Claims for Patent: 8,546,433

Summary for Patent: 8,546,433

Title:	Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
Abstract:	This invention is directed to methods of preventing, treating or managing cancer, preferably metastatic cancer, in a patient. The methods comprise administering an effective amount of an Axl inhibitor in combination with the administration of an effective amount of one or more chemotherapeutic agents.
Inventor(s):	Hitoshi; Yasumichi (Brisbane, CA), Holland; Sacha (San Francisco, CA), Payan; Donald G. (Hillsborough, CA)
Assignee:	Rigel Pharmaceuticals, Inc. (South San Francisco, CA)
Application Number:	12/688,746
Patent Claims:	1. A method for treating or managing cancer associated with Axl catalytic activity in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of an Axl inhibitor selected from 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N.sup.3-(7-(- pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-tri- azole-3,5-diamine, an isolated stereoisomer or mixture thereof or a tautomer or mixture thereof, or a pharmaceutically acceptable salt or N-oxide thereof; and a therapeutically effective amount of one or more chemotherapeutic agents. 2. The method of claim 1 wherein the Axl inhibitor is selected from: 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N.sup.3-(7-(- pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-tri- azole-3,5-diamine, or a pharmaceutically acceptable salt or N-oxide thereof; 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N.s- up.3-((7-(S)-pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)- -1H-1,2,4-triazole-3,5-diamine, or a pharmaceutically acceptable salt or N-oxide thereof; and 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N.sup.3-((7-- (R)-pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4- -triazole-3,5-diamine, or a pharmaceutically acceptable salt or N-oxide thereof. 3. The method of claim 2 wherein the Axl inhibitor is 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N.sup.3-((7-- (8)-pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4- -triazole-3,5-diamine, or a pharmaceutically acceptable salt or N-oxide thereof. 4. The method of claim 3 wherein the one or more chemotherapeutic agents is selected from the group consisting of antimetabolites, alkylating agents, coordination compounds, platinum complexes, DNA cross-linking compounds, inhibitors of transcription enzymes, tyrosine kinase inhibitors, protein kinase inhibitors, topoisomerase inhibitors, DNA minor-groove binding compounds, vinca alkyloids, taxanes, antitumor antibiotics, hormones, aromatase inhibitors, enzymes, growth factor receptors antibodies, cytokines, cell surface markers antibodies, HDAC inhibitors, HSP 90 inhibitors, BCL-2 inhibitors, mTOR inhibitors, proteasome inhibitors and monoclonal antibodies. 5. The method of claim 3 wherein the one or more chemotherapeutic agents is selected from the group consisting of mechlorothamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, ethyleneimines, methylmelamines, procarbazine, dacarbazine, temozolomide, busulfan, carmustine, lomustine, methotrexate, fluorouracil, capecitabine, cytarabine, gemcitabine, cytosine arabinoside, mercaptopurine, fludarabine, cladribine, thioguanine, azathioprine, vinblastine, vincristine, paclitaxel, docetaxel, colchicine, actinomycin D, daunorubicin, bleomycin, L-asparaginase, cisplatin, carboplatin, oxaliplatin, prednisone, dexamethasone, amino glutethimide, formestane, anastrozole, hydroxyprogesterone caproate, medroxyprogesterone, tamoxifen, amsacrine, mitoxantrone, topotecan, irinotecan, camptothecin, axtinib, bosutinib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sunitinib, vandetanib, vatalanib, anti-Her2 antibodies, interferon-.alpha., interferon-.gamma., interleukin-2, GM-CSF, anti-CTLA-4 antibodies, rituximab, anti-CD33 antibodies, MGCD0103, vorinostat, 17-AAG, thalidomide, lenalidomide, rapamycin, CCI-779, sorafenib, doxorubicine, gemcitabine, melphalan, bortezomib, NPI052, gemtuzumab, alemtuzumab, ibritumomab tiuxaetan, tositumomab, iodine-131 tositumomab, trastuzumab, bevacizumab, rituximab, and anti-TRAIL death receptor antibodies. 6. The method of claim 3 wherein the Axl inhibitor and the one or more chemotherapeutic agents are administered concurrently. 7. The method of claim 3 wherein the Axl inhibitor and the one or more chemotherapeutic agents are administered sequentially. 8. The method of claim 3 wherein the cancer is metastatic cancer. 9. The method of claim 1 wherein the cancer is breast cancer. 10. The method of claim 9 wherein the breast cancer is metastatic breast cancer.

Details for Patent 8,546,433

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2029-01-16
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2029-01-16
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2029-01-16
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2029-01-16
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2029-01-16
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2029-01-16