Microvesicles derived from recombinant yeast having haemostatic activities and uses thereof

摘要

Tissue factor-bearing yeast derived microvesicles comprising a yeast membrane and a tissue factor protein, or a fragment thereof, or a tissue factor protein or a fragment thereof fused to another peptide as a fusion protein having pro-coagulant activity are disclosed. Said products can be used as pro-coagulant agents in the treatment of hemorrhages in a subject.

主权项

1. A topical composition comprising a pharmaceutically acceptable vehicle and tissue factor (TF)-bearing yeast derived microvesicles, said TF-bearing yeast derived microvesicles comprising (i) a yeast membrane, and (ii) a tissue factor (TF) protein or a variant thereof having pro-coagulant activity, wherein a portion of said tissue factor (TF) protein or variant thereof having pro-coagulant activity is integrated in said yeast membrane, and wherein said TF variant thereof having pro-coagulant activity is a mature tissue factor protein having at least one modification selected from the group consisting of: the inclusion of a tag bound to the N-terminal or C-terminal domain; the elimination of the signal peptide; the modification of a N-glycosylation site to make it non-functional; the elimination of all or part of the domain responsible for binding to FVIIa; and the introduction of a mutation in the domain responsible for binding to FVIIa which results in a substantially reduced affinity for FVIIa.