PTAB

IPR2026-00166

Sarepta Therapeutics Inc v. Genzyme Corp

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Key Events
Petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Detecting AAV
  • Brief Description: The ’313 patent discloses methods for analyzing preparations of adeno-associated virus (AAV) particles. The methods use liquid chromatography-mass spectrometry (LC-MS) of intact viral proteins (VPs) to detect and characterize post-translational modifications (PTMs) and determine properties such as serotype and heterogeneity.

3. Grounds for Unpatentability

Ground 1: Obviousness over Satkunanathan and Shytuhina - Claims 1-27

  • Prior Art Relied Upon: Satkunanathan (a 2014 article in Human Gene Therapy) and Shytuhina (a 2014 article in Journal of Chromatography A).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Satkunanathan taught the importance of characterizing different AAV serotypes (AAV2, AAV5, AAV8) and their associated capsid proteins (VP1, VP2, VP3) for gene therapy development, using an LC-MS/MS method on enzymatically digested proteins. Shytuhina taught a superior analytical method using reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with MS to analyze intact viral proteins from Chikungunya virus-like particles, specifically to identify PTMs like glycosylation and acylation for vaccine process development. Shytuhina’s method involved denaturing the viral particles and analyzing the intact proteins via LC-MS without a gel separation step, meeting the core limitations of independent claims 1, 11, and 20.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine the teachings to improve upon Satkunanathan’s method. Applying Shytuhina’s intact protein analysis to the AAV context of Satkunanathan would provide a more precise, efficient, and reliable characterization of AAV capsid proteins and their PTMs, avoiding the labor, time, and potential for artificial modifications associated with the enzymatic digestion used by Satkunanathan.
    • Expectation of Success: A POSITA would have a reasonable expectation of success because intact LC-MS was a well-known technique for analyzing viral proteins. Applying the method to AAV capsid proteins would have been more straightforward than applying it to the more complex and variable glycoproteins successfully analyzed by Shytuhina.

Ground 2: Obviousness over Satkunanathan, Shytuhina, and Yuan - Claims 6, 19, and 27

  • Prior Art Relied Upon: Satkunanathan, Shytuhina, and Yuan (a 1998 article in Journal of Chromatography A).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon Ground 1 to address claims reciting the use of a C8 reverse phase chromatography column. While Shytuhina taught using a C4 column, Yuan disclosed an RP-HPLC method for analyzing human papillomavirus (HPV) capsid proteins and expressly taught that both C4 and C8 columns could be used with equal efficiency for the separation.
    • Motivation to Combine: A POSITA seeking to implement the combination of Satkunanathan and Shytuhina would be motivated to optimize the chromatography conditions for AAV proteins. Yuan demonstrated that testing and selecting between common column types like C4 and C8 was a routine part of method development for viral proteins. Therefore, trying a C8 column in the method of Shytuhina was a predictable and obvious optimization step.
    • Expectation of Success: A POSITA would have expected success, as Yuan showed C8 columns were effective for separating viral capsid proteins of a similar size to AAV proteins. This demonstrated that selecting a C8 column was a simple design choice with a high probability of success.

Ground 3: Obviousness over Satkunanathan, Shytuhina, and Zabrouskov - Claims 7-10

  • Prior Art Relied Upon: Satkunanathan, Shytuhina, and Zabrouskov (a 2006 article in Biochemistry).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground extended Ground 1 to address claims requiring the determination of the sequence of one or more VPs that have undergone PTMs. Zabrouskov taught the use of intact or "top-down" tandem mass spectrometry (MS/MS) to analyze intact proteins (RNase A), successfully obtaining sequence information to precisely characterize PTMs like deamidation.
    • Motivation to Combine: A POSITA would be motivated to add Zabrouskov’s intact MS/MS technique to the LC-MS method of the primary combination (Satkunanathan and Shytuhina) to achieve a more precise characterization of AAV PTMs. While the primary combination could detect a PTM by a mass shift, adding Zabrouskov’s sequencing step would allow the POSITA to identify the exact location of that PTM on the protein, a clear benefit for protein characterization.
    • Expectation of Success: A POSITA would expect success because Zabrouskov demonstrated that intact MS/MS was an effective technique for sequencing modified proteins. Applying this well-known "top-down" proteomics technique to the intact AAV proteins separated by Shytuhina’s method would have been a logical and predictable extension of the analysis.

4. Key Claim Construction Positions

  • "heterogeneity": Petitioner stated this term should be understood according to its express definition in the ’313 patent specification, which refers to a capsid characterized by one or more polypeptides observed to deviate from a reference mass of a VP1, VP2, or VP3 protein.
  • "variants/variant": Petitioner analyzed the challenged claims according to the construction proposed by the Patent Owner in related litigation, meaning "AAV mutant capsid protein[s]."

5. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-27 of the ’313 patent as unpatentable.