PTAB

IPR2016-01218

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 COMPOSITION
  • Brief Description: The ’999 patent discloses methods for treating lung cancer by upregulating a patient’s immune response. The method comprises administering a composition containing a human or humanized anti-PD-1 monoclonal antibody that interferes with the inhibitory signaling of the PD-1 pathway.

3. Grounds for Unpatentability

Ground 1: Anticipation over the ’051 patent - Claims 1, 6-14, 19-20, and 24-25 are anticipated by the ’051 patent under 35 U.S.C. §102(e).

  • Prior Art Relied Upon: ’051 patent (Patent 7,521,051).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the ’051 patent is effective prior art because the ’999 patent is not entitled to its claimed priority dates due to a lack of written description support in the priority applications. The ’051 patent allegedly disclosed every element of the challenged claims. It described treating cancer by administering human and humanized antagonistic anti-PD-1 antibodies to enhance a patient's immune response. Petitioner asserted that a person of ordinary skill in the art (POSITA) would have understood "cancer" as used in the ’051 patent to include lung cancer, as it was a well-known immunogenic cancer. The ’051 patent also expressly taught formulations including solutions, saline, excipients, and surfactants (anticipating "solubilizer"), as well as parenteral and intravenous administration, thereby anticipating the dependent claims. The expression of PD-L1/L2 (claims 19, 20, 24, 25) was argued to be an inherent property of the lung cancers that were known to be treatable by this mechanism.

Ground 2: Obviousness over the ’051 patent and Immunogenicity References - Claims 1, 6-14, 19-20, and 24-25 are obvious over the ’051 patent in view of Chen or Weynants.

  • Prior Art Relied Upon: ’051 patent (Patent 7,521,051), Chen (a 1997 journal article), and Weynants (a 1999 journal article).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that, even if the ’051 patent did not explicitly name lung cancer, it taught a general method of treating cancer by upregulating a patient’s immune response using antagonistic anti-PD-1 antibodies. The Chen and Weynants references established that lung cancer was known to be immunogenic, expressing tumor antigens that induce the production of activated T-cells capable of killing lung cancer cells. Therefore, applying the general immunotherapy method of the ’051 patent to the specific, known immunogenic cancer taught by Chen and Weynants would have been obvious.
    • Motivation to Combine: A POSITA would combine these references because they all concerned upregulating immune responses against tumors. The ’051 patent provided a promising agent (anti-PD-1 antibody) to achieve this goal, while Chen and Weynants identified a well-known and suitable target (lung cancer) for such an immunotherapy strategy. Petitioner contended it was a "logical" extension of known principles to apply the PD-1 blocking strategy to a known immunogenic cancer.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. The inhibitory role of the PD-1 pathway was well-established, as was the success of blocking the similar CTLA-4 pathway for cancer treatment. Furthermore, the ’051 patent provided in vitro data demonstrating its anti-PD-1 antibodies stimulated T-cell proliferation and cytokine release, which was known to correlate with in vivo efficacy.

  • Additional Grounds: Petitioner asserted additional obviousness challenges for specific dependent claims. These included arguments that:

    • Claim 7 (comprising polysorbate 80) is obvious over the ’051 patent, Chen/Weynants, and further in view of Parkins (a 2000 journal article) or Jones (a 1997 journal article), which taught using polysorbate 80 as a common surfactant in antibody formulations.
    • Claims 13 and 14 (treating squamous carcinoma and adenocarcinoma) are obvious over the ’051 patent and Chen/Weynants in view of general knowledge that these were common, immunogenic subtypes of lung cancer.
    • Claims 26, 27, 29, and 30 (detecting PD-L1/L2 expression using immunohistochemistry) are obvious over the ’051 patent and Chen/Weynants in view of WO557 or the ’214 patent, which taught the benefits of using this common laboratory technique to identify ligand expression for diagnostic or therapeutic purposes.

4. Key Claim Construction Positions

  • "solubilizer" (claim 6): Petitioner proposed this term should be construed according to its plain and ordinary meaning as "an agent that improves the solubility of the protein in the composition." This construction was central to the argument that the term "surfactants" disclosed in the ’051 patent anticipates or renders obvious the claimed "solubilizer," as surfactants were known agents used to increase protein solubility in pharmaceutical formulations.

5. Key Technical Contentions (Beyond Claim Construction)

  • Effective Filing Date of the ’999 Patent: A central contention was that the ’999 patent was not entitled to the priority dates of its earlier Japanese applications (filed July 3, 2002 and February 6, 2003). Petitioner argued these priority applications failed the written description requirement of §112 because they described the claimed anti-PD-1 antibodies in purely functional terms (e.g., "binds to PD-1") without providing sufficient structural features or representative species to show possession of the claimed genus. This alleged defect was critical to Petitioner's case, as it established the ’051 patent (with a December 23, 2002 effective date) as invalidating prior art under §102(e).

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1, 6-14, 19, 20, 24-27, 29, and 30 of the ’999 patent as unpatentable.