PTAB

IPR2016-01217

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 is directed to methods of treating cancer by upregulating a patient's adaptive immune response. The methods involve administering a composition containing a human or humanized anti-PD-1 monoclonal antibody to block the PD-1 inhibitory pathway, thereby enhancing T-cell activity against cancer cells.

3. Grounds for Unpatentability

Ground 1: Anticipation by WO557 - Claims 1, 6-14, 19-20, 24-26, and 29-30 are anticipated under 35 U.S.C. §102 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, expressly taught every element of the challenged claims. WO557 described methods for upregulating an immune response to treat conditions such as "a tumor" by administering an agent that inhibits signaling via PD-1, including anti-PD-1 antibodies. Crucially, Petitioner asserted that WO557 specifically identified that "lung tumor cells" express PD-L1, thereby explicitly teaching the application of this immunotherapy to the cancer recited in claim 1. Petitioner further contended that WO557 disclosed all limitations of the dependent claims, including administering the antibody in a pharmaceutical composition suitable for intravenous use (claims 11-12), in a saline solution (claims 8-9), and with additives like surfactants, which would be understood by a POSITA to be a "solubilizer" (claim 6). Because polysorbate 80 was a well-known surfactant for such formulations, its use was also anticipated (claim 7).

Ground 2: Obviousness over WO557 and Lung Cancer Art - Claims 1, 6-12, 19-20, 24-26, and 29-30 are obvious over WO557 in view of either Chen 1997 or Weynants 1999.

  • Prior Art Relied Upon: WO557 (WO 01/014557), Chen 1997 (a 1997 journal article), and Weynants 1999 (a 1999 journal article).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that even if WO557’s disclosure of treating "tumors" and its specific mention of "lung tumor cells" were deemed insufficient for anticipation, the claims were obvious. WO557 provided the foundational teaching of treating tumors by administering blocking anti-PD-1 antibodies to upregulate the immune system. The Chen 1997 and Weynants 1999 references independently established that human lung cancers are immunogenic and that T-cells specific to lung cancer can be activated to kill those cancer cells. This confirmed that lung cancer was a known and suitable target for T-cell-mediated immunotherapy.
    • Motivation to Combine: A POSITA would combine the general therapeutic strategy in WO557 with the specific knowledge about lung cancer immunogenicity from Chen or Weynants to arrive at the claimed invention. The motivation was straightforward: to apply a promising, generalized cancer immunotherapy approach (blocking PD-1) to a specific type of cancer (lung cancer) that was known to be susceptible to immune attack. WO557’s own disclosure that lung tumor cells express PD-L1—the ligand for the PD-1 receptor—provided a direct and explicit reason to target lung cancer with the taught anti-PD-1 therapy.
    • Expectation of Success: A POSITA would have had a reasonable expectation that administering the anti-PD-1 antibodies described in WO557 would successfully treat lung cancer. This expectation was based on the collective knowledge that: (1) human lung cancer patients produce T-cells specific for their tumors (Chen, Weynants); (2) PD-1 is an inhibitory receptor that suppresses T-cell function; (3) many cancers, including lung cancer, express PD-L1 to suppress the immune system; and (4) blocking inhibitory pathways like PD-1 (taught in WO557) or the closely related CTLA-4 pathway was a proven strategy to restore T-cell function and enhance anti-tumor immunity.

  • Additional Grounds: Petitioner asserted further obviousness challenges for specific dependent claims, including combining the primary references with Parkins 2000 or Jones 1997 for claim 7 (reciting polysorbate 80), with Wroblewski 2001 for claims 13-14 (reciting specific lung cancer subtypes), and with Latchman 2001 for claim 27 (reciting detection of PD-L2).

4. Key Claim Construction Positions

  • "solubilizer" (claims 6, 7): Petitioner argued this term was not defined in the ’999 patent and should be given its plain and ordinary meaning: "an agent that improves the solubility of the protein in the composition." This construction was central to Petitioner's anticipation and obviousness arguments for claims 6 and 7, as it would encompass common surfactants disclosed in the prior art (like polysorbate 80) for use in antibody formulations.

5. 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.