Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8592390-B2
Publication Date
2013-11-26
Expiration Date
Abstract
Methods for enhancing steroid efficacy in a steroid refractory patient afflicted with an inflammatory condition who does not respond or responds poorly or inadequately to steroid anti-inflammatory treatment or a steroid dependent patient afflicted with an inflammatory condition and currently on steroid anti-inflammatory treatment who shows an inability to be weaned off systemic or topical administered steroid treatment comprise administering an oligonucleotide having the sequence 5′-Xm-CG-Yn-3′ wherein X is A, T, C, or G, Y is A, T, C, or G, m is 1-20 and n is 1-20, or the sequence 5′-CG-3′ and from 8 to 40 nucleotides, wherein at least one CG dinucleotide is unmethylated. The oligonucleotide is administered in an amount effective to improve sensitivity of the patient to the steroid anti-inflammatory treatment and thereby induce a clinical response in the steroid refractory patient or improve a clinical response in the steroid dependent patient.
Core Innovation
The invention relates to an immunostimulatory method for enhancing steroid efficacy in steroid refractory and steroid dependent patients afflicted with an inflammatory condition. The method uses CpG-containing oligonucleotides having at least one unmethylated CG dinucleotide, and administering the oligonucleotide in an amount effective to improve sensitivity of the patient to steroid anti-inflammatory treatment, thereby inducing a clinical response in steroid refractory patients or improving a clinical response in steroid dependent patients.
The oligonucleotide sequence is defined as 5′-X m-CG-Y n-3′, where X is A, T, C, or G, Y is A, T, C, or G, m is 1–20, and n is 1–20, with at least one CG dinucleotide being unmethylated. In an alternative embodiment, the oligonucleotide is 5′-CG-3′ and has from 8 to 40 nucleotides, also requiring at least one unmethylated CG dinucleotide.
The described approach is supported by clinical pilot/phase II findings in inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease, using a specific CpG DNA referred to as SEQ.ID.NO. 1 (DIMS0150). The document also reports immunostimulatory cytokine induction experiments using CpG versus GpC control ODNs, showing CpG-dependent induction of IL-10 and IFN-γ/IFN-α.
Claims Coverage
The document includes two independent claims covering a method to enhance steroid efficacy in steroid refractory or steroid dependent patients with an inflammatory condition through administration of specified CpG-containing oligonucleotides with unmethylated CG dinucleotides to improve steroid sensitivity and induce or improve clinical response. Across the independent claims, the inventive features center on steroid efficacy enhancement and oligonucleotide sequence and methylation constraints.
Enhancing steroid efficacy in steroid refractory or steroid dependent patients
A method for enhancing steroid efficacy in a steroid refractory patient afflicted with an inflammatory condition who does not respond or responds poorly or inadequately to steroid anti-inflammatory treatment, or a steroid dependent patient afflicted with an inflammatory condition and currently on and responding adequately to steroid anti-inflammatory treatment who shows an inability to be weaned off systemically or topically administered steroid treatment without increasing the severity of the inflammatory condition, by administering an oligonucleotide in an amount effective to improve sensitivity of the patient to the steroid anti-inflammatory treatment and thereby induce a clinical response in the steroid refractory patient or improve a clinical response in the steroid dependent patient.
Administering a defined unmethylated CG oligonucleotide sequence pattern
Administering to the patient an oligonucleotide having the sequence 5′-X m-CG-Y n-3′ wherein X is A, T, C, or G, Y is A, T, C, or G, and m is 1-20 and n is 1-20 and wherein at least one CG dinucleotide is unmethylated.
Administering a CG oligonucleotide of specified length with unmethylated CG dinucleotides
Administering to the patient an oligonucleotide having the sequence 5′-CG-3′ and from 8 to 40 nucleotides and wherein at least one CG dinucleotide is unmethylated.
Overall, the claim coverage is directed to methods that enhance steroid efficacy by administering CpG-containing oligonucleotides with at least one unmethylated CG dinucleotide, with sequence definitions including a 5′-X m-CG-Y n-3′ pattern and a 5′-CG-3′ sequence with 8–40 nucleotides, to improve patient sensitivity to steroid anti-inflammatory treatment and induce or improve clinical response.
Stated Advantages
Improves sensitivity of the patient to steroid anti-inflammatory treatment.
Induces a clinical response in a steroid refractory patient.
Improves a clinical response in a steroid dependent patient.
Enables improvement of outcomes without increasing the severity of the inflammatory condition when addressing inability to be weaned off steroid treatment.
Documented Applications
Use in ulcerative colitis and Crohn’s disease involving steroid refractory/dependent patients treated with CpG DNA (SEQ.ID.NO. 1 / DIMS0150).
Cytokine induction/immunostimulatory testing using CpG versus GpC control ODNs measuring IL-10 and IFN-γ/IFN-α.
Interested in licensing this patent?