Antibody conjugates for the delivery of compounds to target sites

Abstract

A method is described for the covalent attachment of linker groups to specific sites on antibody molecules directed against any desired target antigen (tumor, bacterial, fungal, viral, parasitic etc.). These linkers can be attached via amide or ester bonds to compounds for delivery which contain available amino or hydroxy groups (e.g., bioactive agents, cytotoxic agents, dyes, fluors, radioactive compounds, etc.). In addition the linkers can be incorporated into insoluble matrices for use in separation schemes which are based upon antibody-antigen interactions. The linkers may be designed so that they are susceptible to cleavage by any one of the serum complement enzymes. When prepared according to the methods described herein, the resulting modified antibody molecule retains the ability to bind antigen and to fix serum complement. Thus, when administered to a patient the antibody conjugate binds to its target in vivo. As a result of the subsequent activation of the patient's serum complement, the covalently attached compound will be specifically cleaved at the target site by the proteolytic enzymes of the complement system.