IP Verse

Ph20 Polypeptide Variants, Formulations And Uses Thereof

Patent No. US12037618 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Therapeutics Inc on May 21, 2021.

What is this patent about?

’618 is related to the field of hyaluronidase enzymes , specifically modified forms of the PH20 hyaluronidase. Hyaluronidases degrade hyaluronan, a major component of the extracellular matrix, and are used to increase tissue permeability and enhance the delivery of therapeutic agents. Existing hyaluronidase products, often derived from ovine or bovine sources, can be immunogenic, highlighting the need for improved enzymes and compositions.

The underlying idea behind ’618 is to engineer PH20 hyaluronidase variants with improved properties, particularly increased stability . This is achieved by introducing specific amino acid modifications, such as replacements, deletions, or insertions, into the PH20 polypeptide sequence. The goal is to create modified enzymes that retain hyaluronidase activity while exhibiting enhanced resistance to denaturation under various conditions.

The claims of ’618 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 includes a modification at a position corresponding to position 309 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 using recombinant DNA technology, where the gene encoding the modified enzyme is expressed in a host cell, such as a mammalian cell line. The expressed enzyme is then purified and formulated into a pharmaceutical composition. The modifications are designed to enhance the enzyme's stability under conditions that would normally cause denaturation, such as elevated temperatures, agitation, or the presence of preservatives.

The advantage of this approach is that it provides a more stable and potentially less immunogenic hyaluronidase for therapeutic applications. By carefully selecting the amino acid modifications, the resulting enzyme retains its ability to degrade hyaluronan while exhibiting improved resistance to denaturation, leading to enhanced shelf-life and performance in pharmaceutical formulations. This contrasts with prior approaches that relied on animal-derived enzymes, which can be less stable and more prone to eliciting an immune response.

How does this patent fit in bigger picture?

Technical landscape at the time

In the early 2010s when ’618 was filed, hyaluronan was understood to be a key component of the extracellular matrix, at a time when hyaluronidases were typically used to degrade hyaluronan for therapeutic purposes. At that time, protein engineering to improve stability and activity was a common approach, when hardware or software constraints made protein modification and characterization non-trivial.

Novelty and Inventive Step

The claims were rejected as indefinite and for non-statutory double patenting. The examiner's reasoning was based on anticipation by prior art and lack of patentable distinction. The prosecution record does NOT describe the technical reasoning or specific claim changes that led to allowance, but indicates that the application is in condition for allowance except for formal matters.

Claims

This patent contains 40 claims, with claim 1 being the only independent claim. Independent claim 1 is focused 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 PH20 polypeptide, specifically 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 specific positions in SEQ ID NO: 3, as determined by 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. 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.”A PH20 polypeptide that has been altered by at least one amino acid replacement, deletion, or insertion, relative to an unmodified PH20 polypeptide.
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 a sequence of amino acids selected from SEQ ID NO: 3, 7, and 32-66, which serves as the basis for creating 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

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

US12037618

HALOZYME THERAPEUTICS INC
Application Number
US17327586
Filing Date
May 21, 2021
Status
Granted
Expiry Date
Jul 20, 2034
External Links
Slate, USPTO, Google Patents