Acuitas Therap Inc v. Alnylam Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Acuitas Therapeutics Inc., Michael J. Hope, Steven M. Ansell, and Xinyao Du (British Columbia, Canada)
  • Defendant: Alnylam Pharmaceuticals, Inc. (Delaware)
  • Plaintiff’s Counsel: Young Conaway Stargatt & Taylor, LLP; Groombridge, Wu, Baughman & Stone LLP
• Case Identification: 1:24-cv-00816, D. Del., 07/12/2024
• Venue Allegations: Venue is asserted as proper in the District of Delaware because the Defendant is a Delaware corporation.
• Core Dispute: Plaintiffs seek a declaratory judgment to correct the inventorship of seven U.S. patents, assigned to Defendant, to add three Acuitas scientists as co-inventors, alleging they made significant contributions to the claimed inventions.
• Technical Context: The technology involves biodegradable cationic lipids used to form lipid nanoparticles (LNPs) for the systemic delivery of nucleic acid therapeutics, such as siRNA and mRNA, a field that gained significant prominence with the development of COVID-19 vaccines.
• Key Procedural History: The complaint alleges the disputed inventions arose from a collaboration between Plaintiff Acuitas (then AlCana) and Defendant Alnylam from 2009 to 2012, focused on developing LNP delivery for siRNA therapeutics. Plaintiffs allege that after the collaboration ended and after the success of the Comirnaty® mRNA vaccine became public, Alnylam filed a series of continuation patent applications claiming inventions conceived by Acuitas scientists but omitting them as inventors. The complaint also notes that Alnylam is currently asserting six of the seven patents-in-suit against Pfizer and BioNTech, partners of Acuitas, in separate litigation in the same district.

Case Timeline

Date	Event
2011-12-07	Earliest Priority Date for Patents-in-Suit (Provisional App. 61/568,133)
2020-12-11	FDA grants Emergency Use Authorization for Comirnaty® Vaccine
2021-08-23	FDA grants full regulatory approval for Comirnaty® Vaccine
2022-07-12	U.S. Patent No. 11,382,979 Issues
2023-02-15	U.S. Patent No. 11,246,933 Issues
2023-02-28	U.S. Patent No. 11,590,229 Issues
2023-03-28	U.S. Patent No. 11,612,657 Issues
2023-04-25	U.S. Patent No. 11,633,479 Issues
2023-04-25	U.S. Patent No. 11,633,480 Issues
2023-06-20	U.S. Patent No. 11,679,158 Issues
2024-07-12	Complaint for Declaratory Judgment of Co-Inventorship Filed

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

U.S. Patent No. 11,246,933 - "Biodegradable lipids for the delivery of active agents"

The Invention Explained

• Problem Addressed: The patent background describes the difficulty in delivering therapeutic nucleic acids like siRNA into cells systemically, as they are susceptible to degradation in plasma and have limited ability to enter cells on their own (’933 Patent, col. 1:36-45).
• The Patented Solution: The invention provides novel cationic lipids containing one or more biodegradable groups. These lipids are designed to be incorporated into lipid particles that encapsulate and protect nucleic acids, facilitate their delivery into cells, and then biodegrade to reduce potential toxicity associated with lipid accumulation (’933 Patent, col. 1:58-65; col. 2:5-13). The fundamental structure of the cationic lipid is described as a combination of a headgroup, a central moiety, and two hydrophobic groups (’933 Patent, col. 37:1-6).
• Technical Importance: The development of biodegradable lipids for LNP formulations was a key step in improving the safety profile of nucleic acid therapeutics, enabling repeated administration for chronic conditions or widespread use in vaccines (Compl. ¶39).

