US 12195773

US Patent 12195773, titled "PH20 polypeptide variants, formulations and uses thereof," was filed on May 9, 2024, and granted on January 14, 2025. The current assignee is Halozyme Inc. and Halozyme Therapeutics Inc. The inventors are Ge Wei, H. Michael Shepard, Qiping Zhao, and Robert James Connor.

The abstract of the patent describes modified PH20 hyaluronidase polypeptides, specifically those exhibiting increased stability and/or increased activity. The patent also covers compositions, formulations, and uses of these modified polypeptides.

Independent Claims Overview:

• Claim 1: This claim covers a modified PH20 hyaluronidase polypeptide. The modification involves at least one amino acid replacement, which leads to increased stability in the presence of a phenolic preservative. This increased stability means the modified polypeptide retains at least 15% of its hyaluronidase activity for at least 4 hours in the presence of the preservative. The unmodified PH20 polypeptide serves as a reference and either has the amino acid sequence of SEQ ID NO: 7, is a soluble C-terminal truncated fragment of SEQ ID NO: 7, or has at least 85% sequence identity to SEQ ID NO: 7.
• Claim 18: This claim is directed to a modified PH20 hyaluronidase polypeptide with at least one amino acid replacement that results in increased stability at elevated temperatures (specifically, greater than 30° C.). The increased stability is defined as retaining at least 95% of the hyaluronidase activity for at least 4 hours at a temperature between 32° C. and 37° C., when compared to its activity at a temperature between 2° C. and 8° C. The unmodified PH20 polypeptide is defined similarly to Claim 1.
• Claim 31: This claim describes a modified PH20 hyaluronidase polypeptide that has at least one amino acid replacement, resulting in increased hyaluronidase activity. The modified polypeptide must exhibit at least 120% of the hyaluronidase activity of the unmodified PH20 polypeptide (without the replacement). The unmodified PH20 polypeptide has at least 68% amino acid sequence identity to SEQ ID NO: 3.
• Claim 47: This claim covers a method for producing a modified PH20 hyaluronidase polypeptide. The method involves culturing a eukaryotic cell that contains a nucleic acid encoding such a modified PH20 polypeptide (where the modification alters stability and/or activity) and then recovering the polypeptide secreted by the cell. The amino acid replacement(s) are at positions corresponding to specific residues in SEQ ID NO: 3, and the unmodified PH20 polypeptide is defined as in Claim 1.
• Claim 53: This claim describes a pharmaceutical composition that includes a modified PH20 hyaluronidase polypeptide (as defined in Claim 1, demonstrating increased stability to a phenolic preservative) and an insulin.
• Claim 55: This claim outlines a method for identifying or selecting a modified hyaluronan-degrading enzyme that shows stability under denaturing conditions. The method involves testing the enzyme's activity in the presence of a denaturing agent/condition, comparing it to the activity in the absence of such an agent/condition, and then selecting enzymes that retain at least 5% of their activity in the denaturing environment.
• Claim 61: This claim describes another method for identifying or selecting a modified hyaluronan-degrading enzyme with increased stability under denaturing conditions. This method involves comparing the activity of a modified enzyme to its unmodified counterpart while both are exposed to a denaturing agent or condition. A modified enzyme is selected if it exhibits greater activity than the unmodified enzyme under these denaturing conditions.

CAFC 2026 Dockets:

A review of the provided information from Google Patents indicates that there is litigation related to this patent family. Specifically, a PTAB case (PGR2025-00053) was filed and instituted, and a US case was filed in the New Jersey District Court (2:25-cv-03179). While these indicate active litigation, the specific dockets for the CAFC in 2026 are not directly provided or confirmed by the given information. Additional live search of CAFC dockets for 2026 explicitly mentioning US12195773 would be needed to confirm any direct appellate activity at the CAFC level in 2026. However, the existence of PTAB and District Court litigation suggests potential for future CAFC involvement.