Mylan Pharmaceuticals Inc v. Pfizer Inc

1. Case Identification

• Case #: IPR2018-01358
• Patent #: 9,549,938
• Filed: July 6, 2018
• Petitioner(s): Mylan Pharmaceuticals Inc.
• Patent Owner(s): Anacor Pharmaceuticals, Inc.
• Challenged Claims: 1-6

2. Patent Overview

• Title: Boron-Containing Small Molecules
• Brief Description: The ’938 patent claims a method for treating human onychomycosis (a toenail fungal infection) caused by Trichophyton rubrum or Trichophyton mentagrophytes. The method involves topically administering a pharmaceutical composition containing the boron-based compound tavaborole.

3. Grounds for Unpatentability

Ground 1: Claims 1-2 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 ’938 patent, tavaborole (1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole), and taught its potent antifungal activity against Candida albicans, a known cause of onychomycosis. Austin identified tavaborole as a preferred compound and demonstrated its efficacy at low concentrations (5 ppm). Brehove, in turn, taught the topical application of compositions containing different boron-based compounds to treat human onychomycosis caused by pathogens including T. rubrum and T. mentagrophytes. Petitioner asserted that the combination of Austin’s compound with Brehove’s method of treatment rendered the claims obvious.
  • Motivation to Combine: A POSITA would combine these references because both relate to using boron-containing compounds as fungicides. Brehove established a method for safely and effectively treating onychomycosis topically with boron compounds. Austin provided a specific, highly potent boron compound (tavaborole) that was structurally similar to those in Brehove. Petitioner argued a POSITA would be motivated to substitute Austin's superior compound into Brehove’s established therapeutic method. A further motivation was tavaborole’s significantly lower molecular weight compared to the compounds in Brehove, which would be expected to improve nail penetration and efficacy.
  • Expectation of Success: A POSITA would have a reasonable expectation of success because both references demonstrated the efficacy of boron compounds against fungi, including a primary cause of onychomycosis (C. albicans). It was known that antifungal activity against C. albicans was predictive of activity against dermatophytes like T. rubrum. Brehove provided real-world evidence that boron compounds, even those repurposed from industrial biocides, could be safely used in topical human treatments. The structural similarities and shared mechanism of action of boron compounds would lead a POSITA to expect Austin’s tavaborole to function effectively in Brehove’s topical formulation.

Ground 2: Claims 1-2 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: This ground presented a similar argument to Ground 1, but substituted Freeman for Brehove. As before, Austin disclosed tavaborole and its antifungal properties. Freeman disclosed methods for treating onychomycosis by topically applying compositions containing phenyl boronic acid (PBA) and its derivatives, which are also boron-containing compounds. Freeman explicitly identified T. rubrum as a target pathogen and taught various topical formulations (lotion, ointment, etc.) suitable for human use.
  • Motivation to Combine: The motivation was to substitute a known, potent antifungal (tavaborole from Austin) for the active ingredients disclosed in Freeman’s method for treating onychomycosis. Petitioner contended that tavaborole is structurally similar to the PBA derivatives in Freeman, and a POSITA would have been motivated to use Austin's compound to achieve a similar or better therapeutic effect. The shared goal of treating onychomycosis with topically applied boron compounds provided a strong reason to combine the teachings.
  • Expectation of Success: A POSITA would expect success based on the known fungicidal properties of various boron-based compounds. Freeman demonstrated that boron compounds like PBA were effective against T. rubrum in vitro. Given that Austin showed tavaborole was also a potent antifungal, a POSITA would reasonably expect that substituting tavaborole into Freeman's topical delivery system would successfully treat onychomycosis caused by the same pathogens. The similar molecular weight of tavaborole compared to Freeman’s compounds further supported this expectation.

Ground 3: Claims 3-6 are obvious over Austin in view of Brehove/Freeman and Samour

• Prior Art Relied Upon: Austin (WO 1995/033754), Brehove (Application # 2002/0165121) or Freeman (WO 2003/009689), and Samour (Patent 6,224,887).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the previous grounds to address dependent claims 3-6, which recite specific formulation details. Claim 3 requires a 5% w/w concentration of tavaborole. Claim 4 adds the excipients ethanol and propylene glycol. Claims 5 and 6 combine these limitations. Petitioner argued that Samour, which taught topical nail lacquer formulations for treating onychomycosis, disclosed these very elements. Samour taught using an active antifungal agent at a 5% concentration and explicitly listed ethanol and propylene glycol as suitable organic solvents and plasticizers, respectively, in its example formulations.
  • Motivation to Combine: The motivation was to formulate the active ingredient (tavaborole, from Austin) in a well-known and effective delivery vehicle for treating onychomycosis. A POSITA, having decided to use tavaborole based on Austin and Brehove/Freeman, would have turned to the art of topical formulations, such as Samour, to create a stable and effective product. Samour provided a known template for a durable nail lacquer. Replacing Samour's active ingredient (econazole) with a more effective, lower-molecular-weight boron compound like tavaborole was presented as a simple substitution of one known element for another.
  • Expectation of Success: A POSITA would reasonably expect success because formulating topical drugs was a routine and predictable art. Samour provided detailed examples and concentration ranges that were known to be effective. Combining Austin’s active agent with Samour’s vehicle components (5% active ingredient, ethanol, propylene glycol) involved using known ingredients at known concentrations for their established purposes, creating a high likelihood of success.

4. Key Claim Construction Positions

• Petitioner argued that the key terms in the challenged claims should be given their plain and ordinary meaning, which was consistent with their use in the prior art.
• “1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole”: Petitioner identified this as the compound tavaborole, which is explicitly disclosed with the same chemical structure in the Austin reference.
• “Tinea unguium”: Petitioner noted that the ’938 patent itself defines this term as onychomycosis caused by a dermatophyte such as Trichophyton rubrum or Trichophyton mentagrophytes, aligning the claim scope with the disclosures in the prior art.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-6 of the ’938 patent as unpatentable under 35 U.S.C. §103.