On May 12, 2026, the Patent Trial and Appeal Board (“PTAB”) issued a Final Written Decision (“FWD”) in PGR2025-00003 finding all challenged claims of Halozyme’s U.S. Patent No. 11,952,600 (“the ’600 patent”) unpatentable. On May 15, 2026, the Director of the U.S. Patent and Trademark Office issued a bulk order denying institution of PGR2025-00087 involving Halozyme’s U.S. Patent No. 12,371,685 (“the ’685 patent”), and on May 18, 2026, the PTAB issued a FWD in PGR2025-00006 finding all challenged claims of Halozyme’s U.S. Patent No. 12,152,262 (“the ’262 patent”) unpatentable. All of the patents were challenged by Merck and are part of a broader dispute between Merck and Halozyme relating to Keytruda Qlex™ (pembrolizumab; berahyaluronidase alfa-pmph) and Halozyme’s PH20 hyaluronidase patent portfolio.
PGR2025-00003 and PGR2025-00006 FWDs
The ’600 and ’262 patents are directed to modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity. Merck challenged the patents on written description, enablement, and obviousness grounds, arguing that the claims covered very broad genera of modified PH20 proteins defined through sequence identity limitations and amino acid substitutions.
In its PGR2025-00003 FWD, the PTAB concluded that Merck had demonstrated by a preponderance of the evidence that challenged claims 1–4 and 8–21 of the ’600 patent were unpatentable for lack of written description and enablement, but were not unpatentable as obvious.
In its discussion of claim construction, the Board found that the claims, while not expressly reciting a function for the claimed modified PH20 polypeptides, required hyaluronidase activity for several reasons, including intrinsic evidence in the patent specification that defined the polypeptide as requiring activity.
In its discussion of written description, the Board found that the claims defined an enormous genera of approximately 1063 distinct polypeptides, and the specification lacked teaching on how to determine which modified polypeptides would retain hyaluronidase activity, including a lack of disclosure of sufficient structural features in the PH20 sequences associated with hyaluronidase or contraceptive activity. The Board found that the claims allowed up to 23 modifications, and modeling software as of the priority date became unreliable at predicting structure and function after 2-3 modifications. The Board found that the specification only referenced seven examples having more than one modification (up to three) and was not representative of the breadth of the claims covering up to 23 modifications, particularly because multiple modifications greatly complicated the interactions and caused unpredictability in determining whether the protein would retain hyaluronidase activity. The Board also found that there was not adequate evidence that inactive modified polypeptides could serve as antigens to provide a contraceptive effect.
In its discussion of enablement, the Board recognized the approximately 6,000 single-replacement examples in the specification, about 2,500 of which were active, and information about which positions were more tolerant to changes, but found this insufficient to enable the immense number of claimed polypeptides, particularly because more than half of the working examples would not have been covered by the claims because they were inactive, there was very limited guidance on how to identify which of the 1049 modified polypeptides would retain their activity, and there were no examples of inactive polypeptides that provided a contraceptive effect. The Board found that the specification lacked information for polypeptides with multiple substitutions, and accepted expert testimony showing that a POSA at the time of the invention could not have predicted whether a polypeptide with more than five changes would be enzymatically active. The Board determined that knowing how structural modifications to PH20 polypeptides affected hyaluronidase activity was unpredictable at the time of the invention, and that an undue amount of experimentation was needed to practice the full scope of the claims.
The Board found that the claims were nonobvious because the prior art did not teach the particular claimed PH20 modifications.
In PGR2025-00006, the PTAB concluded that Merck had demonstrated by a preponderance of the evidence that claims 1–4 and 8–13 of the ’262 patent were unpatentable for a lack of written description and enablement and were nonobvious, using a similar analysis as in PGR2025-00003.
PGR2025-00087 Institution Decision
Merck’s PGR2025-00087 challenged claims 1–10 of the ’685 patent, which is directed to modified PH20 hyaluronidase polypeptides exhibiting increased hyaluronidase activity. The petition asserted written description and enablement grounds under 35 U.S.C. § 112, arguing that the challenged claims covered very broad genera of modified PH20 proteins defined through sequence identity limitations and amino acid substitutions.
The Director denied institution after review of discretionary and non-merits considerations. Unlike in the earlier Halozyme PGR proceedings that were instituted, the Director did not reach the merits of the asserted invalidity grounds before denying institution. As part of the recent change to PTAB procedure, the opinion was issued as part of a bulk order without any analysis, so there is no discussion of how this PGR differed from others that were instituted and decided.
There is one co-pending New Jersey litigation between Merck and Halozyme, Case No. 2:25-cv-03179 (D.N.J.) and 12 PGRs that have been instituted and are awaiting FWDs.
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.
