Delivery of diagnostic and therapeutic agents to a target site
AssigneeImmunomedics, Inc.
InventorsGary L. Griffiths, Hans J. Hansen, Serengulam V. Govindan, Habibe Karacay
Life of this patent
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Abstract
An improvement in in vivo pretargeting methods for delivering diagnostic or therapeutic agents to a target site in a mammal uses a clearing agent that binds to the target-binding site of the targeting species, whereby non-bound primary targeting species is cleared from circulation but the clearing agent does not remove the bound primary targeting species. Anti-idiotype antibodies and antibody fragments are preferred clearing agents. Fast clearance is achieved by glycosylating the clearing agent with sugar residues that bind to the hepatic asialoglycoprotein receptor.
Claims24
An in vivo pretargeting method for delivering a diagnostic or therapeutic agent to a target site in a mammal, comprising the steps of:
- administering a primary targeting species 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 peptidyl nucleic acid, and allowing the targeting species to localize at the target site;
- administering a clearing agent that specifically binds to the primary binding site of the primary targeting species and allowing the clearing agent to clear the primary targeting species from circulation, whereby substantially only non-bound primary targeting species is cleared and targeted primary targeting species is not competitively removed from the target site, nor is the peptidyl nucleic acid of the primary targeting species blocked by the clearing agent, and wherein the clearing agent is an antibody or an antigen-binding fragment of an antibody, wherein at least about 48% of the lysine residues of the clearing agent are modified by introduction of galactose residues;
- and
- administering an active agent conjugate comprising a diagnostic or therapeutic agent conjugated to a complementary peptidyl nucleic acid that binds to the peptidyl nucleic acid of the primary targeting species.
A kit for the in vivo pretargeting of a diagnostic or therapeutic agent to a target site in a mammal, comprising:
- a primary targeting species 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 peptidyl nucleic acid;
- a clearing agent that specifically binds to the primary binding site of the primary targeting species and which does not block the peptidyl nucleic acid of the primary targeting species, wherein the clearing agent is an antibody or an antigen-binding fragment of an antibody, wherein at least about 48% of the lysine residues of the clearing agent are modified by introduction of galactose residues;
- and
- an active agent conjugate comprising a diagnostic or therapeutic agent conjugated to a complementary peptidyl nucleic acid that binds to the peptidyl nucleic acid of the primary targeting species.
Dependencies are inferred from the claim text.