DCT

1:24-cv-01524

Board Of Regents Of University Of Texas System v. Alnylam Pharma Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01524, W.D. Tex., 12/12/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the Western District of Texas because Defendants have regular and established places of business in the district and have committed acts of infringement there, including sales, marketing, patient education, and clinical research.
  • Core Dispute: Plaintiff alleges that Defendant’s Onpattro® (patisiran) medication infringes a patent related to methods for delivering small interfering RNA (siRNA) using neutral lipid compositions.
  • Technical Context: The technology concerns the use of non-charged liposomes as a vehicle to deliver siRNA therapeutics into cells, a foundational challenge in the field of RNA-based medicine for treating genetic disorders.
  • Key Procedural History: The complaint alleges that in 2007, Defendant Alnylam evaluated the patented technology under a non-disclosure agreement and an evaluation agreement with the inventors and Plaintiff, but subsequently informed Plaintiff that it did not require a license before launching the accused product years later.

Case Timeline

Date Event
2005-04-15 Priority Date for U.S. Patent No. 8,895,717
2007-01-01 Alnylam allegedly evaluates technology under NDA/evaluation agreement
2009-01-08 '717 Patent application published
2014-11-25 U.S. Patent No. 8,895,717 issued
2018-01-01 Onpattro® (patisiran) launched after FDA approval
2024-12-12 Complaint filed

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

U.S. Patent No. 8,895,717 - “Delivery of siRNA by neutral lipid compositions”

(Issued November 25, 2014. Compl. ¶15; ’895,717 Patent, front page).

The Invention Explained

  • Problem Addressed: The patent’s background section describes that the in vivo delivery of small interfering RNA (siRNA) has proven "very difficult," which limits the therapeutic potential of siRNA-based treatments (’717 Patent, col. 1:26-29). While liposomes had been used for drug delivery, the patent notes that it was not clear to what degree neutral (non-charged) liposomes could be used to effectively deliver siRNA, particularly as compared to the more commonly studied cationic liposomes (’717 Patent, col. 2:1-10).
  • The Patented Solution: The invention provides compositions and methods for delivering siRNA to a cell using a non-charged, or neutral, liposome (’717 Patent, Abstract). The specification explains that the inventors discovered that these neutral liposomes can efficiently deliver siRNA to cells in vivo, resulting in a significant improvement in delivery compared to cationic liposomes (’717 Patent, col. 2:18-24). The patent describes compositions where the siRNA is encapsulated within the liposome, which is formulated in a pharmaceutically acceptable carrier for administration to a patient (’717 Patent, col. 2:32-43).
  • Technical Importance: This approach offered a potential solution to the critical challenge of systemic siRNA delivery, proposing a vehicle that could be more effective and potentially less toxic than the charged liposome alternatives being explored at the time (’717 Patent, col. 1:45-54).

Key Claims at a Glance

  • The complaint asserts at least claims 2, 10, and 11, which depend from independent claims 1 and 6.
  • Independent Claim 1:
    • A pharmaceutical composition comprising (a) an siRNA component with a negatively charged backbone moiety; and (b) a lipid component comprising a phospholipid component consisting of 1,2-Dioleoyl-sn-Glycero-3-phosphatidylcholine (DOPC);
    • The lipid component has a neutral charge;
    • The lipid component forms a liposome that encapsulates the siRNA such that greater than 90% of the liposomes encapsulate the siRNA;
    • The siRNA is a double stranded nucleic acid of 18 to 100 nucleobases; and
    • The composition is in a pharmaceutically acceptable carrier.
  • Independent Claim 6:
    • A pharmaceutical composition comprising (a) an siRNA component with a negatively charged backbone; and (b) a lipid component with a phospholipid of one or more neutral phospholipids from a specified group;
    • The lipid component has a neutral charge and forms a liposome encapsulating the siRNA with greater than 90% efficiency;
    • The composition is in a pharmaceutically acceptable carrier; and
    • The siRNA inhibits the translation of a gene that promotes cancer, wherein the gene is focal adhesion kinase (FAK).
  • The complaint states that Onpattro infringes "at least claims 2, 10, and 11," reserving the right to assert other claims (Compl. ¶20).

III. The Accused Instrumentality

Product Identification

The accused product is the medication Patisiran, which is sold under the brand name Onpattro® (Compl. ¶4).

Functionality and Market Context

  • Onpattro is a prescription medicine used to treat the rare genetic disease known as hereditary transthyretin-mediated (hATTR) amyloidosis (Compl. ¶5).
  • The complaint alleges that the medication functions by delivering siRNA into a patient's cells to achieve its therapeutic effect (Compl. ¶5). The complaint further alleges that Onpattro uses the composition claimed in the ’717 Patent to accomplish this delivery (Compl. ¶5).
  • Onpattro was Defendant's first commercial product, receiving FDA approval in 2018, and was for a time the only FDA-approved treatment for its indication (Compl. ¶¶4, 6). The complaint alleges it has generated revenue exceeding $1.3 billion (Compl. ¶6).

