Unmethylated CpG Oligonucleotide for Ulcerative Colitis Remission
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Solution Overview
Problem
Current treatments for chronic active ulcerative colitis often fail to adequately manage the condition, leading to a significant proportion of patients requiring surgical intervention, such as colectomy, which carries risks and economic burdens.
Innovation Solution
An oligonucleotide with the sequence 5'-G*G*A*ACAGTTCGTCCAT*G*G*C-3' (SEQ ID NO:1), where the CG dinucleotide is unmethylated, is repetitively administered as a single exposure on two or more separate occasions 4 or more weeks apart, either alone or in combination with other therapies, to treat chronic active ulcerative colitis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-inflammatory therapy is used to treat chronic active ulcerative colitis, then initial symptom management may be achieved, but a significant proportion of patients will fail to respond or require surgical intervention (colectomy) within 10 years
Solution Approach 1:
The patent applies parameter changes by using an unmethylated CG dinucleotide sequence in the oligonucleotide, which fundamentally alters the immunomodulatory mechanism compared to conventional therapies. This specific nucleotide configuration triggers a distinct immune response pathway that maintains long-term efficacy without leading to the treatment failure and surgical intervention seen with traditional anti-inflammatory drugs
Solution Approach 2:
The oligonucleotide acts as an intermediary substance that mediates the immune response in ulcerative colitis. By introducing this specific unmethylated CG dinucleotide sequence, the patent creates a new therapeutic intermediary that bridges the gap between conventional therapy and complete remission, preventing the progression to surgical intervention
2Reliability
If surgical intervention (colectomy) is performed to treat refractory ulcerative colitis, then the disease is curative and quality of life improves, but the procedure carries considerable risks and presents significant pre- and postoperative morbidity
Solution Approach 1:
The patent applies preliminary anti-action by using the oligonucleotide therapy to prevent the development of refractory disease that would otherwise require surgical intervention. By administering this unmethylated CG dinucleotide sequence, the treatment preemptively addresses the underlying immune dysregulation, preventing the condition from progressing to a state where colectomy would be necessary and thereby avoiding surgical risks entirely
3Productivity
If conventional therapy is continued for extended periods to avoid colectomy, then surgical intervention may be prevented, but a significant proportion of patients will have recurrent flares or chronic continuous disease
Solution Approach 1:
The patent applies parameter changes by introducing the unmethylated CG dinucleotide sequence that fundamentally alters the disease course. This specific nucleotide parameter change induces a stable remission state that prevents recurrent flares, thereby maintaining both surgical intervention avoidance and long-term disease stability simultaneously
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively reduces the need for colectomy by improving clinical, endoscopic, and histological outcomes, with a significant proportion of patients achieving remission and avoiding surgical intervention for extended periods.
Implementation Method 1
an oligonucleotide having the sequence 5'-G*G*A*ACAGTTCGTCCAT*G*G*C-3' (SEQ ID NO:1), wherein the CG dinucleotide is unmethylated
Data Source
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AI summary
The present invention relates to methods of preventing or reducing the need of colectomy. In particular, the present invention relates to an oligonucleotide, for use in the treatment of an inflammatory bowel disease, such as ulcerative colitis (UC) or Crohn's disease, in a subject that is refractory or responds insufficiently or is intolerant to anti-inflammatory therapy, wherein said oligonucleotide is repetitively administered as a single exposure.