| abstract |
The invention relates to the discovery of active, neutral, soluble hyaluronidase glycoproetins (sHASEGP's), novel, manufacturing methods, and their use to facilitate the administration of other molecules or to alleviate pathologies associated with glycosaminoglycan. Minimally active polypeptide domains of the active, neutral, soluble sHASEGP domains are described, including asparagine-linked sugar moieties required for an active, neutral, functional hyaluronidase domain. Modified amino-terminal leader peptides that increase sHASEGP secretion are included. The invention further comprises isolated and pegylated forms of recombinant sHASEGP to increase stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Suitable formulations of recombinant, substantially purified sHASEGP glycoprotein derived from a eukaryotic cell that generates the glycosylation required for optimal activity are also described. |