DCT
1:22-cv-02229
Acuitas Therap Inc v. Genevant Sciences GmbH
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Acuitas Therapeutics Inc. (British Columbia, Canada)
- Defendant: Genevant Sciences GmbH (Switzerland) and Arbutus Biopharma Corp. (British Columbia, Canada)
- Plaintiff’s Counsel: Paul, Weiss, Rifkind, Wharton & Garrison LLP
- Case Identification: 1:22-cv-02229, S.D.N.Y., 03/18/2022
- Venue Allegations: Plaintiff Acuitas alleges venue is proper in the Southern District of New York because Defendants sent demand letters asserting patent infringement to Pfizer's headquarters in Manhattan.
- Core Dispute: Plaintiff seeks a declaratory judgment that the lipid nanoparticle (LNP) technology it supplies for the Pfizer-BioNTech COVID-19 vaccine, COMIRNATY®, does not infringe nine patents owned by Defendant Arbutus, and that the patents are invalid.
- Technical Context: The technology involves lipid nanoparticles, which are microscopic spheres of fat used as a critical delivery system to protect and transport fragile messenger RNA (mRNA) molecules into human cells for therapeutic purposes, most notably in mRNA vaccines.
- Key Procedural History: The complaint notes that this declaratory judgment action follows demand letters sent by Defendants to Pfizer in November 2020 and October 2021, asserting infringement by the COMIRNATY® vaccine. The complaint also highlights that claims of several of the asserted patents have previously been found invalid by the U.S. Patent and Trademark Office in Inter Partes Review (IPR) proceedings.
Case Timeline
| Date | Event |
|---|---|
| 2002-06-28 | Earliest Priority Date ('651 Patent) |
| 2008-04-15 | Earliest Priority Date ('069, '359, '668, '417, '435, '127, '272, '378 Patents) |
| 2011-11-15 | '069 Patent Issued |
| 2013-07-23 | '359 Patent Issued |
| 2014-09-02 | '668 Patent Issued |
| 2015-04-14 | '417 Patent Issued |
| 2016-06-14 | '435 Patent Issued |
| 2016-08-02 | '127 Patent Issued |
| 2016-11-29 | '651 Patent Issued |
| 2016-12-13 | '272 Patent Issued |
| 2020-01-01 | COMIRNATY® Development Began |
| 2020-05-01 | COMIRNATY® Phase 1/2 Clinical Trial Initiated |
| 2020-07-01 | COMIRNATY® Phase 2/3 Clinical Trials Began |
| 2020-11-23 | Defendants' First Demand Letter to Pfizer |
| 2020-12-11 | COMIRNATY® Received FDA Emergency Use Authorization |
| 2021-08-23 | COMIRNATY® Received Full FDA Approval |
| 2021-10-12 | Defendants' Second Demand Letter to Pfizer |
| 2021-10-12 | '378 Patent Issued |
| 2022-03-18 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,058,069 - "Lipid Formulations for Nucleic Acid Delivery"
Issued November 15, 2011 (Compl. ¶50)
The Invention Explained
- Problem Addressed: The patent addresses the challenge of creating a safe and effective nonviral delivery system for therapeutic nucleic acids, such as small interfering RNA (siRNA). Previous systems suffered from limitations including toxicity, rapid clearance from circulation, and an inability to reach target tissues systemically ('069 Patent, col. 1:11-2:13).
- The Patented Solution: The invention provides stable nucleic acid-lipid particles (SNALPs) that fully encapsulate nucleic acids. This is achieved through a specific formulation of lipids: a cationic lipid, a non-cationic lipid (such as a phospholipid and cholesterol), and a conjugated lipid (such as a PEG-lipid) that prevents the particles from aggregating ('069 Patent, Abstract; col. 3:20-44). This composition protects the nucleic acid from degradation in the bloodstream and allows for systemic delivery to target cells ('069 Patent, col. 3:1-13).
- Technical Importance: The development of stable, fully-encapsulated lipid particles provided a viable mechanism for delivering fragile nucleic acid therapeutics throughout the body, a significant hurdle for therapies like RNA interference (RNAi) (Compl. ¶¶4-5).
Key Claims at a Glance
- Independent Claim 1 is asserted (Compl. ¶51).
- The essential elements of Claim 1 are:
- 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;
- (c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof; and
- (d) a conjugated lipid that inhibits aggregation of particles.
U.S. Patent No. 8,492,359 - "Lipid Formulations for Nucleic Acid Delivery"
Issued July 23, 2013 (Compl. ¶52)
The Invention Explained
- Problem Addressed: Similar to its parent '069 patent, the '359 Patent addresses the need for a nonviral delivery system capable of safely and effectively administering nucleic acid-based therapies systemically throughout the body ('359 Patent, col. 1:13-2:14).
- The Patented Solution: The patent describes stable nucleic acid-lipid particles (SNALPs) comprising specific molar ratios of a cationic lipid, a non-cationic lipid, and a particle-stabilizing conjugated lipid. The claimed formulation is designed to fully encapsulate a nucleic acid payload, protecting it from degradation and facilitating delivery to target tissues after intravenous injection ('359 Patent, Abstract; col. 3:20-50).
