PTAB

IPR2025-01194

Sarepta Therapeutics Inc v. Genzyme Corp

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Compositions and Methods to Prevent AAV Vector Aggregation
  • Brief Description: The ’542 patent relates to stable, high-concentration storage compositions for purified recombinant adeno-associated virus (rAAV) vectors. The compositions use specific parameters, including a pH between 7.5 and 8.0, ionic strength greater than 200 mM, and certain multivalent ions, to prevent viral particle aggregation during storage.

3. Grounds for Unpatentability

Ground 1: Claims 3-6 are obvious over Wu and Konz

  • Prior Art Relied Upon: Wu (a 2001 journal article on rAAV purification) and Konz (WO 03/097797 on adenovirus purification).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued Wu taught a method to produce stable, high-titer rAAV stocks (around 5 x 10¹³ vg/ml) in a buffer (PBS²⁺ with NaCl) that met the claimed pH (7.5-8.0), high ionic strength (>200 mM), and multivalent ion (phosphate, magnesium) limitations. Wu confirmed a lack of aggregation using electron microscopy. Konz was argued to teach formulation buffers for viral stability, including those with high ionic strength and multivalent ions at pH 8.0 (via its incorporated reference, Evans), and the addition of Pluronic non-ionic surfactants (like Pluronic F68) to further inhibit aggregation. Konz also disclosed modern analytical techniques like dynamic light scattering (DLS) and 0.22 µm filtration (with >90% recovery) to confirm stability.
    • Motivation to Combine: A POSITA would combine Wu with Konz to replace residual chloroform in Wu’s preparation with a well-defined stable buffer from Konz, substitute Wu’s labor-intensive electron microscopy with Konz’s more efficient and scalable DLS and filtration analysis, and further enhance stability by adding a non-ionic surfactant as taught by Konz.
    • Expectation of Success: Petitioner asserted a high expectation of success. This was based on Wu already providing a stable, non-aggregated starting formulation, and Konz teaching the use of routine techniques like buffer exchange and adding common excipients for well-understood purposes of enhancing stability.

Ground 2: Claims 3-6 are obvious over Potter and Konz

  • Prior Art Relied Upon: Potter (a 2002 journal article on rAAV production) and Konz (WO 03/097797).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner asserted Potter disclosed a method to produce a stable rAAV reference standard at concentrations within the claimed range (1.12-1.46 x 10¹³ vg/ml) in a phosphate-buffered saline (PBS) solution containing 0.5 M NaCl. This buffer was argued to meet the patent's limitations for high ionic strength (>500 mM), pH (~7.4-8.0), and multivalent ions (phosphate). Potter also confirmed no aggregation using electron microscopy. Konz provided complementary teachings on improved formulation buffers, adding surfactants like Pluronic F68, and using more efficient analytical methods like DLS and filtration to assess aggregation.
    • Motivation to Combine: A POSITA would combine Potter’s successful high-titer rAAV production method with Konz's teachings to streamline production for scale-up. The primary motivations were to replace Potter’s time-consuming electron microscopy with Konz’s more efficient DLS and filtration analysis and to further enhance stability with the non-ionic surfactants taught by Konz.
    • Expectation of Success: Success was argued to be highly predictable. Potter provided a stable, high-titer formulation as a starting point, and Konz taught standard, well-understood methods for formulation optimization and analysis that were well within the skill of a POSITA.

  • Additional Grounds: Petitioner asserted additional obviousness challenges for claim 3 based on combinations of Wu, Konz, and Croyle, and Potter, Konz, and Croyle. These grounds argued that Croyle (a 2001 journal article) provided a specific motivation to select 0.001% Pluronic F68 to completely inhibit aggregation and improve viral vector transduction.

4. Key Claim Construction Positions

  • Petitioner argued that the key limitation "without significant aggregation" does not require construction for the purposes of the IPR. The rationale was that the cited prior art discloses formulations showing no evidence of aggregation upon storage, thereby satisfying the limitation regardless of its precise scope. Petitioner noted that while other terms were construed in a related district court case, its arguments were valid under either the plain and ordinary meaning or those constructions.

5. Key Technical Contentions (Beyond Claim Construction)

  • Petitioner contended that the ’542 patent is not entitled to its earliest provisional priority date of June 1, 2004. This argument was based on an alleged failure of the provisional application to provide adequate written description and enablement for the full scope of the claims, specifically regarding compositions containing empty viral capsids and compositions within the claimed pH range of 7.5-8.0. Establishing a later priority date of December 22, 2004, would make the Konz reference prior art under 35 U.S.C. §102(b).

6. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate because the current petition is not substantially the same as prior, denied IPRs against the ’542 patent. It was emphasized that the core prior art references of Wu, Konz, and Croyle were not previously before the Board. Petitioner also argued that the Potter reference, while mentioned in a prior IPR, was materially mischaracterized by the Patent Owner and thus never properly considered on its merits.

7. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 3-6 of the ’542 patent as unpatentable.