Tumoricidal methotrexate-antibody conjugate
AssigneeCenter for Molecular Medicine and Immunology
InventorsLisa B. Shih, Frederick J. Primus, Milton D. Goldenberg
Life of this patent
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Abstract
A conjugate of methotrexate to an antibody is prepared by loading methotrexate onto an aminodextran, then specifically conjugating the polymer carrier to the carbohydrate portion of an antitumor antibody, using a reduced Schiff base linkage. The conjugate is useful for tumor targeted therapy.
Claims12
An antibody conjugate, comprising methotrexate linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a reduced Schiff base linkage.
A method of preparing a methotrexate-aminodextran-antibody conjugate wherein the methotrexate is linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a Reduced Schiff base linkage, comprising the steps of:
- (a) reacting an aminodextran containing about 25-40 methotrexate molecules linked thereto with an anti-cancer antibody having an oxidized carbohydrate portion;
- and
- (b) reductively stabilizing the resultant Schiff base adduct.
A method of tumor therapy, comprising administering to an animal or human having a tumor a therapeutically effective amount of an antibody conjugate, comprising methotrexate linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a reduced Schiff base linkage.
Dependencies are inferred from the claim text.