JP2008523084A - 免疫賦活用合剤および方法 - Google Patents
免疫賦活用合剤および方法 Download PDFInfo
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- JP2008523084A JP2008523084A JP2007545629A JP2007545629A JP2008523084A JP 2008523084 A JP2008523084 A JP 2008523084A JP 2007545629 A JP2007545629 A JP 2007545629A JP 2007545629 A JP2007545629 A JP 2007545629A JP 2008523084 A JP2008523084 A JP 2008523084A
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- immunostimulatory
- tlr8
- biological activity
- oligonucleotide
- agonist
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| JP2007545629A Withdrawn JP2008523084A (ja) | 2004-12-08 | 2005-12-08 | 免疫賦活用合剤および方法 |
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| EP (1) | EP1819226A4 (enExample) |
| JP (1) | JP2008523084A (enExample) |
| WO (1) | WO2006063152A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023526090A (ja) * | 2020-05-19 | 2023-06-20 | ハドソン インスティチュート オブ メディカル リサーチ | オリゴヌクレオチド |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN102712925B (zh) * | 2009-07-24 | 2017-10-27 | 库尔纳公司 | 通过抑制sirtuin(sirt)的天然反义转录物来治疗sirtuin(sirt)相关性疾病 |
| US9242980B2 (en) | 2010-08-17 | 2016-01-26 | 3M Innovative Properties Company | Lipidated immune response modifier compound compositions, formulations, and methods |
| JP6460789B2 (ja) | 2011-06-03 | 2019-01-30 | スリーエム イノベイティブ プロパティズ カンパニー | ポリエチレングリコールセグメントを有するヘテロ２官能性リンカー及び該リンカーから調製された免疫反応調節複合体 |
| BR112013031039B1 (pt) | 2011-06-03 | 2020-04-28 | 3M Innovative Properties Co | compostos de hidrazino 1h-imidazoquinolina-4-aminas, conjugados feitos destes compostos, composição e composição farmacêutica compreendendo ditos compostos e conjugados, usos dos mesmos e método de fabricação do conjugado |
| US9228184B2 (en) | 2012-09-29 | 2016-01-05 | Dynavax Technologies Corporation | Human toll-like receptor inhibitors and methods of use thereof |
| US9868955B2 (en) | 2012-09-29 | 2018-01-16 | Dynavax Technologies Corporation | Human toll-like receptor inhibitors and methods of use thereof |
| WO2015095780A1 (en) * | 2013-12-20 | 2015-06-25 | The University Of Kansas | Toll-like receptor 8 agonists |
| WO2017038909A1 (en) * | 2015-08-28 | 2017-03-09 | Takeda Pharmaceutical Company Limited | Heterocyclic compounds |
| WO2019123178A1 (en) | 2017-12-20 | 2019-06-27 | 3M Innovative Properties Company | Amide substitued imidazo[4,5-c]quinoline compounds with a branched chain linking group for use as an immune response modifier |
| US11365413B2 (en) * | 2018-08-22 | 2022-06-21 | Board Of Regents, The University Of Texas System | Inhibition of poly(A) binding protein and the treatment of pain |
Family Cites Families (5)
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|---|---|---|---|---|
| US20030139364A1 (en) * | 2001-10-12 | 2003-07-24 | University Of Iowa Research Foundation | Methods and products for enhancing immune responses using imidazoquinoline compounds |
| EP3006043B1 (en) * | 2002-04-04 | 2019-05-29 | Zoetis Belgium S.A. | Immunostimulatory g,u-containing oligoribonucleotides |
| EP2572714A1 (en) * | 2002-12-30 | 2013-03-27 | 3M Innovative Properties Company | Immunostimulatory Combinations |
| JP2006517974A (ja) * | 2003-02-13 | 2006-08-03 | スリーエム イノベイティブ プロパティズ カンパニー | Ｉｒｍ化合物およびトル様受容体８に関する方法および組成物 |
| US8940755B2 (en) * | 2003-12-02 | 2015-01-27 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
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2005
- 2005-12-08 EP EP05853384A patent/EP1819226A4/en not_active Withdrawn
- 2005-12-08 US US11/720,872 patent/US20100113565A1/en not_active Abandoned
- 2005-12-08 WO PCT/US2005/044448 patent/WO2006063152A2/en not_active Ceased
- 2005-12-08 JP JP2007545629A patent/JP2008523084A/ja not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023526090A (ja) * | 2020-05-19 | 2023-06-20 | ハドソン インスティチュート オブ メディカル リサーチ | オリゴヌクレオチド |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006063152A8 (en) | 2007-03-01 |
| WO2006063152A2 (en) | 2006-06-15 |
| EP1819226A2 (en) | 2007-08-22 |
| WO2006063152A3 (en) | 2007-02-08 |
| EP1819226A4 (en) | 2010-12-29 |
| US20100113565A1 (en) | 2010-05-06 |
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