IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US11066656 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on Jun 25, 2020.

What is this patent about?

’656 is related to the field of modified hyaluronidase enzymes , specifically PH20 variants. Hyaluronidases degrade hyaluronan, a major component of the extracellular matrix, and are used to enhance drug delivery and treat hyaluronan-associated diseases. Existing hyaluronidase formulations often suffer from instability issues, requiring improvements to enzyme stability and activity.

The underlying idea behind ’656 is to engineer PH20 variants with improved properties by introducing specific amino acid replacements. The key inventive insight is that certain amino acid substitutions, particularly at residue 309 (with reference to SEQ ID NO:3), can lead to a modified PH20 polypeptide that exhibits increased hyaluronidase activity compared to the unmodified enzyme. This addresses the need for more effective and stable hyaluronidase formulations.

The claims of ’656 focus on a modified PH20 polypeptide that contains one or more amino acid replacements in an unmodified PH20 polypeptide. The unmodified PH20 polypeptide must have an amino acid sequence selected from SEQ ID NOs: 3, 7, and 32-66, and the modified PH20 polypeptide must exhibit increased hyaluronidase activity. Crucially, the independent claim specifies that at least one amino acid replacement that confers the increased hyaluronidase activity must be at a position corresponding to residue 309, with reference to amino acid positions of SEQ ID NO:3. The modified PH20 polypeptide must also have at least 91% sequence identity to the amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 7 and 32-66.

In practice, the invention involves identifying suitable amino acid replacements at the specified positions through mutagenesis and screening. The modified PH20 polypeptide is then produced using recombinant DNA technology, expressed in a suitable host cell (e.g., CHO cells), and purified. The resulting enzyme exhibits enhanced hyaluronidase activity, making it more effective at degrading hyaluronan.

This approach differs from prior art by specifically targeting amino acid replacements at residue 309 to enhance hyaluronidase activity. While previous efforts focused on improving stability or reducing immunogenicity, ’656 provides a method for creating PH20 variants with superior enzymatic performance . The resulting modified enzymes are expected to be more efficient in drug delivery and other therapeutic applications, offering a significant advantage over existing hyaluronidase products. The increased stability of the modified PH20 polypeptide is also a key factor in its improved performance.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’656 was filed, hyaluronan-degrading enzymes were typically implemented using recombinant protein expression and purification techniques at a time when protein stability was commonly addressed through formulation optimization. When hardware or software constraints made protein engineering for enhanced stability non-trivial, systems commonly relied on excipients and storage conditions to maintain activity rather than amino acid sequence modifications.

Novelty and Inventive Step

The examiner approved the application because the claimed modified PH20 polypeptide, which includes a specific amino acid substitution at residue 309, exhibits increased hyaluronidase activity compared to unmodified PH20. The prior art does not teach or suggest which amino acid residues are substituted to achieve increased hyaluronidase activity.

Claims

This patent contains 25 claims, with claim 1 being the only independent claim. Independent claim 1 is directed to a modified PH20 polypeptide with specific amino acid replacements that increase hyaluronidase activity. The dependent claims generally specify further limitations and embodiments of the modified PH20 polypeptide described in the independent claim.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Amino acid replacement(s)
(Claim 1)		“The modifications include amino acid replacement, deletion and/or insertions. For purposes herein, amino acid replacements are denoted by the single amino acid letter followed by the corresponding amino acid position in SEQ ID NO:3 in which the replacement occurs. Single amino acid abbreviations for amino acid residues are well known to a skilled artisan (see e.g. Table 1), and are used herein throughout the description and examples.”The substitution of one or more amino acid residues in a PH20 polypeptide sequence with different amino acid residues.
Increased hyaluronidase activity
(Claim 1)		“Also provided are modified PH20 polypeptides that contain at least one amino acid replacement in a PH20 polypeptide, where the modified PH20 polypeptide exhibits increased hyaluronidase activity compared to the PH20 polypeptide not containing the amino acid replacement. When comparing activity among polypeptides, activity is compared under the same conditions. Among the modified PH20 polypeptides are those that that exhibit at least 120%, 130%, 135%, 140%, 145%, 150%, 160%, 170%, 180%, 200%, 250%, 300%, 350%, 400%, 500%, 1500%, 2000%, 3000%, 4000%, 5000% or more of the hyaluronidase activity of the PH20 polypeptide not containing the amino acid replacement.”The modified PH20 polypeptide exhibits a higher level of hyaluronidase enzymatic activity compared to the unmodified PH20 polypeptide when measured under the same conditions.
Modified Ph20 polypeptide
(Claim 1)		“Provided are modified PH20 polypeptides that have an altered property or properties compared to the PH20 polypeptide that do not have the modification(s). The modifications include amino acid replacement, deletion and/or insertions. For purposes herein, amino acid replacements are denoted by the single amino acid letter followed by the corresponding amino acid position in SEQ ID NO:3 in which the replacement occurs.”A PH20 polypeptide that has been altered by amino acid replacement(s), insertion(s), and/or deletion(s) compared to an unmodified PH20 polypeptide.

Litigation Cases New

US Latest litigation cases involving this patent.

Case NumberFiling DateTitle
2:25-cv-03179Apr 10, 2025People Co. Ltd. V. Lakeshore Learning Materials, Llc

Patent Family

Patent Family

File Wrapper

The dossier documents provide a comprehensive record of the patent's prosecution history - including filings, correspondence, and decisions made by patent offices - and are crucial for understanding the patent's legal journey and any challenges it may have faced during examination.

  • Date

    Description

  • Get instant alerts for new documents

US11066656

HALOZYME INC
Application Number
US16912590
Filing Date
Jun 25, 2020
Status
Granted
Expiry Date
Dec 28, 2032
External Links
Slate, USPTO, Google Patents