Method for screening prophylactic or therapeutic agents for diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5 and agent for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5
Inventors
Akiyama, Tetsu • Harada, Hiroaki • YAMAZUMI, YUSUKE • ODA, TAKEAKI • SASAKI, OH • KOFU, KAZUYOSHI
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11279935-B2
Publication Date
2022-03-22
Expiration Date
Abstract
Provided are a method for screening agents for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5 and an agent for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5. A method for screening agents for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5 having as the index at least one selected from the group consisting of changes in the expression of the MEX3B gene or MEX3B protein and changes in the function of the MEX3B protein.
Core Innovation
The patent describes screening and therapeutic approaches for diseases driven by IL-6, IL-13, TNF, G-CSF, and CXCL1/2/5 using MEX3B as an index or target. The described screening method selects agents based on changes in MEX3B gene or protein expression, or MEX3B protein function.
The therapeutic concept centers on administering a substance that decreases MEX3B expression or function to a patient with a respiratory or pulmonary disease. The therapeutic substances described include antisense oligonucleotides, siRNA/dsRNA or DNA encoding them, and genome-editing nucleases such as CRISPR/Cas using a guide RNA targeting a partial region of the MEX3B gene.
The patent provides experimental support linking MEX3B to inflammatory disease features. Using MEX3B knockout mice and a severe asthma model, the document reports reduced IL-6 and CXCL5 with Mex3b deficiency and amelioration of severe asthma features.
Claims Coverage
The document provides coverage for at least one independent therapeutic method and its refinements, with seven inventive features spanning MEX3B-based treatment, three substance classes, gene sequence limitations, severe asthma limitations, and a CRISPR/Cas9 subtype limitation.
MEX3B expression decrease for respiratory or pulmonary disease
A therapeutic method for a respiratory disease or a pulmonary disease comprising administering a substance for decreasing expression of MEX3B gene to a patient with a respiratory disease or a pulmonary disease.
Antisense oligonucleotide complementary to MEX3B gene region
The substance for decreasing of the MEX3B gene is an antisense oligonucleotide having a sequence complementary to an oligonucleotide comprising at least 10 contiguous nucleotides contained in the MEX3B gene or in an expression control region of the gene.
Double-stranded RNA (or encoding DNA) targeting MEX3B RNA regions
The substance for decreasing of the MEX3B gene is a double-stranded RNA containing at least 20 contiguous nucleotides in a coding region or an untranslated region in the sequence of an RNA to be transcribed from the sequence of the MEX3B gene, or a DNA encoding the double-stranded RNA.
CRISPR/Cas nuclease with guide RNA complementary to 15 to 25 bases of MEX3B
The substance for decreasing of the MEX3B gene is an artificial nuclease that is CRISPR/Cas nuclease, wherein the CRISPR/Cas nuclease comprises a guide RNA having a sequence complementary to a partial sequence of 15 to 25 bases of the MEX3B gene and Cas nuclease.
MEX3B gene sequence specified by SEQ ID NO: 1 or 4
The MEX3B gene is a gene consisting of the sequence described in SEQ ID NO: 1 or 4 of the Sequence Listing.
Severe asthma associated with IL-6, IL-13, TNF, G-CSF, or CXCL1/2/5
The respiratory or pulmonary disease is severe asthma caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5.
CRISPR/Cas nuclease as CRISPR/Cas9
The method uses the CRISPR/Cas nuclease CRISPR/Cas9.
Overall, the claim coverage centers on a therapeutic method for respiratory or pulmonary disease that decreases MEX3B gene expression using antisense oligonucleotides, double-stranded RNA or encoding DNA, or CRISPR/Cas nuclease with a guide RNA complementary to a 15 to 25 base partial sequence of the MEX3B gene, with additional narrowing to severe asthma associated with selected cytokines/chemokines and CRISPR/Cas9.
Stated Advantages
Amelioration of severe asthma features in a severe asthma model with Mex3b deficiency and/or MEX3B-targeting intervention.
Reduced inflammatory cytokine and chemokine expression after administering an MEX3B-specific gapmer.
Reduced IL-6 and CXCL5 with Mex3b deficiency.
Reduced lung pathology.
Documented Applications
Therapeutic treatment of a respiratory or pulmonary disease, including severe asthma caused by interleukin 6, interleukin 13, TNF, G-CSF, and CXCL1/2/5, via decreasing MEX3B gene expression or function.
Screening method to select agents based on changes in MEX3B gene/protein expression or MEX3B protein function.
Interested in licensing this patent?