- Technical Importance: This technology offered a potential solution to the critical delivery problem that limited the therapeutic application of nucleic acids like siRNA (Compl. ¶¶4-5).
Key Claims at a Glance
- Independent Claim 1 is asserted (Compl. ¶53).
- The essential elements of Claim 1 are:
- 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;
- (c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof; and
- (d) a conjugated lipid that inhibits aggregation of particles.
U.S. Patent No. 8,822,668 - "Lipid Formulations for Nucleic Acid Delivery"
Issued September 2, 2014 (Compl. ¶54)
- Technology Synopsis: This patent, related to the '069 and '359 patents, claims nucleic acid-lipid particles with the same specific molar percentages of cationic lipid (50-65 mol %). It further claims methods for treating a disease or disorder and for in vivo delivery of a nucleic acid by administering the claimed particle (Compl. ¶55).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶55).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not contain the claimed percentage of cationic lipid (Compl. ¶123).
U.S. Patent No. 9,006,417 - "Non-Liposomal Systems for Nucleic Acid Delivery"
Issued April 14, 2015 (Compl. ¶56)
- Technology Synopsis: This patent claims a composition comprising a plurality of nucleic acid-lipid particles where at least 95% of the particles have a "non-lamellar morphology." It requires a cationic lipid concentration of 50 mol % to 85 mol % of the total lipid (Compl. ¶57).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶57).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not contain the claimed percentage of cationic lipid (Compl. ¶136).
U.S. Patent No. 9,364,435 - "Lipid Formulations for Nucleic Acid Delivery"
Issued June 14, 2016 (Compl. ¶58)
- Technology Synopsis: This patent claims a nucleic acid-lipid particle with a cationic lipid concentration ranging from 50 mol % to 85 mol % of the total lipid. The patent also claims methods of using this particle for introducing a nucleic acid into a cell and treating a disease (Compl. ¶59).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶59).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not contain the claimed percentage of cationic lipid (Compl. ¶84).
U.S. Patent No. 9,404,127 - "Non-Liposomal Systems for Nucleic Acid Delivery"
Issued August 2, 2016 (Compl. ¶60)
- Technology Synopsis: This patent claims a composition of nucleic acid-lipid particles requiring that "at least about 95% of the particles... have a non-lamellar morphology." This patent is a continuation of the family that includes the '417 patent (Compl. ¶61).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶61).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not comprise "nucleic acid-lipid particles" that contain "a cationic lipid" as those terms are used in the patent (Compl. ¶71).
U.S. Patent No. 9,504,651 - "Lipid Compositions for Nucleic Acid Delivery"
Issued November 29, 2016 (Compl. ¶62)
- Technology Synopsis: This patent claims a lipid vesicle formulation specifically comprising "messenger RNA." The claim also requires a cationic lipid, an amphipathic lipid, and a polyethyleneglycol (PEG)-lipid (Compl. ¶63).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶63).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not comprise "a cationic lipid" as required by the claims of this patent (Compl. ¶149).
U.S. Patent No. 9,518,272 - "Non-Liposomal Systems for Nucleic Acid Delivery"
Issued December 13, 2016 (Compl. ¶64)
- Technology Synopsis: This patent claims a composition of nucleic acid-lipid particles, requiring that "at least 95% of the particles... are electron-dense." This patent is also part of the family requiring a specific morphology (Compl. ¶65).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶65).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not comprise "nucleic-acid lipid particles" that contain "a cationic lipid" as those terms are used in the patent (Compl. ¶162).
U.S. Patent No. 11,141,378 - "Lipid Formulations for Nucleic Acid Delivery"
Issued October 12, 2021 (Compl. ¶66)
- Technology Synopsis: This patent claims a nucleic acid-lipid particle using the restrictive "consisting essentially of" language. The claim requires specific components: an RNA, a cationic lipid having a "protonatable tertiary amine," a mixture of phospholipid and cholesterol, and a PEG-lipid conjugate (Compl. ¶67).
- Asserted Claims: Independent Claim 1 is asserted (Compl. ¶67).
- Accused Features: The complaint alleges the COMIRNATY® LNP does not "consist[] essentially of" the claimed components (Compl. ¶175).
III. The Accused Instrumentality
Product Identification
The lipid nanoparticle (LNP) formulation supplied and licensed by Acuitas for use in the Pfizer-BioNTech COVID-19 vaccine, COMIRNATY® (Compl. ¶¶14, 16).
