Merck Sharp & Dohme Corp v. Ono Pharmaceutical Co Ltd

1. Case Identification

• Case #: IPR2016-01221
• Patent #: 9,073,994
• Filed: June 29, 2016
• Petitioner(s): Merck Sharp & Dohme Corp.
• Patent Owner(s): Ono Pharmaceutical Co., LTD. and Tasuku Honjo
• Challenged Claims: 1-3, 8-9, 14-15, 19-22, and 25-26

2. Patent Overview

• Title: IMMUNOPOTENTIATIVE COMPOSITION
• Brief Description: The ’994 patent relates to methods of treating cancer, specifically metastatic melanoma, by upregulating a patient's adaptive immune response. The claimed method involves administering a composition containing a human or humanized anti-PD-1 monoclonal antibody to block inhibitory signaling through the PD-1 pathway.

3. Grounds for Unpatentability

Ground 1: Anticipation over the '051 Patent - Claims 1-3, 8-9, 14-15, and 19-22 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 the ’051 patent explicitly teaches every element of the challenged claims. It discloses treating cancer, including melanoma, by administering an antagonistic anti-PD-1 antibody to augment a patient’s immune response. The ’051 patent allegedly describes and enables human and humanized monoclonal anti-PD-1 antibodies, their formulation into pharmaceutical compositions suitable for intravenous administration, and the inclusion of surfactants, which Petitioner equated with the claimed "solubilizer." For dependent claims, Petitioner asserted that the '051 patent’s teaching to include "surfactants" would lead a POSITA to envision polysorbate 80 (claim 2), that it expressly teaches including "excipients" (claim 3), and that it enables both humanized (claim 8) and human (claim 9) antibodies. The expression of PD-L1/L2 (claims 14-15, 19-22) was argued to be an inherent property of the melanoma cells being treated.

Ground 2: Obviousness over '051 in View of Boon or Van Elsas - Claims 1, 3, 8-9, 14-15, and 19-22 are obvious over the '051 patent in view of Boon 1994 or Van Elsas 1999.

• Prior Art Relied Upon: '051 patent (Patent 7,521,051), Boon 1994 (a 1994 journal article on tumor antigens), and Van Elsas 1999 (a 1999 journal article on combination immunotherapy for melanoma).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that the ’051 patent provides the foundational teaching of using antagonistic anti-PD-1 antibodies to enhance an immune response against melanoma. While the ’051 patent teaches treating melanoma generally, Boon and Van Elsas specifically address the treatment of metastatic melanoma.
  • Motivation to Combine: A POSITA would combine the teachings because it was a known and "logical" step. The ’051 patent provides a specific agent (anti-PD-1 antibody) to achieve a general goal (immune upregulation against cancer). Boon and Van Elsas established that this general goal was an effective strategy for treating metastatic melanoma specifically. Therefore, a POSITA would have been motivated to apply the specific agent from the '051 patent to the particular disease stage (metastatic) taught as treatable by immune upregulation in Boon and Van Elsas.
  • Expectation of Success: Petitioner argued a POSITA would have had a strong expectation of success. By 2002, the scientific literature had established that PD-1 was an inhibitory receptor, that blocking inhibitory signals (e.g., via the analogous CTLA-4 pathway) enhanced anti-tumor immunity, and that melanoma cells were immunogenic. The in vitro data in the '051 patent showing that its antibodies stimulated T-cell proliferation would have provided a reasonable basis to expect a similar therapeutic effect in a human patient.
• Additional Grounds: Petitioner asserted additional obviousness challenges for dependent claims. These included combining the '051 patent and Boon/Van Elsas with references like Jones 1997 or Parkins 2000 to show the obviousness of using polysorbate 80 (claim 2), and with WO557 or the '214 patent to show the obviousness of detecting PD-L1/L2 expression using immunohistochemistry (claims 25-26).

4. Key Claim Construction Positions

• "Metastatic Melanoma": Petitioner argued this term was not defined in the patent and should be given its plain meaning: "a melanoma which has metastasized in a patient." This construction was central to their argument that prior art teaching treatment of melanoma generally would be understood to include its metastatic form.
• "Solubilizer": Petitioner proposed this term means "an agent that improves the solubility of a protein in a composition." This construction was used to argue that the '051 patent's disclosure of "surfactants" in pharmaceutical formulations directly taught or rendered obvious the claimed "solubilizer."

5. Key Technical Contentions (Beyond Claim Construction)

• Effective Filing Date of the '994 Patent: A central contention was that the ’994 patent was not entitled to its earliest claimed priority date of July 3, 2002. Petitioner argued the priority applications failed to meet the written description requirement of 35 U.S.C. §112 because they described the genus of anti-PD-1 antibodies using only functional language (e.g., binds to PD-1, treats melanoma) without providing a representative number of species or common structural features. This failure, Petitioner contended, pushes the patent’s effective filing date to July 2, 2003, making the ’051 patent (with a December 23, 2002 filing date) available as prior art under §102(e).

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-3, 8-9, 14-15, 19-22, and 25-26 as unpatentable.