Promosome LLC v. Moderna, Inc.

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Promosome LLC (Delaware)
  • Defendant: Moderna, Inc., Moderna US, Inc., and ModernaTX, Inc. (Delaware corporations with principal places of business in Massachusetts)
  • Plaintiff’s Counsel: Susman Godfrey L.L.P.
• Case Identification: 3:23-cv-01047, S.D. Cal., 06/06/2023
• Venue Allegations: Plaintiff alleges venue is proper in the Southern District of California based on Defendants' sales of the accused vaccine in the district, the presence of employees and agents who maintain regular and established places of business in the district, and prior business dealings between the parties that occurred in the district, including in-person meetings and disclosures related to the asserted technology.
• Core Dispute: Plaintiff alleges that Defendants’ method for developing their Spikevax® COVID-19 vaccine infringes a patent related to re-engineering mRNA sequences to enhance protein production efficiency.
• Technical Context: The lawsuit concerns foundational mRNA technology for improving the yield of a desired protein from a given amount of mRNA, a critical factor for the efficacy and safety of mRNA-based vaccines and therapeutics.
• Key Procedural History: The complaint alleges an extensive history of pre-suit interactions between 2013 and 2016, during which Plaintiff disclosed its technology (under a CDA) and the patent-in-suit to Defendant. Plaintiff also alleges that Defendant's own patents have repeatedly cited the patent-in-suit and its family members, which may be relevant to the allegations of willful infringement.

Case Timeline

Date	Event
2009-02-24	'179 Patent Priority Date (Provisional App. 61/155,049 filed)
2013-07-05	Promosome and Moderna enter into a Confidential Disclosure Agreement (CDA)
2013-07-29	Moderna's Dr. Hoge visits Promosome's facilities; Promosome presents its technology
2014-10-07	U.S. Patent No. 8,853,179 issues
2015-06-19	Promosome presents again to Moderna scientists, rebutting compatibility concerns
2016-03-30	Promosome sends a copy of the '179 Patent to Moderna's Head of Business Development
2020-12-18	FDA grants Emergency Use Authorization for Moderna's COVID-19 Vaccine (Spikevax®)
2023-06-06	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,853,179 - Reengineering mRNA Primary Structure for Enhanced Protein Production

• Patent Identification: U.S. Patent No. 8,853,179, "Reengineering mRNA Primary Structure for Enhanced Protein Production," issued October 7, 2014.

The Invention Explained

• Problem Addressed: In mRNA-based therapies, a key challenge is maximizing the amount of the desired protein produced from the mRNA template. The patent’s background describes a problem called "ribosomal diversion," where cellular machinery (ribosomes) responsible for protein synthesis mistakenly starts its work at incorrect locations, called "secondary initiation codons," within the mRNA's coding sequence (Compl. ¶¶ 36-38; ’179 Patent, col. 9:1-5). This diversion reduces the production of the intended full-length protein and can create unwanted and potentially harmful peptide fragments (Compl. ¶38; ’179 Patent, col. 9:10-20).
• The Patented Solution: The invention is a method to improve protein expression efficiency by "reengineering" the mRNA sequence. The method involves identifying one or more of these secondary initiation codons and mutating them into codons that do not trigger initiation. Critically, these mutations are selected from synonymous codons, meaning they change the mRNA sequence but do not alter the amino acid sequence of the final protein, thus preserving its function (’179 Patent, Abstract; col. 2:44-51). This modification effectively removes the "detours," directing more ribosomes to the correct start site and thereby increasing the yield of the desired full-length protein (’179 Patent, col. 9:5-9).
• Technical Importance: This approach provides a way to increase the potency of mRNA vaccines and therapeutics, potentially allowing for smaller, safer doses while still generating a sufficient therapeutic or immune response (’179 Patent, col. 4:1-10; Compl. ¶50).

