PTAB

IPR2017-01256

Incyte Corp v. Concert Pharmaceuticals Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Deuterated derivatives of ruxolitinib
  • Brief Description: The ’149 patent claims deuterated analogs of ruxolitinib, an FDA-approved small-molecule pharmaceutical, and pharmaceutical compositions containing these deuterated analogs. The claims cover specific patterns of deuterium substitution on the ruxolitinib molecule.

3. Grounds for Unpatentability

Ground 1: Obviousness over Jakafi, Shilling, and Concert Backgrounder - Claims 1-15 are obvious over the combination of these references.

  • Prior Art Relied Upon: Jakafi® (ruxolitinib) Prescribing Information (2011), Shilling (a 2010 journal article on ruxolitinib metabolism), and the Concert Backgrounder (a 2007 corporate publication on deuterium chemistry).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the Jakafi Prescribing Information established ruxolitinib as a well-known, safe, and effective FDA-approved drug. The Shilling reference was cited to teach a person of ordinary skill in the art (POSA) that the dominant metabolic pathway for ruxolitinib involves oxidation on its cyclopentyl ring, identifying this as a "metabolic hotspot." The Concert Backgrounder was presented as teaching the general strategy of "site-selective deuteration," where known drugs are modified by substituting deuterium for hydrogen at known metabolic hotspots to improve pharmacokinetic properties (ADME).
    • Motivation to Combine: A POSA would combine these teachings to improve a known, successful drug. Petitioner asserted that a POSA would have been motivated to apply the established deuteration strategy taught by the Concert Backgrounder to the known drug ruxolitinib (disclosed in Jakafi) specifically at the metabolic hotspots on the cyclopentyl ring identified by Shilling. The goal would be to create a new chemical entity with potentially superior ADME properties, reduced R&D risk, and a high likelihood of retaining the therapeutic efficacy of the parent drug.
    • Expectation of Success: Petitioner contended that a POSA would have a reasonable expectation of success. The known effect of deuteration (the kinetic isotope effect) was expected to slow metabolism at the targeted sp3-hybridized carbons of the cyclopentyl ring. Because deuterium substitution does not significantly alter molecular size or electronic properties, the resulting deuterated ruxolitinib analogs would be expected to retain the efficacy and safety profile of the original compound while likely exhibiting improved metabolic stability.

Ground 2: Anticipation by Rodgers - Claims 1-15 are anticipated by Rodgers.

  • Prior Art Relied Upon: Rodgers (Patent 7,598,257).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Rodgers, which claims ruxolitinib, explicitly discloses that the scope of its invention includes all isotopic variations of the claimed compounds. The specification states: "Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium." Petitioner asserted that this disclosure of a genus of deuterated ruxolitinib analogs, combined with the specific disclosure of the ruxolitinib structure, anticipates the specifically claimed deuterated compounds in the ’149 patent. It was argued that a POSA could "at once envisage" the relatively small and well-defined number of possible deuterated species (1,023 based on 10 distinct sites for deuteration) derived from a simple binary choice (hydrogen or deuterium) at each site.

Ground 3: Obviousness over Rodgers, Shilling, and Concert Backgrounder - Claims 1-15 are obvious over the combination of these references.

  • Prior Art Relied Upon: Rodgers (Patent 7,598,257), Shilling (a 2010 journal article), and the Concert Backgrounder (2007).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground is structurally similar to Ground 1 but uses Rodgers as the primary reference for ruxolitinib instead of the Jakafi Prescribing Information. Petitioner argued that Rodgers taught the ruxolitinib compound and disclosed a genus of deuterated analogs. Even if this disclosure was not found to be anticipatory, it rendered the specific deuterated analogs obvious when combined with the other references. Shilling again provided the specific location of the metabolic hotspots on the cyclopentyl ring, and the Concert Backgrounder provided the rationale for targeting such hotspots with deuterium substitution.
    • Motivation to Combine: The motivation was identical to that in Ground 1: a POSA, knowing the ruxolitinib structure from Rodgers and its primary metabolic sites from Shilling, would be motivated by the Concert Backgrounder's teachings to deuterate those specific sites to create improved versions of the drug. The combination of these references narrowed the broad genus disclosed in Rodgers to the specific, logical deuterated compounds claimed in the ’149 patent.
    • Expectation of Success: The argument for expectation of success mirrored that of Ground 1. A POSA would reasonably expect that deuterating the known metabolic hotspots of ruxolitinib would slow its metabolism without negatively impacting its known therapeutic activity.

4. Key Claim Construction Positions

  • Petitioner noted that the term “D” or “deuterium” is defined in the ’149 patent specification and requires a specific construction beyond its plain meaning. The proposed construction, taken from the patent, is "deuterium at an abundance that is at least 3000 times greater than the natural abundance of deuterium, which is 0.015% (i.e., at least 45% incorporation of deuterium)."

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-15 of Patent 9,249,149 as unpatentable under 35 U.S.C. §102 and §103.