Antisense oligonucleotides (ODN) against SMAD7 and uses thereof in medical field
The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.
1. An oligonucleotide comprising SEQ ID NO:2 (5′-GTXYCCCCTTCTCCCXYCAG-3′) wherein X is C and Y is G, and wherein at least one CG grouping is modified.
2. The oligonucleotide of claim 1 , wherein at least one of the nucleotides X comprises a methylated nitrogenous base.
3. The oligonucleotide of claim 2 , wherein the nitrogenous base is 5-methyl-cytosine.
4. The oligonucleotide of claim 1 , wherein at least one internucleoside linkage is a phosphorothioate linkage or a methylphosphonate linkage.
5. The oligonucleotide of claim 1 , wherein all internucleoside linkages are phosphorothioate linkages.
6. A pharmaceutical composition comprising the oligonucleotide of claim 1 , and a pharmaceutically acceptable adjuvant and/or excipient.
7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is an oral pharmaceutical composition.
8. A method of treating inflammatory bowel disease, comprising administering to a patient in need thereof an effective amount of the oligonucleotide of claim 1 , wherein the oligonucleotide is effective to treat inflammatory bowel disease.
9. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.
10. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.