Merck Sharp & Dohme LLC v. Halozyme Inc

1. Case Identification

• Case #: PGR2025-00030
• Patent #: 12,054,758
• Filed: February 4, 2025
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): Halozyme Inc.
• Challenged Claims: 1-40

2. Patent Overview

• Title: Modified Human Hyaluronidase (PH20) Polypeptides
• Brief Description: The ’758 patent relates to structurally altered forms of the human PH20 hyaluronidase enzyme. The claimed modified polypeptides must contain at least one specific amino acid substitution at position 317, may contain numerous other modifications, and are required to retain enzymatic activity.

3. Grounds for Unpatentability

Ground 1: Lack of Written Description and Enablement under 35 U.S.C. § 112 - Claims 1-40

• Prior Art Relied Upon: Not applicable; this ground is based on deficiencies in the ’758 patent’s own specification.
• Core Argument for this Ground: Petitioner argued that all challenged claims are unpatentable under 35 U.S.C. § 112 because the specification fails to provide adequate written description for and does not enable the full scope of the claimed subject matter.
  • Written Description: Petitioner asserted that the claims encompass an immense and structurally diverse genus of polypeptides, with the narrowest claims covering over 10^59 distinct species. The specification, however, only discloses a narrow set of working examples limited to singly-modified PH20 polypeptides. Petitioner argued these examples are not representative of the claimed genus, which primarily consists of multiply-modified polypeptides. Furthermore, the claims improperly capture polypeptides that the specification instructs a person of ordinary skill in the art (POSITA) to avoid, such as those with inactivating mutations or certain C-terminal truncations known to eliminate activity. The disclosure allegedly provides no common structural features that would allow a POSITA to identify which members of the vast genus possess the claimed functionality, offering only a prophetic "make-and-test" research plan.
  • Enablement: Petitioner contended that practicing the full scope of the claims would require undue experimentation. To identify the active mutants from the trillions of possibilities within the claimed genus, a POSITA would have to engage in an iterative, trial-and-error process of creating and testing a practically infinite number of polypeptides. Petitioner argued this is an impossible task, particularly because the effects of multiple concurrent amino acid substitutions on protein function were highly unpredictable at the time of the invention. The specification provides no guidance to navigate this unpredictability, effectively requiring a research project rather than enabling a claimed invention.

Ground 2: Obviousness over the ’429 patent and Chao - Claims 1-2, 5-6, 8, and 10-40 are obvious over the ’429 patent in view of Chao

• Prior Art Relied Upon: Patent 7,767,429 (’429 patent) and Chao (a 2007 Biochemistry journal article).
• Core Argument for this Ground: Petitioner argued that the challenged claims are obvious because they encompass at least one specific, obvious modified polypeptide: a PH201-447 protein with a leucine-to-glutamine substitution at position 317 (L317Q).
  • Prior Art Mapping: The ’429 patent, owned by the Patent Owner, teaches that making single amino acid substitutions in non-essential regions of the PH201-447 polypeptide can create "equivalent" proteins that retain biological activity. Chao provides detailed structural information about human hyaluronidases, including sequence alignments that allow a POSITA to distinguish essential (conserved) regions from non-essential (variable) regions. Petitioner argued a POSITA would have readily identified position 317 as being within a non-essential region. A multiple-sequence alignment of homologous proteins, a standard tool at the time, would have shown that glutamine (Q) is the most prevalent and well-tolerated amino acid at the position corresponding to 317, making the L317Q substitution an obvious choice to try.
  • Motivation to Combine: A POSITA would combine the general motivation from the ’429 patent to create modified, active PH20 proteins with the specific structural guidance from Chao to identify promising locations and substitutions. The goal was to produce equivalent proteins with retained enzymatic activity, as taught by the ’429 patent.
  • Expectation of Success: Petitioner asserted there was a strong expectation of success. The ’429 patent explicitly states that a POSITA would "recognize that, in general, single amino acid substitutions in non-essential regions of a polypeptide do not substantially alter biological activity." This, combined with data showing glutamine is naturally prevalent at the target position in related proteins, would give a POSITA a reasonable expectation that the L317Q mutant would be an active enzyme.

4. Key Technical Contentions (Beyond Claim Construction)

• The central technical contention underpinning the §112 grounds is the immense scope of the claims. Petitioner argued that the claims, defined by broad sequence identity percentages, encompass a staggering number of potential polypeptides (between 10^59 and 10^112). This vastness makes it impossible for the limited examples to be representative (violating written description) and for a POSITA to practice the full scope without undue, near-infinite experimentation (violating enablement).

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the Board should not exercise its discretion to deny institution under §324(a) or §325(d).
• No parallel litigation involving the ’758 patent is pending, making discretionary denial under Fintiv inapplicable.
• Petitioner asserted the examiner erred during prosecution by failing to reject the claims for lack of written description and enablement, despite their immense scope. Additionally, the obviousness ground relies on the Chao reference, which was not cited or considered by the examiner, and is supported by new expert testimony not available during prosecution.

6. Relief Requested

• Petitioner requests that the Board institute a Post Grant Review (PGR) of claims 1-40 of the ’758 patent and issue a final written decision canceling those claims as unpatentable.