DCT
3:23-cv-04200
Acuitas Therap Inc v. Genevant Sciences GmbH
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Acuitas Therapeutics Inc. (Canada)
- Defendant: Genevant Sciences GmbH (Switzerland) and Arbutus Biopharma Corp. (Canada)
- Plaintiff’s Counsel: Marino, Tortorella & Boyle, P.C.; Groombridge, Wu, Baughman & Stone LLP
- Case Identification: 3:23-cv-04200, D.N.J., 08/04/2023
- Venue Allegations: Plaintiff Acuitas alleges that venue is proper because Defendants purposefully availed themselves of the jurisdiction by filing a patent infringement suit in the same district against Acuitas's partners, Pfizer and BioNTech, concerning the same underlying technology.
- Core Dispute: Plaintiff Acuitas seeks a declaratory judgment that its lipid nanoparticle (LNP) technology, used in the Pfizer-BioNTech COMIRNATY® vaccine, does not infringe ten patents owned by Defendants, and/or that those patents are invalid.
- Technical Context: The technology concerns lipid nanoparticle (LNP) formulations used as a delivery vehicle for messenger RNA (mRNA), a critical component for the rapid development and success of certain COVID-19 vaccines.
- Key Procedural History: This action is procedurally intertwined with a prior lawsuit filed by Defendants Arbutus and Genevant against Pfizer and BioNTech in the same court, alleging infringement of some of the same patents by the COMIRNATY® vaccine. Acuitas notes that its customer, BioNTech, has asserted a claim for indemnification against Acuitas based on that litigation. The complaint also references Inter Partes Review (IPR) proceedings involving some of the asserted patents, arguing that Defendants’ own statements to the patent office regarding the unpredictability of the technology undermine the validity of their claims.
Case Timeline
| Date | Event |
|---|---|
| 2008-04-15 | Earliest Priority Date ('435, '069, '359, '668, '417, '272 Patents) |
| 2011-11-15 | U.S. Patent No. 8,058,069 Issues |
| 2013-07-23 | U.S. Patent No. 8,492,359 Issues |
| 2014-09-02 | U.S. Patent No. 8,822,668 Issues |
| 2015-04-14 | U.S. Patent No. 9,006,417 Issues |
| 2016-06-14 | U.S. Patent No. 9,364,435 Issues |
| 2016-11-29 | U.S. Patent No. 9,504,651 Issues |
| 2016-12-13 | U.S. Patent No. 9,518,272 Issues |
| 2020-01-01 | Development of COMIRNATY® begins (approximate date) |
| 2020-04-30 | Clinical trials of COMIRNATY® begin (approximate date) |
| 2020-11-23 | Defendants send first patent infringement notice letter to Pfizer and BioNTech |
| 2020-12-10 | FDA approves COMIRNATY® under Emergency Use Authorization |
| 2021-08-23 | FDA grants full approval to COMIRNATY® |
| 2021-10-12 | U.S. Patent No. 11,141,378 Issues |
| 2022-03-18 | Acuitas files its "New York Action" for declaratory judgment |
| 2022-04-12 | U.S. Patent No. 11,298,320 Issues |
| 2022-05-03 | U.S. Patent No. 11,318,098 Issues |
| 2023-04-03 | Defendants sue Pfizer and BioNTech in the District of New Jersey |
| 2023-08-04 | Complaint for Declaratory Judgment filed by Acuitas |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,364,435 - "Lipid Formulations for Nucleic Acid Delivery"
- Patent Identification: U.S. Patent No. 9,364,435, “Lipid Formulations for Nucleic Acid Delivery,” issued June 14, 2016.
The Invention Explained
- Problem Addressed: The patent describes the need for safe and effective non-viral delivery systems for therapeutic nucleic acids, noting that existing viral vectors have limitations and prior non-viral systems like cationic liposomes can be toxic and are not well-suited for systemic applications ('435 Patent, col. 2:10-44).
- The Patented Solution: The invention provides stable, serum-resistant nucleic acid-lipid particles (SNALPs) that fully encapsulate nucleic acids like siRNA. The solution is defined by specific molar percentage ranges of three key lipid components: a cationic lipid, a non-cationic lipid, and a conjugated lipid that prevents the particles from aggregating, thereby enabling systemic delivery ('435 Patent, col. 3:35-50).
