Partially loaded antibodies and methods of their conjugation

Abstract

A protein containing one or more activatable groups, e.g., an antibody, is subjected to partial or complete reduction of one or more such bonds to form reactive groups; the resulting protein is reacted with a drug which is reactive with some of the reactive groups, such as certain radiometals, chelating agents, and toxins, so as to form a conjugate useful in, e.g., in vitro diagnosis, in vivo imaging, and therapy.

1 - 75 . (canceled) 
     
     
         76 . A method for the treatment of cancer, immune disease, autoimmune disease or infectious disease in a patient, comprising administering to the patient an amount of a modified protein, which is an antibody, comprising:
 points of conjugation for a cytotoxic or cytostatic agent, wherein at least one point of conjugation for the cytotoxic or cytostatic agent on the antibody can be readily assigned, and wherein less than all possible points of conjugation are available for conjugation to the cytotoxic or cytostatic agent.   
     
     
         77 . A method for the treatment of cancer, immune disease, autoimmune disease or infectious disease in a patient, comprising administering to the patient an amount of a modified protein, which is a partially loaded, modified protein, comprising:
 a binding region for interaction with a binding partner;   at least two points of conjugation having a similar accessibility or activability for conjugation of a drug or label by chemical means;   at least two drugs or labels, each drug or label covalently linked to one point of conjugation;   wherein less than all of the possible points of conjugation having a similar accessibility or activability are linked to a drug or label.   
     
     
         78 . The method of  claim 77 , wherein:
 the modified protein is an antibody;   the binding region is an antigen-binding domain of the antibody;   the points of conjugation are thiol groups; and   the antibody comprises at least one interchain disulfide bond.