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Inhibitor of hmgb protein-mediated immune response activation, and screening method

Foreign code F130007602
File No. AF22-02WO
Posted date Aug 9, 2013
Country Canada
Application number 2811501
Gazette No. 2811501
Gazette No. 2811501
Date of filing Sep 14, 2011
Gazette Date Mar 22, 2012
Gazette Date Jan 10, 2017
International application number JP2011071023
International publication number WO2012036215
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, and screening method
Abstract (CA2811501)
Provided is an inhibitor of HMGB protein-mediated immune response activation, comprising one or more compounds selected from the group consisting of phosphorothioate oligonucleotides and derivatives thereof.
Also provided is a method for screening an inhibitor or promoter of HMGB protein-mediated immune response activation, comprising: a mixing step of mixing an HMGB protein and a labeled nucleic acid in the presence and absence of a test substance; a assaying step of assaying the HMGB protein bound to the labeled nucleic acid; and a determination step of determining that the test substance is an inhibitor of HMGB protein-mediated immune response activation in the case that the quantity of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is less than the quantity of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance, and determining that the test substance is a promoter of HMGB protein-mediated immune response activation in the case that the quantity of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is greater than the quantity of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance.
Scope of claims [claim1]
1. A phosphorothioate oligonucleotide for use in treating or preventing a disease selected from the group consisting of 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 acidcontaining pathogen, wherein the phosphorothioate oligonucleotide is characterized by absence of an unmethylated CG sequence and by a nucleotide sequence that consists of:
the nucleotide sequence as set forth in SEQ ID NO: 40;
or a nucleotide sequence having deletion, substitution, or addition of one to three nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to a high-mobility group box (HMGB) protein.
[claim2]
2. The phosphorothioate oligonucleotide for use according to claim 1
wherein the phosphorothioate oligonucleotide is characterized by a nucleotide sequence that consists of:
the nucleotide sequence as set forth in SEQ ID NO: 40;
or a nucleotide sequence having deletion, substitution, or addition of one nucleotide in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim3]
3. The phosphorothioate oligonucleotide for use according to claim 1
wherein the phosphorothioate oligonucleotide is characterized by a nucleotide sequence that consists of the nucleotide sequence as set forth in SEQ ID NO: 40.
[claim4]
4. The phosphorothioate oligonucleotide for use according to any one of claims 1
to 3, wherein the phosphorothioate oligonueleotide inhibits binding between a nucleic acid activating an immune response and an HMGB protein in a cell.
[claim5]
5. A composition for use in treating or preventing a disease selected from the group consisting of 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 acidcontaining pathogen, the composition comprising the phosphorothioate oligonucleotide as defined in any one of claims 1 to 4 and a pharmaceutically acceptable carrier.
[claim6]
6. Use of a phosphorothioate oligonucleotide for treating or preventing a disease selected from the group consisting of 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 acidcontaining pathogen, wherein the phosphorothioate oligonucleotide is characterized by absence of an unmethylated CG sequence and by a nucleotide sequence that consists of:
the nucleotide sequence as set forth in SEQ ID NO: 40;
or a nucleotide sequence having deletion, substitution, or addition of one to three nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to a high-mobility group box (HMGB) protein.
[claim7]
7. The use according to claim 6 wherein the phosphorothioate oligonucleotide is characterized by a nucleotide sequence that consists of:
the nucleotide sequence as set forth in SEQ ID NO: 40;
or a nucleotide sequence having deletion, substitution, or addition of one nucleotide in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim8]
8. The use according to claim 6 wherein the phosphorothioate oligonucleotide is characterized by a nucleotide sequence that consists of the nucleotide sequence as set forth in
SEQ ID NO: 40.
[claim9]
9. The use according to any one of claims 6 to 8, wherein the phosphorothioate oligonucleotide inhibits binding between a nucleic acid activating an immune response and an
HMGB protein in a cell.
  • Applicant
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • Inventor
  • TANIGUCHI TADATSUGU
  • YANAI HIDEYUKI
IPC(International Patent Classification)
Reference ( R and D project ) CREST Etiological Basics of and Techniques for Treatment of Allergic and Autoimmune Diseases AREA
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