DCT

3:23-cv-01876

Arbutus Pharma Corp v. Pfizer Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:23-cv-01876, D.N.J., 04/04/2023
  • Venue Allegations: Venue is alleged as proper in the District of New Jersey because Defendant Pfizer has a regular and established place of business in the district and has committed alleged acts of infringement there. Venue over BioNTech is alleged on the basis of its subjection to personal jurisdiction in the district.
  • Core Dispute: Plaintiffs allege that Defendants’ Pfizer-BioNTech COVID-19 vaccine infringes five U.S. patents related to the lipid nanoparticle (LNP) compositions used to deliver the mRNA payload and the apparatus and methods for manufacturing those LNPs.
  • Technical Context: The technology concerns lipid nanoparticle delivery systems, which are essential for protecting fragile messenger RNA (mRNA) molecules and delivering them into human cells to trigger an immune response.
  • Key Procedural History: The complaint alleges that Defendant BioNTech entered into a license agreement with Plaintiff Genevant in 2018 for the use of the LNP technology in fields excluding infectious diseases. Plaintiffs also allege providing Defendants with written notice of potential infringement of the asserted patents beginning in November 2020 and continuing as later patents issued.

Case Timeline

Date Event
2002-06-28 Earliest Priority Date for ’320 and ’098 Patents
2008-04-15 Earliest Priority Date for ’651, ’359, and ’378 Patents
2013-07-23 U.S. Patent No. 8,492,359 Issues
2016-11-29 U.S. Patent No. 9,504,651 Issues
2018-07-04 BioNTech signs license agreement with Genevant
2020-01-24 BioNTech designs COVID-19 vaccine candidates
2020-11-23 Plaintiffs notify Defendants of potential infringement of ’651 and ’359 Patents
2020-12-11 FDA grants Emergency Use Authorization for Accused Product
2021-10-12 U.S. Patent No. 11,141,378 Issues; Plaintiffs notify Defendants of potential infringement
2022-04-12 U.S. Patent No. 11,298,320 Issues
2022-05-03 U.S. Patent No. 11,318,098 Issues
2022-06-03 Plaintiffs notify Defendants of potential infringement of ’320 and ’098 Patents
2023-04-04 Complaint Filed

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

U.S. Patent No. 9,504,651 - "Lipid Compositions for Nucleic Acid Delivery"

  • Patent Identification: U.S. Patent No. 9,504,651, "Lipid Compositions for Nucleic Acid Delivery," issued November 29, 2016.
  • The Invention Explained:
    • Problem Addressed: The development of medicines based on ribonucleic acid (RNA) was historically hindered by a significant "delivery problem" (Compl. ¶34, 36). RNA molecules are inherently fragile, susceptible to degradation in the body, and unable to cross cell membranes on their own to reach their intracellular targets (Compl. ¶33).
    • The Patented Solution: The invention provides a delivery vehicle in the form of lipid nanoparticles (LNPs), which are microscopic particles composed of specific lipids (Compl. ¶4, 37). These particles are designed to encapsulate and protect the fragile RNA payload, remain stable during circulation in the bloodstream, and facilitate the RNA's entry into target cells (’378 Patent, col. 2:52-61). The ’651 Patent claims a specific formulation of these particles for delivering messenger RNA (mRNA) (Compl. ¶67, 70).
    • Technical Importance: This LNP technology was a widely recognized achievement considered essential for making mRNA vaccines, like the accused COVID-19 vaccine, a practical reality (Compl. ¶4, 49).
  • Key Claims at a Glance:
    • The complaint asserts infringement of at least Claim 1 (Compl. ¶70).
    • Independent Claim 1:
      • A lipid vesicle formulation comprising:
      • (a) a plurality of lipid vesicles, wherein each lipid vesicle comprises: a cationic lipid; an amphipathic lipid; and a polyethyleneglycol (PEG)-lipid; and
      • (b) messenger RNA (mRNA),
      • wherein at least 70% of the mRNA in the formulation is fully encapsulated in the lipid vesicles.
    • The complaint also references dependent Claim 9 but does not explicitly assert other dependent claims (Compl. ¶70).

