Merck Sharp & Dohme LLC v. Halozyme Inc

1. Case Identification

• Case #: PGR2025-00024
• Patent #: 12,060,590
• Filed: February 21, 2025
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): Halozyme Inc.
• Challenged Claims: 1-35

2. Patent Overview

• Title: Modified Human Hyaluronidase (PH20) Polypeptides
• Brief Description: The ’590 patent relates to modified human hyaluronidase (PH20) polypeptides that retain enzymatic activity. The claims require at least one specific amino acid substitution at position 307 and permit numerous additional modifications, defined by sequence identity thresholds to reference sequences.

3. Grounds for Unpatentability

Ground 1: Claims 1-35 are unpatentable under 35 U.S.C. § 112 for lack of written description.

• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the challenged claims define astronomically large genera of modified PH20 polypeptides, ranging from 10^59 to 10^112 distinct species. This scope arises from claim language allowing up to 41 additional substitutions at any of 430+ positions, in addition to the required substitution at position 307. The specification, in contrast, provides a meager disclosure limited to experimental data for singly-modified PH20 polypeptides.
  • Key Aspects: The petition asserted that the disclosure fails the written description requirement for genus claims because it provides neither a representative number of species nor common structural features that would identify the members of the claimed genera. The disclosed single-substitution examples are not structurally representative of the claimed multiply-substituted polypeptides, which would have different and unpredictable structural and functional properties. Furthermore, the specification provides only a prophetic, iterative "make-and-test" research plan to discover multiply-modified active mutants, which Petitioner argued is an admission that the inventors were not in possession of the claimed invention. The claims also improperly capture polypeptides that the specification teaches to avoid, such as those with inactivating mutations or certain C-terminal truncations.

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

• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner contended that practicing the full scope of the immense claimed genera would require undue experimentation. A person of ordinary skill in the art (POSA), guided only by the specification, would have to engage in an iterative, trial-and-error process of making and screening trillions of potential polypeptide variants to determine which ones are enzymatically active as claimed.
  • Key Aspects: The petition emphasized the unpredictability in the field of protein engineering as of the filing date, especially concerning the cumulative effects of multiple concurrent amino acid substitutions on protein structure and function. The specification provided no guidance to navigate this unpredictability, offering only a prophetic research plan without disclosing any actual working examples of multiply-modified PH20 polypeptides. Petitioner argued that this "trial-and-error discovery" methodology is incapable of enabling the full scope of the claims, forcing a POSA to perform undue experimentation to determine which of the vast number of claimed species actually possess the recited functionality.

Ground 3: Claims 1-2 and 5-35 are obvious over the ’429 patent in view of Chao.

• Prior Art Relied Upon: Patentee’s own ’429 patent (Patent 7,767,429) and Chao (a 2007 Biochemistry journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued the claims encompass specific, obvious single-replacement mutants of the PH201-447 polypeptide, including L307W, L307T, and L307S. Because the claims read on these obvious species, the claims themselves are unpatentable under 35 U.S.C. § 103.
  • Motivation to Combine (for §103 grounds): The ’429 patent explicitly taught that single amino acid substitutions in non-essential regions of a polypeptide generally do not alter biological activity and motivated a POSA to create such "equivalent" proteins. A POSA seeking to implement this teaching would have consulted subsequent literature, such as Chao, which provided structural insights into human hyaluronidases like PH20.
  • Expectation of Success (for §103 grounds): A POSA combining the teachings would have readily identified position 307 as being in a non-essential region of PH20. Analysis of homologous proteins, taught by Chao and available in the art, revealed that tryptophan, threonine, and serine were naturally tolerated at the corresponding position. This, combined with the ’429 patent’s own assurance, would have provided a POSA with a reasonable expectation of success that substituting leucine with tryptophan, threonine, or serine at position 307 would result in an enzymatically active PH20 polypeptide.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under § 324(a) or § 325(d) is unwarranted. No parallel litigation involving the ’590 patent is pending, making denial under Fintiv inappropriate. Furthermore, the Examiner did not raise any obviousness rejections during prosecution, and the current §103 ground relies on the Chao reference, which was not cited or considered during examination, as well as expert testimony unavailable to the Examiner.

5. Relief Requested

• Petitioner requests institution of post-grant review and cancellation of claims 1-35 of the ’590 patent as unpatentable.