Dosage forms of tissue kallikrein 1
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Publication Number
US-12329805-B2
Publication Date
2025-06-17
Expiration Date
Abstract
Provided are dosage forms of one or more tissue kallikrein-1 (KLK1) polypeptides which have a total KLK1 polypeptide dosage of about 0.1 μg/kg to about 10.0 μg/kg, including subcutaneous and intravenous dosage forms. Also provided are related devices and methods of use thereof, for example, for treating ischemic and hemorrhagic conditions.
Core Innovation
The disclosed invention relates to treating vascular dementia in a subject in need thereof by subcutaneously or intravenously administering a dosage form comprising tissue kallikrein (KLK1) polypeptides. The dosage form includes a first KLK1 polypeptide and a second KLK1 polypeptide formulated at a total KLK1 polypeptide dosage of 0.5 μg/kg to 5.0 μg/kg.
The first KLK1 polypeptide has three N-linked glycans attached at residues 78, 84, and 141 as defined by SEQ ID NO: 3 or 4, while the second KLK1 polypeptide has two N-linked glycans attached at residues 78 and 84 but not 141 as defined by SEQ ID NO: 3 or 4. The first and second KLK1 polypeptides are present at a ratio of about 45:55 to about 55:45.
The document further describes product and formulation constraints for the KLK1-containing dosage form, including being substantially free of other glycosylated isoforms (glycoforms) of KLK1. It also specifies limits and criteria related to impurities and aggregation, including endotoxin, host cell protein, host cell DNA, and aggregation assessed by SEC HPLC single-peak criteria.
Claims Coverage
The claims center on 5 inventive features involving treatment of vascular dementia with a defined KLK1 glycoform mixture at a specified total dosage, with additional purity and quality constraints in dependent claims.
Treating vascular dementia with subcutaneous or intravenous KLK1 glycoform mixture
A method of treating vascular dementia in a subject in need thereof, comprising subcutaneously or intravenously administering a dosage form comprising a first tissue kallikrein (KLK1) polypeptide and a second KLK1 polypeptide formulated at a total KLK1 polypeptide dosage of 0.5 μg/kg to 5.0 μg/kg.
Three-glycan vs two-glycan KLK1 polypeptides at defined residues
The first KLK1 polypeptide has three N-linked glycans attached at residues 78, 84, and 141 as defined by SEQ ID NO: 3 or 4, and the second KLK1 polypeptide has two N-linked glycans attached at residues 78 and 84 but not 141 as defined by SEQ ID NO: 3 or 4.
Defined mixture ratio of the two KLK1 polypeptides
The first KLK1 polypeptide and the second KLK1 polypeptide are present in the dosage form at a ratio of about 45:55 to about 55:45.
Substantially free of other glycosylated isoforms
The dosage form is substantially free of other glycosylated isoforms (glycoforms) of KLK1.
Impurity and aggregation criteria by endotoxin, HCP, host-cell DNA, and SEC HPLC single peak
The dosage form meets specified impurity and aggregation criteria, with endotoxin, host cell protein, host cell DNA, and aggregation determined by SEC HPLC criteria including greater than about 95% appearing as a single peak.
The claims are directed to treating vascular dementia using a subcutaneous or intravenous KLK1 dosage form defined by two KLK1 glycoforms, a specified total dosage, a defined mixture ratio, and additional purity and aggregation criteria.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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