U.S. Patent No. 8,492,359 - "Lipid Formulations for Nucleic Acid Delivery"

  • Patent Identification: U.S. Patent No. 8,492,359, "Lipid Formulations for Nucleic Acid Delivery," issued July 23, 2013.
  • The Invention Explained:
    • Problem Addressed: As with the ’651 Patent, this invention addresses the technical challenge of systemic delivery for nucleic acid therapeutics (Compl. ¶33-34). The background of a related patent notes that prior non-viral delivery systems were often large, poorly defined, and rapidly cleared from circulation, limiting their effectiveness (’378 Patent, col. 2:10-44).
    • The Patented Solution: The invention claims a specific composition for a nucleic acid-lipid particle, defining the formulation by the molar percentages of its constituent lipid components (’359 Patent, Claim 1, as recited in Compl. ¶87). By defining the ratios of the cationic lipid, non-cationic lipids (phospholipid and cholesterol), and a conjugated lipid, the invention purports to create stable and effective particles for in vivo nucleic acid delivery (’378 Patent, Abstract; col. 3:41-50).
    • Technical Importance: The complaint alleges that the specific, balanced lipid ratios taught by the patent family are critical to the stability and efficacy of the LNP delivery system used in the accused vaccine (Compl. ¶2, 49).
  • Key Claims at a Glance:
    • The complaint asserts infringement of at least Claim 1 (Compl. ¶87).
    • Independent Claim 1:
      • A nucleic acid-lipid particle comprising:
      • (a) a nucleic acid;
      • (b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid present in the particle;
      • (c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof, wherein the phospholipid comprises from 3 mol % to 15 mol % and the cholesterol comprises from 30 mol % to 40 mol % of the total lipid present in the particle; and
      • (d) a conjugated lipid that inhibits aggregation of particles comprising from 0.5 mol % to 2 mol % of the total lipid present in the particle.
    • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 11,141,378 - "Lipid Formulations for Nucleic Acid Delivery"

  • Patent Identification: U.S. Patent No. 11,141,378, "Lipid Formulations for Nucleic Acid Delivery," issued October 12, 2021.
  • Technology Synopsis: This patent, related to the ’359 Patent, addresses the problem of effective in vivo RNA delivery (’378 Patent, col. 2:10-14). It claims a stable nucleic acid-lipid particle defined by specific molar percentage ranges of its core components: an RNA, a cationic lipid, a mixture of phospholipid and cholesterol, and a PEG-lipid conjugate (’378 Patent, Abstract; col. 28:28-44).
  • Asserted Claims: Claim 1 (Compl. ¶106).
  • Accused Features: The composition of the Pfizer-BioNTech vaccine is accused of infringing, specifically its alleged use of a cationic lipid, a mixture of DSPC and cholesterol, and a PEG-lipid conjugate within the claimed molar percentage ranges (Compl. ¶108-109).

U.S. Patent No. 11,298,320 - "Liposomal Apparatus and Manufacturing Methods"

  • Patent Identification: U.S. Patent No. 11,298,320, "Liposomal Apparatus and Manufacturing Methods," issued April 12, 2022.
  • Technology Synopsis: This patent addresses challenges in manufacturing LNPs by claiming an apparatus for their production (’320 Patent, Abstract). The claimed apparatus mixes an aqueous solution containing a nucleic acid from a first reservoir with an organic lipid solution from a second reservoir, introducing them as "opposing flows at about 180°" into a mixing chamber to instantaneously form lipid vesicles (’320 Patent, Claim 1).
  • Asserted Claims: Claim 1 (Compl. ¶122).
  • Accused Features: The manufacturing apparatus used for the Accused Product is alleged to infringe, based on public descriptions of "high pressure pumps" moving aqueous and organic streams into a "T-mixer" where they are combined as opposing streams (Compl. ¶124-125).