Key Claims at a Glance

• The complaint asserts independent Claim 1, the only claim in the patent (Compl. ¶54).
• The essential elements of Claim 1 are:
  • Providing a polynucleotide that comprises a coding sequence for a full-length protein, a primary initiation codon upstream of that coding sequence, and one or more secondary initiation codons located downstream of the primary initiation codon.
  • Mutating the one or more secondary initiation codons.
  • The mutation results in a decrease in the initiation of protein synthesis at those secondary codons.
  • This thereby increases the expression efficiency of the full-length protein initiated at the primary codon.
  • The mutation comprises mutating nucleotides such that the amino acid sequence of the protein remains unaltered.

III. The Accused Instrumentality

Product Identification

• The accused products are Moderna's COVID-19 vaccines, including mRNA-1273/Spikevax® and its various bivalent and booster versions, which are all based on engineered mRNA that encodes the SARS-CoV-2 spike protein (Compl. ¶112).

Functionality and Market Context

• The complaint alleges that Moderna developed a sophisticated mRNA "platform" or "research engine" to design and generate its vaccine sequences (Compl. ¶¶ 77-80). This platform allegedly includes tools for "mRNA sequence engineering" to optimize the mRNA for desired properties (Compl. ¶¶ 80-81).
• A key aspect of this platform is the optimization of "translation initiation and efficiency" to increase the average number of full-length desired proteins per molecule of mRNA (Compl. ¶81, citing Moderna’s 2019 10-K). The complaint presents a slide from a Moderna presentation, shown in Figure 8, that explicitly identifies "Translation initiation fidelity" as a core component of its engineering platform, described as ensuring the ribosome "always start[s] at the right place" (Compl. ¶¶ 81-82).
• The complaint alleges the Spikevax® vaccine has generated tens of billions of dollars in revenue for Moderna (Compl. ¶¶ 3, 93-94).

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,853,179 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of improving full-length protein expression efficiency comprising: a) providing a polynucleotide comprising: i) a coding sequence for the full-length protein; ii) a primary initiation codon that is upstream of the coding sequence...; and iii) one or more secondary initiation codons located within the coding sequence...	Moderna's development process begins with a polynucleotide (cDNA or pDNA) that contains the coding sequence for the COVID-19 spike protein, a primary initiation codon, and numerous secondary initiation codons.	¶115	col. 8:12-23
b) mutating the one or more secondary initiation codons located within the coding sequence of the full-length protein downstream of the primary initiation codon...	In order to create the accused vaccines, Moderna allegedly mutated numerous secondary initiation codons within the coding sequence for the spike protein.	¶115	col. 2:42-44
wherein the mutation results in a decrease in initiation of protein synthesis at the one or more secondary initiation codons, thereby increasing expression efficiency of the full-length protein initiated at the primary initiation codon...	By mutating these codons, Moderna's process allegedly decreases initiation at incorrect sites and increases the expression efficiency of the full-length spike protein. The complaint points to Moderna's own statements about optimizing "translation initiation" to "increase[] the average number of full-length desired proteins per molecule mRNA."	¶¶ 81, 115	col. 2:45-49
wherein mutating the one or more secondary initiation codons... comprises mutating one or more nucleotides such that the amino acid sequence of the protein remains unaltered.	The complaint alleges that Moderna performed these mutations without altering the amino acid sequence of the spike protein, leveraging the redundancy of the genetic code.	¶115	col. 2:50-51

• Identified Points of Contention:
  • Evidentiary Questions: The '179 patent claims a method. A central issue will be whether Plaintiff can produce sufficient evidence of Moderna’s internal development and manufacturing processes to prove that Moderna actually performs the claimed steps of identifying and mutating secondary initiation codons for the purpose of increasing expression efficiency. The complaint heavily relies on Moderna's public statements, such as those in Figure 8 (Compl. ¶82) and SEC filings (Compl. ¶81), to infer these internal processes.
  • Scope Questions: The case may raise questions about the definition of a "secondary initiation codon." Must a codon be proven to be actively used for initiation in a cell before it can be considered a "secondary initiation codon" under the claim, or is its mere presence as a potential start codon (e.g., AUG, CUG) sufficient? The answer will affect whether Moderna’s modifications fall within the claim scope.
  • Causation Questions: What is the required causal link between the alleged mutation and the "increas[e] in expression efficiency"? The defense may argue that any efficiency gains in its platform are attributable to other, non-infringing optimization techniques, raising a question of whether the specific mutations of secondary start codons are the actual cause of the increased efficiency.

