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

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: The Board of Regents of The University of Texas System (Texas)
  • Defendant: Alnylam Pharmaceuticals Inc. and Alnylam U.S., Inc. (Delaware)
  • Plaintiff’s Counsel: McKool Smith, P.C.
• 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 Defendant maintains regular and established places of business in the District and commits acts of infringement there, including sales, marketing, patient education, and clinical research related to the accused product.
• Core Dispute: Plaintiff alleges that Defendant’s drug, Onpattro, infringes a patent related to compositions and methods for delivering small interfering RNA (siRNA) into cells using neutral lipid formulations.
• Technical Context: The technology concerns drug delivery vehicles for RNA interference (RNAi) therapeutics, a field focused on using small nucleic acid sequences to silence disease-causing genes.
• Key Procedural History: The complaint alleges that in 2007, Defendant Alnylam evaluated the inventors' technology under a non-disclosure agreement and an evaluation agreement. Plaintiff further alleges that after substantial discussions, Alnylam stated it did not need a license but proceeded to use the invention, forming a basis for the willfulness allegation.

Case Timeline

Date	Event
2005-04-15	U.S. Patent No. 8,895,717 Priority Date
2007-01-01	Defendant allegedly expressed interest in and evaluated the patented technology under an NDA
2009-01-08	Patent application that became the ’717 Patent published
2014-11-25	U.S. Patent No. 8,895,717 Issued
2018-01-01	Defendant announced FDA approval for accused product Onpattro
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

• Patent Identification: U.S. Patent No. 8,895,717 ("Delivery of siRNA by neutral lipid compositions"), issued November 25, 2014 (the "’717 Patent"). (Compl. ¶15; ’717 Patent, cover page).

The Invention Explained

• Problem Addressed: The patent describes that while short interfering RNA (siRNA) has significant therapeutic potential, its delivery into cells in vivo has proven "very difficult." (’717 Patent, col. 1:26-30). Prior art methods using cationic (positively charged) liposomes were observed to be taken up by cells more efficiently than neutral liposomes, which the patent asserts taught away from using neutral liposomes for siRNA delivery. (’717 Patent, col. 2:1-8).
• The Patented Solution: The invention is directed to compositions and methods that use non-charged (neutral) liposomes to deliver siRNA into cells. (’717 Patent, Abstract). The inventors state they discovered that these neutral liposomes can achieve a "significant (~10 fold) improvement in delivery as compared with cationic liposomes in vivo," providing a more effective vehicle for siRNA-based drugs. (’717 Patent, col. 2:19-24). The specification highlights specific neutral phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), as key components of these compositions. (’717 Patent, col. 2:45-61).
• Technical Importance: The claimed solution offered a potential pathway for safer and more effective systemic delivery of siRNA therapeutics, a critical challenge for the entire field of RNAi medicine. (Compl. ¶2).

Key Claims at a Glance

The complaint asserts claims 2, 10, and 11, which depend from independent claims 1 and 6, respectively. (Compl. ¶20).

• Independent Claim 1:

  • A pharmaceutical composition comprising a short inhibitory ribonucleic acid (siRNA) component and a lipid component.
  • The siRNA has a backbone moiety that is negatively charged.
  • The lipid component consists of one or more neutral phospholipids (e.g., phosphatidylcholine) but not lysophosphatidylcholine.
  • The lipid component has a neutral charge and forms a liposome that encapsulates the siRNA.
  • The encapsulation is such that "greater than 90% of the liposomes encapsulate siRNA."
  • The siRNA is a double-stranded nucleic acid of 18 to 100 nucleobases.
  • The composition is comprised in a pharmaceutically acceptable carrier.

• Independent Claim 6:

  • Includes all elements of Claim 1.
  • Further requires that the siRNA "inhibits the translation of a gene that promotes growth of a hyperplastic or cancerous mammalian cell."

The complaint also asserts infringement under the doctrine of equivalents and notes that Plaintiff may assert other claims. (Compl. ¶20).

III. The Accused Instrumentality

Product Identification

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

Functionality and Market Context

Onpattro is a drug used to treat hereditary transthyretin-mediated (hATTR) amyloidosis, a rare genetic disease. (Compl. ¶5). The complaint alleges that Onpattro functions by "delivering siRNA into the patient's cell, using the composition that Drs. Sood and Lopez-Berestein invented and claimed in the '717 Patent." (Compl. ¶5). The complaint alleges Onpattro was Defendant's first commercial product and, for a time, the only FDA-approved treatment for hATTR amyloidosis, generating revenue exceeding $1.3 billion. (Compl. ¶4, ¶6).

