PTAB

IPR2025-01195

Sarepta Therapeutics Inc v. Genzyme Corp

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Compositions and Methods to Prevent AAV Vector Aggregation
  • Brief Description: The ’721 patent discloses methods for preventing the aggregation of recombinant adeno-associated virus (rAAV) virions in purified preparations. The methods involve controlling formulation parameters such as ionic strength, pH, and the addition of specific multivalent ions to maintain stability.

3. Grounds for Unpatentability

Ground 1: Claims 1-4, 6, 7, and 11 are obvious over Auricchio in view of Konz.

  • Prior Art Relied Upon: Auricchio (a 2001 journal article titled "Isolation of Highly Infectious And Pure Adeno-Associated Virus Type 2 Vectors with a Single-Step Gravity-Flow Column") and Konz (WO 03/097797, "Methods of Adenovirus Purification").
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Auricchio taught a scalable method for purifying rAAV that meets most limitations of claim 1. Auricchio disclosed purifying a cell lysate via chromatography, eluting the virions in a high ionic strength (>550 mM) phosphate buffer (a multivalent ion) at pH 7.4, and obtaining rAAV concentrations (1.1 x 10¹³ and 1.4 x 10¹³ vg/ml) that fall squarely within the claimed range. While Auricchio achieved a stable, high-titer preparation, its method for assessing aggregation (an infectivity assay) was labor-intensive. Konz addressed the need for scalable manufacturing and disclosed modern analytical techniques to assess aggregation, including dynamic light scattering (DLS) and sterile filtration through a 0.22 µm filter with >90% recovery, which directly teach the limitations of dependent claims 6 and 7. Konz, incorporating Evans (WO 01/66137), also taught formulating viral particles at a higher pH of 8.0 with multivalent ions like magnesium and citrate to maximize stability, meeting the pH and specific ion limitations of claims 1 and 4. Further, Konz taught adding a nuclease like Benzonase (an endonuclease from Serratia marcescens) to reduce contaminating DNA, mapping to claims 2 and 3.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Auricchio's effective purification protocol with Konz's more efficient, scalable, and cost-effective analytical techniques (DLS, filtration) to better assess the stability of the resulting rAAV preparation. A POSA would also be motivated to adopt Konz's superior buffer formulations (e.g., pH 8.0, addition of citrate) to further improve the stability of the purified virions produced by Auricchio's method.
    • Expectation of Success: A POSA would have had a reasonable expectation of success, as both references aimed to produce stable, high-titer viral vector preparations for clinical use. The techniques involved—such as diafiltration to exchange buffers, DLS, and sterile filtration—were all well-known and their application would have required no more than routine experimentation.

Ground 2: Claims 1-4, 6, 7, and 11 are obvious over Potter in view of Konz.

  • Prior Art Relied Upon: Potter (a 2002 journal article titled "Streamlined Large-Scale Production of Recombinant Adeno-Associated Virus (rAAV) Vectors") and Konz (WO 03/097797).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Potter disclosed a method for large-scale rAAV production that meets nearly all limitations of claim 1. Potter taught creating a lysate, purifying it using three chromatography steps, and eluting the rAAV in a phosphate-buffered saline (PBS) solution containing 0.5 M NaCl. This buffer contained a multivalent ion (phosphate), had an ionic strength well over 200 mM, and a pH understood to be around 7.4-7.5. The resulting rAAV concentrations (1.12 x 10¹³ and 1.46 x 10¹³ vg/ml) were within the claimed range. Potter used electron microscopy to confirm a lack of aggregation, a method Petitioner described as labor-intensive. As in Ground 1, Konz supplied the teachings for the remaining limitations, including the use of DLS (claim 6), >90% recovery after 0.22 µm filtration (claim 7), nuclease treatment (claims 2-3), and the use of citrate in pH 8.0 buffers (claims 1 and 4).
    • Motivation to Combine: A POSA would have been motivated to combine Potter's successful large-scale purification method with Konz's more efficient and scalable analytical and formulation improvements. Specifically, a POSA would replace Potter's time-consuming electron microscopy with Konz's DLS and filtration assays to streamline quality control. A POSA would also incorporate Konz's teachings on buffer optimization (e.g., pH 8.0, surfactants, citrate) to further enhance the stability of the final product from Potter's process.
    • Expectation of Success: A POSA would have had a reasonable expectation of successfully combining these teachings. The combination represented a straightforward optimization of a known purification process (Potter) using well-established analytical techniques and formulation strategies (Konz) to improve efficiency and stability, which were common goals in the field.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial would be inappropriate because the primary prior art references, Auricchio and Konz, were not cited or considered during the original prosecution of the ’721 patent or during prior IPRs filed against a related patent. Petitioner contended these new references and the arguments based upon them are materially different from those previously before the Patent Office and the Board.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-4, 6, 7, and 11 of the ’721 patent as unpatentable.