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US 2010/0137214 A1Published application
Chimeric hirudin proteins
AssigneeCanadian Blood Services
InventorWilliam P. Sheffield
Life of this patent
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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.
Claims21
A chimeric hirudin protein comprising:
- a carrier 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 and having the following sequence:
- NH2-X1-X2-X3-X4-X5-X6-COOH
- wherein:
- X1, X2 and X5 are the same or different and are an uncharged polar amino acids;
- X3 is an hydrophobic amino acid or an uncharged polar amino acid;
- X4 is an hydrophobic amino acid;
- and
- X6 is a basic hydrophilic amino acid.
- a hirudin covalently attached by its amino-terminus to the carboxy terminus of said plasmin cleavage site,
- wherein said hirudin is releasable from said chimeric hirudin protein in the presence of plasmin.
8 more elements
Dependencies are inferred from the claim text.