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THERAPEUTIC AGENT FOR ADHESION, METHOD FOR TREATING ADHESION, POSTOPERATIVE ADHESION MARKER, AND METHOD FOR EXAMINING SUSCEPTIBILITY TO POSTOPERATIVE ADHESION UPDATE

外国特許コード F180009421
整理番号 2016-002
掲載日 2018年4月26日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2017JP028869
国際公開番号 WO 2018030451
国際出願日 平成29年8月9日(2017.8.9)
国際公開日 平成30年2月15日(2018.2.15)
優先権データ
  • 特願2016-156962 (2016.8.9) JP
発明の名称 (英語) THERAPEUTIC AGENT FOR ADHESION, METHOD FOR TREATING ADHESION, POSTOPERATIVE ADHESION MARKER, AND METHOD FOR EXAMINING SUSCEPTIBILITY TO POSTOPERATIVE ADHESION UPDATE
発明の概要(英語) The present invention provides a therapeutic agent for an adhesion, a method for treating an adhesion, a postoperative adhesion marker and a method for testing for susceptibility to a postoperative adhesion, each of which can be applied to an adhesion occurring, for example, during an operation with an endoscope or the like or in an endogenous disease. The therapeutic agent for an adhesion according to the present invention is characterized by containing an expression-inhibiting substance capable of inhibiting the expression of periostin and/or a binding substance capable of binding to periostin. In the therapeutic agent for an adhesion according to the present invention, the expression-inhibiting substance comprises at least one substance selected from the group consisting of a substance capable of inhibiting the expression of mRNA for a periostin gene, a substance capable of cleaving the expressed mRNA and a substance capable of inhibiting the translation of a protein from the expressed mRNA.
特許請求の範囲(英語) [claim1]
1. And a substance which can suppress expression in inhibiting the expression of a fibroblast fibroblast binding agents and containing at least one of, adhesion therapeutic agent.
[claim2]
2. In which the expression suppressing substance, a fibroblast mRNA expression-suppressing substance of genes, mRNA expressed cut material, and the translation of the mRNA expressed proteins from a material for suppressing at least one resin selected from the group consisting of one of 1, according to claim 1 adhesion of the therapeutic agent.
[claim3]
3. In which the expression suppressing substance, a fibroblast suppression of expression of the gene is a nucleic acid molecule, nucleic acid molecules can be suppressed in which the expression, the expression of the gene as a sequence to suppress a fibroblast, (as4) including the following nucleotides, claims 1 or 2 adhesion therapeutic agent. (as4) 1-7 1 any one of the sequence of the polynucleotide comprising a nucleotide sequence that hybridizes under stringent conditions to and from the base sequence, a polynucleotide having a function of preventing the expression of the fibroblast
[claim4]
4. (as4) Of the nucleotides wherein, any one of SEQ ID NO:1-7 1 polynucleotide comprising a nucleotide sequence of the coding region and 3' untranslated region with respect to the at least one of a nucleotide sequence that hybridizes under stringent conditions and, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 3 adhesion of the therapeutic agent.
[claim5]
5. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:1 1229-3132 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, claims 3 or 4 adhesion therapeutic agent.
[claim6]
6. (as4) Of the nucleotides wherein, in the nucleotide sequence of SEQ ID NO:1 1229-1257 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 5 adhesion of the therapeutic agent.
[claim7]
7. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:1 1270-1301 with respect to the second polynucleotide comprising a nucleotide sequence that hybridizes under stringent conditions and to the base sequence, the expression of a gene to a fibroblast polynucleotide having a function of preventing, according to claim 5 adhesion of the therapeutic agent.
[claim8]
8. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:1 1426-1445 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 5 adhesion of the therapeutic agent.
[claim9]
9. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:1 1488-1509 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 5 adhesion of the therapeutic agent.
[claim10]
10. (as4) Of the nucleotides wherein, in the nucleotide sequence of SEQ ID NO:1 1706-1965 th polynucleotide comprising a nucleotide sequence that hybridizes under stringent conditions to and from the base sequence, the expression of a gene to a fibroblast polynucleotide having a function of preventing, according to claim 5 adhesion of the therapeutic agent.
[claim11]
11. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:1 2078-2103 th polynucleotide comprising a nucleotide sequence that hybridizes under stringent conditions to and from the base sequence, the expression of a gene to a fibroblast is a polynucleotide having a function of preventing, according to claim 5 adhesion of the therapeutic agent.
[claim12]
12. (as4) Of the nucleotides wherein, in the nucleotide sequence of SEQ ID NO:1 2630-3390 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 5 adhesion of the therapeutic agent.
[claim13]
13. (as4) Of the nucleotides wherein, in the nucleotide sequence of SEQ ID NO:1 2921-3132 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, a fibroblast polynucleotide having a function of preventing the expression of the gene, according to claim 5 adhesion of the therapeutic agent.
[claim14]
14. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:1 2922-3078 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 13 adhesion of the therapeutic agent.
[claim15]
15. (as4) Of the nucleotides and wherein, in the nucleotide sequence of SEQ ID NO:815-1127 1 of the second polynucleotide comprising a nucleotide sequence that hybridizes under stringent conditions to and from the base sequence, the expression of a gene to a fibroblast polynucleotide having a function of preventing, claims 3 or 4 adhesion therapeutic agent.
[claim16]
16. (as4) Of the nucleotides wherein, in the nucleotide sequence of SEQ ID NO:1 965-988 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 15 adhesion of the therapeutic agent.
[claim17]
17. (as4) Of the nucleotides wherein, in the nucleotide sequence of SEQ ID NO:1 1105-1127 with respect to the second polynucleotide comprising a nucleotide sequence and nucleotide sequence that hybridizes under stringent conditions, having a function of preventing the expression of a gene to a fibroblast polynucleotide, according to claim 15 adhesion of the therapeutic agent.
