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Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12018298 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on Jun 23, 2023.

What is this patent about?

’298 is related to the field of hyaluronidase enzymes, specifically modified versions of the PH20 hyaluronidase. Hyaluronidases degrade hyaluronan, a major component of the extracellular matrix. Native PH20 is a sperm-associated protein involved in fertilization. There is a need for improved hyaluronan-degrading enzymes with altered properties, such as increased stability and activity, for therapeutic applications.

The underlying idea behind ’298 is to engineer PH20 variants with improved characteristics by modifying the amino acid sequence. The inventors recognized that specific amino acid substitutions could enhance the enzyme's stability and activity. By modifying the amino acid at position 313 of the PH20 polypeptide, the resulting enzyme exhibits altered properties.

The claims of ’298 focus on a modified PH20 polypeptide with at least 95% sequence identity to SEQ ID NO: 3 or 32-66, containing an amino acid replacement at position 313 (relative to SEQ ID NO:3). The replacement amino acid must be selected from the group consisting of A, H, K, L, P, R, and Y. Thus, the claims cover a specific set of PH20 variants with a defined mutation .

In practice, the invention involves creating a library of PH20 variants, each with a different amino acid at position 313. These variants are then screened for desired properties, such as increased stability or activity. The patent suggests that these modifications can lead to a PH20 enzyme that is more robust and effective in degrading hyaluronan under various conditions.

This approach differs from prior art by focusing on specific amino acid modifications to improve PH20's properties. While previous hyaluronidases might have been derived from different sources or modified in other ways, ’298 targets a particular residue for replacement, aiming to create a more stable and active enzyme for therapeutic use. The resulting modified PH20 polypeptide can be used to enhance drug delivery or treat hyaluronan-associated diseases.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’298 was filed, hyaluronan-degrading enzymes were already used to treat diseases associated with hyaluronan accumulation and to increase tissue permeability for drug delivery. At a time when many hyaluronidases used therapeutically were derived from ovine or bovine sources, the immunogenicity of these animal-derived enzymes in humans was a known limitation. Thus, improved hyaluronan-degrading enzymes with reduced immunogenicity and enhanced properties were needed.

Novelty and Inventive Step

The examiner approved the application because the claims relate to a modified PH20 polypeptide with specific amino acid modifications. The examiner noted that the instant specification discloses that PH20 hyaluronidase has been shown to treat various tumors and cites references demonstrating anti-cancer and other therapeutic benefits of hyaluronidases. The examiner stated that the instant specification's disclosure that the modified PH20 polypeptides are at least as effective hyaluronidases as the natural PH20 protein indicates that the modified PH20 polypeptides are capable of use in the claimed manner.

Claims

This patent contains 22 claims, with claim 1 being the sole independent claim. Independent claim 1 focuses on a modified PH20 polypeptide with specific amino acid sequence identity and a modification at position 313. The dependent claims generally elaborate on specific characteristics of the modified polypeptide, nucleic acids encoding it, vectors and host cells containing the nucleic acids, pharmaceutical compositions containing the polypeptide, and methods of using the pharmaceutical compositions for drug delivery and cancer treatment, as well as a method for manufacturing the modified polypeptide.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Amino acid modification
(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. For example, replacement with P at a position corresponding to position 204 in a PH20 polypeptide with reference to amino acid residue positions set forth in SEQ ID NO:3 means that the replacement encompasses F204P in a PH20 polypeptide set forth in SEQ ID NO:3, or the same replacement at the corresponding position in another PH20 polypeptide.”An alteration to the amino acid sequence of a PH20 polypeptide, specifically a replacement at a position corresponding to position 313 with reference to amino acid positions set forth in SEQ ID NO: 3, wherein the replacement is selected from among A, H, K, L, P, R, and Y.
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. The modified PH20 polypeptide can be one in which the unmodified form thereof has at least about 68% sequence identity to SEQ ID NO: 3 and further contains modifications that alter stability and/or can be a PH20 polypeptide that includes as many as about up to 100, 110, 120, 130, 150 amino acid differences from PH20 but retains enzymatic activity, particularly, at least about 40% of the activity of the unmodified PH20 polypeptide and exhibits increased stability, such as stability under denaturing conditions.”A PH20 polypeptide that has been altered by at least one amino acid modification, such as a replacement, insertion, or deletion, compared to a reference PH20 polypeptide. The modified polypeptide retains at least 95% sequence identity to SEQ ID NO: 3 or 32-66.

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

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US12018298

HALOZYME INC
Application Number
US18340482
Filing Date
Jun 23, 2023
Status
Granted
Expiry Date
Dec 28, 2032
External Links
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