PTAB

IPR2016-01186

Merck Sharp & Dohmen Corp. v. Mayne Pharma International Pty Ltd.

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1. Case Identification

  • Case #: IPR2016-____
  • Patent #: Patent 6,881,745
  • Filed: June 11, 2016
  • Petitioner(s): Merck Sharp & Dohme Corp.
  • Patent Owner(s): Mayne Pharma International Pty Ltd.
  • Challenged Claims: 1-3, 5-7, and 9-14

2. Patent Overview

  • Title: Pharmaceutical Compositions for Poorly Soluble Drugs
  • Brief Description: The ’745 patent discloses pharmaceutical compositions designed to improve the bioavailability of poorly soluble drugs. The claims are directed to a composition consisting essentially of an azole antifungal drug (e.g., itraconazole) and, in most claims, a polymer with acidic functional groups.

3. Grounds for Unpatentability

Ground 1: Anticipation by Kai - Claims 1-3, 5-7, and 9-14 are anticipated under 35 U.S.C. §102 by Kai.

  • Prior Art Relied Upon: Kai, et al., Oral Absorption Improvement of Poorly Soluble Drug Using Solid Dispersion Technique, Chemical and Pharmaceutical Bulletin, 44(3): 568-571 (1996) (“Kai”).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Kai discloses every element of the challenged claims. Kai describes solid dispersion formulations using 100 mg of the triazole MFB-1041, which Petitioner’s expert identified as an "azole antifungal drug." Kai combines this drug with polymers having acidic functional groups, including hydroxypropyl methylcellulose phthalate (“HP-55”), which is a "particularly preferred" polymer in the ’745 patent. Furthermore, Kai reports in vivo Cmax and AUC data in dogs that far exceed the minimum thresholds recited in the challenged claims, satisfying even the purportedly limiting "wherein" clauses.
    • Key Aspects: The argument emphasized that Kai alone provides a complete blueprint for the claimed invention, including the specific drug type, dosage, polymer type, and resulting bioavailability benchmarks, rendering the claims not novel.

Ground 2: Obviousness over Kai, Sangekar, and Babcock - Claims 1-3, 5-7, and 9-14 are obvious over Kai in view of Sangekar and Babcock.

  • Prior Art Relied Upon: Kai (a 1996 journal article), Sangekar (WO 98/00113), and Babcock (European Publication 1 027 886 A2).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner contended that by the priority date, the state of the art was replete with examples of combining poorly soluble drugs, including azoles, with acidic polymers to enhance bioavailability. Kai, Sangekar, and Babcock each taught compositions with "about 100 mg" of an azole antifungal drug combined with a qualifying polymer. For instance, Sangekar discloses 100 mg dosage forms of a "tetrahydrofuran azole antifungal," and Babcock identifies 100 mg as a therapeutic dose and explicitly names the azole fluconazole as a suitable drug.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine the teachings of these references because they address the same well-known problem: improving the oral bioavailability of poorly soluble azole antifungals. The pressing need for effective antifungals during the AIDS epidemic provided a strong motivation to use known formulation strategies, like those in the prior art, to improve existing drugs.
    • Expectation of Success: A POSITA would have a reasonable expectation of success. The art demonstrated that combining azoles with acid-resistant polymers was a proven, predictable strategy for improving solubility and absorption. Kai itself showed that adjusting the polymer-to-azole ratio was a routine method to achieve desired Cmax and AUC levels.

Ground 3: Obviousness over Kohri, Baert, and Vandecruys - Claims 1-3, 5-7, and 9-14 are obvious over Kohri, Baert, and Vandecruys.

  • Prior Art Relied Upon: Kohri (a 1999 journal article), Baert (Patent 6,509,038), and Vandecruys (WO 98/42318).

  • Core Argument for this Ground:

    • Prior Art Mapping: This combination presented an alternative set of primary references demonstrating the same inventive concept. Kohri taught 100 mg of the azole albendazole with a preferred polymer from the ’745 patent. Baert and Vandecruys both taught 100 mg dosage forms of itraconazole (a poorly soluble azole) combined with various polymers having acidic functional groups (e.g., carboxymethylethyl cellulose, polyacrylic acids).
    • Motivation to Combine: The motivation was identical to the previous ground: to solve the known problem of poor azole bioavailability using established formulation techniques. These references specifically addressed improving the bioavailability of azoles like itraconazole, directly teaching the combination claimed in the ’745 patent.
    • Expectation of Success: Success was predictable. Given the extensive literature showing the efficacy of these combinations, a POSITA would have expected that combining an azole like itraconazole with an acidic polymer, as taught by Baert and Vandecruys, would yield improved bioavailability, as confirmed by the data in Kohri and the broader art.

  • Additional Grounds: Petitioner asserted numerous additional anticipation challenges against claims 1-3, 5-7, and 9-14 based on Sangekar, Kohri, Babcock, Baert, and Vandecruys individually. Further, Petitioner challenged claims 1, 3, 5, and 7 (where the polymer is "optional") as anticipated by Thorpe, Tett, and Lin, each of which disclosed 100 mg doses of an azole antifungal alone.

4. Key Claim Construction Positions

  • "consisting essentially of": Petitioner argued this phrase should be construed as coextensive with the open-ended term "comprising." The rationale was that the ’745 patent specification focuses on a "solid dispersion" as the invention, but the claims are not limited to solid dispersions. Because the specification fails to describe the basic and novel characteristics of the actual claimed invention, the transitional phrase cannot be given its typical limiting effect.
  • "wherein in vivo the composition provides [a certain CMAX or AUC level]...": Petitioner contended this clause is a non-limiting statement of intended result and should be given no patentable weight. The argument was that the body of the claims defines a structurally complete composition (an azole and a polymer). The "wherein" clause merely states a functional result of that structure, adding nothing to the structure itself, and is thus legally irrelevant to patentability.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-3, 5-7, and 9-14 of Patent 6,881,745 as unpatentable.