- Technical Importance: The technology aimed to overcome the instability and delivery challenges of nucleic acid therapeutics, making systemic (e.g., intravenous) administration a more viable option for treating diseases like cancer and atherosclerosis ('435 Patent, col. 2:1-9).
Key Claims at a Glance
- The complaint challenges claims related to independent claim 1 (Compl. ¶59).
- Claim 1 of the '435 patent includes the following essential elements:
- A nucleic acid-lipid particle comprising a nucleic acid.
- A cationic lipid comprising from 50 mol % to 85 mol % of the total lipid present in the particle.
- A non-cationic lipid.
- A conjugated lipid that inhibits aggregation of particles.
- The complaint notes the patent also claims methods of using the particle (Compl. ¶59).
U.S. Patent No. 8,058,069 - "Lipid Formulations for Nucleic Acid Delivery"
- Patent Identification: U.S. Patent No. 8,058,069, “Lipid Formulations for Nucleic Acid Delivery,” issued November 15, 2011.
The Invention Explained
- Problem Addressed: Similar to the '435 patent, the '069 Patent addresses the challenge of creating safe and effective non-viral systems for delivering nucleic acid therapeutics systemically ('069 Patent, col. 2:10-44).
- The Patented Solution: The patent describes stable nucleic acid-lipid particles (SNALPs) comprising a nucleic acid encapsulated within a specific formulation of lipids. This formulation includes a cationic lipid within a particular molar range (50-65 mol %), a non-cationic lipid that is a mixture of a phospholipid and cholesterol, and a conjugated lipid to prevent aggregation ('069 Patent, col. 3:35-50).
- Technical Importance: This approach sought to create serum-stable particles suitable for intravenous injection that could deliver nucleic acids to distal sites like tumors, which was a significant challenge for prior delivery technologies ('069 Patent, col. 3:5-14).
Key Claims at a Glance
- The complaint challenges claims related to independent claim 1 (Compl. ¶61).
- Claim 1 of the '069 patent includes the following essential elements:
- A nucleic acid-lipid particle comprising a nucleic acid.
- A cationic lipid comprising from 50 mol % to 65 mol % of the total lipid.
- A non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof.
- A conjugated lipid that inhibits aggregation of particles.
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.
- Technology Synopsis: This patent relates to stable nucleic acid-lipid particle (SNALP) formulations for systemic delivery of nucleic acids. The invention focuses on specific molar ratios of cationic lipids, non-cationic lipids (phospholipid and cholesterol), and aggregation-inhibiting conjugated lipids ('359 Patent, Abstract).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶63).
- Accused Features: The complaint alleges that the mRNA-LNP formulation in COMIRNATY® does not meet the claimed molar percentages of the lipid components (Compl. ¶107).
U.S. Patent No. 8,822,668 - "Lipid Formulations for Nucleic Acid Delivery"
- Patent Identification: U.S. Patent No. 8,822,668, "Lipid Formulations for Nucleic Acid Delivery," issued September 2, 2014.
- Technology Synopsis: This patent describes serum-stable nucleic acid-lipid particles (SNALPs) comprising an encapsulated nucleic acid. The invention specifies a formulation with particular molar ranges of a cationic lipid, a non-cationic lipid mixture (phospholipid and cholesterol), and a conjugated lipid to enable systemic delivery ('668 Patent, Abstract).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶65).
- Accused Features: The complaint alleges that the mRNA-LNP formulation in COMIRNATY® does not contain the claimed molar percentage of cationic lipid (Compl. ¶120).
U.S. Patent No. 9,006,417 - "Non-Liposomal Systems for Nucleic Acid Delivery"
- Patent Identification: U.S. Patent No. 9,006,417, "Non-Liposomal Systems for Nucleic Acid Delivery," issued April 14, 2015.
- Technology Synopsis: This patent relates to compositions of nucleic acid-lipid particles characterized by having a non-lamellar morphology. The invention specifies that at least about 95% of the particles have this morphology, in addition to claiming specific molar ranges for the lipid components ('417 Patent, Abstract).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶67).
- Accused Features: The complaint alleges that the mRNA-LNP formulation in COMIRNATY® does not meet the claimed molar percentage of cationic lipid (Compl. ¶133).
