Modulation of signal transducer and activator of transcription 3 (stat3) expression

Abstract

Disclosed herein are antisense compounds and methods for decreasing STAT3 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate hyperproliferative diseases.

1 - 76 . (canceled) 
     
     
         77 . A sodium salt of a single stranded modified oligonucleotide consisting of 12 to 30 linked nucleosides having a nucleobase sequence comprising at least 12 contiguous nucleobases of the nucleobase sequence of SEQ ID NO: 245. 
     
     
         78 . The sodium salt of a single stranded modified oligonucleotide of  claim 77 , wherein the nucleobase sequence of the modified single-stranded oligonucleotide comprises the sequence of SEQ ID NO: 245. 
     
     
         79 . The sodium salt of a single stranded modified oligonucleotide of  claim 77 , wherein the nucleobase sequence of the modified single-stranded oligonucleotide consists of the sequence of SEQ ID NO: 245. 
     
     
         80 . A pharmaceutical composition comprising the sodium salt of a single stranded modified oligonucleotide of  claim 77 , and a pharmaceutically acceptable diluent or carrier. 
     
     
         81 . A method of treating cancer in an animal, comprising administering to the animal the pharmaceutical composition of  claim 80 . 
     
     
         82 . The method of  claim 81 , wherein the cancer is chosen from lung cancer, pancreatic cancer, colorectal cancer, multiple myeloma, hepatocellular carcinoma (HCC), glioblastoma, ovarian cancer, osteosarcoma, head and neck cancer, breast cancer, epidermoid carcinomas, intestinal adenomas, prostate cancer, and gastric cancer. 
     
     
         83 . The method of  claim 82 , wherein the cancer is non-small cell lung cancer. 
     
     
         84 . The method of  claim 82 , wherein the cancer is hepatocellular carcinoma. 
     
     
         85 . The method of  claim 82 , wherein the cancer is head and neck cancer. 
     
     
         86 . The sodium salt of a single stranded modified oligonucleotide of  claim 77 , wherein the single-stranded modified oligonucleotide consists of 16 linked nucleosides having a nucleobase sequence consisting of SEQ ID NO: 245, and comprises:
 a gap segment consisting often linked deoxynucleosides;   a 5′ wing segment consisting of 3 linked nucleosides; and   a 3′ wing segment consisting of 3 linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of each wing segment comprises a constrained ethyl nucleoside; wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage; and wherein each cytosine of the modified oligonucleotide is a 5-methylcytosine.   
     
     
         87 . A potassium salt of a single stranded modified oligonucleotide consisting of 12 to 30 linked nucleosides having a nucleobase sequence comprising at least 12 contiguous nucleobases of the nucleobase sequence of SEQ ID NO: 245. 
     
     
         88 . The potassium salt of a single stranded modified oligonucleotide of  claim 87 , wherein the nucleobase sequence of the modified single-stranded oligonucleotide comprises the sequence of SEQ ID NO: 245. 
     
     
         89 . The potassium salt of a single stranded modified oligonucleotide of  claim 87 , wherein the nucleobase sequence of the modified single-stranded oligonucleotide consists of the sequence of SEQ ID NO: 245. 
     
     
         90 . A pharmaceutical composition comprising a potassium salt of the single stranded modified oligonucleotide of  claim 87 , and a pharmaceutically acceptable diluent or carrier. 
     
     
         91 . A method of treating cancer in an animal, comprising administering to the animal the pharmaceutical composition of  claim 90 . 
     
     
         92 . The method of  claim 91 , wherein the cancer is chosen from lung cancer, pancreatic cancer, colorectal cancer, multiple myeloma, hepatocellular carcinoma (HCC), glioblastoma, ovarian cancer, osteosarcoma, head and neck cancer, breast cancer, epidermoid carcinomas, intestinal adenomas, prostate cancer, and gastric cancer. 
     
     
         93 . The method of  claim 92 , wherein the cancer is non-small cell lung cancer. 
     
     
         94 . The method of  claim 92 , wherein the cancer is hepatocellular carcinoma. 
     
     
         95 . The method of  claim 92 , wherein the cancer is head and neck cancer. 
     
     
         96 . The potassium salt of the single stranded modified oligonucleotide of  claim 87 , wherein the single-stranded modified oligonucleotide consists of 16 linked nucleosides having a nucleobase sequence consisting of SEQ ID NO: 245 and comprises:
 a gap segment consisting of ten linked deoxynucleosides;   a 5′ wing segment consisting of 3 linked nucleosides; and   a 3′ wing segment consisting of 3 linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of each wing segment comprises a constrained ethyl nucleoside; wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage; and wherein each cytosine of the modified oligonucleotide is a 5-methylcytosine.