DCT

1:24-cv-01151

Northwestern University v. Moderna Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01151, D. Del., 10/16/2024
  • Venue Allegations: Venue is asserted in the District of Delaware on the basis that all Defendant entities are incorporated in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant’s Spikevax COVID-19 vaccines and mRESVIA RSV vaccine infringe three patents related to lipid nanoparticle (LNP) technology used to deliver messenger RNA (mRNA) into human cells.
  • Technical Context: The lawsuit concerns the foundational delivery system for mRNA vaccines, a critical component that protects the fragile mRNA payload and facilitates its entry into cells to trigger an immune response.
  • Key Procedural History: The complaint alleges that Northwestern notified Moderna of its infringement on October 13, 2023. It also notes that Northwestern previously licensed the Asserted Patents to Zylem Biosciences, Inc. in 2021 and amended that agreement on July 21, 2023, to possess the exclusive right to sue for infringement.

Case Timeline

Date Event
2008-04-25 ’686 Patent Priority Date
2010-01-19 ’155 Patent Priority Date
2010-01-19 ’026 Patent Priority Date
2012-12-04 ’686 Patent Issue Date
2015-12-22 ’155 Patent Issue Date
2019-06-25 ’026 Patent Issue Date
2020-12-18 Moderna receives Emergency Use Authorization for mRNA-1273 vaccine
2021-11-19 FDA authorizes booster dose of mRNA-1273
2022-01-31 Moderna receives full FDA approval for mRNA-1273 (Spikevax)
2022-03-29 Moderna receives approval for a second booster dose
2022-08-31 FDA authorizes bivalent booster vaccine (mRNA-1273.222)
2023-07-21 Northwestern and Zylem amend license agreement
2023-09-11 FDA approves updated COVID-19 vaccine
2023-10-13 Northwestern sends notice letter to Moderna regarding infringement
2024-05-31 Moderna receives FDA approval for mRESVIA
2024-10-16 Complaint Filing Date

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

U.S. Patent No. 9,216,155 - “Synthetic Nanostructures Including Nucleic Acids and/or Other Entities”

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of delivering nucleic acids (like oligonucleotides) into cells to regulate gene expression for therapeutic purposes (Compl. ¶122; ’155 Patent, Abstract). The complaint frames this problem in the context of overcoming the body's natural defenses that degrade foreign genetic material and the difficulty of getting such material across the cell membrane (Compl. ¶¶ 37-39).
  • The Patented Solution: The invention is a method for promoting cellular uptake of an oligonucleotide using a specially designed nanostructure. This structure has a core, a lipid-based or hydrophobic shell, and the therapeutic oligonucleotide, which is "electrostatically physiosorbed" to the shell's surface. A key feature is that the structure is also adapted to "sequester cholesterol," mimicking the function of naturally occurring lipoproteins to achieve better integration into biological systems (’155 Patent, Claim 2; Compl. ¶66). The complaint explains this mimics lipoproteins to evade the body's immune response and gain entry into cells (Compl. ¶¶ 59, 61).
  • Technical Importance: This approach provided a method for creating synthetic particles that the body would recognize as "naturally-occurring materials," solving long-standing problems of delivery, degradation, and toxicity that had stymied the development of nucleic acid-based therapies (Compl. ¶¶ 10, 41-42, 61).

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 2, an independent method claim (Compl. ¶66).
  • The essential elements of Claim 2 are:
    • A method for promoting cellular uptake of an oligonucleotide comprising:
    • delivering an oligonucleotide structure to a subject or biological sample,
    • the structure comprising a nanostructure core;
    • a shell comprising a lipid or a hydrophobic material surrounding the core; and
    • an oligonucleotide adapted to regulate gene expression associated with the shell,
    • wherein the structure is adapted to sequester cholesterol,
    • wherein the structure promotes cellular uptake, and
    • wherein the oligonucleotide is electrostatically physiosorbed to a surface of the shell.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,328,026 - “Synthetic Nanostructures Including Nucleic Acids and/or Other Entities”

