US2009275631A1PendingUtilityA1

Therapeutic antisense oligonucleotide composition for the treatment of inflammatory bowel disease

57
Assignee: ISIS PHARMACEUTICALS INCPriority: Dec 2, 2004Filed: Dec 2, 2005Published: Nov 5, 2009
Est. expiryDec 2, 2024(expired)· nominal 20-yr term from priority
Inventors:Mark K. Wedel
A61K 31/7088A61K 31/7125C12N 2310/11A61K 31/7105A61K 9/0031C12N 2310/315C12N 15/1138A61K 31/711A61K 47/38A61P 1/00A61P 1/04A61K 48/00A61K 38/16
57
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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′-GCCCAAGCTGGCATCCGTCA-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
1 - 37 . (canceled) 
     
     
         38 . A method for sustained amelioration of at least one indication of ulcerative colitis in an individual comprising:
 rectally administering, at a frequency of not more than once every other day, 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.   
     
     
         39 . The method of  claim 38 , wherein the indication of ulcerative colitis comprises mucosal friability. 
     
     
         40 . The method of  claim 38 , wherein the indication of ulcerative colitis comprises stool frequency. 
     
     
         41 . The method of  claim 38 , wherein the indication of ulcerative colitis comprises rectal bleeding. 
     
     
         42 . The method of  claim 38 , wherein the indication of ulcerative colitis comprises disease activity index. 
     
     
         43 . The method of  claim 38 , wherein the antisense oligonucleotide is modified. 
     
     
         44 . The method of  claim 43 , wherein the antisense oligonucleotide comprises at least one phosphorothioate nucleotide linkage. 
     
     
         45 . The method of  claim 43 , wherein the antisense oligonucleotide comprises exclusively phosphorothioate nucleotide linkages. 
     
     
         46 . The method of  claim 38 , 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. 
     
     
         47 . The method of  claim 38 , 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. 
     
     
         48 . The method of  claim 38 , wherein the rectally administered composition is an enema. 
     
     
         49 . The method of  claim 38 , wherein the therapeutic dose comprises at least about 240 mg of the antisense oligonucleotide per administration. 
     
     
         50 . The method of  claim 38 , wherein the oligonucleotide is about 18 to 22 nucleic acid base units in length. 
     
     
         51 . The method of  claim 38 , wherein the composition further comprises hydroxypropyl methylcellulose. 
     
     
         52 . The method of  claim 51 , wherein systemic exposure to the oligonucleotide is less than 5% of the dose administered. 
     
     
         53 . The method of  claim 38 , wherein the composition is administered once every other day. 
     
     
         54 . A method for sustained amelioration of at least one indication of ulcerative colitis in an individual comprising:
 rectally administering, at a frequency of not more than once every other day, a therapeutic dose of a composition comprising an antisense oligonucleotide of SEQ ID 2; and   monitoring the individual for the amelioration of at least one indication of ulcerative colitis.   
     
     
         55 . The method of  claim 54 , wherein the indication of ulcerative colitis comprises mucosal friability. 
     
     
         56 . The method of  claim 54 , wherein the indication of ulcerative colitis comprises stool frequency. 
     
     
         57 . The method of  claim 54 , wherein the indication of ulcerative colitis comprises rectal bleeding. 
     
     
         58 . The method of  claim 54 , wherein the indication of ulcerative colitis comprises disease activity index. 
     
     
         59 . The method of  claim 54 , wherein the antisense oligonucleotide is modified. 
     
     
         60 . The method of  claim 59 , wherein the antisense oligonucleotide comprises at least one phosphorothioate nucleotide linkage. 
     
     
         61 . The method of  claim 59 , wherein the antisense oligonucleotide comprises exclusively phosphorothioate nucleotide linkages. 
     
     
         62 . The method of  claim 54 , 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. 
     
     
         63 . The method of  claim 54 , 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. 
     
     
         64 . The method of  claim 54 , wherein the rectally administered composition is an enema. 
     
     
         65 . The method of  claim 54 , wherein the therapeutic dose comprises at least about 240 mg of the antisense oligonucleotide per administration. 
     
     
         66 . The method of  claim 54 , wherein the composition further comprises hydroxypropyl methylcellulose. 
     
     
         67 . The method of  claim 66 , wherein systemic exposure to the oligonucleotide is less than 5% of the dose administered. 
     
     
         68 . The method of  claim 54 , wherein the composition is administered once every other day. 
     
     
         69 . A method for ameliorating at least one indication of ulcerative colitis in an individual comprising:
 rectally administering at a therapeutic dose of a composition comprising an antisense oligonucleotide about 15 to 30 nucleic acid base units in length and hydroxypropyl methylcellulose to an individual, wherein the oligonucleotide specifically hybridizes with nucleotides 2114 to 2133 of SEQ ID 1, and wherein the administration results in minimal systemic exposure to the oligonucleotide; and   monitoring the individual for the amelioration of at least one indication of ulcerative colitis.   
     
     
         70 . The method of  claim 69 , wherein the systemic exposure to the oligonucleotide is less than 5% of the dose administered. 
     
     
         71 . The method of  claim 69 , wherein the indication of ulcerative colitis comprises mucosal friability. 
     
     
         72 . The method of  claim 69 , wherein the indication of ulcerative colitis comprises stool frequency. 
     
     
         73 . The method of  claim 69 , wherein the indication of ulcerative colitis comprises rectal bleeding. 
     
     
         74 . The method of  claim 69 , wherein the indication of ulcerative colitis comprises disease activity index. 
     
     
         75 . The method of  claim 69 , wherein the antisense oligonucleotide is modified. 
     
     
         76 . The method of  claim 75 , wherein the antisense oligonucleotide comprises at least one phosphorothioate nucleotide linkage. 
     
     
         77 . The method of  claim 75 , wherein the antisense oligonucleotide comprises exclusively phosphorothioate nucleotide linkages. 
     
     
         78 . The method of  claim 69 , wherein the rectally administered composition is an enema. 
     
     
         79 . The method of  claim 69 , wherein the therapeutic dose comprises at least about 240 mg of the antisense oligonucleotide per administration. 
     
     
         80 . The method of  claim 69 , wherein the oligonucleotide is about 18 to 22 nucleic acid base units in length. 
     
     
         81 . The method of  claim 69 , wherein the oligonucleotide is 20 nucleic acid base units in length. 
     
     
         82 . The method of  claim 81 , wherein the oligonucleotide has the sequence of SEQ ID NO: 2. 
     
     
         83 . The method of  claim 69 , wherein the composition is administered at a frequency of not more than once every other day. 
     
     
         84 . The method of  claim 83 , wherein the composition is administered once every other day.

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