Ph20 Polypeptide Variants, Formulations And Uses Thereof
Patent No. US12264345 (titled "Ph20 Polypeptide Variants, Formulations And Uses Thereof") was filed by Halozyme Inc on Jul 19, 2024.
What is this patent about?
’345 is related to the field of hyaluronidase enzymes , specifically focusing on modified versions of the PH20 hyaluronidase. Hyaluronidases are enzymes that degrade hyaluronan, a major component of the extracellular matrix. These enzymes are used to treat diseases associated with hyaluronan accumulation and to increase tissue permeability for drug delivery. Existing hyaluronidases, often derived from ovine or bovine sources, can be immunogenic in humans, creating a need for improved hyaluronidases with enhanced properties.
The underlying idea behind ’345 is to engineer PH20 hyaluronidase variants with improved characteristics, particularly increased stability and activity . This is achieved by introducing specific amino acid substitutions into the PH20 polypeptide sequence. The modifications are designed to enhance the enzyme's resistance to denaturation under various conditions, such as elevated temperature, agitation, low salt concentrations, and the presence of preservatives, while maintaining or even increasing its hyaluronidase activity.
The claims of ’345 focus on modified PH20 polypeptides containing a hyaluronidase domain corresponding to amino acids 3-339 of SEQ ID NO:7 and an amino acid replacement at the residue corresponding to M313 of SEQ ID NO:7, with the hyaluronidase domain containing up to 20 modifications. This claim structure covers a specific region of the PH20 enzyme with a defined modification, allowing for a range of other modifications within the specified domain.
The invention works by identifying specific amino acid residues within the PH20 polypeptide that, when replaced, result in a more stable and/or active enzyme. For example, replacing phenylalanine at position 204 with proline (F204P) significantly enhances the enzyme's stability in the presence of phenolic preservatives. The modified enzymes are produced using recombinant DNA technology, expressed in host cells, and then purified. The resulting modified PH20 polypeptides exhibit improved resistance to denaturation and maintain their hyaluronidase activity under conditions that would typically degrade the wild-type enzyme.
This approach differs from prior solutions by focusing on rational design through specific amino acid substitutions to enhance stability and activity, rather than relying solely on animal-derived enzymes or broad modifications. The resulting modified PH20 polypeptides are less likely to be immunogenic and can be formulated with a wider range of therapeutic agents and preservatives, leading to more effective and stable pharmaceutical compositions. The increased stability also allows for easier storage and handling of the enzyme, making it more suitable for therapeutic applications.
How does this patent fit in bigger picture?
Technical landscape at the time
In the early 2010s when ’345 was filed, hyaluronan was known as a key component of the extracellular matrix, and hyaluronidases were used to degrade hyaluronan. At a time when therapeutic hyaluronidases were typically derived from ovine or bovine sources, the potential for immunogenicity was a non-trivial engineering constraint. When protein formulations commonly relied on preservatives to ensure stability and prevent microbial growth, protein stability in the presence of such excipients was a key consideration.
Novelty and Inventive Step
The claims were amended during prosecution. The application was later rejected for non-statutory double patenting. The prosecution record does NOT describe the technical reasoning or specific claim changes that led to allowance.
Claims
This patent contains 17 claims, with claim 1 being the only independent claim. Independent claim 1 focuses on a modified PH20 polypeptide with a specific hyaluronidase domain and an amino acid replacement. The dependent claims generally elaborate on specific features, modifications, 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.
Litigation Cases New
US Latest litigation cases involving this patent.
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
US12264345
- Application Number
- US18778554
- Filing Date
- Jul 19, 2024
- Status
- Granted
- Expiry Date
- Dec 28, 2032
- External Links
- Slate, USPTO, Google Patents