[claim18]
18. Wherein the nucleic acid molecule to a fibroblast suppression of expression of the genes, the expression of the gene as a sequence to suppress a fibroblast, (as1) below, (as2), or (as3) comprising the nucleotides, from any one of claims 17 to claim 3 adhesion therapeutic agent. (as1) Sequence number 24-144 and 230-244 of any one of 1 (as2) wherein the polynucleotide comprising a nucleotide sequence in the nucleotide sequence of (as1), one or a few of the 1 deletion, substitution and/or added and the nucleotide sequence, a fibroblast gene expression of a polynucleotide having a function of preventing (as1) (as3) The identity of the nucleotide sequence of 80% or more and a nucleotide sequence, a polynucleotide having a function of preventing the expression of the fibroblast
[claim19]
19. Wherein the suppression of expression of the gene is a nucleic acid molecule to a fibroblast, single stranded nucleic acid molecule, 5 'from 3' to the side, 5 'side region, the inner region, and 3' side region, and in said order, included in the area inside the nucleotide residues, a residue deoxynbonucleotides, from any one of claims 18 to claim 3 adhesion therapeutic agent.
[claim20]
20. 5 The 'side region and the 3' side region to the at least one of the nucleotide residues, a residue ribonucleotides, according to claim 19 adhesion of the therapeutic agent.
[claim21]
21. Wherein the nucleic acid molecule to a fibroblast suppression of expression of the gene, and a single-stranded nucleic acid molecule, 5 '3 from the side of the' side to the outer circumference, 5 'side region, the inner region, and 3' side region, and in said order, wherein the 5 'side region and the 3' side region to the at least one of the nucleotide residues, a residue of a modified nucleotide, from any one of claims 20 to claim 3 adhesion therapeutic agent.
[claim22]
22. Wherein the modified nucleotide residues, sugar residues is modified with the modified nucleotide residues, according to claim 21 adhesion of the therapeutic agent.
[claim23]
23. Wherein the modified sugar residues modified nucleotide residues, 2' -O- methylribose including LNA(Locked Nucleic Acid) residues or nucleotides is modified, according to claim 22 adhesion of the therapeutic agent.
[claim24]
24. 5 The 'side region, the internal region, and a 3' nucleotide residues included in the area side, to which a phosphate group containing a modified nucleotide residue which has been modified, from any one of claims 23 to claim 19 adhesion therapeutic agent.
[claim25]
25. By making the phosphate group is modified with the modified nucleotide residues, including residues phophorothioate modified nucleotides, according to claim 24 adhesion of the therapeutic agent.
[claim26]
26. 5 The ' is the number of nucleotides in the inner region, and the number 1-14, from any one of claims 25 to claim 19 adhesion therapeutic agent.
[claim27]
27. 3 The method of ' the number of nucleotides in the side region, 1-14 in number, from any one of claims 26 to claim 19 adhesion therapeutic agent.
[claim28]
28. Wherein the number of the bases of the inner area, a one-to-5-16, from any one of claims 27 to claim 19 adhesion therapeutic agent.
[claim29]
29. Wherein the nucleic acid molecule to a fibroblast suppression of expression of the gene, a nucleic acid molecule having a protective group, from any one of claims 28 to claim 3 adhesion therapeutic agent.
[claim30]
30. Wherein the binding material, an antibody against a fibroblast, according to claim 1 adhesion of the therapeutic agent.
[claim31]
31. The pleurodesis, post-operative adhesion, endometriosis, endogenous inflammatory diseases to intercurrent and adhesion, and tumors pleurodesis intercurrent selected from the group consisting of the at least one of 1, any one of claims 30 to claim 1 from adhesion therapeutic agent.
[claim32]
32. Claim 1 from any one of claims 31 adhesion of the therapeutic agent, administering to the patient and including, a method of treating a pleurodesis.
[claim33]
33. And characterized in that a fibroblast, post-operative adhesion marker.
[claim34]
34. The subject's biological sample the amount of expression of a fibroblast characterized in comprising the steps of, post-operative adhesion of the possibility of suffering from testing method.
[claim35]
35. Further, said subject biological sample the amount of expression of a fibroblast, by comparing the reference value, post-operative adhesion of said subject comprises the step of testing the possibility of suffering from, the reference value, the amount of expression of a fibroblast in a biological sample in a healthy patient post-operative adhesion or the amount of expression of a fibroblast is in the biological sample, the test method according to claim 34.
[claim36]
36. Wherein the test step, said subject in the biological sample is the amount of expression of a fibroblast, wherein the amount of expression of a healthy person in the biological sample is higher than a fibroblast, post-operative adhesion wherein the amount of expression of the patient in the biological sample or the same as a fibroblast, post-operative adhesion wherein the amount of expression of the patient in the biological sample is higher than a fibroblast, the test subject is instructed, post-surgical adhesions and is likely to suffer from, the test method according to claim 35.
[claim37]
37. Wherein the biological sample is, blood, lymph, urine, ascites fluid, and pleural fluid selected from the group consisting of at least one of 1, 36 from any one of claims claim 34 test method.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • EDUCATIONAL FOUNDATION OF OSAKA MEDICAL AND PHARMACEUTICAL UNIVERSITY
  • AQUA THERAPEUTICS CO., LTD.
  • 発明者(英語)
  • TAKAI SHINJI
  • KIN TOKUNAN
  • YOSHIKAWA KAZUNORI
  • TAKAO KAZUMASA
  • YOSHINO MASAFUMI
国際特許分類(IPC)
指定国 (WO201830451)
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG

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