The Invention Explained

  • Problem Addressed: The patent background identifies the need for improvements in non-viral nanoparticle formulations to overcome "interfacial hurdles that arise when cellular biological systems are exposed to synthetic nanostructures" (’026 Patent, col. 1:55-59). The technology aims to create "biomimetic nanostructures which naturally interface with biological systems to deliver nucleic acids" (’026 Patent, col. 2:38-41).
  • The Patented Solution: The invention is a composition of matter: a nanostructure that acts as a synthetic carrier for oligonucleotides. The structure comprises a core surrounded by a lipid bilayer, an apolipoprotein, and the therapeutic oligonucleotide, which is "physisorbed" to the surface. By incorporating an apolipoprotein—the protein component of natural lipoproteins like HDL—the structure is designed to mimic these natural particles to facilitate cellular entry (’026 Patent, Claim 1; Compl. ¶¶ 69, 78-79). The complaint notes this design could "successfully navigate the bio-nano interface" for targeted delivery (Compl. ¶76).
  • Technical Importance: This technology provided a structural blueprint for a synthetic particle that mimics high-density lipoprotein (HDL), enabling it to interact with cellular receptors and efficiently deliver nucleic acid payloads into the cytoplasm for gene regulation (’026 Patent, col. 2:36-43; Compl. ¶¶ 78-80).

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1, an independent composition claim (Compl. ¶69).
  • The essential elements of Claim 1 are:
    • A nanostructure comprising:
    • an oligonucleotides adapted to regulate gene expression physisorbed to the surface of a synthetic carrier,
    • the synthetic carrier comprising a core surrounded by a lipid bilayer, and
    • an apolipoprotein.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,323,686 - “Nanostructures Suitable for Sequestering Cholesterol and Other Molecules”

  • Patent Identification: U.S. Patent No. 8,323,686, “Nanostructures Suitable for Sequestering Cholesterol and Other Molecules,” issued December 4, 2012 (Compl. ¶70).
  • Technology Synopsis: The invention addresses "structures having a core-shell type arrangement" capable of interacting with cholesterol and other lipids (’686 Patent, Abstract). The claimed structure consists of an inorganic core, a lipid bilayer shell surrounding the core, and an apolipoprotein bound to the shell's outer surface, designed to sequester cholesterol (’686 Patent, Claim 1; Compl. ¶72).
  • Asserted Claims: The complaint asserts infringement of at least Claim 1 (Compl. ¶72).
  • Accused Features: The complaint alleges that the Accused Products infringe by comprising a nanostructure with an "inorganic material" core (water), a shell with a lipid bilayer, and by binding with an apolipoprotein on its outer surface after administration to a patient (Compl. ¶155).

III. The Accused Instrumentality

Product Identification

  • The Accused Products are identified as Moderna’s Spikevax COVID-19 vaccines (including the original mRNA-1273, bivalent, and updated versions) and its mRESVIA vaccine for RSV (Compl. ¶¶ 87-90, 117). The complaint alleges that mRESVIA "uses the same lipid nanoparticles (LNPs) as the Moderna COVID-19 vaccines" (Compl. ¶87).

Functionality and Market Context

  • The Accused Products are mRNA vaccines that use an LNP delivery system. This system is described as a particle formulated with four specific lipids: SM-102 (a cationic lipid), DMG (a PEGylated lipid), cholesterol, and DSPC (a phospholipid) (Compl. ¶¶ 91, 98-102). These components allegedly self-assemble into a core-shell structure that encapsulates and protects the mRNA payload (Compl. ¶104). Upon administration, the LNP enables delivery of the mRNA into host cells, which then produce a viral protein (e.g., the SARS-CoV-2 spike protein) to elicit a protective immune response (Compl. ¶95). The complaint highlights the commercial success of this technology, noting Moderna's significant revenues and 45% market share for COVID-19 vaccines (Compl. ¶13). The complaint includes a diagram from a Moderna presentation illustrating the central role of mRNA in producing proteins (Compl. ¶34, p. 9).

