COMBINATIONS FOR THE TREATMENT OF PROLIFERATIVE DISEASES

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COMBINATIONS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
Publication number: CA2545423
Publication date: 2005-05-26
Inventor: LEE MARGARET S (US); NICHOLS M JAMES (US); KEITH CURTIS (US); ZHANG YANZHEN (US)
Applicant: COMBINATORX INC (US)
Classification:
- international: A61K39/395; A61K31/225; A61K31/7105; A61P35/00; C12Q1/02; G01N33/50; A61K39/395; A61K31/21; A61K31/7105; A61P35/00; C12Q1/02; G01N33/50;
- european: A61K31/225; G01N33/50D2B
Application number: CA20042545423 20041109
Priority number(s): US20030519551P 20031112; US20040855130 20040527; WO2004US37527 20041109

Also published as:

EP1689352 (A2)
US2006177864 (A1)
US2005158320 (A1)
US2005100508 (A1)
EP1689352 (A0)

Abstract of CA2545423

The invention features combinations of drugs for the treatment of proliferative diseases (e.g., cancer). The invention also features methods f or identifying new combination therapies for the treatment of cancer and other proliferative diseases. <SDOCL LA=EN> Claims 1. A composition comprising a first agent that reduces mitotic kinesin biological activity and a second agent that reduces protein tyrosine phosphatase biological activity, wherein said first and second agents are present in amounts that, when administered to a patient having a proliferative disease, are sufficient to treat said disease. 2. The composition of claim 1, wherein said first agent is a mitotic kinesin inhibitor. 3. The composition of claim 1, wherein said first agent is an antisense compound or RNAi compound that reduces the expression levels of said mitotic kinesin. 4. The composition of claim 1, wherein said first agent is a dominant negative mitotic kinesin or an expression vector encoding said dominant negative mitotic kinesin. 5. The composition of claim 1, wherein said first agent is an antibody that binds said mitotic kinesin and reduces mitotic kinesin biological activity. 6. The composition of any one of claims 1-5, wherein said mitotic kinesin is HsEg5/KSP. 7. The composition of claim 1, wherein said first agent in an aurora kinase inhibitor. 8. The composition of claim 1, wherein said mitotic kinesin biological activity is enzymatic activity, motor activity, or binding activity. 28 9. The composition of claim 1, wherein said second agent is a protein tyrosinephosphatase inhibitor. 10. The composition of claim 1, wherein said second agent is an antisense compound or RNAi compound that reduces the expression levels of said protein tyrosine phosphatase. 11. The composition of claim 1, wherein said second agent is a dominant negative protein tyrosine phosphatase or an expression vector encoding said dominant negative protein tyrosine phosphatase. 12. The composition of claim 1, wherein said second agent is an antibody that binds said protein tyrosine phosphatase and reduces protein tyrosine phosphatase biological activity. 13. The composition of any one of claims 9-12, wherein said protein tyrosine phosphatase is PTP1B, PRL-1, PRL-2, PRL-3, SHP-1, SHP-2, MKP- 1, MKP-2, CDC14, CDC25A, CDC25B, or CDC25C. 14. The composition of claim 1, wherein said second agent is a farnesyltransferase inhibitor. 15. The composition of any one of claims 1-14, wherein said first or second agent is present in said composition in a low dosage. 16. The composition of any one of claims 1-14, wherein said first or second agent is present in said composition in a high dosage. 17. The composition of any one of claims 1-16, wherein said composition is formulated for topical administration. 29 18. The composition of any one of claims 1-16, wherein said composition is formulated for systemic administration. 19. A method for treating a patient who has a proliferative disease, said method comprising administering to said patient a combination of: a) a first agent that reduces mitotic kinesin biological activity; and b) a second agent that reduces protein tyrosine phosphatase biological activity, wherein the first and second agents are administered simultaneously or within 28 days of each other, in amounts that together are sufficient to tre at said patient. 20. The method of claim 19, wherein said first agent is a mitotic kinesin inhibitor. 21. The method of claim 19, wherein said first agent is an antisense compound or RNAi compound that reduces the expression levels of said mitotic kinesin. 22. The method of claim 19, wherein said first agent is a dominant negative mitotic kinesin or an expression vector encoding said dominant negative mitotic kinesin. 23. The method of claim 19, wherein said first agent is an antibody that binds said mitotic kinesin and reduces mitotic kinesin biological activity. 24. The method of any one of claims 19-23, wherein said mitotic kinesin is HsEg5/KSP. 30 25. The method of claim 19, wherein said first agent in an aurora kinase inhibitor. 26. The method of claim 19, wherein said second agent is a protein tyrosine phosphatase inhibitor. 27. The method of claim 19, wherein said second agent is an antisense compound or RNAi compound that reduces the expression levels of said protein tyrosine phosphatase. 28. The method of claim 19, wherein said second agent is a dominant negative protein tyrosine phosphatase or an expression vector encoding said dominant negative protein tyrosine phosphatase. 29. The method of claim 19, wherein said second agent is an antibody that binds said protein tyrosine phosphatase and reduces protein tyrosine phosphatase biological activity. 30. The method of any one of claims 21-25, wherein said protein tyrosine phosphatase is PTP1B, PRL-1, PRL-2, PRL-3, SHP-1, SHP-2, MKP- 1, MKP-2, CDC14, CDC25A, CDC26B, or CDC25C. 31. The method of claim 19, wherein said second agent is