IV. Analysis of Infringement Allegations

The complaint references an infringement analysis in Exhibit 2, which was not provided. (Compl. ¶1, ¶20). Therefore, the infringement theory is summarized from the complaint's narrative allegations.

The core of the infringement allegation is that Defendant's Onpattro product is a pharmaceutical composition that embodies the invention claimed in the ’717 Patent. (Compl. ¶5). The complaint asserts that Onpattro "literally meets each claim limitation of at least claims 2, 10, and 11 of the ’717 Patent." (Compl. ¶20). The complaint does not, however, provide specific factual support or evidence mapping the composition of Onpattro to these claim limitations, instead relying on the general allegation that Onpattro works by delivering siRNA using the patented composition. (Compl. ¶5).

No probative visual evidence provided in complaint.

Identified Points of Contention

• Scope Questions: The dispute may center on the scope of the term "neutral lipid composition." A central question will be whether the specific formulation of lipids used in Onpattro, which is not detailed in the complaint, falls within the patent's definition of a composition with an "essentially neutral charge." (’717 Patent, col. 13:5-8).
• Technical Questions: A key evidentiary question will be whether the Onpattro product meets the quantitative limitation that "greater than 90% of the liposomes encapsulate siRNA" as required by the independent claims. (’717 Patent, col. 75:46-48). The complaint does not provide data or testing methodology to support this allegation, suggesting this will be a focus of expert discovery.

V. Key Claim Terms for Construction

The Term: "essentially neutral charge"

• Context and Importance: This term is central to defining the scope of the invention and distinguishing it from prior art cationic liposomes. Practitioners may focus on this term because the infringement analysis will depend on whether Onpattro's lipid formulation, once revealed in discovery, possesses this characteristic.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification defines the term to mean that "few, if any, lipids within a given population... include a charge that is not canceled by an opposite charge." (’717 Patent, col. 13:8-12). This language could support an interpretation that includes compositions containing both positively and negatively charged lipids, so long as their charges substantially cancel each other out.
  • Evidence for a Narrower Interpretation: The patent's summary and detailed description repeatedly highlight embodiments comprising phospholipids that are themselves neutral, such as DOPC. (’717 Patent, col. 2:45-61). A party might argue that the invention is focused on compositions primarily made of neutral components, rather than complex mixtures of charged components that sum to neutral.

The Term: "a liposome that encapsulate the siRNA such that greater than 90% of the liposomes encapsulate siRNA"

• Context and Importance: This quantitative limitation sets a specific, high-performance standard for the claimed composition. Proving that the accused product meets this precise efficiency threshold will be a critical and likely contested element of the infringement case.
• Intrinsic Evidence for Interpretation: The patent describes a method for estimating encapsulation efficiency by separating free siRNA from liposomes using filter units and then measuring the remaining siRNA via spectrophotometry. (’717 Patent, col. 32:38-48). The claims, however, are directed to the composition itself, not the method of its creation or measurement. The debate over this term may therefore revolve around the appropriate scientific methodology for measuring the encapsulation percentage of the accused product as it is made, sold, or used.

VI. Other Allegations

• Indirect Infringement: The complaint alleges induced infringement, stating that Defendant markets Onpattro to doctors, patients, and infusion centers and provides instructions on how to use and sell the product. (Compl. ¶24).
• Willful Infringement: Willfulness is alleged based on pre-suit knowledge of the technology. The complaint alleges that Defendant was "aware of the then-pending patent application" because its scientists received presentations from the inventors under a non-disclosure agreement in 2007 and had "subsequent interactions" regarding the technology. (Compl. ¶3, ¶25).

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

• A primary issue will be one of evidentiary proof: can Plaintiff produce technical evidence from discovery demonstrating that Alnylam's Onpattro product, as commercially manufactured and sold, meets the specific quantitative limitations of the asserted claims, most notably the requirement that "greater than 90% of the liposomes encapsulate the siRNA"?
• A central question for willfulness and potential damages enhancement will be one of historical intent: what does the evidence from the 2007 interactions between Alnylam and the inventors reveal about Alnylam's knowledge of the claimed technology during the development of Onpattro?