IV. Analysis of Infringement Allegations

’9,216,155 Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for promoting cellular uptake of an oligonucleotide comprising: delivering a oligonucleotide structure to a subject... Moderna's making, use, sale, and testing of the Accused Products, which are administered to patients or used in clinical trials, delivering the mRNA structure. ¶¶123-125, 127 col. 4:10-14
...the structure comprising a nanostructure core; The Accused Products contain an LNP with a core comprising water and the mRNA payload. ¶¶96, 127 col. 7:5-10
...a shell comprising a lipid surrounding...or a hydrophobic shell surrounding the nanostructure core; The LNP has a shell composed of a lipid bilayer (including SM-102, DMG, cholesterol, and DSPC), which is hydrophobic. ¶¶98, 103, 127 col. 3:41-44
...an oligonucleotide adapted to regulate gene expression associated with at least a portion of the shell... The Accused Products contain mRNA, an oligonucleotide, which encodes for viral antigens to regulate gene expression. ¶¶97, 127 col. 3:41-44
...wherein the structure is adapted to sequester cholesterol... The LNP structure is formulated with cholesterol as a key component of its shell, which allegedly regulates shell stability and is sequestered by the structure. ¶¶101, 127 col. 4:15-18
...wherein the oligonucleotide is electrostatically physiosorbed to a surface of the shell. The negatively charged mRNA is alleged to associate with the lipid shell through electrostatic physisorption due to the charge difference with the cationic lipids. ¶¶106, 127 col. 7:23-30

Identified Points of Contention:

  • Scope Questions: What is the scope of "delivering"? Does Moderna's testing of the Accused Products constitute direct infringement of this method step, and do its sales and marketing activities constitute inducement of healthcare providers and patients to perform the claimed method?
  • Technical Questions: Does the encapsulation of mRNA within a lipid shell, driven by the interaction between a cationic lipid and the negatively charged mRNA, meet the claim limitation of being "electrostatically physiosorbed to a surface of the shell"? A court may need to determine if "encapsulation within" is the same as "physisorbed to a surface." The complaint provides a side-by-side comparison of a patent figure and a Moderna diagram to support its structural infringement theory (Compl. ¶128, p. 35).

’10,328,026 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A nanostructure comprising an oligonucleotides adapted to regulate gene expression... The Accused Products are nanostructures containing mRNA, which directs the patient's cells to express viral antigens. ¶¶97, 141 col. 3:53-56
...physisorbed to the surface of a synthetic carrier... The mRNA is allegedly physisorbed to the surface of the LNP due to charge differences between the mRNA and the lipids in the shell. ¶¶106, 141 col. 7:23-30
...the synthetic carrier comprising a core surrounded by a lipid bilayer... The LNP in the Accused Products acts as the synthetic carrier and is composed of a core (water and mRNA) surrounded by a lipid bilayer shell. A Moderna diagram shows this core-shell structure (Compl. ¶43, p. 13). ¶¶96, 103, 141 col. 7:5-13
...and an apolipoprotein. After administration, the LNP allegedly binds with apolipoproteins (such as ApoE) present in the patient's body, which facilitates cellular uptake. ¶¶107, 110, 114, 141 col. 3:56-57

Identified Points of Contention:

  • Scope Questions: Does the term "comprising... an apolipoprotein" read on a product that is manufactured and sold without an apolipoprotein but is designed to acquire one in vivo after administration? The infringement theory depends on events that occur post-sale in the patient's body.
  • Technical Questions: What is the factual mechanism of the mRNA's association with the LNP? Is it "physisorbed to the surface" as claimed, or is it primarily encapsulated within the core, a distinction that may be critical for claim construction and infringement analysis?

