Recombinant elastase proteins and methods of manufacturing and use thereof

摘要

The present invention relates to methods for the manufacture, purification, formulation, and use of biologically active recombinant elastase proteins. Described are recombinant methods for producing therapeutically useful elastase proteins, as are pharmaceutical compositions comprising said elastase proteins. Novel recombinant elastase proteins and protein preparations are also disclosed. Methods are described for treating and preventing diseases of biological conduits using pharmaceutical compositions containing the elastase proteins of the invention.

主权项

1. A method of producing a mature type I pancreatic elastase protein comprising subjecting a recombinant autoactivated type I pancreatic proelastase protein to autoactivation conditions, contacting a recombinant autoactivated type I pancreatic proelastase protein with a catalytic amount of elastase, or both, said recombinant autoactivated type I pancreatic proelastase protein comprising an amino acid sequence of an elastase activation peptide sequence operably linked to an amino acid sequence of a mature type I pancreatic elastase, wherein the activation peptide is not native to the mature type I pancreatic elastase protein, and wherein:
(a) the mature type I pancreatic elastase protein is a mature human type I pancreatic elastase protein and wherein the recombinant autoactivated type I pancreatic proelastase protein elastase comprises a recognition sequence of the amino acid sequence of SEQ ID NO:20; or (b) the mature type I pancreatic elastase protein is a mature porcine type I pancreatic elastase protein and the recombinant autoactivated type I pancreatic proelastase protein has a propeptide sequence comprising the amino acid sequence of SEQ ID NO:117 or SEQ ID NO:118, thereby producing a mature type I pancreatic elastase protein.