Chimeric hirudin proteins
AssigneeCanadian Blood Services
InventorWilliam P. Sheffield
Life of this patent
Estimating the term…
Abstract
The present invention relates to a chimeric hirudin protein comprising a carrier attached to the N-terminus of hirudin, with an intervening plasmin cleavage site. The chimeric hirudin protein contains a relatively inactive form of hirudin. However, when such chimeric hirudin protein being cleaved by plasmin in the vicinity of a clot and, ultimately causing the release of active hirudin and the reduction of the size of the clot. The chimeric hirudin protein exhibited much slower clearance in mice than unfused wild-type hirudin.
Claims11
A chimeric hirudin protein comprising in this specific order:
- a carrier protein having a molecular weight equal to or greater than 40 kDa and being physiologically acceptable;
- a plasmin cleavage site covalently attached through its amino terminus to the carrier protein and consisting of the amino acid sequence of SEQ ID NO:7 or SEQ ID NO:
- 13;
- a scissile peptide bond covalently attached to the carboxyl terminus of said plasmin cleavage site;
- and
- a latent hirudin covalently and directly attached by its amino terminus to said scissile peptide bond on the carboxyl terminus of said plasmin cleavage site, wherein when cleaved at said scissile peptide bond in the presence of plasmin the latent hirudin is released from said chimeric hirudin protein as activated hirudin.
The chimeric hirudin protein of claim, wherein said hirudin is a hirudin variant 3.
Dependencies are inferred from the claim text.