Anti-inflammatory containing monoclonal antibodies having...

A - Human Necessities – 61 – K

Patent

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Details

A61K 39/395 (2006.01) C07K 16/18 (2006.01) C07K 16/28 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2182215

A leukocyte rolling inhibitor, a leukocyte adhesion inhibitor, an inhibitor of infiltration of leukocytes into tissues and an anti- inflammatory agent, comprising a monoclonal antibody having reactivity to a sialyl Lewis X sugar chain derived from vascular endothelial cell membrane of a nonlymphoid tissue (e.g., brain, trachea, lung, liver, heart, pancreas, intestine, mesentery, kidney, skin and joint), preferably a monoclonal antibody further having reactivity to a sialyl Lewis X sugar chain derived from a cell membrane of leukocytes. The monoclonal antibody of the present invention combinedly has the anti-inflammatory actions that known monoclonal antibodies to L-, E- or P-selectin protein have. In addition, it has effects of inhibiting rolling and adhesion of leukocytes on vascular endothelial cell membrane, and of inhibiting infiltration of leukocytes into extravascular tissues in the very early stages of inflammatory responses in local tissue. According to the present invention, therefore, a potent anti-inflammatory agent based on a new action mechanism heretofore unknown can be provided.

Cette invention se rapporte à un inhibiteur de roulement de leucocytes, à un inhibiteur d'adhésion de leucocytes, à un inhibiteur d'infiltration des leucocytes dans les tissus, ainsi qu'à un anti-inflammatoire, contenant chacun des anticorps monoclonaux ayant une réactivité avec les chaînes de sucres sialyl-Lewis X prenant naissance dans les membranes des cellules hémangioendothéliales des tissus non lymphatiques (par exemple du cerveau, de la trachée, des poumons, du foie, du coeur, du pancréas, des intestins, du mésentère, des reins, de la peau ou des articulations), et de préférence avec d'autres chaînes de sucres sialyl-Lewis X prenant naissance dans les membranes des leucocytes. Ces anticorps monoclonaux possèdent non seulement tous les effets anti-inflammatoires des anticorps monoclonaux classiques contre les protéines de L-sélectine, de E-sélectine et de P-sélectine, mais également un effet inhibiteur sur les phases précoces que l'inflammation tissulaire locale, c'est-à-dire le roulement et l'adhésion des leucocytes sur une membrane cellulaire hémangioendothéliale et l'infiltration de leucocytes dans les tissus extravasculaires. Cette invention fournit par conséquent un anti-inflammatoire puissant ayant un nouveau mécanisme d'action.

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