Ligand-targeted molecules and methods thereof

Abstract

The present invention relates to ligand-targeted molecules and ligand drug conjugates (LDCs) comprising a ligand connected to a functional group, which is connected to a linker, with in turn is bonded to a drug. The LDCs of the present invention also comprise platinum coordination complex wherein the platinum is connected to the linker through monocarboxylato and O—*Pt coordinate bonds. The present invention also relates to methods for preparing these ligand drug conjugates. The present invention further relates to methods for the treatment of tumours using the ligand drug conjugates of the present invention.

What is claimed: 
     
         1 . A ligand-targeted molecule comprising:
 a functional moiety;   (ii) a linker connected to said functional moiety;   (iii) a dicarbonyl moiety connected to said linker; and   (iv) a drug connected to said dicarbonyl moiety;   wherein said drug is a platinum chemotherapeutic agent.   
     
     
         2 . The ligand-targeted molecule of  claim 1  wherein said functional moiety is thiol reactive, amine reactive or azide reactive. 
     
     
         3 . The ligand-targeted molecule of  claim 1  wherein said linker is a hydrocarbon, polyethylene glycol (PEG), an amino acid, a peptide, or a combination thereof, said hydrocarbon or PEG being substituted or unsubstituted. 
     
     
         4 . The ligand-targeted molecule of  claim 3  wherein said linker comprises a combination of at least one amino acid and substituted or unsubstituted PEG. 
     
     
         5 . The ligand-targeted molecule of  claim 3  wherein said dicarbonyl moiety is succinate. 
     
     
         6 . A pharmaceutical composition comprising a conjugate of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         7 . A method of treating a cancer in a subject in need thereof, the method comprising administering an effective amount of a conjugate of  claim 1 . 
     
     
         8 . A ligand drug conjugate comprising a ligand connected to a ligand-targeted molecule, wherein said ligand-targeted molecule comprises a functional moiety, at least one linker connected to said functional moiety, a dicarbonyl moiety connected to said linker, and a drug connected to said dicarbonyl moiety, said drug being a platinum chemotherapeutic agent, and said ligand being connected to said functional moiety. 
     
     
         9 . The ligand drug conjugate of  claim 8  wherein said ligand is an antibody, antibody fragment, peptide, agonist, antagonist or aptamer. 
     
     
         10 . The ligand drug conjugate of  claim 9  wherein said antibody is connected to said functional moiety through a thioether bond. 
     
     
         11 . A pharmaceutical composition comprising a conjugate of  claim 8  and a pharmaceutically acceptable carrier. 
     
     
         12 . A method of treating a cancer in a subject in need thereof, the method comprising administering an effective amount of a conjugate of  claim 8 . 
     
     
         13 . A ligand drug conjugate comprising a ligand connected to a ligand-targeted molecule, wherein said ligand-targeted molecule comprises a functional moiety, at least one linker connected to said functional moiety, a first drug connected to said linker, a dicarbonyl moiety connected to said linker, and a second drug connected to said dicarbonyl moiety, said second drug being a platinum compound, and said ligand being connected to said functional moiety. 
     
     
         14 . The conjugate of  claim 13 , wherein said first drug is an anti-cancer agent. 
     
     
         15 . The conjugate of  claim 13 , wherein said linker is a hydrocarbon, polyethylene glycol (PEG), an amino acid, a peptide, or a combination thereof, said hydrocarbon or PEG being substituted or unsubstituted. 
     
     
         16 . The conjugate of  claim 13 , wherein said ligand is an antibody, antibody fragment, peptide, agonist, antagonist or aptamer. 
     
     
         17 . The conjugate of  claim 13 , wherein said linker comprises a combination of at least one amino acid and substituted or unsubstituted PEG. 
     
     
         18 . The conjugate of  claim 13 , wherein said dicarbonyl moiety is succinate. 
     
     
         19 . A pharmaceutical composition comprising a conjugate of  claim 13  and a pharmaceutically acceptable carrier. 
     
     
         20 . A method of treating a cancer in a subject in need thereof, the method comprising administering an effective amount of a conjugate of  claim 13 .