Intracellular delivery of charged therapeutic moieties to...

A - Human Necessities – 61 – K

Patent

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A61K 47/48 (2006.01) A61P 25/00 (2006.01)

Patent

CA 2436830

A method for improving intercellular administration of a therapeutic agent is provided comprising: contacting cells with a compound comprising a charged derivative of a therapeutic agent, the charged derivative being conjugated to a protein having a biological activity of being transported across a cell membrane into a cell; and having the transport the compound into the cell, where the cell metabolizes at least a portion of the compound to form a charged metabolite product that possesses the therapeutic activity of the therapeutic agent, the charged metabolite product being less prone to being transported across the cell membrane out of the cell relative to the compound and less prone to being transported across the cell membrane out of the cell relative to the therapeutic agent. For example, the target cells are nerve cells and the protein is selected from nerve growth factors, antibodies to nerve cell surface receptors, and members of the nerve growth factor family (e.g. MGF, BDMF, MT-4, NT-6).

Cette invention concerne une méthode propre à améliorer l'administration intracellulaire d'un agent thérapeutique. Cette méthode consiste à: mettre des cellules en contact avec un composé qui renferme un dérivé chargé d'agent thérapeutique doté d'une activité thérapeutique, ledit dérivé chargé étant conjugué à une protéine qui, de part son activité biologique, pénètre dans la cellule après avoir traversé la membrane cytoplasmique de la cellule; et utiliser la cellule pour transporter le composé à l'intérieur de ladite cellule, cette cellule métabolisant au moins une partie du composé pour former un produit métabolite chargé qui reprend l'activité thérapeutique de l'agent thérapeutique. Le produit métabolite chargé est moins enclin à quitter la cellule après en avoir traversé la membrane par rapport au composé, de même qu'il risque moins de quitter la cellule après en avoir traversé la membrane par rapport à l'agent thérapeutique.

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