V. Key Claim Terms for Construction

The Term: "apolipoprotein" (’026 Patent, Claim 1)

  • Context and Importance: This term is central because the Accused Products are not formulated with an apolipoprotein. The complaint alleges infringement occurs because the LNPs are designed to, and do, bind with apolipoproteins in the patient's body post-administration (Compl. ¶¶ 114, 141). The case may turn on whether a claim to a composition "comprising" a component can be met by a product that only acquires that component after it has been sold and administered.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent frequently describes the structures as "biomimetic" of HDL and notes that they may be "engineered to mimic endogenous spherical HDLs" (’026 Patent, col. 2:60-61). This focus on in vivo mimicry may support an interpretation where the claimed structure is defined by its state and function within a biological system, not just its pre-administration formulation.
    • Evidence for a Narrower Interpretation: The patent's abstract and detailed description describe the fabrication of the nanostructures, which may imply that the claimed components are those present at the time of manufacture. For example, Figure 3 depicts a method of "fabricating structures including one or more apolipoproteins" as part of the synthesis process, which could suggest the apolipoprotein is part of the manufactured article (’026 Patent, FIG. 3).

The Term: "electrostatically physiosorbed to a surface of the shell" (’155 Patent, Claim 2) / "physisorbed to the surface of a synthetic carrier" (’026 Patent, Claim 1)

  • Context and Importance: Practitioners may focus on this term because the actual physical state of the mRNA in the LNP is a key technical question. The complaint alleges this limitation is met by the electrostatic attraction between the negatively charged mRNA and positively charged cationic lipids in the shell (Compl. ¶¶ 106, 127). A defendant may argue that the mRNA is primarily encapsulated within an aqueous core, not "physiosorbed to a surface," which implies a surface-binding phenomenon.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification of the ’155 Patent is not provided. The ’026 Patent specification states that oligonucleotides may be attached to a nanostructure core using "electrostatic adsorption" (’026 Patent, col. 3:24-27). This could support the plaintiff's theory that electrostatic attraction satisfies the "physisorbed" limitation.
    • Evidence for a Narrower Interpretation: The term "physisorbed" has a specific technical meaning involving van der Waals forces. The specification also discusses "covalently or near-covalently" bonding nucleic acids (’026 Patent, col. 7:21-23), suggesting the patent contemplates different, distinct modes of attachment. A defendant might argue that simple electrostatic encapsulation within a core is distinct from being "physisorbed to a surface."

VI. Other Allegations

Indirect Infringement

  • The complaint alleges induced infringement under 35 U.S.C. § 271(b), stating that Moderna intends for healthcare providers and patients to use the Accused Products in an infringing manner, as directed by product inserts and instructions (Compl. ¶¶ 125, 139). Contributory infringement under § 271(c) is also alleged on the basis that the Accused Products are specially adapted for practicing the invention and have no substantial non-infringing uses (Compl. ¶¶ 126, 140).

Willful Infringement

  • Willfulness is alleged based on Moderna's continued infringement after receiving actual notice of the Asserted Patents via a letter from Northwestern's counsel dated no later than October 13, 2023 (Compl. ¶¶ 130, 144, 158).

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

  • A core issue will be one of temporal scope: can a composition claim requiring "an apolipoprotein" be infringed by a product that is manufactured without it but is designed to bind with one after administration in vivo? The resolution will depend on how the court construes the claim in light of the patent's description of a "biomimetic" technology intended to function within a biological system.
  • A second central issue will be one of technical mechanism: what does "physisorbed to the surface" mean in the context of these patents, and does the encapsulation of mRNA within the aqueous core of the LNP, stabilized by cationic lipids, meet that definition? This will likely require expert testimony on the specific physical and chemical interactions occurring during the LNP's self-assembly.
  • A third key question will be one of definitional scope, particularly for the ’686 Patent: does the term "nanostructure core comprising an inorganic material" read on the aqueous core of the accused LNP, where the complaint identifies water as the "inorganic material"? The interpretation of this term will be critical to the infringement analysis for that patent.