PTAB

IPR2016-01332

Mylan Pharmaceuticals Inc v. Janssen Oncology Inc

Log In

1. Case Identification

2. Patent Overview

  • Title: Methods and Compositions for Treating Cancer
  • Brief Description: The ’438 patent is directed to methods of treating prostate cancer by administering a therapeutically effective amount of abiraterone acetate, a CYP17 inhibitor, in combination with a therapeutically effective amount of prednisone, a glucocorticoid.

3. Grounds for Unpatentability

Ground 1: Claims 1-20 are obvious over O’Donnell in view of Gerber.

  • Prior Art Relied Upon: O’Donnell (a 2004 journal article) and Gerber (a 1990 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that O’Donnell taught treating prostate cancer patients with abiraterone acetate, a potent CYP17 inhibitor, to suppress testosterone synthesis. O’Donnell explicitly noted that the resulting suppression of cortisol might necessitate concomitant administration of a replacement glucocorticoid to manage side effects. Gerber taught that combining ketoconazole, another CYP17 inhibitor, with prednisone was a safe and effective treatment for patients with hormone-refractory metastatic prostate cancer. Together, the references disclosed all elements of independent claim 1: treating prostate cancer with a combination of abiraterone acetate and prednisone.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine O’Donnell and Gerber to create a safer and more effective treatment. O’Donnell identified the need for a glucocorticoid to manage the known side effects of abiraterone acetate. Gerber provided a successful, established example of using prednisone with a similar drug (ketoconazole) for the same purpose in the same patient population. A POSITA would have been motivated to substitute the more potent abiraterone acetate from O’Donnell into the safe and effective combination therapy taught by Gerber to manage predictable side effects.
    • Expectation of Success: A POSITA would have a high expectation of success. Since both abiraterone acetate and ketoconazole are CYP17 inhibitors that cause mineralocorticoid excess, and Gerber demonstrated that prednisone safely and effectively managed this side effect for ketoconazole, it would be predictable that prednisone would do the same for abiraterone acetate.

Ground 2: Claims 1-4 and 5-11 are obvious over the ’213 patent in view of Gerber.

  • Prior Art Relied Upon: Patent 5,604,213 (’213 patent) and Gerber (a 1990 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented a similar argument to Ground 1, substituting the ’213 patent as the primary reference. Petitioner asserted the ’213 patent disclosed abiraterone acetate and its use in treating prostate cancer. The ’213 patent also established through in vitro and in vivo data that abiraterone acetate was a significantly more potent and selective CYP17 inhibitor than ketoconazole. Gerber, as in Ground 1, taught the safe and effective co-administration of prednisone with ketoconazole.
    • Motivation to Combine: The motivation was based on improving a known therapy. A POSITA, aware of the superior potency of abiraterone acetate from the ’213 patent, would be motivated to substitute it for the older, less effective ketoconazole in the combination therapy described by Gerber. The rationale for adding prednisone remained the same: to mitigate the known class-wide side effects of CYP17 inhibitors, which would be expected to occur with the more potent abiraterone acetate.
    • Expectation of Success: The expectation of success was strong. Given that the combination of ketoconazole and prednisone was known to be safe and effective, a POSITA would reasonably expect that replacing ketoconazole with a more potent drug from the same class would yield a similarly safe, and likely more effective, treatment for prostate cancer.

4. Key Claim Construction Positions

  • Petitioner argued that for the purposes of this inter partes review (IPR), key terms should be construed according to their definitions in the ’438 patent specification.
  • "treat," "treating," and "treatment": Construed to mean "include the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the minimization or delay of the spread of cancer."
  • "anti-cancer agent": Construed to mean "any therapeutic agent that directly or indirectly kills cancer cells or directly or indirectly prohibits, stops or reduces the proliferation of cancer cells."
  • "refractory cancer": Construed to mean "cancer that is not responding to an anti-cancer treatment or cancer that is not responding sufficiently to an anti-cancer treatment."

5. Key Technical Contentions (Beyond Claim Construction)

  • Role of Prednisone: A central contention was that the prior art established the role of prednisone in the combination therapy as being purely for hormone replacement to manage the side effects (mineralocorticoid excess) caused by CYP17 inhibition, not to provide a synergistic anti-cancer effect. Petitioner argued that a POSITA would not have expected any unexpected anti-cancer benefit from the combination, only an expected improvement in safety and tolerability.
  • Rebuttal of Secondary Considerations: Petitioner preemptively argued that any commercial success of Zytiga® (the brand name for abiraterone acetate) did not support the non-obviousness of the claimed method. The argument was that Zytiga® is a commercial embodiment of the prior art ’213 patent, which claims the abiraterone acetate compound. Petitioner asserted that the Patent Owner failed to show a nexus between the claimed combination method and the drug's success, which is attributable to the efficacy of the abiraterone acetate active ingredient alone.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-20 of the ’438 patent as unpatentable.