Functionality and Market Context
The LNP is described as a "microscopic sphere of fats" designed to solve the challenges of delivering messenger RNA (mRNA), which is exceptionally fragile and too large to enter cells on its own (Compl. ¶4). The LNP envelops and protects the mRNA, facilitates its transport across the human cell membrane, and then releases it inside the cell to trigger an immune response (Compl. ¶5). The complaint notes that the LNP in COMIRNATY® uses the ionizable cationic lipid ALC-0315, which was developed by Acuitas (Compl. ¶¶12, 30). The COMIRNATY® vaccine is alleged to have achieved "worldwide commercial success," with over 320 million doses administered in the United States alone (Compl. ¶5).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'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 dispute that the COMIRNATY® LNP is a particle containing a nucleic acid. | ¶97 | col. 3:36-38 |
| (b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid; | The mRNA-LNP formulation in COMIRNATY® does not comprise a cationic lipid in the claimed molar percentage range of 50% to 65%. | ¶97 | col. 3:39-40 |
| (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. | ¶97 | col. 3:40-42 |
| (d) a conjugated lipid that inhibits aggregation of particles. | The complaint does not specifically contest this element. | ¶97 | col. 3:42-44 |
'359 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 dispute that the COMIRNATY® LNP is a particle containing a nucleic acid. | ¶110 | col. 3:36-38 |
| (b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid; | The mRNA-LNP formulation in COMIRNATY® does not comprise a cationic lipid in the claimed molar percentage range of 50% to 65%. | ¶110 | col. 3:39-40 |
| (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. | ¶110 | col. 3:40-42 |
| (d) a conjugated lipid that inhibits aggregation of particles. | The complaint does not specifically contest this element. | ¶110 | col. 3:42-44 |
Identified Points of Contention
- Factual Questions: The central point of contention for many of the asserted patents appears to be factual: what is the precise molar percentage of the cationic lipid component in the COMIRNATY® LNP? The complaint alleges this percentage falls outside the ranges claimed in patents like the ’069, ’359, ’668, ’417, and ’435 patents, but does not provide the specific figure (Compl. ¶¶84, 97, 110, 123, 136). This suggests that discovery and expert testimony on the vaccine's chemical composition will be a determinative factor.
- Scope Questions: For patents requiring specific physical characteristics, such as "non-lamellar morphology" (’127 Patent) or being "electron-dense" (’272 Patent), a key question will be whether the COMIRNATY® LNP, described as a "microscopic sphere," meets these structural limitations (Compl. ¶¶61, 65). Further, for the ’378 Patent, the use of "consisting essentially of" language raises the question of whether any unlisted components in the COMIRNATY® LNP materially affect the basic and novel properties of the claimed invention, thereby placing it outside the claim's scope (Compl. ¶175).
V. Key Claim Terms for Construction
"cationic lipid"
Context and Importance
This term is central to the dispute across nearly all asserted patents. Acuitas's non-infringement arguments rest on two potential pillars: first, a factual argument that the molar percentage of this component is not met, and second, a legal argument that the lipid used in COMIRNATY® (ALC-0315) is not a "cationic lipid" as the term is used in the patents (Compl. ¶¶71, 149, 162). Practitioners may focus on this term because Acuitas highlights Arbutus's own arguments to the Patent Office in prior IPRs that the effects of changing lipid proportions are "unpredictable," which may be used to argue for a narrow construction or to support an invalidity defense of indefiniteness (Compl. ¶79).
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The specifications provide a broad functional definition, stating the term refers to "any of a number of lipid species that carry a net positive charge at a selected pH, such as physiological pH" ('069 Patent, col. 13:19-22).
- Evidence for a Narrower Interpretation: The specifications list numerous exemplary cationic lipids ('069 Patent, col. 13:34-14:10). Defendants may argue that the term should be construed as limited to lipids structurally similar to these examples, particularly in light of arguments made to the patent office about the unpredictability of the technology.
"nucleic acid-lipid particle"
Context and Importance
This term defines the fundamental structure being claimed. Its construction is critical for patents that add morphological requirements, such as the '417 and '127 patents (requiring "non-lamellar morphology") and the '272 patent (requiring particles to be "electron-dense") (Compl. ¶¶57, 61, 65). The dispute may turn on whether the COMIRNATY® LNP, described as a "sphere of fats," possesses the specific internal structure contemplated by the patents.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The patents define the particle functionally as a formulation that can deliver a nucleic acid to a target site and in which the nucleic acid is fully encapsulated within the lipid portion ('069 Patent, col. 11:34-49).
- Evidence for a Narrower Interpretation: Defendants may point to specific embodiments and figures in the patents that illustrate particular structures. For patents with morphological limitations, the definitions of terms like "non-lamellar" (defined as including, for example, an inverse hexagonal phase structure) will be paramount ('417 Patent, col. 2:63-66).
VI. Other Allegations
The complaint does not provide sufficient detail for analysis of Indirect Infringement.
The complaint does not provide sufficient detail for analysis of Willful Infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: can Acuitas demonstrate through chemical analysis that the precise molar percentages of the lipid components in the commercial COMIRNATY® vaccine fall outside the specific numerical ranges recited in many of the Arbutus patents?
- A key legal question will be one of claim scope and estoppel: how will the court construe the term "cationic lipid," and will Arbutus be constrained by its prior arguments to the U.S. Patent and Trademark Office regarding the "unpredictable" nature of lipid formulations, which Acuitas has put at issue to support its claims of invalidity for indefiniteness and lack of enablement?
- A core technical question will be one of structural and compositional equivalence: for the patents with more specific limitations, does the COMIRNATY® LNP possess the claimed "non-lamellar" or "electron-dense" morphology, and for the most recent patent, does it "consist essentially of" the claimed components, or does it contain additional ingredients that materially alter its fundamental characteristics?