PTAB

IPR2016-01219

Merck Sharp & Dohme Corp v. Ono Pharmaceutical Co Ltd

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Immunopotentiative Compositions
  • Brief Description: The ’994 patent describes methods for treating cancer, specifically metastatic melanoma, by upregulating a patient's adaptive immune response. The method involves administering a human or humanized monoclonal antibody that blocks the PD-1 inhibitory receptor, thereby enhancing T-cell activity against tumor cells.

3. Grounds for Unpatentability

Ground 1: Anticipation by WO557 - Claims 1-3, 8-9, 14-15, 19-21, and 25 are anticipated by WO557

  • Prior Art Relied Upon: WO557 (International Publication No. WO 01/014557).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that WO557, published in March 2001, discloses every element of the challenged claims. Independent claim 1 recites intravenously administering an effective amount of a composition comprising a human or humanized anti-PD-1 monoclonal antibody and a solubilizer to treat metastatic melanoma. Petitioner contended WO557 teaches using blocking anti-PD-1 antibodies to upregulate the immune response to treat tumors and explicitly identifies melanoma as a type of tumor that can be treated. Petitioner asserted that a person of ordinary skill in the art (POSITA) would understand this disclosure to inherently cover metastatic melanoma, as it is an advanced stage of the same disease, and the underlying mechanism of T-cell targeting is identical. Furthermore, WO557 allegedly discloses human and humanized antibodies (claims 8-9), intravenous formulations containing surfactants that function as solubilizers (claim 1), and excipients (claim 3). Petitioner argued that the expression of PD-L1/L2 (claims 14-15, 19-22) is an inherent property of the melanoma cells being treated and that WO557 teaches using immunohistochemistry to identify PD-L1 expression (claim 25).

Ground 2: Obviousness over WO557 and Immunotherapy Art - Claims 1, 3, 8-9, 14-15, 19-22, and 25 are obvious over WO557 in view of Boon 1994 or van Elsas 1999

  • Prior Art Relied Upon: WO557 (WO 01/014557), Boon 1994 (a journal article describing T-cell therapy for melanoma), and van Elsas 1999 (a journal article describing anti-CTLA-4 immunotherapy for melanoma).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that even if WO557 does not explicitly disclose treating metastatic melanoma, it would have been obvious to a POSITA to do so. WO557 provides the core teaching: using anti-PD-1 antibodies to block an inhibitory pathway and upregulate the immune system to treat tumors, including melanoma. The secondary references, Boon 1994 and van Elsas 1999, established that stimulating T-cell mediated immune responses was a known and effective strategy for treating metastatic melanoma in humans. Boon 1994 showed that activated T-cells could eradicate metastatic melanoma, and van Elsas 1999 demonstrated that blocking a similar inhibitory receptor, CTLA-4, was effective against metastatic melanoma in mice.
    • Motivation to Combine: A POSITA would combine the teachings of WO557 with the knowledge from Boon or van Elsas to improve cancer immunotherapy. Knowing from Boon and van Elsas that upregulating T-cell responses could treat metastatic melanoma, a POSITA would have been motivated to apply the specific PD-1 blockade mechanism taught in WO557 to this known clinical challenge. The motivation was to apply a promising new therapeutic agent (anti-PD-1 antibody) to a recognized problem (treating metastatic melanoma) using an established, successful therapeutic strategy (T-cell upregulation).
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. The art established that PD-1 and CTLA-4 were similar inhibitory T-cell receptors. Since blocking CTLA-4 was shown by van Elsas to be a successful strategy against metastatic melanoma, it would have been reasonable to expect that blocking PD-1, as taught by WO557, would yield similar beneficial results against the same disease. The extensive prior art demonstrating that T-cell mediated therapies were effective against metastatic melanoma provided a strong scientific basis for this expectation.

  • Additional Grounds: Petitioner asserted additional obviousness challenges, including that claim 2 would have been obvious by further combining the primary references with Jones 1997 or Parkins 2000, which taught the use of polysorbate 80 as a common surfactant in protein-based pharmaceuticals. Petitioner also argued claim 26 was obvious by further combining the primary references with Latchman 2001, which described the PD-L2 protein and methods for its detection, motivating a POSITA to use immunohistochemistry to detect PD-L2 expression for diagnostic or monitoring purposes.

4. Relief Requested

  • Petitioner requests that the Board institute an inter partes review and cancel claims 1-3, 8-9, 14-15, 19-22, and 25-26 of the ’994 patent as unpatentable.