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.
- Technology Synopsis: This patent describes a lipid vesicle formulation specifically for encapsulating messenger RNA (mRNA). The formulation comprises a plurality of lipid vesicles, each containing a cationic lipid, an amphipathic lipid, and a polyethyleneglycol (PEG)-lipid ('651 Patent, Abstract).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶69).
- Accused Features: The complaint alleges that the mRNA-LNP formulation in COMIRNATY® does not comprise "a cationic lipid" as required by the claims (Compl. ¶146).
U.S. Patent No. 9,518,272 - "Non-Liposomal Systems for Nucleic Acid Delivery"
- Patent Identification: U.S. Patent No. 9,518,272, "Non-Liposomal Systems for Nucleic Acid Delivery," issued December 13, 2016.
- Technology Synopsis: This patent relates to compositions of nucleic acid-lipid particles that are "electron-dense." The invention specifies that at least 95% of the particles are electron-dense, in addition to containing a nucleic acid and various lipid components ('272 Patent, Abstract).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶71).
- Accused Features: The complaint alleges that the mRNA-LNP formulation in COMIRNATY® does not comprise "nucleic-acid lipid particles" that contain "a cationic lipid" as those terms are used in the patent (Compl. ¶159).
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 describes a nucleic acid-lipid particle that "consist[s] essentially of" an RNA, a specific type of cationic lipid (having a protonatable tertiary amine), a mixture of phospholipid and cholesterol, and a PEG-lipid conjugate ('378 Patent, Abstract).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶73).
- Accused Features: The complaint alleges the LNP formulation in COMIRNATY® does not "consist essentially of" the claimed components (Compl. ¶172).
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 relates to an apparatus for producing lipid vesicles. The apparatus comprises reservoirs for aqueous and organic lipid solutions and a pump mechanism configured to mix the solutions in a specific manner (e.g., as opposing flows) to instantaneously produce the vesicles ('320 Patent, Abstract).
- Asserted Claims: Independent claims 1 and 18 are asserted (Compl. ¶75).
- Accused Features: The complaint alleges the mRNA-LNP formulation in COMIRNATY® does not comprise "a cationic lipid" as required by the claims (Compl. ¶184).
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 describes a process, rather than an apparatus, for producing lipid vesicles. The claimed process involves providing aqueous and organic lipid solutions in separate reservoirs and introducing them into a mixing chamber as opposing flows to instantaneously produce the vesicles ('098 Patent, Abstract).
- Asserted Claims: Independent claims 1 and 18 are asserted (Compl. ¶77).
- Accused Features: The complaint alleges the mRNA-LNP formulation in COMIRNATY® does not comprise "a cationic lipid" as required by the claims (Compl. ¶196).
III. The Accused Instrumentality
- Product Identification: The accused instrumentalities are the lipid nanoparticle (LNP) formulations developed and licensed by Acuitas, which are used in the Pfizer-BioNTech COVID-19 vaccine, COMIRNATY® (Compl. ¶2, 44).
- Functionality and Market Context:
- The complaint describes mRNA as an exceptionally fragile molecule that is too large to enter human cells on its own, requiring a specialized delivery system (Compl. ¶11). The Acuitas LNP technology is described as a microscopic sphere of fats that envelops and protects the mRNA payload, allows it to cross the cell membrane, and then releases the mRNA to generate an immune response (Compl. ¶12). This LNP technology, including the proprietary cationic lipid ALC-0315, is identified as a critical component of the COMIRNATY® vaccine (Compl. ¶19).
- The complaint alleges that this technology was instrumental to the success of COMIRNATY®, a vaccine that has been administered in over 350 million doses in the United States and has been crucial in combating the COVID-19 pandemic (Compl. ¶12). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'435 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Non-Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a nucleic acid-lipid particle comprising: (a) a nucleic acid; | The complaint does not contest that the accused product contains a nucleic acid. | ¶80-81 | col. 3:36 |
| (b) a cationic lipid comprising from 50 mol % to 85 mol % of the total lipid present in the particle; | The mRNA-LNP formulation in COMIRNATY® does not comprise the claimed molar percentage of cationic lipid. | ¶81 | col. 3:38-40 |
| (c) a non-cationic lipid; and | The complaint does not specifically contest this element for non-infringement. | ¶80 | col. 3:40-41 |
| (d) a conjugated lipid that inhibits aggregation of particles. | The complaint does not specifically contest this element for non-infringement. | ¶80 | col. 3:42-44 |
- Identified Points of Contention:
- Quantitative Scope Question: The central non-infringement argument is quantitative. A primary question will be whether the actual molar percentage of the cationic lipid in the COMIRNATY® LNP falls outside the range of "from 50 mol % to 85 mol %" required by the claim.
