PTAB

IPR2026-00167

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 ’377 patent discloses methods for determining the serotype of an adeno-associated virus (AAV) particle. The methods involve denaturing the AAV particle and analyzing its intact capsid proteins (e.g., VP1, VP2, VP3) using liquid chromatography/mass spectrometry (LC/MS) to determine their specific masses, which are indicative of the serotype.

3. Grounds for Unpatentability

Ground 1: Obviousness over Satkunanathan and Shytuhina - Claims 1-20

  • Prior Art Relied Upon: Satkunanathan (a 2014 journal article on AAV vector production) and Shytuhina (a 2014 journal article on vaccine characterization).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Satkunanathan teaches the importance of characterizing different AAV serotypes (AAV2, AAV5, AAV8) and identifies their unique capsid proteins using LC-MS/MS after enzymatic digestion. This "bottom-up" approach, however, cannot reliably characterize the complete, intact VP1, VP2, and VP3 proteins. Shytuhina discloses a "top-down" method using reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with online mass spectrometry (intact LC-MS) to analyze the intact structural proteins of Chikungunya virus. Shytuhina's method, used for process development and monitoring post-translational modifications (PTMs), involves denaturing steps and analysis without gel separation. Petitioner asserted that combining these teachings renders obvious a method of denaturing an AAV particle and directly subjecting it to intact LC-MS to determine the masses of its capsid proteins, thereby identifying its serotype.
    • Motivation to Combine: A POSITA seeking to improve upon Satkunanathan's method for AAV characterization would be motivated to adopt Shytuhina's superior intact protein analysis technique. The goal would be to achieve a more efficient, reliable, and accurate analysis of individual AAV capsid proteins to distinguish serotypes and monitor PTMs, which are critical for process development in gene therapy vector production.
    • Expectation of Success: Petitioner asserted that a POSITA would have had a reasonable expectation of success. Intact LC-MS was a well-known technique, and applying Shytuhina's established method to AAV capsid proteins would be more straightforward than its application to the more complex glycoproteins Shytuhina successfully analyzed, requiring only routine experimentation.

Ground 2: Obviousness over Satkunanathan, Shytuhina, and Ansong - Claims 8 and 17

  • Prior Art Relied Upon: Satkunanathan (a 2014 journal article), Shytuhina (a 2014 journal article), and Ansong (a 2013 journal article on top-down proteomics).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground builds on the combination in Ground 1 to address claims 8 and 17, which add the limitation of using ultra-performance liquid chromatography (UPLC). Ansong teaches the use of intact LC-MS with a UPLC system, including long columns and gradients, to achieve improved proteome coverage and identify PTMs. Petitioner contended it would have been obvious to a POSITA to substitute the RP-HPLC system used in Shytuhina's method with the more advanced UPLC system taught by Ansong.
    • Motivation to Combine: A POSITA would be motivated to incorporate Ansong's UPLC technique into the Satkunanathan/Shytuhina method to gain the well-known benefits of UPLC over HPLC. These advantages, including increased resolution, higher sensitivity, and faster analysis speed, are highly desirable for a chromatographic method intended for in-process control and protein quantification.
    • Expectation of Success: Petitioner argued that replacing HPLC with UPLC was a routine and predictable optimization for a POSITA at the time, with a high likelihood of success.

Ground 3: Obviousness over Satkunanathan, Shytuhina, and Byeon - Claims 9, 10, 18, and 19

  • Prior Art Relied Upon: Satkunanathan (a 2014 journal article), Shytuhina (a 2014 journal article), and Byeon (a 2015 journal article on LC/MS analysis of erythropoietin).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground addresses claims requiring mass spectrometry with "assisted calibration" (claims 9, 18) and the specific use of sodium iodide (NaI) as a calibrant (claims 10, 19). Byeon discloses using UPLC-MS and calibrating the mass spectrometer with NaI before data acquisition, then processing the data with software. This method of using software to correlate a known standard to a mass-to-charge ratio aligns with the patent's description of "assisted calibration."
    • Motivation to Combine: A POSITA would understand that any LC-MS system requires calibration to ensure accurate mass measurements. Petitioner argued a POSITA would be motivated to incorporate Byeon's efficient and straightforward method of external, assisted calibration into the base method of Satkunanathan/Shytuhina. Using an external calibrant like NaI, as taught by Byeon, avoids potential complications and sample compatibility issues that arise from adding a calibrant directly to the sample being analyzed.
    • Expectation of Success: Calibrating a mass spectrometer was a necessary and routine procedure. Petitioner asserted that implementing a known, simple, and effective external calibration method as taught by Byeon would have been a standard practice with a high expectation of success.

4. Relief Requested

  • Petitioner requests institution of IPR and cancellation of claims 1-20 of Patent 11,698,377 as unpatentable.