V. Key Claim Terms for Construction

• The Term: "mutating the one or more secondary initiation codons"

• Context and Importance: This term is the core active step of the method claim. Its construction will determine what actions constitute infringement. Practitioners may focus on this term because the dispute will likely center on whether Moderna's sequence optimization process, which may involve a holistic algorithm, can be characterized as the specific act of "mutating" codons because they are secondary initiation sites, as opposed to changing them for other reasons (e.g., overall codon optimization, GC content) with the reduction of start sites being an incidental effect.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification repeatedly describes the overall goal as "reengineering mRNA primary structure" (Title) and provides lists of potential secondary initiation codons (e.g., AUG, ACG, GUG, etc.) ('179 Patent, col. 2:58-59). This could support an interpretation where any intentional modification of the coding sequence that results in the removal of a potential secondary start site (from the patent's list) and increases efficiency meets the limitation.
  • Evidence for a Narrower Interpretation: The claim language "mutating the one or more secondary initiation codons... wherein the mutation results in a decrease in initiation" suggests a targeted action with a specific purpose and result. This could support an interpretation requiring proof that a specific codon was identified as a secondary initiation site and was changed for the purpose of reducing ribosomal diversion at that site.

• The Term: "increasing expression efficiency of the full-length protein"

• Context and Importance: This is the stated result of the claimed method. Infringement requires this outcome to be achieved. The debate will be over what baseline is used for comparison. Is it the "native" viral sequence, an earlier version of Moderna's own sequence, or some other hypothetical construct? The answer is critical for determining whether an "increase" occurred.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent focuses on the general problem of suboptimal protein yield and ribosomal diversion. This could support using a theoretical, un-optimized sequence as the baseline, making it easier to show an "increase." The complaint's Figure 5, which contrasts a "Pre-Modification" state with a "Post-Modification" state showing more desired protein, supports this framing (Compl. ¶48).
  • Evidence for a Narrower Interpretation: The patent details its invention by comparing modified constructs to their specific, unmodified "wild type" counterparts (e.g., comparing "mCAT" to "CAT" in the examples) ('179 Patent, col. 13:50-59). This could support a narrower view where the "increase" must be shown relative to the specific, immediate predecessor sequence that was modified.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Moderna induced infringement by its contract manufacturers who produce the vaccine (Compl. ¶¶ 117-118). It also alleges contributory infringement, stating the accused vaccines are not staple articles of commerce and are especially made for a use that infringes the patent (Compl. ¶119).
• Willful Infringement: The complaint alleges that Moderna's infringement was willful, pointing to a long history of pre-suit interactions where Promosome allegedly disclosed its technology, the patent family, and a copy of the issued '179 patent itself to Moderna's leadership, including its now-CEO and President (Compl. ¶¶ 61-74). Further, it provides a table listing over two dozen Moderna patents that cite the '179 patent or its application, alleging this demonstrates long-standing knowledge of the technology (Compl. ¶75). These allegations form the basis for a claim for enhanced damages (Compl. ¶105).

VII. Analyst’s Conclusion: Key Questions for the Case

• A central question will be one of intent and knowledge: Will the extensive history of pre-suit meetings, confidential disclosures, and patent citations alleged in the complaint be sufficient to establish that Moderna had pre-suit knowledge of the '179 patent and its applicability to mRNA vaccine optimization, thereby supporting the claim for willful infringement?
• A key evidentiary question will be one of methodological proof: Can Promosome demonstrate, through discovery into Moderna's proprietary development platform, that Moderna's process for designing its Spikevax® mRNA performs the specific, claimed method of identifying and "mutating... secondary initiation codons" for the express purpose of "increasing expression efficiency," or will Moderna be able to show its sequence optimization relies on different, non-infringing principles?
• The case will also turn on a question of claim construction: How will the court define "secondary initiation codon" and the baseline for "increasing expression efficiency"? The resolution of these terms will be critical in determining the scope of the patent and whether Moderna's specific actions and resulting mRNA sequences fall within it.