IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12091692 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on May 21, 2021.

What is this patent about?

’692 is related to the field of hyaluronidase enzymes , specifically modified PH20 hyaluronidases. Hyaluronan (HA) is a key component of the extracellular matrix and interstitial barrier, playing roles in tissue permeability and various physiological processes. Hyaluronidases, like PH20, degrade HA and can be used to treat HA-associated diseases or to enhance the dispersion and delivery of therapeutic agents. Existing hyaluronidases, often derived from ovine or bovine sources, can be immunogenic in humans, creating a need for improved enzymes and compositions.

The underlying idea behind ’692 is to engineer PH20 hyaluronidase to improve its properties, particularly its stability and activity . This is achieved through amino acid modifications, including replacements, deletions, and insertions, guided by detailed structure/function knowledge of the PH20 polypeptide. The goal is to create modified PH20 polypeptides that retain enzymatic activity while exhibiting increased resistance to denaturation under various conditions, such as elevated temperature, agitation, low salt, and the presence of denaturing excipients.

The claims of ’692 focus on a modified PH20 polypeptide that includes one or more amino acid modifications in an unmodified PH20 polypeptide. The unmodified PH20 polypeptide consists of the amino acid sequence selected from the group consisting of SEQ ID NO: 3, 7 and 32-66. The modified PH20 polypeptide comprises a modification at a position corresponding to position 313 with reference to amino acid positions of SEQ ID NO:3. The modified PH20 polypeptide has at least 91% sequence identity to the amino acid sequence selected from the group consisting of SEQ ID NO: 3, 7 and 32-66.

In practice, the modified PH20 polypeptide is produced recombinantly, often in mammalian cells like CHO cells to ensure proper glycosylation. The modified enzyme's activity and stability are then assessed under various stress conditions, such as elevated temperatures or in the presence of preservatives. The most promising variants are those that maintain a high level of hyaluronidase activity even when subjected to these denaturing conditions, indicating improved robustness for pharmaceutical applications.

This approach differs from prior art by providing specific modifications to the PH20 enzyme that enhance its stability and activity, particularly in the presence of common formulation excipients like phenolic preservatives. This is crucial for creating stable, multi-dose formulations of PH20 that can be used to improve the delivery of other therapeutic agents or to treat HA-associated diseases, overcoming the limitations of existing hyaluronidase products that may be less stable or immunogenic.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’692 was filed, at a time when X was typically implemented using Y, when systems commonly relied on Z rather than A, and when hardware or software constraints made B non-trivial. Specifically, hyaluronan-degrading enzymes were known and used therapeutically, but improved enzymes with altered properties, such as increased stability, were needed. Formulations often included preservatives to maintain sterility, but these could sometimes destabilize the protein.

Novelty and Inventive Step

The examiner approved the application because the claimed polypeptide, which has a modification at a position corresponding to position 313 of SEQ ID NO:3 and at least 91% sequence identity to SEQ ID NOs: 3, 7, and 32-66, is not taught or suggested by the prior art.

Claims

This patent contains 40 claims, with claim 1 being the only independent claim. Independent claim 1 focuses on a modified PH20 polypeptide with specific amino acid modifications. The dependent claims generally elaborate on the characteristics, compositions, and uses 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 modifications
(Claim 1)		“The modifications include amino acid replacement, deletion and/or insertions. Detailed structure/function of virtually each amino acid in a PH20 polypeptide is provided herein, as well as the identification of residues and loci that contribute to alteration of a property, such as stability in particular conditions, is provided.”Changes to the amino acid sequence of the unmodified PH20 polypeptide, specifically amino acid replacements, deletions, and/or insertions.
Corresponding amino acid positions
(Claim 1)		“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.”Amino acid positions in a PH20 polypeptide that align with positions in SEQ ID NO:3, determined through sequence alignment.
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.”A PH20 polypeptide that has been altered by at least one amino acid replacement, deletion, or insertion, relative to an unmodified PH20 polypeptide.
Sequence identity
(Claim 1)		“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.”The percentage of identical amino acid residues between the modified PH20 polypeptide and the amino acid sequence of SEQ ID NO: 3, 7 or 32-66.
Unmodified PH20 polypeptide
(Claim 1)		“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 having the amino acid sequence of SEQ ID NO: 3, 7 or 32-66, which serves as the basis for introducing modifications to create the modified 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

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US12091692

HALOZYME INC
Application Number
US17327568
Filing Date
May 21, 2021
Status
Granted
Expiry Date
Nov 28, 2034
External Links
Slate, USPTO, Google Patents