureVac

In 2017, Moderna filed an IPR challenging the validity of a CureVac patent directed to RNA purification. The PTAB found CureVac’s patent obvious and cancelled all claims. See ModernaTX, Inc. v. CureVac AG, No. IPR2017-02194 (P.T.A.B.).  No appeal was filed.

In 2022, Pfizer/BioNTech sued CureVac, seeking a declaratory judgment that their COVID-19 vaccine did not infringe three CureVac patents, which were directed to stabilized mRNA, mRNA vaccine in general, and the sequence encoding the spike protein for the virus causing COVID-19. See BioNTech SE v. CureVac AG, No. 22-cv-11202 (D. Mass.). According to the complaint, after BioNTech refused to take a license, CureVac sued BioNTech in Germany for infringing the foreign counterparts of the asserted patents.  

CureVac moved to dismiss the U.S. complaint for lack of personal jurisdiction. The district court agreed but rather than dismissing the action, the court transferred it to the eastern district of Virginia under 28 U.S.C. §1631 and 35 U.S.C. §293. After the case was transferred, CureVac answered the complaint and counterclaimed, asserting infringement of seven new CureVac patents. See BioNTech SE v. CureVac AG, No. 23-cv-00222 (E.D. Va.).  

In November 2023, Acuitas sued CureVac to correct inventorship of four patents that had been asserted against Pfizer/BioNTech. See Acuitas Therapeutics, Inc. v. CureVac SE, No. 23-cv-00610 (E.D. Va.) According to the complaint, Acuitas and CureVac had been collaborating on mRNA vaccines since 2014, and CureVac used Acuitas’s LNP technology to develop its COVID-19 mRNA vaccine. The complaint alleged that CureVac applied for and obtained patents based on its joint work with Acuitas but omitted Acuitas’s scientists as inventors.  

Acuitas and CureVac settled their disputes in April 2024. Under that settlement agreement, CureVac agreed to withdraw three of the four patents in the case against Pfizer/BioNTech.

Acuitas, one day after suing CureVac to correct inventorship, moved to intervene, sever or stay matters related to some of the patents in the declaratory judgment action filed by Pfizer against CureVac. In April 2024, the magistrate judge recommended granting that motion. Trial is currently set for January 2025. 

Promosome

In June 2023, Connecticut based biotech company, Promosome, filed separate patent infringement actions against Pfizer and Moderna, asserting a single patent in each that claims methods for increasing protein expression by modifying the mRNA. See Promosome LLC v. Moderna, Inc. , No. 23-cv-01047 (S.D. Cal.); Promosome LLC v. Pfizer Inc., Case No. 23-cv-01048 (S.D. Cal.).

The Moderna case was voluntarily dismissed without prejudice, prior to Moderna filing its answer.

The Pfizer case settled shortly after Pfizer answered the complaint. According to the dismissal stipulation, Promosome’s claims were dismissed with prejudice and Promosome covenanted not to assert the patent against Pfizer/BioNTech or any of their products. Pfizer/BioNTech’s claims and counterclaims were dismissed without prejudice.

The Future of Patent Disputes Concerning mRNA-based Therapeutics

Most of the patent disputes relating to COVID-19 mRNA vaccines are still pending before various district courts. Given the current schedules and likely appeals, it will probably take a few years for courts to resolve the disputes between Moderna and Pfizer/BioNTech and to determine whether COVID-19 mRNA vaccines by Moderna and Pfizer/BioNTech infringe any patents asserted by Alnylam, Arbutus/Genevant, CureVac, and GSK. And, new players with new patents may surface in the interim. 

One signature of the patent disputes concerning COVID-19 mRNA vaccines is that mRNA based therapeutics often involve patents that are directed to different technical aspects of the product, such as mRNA technology, LNP technology, and combining the mRNA with LNP technology. Each technical aspect may also require and be supported by many different inventions. For example, mRNA needs to be modified to evade innate immune response and to exhibit a high protein expression rate. Evading innate immune response can be achieved by replacing uridine with 1-methylpseudouridine. Several methods have been patented to increase protein expression rate. Thus, for companies in the space of mRNA based therapeutics, it is crucial to understand the multi-faceted nature of the mRNA based technology and strategize accordingly.