Preparation of antibody or an antibody fragment targeted immunoliposomes for systemic administration of therapeutic or diagnostic agents and uses thereof

Abstract

The present invention provides methods of preparing an antibody- or antibody fragment-targeted cationic immunoliposome or polymer complex comprising (a) preparing an antibody or antibody fragment; (b) mixing said antibody or antibody fragment with a cationic liposome to form a cationic immunoliposome or with a cationic polymer to form a polyplex; and (c) mixing said cationic immunoliposome or said polyplex with a therapeutic or diagnostic agent to form said antibody- or antibody fragment-targeted cationic immunoliposome or polymer complex. The present invention also provides cationic immunoliposome or polymer complexes produced by such methods and compositions comprising such complexes. The present invention also provides methods for treating various diseases and disorders, including cancers, by administering the complexes and compositions of the invention to a patient.

What is claimed is: 
     
         1 . An antibody- or antibody fragment-targeted cationic immunoliposome complex comprising a cationic liposome that does not comprise maleimido-phenylbutyrate-lipid (MPB-lipid), an antibody or antibody fragment, and an siRNA directed against a non-tumor disease, wherein said antibody or antibody fragment is complexed with said cationic liposome but is not chemically conjugated to said cationic liposome and wherein said antibody or antibody fragment does not comprise a lipid tag, wherein said cationic immunoliposome complex is 50-400 nm in size. 
     
     
         2 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA is encapsulated within said cationic liposome. 
     
     
         3 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA is associated with an inner or outer monolayer of said cationic liposome. 
     
     
         4 . The cationic immunoliposome complex of  claim 1 , wherein said antibody fragment is a single chain Fv fragment. 
     
     
         5 . The cationic immunoliposome complex of  claim 1 , wherein said antibody fragment is an anti-transferrin receptor single chain Fv (TfRscFv). 
     
     
         6 . The cationic immunoliposome complex of  claim 1 , wherein said cationic liposome comprises a mixture of one or more cationic lipids and one or more neutral or helper lipids. 
     
     
         7 . The cationic immunoliposome complex of  claim 1 , wherein said antibody or antibody fragment and said cationic liposome are present at a ratio in the range of about 1:20 to about 1:40 (w:w). 
     
     
         8 . The cationic immunoliposome complex of  claim 1 , wherein said cationic liposome comprises a mixture of dioleoyitrimethylammonium phosphate with dioleoylphosphatidylethanolamine and cholesterol, a mixture of dioleoyltrimethylammomium phosphate with cholesterol, a mixture of dimethyldioctadecylammonium bromide with dioleoylphosphatidylethanolamine and cholesterol, a mixture of dimethyldioctadecylammonium bromide with dioleoylphosphatidylethanolamine, a mixture of dimethyldioctadecylammonium bromide with cholesterol, or a mixture of dioleoyltrimethylammonium phosphate with dioleoylphosphatidylethanolamine. 
     
     
         9 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA and said cationic immunoliposome are present at a ratio in the range of about 1:3.5 to about 1:14 (μg siRNA:nmol liposome). 
     
     
         10 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA and said cationic immunoliposome are present at a molar ratio of about 1:7 (μg siRNA:nmol liposome). 
     
     
         11 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA and said cationic immunoliposome are present at a molar ratio of about 1:5 (μg siRNA:nmol liposome). 
     
     
         12 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA is an anti-HER-2 siRNA. 
     
     
         13 . The cationic immunoliposome complex of  claim 1 , wherein said siRNA is directed against a neurologic disease.