US2015231169A1PendingUtilityA1

Therapeutic antisense oligonucleotide composition for the treatment of inflammatory bowel disease

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Assignee: ATLANTIC PHARMACEUTICALS HOLDINGS LTDPriority: Dec 2, 2004Filed: May 6, 2015Published: Aug 20, 2015
Est. expiryDec 2, 2024(expired)· nominal 20-yr term from priority
Inventors:Mark K. Wedel
A61K 31/7125A61K 31/7105C12N 15/1138A61P 1/04C12N 2310/11A61K 31/7088A61K 31/711A61K 9/0031A61P 1/00C12N 2310/315A61K 47/38A61K 48/00A61K 38/16
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Claims

Abstract

Disclosed herein is a method for the sustained amelioration and/or treatment of ulcerative colitis comprising rectal administration of a compound comprising an antisense oligonucleotide having the sequence 5′-GCCCAAGCTOGCATCCOTCA-3′, ISIS 2302. The method results in a decrease in the indications of ulcerative colitis for an extended period (greater than 90 days) after the conclusion of the administration of the composition. The composition is well tolerated and systemic exposure is minimal.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A use of a composition comprising an oligonucleotide having a sequence comprising SEQ ID NO 2 and hydroxypropyl methylcellulose for the preparation of a medicament for rectal administration wherein the composition results in minimal systemic exposure to the oligonucleotide. 
     
     
         2 . The use of  claim 1 , wherein minimal systemic exposure comprises systemic availability of less than about 5% of a rectally administered dose. 
     
     
         3 . The use of  claim 1 , wherein the medicament results in amelioration of at least one indication of ulcerative colitis. 
     
     
         4 . The use of  claim 1 , wherein the medicament results in amelioration of at least one of mucosal friability, stool frequency, rectal bleeding, or disease activity index. 
     
     
         5 . The use of  claim 1 , wherein the oligonucleotide comprises at least one phosphorothioate linkage. 
     
     
         6 . The use of  claim 1 , wherein the medicament results in sustained mucosal healing. 
     
     
         7 . The use of  claim 6 , wherein sustained mucosal healing is maintained for at least about 90 days. 
     
     
         8 . The use of  claim 6 , wherein sustained mucosal healing is maintained for at least about 120 days. 
     
     
         9 . The use of  claim 1 , wherein the medicament has disease modifying activity. 
     
     
         10 . The use of  claim 2 , wherein ulcerative colitis is moderate to severe ulcerative colitis. 
     
     
         11 . A method for sustained amelioration of at least one indication of ulcerative colitis in an individual comprising:
 rectally administering a therapeutic dose of a composition comprising an antisense oligonucleotide about 15 to 30 nucleic acid base units in length to an individual wherein the oligonucleotide specifically hybridizes with nucleotides 2114 to 2133 of SEQ ID 1, and   monitoring the individual for the amelioration of at least one indication of ulcerative colitis   
     
     
         12 . The method of  claim 11 , wherein the indication of ulcerative colitis comprises mucosal friability. 
     
     
         13 . The method of  claim 11 , wherein the indication of ulcerative colitis comprises stool frequency. 
     
     
         14 . The method of  claim 11 , wherein the indication of ulcerative colitis comprises rectal bleeding. 
     
     
         15 . The method of  claim 11 , wherein the indication of ulcerative colitis comprises disease activity index. 
     
     
         16 . The method of  claim 11 , wherein the antisense oligonucleotide is modified. 
     
     
         17 . The method of  claim 16 , wherein the antisense oligonucleotide comprises at least one phosphorothioate nucleotide linkage. 
     
     
         18 . The method of  claim 16 , wherein the antisense oligonucleotide comprises exclusively phosphorothioate nucleotide linkages. 
     
     
         19 . The method of  claim 11 , wherein sustained amelioration of ulcerative colitis comprises amelioration of at least one indication of ulcerative colitis after termination of a treatment period of administration of the composition to the individual for at least 60 days. 
     
     
         20 . The method of  claim 11 , wherein sustained amelioration of ulcerative colitis comprises amelioration of at least one indication of ulcerative colitis after termination of a treatment period of administration of the composition to the individual for at least 90 days. 
     
     
         21 . The method of  claim 11 , wherein the rectally administered composition is an enema. 
     
     
         22 . The method of  claim 11 , wherein the therapeutic dose comprises at least about 240 mg of the antisense oligonucleotide per day. 
     
     
         23 . The method of  claim 11 , wherein systemic exposure to the composition is less than 5% of the dose administered. 
     
     
         24 . The method of  claim 11  wherein the oligonucleotide is about 18 to 22 nucleic acid base units in length. 
     
     
         25 . A method for sustained amelioration of at least one indication of ulcerative colitis in an individual comprising:
 rectally administering a therapeutic dose of a composition comprising an antisense oligonucleotide comprising SEQ ID 2, and   monitoring the individual for the amelioration of at least one indication of ulcerative colitis.   
     
     
         26 . The method of  claim 25 , wherein the indication of ulcerative colitis comprises mucosal friability. 
     
     
         27 . The method of  claim 25 , wherein the indication of ulcerative colitis comprises stool frequency. 
     
     
         28 . The method of  claim 25 , wherein the indication of ulcerative colitis comprises rectal bleeding. 
     
     
         29 . The method of  claim 25 , wherein the indication of ulcerative colitis comprises disease activity index. 
     
     
         30 . The method of  claim 25 , wherein the antisense oligonucleotide is modified. 
     
     
         31 . The method of  claim 30 , wherein the antisense oligonucleotide comprises at least one phosphorothioate nucleotide linkage. 
     
     
         32 . The method of  claim 30 , wherein the antisense oligonucleotide comprises exclusively phosphorothioate nucleotide linkages. 
     
     
         33 . The method of  claim 25 , wherein sustained amelioration of ulcerative colitis comprises amelioration of at least one indication of ulcerative colitis after termination of a treatment period of administration of the composition to the individual for at least 60 days. 
     
     
         34 . The method of  claim 25 , wherein sustained amelioration of ulcerative colitis comprises amelioration of at least one indication of ulcerative colitis after termination of a treatment period of administration of the composition to the individual for at least 90 days. 
     
     
         35 . The method of  claim 25 , wherein the rectally administered composition is an enema. 
     
     
         36 . The method of  claim 25 , wherein the therapeutic dose comprises at least about 240 mg of the antisense oligonucleotide per day. 
     
     
         37 . The method of  claim 25 , wherein systemic exposure to the composition is less than 5% of the dose administered.

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