Water soluble paclitaxel prodrugs

• US 20060287220A1
• Filed: 08/31/2006
• Published: 12/21/2006
• Est. Priority Date: 03/12/1996
• Status: Active Grant

• Current Assignee: Cell Therapeutics, Inc.
• Original Assignee: Cell Therapeutics, Inc.
• Inventors: Li, Chun, Yu, Dong-Fang, Yang, David J., Wallace, Sidney
• Granted Patent: US 7,384,977 B2
• Time in Patent Office: Days
• US Class Current: 514/511
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 47/547 Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61K 51/065 conjugates with carriers being macromolecules
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C08G 73/1092 Polysuccinimides

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.

Claims

1. A method of treating an individual suffering from a cancerous condition, comprising administering to said individual a conjugate comprised of a therapeutic taxoid agent covalently bonded to a water-soluble amino acid copolymer, wherein said copolymer has (i) 50% residues or greater of a first amino acid content of that is glutamic acid, aspartic acid and/or lysine residues and (ii) at least about 1% residues of a second amino acid content comprising amino acid residues that are different than the amino acid residue or residues of said first amino acid content, wherein the cancerous condition is selected from the group consisting of prostate cancer, breast cancer, ovarian cancer, colon cancer, leukemia, and lung cancer.

2. The method of claim 1, wherein the condition is prostate cancer.

3. The method of claim 1, wherein the condition is ovarian cancer.

4. The method of claim 1, wherein the condition is colon cancer.

5. The method of claim 1, wherein the condition is leukemia.

6. The method of claim 1, wherein the condition is lung cancer.

7. The method of claim 1, wherein the condition is breast cancer.

8. The method of claim 1 wherein the therapeutic taxoid agent is paclitaxel or taxotere.

9. The method of claim 1, wherein the therapeutic agent is paclitaxel.

10. The method of claim 1, wherein said first amino acid content is glutamic acid residues.