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

外国特許コード F130007604
整理番号 AF22-02WO
掲載日 2013年8月9日
出願国 アメリカ合衆国
出願番号 201113823913
公報番号 20130183348
公報番号 9186371
出願日 平成23年9月14日(2011.9.14)
公報発行日 平成25年7月18日(2013.7.18)
公報発行日 平成27年11月17日(2015.11.17)
国際出願番号 JP2011071023
国際公開番号 WO2012036215
国際出願日 平成23年9月14日(2011.9.14)
国際公開日 平成24年3月22日(2012.3.22)
優先権データ
  • 特願2010-209587 (2010.9.17) JP
  • 特願2011-138825 (2011.6.22) JP
  • 2011WO-JP71023 (2011.9.14) WO
発明の名称 (英語) Inhibitor of HMGB protein-mediated immune response activation, and screening method
発明の概要(英語) (US9186371)
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.
特許請求の範囲(英語) [claim1]
1. A method of inhibiting activation of an immune response mediated by a high-mobility group box (HMGB) protein, the method comprising administering to a subject in need thereof a phosphorothioate oligonucleotide of 20 to 40 nucleotides in length in an amount effective to inhibit an immune response in the subject, wherein
the phosphorothioate oligonucleotide binds to HMGB protein,
the phosphorothioate oligonucleotide does not have an unmethylated CG sequence, and
the phosphorothioate oligonucleotide does not have a methylated guanine.
[claim2]
2. The method according to claim 1, wherein the phosphorothioate oligonucleotide 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 or more nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim3]
3. The method according to claim 1, wherein the phosphorothioate oligonucleotide inhibits a binding between a nucleic acid activating the immune response and the HMGB protein in a cell.
[claim4]
4. The method according to claim 1, 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.
[claim5]
5. The method according to claim 1, wherein the phosphorothioate oligonucleotide 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 five nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim6]
6. The method according to claim 1, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim7]
7. The method according to claim 5, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim8]
8. The method according to claim 1, wherein the phosphorothioate oligonucleotide 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 three nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim9]
9. The method according to claim 8, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim10]
10. The method according to claim 1, wherein the phosphorothioate oligonucleotide is a phosphorothioate oligonucleotide consisting of a nucleotide sequence as set forth in SEQ ID NO: 40.
[claim11]
11. The method according to claim 10, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim12]
12. The method according to claim 1, wherein the phosphorothioate oligonucleotide is a phosphorothioate oligonucleotide comprising: a nucleotide sequence as set forth in SEQ ID NO: 40; or
a nucleotide sequence having deletion, substitution, or addition of one or more nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim13]
13. The method according to claim 1, wherein the phosphorothioate oligonucleotide is a phosphorothioate oligonucleotide comprising: a nucleotide sequence as set forth in SEQ ID NO: 40; or
a nucleotide sequence having deletion, substitution, or addition of one to five nucleotides in the nucleotide sequence as set forth in SEQ ID NO: 40 and having a binding ability to an HMGB protein.
[claim14]
14. The method according to claim 13, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim15]
15. The method according to claim 1, wherein the phosphorothioate oligonucleotide is a phosphorothioate oligonucleotide comprising: a 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 an HMGB protein.
[claim16]
16. The method according to claim 15, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim17]
17. The method according to claim 1, wherein the phosphorothioate oligonucleotide is a phosphorothioate oligonucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 40.
[claim18]
18. The method according to claim 17, wherein the activation of an immune response mediated by an HMGB protein causes multiple sclerosis or septicemia.
[claim19]
19. The method according to claim 1, wherein the activation of an immune response mediated by an HMGB protein causes an inflammatory disease.
[claim20]
20. The method according to claim 1, wherein the phosphorothioate oligonucleotide is unmethylated.
[claim21]
21. The method according to claim 1, wherein the phosphorothioate oligonucleotide does not comprise a CG sequence.
  • 発明者/出願人(英語)
  • TANIGUCHI TADATSUGU
  • YANAI HIDEYUKI
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)
参考情報 (研究プロジェクト等) CREST Etiological Basics of and Techniques for Treatment of Allergic and Autoimmune Diseases AREA
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