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US 5,326,700 AGranted
DNA sequences encoding t-PA derivatives with cleavable sites
AssigneeEli Lilly and Company
InventorsDavid T. Berg, Brian W. Grinnell
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Abstract
The invention concerns compounds and methods for the recombinant production of a homogeneous population of tissue plasminogen activator molecules and derivatives thereof through the use of heterologous propeptide regions that are uniformly cleaved upon secretion from the host cell.
Claims7
A recombinant DNA molecule that comprises a DNA sequence encoding a protein comprising, from amino-terminus to carboxy-terminus:
- a) a t-PA signal peptide;
- b) a t-PA propeptide region which contains an amino acid sequence that is capable of being uniformly cleaved by a mammalian cell associated protease, said amino acid sequence selected from the group consisting of;
- Arg Ile Xaa Xaa Xaa (SEQ. ID NO:7):
- Ser Arg Xaa Xaa Xaa (SEQ. ID NO:8):
- Glu Arg Xaa Xaa Xaa (SEQ. ID NO:9):
- and Val Arg Xaa Xaa Xaa (SEQ. ID NO:10), wherein the amino acids at positions Xaa are Lys or Arg;
- and
- c) a human tissue plasminogen activator derivative lacking the Finger, Growth Factor and Kringle 1 domains.
5 more elements
Dependencies are inferred from the claim text.