Delivery of diagnostic and therapeutic agents to a target site

In an in vivo pretargeting method for delivering a diagnostic or therapeutic agent to a target site in a mammal, wherein:

• a primary targeting species is administered to the mammal which binds via a primary, target-specific binding site to the target site or to a substance produced by or associated with the target site, and which comprises a second binding site which can bind a subsequently administered active agent conjugate or which can bind a subsequently administered intermediate which in turn can bind a subsequently administered active agent conjugate, sufficient time being allowed for said primary targeting species to localize at the target site;
• a clearing agent is then administered that binds to the primary targeting species, sufficient time being allowed for said clearing agent to clear said primary targeting species from circulation;
• optionally, before or after said clearing agent is administered, an intermediate is administered which binds to said second binding site of said primary targeting species and which can bind a subsequently administered active agent conjugate;
• and
• an active agent conjugate, comprising a diagnostic or therapeutic agent conjugated to a moiety that binds to the second binding site of the primary targeting species or that binds to the intermediate, is then administered to said mammal, sufficient time being allowed for the conjugate to localize at the target site,
• the improvement wherein the clearing agent comprises a galactosylated antibody or a galactosylated antigen-binding antibody fragment wherein at least about 48% of the lysine residues of the clearing agent are modified by introduction of galactose residues, and wherein the clearing agent specifically binds to the primary binding site of the primary targeting species, whereby non-bound primary targeting species is cleared and targeted primary targeting species is not removed from the target site, nor is the second binding site of the primary targeting species blocked by the clearing agent.