U.S. Patent No. 11,318,098 - "Liposomal Apparatus and Manufacturing Methods"

  • Patent Identification: U.S. Patent No. 11,318,098, "Liposomal Apparatus and Manufacturing Methods," issued May 3, 2022.
  • Technology Synopsis: This patent, related to the ’320 Patent, claims a process for producing lipid vesicles (’098 Patent, Abstract). The claimed process involves providing separate aqueous and organic lipid solutions and introducing them as opposing flows into a mixing chamber to instantaneously produce the vesicles by diluting the alkanol concentration of the lipid solution (’098 Patent, Claim 1).
  • Asserted Claims: Claim 1 (Compl. ¶141).
  • Accused Features: The process used to manufacture the Accused Product is alleged to infringe, based on descriptions of pumping aqueous and organic streams into a "T-mixer" to be combined (Compl. ¶144-145).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality includes the Pfizer-BioNTech COVID-19 vaccine (marketed as Comirnaty and identified by other names such as BNT162b2) as well as the apparatus and processes used for its manufacture (Compl. ¶8, 121, 140).
  • Functionality and Market Context: The Accused Product is a vaccine that works by delivering mRNA encoding the SARS-CoV-2 spike protein to human cells, triggering an immune response (Compl. ¶3, 23, 68). The mRNA is encapsulated within lipid nanoparticles composed of four lipid types: an ionizable cationic lipid, a phospholipid (DSPC), cholesterol, and a PEG-lipid (Compl. ¶68, 72). For the manufacturing patents, the accused instrumentality is the apparatus that allegedly uses a "T-mixer" to combine an aqueous mRNA solution with an organic lipid solution via opposing flows to form the LNPs (Compl. ¶124-126). The complaint includes a screenshot from a CNN interview showing the "T-mixer" allegedly used in Pfizer's manufacturing process (Compl. ¶126). The complaint alleges the vaccine generated tens of billions of dollars in revenue, with billions of doses manufactured and administered worldwide (Compl. ¶2, 51).

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,504,651 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a lipid vesicle formulation comprising: (a) a plurality of lipid vesicles, wherein each lipid vesicle comprises: a cationic lipid; The Accused Product is a lipid vesicle formulation containing the ionizable cationic lipid ((4-hydroxybutyl) azanediyl)bis (hexane-6,1-diyl)bis(2-hexyldecanoate). ¶71, 72 col. 3:56-61
an amphipathic lipid; The Accused Product contains the amphipathic lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (“DSPC”). ¶72 col. 12:55-65
and a polyethyleneglycol (PEG)-lipid; The Accused Product contains the PEG-lipid 2[(polyethylene glycol)-2000]-N,N ditetradecylacetamide. ¶72 col. 12:26-34
and (b) messenger RNA (mRNA), The Accused Product contains a nucleoside-modified mRNA that encodes the viral spike protein of SARS-CoV-2. ¶68, 71 col. 8:51-62
wherein at least 70% of the mRNA in the formulation is fully encapsulated in the lipid vesicles. The complaint alleges, upon information and belief, that the Accused Product meets this limitation. ¶73 col. 23:25-30
  • Identified Points of Contention:
    • Factual Question: A primary point of contention may be evidentiary: what proof will be offered that "at least 70%" of the mRNA in the final vaccine product is "fully encapsulated"? The complaint alleges this element upon "information and belief," indicating it is a subject for discovery.
    • Scope Question: The parties may dispute whether the specific lipid molecules used in the accused vaccine, such as the identified ionizable cationic lipid, fall within the patent’s construction of the claim terms "cationic lipid" and "amphipathic lipid."

