Merck Sharp & Dohme LLC v. Halozyme Inc

1. Case Identification

• Case #: PGR2025-00006
• Patent #: 12,152,262
• Filed: December 10, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): Halozyme Inc.
• Challenged Claims: 1-13

2. Patent Overview

• Title: Modified PH20 Polypeptides
• Brief Description: The ’262 patent discloses modified human hyaluronidase (PH20) polypeptides that retain enzymatic activity. The claims are directed to a massive genus of PH20 polypeptides that require at least one specific amino acid replacement at position 317 but permit numerous additional modifications defined by sequence identity percentages.

3. Grounds for Unpatentability

Ground 1: Claims 1-13 Lack Written Description and Enablement under 35 U.S.C. § 112

• Core Argument for this Ground: Petitioner argued that the 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 immensely broad claimed genera.
  • Lack of Written Description: Petitioner asserted that the specification does not demonstrate possession of the claimed invention. The claims encompass a staggering number of potential polypeptides (estimated between 10⁴⁹ and 10⁶⁶), yet the disclosure’s working examples are limited to only singly-modified PH20 polypeptides. Petitioner argued these few examples are not representative of the vast and structurally diverse genus of multiply-modified polypeptides covered by the claims. The disclosure allegedly fails to identify any common structural features or provide "blaze marks" that would guide a person of ordinary skill in the art (POSITA) to the subset of active polypeptides within the claimed genus.
  • Lack of Enablement: Petitioner contended that practicing the full scope of the claims would require undue experimentation. The specification provides only a prophetic, iterative "make-and-test" research plan to discover multiply-modified active mutants. Given the unpredictability of how multiple concurrent amino acid substitutions affect protein structure and function, a POSITA would be forced to synthesize and screen a scientifically infeasible number of candidates to determine which fall within the claims. Petitioner argued this amounts to an impossible task, far exceeding routine experimentation.

Ground 2: Claims 1-4 and 7-13 are obvious over the ’429 patent in view of Chao under 35 U.S.C. § 103

• 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 because the challenged claims encompass at least one specific, obvious polypeptide—the L317Q PH20(1-447) mutant—the claims covering it are unpatentable.
  • Prior Art Mapping: The ’429 patent, also owned by Halozyme, teaches making modified PH20(1-447) polypeptides via single amino acid substitutions in "non-essential regions" to create equivalents that retain biological activity. The Chao reference, through structural analysis and sequence alignments of homologous hyaluronidases, provided a POSITA with the necessary information to identify position 317 as being within such a non-essential region of the PH20 protein.
  • Motivation to Combine: A POSITA, motivated by the ’429 patent to create improved or equivalent PH20 polypeptides, would have consulted subsequent scientific literature like Chao for guidance. Chao's alignment of known, functional hyaluronidases revealed that glutamine (Q) is the most frequently occurring amino acid at the position corresponding to 317 in human PH20, where the native residue is leucine (L). This evolutionary data would have made substituting leucine with glutamine an obvious choice to explore.
  • Expectation of Success: The ’429 patent explicitly states that single amino acid substitutions in non-essential regions generally do not substantially alter biological activity. This teaching, combined with Chao’s evidence that glutamine is well-tolerated by evolution at that position and known to support α-helix structures present at that site, would have given a POSITA a reasonable expectation of success that the L317Q mutant would retain its enzymatic activity.

4. Key Technical Contentions (Beyond Claim Construction)

• Vast Genus of Claimed Polypeptides: A central technical contention underpinning the § 112 challenges is the astronomical scope of the claims. Petitioner argued that the sequence identity language, combined with the number of possible substitutions, defines genera encompassing between 10⁴⁹ and 10⁶⁶ distinct polypeptides. This immense number was used to argue that the patent's limited examples are not representative and that enabling the full scope would require an impossible amount of "make-and-test" experimentation.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) is unwarranted. While an obviousness rejection was made during prosecution, it was based on different prior art (Lin and Morrison) and a different rationale. The present obviousness ground relies on the Chao reference, which was not cited or considered by the examiner, and is supported by new expert testimony. Therefore, the Board would be considering these invalidity arguments on a new record.

6. Relief Requested

• Petitioner requests that the Board institute a post-grant review and cancel claims 1-13 of Patent 12,152,262 as unpatentable.