Key Claims at a Glance

• The complaint alleges the Acuitas Scientists contributed to the conception of the subject matter of claims 16-17 and 18-28 (Compl. ¶¶ 59-60). Independent claim 18 is representative of the cationic lipid composition claims.
• Claim 18 (paraphrased elements): A cationic lipid comprising a primary group and two biodegradable hydrophobic tails, wherein:
  • The primary group comprises a head group that is a protonatable tertiary amine, and a central moiety to which the head group and hydrophobic tails are directly bonded;
  • The central moiety is a central carbon or nitrogen atom;
  • Each hydrophobic tail independently has the formula –R¹²-M¹-R¹³, where R¹² is a C₄-C₁₄ alkylene or C₄-C₁₄ alkenylene, M¹ is the biodegradable group, and R¹³ is a branched C₁₀-C₂₀ alkyl;
  • The biodegradable group is separated from a terminus of the hydrophobic tail by from 6 to 12 carbon atoms; and
  • The total carbon atom content of the hydrophobic tail is from 21 to 26 atoms.

U.S. Patent No. 11,382,979 - "Biodegradable lipids for the delivery of active agents"

The Invention Explained

• Problem Addressed: Similar to the ’933 Patent, the ’979 Patent addresses the need for improved cationic lipids and lipid nanoparticles for the delivery of oligonucleotides, seeking to provide high drug-to-lipid ratios, protection from degradation, and effective intracellular delivery with a favorable therapeutic index (’979 Patent, col. 1:46-59).
• The Patented Solution: This invention relates to specific lipid particle compositions comprising defined molar percentages of a cationic lipid, a phospholipid (DSPC), cholesterol, and a PEG-modified lipid, encapsulating a nucleic acid (’979 Patent, col. 493:40-52). The cationic lipid component itself is defined by a specific chemical structure including a head group, two hydrophobic tails, and a central moiety, consistent with the technology described in the ’933 Patent.
• Technical Importance: Defining precise molar ratios of lipid components is crucial for creating stable, effective, and reproducible LNP formulations for clinical use (Compl. ¶¶ 40-41).

Key Claims at a Glance

• The complaint alleges the Acuitas Scientists contributed to the conception of each of the claims of the ’979 Patent (Compl. ¶72). Independent claim 1 is representative of the lipid particle composition claims.
• Claim 1 (paraphrased elements): A lipid particle comprising:
  • a nucleic acid;
  • 35-65 mol % of a cationic lipid;
  • 3-12 mol % distearoylphosphatidylcholine (DSPC);
  • 15-45 mol % cholesterol; and
  • 0.5-10 mol % of a PEG-modified lipid.
  • The claim further defines the chemical structure of the cationic lipid, including features such as two hydrophobic tails, a central moiety, and specific branching and carbon content characteristics.

U.S. Patent No. 11,590,229 - "Biodegradable lipids for the delivery of active agents"

• Technology Synopsis: The patent claims pharmaceutical compositions comprising a nucleic acid (such as RNA) and a specific LNP formulation defined by molar ratios of four lipid components: a cationic lipid, DSPC, cholesterol, and a PEG-modified lipid. The invention is directed at the composition itself and methods of using it to deliver nucleic acids.
• Asserted Claims: All claims (Compl. ¶85).
• Alleged Inventive Contribution: Conception of the pharmaceutical compositions, including the specific molar ratios and the structure of the cationic lipid, which includes a head group, central moiety, and two hydrophobic tails with biodegradable and branched features (Compl. ¶86).

U.S. Patent No. 11,612,657 - "Biodegradable lipids for the delivery of active agents"

• Technology Synopsis: The patent claims pharmaceutical compositions comprising a nucleic acid (such as RNA) formulated in an LNP with specific molar percentages of a cationic lipid, DSPC, cholesterol, and a PEG-modified lipid. The claims are directed to the compositions and methods of their use.
• Asserted Claims: All claims (Compl. ¶97).
• Alleged Inventive Contribution: Conception of the claimed pharmaceutical compositions, including the specific molar ratios and the chemical structure of the cationic lipid (Compl. ¶98).

U.S. Patent No. 11,633,479 - "Biodegradable lipids for the delivery of active agents"

• Technology Synopsis: The patent claims a genus of lipid compounds having a protonatable group and a specific chemical structure comprising a head group, a central moiety, and two hydrophobic tails. The tails are characterized by containing a biodegradable group (e.g., an ester) and a branched alkyl group.
• Asserted Claims: All claims (Compl. ¶109).
• Alleged Inventive Contribution: Conception of the claimed genus of lipid compounds, including their core structural features and protonatable nature, through the design and synthesis of numerous specific lipid compounds within that genus (Compl. ¶110).

