Canadian Blood Services

Mcmaster University

University of Ottawa

William Peter Sheffield

David Apraku Donkor

Adolfo J De Bold

Mercedes L Kuroski De Bold

The present disclosure concerns aptamers of formula (I) capable of specifically binding to Factor XIa. The aptamers can be used to prevent, treat or alleviate the symptoms of thrombosis. The aptamers can also be used to detect Factor XIa in a sample and/or purify Factor XIa from a sample. The aptamers can further be used to identity putative therapeutic agents for the prevention, treatment or alleviation of symptoms associated with thrombosis.

Factor XIa-specific aptamers

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.

Chimeric hirudin proteins

A fusion protein comprising an arterial natriuretic factor (ANF) amino acid sequence linked to an albumin amino acid sequence by one or more peptide bonds is provided. The ANF amino acid sequence may be linked to the N-terminal, the C-terminal, or both the N-terminal and the C-terminal of the albumin amino acid sequence. Also provided is a nucleic acid molecule encoding the fusion protein and a vector comprising the nucleic acid molecule. Methods for treating or preventing cardiovascular or renal disease comprising administration of an effective amount of the fusion protein, or nucleic acid encoding the fusion protein, are also disclosed.

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Hamilton, Canada

William Peter Sheffield