Cancer Therapies and Pharmaceutical Compositions Used Therein

Abstract

The invention relates to compositions and methods to inhibit gene expression. In particular, the invention provides co-therapies comprising oligonucleotides plus other therapies to treat cancer.

1 . A pharmaceutical composition comprising:
 an oligonucleotide and   a chemotherapeutic or immunotherapeutic agent, or a combination thereof,   
       wherein the oligonucleotide is any oligomer of at least 10 nucleotides that hybridizes under physiological conditions to SEQ ID NO:1249 or the complement thereof. 
     
     
         2 . The composition of  claim 1 , wherein the chemotherapeutic agent comprises an anti-metabolite, an anthracycline, an EGFR inhibitor, a kinase inhibitor or combinations thereof. 
     
     
         3 . The composition of  claim 2 , wherein the chemotherapeutic agent-comprises methotrexate, 5-fluorouracil, gemcitabine, 6-mercaptopurine, 6-thioguanine, fludarabine, cladarabine, cytarabine, daunorubicin, doxorubicin, idarubicin, epirubicin, mitoxantrone, gefitinib. erlotinib, cetuximab, imatinib mesylate, lefunomide, midostaurin or combinations thereof. 
     
     
         4 - 5 . (canceled) 
     
     
         6 . The composition of  claim 1 , wherein the chemotherapeutic agent comprises a taxane. 
     
     
         7 . The composition of  claim 6 , wherein the taxane is selected from paclitaxel, docetaxel, or combinations thereof. 
     
     
         8 . The composition of  claim 1 , wherein the chemotherapeutic agent comprises a camptothecin. 
     
     
         9 . The composition of  claim 8 , wherein the camptothecin is selected from irinotecan, topotecan, etoposide, vincristine, vinblastine, vinorelbine, or combinations thereof. 
     
     
         10 - 12 . (canceled) 
     
     
         13 . The composition of  claim 1 , wherein the immunotherapeutic agent is selected from rituximab, tositumomab, ibritumomab, bevacizumab, trastuzumab or combinations thereof. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . The composition of  claim 1 , wherein the chemotherapeutic agent comprises a cocktail comprising an immunotherapy, an alkylating agent, an anthracycline, a camptothecin and prednisone. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The composition of  claim 16 , wherein the chemotherapeutic agent comprises a cocktail comprising rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. 
     
     
         20 . (canceled) 
     
     
         21 . The composition of  claim 1  wherein the oligonucleotide comprises an oligomer that hybridizes under physiological conditions to nucleotides 500-1525 of SEQ ID NO:1249 or the complement thereof. 
     
     
         22 . (canceled) 
     
     
         23 . The composition of  claim 1  wherein the oligonucleotide comprises an oligomer that hybridizes under physiological conditions to nucleotides 900-1125 of SEQ ID NO:1249 or the complement thereof. 
     
     
         24 . (canceled) 
     
     
         25 . The composition of  claim 1  wherein the oligonucleotide comprises an oligomer that hybridizes under physiological conditions to nucleotides 970-1045 of SEQ ID NO:1249 or the complement thereof. 
     
     
         26 . The composition of  claim 1  wherein the oligonucleotide comprises an oligomer selected from the group consisting of SEQ ID NOs:1250, 1251, 1252, 1253, 1267-1477 or the complements thereof. 
     
     
         27 - 28 . (canceled) 
     
     
         29 . The composition of  claim 1 , wherein the oligonucleotide comprises SEQ ID NO:1250 or 1251. 
     
     
         30 - 31 . (canceled) 
     
     
         32 . The composition of  claim 1 , further comprising an additional oligonucleotide. 
     
     
         33 . The composition of  claim 32 , wherein the additional oligomer comprises any one of SEQ ID NOs:1250-1253, 1267-1477. 
     
     
         34 . The composition of  claim 32  wherein the additional oligomer comprises SEQ ID NO: 940 or SEQ ID NO:943. 
     
     
         35 . (canceled) 
     
     
         36 . The composition of  claim 1 , wherein the length of the oligonucleotide is about 15 to 35 nucleotides. 
     
     
         37 . The composition of  claim 1  wherein the oligonucleotide has a phosphorothiolate backbone. 
     
