CN109153703B - 免疫调节剂 - Google Patents
免疫调节剂 Download PDFInfo
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- CN109153703B CN109153703B CN201780026544.7A CN201780026544A CN109153703B CN 109153703 B CN109153703 B CN 109153703B CN 201780026544 A CN201780026544 A CN 201780026544A CN 109153703 B CN109153703 B CN 109153703B
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Landscapes
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| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
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| TW202017569A (zh) | 2018-05-31 | 2020-05-16 | 美商佩樂敦治療公司 | 用於抑制cd73之組合物及方法 |
| WO2019230919A1 (ja) | 2018-05-31 | 2019-12-05 | 小野薬品工業株式会社 | 免疫チェックポイント阻害薬の有効性判定バイオマーカー |
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| TW202446772A (zh) | 2018-10-11 | 2024-12-01 | 日商小野藥品工業股份有限公司 | Ｓｔｉｎｇ促效化合物 |
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| CN114174538A (zh) | 2019-05-30 | 2022-03-11 | 百时美施贵宝公司 | 适合于免疫肿瘤学疗法的多肿瘤基因特征 |
| KR20220016155A (ko) | 2019-05-30 | 2022-02-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역-종양학 (i-o) 요법에 적합한 대상체를 확인하는 방법 |
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| TW202120692A (zh) | 2019-08-05 | 2021-06-01 | 日商小野藥品工業股份有限公司 | 免疫檢查點阻礙藥的有效性判定用生物標記 |
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| WO2024196952A1 (en) | 2023-03-20 | 2024-09-26 | Bristol-Myers Squibb Company | Tumor subtype assessment for cancer therapy |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1942190A (zh) * | 2004-02-20 | 2007-04-04 | 阿斯利康(瑞典)有限公司 | 用作促性腺激素释放激素(GnRH)拮抗剂的吡咯衍生物 |
| WO2014151634A1 (en) * | 2013-03-15 | 2014-09-25 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the pd-1/pd-l1 and cd80(b7-1)/pd-l1 protein/protein interactions |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
| US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
| US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4447224A (en) | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
| US4487603A (en) | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
| US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
| MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5869451A (en) | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
| US6410690B1 (en) | 1995-06-07 | 2002-06-25 | Medarex, Inc. | Therapeutic compounds comprised of anti-Fc receptor antibodies |
| US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| US5922845A (en) | 1996-07-11 | 1999-07-13 | Medarex, Inc. | Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies |
| US6277818B1 (en) | 1998-10-29 | 2001-08-21 | Angstrom Pharmaceuticals, Inc. | Cyclic peptide ligands that target urokinase plasminogen activator receptor |
| WO2004056875A1 (en) | 2002-12-23 | 2004-07-08 | Wyeth | Antibodies against pd-1 and uses therefor |
| EP1896582A4 (en) | 2005-05-09 | 2009-04-08 | Ono Pharmaceutical Co | HUMAN MONOCLONAL ANTIBODIES AGAINST PROGRAMMED CELL DEATH 1 (PD-1) AND METHOD FOR CREATING TREATMENT WITH ANTI-PD-1 ANTIBODIES ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPEUTICS |
| PT1907424E (pt) | 2005-07-01 | 2015-10-09 | Squibb & Sons Llc | Anticorpos monoclonais humanos para o ligando 1 de morte programada (pd-l1) |
| US9090668B2 (en) | 2007-03-26 | 2015-07-28 | The University Of Tokyo | Process for synthesizing cyclic peptide compound |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
| CA2735006A1 (en) | 2008-08-25 | 2010-03-11 | Amplimmune, Inc. | Pd-1 antagonists and methods of use thereof |
| US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| JP5818237B2 (ja) | 2010-09-09 | 2015-11-18 | 国立大学法人 東京大学 | Ｎ−メチルアミノ酸およびその他の特殊アミノ酸を含む特殊ペプチド化合物ライブラリーの翻訳構築と活性種探索法 |
| US10195578B2 (en) | 2010-12-03 | 2019-02-05 | The University Of Tokyo | Peptide library production method, peptide library, and screening method |
