Moderna Therapeutics Inc v. Arbutus Biopharma Corp

1. Case Identification

• Case #: IPR2019-00554
• Patent #: 8,058,069
• Filed: January 9, 2019
• Petitioner(s): Moderna Therapeutics, Inc.
• Patent Owner(s): Arbutus Biopharma Corporation
• Challenged Claims: 1-22

2. Patent Overview

• Title: Lipid Formulations for Nucleic Acid Delivery
• Brief Description: The ’069 patent discloses nucleic acid-lipid particles (e.g., Stable Nucleic Acid Lipid Particles or SNALPs) for delivering therapeutic nucleic acids, such as small interfering RNA (siRNA). The claims are directed to compositions defined by specific molar percentage ranges of four lipid components: a cationic lipid, a phospholipid, cholesterol, and a conjugated lipid.

3. Grounds for Unpatentability

Ground 1: Claims 1-22 are anticipated by or obvious over Patent Owner's prior disclosures.

• Prior Art Relied Upon: The ’196 PCT (WO 2005/007196) or the ’189 publication (Application # 2006/0134189).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that these references, which are prior art under 35 U.S.C. §102(b) due to different inventive entities and no priority claim, disclose the same four lipid components for delivering siRNA as claimed in the ’069 patent. Critically, the references disclose broad and preferred ranges for each component that overlap with and, in some cases, encompass the ranges recited in claim 1. For example, the ’196 PCT taught a cationic lipid range of 2-60 mol%, a non-cationic lipid range of 5-90 mol%, a cholesterol range of 20-45 mol%, and a conjugated lipid range of 0.5-25 mol%, all of which overlap with the claimed ranges.
  • Motivation to Combine (for §103 grounds): The explicit disclosure of overlapping ranges for all components established a prima facie case of obviousness. Petitioner asserted that determining the optimal proportions within these known ranges would have been a simple matter of routine optimization for a person of ordinary skill in the art (POSITA). The patent owner’s reliance on "unexpected results" to overcome this presumption was argued to be insufficient because the testing was limited to a single formulation and did not support the full scope of the claims.
  • Expectation of Success: A POSITA would have had a reasonable expectation of successfully formulating nucleic acid-lipid particles within the claimed ranges, as the prior art taught that the proportions of these known components could be varied to optimize delivery.

Ground 2: Claims 1-22 are obvious over the Patent Owner's prior disclosures in light of Lin and Ahmad.

• Prior Art Relied Upon: The ’196 PCT or the ’189 publication, in view of Lin (a 2003 journal article) and Ahmad (a 2005 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground asserted that to the extent the primary references were found not to explicitly disclose a cationic lipid proportion in the claimed 50-65 mol% range, the combination with Lin and Ahmad rendered it obvious. The ’196 PCT and ’189 publication provided the foundational four-component lipid nanoparticle system for siRNA delivery.
  • Motivation to Combine: Petitioner argued that both Lin and Ahmad taught that increasing the molar percentage of cationic lipid above 50% could increase the transfection efficiency of lipid delivery systems. For instance, Ahmad reported optimal transfection for one lipid at 55 mol%, and Lin showed monotonically increasing efficiency for DOTAP lipids above 50 mol%. A POSITA seeking to improve the efficiency of the system disclosed in the ’196 PCT or ’189 publication would have been motivated to increase the cationic lipid percentage into the 50-65 mol% range as taught by Lin and Ahmad.
  • Expectation of Success: Given that the base components and formulation methods were known from the primary references, and the secondary references demonstrated a clear trend of improved efficacy with higher cationic lipid content, a POSITA would have had a reasonable expectation of success in achieving a functional, and potentially improved, formulation.

Ground 3: Claims 1-22 are anticipated by or obvious over the ’554 publication.

• Prior Art Relied Upon: The ’554 publication (Application # 2006/0240554).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the ’554 publication, like the references in Ground 1, disclosed nucleic acid-lipid particles comprising the same four classes of lipid components and disclosed overlapping percentage ranges. The ’554 publication taught a cationic lipid range of 2-60 mol%, a neutral/non-cationic lipid range of 5-90 mol%, a cholesterol range of 20-45 mol%, and a PEG-conjugate range of 1-20 mol%. Petitioner further noted that specific examples in the ’554 publication disclosed formulations with 50% or 52% cationic lipid, falling within the claimed range.
  • Motivation to Combine (for §103 grounds): The disclosure of overlapping ranges and specific examples within those ranges established a prima facie case of obviousness. A POSITA would have been motivated to optimize the disclosed formulation by selecting proportions within the disclosed ranges to achieve a desired delivery profile.
  • Expectation of Success: The ’554 publication provided all the necessary components and formulation principles, giving a POSITA a clear basis and a reasonable expectation of success for creating particles with the component ratios recited in the challenged claims.

4. Key Claim Construction Positions

• "Nucleic acid-lipid particle": Petitioner noted that in a related IPR for a descendant patent, the Board construed this term to mean “a particle that comprises a nucleic acid and lipids, in which the nucleic acid may be encapsulated in the lipid portion of the particle.” Petitioner asserted this construction, based on the specification, was applicable and was the only construction necessary for the ’069 patent.

5. Key Technical Contentions (Beyond Claim Construction)

• Insufficiency of "Unexpected Results" Data: A central argument across all grounds was that the Patent Owner's assertion of unexpected results, which was used to overcome rejections during prosecution, was fatally flawed. Petitioner contended that the patent’s efficacy data relied on a single specific formulation (the "1:57 SNALP") that fell within the broad claimed ranges. This single data point was argued to be insufficient to demonstrate unexpected results across the entire claimed scope, which covers a wide variety of lipid species and a continuous range of proportions.
• Patent Data Does Not Show Superiority: Petitioner further argued that the patent's own in vitro and in vivo test data did not demonstrate a clear or consistent advantage for the claimed formulation. The data allegedly showed that the "1:57 SNALP" was no more effective than certain prior art formulations and that minor, obvious variations in lipid proportions outside the claimed range yielded comparable or superior results, undermining any claim of criticality or unexpectedness for the recited ranges.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-22 of Patent 8,058,069 as unpatentable.