Trifunctional and completely clearable specific targeting agents and methods thereof

Abstract

The invention provides a novel trifunctional targeting construct and related compositions and methods that are useful in therapeutic, diagnostic (including imaging) of various biological and/or pathological conditions and diseases such as cancers and diabetes. The trifunctional targeting construct of the invention provides enhanced clearing step and reduced non-specific background via complete clearance of undesired antibody conjugates.

What is claimed is: 
     
         1 . A conjugate compound comprising:
 a targeting moiety capable of selectively binding to a primary and specific target site or to a substance produced by or associated with the target site;   a first conjugate moiety comprising two covalently linked ligand groups, a first ligand group and a second ligand group; and   a covalent linkage between the targeting moiety and the first conjugate to form a second-order conjugate compound.   
     
     
         2 . The compound of  claim 1 , wherein the first ligand group is selected from Morpholino oligomers, peptides, toxins, enzyme, hormones, immunomodulators, chelators, photoactive agents, dyes, optical probes, and radionuclides. 
     
     
         3 . The compound of  claim 1 , wherein the targeting moiety is an antibody or an antibody fragment. 
     
     
         4 . The compound of  claim 3 , wherein the antibody or antibody fragment are humanized. 
     
     
         5 . The compound of  claim 1 , wherein the targeting moiety is selected from the group consisting of proteins, small peptides, polypeptides, enzymes, hormones, steroids, cytokines, neurotransmitters, oligomers, vitamins and receptor binding molecules. 
     
     
         6 . The compound of  claim 2 , wherein the length of the Morpholino oligomer is from about 6 bases to about 100 bases. 
     
     
         7 . The compound of  claim 6 , wherein the length of the Morpholino oligomer is from about 10 bases to about 50 bases. 
     
     
         8 . A kit for delivering a diagnostic or therapeutic agent to a target site, the kit comprising:
 a compound comprising:
 a targeting moiety capable of selectively binding to a primary and specific target site or to a substance produced by or associated with the target site, 
 a first conjugate comprising two covalently linked ligand groups, a first ligand group and a second ligand group, and 
 a covalent linkage between the targeting moiety and the first conjugate; 
   a clearing agent comprising a group capable of selective binding to the second ligand group; and   an effector conjugate, wherein the effector conjugate comprises an effecting group covalently linked to a group capable of selective binding to the first ligand group.   
     
     
         9 . The kit of  claim 8 , wherein the first ligand group is a Morpholino oligomer and the second ligand group is a biotin group. 
     
     
         10 . The kit of  claim 8 , wherein the agent is a therapeutic agent. 
     
     
         11 . The kit of  claim 8 , wherein the agent is a diagnostic agent. 
     
     
         12 . The kit of  claim 10 , wherein the therapeutic agent is selected from the group consisting of antibodies, antibody fragments, drugs, toxins, nucleases, hormones, immunomodulators, chelators, boron compounds, photoactive agents or dyes and radionuclides. 
     
     
         13 . The kit of  claim 11 , wherein the diagnostic agent is selected from the group consisting of radionuclides, dyes, contrast agents, fluorescent compounds or molecules. 
     
     
         14 . The kit of  claim 8 , wherein administration is by intravenous, intraarterial, intrapleural, intraperitoneal, intrathecal, subcutaneous or perfusion administration. 
     
     
         15 . The kit of  claim 8 , used for internal detection or treatment of tumors or other lesions, infectious diseases, inflammatory diseases, and autoimmune diseases. 
     
     
         16 . The kit of  claim 15 , wherein the targeting moiety is a tumor-specific antibody or an antibody fragment. 
     
     
         17 . The kit of  claim 16 , wherein the antibody or antibody fragment are humanized. 
     
     
         18 . The kit of  claim 9 , wherein the length of the Morpholino oligomer is from about 6 bases to about 100 bases. 
     
     
         19 . The kit of  claim 8 , wherein the target site are pancreatic islets. 
     
     
         20 . The kit of  claim 19 , wherein the pancreatic islets are imaged in diagnosis of diabetes.