- Definitional Scope Question: The complaint raises invalidity challenges based on the alleged indefiniteness of the term "cationic lipid" (Compl. ¶88). This suggests a potential dispute over whether Acuitas's proprietary lipid, ALC-0315, falls within the patent's definition of "cationic lipid," irrespective of its percentage in the formulation.
'069 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Non-Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a nucleic acid-lipid particle comprising: (a) a nucleic acid, | The complaint does not contest that the accused product contains a nucleic acid. | ¶93-94 | col. 31:59 |
| (b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid, | The mRNA-LNP formulation in COMIRNATY® does not comprise the claimed molar percentage of cationic lipid. | ¶94 | col. 31:60-61 |
| (c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof, and | The complaint does not specifically contest this element for non-infringement. | ¶93 | col. 31:62-64 |
| (d) a conjugated lipid that inhibits aggregation of particles. | The complaint does not specifically contest this element for non-infringement. | ¶93 | col. 31:65-66 |
- Identified Points of Contention:
- Quantitative Scope Question: Similar to the '435 patent, the key non-infringement allegation is that the molar percentage of the cationic lipid in the accused LNP is outside the claimed range of "from 50 mol % to 65 mol %."
- Technical Question: The complaint alleges that the '069 patent's specification does not describe or enable a formulation like Acuitas's mRNA-LNP, suggesting a potential dispute over whether technology developed for siRNA is applicable to the much larger mRNA molecules used in COMIRNATY® (Compl. ¶16, 100).
V. Key Claim Terms for Construction
- The Term: "cationic lipid"
- Context and Importance: This term appears in the independent claims of nearly all asserted patents. Acuitas's primary non-infringement argument is that its LNP formulation does not meet the specific molar percentage ranges required for the "cationic lipid." Furthermore, Acuitas repeatedly argues for invalidity on the basis that the specification fails to inform, with reasonable certainty, which lipids constitute a "cationic lipid," making its definition central to both infringement and validity (Compl. ¶81, 88, 94, 102).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specifications may support a broad definition, defining the term as "any of a number of lipid species that carry a net positive charge at a selected pH, such as physiological pH" ('069 Patent, col. 13:12-15).
- Evidence for a Narrower Interpretation: The specifications also provide an extensive list of exemplary cationic lipids ('069 Patent, col. 13:22-14:5). Defendants may argue that the term's scope should be understood in the context of these specific examples, potentially limiting it to compounds with similar structures or properties.
VI. Other Allegations
- Indirect Infringement: The complaint is a declaratory judgment action where Acuitas seeks a declaration of non-infringement. Acuitas acknowledges it faces potential liability for induced and contributory infringement because its business model is to develop and license its LNP technology to partners like Pfizer and BioNTech, who incorporate it into the final vaccine product sold to the public (Compl. ¶6). The lawsuit against Acuitas’s partners by the Defendants is the basis for the alleged controversy (Compl. ¶4).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of quantitative scope: does the precise molar percentage of the cationic lipid in Acuitas's LNP formulation, as used in COMIRNATY®, fall outside the specific numerical ranges recited in the asserted claims? The plaintiff's non-infringement case appears to rest heavily on this factual, quantitative distinction.
- A central validity question will be one of enablement and written description: do the patent specifications, which the complaint alleges were focused on the delivery of small interfering RNA (siRNA), adequately describe and enable a person of skill in the art to use the claimed lipid compositions to effectively deliver the significantly larger and structurally distinct mRNA molecules used in the accused vaccine?
- A key question for claim construction and validity will be one of definiteness: does the term "cationic lipid," as used across the patent portfolio, provide sufficient clarity for a person of ordinary skill to determine the scope of the claims with reasonable certainty, or is the term, as the plaintiff alleges, fatally indefinite under 35 U.S.C. § 112?