Modified annexin proteins and methods for preventing thrombosis

Details Modified annexin proteins and methods for preventing thrombosis Modified annexin proteins and methods for preventing thrombosis

A - Human Necessities

61

K

A61K 38/17 (2006.01)

Patent

CA 2559167

A modified annexin protein, preferably annexin V, is used to prevent thrombosis without increasing hemorrhage. Annexin binds to phosphatidylserine on the outer surface of cell membranes, thereby preventing binding of the prothrombinase complex necessary for thrombus formation. It does not, however, affect platelet aggregation necessary for hemostasis. The modified annexin molecule can be a homodimer of annexin, an annexin molecule coupled to one or more polyethylene glycol chains, or an annexin molecule coupled to another protein. By increasing the molecular weight of annexin, the modified annexin is made to remain in circulation for sufficient time to provide a sustained therapeutic effect.

L'invention concerne une protéine d'annexine modifiée, de préférence de l'annexine V, utilisée afin de prévenir la thrombose sans augmentation d'hémorragie. L'annexine se lie à la phosphatidylsérine sur la surface extérieure des membranes cellulaires, empêchant ainsi la liaison du complexe prothrombinase nécessaire à la formation d'un thrombus. Cependant, il n'affecte pas l'agrégation plaquetaire nécessaire à l'hémostase. La molécule d'annexine modifiée peut consister en un homodimère d'annexine, une molécule d'annexine couplée à une ou plusieurs chaînes de polyéthylène glycol, ou une molécule d'annexine couplée à une autre protéine. Par augmentation du poids moléculaire d'annexine, l'annexine modifiée peut rester en circulation durant un temps suffisant aux fins de fournir un effet thérapeutique soutenu.

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