     
         38 . A method of treating cancer comprising:
 (a) administering to a patient an effective amount of an oligonucleotide comprising an oligomer of at least 10 nucleotides that hybridizes under physiological conditions to SEQ ID NO:1249 or the complement thereof; and   (b) administering to the patient an effective amount of a chemotherapeutic or immunotherapeutic agent or a combination thereof.   
     
     
         39 . The method of  claim 38 , wherein the chemotherapeutic agent comprises a cocktail comprising rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. 
     
     
         40 . The method of  claim 38 , wherein the immunotherapeutic agent comprises rituximab. 
     
     
         41 . The method of  claim 38 , further comprising administering to the patient a radiation therapy. 
     
     
         42 . The method of  claim 38 , further comprising excising cancerous tissue from a patient. 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 38  wherein the oligonucleotide comprises an oligomer that hybridizes under physiological conditions to nucleotides 500-1525 of SEQ ID NO:1249 or the complement thereof. 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 38  wherein the oligonucleotide comprises an oligomer that hybridizes under physiological conditions to nucleotides 900-1125 of SEQ ID NO:1249 or the complement thereof. 
     
     
         47 . (canceled) 
     
     
         48 . The method of  claim 38  wherein the oligonucleotide comprises an oligomer that hybridizes under physiological conditions to nucleotides 970-1045 of SEQ ID NO:1249 or the complement thereof. 
     
     
         49 . The method of  claim 38  wherein the oligonucleotide comprises an oligomer selected from the group consisting of SEQ ID NOs:1250, 1251, 1252, 1253, 1267-1477 or the complements thereof. 
     
     
         50 - 51 . (canceled) 
     
     
         52 . The method of  claim 38 , wherein the oligonucleotide comprises SEQ ID NO:1250 or 1251. 
     
     
         53 . (canceled) 
     
     
         54 . The method of  claim 38 , further comprising an additional oligonucleotide. 
     
     
         55 . The method of  claim 54 , wherein the additional oligonucleotide comprises any one of SEQ ID NOs:1250-1253 and 1267-1477. 
     
     
         56 . The method of  claim 54  wherein the additional oligonucleotide comprises SEQ ID NO:940 or 943. 
     
     
         57 . (canceled) 
     
     
         58 . The method  claim 38 , wherein the length of the oligonucleotide is about 15 to 35 nucleotides. 
     
     
         59 . The method of  claim 38  wherein the oligonucleotide has a phosphorothiolate backbone. 
     
     
         60 . A method of treating cancer comprising:
 administering to a patient an effective amount of an oligonucleotide comprising SEQ ID NO:1251 and administering to the patient an effective amount of rituximab.   
     
     
         61 . The method of  claim 38 , wherein the chemotherapy agent comprises an immunotherapeutic agent, an alkylating agent, an anthracycline, a camptothecin and Prednisone. 
     
     
         62 . The method of  claim 38 , wherein the chemotherapy agent comprises a taxane or a camptothecin. 
     
     
         63 . The method of  claim 62 , wherein the chemotherapy agent comprises docetaxel. 
     
     
         64 . The method of  claim 62 , wherein the chemotherapy agent comprises vincristine. 
     
     
         65 . The method of  claim 38 , wherein the wherein the oligonucleotide comprises SEQ ID NO:1251 and the chemotherapy agent comprises docetaxel. 
     
     
         66 . The method of  claim 38 , wherein the oligonucleotide comprises SEQ ID NO:1251 and the chemotherapy agent comprises vincristine. 
     
     
         67 . The method of  claim 38 , wherein the cancer is selected from prostate cancer, lymphoma, non-Hodgkin's lymphoma, Burkitt's lymphoma, melanoma, breast cancer, myeloma, ovarian cancer, colon cancer, lung cancer, adenocarcinoma and gastric cancer. 
     
     
         68 . The method of  claim 38 , wherein the cancer is selected from prostate cancer, melanoma, lymphoma, non-Hodgkin's lymphoma, and Burkitt's lymphoma. 
     
     
         69 . The pharmaceutical composition of  claim 1 , wherein the oligonucleotide comprises SEQ ID NO:1251 and the immunotherapeutic agent comprises rituximab. 
     
     
         70 . The pharmaceutical composition of  claim 1 , wherein the oligonucleotide comprises SEQ ID NO:1251 and the chemotherapy agent comprises docetaxel. 
     
     
         71 . The pharmaceutical composition of  claim 1 , wherein the oligonucleotide comprises SEQ ID NO:1251 and the chemotherapy agent comprises vincristine.