U.S. Patent No. 11,633,480 - "Biodegradable lipids for the delivery of active agents"

• Technology Synopsis: This patent claims lipid particles comprising a nucleic acid and a specific formulation of lipids defined by molar ratios. It also claims methods for preparing such lipid particles, for example by mixing a lipid solution in an organic solvent with an aqueous solution of nucleic acid.
• Asserted Claims: All claims (Compl. ¶121).
• Alleged Inventive Contribution: Conception of the lipid particle compositions, the chemical structure of the cationic lipids within them, and the methods for preparing the lipid particles (Compl. ¶¶ 122-123).

U.S. Patent No. 11,679,158 - "Biodegradable lipids for the delivery of active agents"

• Technology Synopsis: The patent claims a genus of cationic lipids with specific structural features, including a protonatable group, and methods for delivering siRNA using lipid particles containing these lipids in defined molar ratios with other components.
• Asserted Claims: All claims (Compl. ¶135).
• Alleged Inventive Contribution: Conception of the claimed genus of cationic lipids and the methods for delivering siRNA using particles formulated with these lipids (Compl. ¶¶ 136-137).

III. The Technology at Issue

Product Identification

The complaint centers on the inventorship of lipid nanoparticle (LNP) technology for delivering nucleic acids, as embodied in products like the Comirnaty® COVID-19 vaccine developed by Acuitas, BioNTech, and Pfizer (Compl. ¶¶ 2, 4).

Functionality and Market Context

The LNP technology functions by encapsulating fragile nucleic acid payloads, such as mRNA or siRNA, within a microscopic sphere of lipids (Compl. ¶¶ 4, 24). This protective shell prevents the rapid breakdown of the nucleic acid in the body and facilitates its entry into target cells, where it can exert its therapeutic effect (Compl. ¶4). The complaint alleges this LNP technology is comprised of four lipid components: an ionizable cationic lipid, cholesterol, a phospholipid, and a pegylated lipid (Compl. ¶¶ 17, 40). The complaint highlights the immense market importance of this technology, stating that the success of mRNA vaccines was instrumental in vanquishing the COVID-19 pandemic (Compl. ¶1). Figure 1 of the complaint illustrates the proposed mechanism by which the shape of cationic lipids allows the therapeutic payload to escape the endosome and enter the cell's cytoplasm (Compl. p. 13, Fig. 1).

IV. Analysis of Co-Inventorship Allegations

’933 Patent Co-Inventorship Allegations

Claim Element (from Independent Claim 18)	Alleged Inventive Contribution by Acuitas Scientists	Complaint Citation	Patent Citation
A cationic lipid comprising a primary group and two ... biodegradable hydrophobic tails...	Drs. Hope, Ansell, and Du allegedly conceived of and developed the core structure of cationic lipids comprising a head group, a central moiety, and two hydrophobic tails. (Compl. ¶59). This work was guided by the "shape" hypothesis, proposing that cone-shaped lipids with non-linear tails would disrupt endosomal membranes to release the payload. (Compl. ¶30).	¶59	col. 15:31-36
...each of the two hydrophobic tails independently consists of an aliphatic group interrupted by an ester group...	Acuitas Scientists allegedly conceived, synthesized, and confirmed that a biodegradable ester group could replace a double bond in the lipid tail to maintain or enhance efficacy and improve the safety profile by increasing biodegradability. (Compl. ¶39).	¶39, ¶59	col. 535:40-44
...R¹³ is a branched C₁₀-C₂₀ alkyl where the branching occurs at the a-position relative to M¹...	Acuitas Scientists allegedly conceived, synthesized, and confirmed that branched groups along the hydrophobic tails after the ester could amplify the "kink" needed for the cone shape, improving membrane disruption. (Compl. ¶39). Drs. Hope, Ansell, and Du are specifically alleged to have conceived of lipids with branched alkyl chains at the alpha position of the biodegradable group. (Compl. ¶59).	¶39, ¶59	col. 535:45-53
...the total carbon atom content of each hydrophobic tail is 21 to 26 carbon atoms...	The complaint alleges that Drs. Hope, Cullis, and/or Madden understood early on that lipid tails would need to be of a certain length, such as at least 18 carbons, to achieve the necessary cone shape for efficacy. (Compl. ¶30).	¶30	col. 535:54-62

