Anti-integrin immunoconjugates, methods and uses

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01) C07K 16/46 (2006.01)

Patent

CA 2591148

The invention relates to conjugates of anti-integrin specific antibodies with cytotoxic compounds, the synthesis, selection, and use of such conjugates for use in cancer therapy or other diseases mediated by cell proliferation, cell migration, or inflammation and which pathology involves angiogenesis or neovascularization of new tissue. In addition the invention relates to combination therapy of such diseases wherein the treatment comprises use of said conjugates in combination with one or more other treatment modalities including but not limited to: chemotherapy, surgery or radiation therapy. The preferred conjugates contain maytansinoid compounds linked to the antibody by a disulfide linkage, and preferred chemotherapeutic agents are doxorubicin, a taxane, a camptothecin, a podophyllotoxin, a nucleoside analog, or a pyrimidine analog.

L'invention concerne des conjugués d'anticorps spécifiques anti-intégrines avec des composés cytotoxiques, la synthèse, la sélection et l'utilisation de ces conjugués pour le traitement du cancer ou d'autres maladies induites par la prolifération cellulaire, la migration cellulaire ou l'inflammation, et dont la pathologie implique l'angiogenèse ou la néovascularisation de nouveaux tissus. L'invention concerne également une polythérapie destinée au traitement de ces maladies, consistant à utiliser ces conjugués avec une ou plusieurs autres moyens de traitement, y compris, sans en exclure d'autres, la chimiothérapie, la chirurgie ou la radiothérapie. Les conjugués préférés contiennent des composés maytansinoïdes liés à l'anticorps par une élément de liaison disulfure. Les agents chimiothérapeutiques préférés sont la doxorubicine, un taxane, une camptothécine, une podophyllotoxine, un analogue nucléosidique ou un analogue pyrimidinique.

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