PTAB

IPR2018-00123

Initiative for Medicines Access & Knowledge I MAK Inc v. Gilead Pharmasset LLC

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Phosphoramidate Prodrugs for Treating Viral Infections
  • Brief Description: The ’372 patent claims methods for treating hepatitis C virus (HCV) by co-administering an NS5A inhibitor and a phosphoramidate prodrug of a specific nucleoside derivative. The core active compound is a (2'R)-2'-deoxy-2'-fluoro-2'-C-methyluridine analog, formulated as a single diastereomer phosphoramidate to enhance its antiviral activity.

3. Grounds for Unpatentability

Ground 1: Obviousness over Sofia, Congiatu, and Serrano-Wu - Claims 1-2 are obvious over Sofia, Congiatu, and Serrano-Wu.

  • Prior Art Relied Upon: Sofia (a 2007 conference poster), Congiatu (a 2006 journal article), and Serrano-Wu (Application # 2006/0276511).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of these references teaches every element of the challenged claims. Sofia disclosed the core nucleoside structure claimed in the ’372 patent, (2'R)-2'-deoxy-2'-fluoro-2'-C-methyluridine (referred to as PSI-6206), and identified it as a promising anti-HCV agent that was inactive on its own but potent in its triphosphate form. Sofia further suggested using a phosphoramidate prodrug approach to bypass the inefficient initial phosphorylation step. Congiatu taught the well-known phosphoramidate "ProTide" strategy for activating nucleosides and, critically, instructed that the resulting diastereomers at the phosphorous center must be separated and tested individually because they often exhibit significantly different biological activities (noting a 15-fold difference in its example). Finally, Serrano-Wu taught the standard practice of combining NS5B polymerase inhibitors (the class of drug in the ’372 patent) with NS5A inhibitors for a more effective combination therapy against HCV.
    • Motivation to Combine: A person of ordinary skill in the art (POSA) would have been motivated to combine the teachings of Sofia and Congiatu to solve the exact problem identified by Sofia: activating the inactive PSI-6206 nucleoside. The ProTide strategy detailed in Congiatu was a well-known and successful tool for this purpose. A POSA would have been further motivated by Congiatu to separate the resulting diastereomers to identify the most potent one, which Petitioner asserted is a routine step in drug optimization, not an inventive act. The motivation to then combine this optimized NS5B inhibitor with an NS5A inhibitor, as taught by Serrano-Wu, stemmed from the established knowledge that combination therapy was the standard of care for treating HCV, offering improved efficacy and a way to combat drug resistance.
    • Expectation of Success: Petitioner contended a POSA would have had a reasonable expectation of success. The ProTide approach was a highly predictable and widely used technology for converting inactive nucleoside analogs into potent antiviral drugs, with numerous publications (including by Perrone and McGuigan, cited in the petition) demonstrating its success across a range of compounds. Applying this known solution to Sofia's identified lead compound would have been a straightforward path with a high probability of success. The resulting improvement in potency was an expected, not surprising, result of this routine drug development strategy.

4. Key Technical Contentions (Beyond Claim Construction)

  • Priority Date Challenge: Petitioner argued that the ’372 patent is not entitled to the priority date of its earlier provisional applications (filed in 2007) because they allegedly fail to provide adequate written description for the specific compound and stereochemistry claimed. Petitioner contended the earliest valid priority date is March 21, 2008, the filing date of the ’015 application. This assertion is critical, as it renders the Sofia poster (September 2007) and Serrano-Wu publication (December 2006) valid prior art under 35 U.S.C. §102.
  • Diastereomer Separation as Routine Optimization: A central theme of the petition is that the '372 patent's claim to a single, specific diastereomer does not confer patentability. Petitioner asserted, based on teachings like Congiatu, that separating and testing diastereomers to find the most active form was a standard, obvious, and necessary step in the drug development process for this class of compounds. Therefore, isolating the more active diastereomer was merely the result of routine optimization, not an unexpected discovery.

5. Relief Requested

  • Petitioner requests institution of IPR and cancellation of claims 1 and 2 of the ’372 patent as unpatentable.