New therapy

Abstract

The present invention provides an oligonucleotide comprising the sequence 5′-GGAACAGTTCGTCCATGGC-3′ (SEQ ID NO:2) for use in the treatment of inflammatory bowel disease in a human subject, wherein individual doses of from 100 mg to 350 mg of said oligonucleotide are administered to the subject on at least four separate occasions, wherein the separate occasions are each a week apart.

1 . An oligonucleotide comprising the sequence 5′-GGAACAGTTCGTCCATGGC-3′ (SEQ ID NO:2) for use in the treatment of an inflammatory bowel disease in a human subject, wherein individual doses of from 100 mg to 350 mg of said oligonucleotide are administered to the subject on at least four separate occasions, wherein the separate occasions are each a week apart. 
     
     
         2 . The oligonucleotide for use according to  claim 1 , wherein said inflammatory bowel disease is ulcerative colitis. 
     
     
         3 . The oligonucleotide for use according to  claim 2 , wherein said ulcerative colitis is active ulcerative colitis. 
     
     
         4 . The oligonucleotide for use according to  claim 2  or  3 , wherein said ulcerative colitis is chronic active ulcerative colitis. 
     
     
         5 . The oligonucleotide for use according to any of the preceding claims, wherein the subject is refractory or responds insufficiently or is intolerant to anti-inflammatory therapy. 
     
     
         6 . The oligonucleotide for use according to any of the preceding claims, wherein said subject is elective for colectomy. 
     
     
         7 . The oligonucleotide for use according to any of the preceding claims, wherein at least one CG dinucleotide is unmethylated. 
     
     
         8 . The oligonucleotide for use according to any of the preceding claims, wherein at least one nucleotide in said oligonucleotide has a backbone modification. 
     
     
         9 . The oligonucleotide for use according to  claim 8 , wherein said backbone modification is a phosphate backbone modification represented by a phosphorothioate or a phosphorodithioate modification. 
     
     
         10 . The oligonucleotide for use according to any of  claims 8  and  9 ,
 wherein said backbone modification is located in the 5′- and/or the 3′-end of said oligonucleotide. 
 
     
     
         11 . The oligonucleotide for use according to any of the preceding claims,
 wherein said oligonucleotide has the sequence 5′-GGAACAGTTCGTCCATGGC-3′ (SEQ ID NO:2), wherein the CG dinucleotide is unmethylated.   
     
     
         12 . The oligonucleotide for use according to any of the preceding claims,
 wherein said oligonucleotide has the sequence 5′-G*G*A*ACAGTTCGTCCAT*G*G*C-3′ (SEQ ID NO:1), wherein the CG dinucleotide is unmethylated.   
     
     
         13 . The oligonucleotide for use according to any of the preceding claims,
 wherein said oligonucleotide is cobitolimod.   
     
     
         14 . The oligonucleotide for use according to any of the preceding claims, wherein individual doses of 100 mg to 150 mg, preferably 120 mg to 130 mg of said oligonucleotide are administered. 
     
     
         15 . The oligonucleotide for use according to any of the preceding claims, wherein individual doses of about 125 mg of said oligonucleotide are administered. 
     
     
         16 . The oligonucleotide for use according to any of the preceding claims, wherein individual doses of said oligonucleotide are administered to the subject on only four separate occasions, wherein the separate occasions are each a week apart. 
     
     
         17 . The oligonucleotide for use according to any of  claims 1  to  15 , wherein individual doses of said oligonucleotide are administered to the subject on at least four separate occasions, wherein the separate occasions are each a week apart, until the subject is in remission. 
     
     
         18 . The oligonucleotide for use according to any of the preceding claims, wherein the subject receives one or more additional therapeutic agents for the treatment of an inflammatory bowel disease, typically ulcerative colitis. 
     
     
         19 . The oligonucleotide for use according to any of the preceding claims, wherein said oligonucleotide is administered topically to mucosal membranes. 
     
     
         20 . The oligonucleotide for use according to any of the preceding claims, wherein said oligonucleotide is administered rectally. 
     
     
         21 . The oligonucleotide for use according to any of the preceding claims, wherein the oligonucleotide is cobitolimod, and individual doses of about 125 mg of cobitolimod are administered to the subject on only four separate occasions, wherein the separate occasions are each a week apart. 
     
     
         22 . A pharmaceutical composition comprising an oligonucleotide as defined in any of  claims 1  and  7  to  13 , together with one or more pharmaceutically acceptable carriers, for use in the treatment of an inflammatory bowel disease as defined in any of  claims 1  to  4  in a human subject as defined in any of  claims 1 ,  5  and  6 , wherein individual administrations of said composition are administered to the subject on at least four separate occasions, wherein the separate occasions are each a week apart, and wherein each administration of the composition delivers an amount of the oligonucleotide as defined in any of  claims 1 ,  14  and  15 . 
     
     
         23 . The composition for use according to  claim 22 , wherein the pharmaceutically acceptable carrier is water. 
     
     
         24 . The composition for use according to any of  claims 22  and  23 , wherein the pharmaceutical composition consists essentially of said oligonucleotide and water. 
     
     
         25 . A method of treating an inflammatory bowel disease as defined in any of  claims 1  to  4 , in a human subject as defined in any of  claims 1 ,  5  and  6 , comprising administering to said subject an oligonucleotide as defined in any of  claims 1  and  7  to  13  or a composition as defined in any of  claims 21  to  23 , wherein individual administrations of said oligonucleotide or composition are administered to the patient on at least four separate occasions, wherein the separate occasions are each a week apart, and wherein each administration of the oligonucleotide or composition delivers an amount of the oligonucleotide as defined in any of  claims 1 ,  14  and  15 . 
     
     
         26 . An oligonucleotide as defined in any one of  claims 1  and  7  to  13  for use in the treatment of an inflammatory bowel disease as defined in any of  claims 1  to  4  in a human subject as defined in any of  claims 1 ,  5  and  6 , wherein individual doses of from 100 mg to 350 mg of said oligonucleotide are administered to the subject every week until the patient is in remission.