PTAB

PGR2025-00087

Merck Sharp & Dohme LLC v. Halozyme Inc

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Modified Human PH20 Hyaluronidase Polypeptides
  • Brief Description: The ’685 patent claims modified human PH20 hyaluronidase polypeptides that contain specific amino acid substitutions, have at least 95% sequence identity to a reference sequence, and exhibit increased hyaluronidase activity compared to an unmodified version.

3. Grounds for Unpatentability

Ground 1: Claims 1-10 are unpatentable under 35 U.S.C. § 112 for lacking adequate written description.

  • Prior Art Relied Upon: This ground is based on the deficiencies of the patent’s own specification (the “common disclosure” shared with the priority ’731 application).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the claims define an immense genus of modified PH20 polypeptides, capturing between 10⁴⁹ and 10⁶⁰ distinct sequences, based on functional language (increased activity) and broad structural parameters (a required substitution at position 324 plus at least 95% sequence identity to a 433-residue reference sequence, allowing up to 20 additional modifications). The specification, however, fails to provide a disclosure commensurate with this scope. Petitioner contended the disclosure does not demonstrate that the inventors were in possession of this vast genus at the time of filing.
    • Lack of Representative Species: The disclosure’s examples are limited to singly-modified polypeptides based on a different, 447-residue PH20 sequence (SEQ ID NO: 3). Petitioner argued these examples are not structurally representative of the claimed genus, which requires multiply-modified polypeptides based on a 433-residue sequence (SEQ ID NO: 35). No examples of any modified polypeptide based on the claimed 433-residue sequence are provided.
    • No Common Identifying Feature: Petitioner asserted that the disclosure fails to identify any common structural features shared by the members of the claimed genus that would explain why they possess the claimed functional property of increased hyaluronidase activity. The specification merely provides a prophetic "research plan" for discovering such mutants through trial-and-error, rather than describing the successfully identified mutants themselves.

Ground 2: Claims 1-10 are unpatentable under 35 U.S.C. § 112 for lacking enablement.

  • Prior Art Relied Upon: This ground is based on the deficiencies of the patent’s own specification.
  • Core Argument for this Ground:
    • Undue Experimentation: Petitioner argued that practicing the full scope of the claims would require undue experimentation. To identify which of the 10⁴⁹+ possible polypeptides meet the functional requirement of "increased hyaluronidase activity," a person of ordinary skill in the art (POSITA) would have to engage in an iterative "make-and-test" process for a literally impossible number of candidates. The patent provides no guidance or predictable principles to narrow this search.
    • Unpredictability of the Art: The field of protein engineering, particularly concerning multiple concurrent amino acid substitutions, was highly unpredictable at the time of filing. Petitioner contended that the cumulative effects of multiple mutations on protein folding, stability, and enzymatic activity cannot be reliably predicted. The handful of single-substitution examples provided in the disclosure offer no predictable guidance for the claimed multiply-substituted polypeptides.
    • Insufficient Guidance: The specification’s only guidance is a prophetic research plan involving iterative rounds of mutagenesis and screening. Petitioner argued this is an invitation to experiment, not an enabling disclosure. It does not teach a POSITA how to make and use the full scope of the claimed invention without engaging in the very discovery process the inventors purportedly undertook, a task of impossible scale. The presence of numerous inoperative embodiments within the claim scope further complicates enablement.

4. Relief Requested

  • Petitioner requests institution of post-grant review and cancellation of claims 1-10 of the ’685 patent as unpatentable under §112.