ES2997757T3 - Cyclic dinucleotides as anticancer agents - Google Patents
Cyclic dinucleotides as anticancer agents Download PDFInfo
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- ES2997757T3 ES2997757T3 ES18797354T ES18797354T ES2997757T3 ES 2997757 T3 ES2997757 T3 ES 2997757T3 ES 18797354 T ES18797354 T ES 18797354T ES 18797354 T ES18797354 T ES 18797354T ES 2997757 T3 ES2997757 T3 ES 2997757T3
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- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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| PT2838900T (pt) * | 2012-04-17 | 2019-11-15 | Gilead Sciences Inc | Compostos e métodos para tratamento antiviral |
| BR112014028013A2 (pt) | 2012-05-11 | 2018-02-27 | Five Prime Therapeutics Inc | métodos para tratar uma condição associada com artrite reumatoide, artrite reumatoide, lesões de pele, nefrite lúpica, lúpus, uma condição inflamatória, distúrbio de cd16+, método para reduzir o número de monócitos cd16+, métodos para desacelerar a progressão de uma condição renal,de formação de panos e de perda óssea |
| KR102410078B1 (ko) | 2012-05-31 | 2022-06-22 | 소렌토 쎄라퓨틱스, 인코포레이티드 | Pd-l1에 결합하는 항원 결합 단백질 |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| CN107759690A (zh) | 2012-08-31 | 2018-03-06 | 戊瑞治疗有限公司 | 用结合群落刺激因子1受体(csf1r)的抗体治疗病状的方法 |
| AU2013363087B2 (en) * | 2012-12-19 | 2018-07-19 | Board Of Regents, The University Of Texas System | Pharmaceutical targeting of a mammalian cyclic di-nucleotide signaling pathway |
| HRP20210122T1 (hr) | 2013-05-02 | 2021-04-16 | Anaptysbio, Inc. | Protutijela usmjerena protiv programirane smrti-1 (pd-1) |
| US9549944B2 (en) * | 2013-05-18 | 2017-01-24 | Aduro Biotech, Inc. | Compositions and methods for inhibiting “stimulator of interferon gene”—dependent signalling |
| JP6400082B2 (ja) * | 2013-05-18 | 2018-10-03 | アデュロ バイオテック，インコーポレイテッド | 「インターフェロン遺伝子の刺激因子」依存性シグナル伝達を抑制するための組成物および方法 |
| US9676853B2 (en) | 2013-05-31 | 2017-06-13 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind PD-1 |
| SG11201601844TA (en) | 2013-09-13 | 2016-04-28 | Beigene Ltd | Anti-pd1 antibodies and their use as therapeutics and diagnostics |
| SG11201604738TA (en) | 2013-12-12 | 2016-07-28 | Shanghai Hengrui Pharm Co Ltd | Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| PL3233882T3 (pl) * | 2014-12-16 | 2020-04-30 | Kayla Therapeutics | Fluorowane cykliczne dinukleotydy do indukcji cytokin |
| CA2978942A1 (en) | 2015-03-13 | 2016-09-22 | Cytomx Therapeutics, Inc. | Anti-pdl1 antibodies, activatable anti-pdl1 antibodies, and methods of use thereof |
| MX2018001814A (es) * | 2015-08-13 | 2018-05-07 | Merck Sharp & Dohme | Compuestos dinucleotidos ciclicos como agonistas del estimulador de genes de interferon. |
| CN114751950B (zh) * | 2016-03-18 | 2025-04-18 | 免疫传感器公司 | 环二核苷酸化合物及使用方法 |
| WO2018118665A1 (en) * | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Cyclic dinucleotide sting agonists for cancer treatment |
| RU2019122602A (ru) * | 2016-12-20 | 2021-01-22 | Мерк Шарп И Доум Корп. | Комбинации антагонистов pd-1 и циклических динуклеотидных агонистов sting для лечения рака |
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2018
- 2018-10-16 CN CN201880072955.4A patent/CN111406063B/zh active Active
- 2018-10-16 JP JP2020542056A patent/JP7254821B2/ja active Active
- 2018-10-16 WO PCT/US2018/056030 patent/WO2019079261A1/en not_active Ceased
- 2018-10-16 EP EP18797354.0A patent/EP3697801B1/en active Active
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| Publication number | Publication date |
|---|---|
| US20210253624A1 (en) | 2021-08-19 |
| CN111406063B (zh) | 2023-09-15 |
| KR20200065065A (ko) | 2020-06-08 |
| EP3697801B1 (en) | 2024-11-20 |
| CN111406063A (zh) | 2020-07-10 |
| JP2020536971A (ja) | 2020-12-17 |
| JP7254821B2 (ja) | 2023-04-10 |
| KR102747388B1 (ko) | 2024-12-26 |
| WO2019079261A1 (en) | 2019-04-25 |
| EP3697801A1 (en) | 2020-08-26 |
| US11427610B2 (en) | 2022-08-30 |
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