U.S. Patent No. 8,492,359 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a nucleic acid-lipid particle comprising: (a) a nucleic acid; The Accused Product is a nucleic acid-lipid particle containing mRNA which encodes the COVID-19 spike protein. ¶88 col. 8:51-62
(b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid present in the particle; The complaint alleges on information and belief that the Accused Product's cationic lipid component falls within this molar percentage range. ¶90 col. 3:41-47
(c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol ... wherein the phospholipid comprises from 3 mol % to 15 mol % ... and the cholesterol ... comprises from 30 mol % to 40 mol % ...; The complaint alleges on information and belief that the Accused Product's non-cationic lipid components (DSPC and cholesterol) fall within these respective molar percentage ranges. ¶90 col. 4:1-4
and (d) a conjugated lipid that inhibits aggregation ... comprising from 0.5 mol % to 2 mol % of the total lipid present in the particle. The complaint alleges on information and belief that the Accused Product's PEG-lipid conjugate falls within this molar percentage range. ¶90 col. 3:47-50
  • Identified Points of Contention:
    • Factual Question: The central dispute for this patent will likely be factual. The complaint's allegations regarding the specific molar percentages of the four lipid components are made "on information and belief." The actual composition of the Accused Product, which will be determined through discovery, will be critical to proving or disproving infringement.
    • Technical Question: What is the precise composition of the Accused Product? Publicly available documents, such as the FDA Emergency Use Authorization letter cited in the complaint, provide nominal weights but may not be sufficient to definitively resolve the molar percentage calculations required by the claim (Compl. ¶85).

V. Key Claim Terms for Construction

  • The Term: "cationic lipid" (from ’651 Patent, Claim 1; ’359 Patent, Claim 1)

    • Context and Importance: The definition of this term is critical because the specific ionizable lipid used in the Accused Product must be found to fall within the patent's scope. Practitioners may focus on this term because the accused lipid is "ionizable"—meaning its charge may be pH-dependent—and the construction could determine whether such lipids are covered.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A related patent in the family defines the term broadly as "any of a number of lipid species that carry a net positive charge at a selected pH, such as physiological pH" (’378 Patent, col. 13:20-23). This language could support an interpretation covering a wide range of positively charged or ionizable lipids.
      • Evidence for a Narrower Interpretation: The specification provides numerous examples of specific cationic lipid structures, such as DLinDMA (’378 Patent, col. 17:25-67). A defendant may argue that the term should be construed more narrowly in light of these specific embodiments.

  • The Term: "mixing chamber ... configured such that the aqueous solution and the organic lipid solution are introduced into the mixing chamber as opposing flows at about 180° relative to each other" (from ’320 Patent, Claim 1)

    • Context and Importance: Infringement of the apparatus patent hinges on whether the "T-mixer" allegedly used by Defendants meets this structural and functional limitation. The complaint's visual evidence of a T-junction makes this a focal point of the dispute (Compl. ¶126-127).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The plain language of the claim requires a chamber where flows are "introduced ... as opposing flows." A plaintiff could argue this language reads on any T-junction apparatus that brings two fluid streams into direct opposition, regardless of the precise internal mechanics.
      • Evidence for a Narrower Interpretation: The patent specification describes this configuration as achieving "instantaneous" production of a lipid vesicle (’320 Patent, col. 19:1-8). A defendant may argue that the term "configured" implies a specific internal geometry necessary to achieve this result, potentially limiting the claim scope to the specific embodiments disclosed.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for the composition patents, stating that Defendants encouraged healthcare professionals to administer the Accused Product, knew this administration would infringe, and intended for the infringing use to occur (Compl. ¶74, 91, 110).
  • Willful Infringement: Willfulness is alleged for all five patents. The allegations are based on pre-suit knowledge stemming from a 2018 license agreement between Genevant and BioNTech covering related technology, and a series of written notices sent to Defendants beginning in November 2020 and continuing as each of the later patents issued (Compl. ¶43-44, 57-60, 75, 92, 102, 129, 148).

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

  • A core issue will be one of compositional fact: will discovery confirm that the precise molar ratios of the cationic lipid, phospholipid, cholesterol, and PEG-lipid in the commercial Pfizer-BioNTech vaccine fall within the specific numerical ranges recited in the asserted composition claims?
  • A key technical question will be one of structural interpretation: does the "T-mixer" apparatus allegedly used in Defendants' manufacturing process meet the claim limitation of a "mixing chamber" configured to receive "opposing flows at about 180°," and does the manufacturing method practice the claimed process steps?
  • A central issue for damages will be willfulness: given Plaintiffs’ allegations of a pre-existing license agreement and multiple pre-suit notification letters, the court will need to determine whether Defendants acted with the knowledge and intent required for an enhancement of damages.