PTAB

IPR2018-01360

Mylan Pharmaceuticals Inc. v. Pfizer Inc.

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1. Case Identification

2. Patent Overview

  • Title: Boron-Containing Small Molecules
  • Brief Description: The ’290 patent discloses methods for treating onychomycosis (nail fungus) in a human by topically administering a pharmaceutical composition containing a specific boron-based compound, 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole (tavaborole).

3. Grounds for Unpatentability

Ground 1: Obviousness over Austin and Brehove - Claims 1, 4, 7 & 9-10 are obvious over Austin in view of Brehove.

  • Prior Art Relied Upon: Austin (WO 1995/033754) and Brehove (Application # 2002/0165121).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Austin disclosed the exact compound claimed in the ’290 patent, tavaborole, and established its potency as a fungicide against Candida albicans, a known cause of onychomycosis. Brehove taught the specific method of treating human onychomycosis caused by Trichophyton rubrum and Trichophyton mentagrophytes via topical application of other boron-containing compounds. Petitioner contended that combining Austin’s compound with Brehove’s method rendered claim 1 obvious. The further limitation requiring inhibition of an aminoacyl tRNA synthetase was argued to be inherent to the known mechanism of action of tavaborole, thus adding no patentable distinction.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would be motivated to substitute Austin's potent tavaborole for the active ingredients in Brehove’s method. Both references are in the same field of boron-based antifungals. The motivation was strengthened by tavaborole's significantly lower molecular weight compared to the compounds in Brehove, which a POSITA would understand to improve nail penetration and efficacy.
    • Expectation of Success: A POSITA would have a reasonable expectation of success. Both references demonstrated the efficacy of boron heterocycles against onychomycosis-causing fungi. Brehove provided real-world proof that an industrial biocide (BioborJF®) could be safely formulated for topical human use, mitigating any concern over using Austin's compound. The shared fungicidal activity and structural similarities indicated that tavaborole would be a successful active ingredient in Brehove’s treatment method.

Ground 2: Obviousness over Austin, Brehove, and Samour - Claims 2-3, 5-6, 8 & 11-12 are obvious over Austin in view of Brehove and Samour.

  • Prior Art Relied Upon: Austin (WO 1995/033754), Brehove (Application # 2002/0165121), and Samour (Patent 6,224,887).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built on Ground 1 to address dependent claims reciting specific formulation characteristics. Petitioner asserted that Samour taught topical nail lacquer formulations for treating onychomycosis that supplied the missing elements. Specifically, Samour disclosed compositions with a 5% w/w concentration of an active agent (as in claims 2 and 5) and the use of carriers like ethanol and propylene glycol (as in claims 3 and 6).
    • Motivation to Combine: A POSITA seeking to develop an effective and durable delivery vehicle for tavaborole would be motivated to look to art like Samour. Samour explicitly taught how to create nail lacquers with improved physical properties (e.g., durability, water-resistance, flexibility) for treating onychomycosis and provided concrete formulation examples. The combination represents a predictable use of known formulation technology to deliver a known active agent.
    • Expectation of Success: Formulating an active ingredient into a known carrier system was routine and predictable. A POSITA would reasonably expect that substituting tavaborole into Samour's proven nail lacquer formulation—at a concentration taught by Samour and within the preferred range of Austin—would result in a safe and effective treatment.

Ground 3: Obviousness over Austin and Freeman - Claims 1, 4, 7 & 9-10 are obvious over Austin in view of Freeman.

  • Prior Art Relied Upon: Austin (WO 1995/033754) and Freeman (WO 2003/009689).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner presented this ground as an alternative to the Brehove combination. Freeman also taught methods for safely and effectively treating onychomycosis in humans by topically applying boron-containing compounds (phenyl boronic acid and its derivatives). Freeman disclosed using these compounds against the same pathogens and taught once-daily administration, directly mapping to the limitations of claims 1 and 7.
    • Motivation to Combine: The motivation was a simple substitution of one known antifungal boron compound (Austin's tavaborole) for another (Freeman's PBA derivatives) within a known therapeutic framework. A POSITA would have recognized the structural similarity between the compounds and been prompted to use the highly potent tavaborole in the method taught by Freeman.
    • Expectation of Success: Success would be reasonably expected because both references demonstrated the efficacy of structurally similar boron compounds against relevant pathogens. Freeman provided a clear roadmap for formulating such compounds for safe topical human use, and Austin identified tavaborole as a preferred, highly active candidate for such a formulation.
  • Additional Grounds: Petitioner asserted an additional obviousness challenge (Ground 4) for claims 2-3, 5-6, 8, and 11-12 based on the combination of Austin, Freeman, and Samour. This ground relied on similar logic as Ground 2, using Samour to provide the specific formulation elements for the tavaborole-based treatment method established by combining Austin and Freeman.

4. Key Claim Construction Positions

  • Petitioner argued that the central claim term "1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole" refers to the specific compound tavaborole, which was already disclosed in the prior art, particularly Austin.
  • Petitioner noted that the claim term "inhibit," in the context of an aminoacyl tRNA synthetase, describes the inherent, known mechanism of action of tavaborole. This construction was used to argue that the limitation was a necessary outcome of using the compound and did not confer patentability over prior art that disclosed the compound for antifungal use.

5. Key Technical Contentions (Beyond Claim Construction)

  • A core technical contention was that antifungal activity against the yeast Candida albicans (as shown for tavaborole in Austin) was well-understood by a POSITA to be predictive of activity against the dermatophytes T. rubrum and T. mentagrophytes, which are the pathogens recited in the challenged claims.
  • Petitioner consistently argued that a compound’s lower molecular weight is a key factor for effective penetration of the human nail plate. This principle was used to establish the motivation to select tavaborole (MW 151.93 Daltons) over the higher molecular weight compounds taught in references like Brehove (MW ~270-286 Daltons) and Samour (econazole, MW 381.68 Daltons).

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-12 of Patent 9,566,290 as unpatentable under 35 U.S.C. §103.