Water soluble paclitaxel derivatives

Abstract

Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

What is claimed is:  
     
         1 . A conjugate comprising an anti-tumor drug, a water-soluble polymer and a targeting molecule having covalent attachments between said anti-tumor drug, said water soluble polymer and said targeting molecule, wherein said water-soluble polymer is a copolymer comprising an amino acid polymer and polyethylene glycol.  
     
     
         2 . The conjugate of  claim 1 , wherein said amino acid polymer is selected from the group consisting of polyglutamate, polyaspartate and polylysine.  
     
     
         3 . The conjugate of  claim 2 , wherein said amino acid polymer is polyglutamate.  
     
     
         4 . The conjugate of  claim 3 , wherein said targeting molecule is an antibody.  
     
     
         5 . The conjugate of  claim 4 , wherein said antibody has a specificity selected from the group consisting of anti-tumor, anti-cell receptor, tissue specific, hormonal agent, octreotide, estradiol, tamoxifen, growth factors, cell surface receptor ligands, enzymes, hypoxic agents, misonidazole, erythronitroimidazole and anti-angiogenic agents.  
     
     
         6 . A conjugate comprising an anti-tumor drug, a water-soluble polymer and a targeting molecule having covalent attachments between said anti-tumor drug, said water-soluble polymer and said targeting molecule, wherein said water-soluble polymer is a copolymer comprising polyglutamate and polyethylene glycol and said anti-tumor drug is selected from the group consisting of paclitaxel, docetaxel, etoposide, teniposide, camptothecin and epothilone.  
     
     
         7 . The conjugate of  claim 6 , wherein said anti-tumor drug is paclitaxel.  
     
     
         8 . The conjugate of  claim 7 , wherein said targeting molecule is an antibody.  
     
     
         9 . The conjugate of  claim 8 , wherein said antibody has a specificity selected from the group consisting of anti-tumor, anti-cell receptor, tissue specific, hormonal agent, octreotide, estradiol, tamoxifen, growth factors, cell surface receptor ligands, enzymes, hypoxic agents, misonidazole, erythronitroimidazole and anti-angiogenic agents.  
     
     
         10 . The conjugate of  claim 6 , wherein said anti-tumor drug is docetaxel.  
     
     
         11 . The conjugate of  claim 10 , wherein said targeting molecule is an antibody.  
     
     
         12 . The conjugate of  claim 11 , wherein said antibody has a specificity selected from the group consisting of anti-tumor, anti-cell receptor, tissue specific, hormonal agent, octreotide, estradiol, tamoxifen, growth factors, cell surface receptor ligands, enzymes, hypoxic agents, misonidazole, erythronitroimidazole and anti-angiogenic agents.  
     
     
         13 . The conjugate of  claim 6 , wherein said anti-tumor drug is camptothecin.  
     
     
         14 . The conjugate of  claim 13 , wherein said targeting molecule is an antibody.  
     
     
         15 . The conjugate of  claim 14 , wherein said antibody has a specificity selected from the group consisting of anti-tumor, anti-cell receptor, tissue specific, hormonal agent, octreotide, estradiol, tamoxifen, growth factors, cell surface receptor ligands, enzymes, hypoxic agents, misonidazole, erythronitroimidazole and anti-angiogenic agents.  
     
     
         16 . The conjugate of  claim 6 , wherein said anti-tumor drug is epothilone.  
     
     
         17 . The conjugate of  claim 16 , wherein said targeting molecule is an antibody.  
     
     
         18 . The conjugate of  claim 17 , wherein said antibody has a specificity selected from the group consisting of anti-tumor, anti-cell receptor, tissue specific, hormonal agent, octreotide, estradiol, tamoxifen, growth factors, cell surface receptor ligands, enzymes, hypoxic agents, misonidazole, erythronitroimidazole and anti-angiogenic agents.