Identified Points of Contention

• Legal & Evidentiary Question: A central issue will be whether the Plaintiffs' alleged contributions, such as the development of the "cone shape" hypothesis and the synthesis of precursor lipids like MC3 (Compl. ¶35), rise to the level of conception of the claimed invention under the legal standard for joint inventorship, which requires a significant contribution to the "definite and permanent idea of the complete and operative invention."
• Scope Question: The dispute may turn on the relationship between the specific lipid structures allegedly synthesized by Acuitas scientists during the collaboration (Compl. ¶¶ 42-44) and the much broader genus of compounds claimed in the ’933 patent. The court may need to determine if contributing specific species provides an inventive contribution to a claimed genus that encompasses them.

V. Key Claim Terms for Construction

• The Term: "biodegradable group"

• Context and Importance: The inclusion of a "biodegradable group" is a central feature of the claimed lipids, intended to improve their safety profile over prior art lipids (Compl. ¶39). Plaintiffs allege that the idea of using an ester as this biodegradable group was their conception. The scope of this term will be critical to determining the boundaries of the invention to which Plaintiffs allege they contributed. Practitioners may focus on this term because its definition delineates what structural modifications fall within the patent's scope.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent specification provides a list of over a dozen different chemical moieties that can serve as a "biodegradable group," including not only esters (—OC(O)— or —C(O)O—) but also disulfides (—S—S—), oximes (—C(R⁵)=N—O—), and others (’933 Patent, col. 3:1-10).
  • Evidence for a Narrower Interpretation: The detailed examples and preferred embodiments in the patent focus heavily on ester linkages as the biodegradable group (’933 Patent, col. 34:34-40). Defendant may argue that the core of the invention as practiced and enabled is narrower than the full list of theoretical groups might suggest.

• The Term: "branched alkyl"

• Context and Importance: The presence and position of a "branched alkyl" group in the hydrophobic tail is another key structural limitation. Plaintiffs allege this feature was their idea to create a "cone-shaped molecule" essential for efficacy (Compl. ¶39). How broadly this term is construed will directly impact the inventorship analysis.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent defines "branched alkyl" structurally as an alkyl group in which one carbon atom is "bound to at least three other carbon atoms" and is not a ring atom, providing a general chemical definition (’933 Patent, col. 411:18-24).
  • Evidence for a Narrower Interpretation: The claims themselves, such as claim 18 of the ’933 Patent, often add positional limitations, such as requiring the branching to be at the "a-position relative to M¹," the biodegradable group (’933 Patent, col. 536:1-4). This suggests that while the term itself is broad, its inventive significance may be tied to its specific placement within the molecule.

VI. Basis for Correction of Inventorship

The complaint seeks to correct inventorship under 35 U.S.C. § 256, which allows for correction if an inventor was omitted through error and without deceptive intention. The complaint alleges that the omission of Drs. Hope, Ansell, and Du was an "error" (Compl. ¶63). However, it also alleges that Alnylam "deliberately omitted" the Acuitas scientists from the patents-in-suit, while naming them on a related application from a parallel patent family that was later abandoned (Compl. ¶¶ 7, 49). These contrasting allegations may frame a central dispute over whether the omission constitutes a correctable error or was the result of deceptive intent, a key legal distinction under the statute.

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

• A central issue will be one of inventive contribution: can the Plaintiffs demonstrate with clear and convincing evidence that their alleged contributions during the 2009-2012 collaboration—such as developing the "cone shape" hypothesis and synthesizing specific lipid examples—amounted to conception of the complete and operative inventions as broadly claimed in the patents-in-suit, which were filed years after the collaboration ended?
• A second key question will be one of statutory intent: how will the court reconcile the allegation that the inventors were omitted through correctable "error" with the parallel allegation that they were "deliberately omitted"? The determination of whether the omission occurred "without any deceptive intention" will be critical to the Plaintiffs' request for relief under 35 U.S.C. § 256.