| abstract |
The present invention relates to the discovery, preparation of novel soluble neutrally active hyaluronidase glycoproteins (sHASEGPs), and their use to facilitate the administration of other molecules or to mitigate glycosaminoglycan related pathologies. The minimum active polypeptide domain of the soluble neutral active sHASEGP domain is disclosed to contain the asparagine-linked sugar moiety required for the functional neutral active hyaluronidase domain. Included are modified amino terminal leader peptides that increase the secretion of sHASEGP. The present invention further includes sialated and PEGylated forms of recombinant sHASEGP to improve stability and serum pharmacokinetics as compared to natural slaughterhouse enzymes. Further disclosed is the suitable formation of substantially purified recombinant sHASEGP glycoproteins derived from eukaryotic cells that produce the appropriate glycosylation necessary for optimal activity. |