PTAB

IPR2016-01127

Mylan Pharmaceuticals Inc v. Allergan Inc

Key Events

Petition

petition

Title: Topical Ophthalmic Emulsion for Treating Dry Eye Disease
Brief Description: The ’930 patent relates to a topical ophthalmic emulsion for treating dry eye conditions, such as keratoconjunctivitis sicca (KCS). The invention centers on a specific formulation comprising about 0.05% cyclosporin A (CsA) and about 1.25% castor oil in an emulsion with other excipients like polysorbate 80 and a cross-polymer.

Prior Art Relied Upon: Ding (Patent 5,474,979).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Ding anticipates every limitation of the challenged claims. Ding teaches topical ophthalmic emulsions containing CsA and castor oil for treating KCS and discloses all claimed ingredients (polysorbate 80, acrylate cross-polymer, glycerine, water) and formulation parameters (pH range). While Ding does not present a single example combining exactly 0.05% CsA with 1.25% castor oil, it discloses a vehicle with 1.25% castor oil (Example 2C) and teaches CsA concentrations including 0.05%. Petitioner contended a skilled artisan would have at once envisaged this combination, as the resulting CsA-to-castor-oil ratio of 0.04 is squarely within Ding’s "more preferred" ratio range of 0.02-0.12.
- Key Aspects: For dependent claims 11, 23, and 35, which add the limitation of "substantially no detectable concentration" of CsA in the blood, Petitioner asserted this is an inherent property of administering the disclosed 0.05% CsA emulsion and therefore does not confer patentability.

Prior Art Relied Upon: Ding (Patent 5,474,979) and Sall (a 2000 clinical study on CsA ophthalmic emulsions).
Core Argument for this Ground:
- Prior Art Mapping: Ding discloses the necessary formulation components and their use for treating dry eye disease. Sall describes a Phase 3 clinical trial comparing the efficacy and safety of 0.05% and 0.10% CsA ophthalmic emulsions. Sall’s results showed that the 0.05% CsA emulsion was at least as effective as the 0.10% version, but with fewer adverse side effects and a better overall safety profile.
- Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine Ding’s formulation teachings with Sall’s clinical findings. Sall provides a strong rationale to select the lower, safer, and equally effective 0.05% CsA concentration for treating KCS. A POSITA would be motivated to formulate this concentration using the 1.25% castor oil vehicle from Ding’s Example 2C, as Ding teaches this vehicle is suitable for a range of CsA concentrations and Sall used the same vehicle for both its 0.05% and 0.10% test formulations.
- Expectation of Success: The positive clinical trial data reported in Sall for a 0.05% CsA emulsion would have provided a POSITA with a reasonable expectation of success in producing a safe and therapeutically effective treatment for KCS as claimed.

Prior Art Relied Upon: Ding (Patent 5,474,979), Sall (a 2000 journal article), and Acheampong (a 1998 journal article on CsA distribution).
Core Argument for this Ground:
- Prior Art Mapping: This ground specifically targets the dependent claims reciting "substantially no detectable concentration" of CsA in human blood. The formulation itself is rendered obvious by Ding and Sall as argued in Ground 2.
- Motivation to Combine: Sall and Acheampong both directly address the pharmacokinetic profile of topically administered 0.05% CsA emulsions. Sall teaches that trough blood concentrations of CsA in patients were below the 0.1 ng/mL limit of quantitation. Acheampong reinforces and expands upon this teaching by describing a study that measured both peak and trough blood levels, finding no detectable CsA at either level in patients receiving a 0.05% CsA emulsion.
- Expectation of Success: The combined teachings of Sall and Acheampong explicitly disclose the claimed pharmacokinetic property. A POSITA would therefore have a high expectation of success that administering the emulsion of Ding would result in substantially no detectable concentration of CsA in the blood, as recited in the claims.

"substantially no detectable concentration": Petitioner proposed this term means a CsA blood concentration below 0.1 ng/mL, measured at either peak or trough levels. This construction was based on the patent’s specification and was critical for mapping the pharmacokinetic data from the Sall and Acheampong references onto the claims.
"therapeutically effective": Petitioner argued this term should be interpreted broadly to include palliative (remediating) and curative treatments. This construction was based on the prosecution history, where the Patent Owner relied on an increase in tear production as evidence of therapeutic efficacy for treating KCS.

Invalidity of "Unexpected Results" Data: Petitioner mounted a significant technical challenge to the "unexpected results" data that Patent Owner used to overcome obviousness rejections during prosecution. Petitioner argued the data, which purported to show the 0.05% CsA formulation was surprisingly as effective as a 0.10% formulation, appeared to be repackaged graphs from the prior art Sall reference. Crucially, Petitioner contended the data presented by the Patent Owner lacked essential scientific parameters, such as error bars, rendering it impossible to determine statistical significance and thus insufficient to rebut the strong prima facie case of obviousness.

Petitioner requested institution of an inter partes review and cancellation of claims 1-36 of the ’930 patent as unpatentable.