Extracellular targeted drug conjugates

Abstract

The present invention relates to, inter alia, extracellular drug conjugates (EDC) in which an antibody or other targeting agent (e.g. a targeting moiety) is linked to a drug through a linker (e.g. a non-cleavable linker). These conjugates are useful in the treatment of disease and/or as a tool in the evaluation of biological systems.

1 . An extracellular drug conjugate (EDC) comprising a non-internalizing antibody that binds to an extracellular target linked by a non-cleavable linker to a cardiac glycoside. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The EDC of  claim 1 , in which the antibody and the cardiac glycoside bind to extracellular targets. 
     
     
         6 . (canceled) 
     
     
         7 . The EDC of  claim 1 , in which the antibody and the cardiac glycoside bind to the same target complex. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . A pharmaceutical composition comprising a pharmaceutically acceptable vehicle, vector, diluent, and/or excipient and a therapeutically effective amount of a drug conjugate of  claim 1 . 
     
     
         11 . A method for treating a disease, comprising administering to a patient in need of treatment for said disease a therapeutically effective amount of a drug conjugate of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the disease is selected from the group of viral infections, cancers, metastases, cellular apoptosis disorders, degenerative diseases, tissue ischemia, infectious diseases or a viral, bacterial or fungal nature, inflammation disorders and pathological nee-angiogenesis. 
     
     
         13 . The EDC of  claim 1 , in which the antibody specifically binds FXYD5. 
     
     
         14 . The EDC of  claim 1 , in which the drug acts on the alpha subunit of the Na,K-ATPase ion pump. 
     
     
         15 . The EDC of  claim 1  wherein the cardiac glycoside is selected from the group consisting of: CENOS-178 (3-O-digitoxigenin-L-ribosidet CEN08-193 (3-O-isodigitoxigenin-L-xyloside), CEN08-243 ((35)-3-N-methoxyamino-scillarenin-L-neo-4-amino-4-deoxyxyloside), CEN08-244 ((35)-3-N-methoxyamino-scillarenin-L-neo-4-amino-4-deoxyriboside), CEN09-106 or CEN09-107. 
     
     
         16 . An extracellular drug conjugate comprising an antibody that specifically binds FXYDS covalently linked to a cardiac glycoside via a PEG linker. 
     
     
         17 . The extracellular drug conjugate of  claim 16  wherein the cardiac glycoside comprises CEN09-106. 
     
     
         18 . The extracellular drug conjugate of  claim 16  wherein the PEG linker comprises PEG2 to PEG44. 
     
     
         19 . The extracellular drug conjugate of  claim 16  wherein the PEG linker comprises PEG24. 
     
     
         20 . The extracellular drug conjugate of  claim 16  wherein on average loading per antibody is about 4 to about 6 cardiac glycoside molecules.