Antisense Compositions and Methods of Making and Using Same

Abstract

The present invention provides pharmaceutical formulations for oral administration of antisense oligonucleotides, such as antisense oligonucleotides against SMAD7. The pharmaceutical formulations can be used to treat Crohn's disease, ulceralive colitis and chronic inflammatory bowel disease.

1 - 23 . (canceled) 
     
     
         24 . A method of treating an inflammatory bowel disease (IBD) comprising orally administering to a patient in need thereof an oral dosage form comprising a plurality of tablets each comprising:
 an oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, and   a gastro-protective coating comprising an ethylacrylate-methacrylic acid copolymer.   
     
     
         25 . The method of  claim 24 , wherein the oligonucleotide is the sodium salt of SEQ ID NO: 1. 
     
     
         26 . The method of  claim 24 , wherein at least one internucleotide linkage of SEQ ID NO: 1 is an O,O-linked phosphorothioate. 
     
     
         27 . The method of  claim 24 , wherein all of the internucleotide linkages of SEQ ID NO: 1 are O,O-linked phosphorothioates. 
     
     
         28 . The method of  claim 24 , wherein the oral dosage form further comprises a pharmaceutically acceptable filler. 
     
     
         29 . The method of  claim 28 , wherein the pharmaceutically acceptable filler is mannitol. 
     
     
         30 . The method of  claim 24 , wherein the gastro-protective coating is about 5% to about 20% by weight of each tablet. 
     
     
         31 . The method of  claim 24 , wherein the gastro-protective coating is about 8% to about 18% by weight of each tablet. 
     
     
         32 . The method of  claim 24 , wherein the gastro-protective coating is about 8% to about 15% by weight of each tablet. 
     
     
         33 . The method of  claim 24 , wherein the gastro-protective coating is about 12% to about 16% by weight of each tablet. 
     
     
         34 . The method of  claim 24 , wherein the gastro-protective coating is about 10% to about 12% by weight of each tablet. 
     
     
         35 . The method of  claim 24 , wherein the oral dosage form comprises about 35 mg to about 500 mg of the oligonucleotide or a pharmaceutically acceptable salt thereof. 
     
     
         36 . The method of  claim 35 , wherein the oral dosage form comprises about 40 mg of the oligonucleotide or a pharmaceutically acceptable salt thereof. 
     
     
         37 . The method of  claim 35 , wherein the oral dosage form comprises about 50 mg of the oligonucleotide or a pharmaceutically acceptable salt thereof. 
     
     
         38 . The method of  claim 35 , wherein the oral dosage form comprises about 70 mg of the oligonucleotide or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The method of  claim 35 , wherein the oral dosage form comprises 100 mg of the oligonucleotide or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The method of  claim 35 , wherein the oral dosage form comprises 150 mg of the oligonucleotide or a pharmaceutically acceptable salt thereof. 
     
     
         41 . The method of  claim 24 , wherein when orally administered to a patient, results in substantially minimal plasma concentration of the oligonucleotide or a pharmaceutically acceptable salt thereof in the patient. 
     
     
         42 . The method of  claim 24 , wherein the oral dosage form is suitable for delivering the oligonucleotide or a pharmaceutically acceptable salt thereof substantially to the terminal ileum and/or right colon. 
     
     
         43 . The method of  claim 24 , wherein the IBD is Crohn's disease or ulcerative colitis.