Claims for Patent: 8,518,897

Summary for Patent: 8,518,897

Title:	Method of treatment for cancers associated with elevated HER2 levels
Abstract:	Novel methods of treating proliferative disorders characterized by elevated Her-2, and the patient is then administered an effective amount of an HSP90 inhibitor.
Inventor(s):	Rosen; Neal (Englewood, NJ), Munster; Pamela (Tampa, FL)
Assignee:	Sloan-Kettering Institute for Cancer Research (New York, NY)
Application Number:	12/910,513
Patent Claims:	1. A method of treating a patient having HER-2 positive breast cancer characterized by having elevated levels of HER-2 expression as compared to normal cells of the same type, comprising: providing cells, tissue, or fluid from a patient suspected of having HER-2 positive breast cancer, wherein the provided cells, tissue or fluid are selected to be suitable for testing to characterize HER-2 levels in breast cancer; testing said provided cells, tissue, or fluid for one or more of the gene copy number of HER-2, the amount of HER-2 mRNA, or the amount of HER-2 protein as an indication of the level of HER-2 expression; and if said level is elevated, administering to said patient an pharmaceutically effective amount of an HSP90 inhibitor and a second therapeutic agent different from the HSP90 inhibitor, wherein said HSP90 inhibitor has an IC.sub.50 at least two-fold lower for said provided cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2 and the administered amount is correspondingly lower than the amount that would be required for cells that do not have elevated Her-2, and said second therapeutic agent is an anti-cancer or cytotoxic agent. 2. The method of claim 1, wherein said inhibitor is an ansamycin. 3. The method of claim 2, wherein said ansamycin is selected from the group consisting of geldanamycin, 17-AAG, herbimycin A, and macbecin. 4. The method of claim 1, wherein said inhibitor is 17-AAG. 5. The method of claim 1, wherein said inhibitor is an inhibitor that binds into the ATP-binding site of a HSP90. 6. The method of claim 5 wherein said inhibitor is radicicol. 7. The method of claim 1 wherein said testing comprises using nucleic acid hybridization or PCR to determine the level of HER-2 messenger RNA. 8. The method of claim 1 wherein said testing comprises the use of antibodies to determine the level of HER-2. 9. The method of claim 1 wherein one or more of said testing or said administering is done ex vivo. 10. The method of claim 1 wherein said administering is intralesional. 11. The method of claim 1 wherein said administering is parenteral. 12. The method of claim 1 wherein said HSP90 inhibitor has an IC.sub.50 at least five-fold lower for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 13. The method of claim 1 wherein said HSP90 inhibitor has an IC.sub.50 at least ten-fold lower for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 14. The method of claim 1 further comprising testing cells of said patient for sensitivity to HSP90 inhibitors prior to administration of said HSP90 inhibitor. 15. The method of claim 1 wherein said testing comprises the use of one or more standards. 16. The method of claim 1 wherein said inhibitor exhibits an IC.sub.50 of about 100 nM or less in said cells having elevated Her-2. 17. The method of claim 1 wherein said inhibitor exhibits an IC.sub.50 of about 75 nM or less in said cells having elevated Her-2. 18. The method of claim 1 wherein said inhibitor exhibits an IC.sub.50 of about 50 nM or less in said cells having elevated Her-2. 19. The method of claim 1 wherein said inhibitor exhibits an IC.sub.50 of about 25 nM or less in said cells having elevated Her-2. 20. The method of claim 1 wherein said inhibitor exhibits an IC.sub.50 of about 10 nM or less in said cancerous cells. 21. The method of claim 1 wherein said inhibitor exhibits an IC.sub.50 of about 5 nM or less in said cells having elevated Her-2. 22. The method of claim 1 wherein said method further comprises testing to monitor therapeutic effect after said administration. 23. The method of claim 22 wherein said monitoring therapeutic effect comprises measuring a molecular marker indicative of the level of HER-2. 24. The method of claim 23 wherein said molecular marker is selected from one or more of the group consisting of HER-2, a cyclin, and phosphorylated AKT. 25. The method of claim 22 wherein said molecular marker is a cyclin selected from the group consisting of D1 and D3. 26. The method of claim 1, wherein said cells that do not have elevated Her-2 are from said patient. 27. The method of claim 1, wherein said IC.sub.50 value is calculated using one or more standards. 28. The method of claim 1, wherein said testing comprises the use of Southern blotting to determine the HER-2 gene copy number. 29. The method of claim 1 wherein said elevated level is at least two-fold greater for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 30. The method of claim 1 wherein said elevated level is at least three-fold greater for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 31. The method of claim 1 wherein said elevated level is at least five-fold greater for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 32. The method of claim 1 wherein said elevated level is at least ten-fold greater for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 33. The method of claim 1 wherein said elevated level is at least twenty five-fold for said cells in said patient having elevated Her-2 than for cells that do not have elevated Her-2. 34. The method of claim 1, wherein the second therapeutic agent is an agent that inhibits a signaling pathway that links cell surface growth factor receptors to nuclear signals initiating cellular proliferation in the cells. 35. The method of claim 1, wherein the second therapeutic agent is as an inhibitor of angiogenesis. 36. The method of claim 1, wherein the second therapeutic agent is a VEGF receptor inhibitor. 37. The method of claim 1, wherein the second therapeutic is an antineoplastic agent selected from the group consisting of alkylating agents, anti-metabolites; epidophyllotoxin; an antineoplastic enzyme; a topoisomerase inhibitor; procarbazine; mitoxantrone; platinum coordination complexes; biological response modifiers and growth inhibitors; hormonal/anti-hormonal therapeutic agents and haematopoietic growth factors. 38. The method of claim 1, wherein the second therapeutic agent is selected from the group consisting of the anthracycline family of drugs, the vinca drugs, the mitomycins, the bleomycins, the cytotoxic nucleosides, the epothilones, discodermolide, the pteridine family of drugs, diynenes and the podophyllotoxins. 39. The method of claim 38, wherein the second therapeutic agent is selected from the group consisting of caminomycin, daunorubicin, aminopterin, methotrexate, methopterin, dichloromethotrexate, mitomycin C, porfiromycin, 5-fluorouracil, 6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin or podo-phyllotoxin derivatives, etoposide, etoposide phosphate, teniposide, melphalan, vinblastine, vincristine, leurosidine, vindesine, leurosine, paclitaxel, estramustine, carboplatin, cyclophosphamide, bleomycin, gemcitibine, ifosamide, melphalan, hexamethyl melamine, thiotepa, cytarabin, idatrexate, trimetrexate, dacarbazine, L-asparaginase, camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide, leuprolide, pyridobenzoindole derivatives, interferons and interleukins.

Details for Patent 8,518,897

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2039-02-26