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Inhibitor of hmgb protein-mediated immune response activation

Foreign code F170009211
File No. AF22-02WO
Posted date Sep 12, 2017
Country EPO
Application number 11825215
Gazette No. 2617426
Gazette No. 2617426
Date of filing Sep 14, 2011
Gazette Date Jul 24, 2013
Gazette Date Aug 10, 2016
International application number JP2011071023
International publication number WO2012036215
Date of international filing Sep 14, 2011
Date of international publication Mar 22, 2012
Priority data
  • P2010-209587 (Sep 17, 2010) JP
  • P2011-138825 (Jun 22, 2011) JP
  • 2011WO-JP71023 (Sep 14, 2011) WO
Title Inhibitor of hmgb protein-mediated immune response activation
Abstract (EP2617426)
Provided are an inhibitor of activation of an immune response mediated by an HMGB protein, the inhibitor containing at least one compound selected from the group consisting of a phosphorothioate oligonucleotide and a derivative thereof, and a method of screening for an inhibitor or enhancer of activation of an immune response mediated by an HMGB protein, the method including a mixing step of mixing an HMGB protein and a labeled nucleic acid in the presence and absence of a test substance; a quantifying step of quantifying the HMGB protein bound to the labeled nucleic acid; and a determination step of determining that the test substance is an inhibitor of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is less than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance and determining that the test substance is an enhancer of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is higher than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance.
Scope of claims [claim1]
1. An inhibitor of activation of an immune response mediated by an HMGB protein, the inhibitor consisting of at least one compound selected from the group consisting of a phosphorothioate oligonucleotide and a derivative thereof.
[claim2]
2. The inhibitor according to claim 1, wherein the compound is a phosphorothioate oligonucleotide, wherein the phosphorothioate oligonucleotide does not include an unmethylated CG sequence and has a length of 5 to 100 nucleotides.
[claim3]
3. The inhibitor according to claim 2, wherein the compound is a phosphorothioate oligonucleotide consisting of: a nucleotide sequence as set forth in SEQ ID NO: 40; or a nucleotide sequence having deletion, substitution, or addition of one to several nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim4]
4. The inhibitor according to claim 1, wherein the compound is a derivative of a phosphorothioate oligonucleotide, and the derivative is a base-free phosphorothioate deoxyribose homopolymer.
[claim5]
5. The inhibitor according to any one of claims 1 to 4, wherein the inhibitor inhibits a binding between a nucleic acid activating an immune response and an HMGB protein in a cell.
[claim6]
6. The inhibitor according to any one of claims 1 to 5, wherein the activation of an immune response mediated by an HMGB protein is selected from the group consisting of antigen-specific adaptive immune system, multiple sclerosis, excessive immune response to a dead cell, organ transplant rejection, autoimmune disease, inflammatory bowel disease, allergy, septicemia, tumor growth by inflammation and inflammatory disease caused by a nucleic acid-containing pathogen.
[claim7]
7. A composition for use in inhibiting an activation of an immune response mediated by an HMGB protein, the composition comprising the inhibitor according to any one of claims 1 to 6 and a pharmaceutically acceptable carrier.
[claim8]
8. A method of screening for an inhibitor or enhancer of activation of an immune response mediated by an HMGB protein, the method comprising: a mixing step of mixing an HMGB protein and a labeled nucleic acid in the presence and absence of a test substance; a quantifying step of quantifying the HMGB protein bound to the labeled nucleic acid; and a determination step of determining that the test substance is an inhibitor of activation of an immune response mediated by the HMGB protein when an amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is less than an amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance and determining that the test substance is an enhancer of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is higher than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance.
[claim9]
9. A method of screening for an inhibitor or enhancer of activation of an immune response mediated by an HMGB protein, the method comprising: an incubation step of incubating an immobilized HMGB protein in the presence and absence of a test substance; a labeled-nucleic-acid-contacting-step of contacting a labeled nucleic acid with the immobilized HMGB protein after the incubation step; a quantifying step of quantifying the labeled nucleic acid bound to the immobilized HMGB protein; and a determination step of determining that the test substance is an inhibitor of activation of an immune response mediated by the HMGB protein when the amount of the labeled nucleic acid bound to the immobilized HMGB protein on which the incubation step is performed in the presence of the test substance is less than the amount of the labeled nucleic acid bound to the immobilized HMGB protein on which the incubation step is performed in the absence of the test substance and determining that the test substance is an enhancer of activation of an immune response mediated by the HMGB protein when the amount of the labeled nucleic acid bound to the immobilized HMGB protein on which the incubation step is performed in the presence of the test substance is higher than the amount of the labeled nucleic acid bound to the immobilized HMGB protein on which the incubation step is performed in the absence of the test substance.
[claim10]
10. A method of screening for an inhibitor or enhancer of activation of an immune response mediated by an HMGB protein, the method comprising: a contacting step of contacting an HMGB protein with an immobilized nucleic acid in the presence and absence of a test substance; a quantifying step of quantifying the HMGB protein bound to the immobilized nucleic acid; and a determination step of determining that the test substance is an inhibitor of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the immobilized nucleic acid in the presence of the test substance is less than the amount of the HMGB protein bound to the immobilized nucleic acid in the absence of the test substance and determining that the test substance is an enhancer of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the immobilized nucleic acid in the presence of the test substance is higher than the amount of the HMGB protein bound to the immobilized nucleic acid in the absence of the test substance.
  • Applicant
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • Inventor
  • YANAI HIDEYUKI
  • TANIGUCHI TADATSUGU
IPC(International Patent Classification)
Specified countries (EP2617426)
Contracting States: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
Reference ( R and D project ) CREST Etiological Basics of and Techniques for Treatment of Allergic and Autoimmune Diseases AREA
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