PTAB

IPR2017-00596

Akorn Inc v. Allergan Inc

Key Events

Petition

petition Intelligence

Title: Topical Ophthalmic Emulsion
Brief Description: The ’111 patent relates to a topical ophthalmic emulsion for treating eye conditions like keratoconjunctivitis sicca (dry eye). The invention is specifically directed to an emulsion comprising about 0.05% cyclosporin A (CsA), about 1.25% castor oil, and other excipients, wherein CsA is the only peptide present.

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’s Example 1 discloses emulsions with varying CsA concentrations, including 0.05% (Example 1E), and its Example 2 discloses castor oil-based vehicles, including one with 1.25% castor oil (Example 2C). Petitioner asserted that a person of ordinary skill in the art (POSITA) would have at once envisaged combining the 0.05% CsA concentration with the 1.25% castor oil vehicle, as the resulting CsA-to-castor oil ratio (0.04) falls squarely within the preferred ranges explicitly taught by Ding.
- Key Aspects: Petitioner highlighted that during prosecution of a related application, the Patent Owner had conceded that this exact formulation was “squarely within the teachings of the Ding reference” and would have been obvious.

Prior Art Relied Upon: Ding (Patent 5,474,979), Sall (a 2000 publication on the efficacy of cyclosporine ophthalmic emulsion).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner asserted that Ding teaches the base formulation, including all necessary components for a CsA and castor oil emulsion. Sall, a Phase 3 clinical trial publication, provides the results of treating dry eye patients with both 0.05% and 0.10% CsA emulsions. Sall concluded that the 0.05% CsA emulsion was as effective as the 0.10% version but with a better safety profile and fewer side effects.
- Motivation to Combine: A POSITA seeking to develop an effective and safe treatment for dry eye would combine the teachings of Ding and Sall. Sall’s clinical data provides a strong rationale to select the 0.05% CsA concentration for its favorable balance of efficacy and safety. A POSITA would then have been motivated to use the 1.25% castor oil vehicle from Ding (Example 2C), as Ding teaches it is a suitable and preferred vehicle for creating a stable and effective emulsion at this CsA concentration.
- Expectation of Success: The successful clinical trial results reported in Sall for a 0.05% CsA emulsion provided a POSITA with a strong and reasonable expectation of success in creating the claimed therapeutically effective formulation.

Prior Art Relied Upon: Ding (Patent 5,474,979), Sall (2000 publication), Acheampong (a 1998 publication on cyclosporine distribution).
Core Argument for this Ground:
- Prior Art Mapping: This ground specifically addressed the limitation in dependent claims 11 and 16 requiring "substantially no detectable concentration" of CsA in the blood. Petitioner argued that Sall already taught this, reporting that trough blood concentrations of CsA were below the limit of quantitation (0.1 ng/mL). Acheampong further confirmed and strengthened this teaching by describing a study that measured CsA blood levels at both peak and trough times, finding no detectable CsA in patients receiving the 0.05% emulsion at either measurement point.
- Motivation to Combine: A POSITA, having formulated the emulsion based on Ding and Sall, would have been motivated to consult a pharmacokinetic study like Acheampong to confirm the systemic absorption properties. Acheampong’s findings would confirm the expectation that the 0.05% formulation results in negligible systemic exposure, thereby satisfying the claim limitation.

"substantially no detectable concentration": Petitioner argued this term should be construed to mean a blood concentration below 0.1 ng/mL, as measured at either peak or trough levels. This construction is based on the patent's own specification, which identifies a detection limit of 0.1 ng/mL for the preferred assay (LC-MS/MS). This construction is critical to mapping the Sall and Acheampong references to claims 11 and 16.
"buffer": Petitioner contended that the broadest reasonable interpretation of "buffer" includes sodium hydroxide, as the specification and the claims themselves (e.g., claims 5, 10, 14) identify sodium hydroxide as the buffer used to adjust the emulsion's pH.

Rebuttal of "Unexpected Results": A central contention of the petition was that the Patent Owner improperly relied on flawed evidence of "unexpected results" to overcome an obviousness rejection during prosecution. Petitioner argued that the data submitted by the Patent Owner's experts lacked essential scientific parameters, such as error bars, making it impossible to determine statistical significance. Furthermore, Petitioner alleged that the data and graphs presented to the examiner appeared to be repackaged versions of graphs from the Sall prior art reference itself, and therefore could not constitute an "unexpected" result.

Petitioner requested institution of an inter partes review and cancellation of claims 1-27 of the ’111 patent as unpatentable.