Mylan Pharmaceuticals Inc. v. Allergan, Inc.

1. Case Identification

• Case #: IPR2016-01127
• Patent #: 8685930
• Filed: June 3, 2016
• Petitioner(s): Mylan Pharmaceuticals Inc.
• Patent Owner(s): Allergan, Inc.
• Challenged Claims: 1-36

2. Patent Overview

• Title: Topical Ophthalmic Emulsion
• Brief Description: The ’930 patent claims a topical ophthalmic emulsion for treating dry eye disease, specifically keratoconjunctivitis sicca (KCS). The core of the claimed invention is a composition comprising about 0.05% cyclosporin A (CsA) and about 1.25% castor oil in an oil-in-water emulsion.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-36 - Claims 1-36 are anticipated under 35 U.S.C. §102(b) by Ding.

• Prior Art Relied Upon: Ding (Patent 5,474,979).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Ding discloses every element of the claimed emulsion. Ding taught topical ophthalmic emulsions for treating KCS, including specific examples and preferred ranges that encompass the claimed formulation. Specifically, Ding’s Example 2C disclosed a castor oil vehicle with 1.25% castor oil, and its Example 1 disclosed CsA concentrations including 0.05%. Petitioner contended that the combination of 0.05% CsA with the 1.25% castor oil vehicle was explicitly taught or at least immediately apparent from Ding's disclosure of preferred CsA-to-castor-oil ratios (0.02-0.12). The claimed ratio of 0.04 (0.05%/1.25%) fell squarely within this preferred range. Petitioner highlighted that the Patent Owner had conceded during prosecution of a related application that this exact formulation "is squarely within the teaching of the Ding reference" and "would have been obvious."

Ground 2: Obviousness of Claims 1-36 - Claims 1-36 are obvious over Ding in view of Sall.

• Prior Art Relied Upon: Ding (Patent 5,474,979) and Sall (a 2000 clinical study on cyclosporine ophthalmic emulsions).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Ding disclosed the base formulation, while Sall provided key data on its clinical efficacy and safety. Sall described a large, multi-center clinical trial comparing 0.05% and 0.10% CsA emulsions against a vehicle control for treating moderate to severe dry eye disease. The study concluded that both concentrations were safe and effective, with the 0.05% concentration being at least as effective as the 0.10% concentration and showing fewer adverse effects. Sall also provided evidence for the limitation in dependent claims 11, 23, and 35, teaching that the 0.05% CsA emulsion resulted in trough blood concentrations below the limit of quantification (0.1 ng/mL).
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine Ding and Sall because both addressed the same problem: creating a safe and effective topical CsA emulsion for dry eye disease. Sall's clinical results, demonstrating that the lower 0.05% concentration was as effective and safer than the 0.10% concentration, would have provided a strong rationale to select the 0.05% CsA concentration from Ding’s disclosed ranges and combine it with Ding's preferred 1.25% castor oil vehicle.
  • Expectation of Success: Sall's positive clinical trial data, showing significant improvements in objective signs of dry eye disease with the 0.05% CsA emulsion, would have provided a POSITA with a reasonable expectation of success in formulating the claimed invention.

Ground 3: Obviousness of Claims 11, 23, and 35 - Claims 11, 23, and 35 are obvious over Ding in view of Sall and Acheampong.

• Prior Art Relied Upon: Ding (Patent 5,474,979), Sall (a 2000 clinical study), and Acheampong (a 1998 study on cyclosporine distribution).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon Ground 2 to specifically address the limitation that the emulsion results in "substantially no detectable concentration" of CsA in human blood. While Sall taught this property at trough levels, Acheampong provided more comprehensive data. Acheampong described a study that measured both peak and trough blood concentrations of CsA after topical administration and explicitly found "no detectable amount of CsA" in patients receiving a 0.05% CsA emulsion.
  • Motivation to Combine: A POSITA, having arrived at the 0.05% CsA formulation from Ding and Sall, would have been motivated to consult Acheampong to confirm the safety profile and systemic exposure. Acheampong directly addressed the blood concentration of topically administered CsA, making it highly relevant.
  • Expectation of Success: The combined teachings of Sall (showing low trough levels) and Acheampong (showing no detectable peak or trough levels) would give a POSITA a very high expectation of success that the claimed 0.05% emulsion would result in substantially no detectable CsA in the blood.

4. Key Claim Construction Positions

• "buffer": Petitioner argued that in the context of the patent, which states sodium hydroxide can be used to adjust pH, the term "buffer" should be construed to include sodium hydroxide, even though it is technically a strong base rather than a traditional buffering agent.
• "substantially no detectable concentration": Based on the patent’s specification, Petitioner proposed this term means a CsA blood concentration below 0.1 ng/mL, as measured by liquid chromatography-mass spectroscopy (LC-MS/MS) at either peak or trough levels.
• "therapeutically effective": Petitioner contended this term should be given a broad interpretation to include both palliative (remediating) and curative treatments for dry eye disease or KCS, including an increase in tear production, consistent with how the Patent Owner argued for patentability during prosecution.

5. Key Technical Contentions (Beyond Claim Construction)

• Rebuttal of "Unexpected Results": A central theme of the petition was a direct attack on the "unexpected results" evidence submitted by the Patent Owner during prosecution to overcome obviousness rejections. Petitioner argued the evidence was fundamentally flawed because:
  • The data presented to the examiner lacked error bars and other parameters necessary to determine statistical significance.
  • The graphical data appeared to be repackaged from the prior art Sall reference, which was published more than a year before the patent's priority date and therefore could not be "unexpected."
  • The Patent Owner’s conclusion that the 0.05% CsA emulsion was surprisingly as effective as a 0.10% version was not unexpected, as the prior art (Sall) had already taught this exact finding.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-36 of the ’930 patent as unpatentable under 35 U.S.C. §102 and §103.