Formulations of human tissue kallikrein-1 for parenteral delivery and related methods

摘要

Provided are high concentration compositions of tissue kallikrein-1 (KLK1) and methods of parenterally administering such compositions to a subject in need thereof, where absorption into the circulation via, for example, intravenous or subcutaneous administration improves systemic pharmacokinetics, bioavailability, safety, and/or convenience relative to intravenous or other forms of administration. Also provided are recombinant human KLK1 (rhKLK1) polypeptides that can be readily concentrated to high protein concentrations, and substantially pure compositions thereof.

主权项

1. A method of treating a subject in need thereof, the method comprising subcutaneously administering to the subject a composition formulated for parenteral administration, the composition comprising a recombinant mature human tissue kallikrein-1 (hKLK1) polypeptide isolated from recombinant mammalian cells and a pharmaceutically acceptable carrier, where the mature hKLK1 polypeptide has a pI of less than about 5 and a sialic acid content of at least about 4 moles per mole protein, where the composition is substantially free of aggregates (greater than about 95% appearing as a single peak by SEC HPLC) and has endotoxin levels of less than about 1 EU/mg protein, host cell protein of less than about 100 ng/mg protein, and host cell DNA of less than about 10 pg/mg protein, and where administering the composition subcutaneously produces improved systemic pharmacokinetics relative to intravenous administration of the composition, thereby treating the subject.