PTAB

IPR2026-00168

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 ’880 patent discloses methods for analyzing preparations of Adeno-associated virus (AAV) particles. The methods use liquid chromatography-mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS) on intact viral proteins to characterize the preparations, including determining viral serotype and identifying post-translational modifications (PTMs).

3. Grounds for Unpatentability

Ground 1: Claims 1-17 and 21 are obvious over Satkunanathan and Shytuhina.

  • Prior Art Relied Upon: Satkunanathan (a 2014 Human Gene Therapy article) and Shytuhina (a 2014 Journal of Chromatography A article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Satkunanathan teaches analyzing AAV preparations to identify capsid proteins of different serotypes (AAV2, AAV5, AAV8) using LC-MS/MS for gene therapy process development. However, Satkunanathan’s method requires enzymatic digestion of the proteins first. Shytuhina teaches a superior method of analyzing intact viral structural proteins and their PTMs using reversed-phase high-performance liquid chromatography coupled with mass spectrometry (RP-HPLC-MS) for vaccine process development, a method performed without enzymatic digestion. The combination of these references allegedly disclosed all limitations of independent claims 1 and 10, including denaturing viral particles, subjecting them to intact protein LC-MS analysis, and determining viral protein masses, all without a gel separation step.
    • Motivation to Combine: Petitioner asserted a POSITA would combine Shytuhina’s intact protein analysis method with Satkunanathan’s goal of characterizing AAV proteins to improve process development. This combination would overcome the known drawbacks of enzymatic digestion (e.g., it is time-consuming, can introduce artificial modifications, and cannot reliably distinguish between fragments of AAV capsid proteins vp1, vp2, and vp3). Both references address the same technical problem of analyzing viral proteins for process development.
    • Expectation of Success: Petitioner contended that a POSITA would have a reasonable expectation of success because the required techniques (RP-HPLC, intact LC-MS) were well-established. Applying Shytuhina’s method to AAV capsid proteins would have been routine and more straightforward than applying it to the more complex glycoproteins Shytuhina successfully analyzed.

Ground 2: Claims 7 and 15 are obvious over Satkunanathan, Shytuhina, and Ansong.

  • Prior Art Relied Upon: Satkunanathan (a 2014 Human Gene Therapy article), Shytuhina (a 2014 Journal of Chromatography A article), and Ansong (a 2013 PNAS article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground builds upon the combination in Ground 1 to specifically address claims 7 and 15, which require the use of ultra-performance liquid chromatography (UPLC). Petitioner argued that Ansong teaches using intact LC-MS with a UPLC column to study a bacterial proteome, identifying numerous proteins and PTMs. Ansong explicitly discloses that UPLC provides improved proteome coverage.
    • Motivation to Combine: A POSITA, seeking to implement the method of Satkunanathan and Shytuhina, would have been motivated to substitute the HPLC used by Shytuhina with the UPLC taught by Ansong. The motivation stemmed from the known advantages of UPLC over HPLC, such as increased resolution, sensitivity, and speed, which are highly desirable for in-process quality control of biologics like AAV vectors.
    • Expectation of Success: Success was expected because UPLC was a well-known chromatographic technique. A POSITA could have implemented Ansong's UPLC approach into Shytuhina's intact LC-MS method for AAV analysis using nothing more than routine experimentation.

Ground 3: Claims 18-20 are obvious over Shytuhina and Zabrouskov.

  • Prior Art Relied Upon: Shytuhina (a 2014 Journal of Chromatography A article) and Zabrouskov (a 2006 Biochemistry article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground targets claims 18-20, which are directed to determining the extent of deamidation of viral proteins. Petitioner asserted that Shytuhina observed a degradant peak likely corresponding to deamidation but did not provide a method to confirm or quantify it. Zabrouskov discloses the use of top-down (intact) MS/MS to successfully identify and quantify five distinct deamidation sites on a protein (RNase A).
    • Motivation to Combine: A POSITA, having observed likely deamidation as in Shytuhina, would have been motivated to apply Zabrouskov's intact MS/MS method to confirm, identify, and quantify the deamidated forms of the viral proteins. This detailed characterization is critical for process development and ensuring product consistency, which was the goal of Shytuhina’s work.
    • Expectation of Success: While the viral proteins in Shytuhina are larger than the RNase A studied in Zabrouskov, Petitioner argued that a POSITA would have known how to make routine adjustments to the MS/MS method for larger proteins. Such techniques were well-documented in the art, and success in applying the combined method would have been reasonably expected.
  • Additional Grounds: Petitioner asserted additional obviousness challenges, including that claims 8, 9, 16, and 17 are obvious over Satkunanathan, Shytuhina, and Byeon (a 2015 article) for teaching assisted mass spectrometer calibration with sodium iodide, and that claim 20 is obvious over Shytuhina, Zabrouskov, and Yuan (a 1998 article) for teaching the use of C8 chromatography columns.

4. Key Claim Construction Positions

  • Petitioner stated that for the purposes of the petition, it analyzed the challenged claims by adopting the construction for the term “variants/variant” that Patent Owner allegedly proposed in related litigation: “AAV mutant capsid protein[s].”

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-21 of the ’880 patent as unpatentable.