On September 1, 2026, the Patent Trial and Appeal Board (“PTAB”) issued a Final Written Decision (“FWD”) in PGR2025-00017 finding all remaining challenged claims of Halozyme’s U.S. Patent No. 12,110,520 (“the ’520 patent”) unpatentable. The ’520 patent was challenged by Merck and is part of a broader dispute between Merck and Halozyme relating to Keytruda Qlex™ (pembrolizumab; berahyaluronidase alfa-pmph) and Halozyme’s PH20 hyaluronidase patent portfolio.

The ’520 patent is directed to modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity. Merck challenged claims 1–35 on written description and enablement grounds and claims 1–2 and 5–35 on obviousness grounds. After Halozyme disclaimed claims 3–5, 16, and 31–35, claims 1, 2, 6–15, and 17–30 remained at issue.

As in prior FWDs involving related Halozyme PH20 patents (previously reported Keytruda Qlex™ Updates: Final Written Decisions Find Two Halozyme PH20 Patents Unpatentable While Institution is Denied for Third Patent; Keytruda Qlex™ Updates: PTAB Finds Additional Halozyme PH20 Patent Unpatentable in Final Written Decision), the Board found that the term “modified PH20 polypeptide” required hyaluronidase activity. The Board then applied similar written-description and enablement reasoning to the challenged claims of the ’520 patent.

The Board found the challenged claims unpatentable for lack of written description and enablement. Consistent with the Board’s reasoning in prior FWDs involving related Halozyme PH20 patents (previously reported Keytruda Qlex™ Updates: Final Written Decisions Find Two Halozyme PH20 Patents Unpatentable While Institution is Denied for Third Patent; Keytruda Qlex™ Updates: PTAB Finds Additional Halozyme PH20 Patent Unpatentable in Final Written Decision), the Board found that the specification’s single-substitution data and limited disclosure regarding multiply modified PH20 polypeptides did not sufficiently describe or enable the full scope of the challenged claims.

The Board did not find the challenged claims unpatentable as obvious. Consistent with the Board’s reasoning in a prior FWD involving a related Halozyme PH20 patent (previously reported Keytruda Qlex™ Updates: PTAB Finds Additional Halozyme PH20 Patent Unpatentable in Final Written Decision), the Board found that Merck had not shown a sufficient reason to make the particular claimed PH20 modification. Here, the Board found that Merck had not provided a persuasive reason to target position 324 for modification, and therefore did not find the challenged claims unpatentable as obvious.

Separately, in a bulk opinion, the PTAB instituted three additional IPRs involving Halozyme patents related to the Keytruda Qlex™ dispute: IPR2026-00312, IPR2026-00313, and IPR2026-00314. Those IPRs challenge U.S. Patent Nos. 10,865,400, 11,041,149, and 11,066,656, respectively, each of which is also at issue in the co-pending New Jersey litigation between Merck and Halozyme, Case No. 2:25-cv-03179 (D.N.J.).

Keytruda Qlex™ was approved in September 2025 and generated approximately $40 million in 2025 sales, including approximately $35 million in the fourth quarter of 2025.

For more information about these and other biologic drug patent disputes, please visit BiologicsHQ.

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The authors would like to thank April Breyer Menon for her contributions to this article.