Methods for reducing adverse side effects associated with...

A - Human Necessities – 61 – K

Patent

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Details

A61K 48/00 (2006.01) A61K 31/20 (2006.01) A61K 31/7088 (2006.01) A61K 31/715 (2006.01) A61K 35/14 (2006.01) A61K 35/28 (2006.01) A61K 38/00 (2006.01) A61K 39/395 (2006.01) A61P 7/04 (2006.01) A61P 19/08 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2356834

The methods of the present invention are based on the discovery that adverse side effects (such as hemorrhage) can occur upon infusion of cells that express tissue factor. Accordingly, the methods of the invention are aimed at reducing the biological activity of tissue factor (TF) in a patient, and can be carried out by, for example: infusing fewer cells (or infuse the same number of BMSCs over a longer period of time); reducing the expression or activity of TF (within the infused cells specifically) (e.g., by contacting the cells with a TF antagonist in vitro) or within the patient generally (e.g., by administering a TF antagonist to the patient); hampering the interaction of TF with factor VII(a); inhibiting the activity of the TF-factor VII(a) complex once it has formed; or inhibiting the coagulation cascade at any point downstream from formation of the complex (including inhibition of platelet activation).

La présente invention concerne des méthodes basées sur la découverte que des effets secondaires fâcheux (tels qu'une hémorragie) peuvent se produire après une injection de cellules exprimant une thromboplastine tissulaire. Ainsi, les méthodes de la présente invention sont destinées à la réduction de l'activité biologique d'une thromboplastine tissulaire chez un patient et consistent, par exemple: à injecter moins de cellules (ou à injecter le même nombre de cellules stromales de la moelle osseuse pendant une durée plus longue); à réduire l'expression ou l'activité de la thromboplastine tissulaire, notamment dans les cellules injectées (par exemple par mise en contact des cellules avec un antagoniste de thromboplastine tissulaire in vitro) ou dans le corps du patient en général (par exemple par administration d'un antagoniste de thromboplastine tissulaire au patient); à contrarier l'interaction de la thromboplastine tissulaire avec le facteur VII(a); à inhiber l'activité du complexe thromboplastine tissulaire-facteur VII(a) après sa formation; ou à inhiber la cascade de coagulations à n'importe quel point en aval de la formation du complexe (y compris l'inhibition de l'activation plaquettaire).

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