PTAB

PGR2018-00098

Hybrigenic SA v. forma Therapeutics Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: USP7 Inhibitor Compounds
  • Brief Description: The ’491 patent is directed to chemical compounds of a general Formula (I), and pharmaceutical compositions thereof, which function as inhibitors of Ubiquitin-Specific Protease 7 (USP7). The compounds are based on a substituted quinazolin-4-one scaffold and are disclosed for use in treating diseases such as cancer.

3. Grounds for Unpatentability

Ground 1: Obviousness over the ’150 patent - Claims 1-17 are obvious over Patent 9,546,150.

  • Prior Art Relied Upon: Patent 9,546,150 ("the ’150 patent").
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the ’150 patent discloses the same extended chemical core structure for USP7 inhibitors as the ’491 patent: a [1-carbonyl-4-hydroxy-4-piperidyl]-methyl-[quinazolin-4-one] scaffold. The ’150 patent provides 14 specific examples that teach a person of ordinary skill in the art (POSITA) how various substitutions on this core affect USP7 inhibition. Petitioner asserted that the compounds of the ’491 patent, including the 13 specific species listed in claim 16, are merely predictable variations of the compounds disclosed in the ’150 patent. For example, several claimed compounds in the ’491 patent use a 3-phenylbutanoyl side chain, which Petitioner contended is a very close and obvious structural isomer of the 2-methyl-3-phenyl-propanoyl side chain found in the most active examples (13 and 14) of the ’150 patent.
    • Motivation to Combine (Modify): A POSITA would have selected the most active compounds from the ’150 patent as lead compounds for further development. The motivation to modify these lead compounds would be the routine optimization of a known therapeutic scaffold to discover other compounds with similar or improved properties. The ’150 patent’s disclosure of various successful substitutions would have provided a clear roadmap and incentive for a POSITA to explore structurally similar modifications, such as using a close isomer of a known-active side chain.
    • Expectation of Success: Given that the ’150 patent establishes a viable and predictable scaffold for USP7 inhibition, a POSITA would have had a reasonable expectation of success that making minor modifications would result in compounds that retained USP7 inhibitory activity. Petitioner argued there was no evidence of unexpected results, as the Patent Owner’s claims of superior potency for the ’491 compounds were based on a different and less stringent assay than that used in the ’150 patent, making any direct comparison of activity levels invalid.

Ground 2: Lack of Enablement - Claims 1-17 are invalid under 35 U.S.C. §112.

  • Prior Art Relied Upon: None (challenge based on the specification).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the challenged claims are not enabled across their full scope. The specification provides insufficient guidance for a POSITA to make and use the millions of compounds encompassed by the genus of claim 1. While the patent discloses 13 specific compounds, it only provides methods of synthesis for four of them. These few examples are not representative of the vast genus claimed and fail to enable a POSITA to practice the full scope of the invention without undue experimentation.
    • Key Aspects: The argument focused on the vast disparity between the number of claimed compounds (millions) and the number of examples with synthesis details (four). All provided examples also share a highly similar core structure, failing to enable compounds within the claims that deviate from this specific structural template.

Ground 3: Lack of Written Description - Claims 1-15 and 17 are invalid under 35 U.S.C. §112.

  • Prior Art Relied Upon: None (challenge based on the specification and file history).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner contended the specification fails to demonstrate that the inventors were in possession of the claimed invention at the time of filing. The disclosure of only 13 specific species is insufficient to support a claim to a genus covering millions of compounds. Petitioner further argued that amendments made during prosecution to narrow the definitions of various R-group substituents (e.g., limiting heteroaryl groups to "5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms") introduced new matter. The original specification allegedly lacked literal support for these broader, amended limitations, instead only disclosing specific, individual heteroaryl examples.
    • Key Aspects: This ground asserted two distinct written description failures: (1) insufficient species-to-genus support, and (2) lack of support in the original disclosure for claim limitations added during prosecution.

4. Key Technical Contentions (Beyond Claim Construction)

  • Petitioner contended that any claim of unexpected results or superior potency of the ’491 patent’s compounds is unfounded. The argument was based on the fact that the bioassay used to measure USP7 inhibition in the ’491 patent specification was different from, and less stringent than, the assay disclosed in the ’150 patent. Therefore, comparing the resulting IC50 values was akin to "comparing apples to oranges" and could not serve as objective evidence of non-obviousness.

5. Relief Requested

  • Petitioner requested the institution of a post grant review and the cancellation of claims 1-17 of the ’491 patent as unpatentable under §103 and §112.