| WO2012168944A1 (en) | 2011-06-08 | 2012-12-13 | Aurigene Discovery Technologies Limited | Therapeutic compounds for immunomodulation |
| KR20140142736A (ko) | 2012-03-29 | 2014-12-12 | 오리진 디스커버리 테크놀로지스 리미티드 | 인간의 pd1의 bc 루프로부터의 면역조절 사이클릭 화합물 |
| US9617308B2 (en) | 2012-06-06 | 2017-04-11 | Polyphor Ag | Beta-hairpin peptidomimetics |
| EP3967323A3 (en) * | 2012-06-06 | 2022-05-04 | Bionor Immuno AS | Hiv vaccine |
| JP2013253842A (ja) | 2012-06-06 | 2013-12-19 | Univ Of Tokyo | ｐＨ依存的に標的分子に結合するペプチドのスクリーニング方法 |
| KR20220053691A (ko) | 2013-03-15 | 2022-04-29 | 제넨테크, 인크. | Pd-1 및 pd-l1 관련 상태를 치료하기 위한 바이오마커 및 방법 |
| WO2015033303A1 (en) | 2013-09-06 | 2015-03-12 | Aurigene Discovery Technologies Limited | Cyclic peptidomimetic compounds as immunomodulators |
| WO2015044900A1 (en) | 2013-09-27 | 2015-04-02 | Aurigene Discovery Technologies Limited | Therapeutic immunomodulating compounds |
| SG11201701896RA (en) | 2014-09-11 | 2017-04-27 | Bristol Myers Squibb Co | Macrocyclic inhibitors of the pd-1/pd-l1 and cd80 (b7-1)/pd-li protein/protein interactions |
| US9732119B2 (en) | 2014-10-10 | 2017-08-15 | Bristol-Myers Squibb Company | Immunomodulators |
| US9856292B2 (en) | 2014-11-14 | 2018-01-02 | Bristol-Myers Squibb Company | Immunomodulators |
| US9861680B2 (en) | 2014-12-18 | 2018-01-09 | Bristol-Myers Squibb Company | Immunomodulators |
| US9944678B2 (en) | 2014-12-19 | 2018-04-17 | Bristol-Myers Squibb Company | Immunomodulators |
| US20160222060A1 (en) | 2015-02-04 | 2016-08-04 | Bristol-Myers Squibb Company | Immunomodulators |
| US9809625B2 (en) | 2015-03-18 | 2017-11-07 | Bristol-Myers Squibb Company | Immunomodulators |
| US10358463B2 (en) | 2016-04-05 | 2019-07-23 | Bristol-Myers Squibb Company | Immunomodulators |
| DK3458111T3 (da) | 2016-05-19 | 2021-04-26 | Bristol Myers Squibb Co | Immunomodulatorer til pet-billeddannelse |
| JP7085545B2 (ja) | 2016-11-07 | 2022-06-16 | ブリストル－マイヤーズ スクイブ カンパニー | 免疫修飾因子 |
-
2017
- 2017-03-01 US US15/446,298 patent/US10143746B2/en active Active
- 2017-03-02 EP EP17711450.1A patent/EP3423470B1/en active Active
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- 2017-03-03 TW TW106106996A patent/TW201734022A/zh unknown
- 2017-03-03 AR ARP170100541A patent/AR107802A1/es unknown
- 2017-03-03 UY UY0001037143A patent/UY37143A/es unknown
-
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- 2018-08-27 IL IL261408A patent/IL261408B/en unknown
- 2018-09-03 CL CL2018002506A patent/CL2018002506A1/es unknown
- 2018-09-26 CO CONC2018/0010316A patent/CO2018010316A2/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1942190A (zh) * | 2004-02-20 | 2007-04-04 | 阿斯利康(瑞典)有限公司 | 用作促性腺激素释放激素(GnRH)拮抗剂的吡咯衍生物 |
| WO2014151634A1 (en) * | 2013-03-15 | 2014-09-25 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the pd-1/pd-l1 and cd80(b7-1)/pd-l1 protein/protein interactions |
Non-Patent Citations (2)
| Title |
|---|
| 《Cyclic and Macrocyclic Peptides as Chemical Tools To》;Teresa A. F等;《ChemMedChem》;20151113;第787-794页 * |
| PD-1/PD-L信号通路研究进展;赵彦宗;《国外医学》;20050830;第223-227页 * |
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| EA201891879A1 (ru) | 2019-02-28 |
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| JP2019512478A (ja) | 2019-05-16 |
| CL2018002506A1 (es) | 2018-11-09 |
| US10143746B2 (en) | 2018-12-04 |
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| CO2018010316A2 (es) | 2018-10-22 |
| CN109153703A (zh) | 2019-01-04 |
| JP6976263B2 (ja) | 2021-12-08 |
| EP3423470B1 (en) | 2021-08-18 |
| AU2017227777A1 (en) | 2018-10-25 |
| MX379487B (es) | 2025-03-11 |
| SG11201807426WA (en) | 2018-09-27 |
| CA3016024A1 (en) | 2017-09-08 |
| BR112018017114A2 (pt) | 2018-12-26 |
| ES2886635T3 (es) | 2021-12-20 |
| MX2018010414A (es) | 2018-11-09 |
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