PTAB

IPR2017-00600

Akorn Inc v. Allergan Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods of providing therapeutic effects using cyclosporin components
  • Brief Description: The ’048 patent describes methods for treating dry eye disease, specifically keratoconjunctivitis sicca (KCS), by increasing tear production. The method involves the twice-daily topical administration of an ophthalmic emulsion containing specific concentrations of cyclosporin A (0.05%) and castor oil (1.25%), along with other excipients.

3. Grounds for Unpatentability

Ground 1: Obviousness over Ding and Sall - Claims 1-10, 12-14, 16-20, and 22-23 are obvious over Ding in view of Sall.

  • Prior Art Relied Upon: Ding (Patent 5,474,979) and Sall (a 2000 clinical study in Ophthalmology).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Ding taught a complete ophthalmic emulsion for treating KCS that contained all the claimed ingredients within the claimed concentration ranges. Specifically, Ding’s examples disclosed a vehicle with 1.25% castor oil and taught that 0.05% cyclosporin A (CsA) was a suitable concentration, creating a ratio of CsA-to-castor-oil that fell within Ding’s preferred ranges. Petitioner noted that the Patent Owner had conceded during prosecution that this formulation was "squarely within the teachings of the Ding reference." While Ding did not explicitly teach twice-daily administration, Sall, a Phase 3 clinical trial, disclosed the twice-daily administration of both 0.05% and 0.10% CsA-in-castor-oil emulsions for treating KCS. Sall established that the 0.05% concentration was as effective as the 0.10% concentration but resulted in fewer adverse side effects.
    • Motivation to Combine: Petitioner contended a person of ordinary skill in the art (POSITA), starting with the emulsion formulations disclosed in Ding, would have been motivated to consult a large-scale clinical study like Sall to determine the optimal dosage and administration frequency. Sall’s conclusion that the 0.05% CsA emulsion was safer and at least as effective as the 0.10% version provided a clear rationale to select the 0.05% concentration for the formulation taught by Ding and to administer it twice daily as taught by Sall.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success because Ding taught the suitability of the specific emulsion vehicle, and Sall’s robust clinical data confirmed the safety and efficacy of the twice-daily 0.05% CsA dosage regimen for treating KCS and increasing tear production.

Ground 2: Obviousness over Ding, Sall, and Acheampong - Claims 11 and 21 are obvious over Ding, Sall, and Acheampong.

  • Prior Art Relied Upon: Ding (’979 patent), Sall (2000 clinical study), and Acheampong (a 1998 study in Lacrimal Gland, Tear Film, and Dry Eye Syndromes).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon the combination of Ding and Sall to challenge dependent claims 11 and 21, which added the limitation that administration of the emulsion results in "substantially no detectable concentration" of CsA in the blood. Petitioner asserted that Acheampong provided this missing element. Acheampong described a study that measured blood concentrations following topical administration of CsA emulsions and reported that patients receiving the 0.05% CsA emulsion had no detectable CsA in their blood at either peak or trough levels.
    • Motivation to Combine: A POSITA developing the topical formulation from Ding and Sall would have been concerned with systemic safety and absorption. Petitioner argued it would have been obvious to consult a pharmacokinetic study like Acheampong, which directly addressed blood concentration levels after topical application of the same drug at the same concentration, to confirm the safety of the chosen formulation.

Ground 3: Obviousness over Ding, Sall, and Glonek - Claim 15 is obvious over Ding, Sall, and Glonek.

  • Prior Art Relied Upon: Ding (’979 patent), Sall (2000 clinical study), and Glonek (Patent 5,578,586).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground targeted dependent claim 15, which recited that the claimed emulsion "breaks down more quickly" than a second emulsion with only half as much castor oil (0.625%), thereby reducing vision distortion. Petitioner argued that Glonek taught this principle. Glonek disclosed that ophthalmic emulsions are expected to cause blurring, and that increasing the oil concentration in an emulsion (while holding surfactant constant) increases its instability, causing it to differentiate, or "break down," more rapidly in the eye.
    • Motivation to Combine: A POSITA seeking to optimize the formulation from Ding and Sall to improve patient comfort and reduce side effects like blurred vision would have been motivated to consult a reference like Glonek. Glonek explicitly taught the relationship between higher oil concentration and faster emulsion breakdown, providing a clear reason to expect that the claimed 1.25% castor oil formulation would break down faster and cause less blurring than a comparable 0.625% formulation.

4. Key Claim Construction Positions

  • "buffer": Petitioner argued that the broadest reasonable interpretation of "buffer" includes sodium hydroxide. This position was based on the specification and claims 5, 10, and 19, which explicitly state "the buffer is sodium hydroxide."
  • "substantially no detectable concentration": Petitioner contended this phrase should be construed to mean a CsA blood concentration below 0.1 ng/mL, measured at either peak or trough levels. This was based on the specification’s definition and the common practice in the art, as shown in prior art, of measuring both peak and trough levels to assess systemic exposure.

5. Key Technical Contentions (Beyond Claim Construction)

  • Rebuttal of "Unexpected Results": A central contention of the petition was that the Patent Owner overcame an obviousness rejection during prosecution by presenting flawed evidence of unexpected results. Petitioner argued that the data submitted by the Patent Owner to show the claimed 0.05% CsA emulsion was surprisingly effective lacked necessary scientific parameters, such as error bars, to demonstrate statistical significance. Furthermore, Petitioner contended that the data and graphs presented to the USPTO were merely repackaged versions of graphs from the prior art Sall reference, and therefore could not be considered "unexpected."

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-23 of the ’048 patent as unpatentable under 35 U.S.C. §103.