IV. Analysis of Infringement Allegations

The complaint alleges that Defendant’s Onpattro product infringes at least claims 2, 10, and 11 of the ’717 Patent, either literally or under the doctrine of equivalents (Compl. ¶20). The core of the infringement theory is that Onpattro works by delivering siRNA into a patient's cells using the specific neutral lipid composition invented by Plaintiff's researchers and claimed in the patent (Compl. ¶5). The complaint incorporates by reference an "Exhibit 2" that it claims provides a detailed description of the infringement, but this exhibit is not attached to the publicly filed document (Compl. ¶¶1, 20). The complaint itself does not provide further specific factual allegations mapping the individual components or performance characteristics of the Onpattro product to the limitations of the asserted claims. The complaint does, however, provide documents as exhibits that it alleges show acts of infringement occurring in the district, including employee LinkedIn pages and job postings. For example, the complaint references job postings for personnel to work in the district on activities related to Onpattro (Compl. ¶14, Ex. 4).

Identified Points of Contention

  • Evidentiary Question: A primary point of contention will be factual: what evidence will Plaintiff produce to show that the commercial formulation of Onpattro meets the specific limitations of the claims? The analysis will likely focus on the exact chemical makeup of Onpattro's lipid delivery vehicle and whether it meets the "neutral charge" and specific phospholipid composition requirements (e.g., DOPC for claim 1).
  • Quantitative/Technical Question: The infringement analysis will turn on whether the Onpattro product meets the quantitative limitation that "greater than 90% of the liposomes encapsulate siRNA," as required by independent claims 1 and 6. Demonstrating this high level of encapsulation will be a critical technical hurdle requiring specific and reliable measurement methodologies.
  • Scope Question: Independent claim 6 (and its dependent claim 10) is limited to an siRNA that inhibits the translation of "focal adhesion kinase (FAK)." The complaint states that Onpattro treats hATTR amyloidosis, which is caused by a different gene (transthyretin). This raises the question of whether infringement of any claim depending on claim 6 can be established if the accused product does not target the specific gene recited in the claim.

V. Key Claim Terms for Construction

Term: "neutral charge"

Context and Importance

This term is fundamental to distinguishing the invention from prior art that used charged (e.g., cationic) liposomes. The definition will be critical for determining whether the accused product's lipid formulation, which may be complex, falls within the scope of the claims. Practitioners may focus on this term because the boundary between a "neutral" system and one with a functionally meaningful surface charge is often a key issue in lipid-based delivery system patents.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification defines "essentially neutral" as a state where "few, if any, lipids within a given population... include a charge that is not canceled by an opposite charge (e.g., fewer than 10% of components include a non-canceled charge...)" (’717 Patent, col. 13:9-15). A party could argue this supports a functional definition that allows for some minimal or residual charge.
  • Evidence for a Narrower Interpretation: The patent repeatedly highlights the "non-charged" nature of the liposome in its summary and abstract (’717 Patent, Abstract; col. 2:19). A party could argue that in the context of the claims, "neutral charge" should be construed more strictly to mean a net charge of or very near zero, and that the "essentially neutral" language in the specification is merely descriptive and not definitional for the claim term itself.

Term: "encapsulate"

Context and Importance

The claims require the liposome to "encapsulate" the siRNA, and a high percentage of liposomes must do so. The precise physical nature of this association is central to the infringement analysis.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification provides a broad definition: "Encapsulate refers to the lipid or liposome forming an impediment to free diffusion into solution by an association with or around an agent of interest, e.g., a liposome may encapsulate an agent within a lipid layer or within an aqueous compartment inside or between lipid layers" (’717 Patent, col. 2:34-39). This language could support a construction that includes siRNA associated with the lipid layers, not just contained within the aqueous core.
  • Evidence for a Narrower Interpretation: The claim requirement that "greater than 90% of the liposomes encapsulate siRNA" could be argued to imply a more discrete and measurable state of containment. A party might argue that to be quantifiable to such a precise degree, "encapsulate" must mean fully enclosed within the liposome, as mere surface association might be more difficult to measure and distinguish from non-encapsulated material.

VI. Other Allegations

Indirect Infringement

The complaint alleges inducement of infringement under 35 U.S.C. § 271(b), asserting that Defendant markets Onpattro to doctors and patients and provides instructions on its use through materials such as infusion and clinical research documents (Compl. ¶¶14, 24, Ex. 5, Ex. 6).

Willful Infringement

The willfulness allegation is based on alleged pre-suit knowledge of the technology. The complaint asserts that in 2007, Defendant's representatives received presentations from the inventors about the technology under a non-disclosure agreement and entered into an evaluation agreement, making them aware of the invention long before the patent issued and the accused product was launched (Compl. ¶¶3, 25).

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

  • A central issue will be one of evidentiary proof: can Plaintiff produce sufficient evidence to demonstrate that the commercial Onpattro product meets the highly specific quantitative and compositional limitations of the asserted claims? In particular, the case will likely hinge on technical evidence proving both the "neutral charge" of the lipid vehicle and, critically, the "greater than 90%" siRNA encapsulation rate required by the patent.
  • The case will also present a question of claim applicability: given that Onpattro treats hATTR amyloidosis by targeting the TTR gene, can Plaintiff sustain an infringement allegation for claims (such as claim 10) that depend on a requirement that the siRNA inhibits the "focal adhesion kinase (FAK)" gene, a target seemingly unrelated to the accused product's known mechanism of action?
  • Finally, a key question for the fact-finder will be the interpretation of pre-suit conduct: did Defendant's alleged evaluation of the patented technology under a non-disclosure agreement in 2007, followed by its decision to proceed without a license, rise to the level of objective recklessness required to support a finding of willful infringement?