ES2524266T3 - 1,2,5-Oxadiazoles como inhibidores de la indoleamina 2,3-dioxigenasa - Google Patents
1,2,5-Oxadiazoles como inhibidores de la indoleamina 2,3-dioxigenasa Download PDFInfo
- Publication number
- ES2524266T3 ES2524266T3 ES09790108.6T ES09790108T ES2524266T3 ES 2524266 T3 ES2524266 T3 ES 2524266T3 ES 09790108 T ES09790108 T ES 09790108T ES 2524266 T3 ES2524266 T3 ES 2524266T3
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- Prior art keywords
- amino
- compound
- oxadiazol
- pharmaceutically acceptable
- hydroxy
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Applications Claiming Priority (5)
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| US7887608P | 2008-07-08 | 2008-07-08 | |
| US78876P | 2008-07-08 | ||
| US15087309P | 2009-02-09 | 2009-02-09 | |
| US150873P | 2009-02-09 | ||
| PCT/US2009/049794 WO2010005958A2 (en) | 2008-07-08 | 2009-07-07 | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
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| ES2524266T3 true ES2524266T3 (es) | 2014-12-04 |
| ES2524266T9 ES2524266T9 (es) | 2015-10-05 |
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| ES09790108.6T Active ES2524266T3 (es) | 2008-07-08 | 2009-07-07 | 1,2,5-Oxadiazoles como inhibidores de la indoleamina 2,3-dioxigenasa |
| ES14175271.7T Active ES2665419T3 (es) | 2008-07-08 | 2009-07-07 | 1,2,5-Oxadiazoles como inhibidores de la indoleamina 2,3-dioxigenasa |
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| ES14175271.7T Active ES2665419T3 (es) | 2008-07-08 | 2009-07-07 | 1,2,5-Oxadiazoles como inhibidores de la indoleamina 2,3-dioxigenasa |
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Families Citing this family (179)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2559690T3 (en) | 2005-05-10 | 2016-04-25 | Incyte Holdings Corp | Modulators of indoleamine 2,3-dioxygenase and methods of use thereof |
| ES2540561T3 (es) | 2005-12-20 | 2015-07-10 | Incyte Corporation | N-hidroxiamidinoheterociclos como moduladores de indolamina 2,3-dioxigenasa |
| US20080125470A1 (en) * | 2006-09-19 | 2008-05-29 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| CL2007002650A1 (es) | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
| NZ590268A (en) | 2008-07-08 | 2012-11-30 | Incyte Corp | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
| GB0919757D0 (en) * | 2009-11-12 | 2009-12-30 | Johnson Matthey Plc | Polymorphs of bromfenac sodium and methods for preparing bromfenac sodium polymorphs |
| US8299295B2 (en) | 2009-10-15 | 2012-10-30 | Johnson Matthey Public Limited Company | Polymorphs of bromfenac sodium and methods for preparing bromfenac sodium polymorphs |
| NO2694640T3 (enExample) | 2011-04-15 | 2018-03-17 | ||
| EP2781517B1 (en) | 2011-11-09 | 2017-10-11 | Kyowa Hakko Kirin Co., Ltd. | Nitrogen-containing heterocyclic compound |
| GB201120860D0 (en) | 2011-12-05 | 2012-01-18 | Cambridge Entpr Ltd | Cancer immunotherapy |
| SG11201408679XA (en) | 2012-06-26 | 2015-01-29 | Del Mar Pharmaceuticals | Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof |
| WO2014066834A1 (en) | 2012-10-26 | 2014-05-01 | The University Of Chicago | Synergistic combination of immunologic inhibitors for the treatment of cancer |
| US11491154B2 (en) | 2013-04-08 | 2022-11-08 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| CR20160252A (es) * | 2013-11-08 | 2016-09-19 | Incyte Holdings Corp | Proceso para la sintesis de un inhibidor de indolamina 2,3-dioxigenasa |
| MX390904B (es) * | 2014-02-04 | 2025-03-21 | Incyte Corp | Combinación de un antagonista de muerte programada-1 y un inhibidor de indolamina 2,3-dioxigenasa 1 para el tratamiento del cáncer. |
| JP6637439B2 (ja) | 2014-03-31 | 2020-01-29 | ジェネンテック， インコーポレイテッド | 抗ｏｘ４０抗体及び使用方法 |
| AU2015241038A1 (en) | 2014-03-31 | 2016-10-13 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and OX40 binding agonists |
| PH12016502345B1 (en) | 2014-05-28 | 2023-03-01 | Agenus Inc | Anti-gitr antibodies and methods of use thereof |
| EP3151820A4 (en) | 2014-06-06 | 2017-11-22 | Flexus Biosciences, Inc. | Immunoregulatory agents |
| CN114588157A (zh) * | 2014-07-17 | 2022-06-07 | Chdi基金会股份有限公司 | 用于治疗hiv相关病症的方法和组合物 |
| CN105481789B (zh) * | 2014-09-15 | 2020-05-19 | 中国科学院上海有机化学研究所 | 一种吲哚胺-2,3-双加氧酶抑制剂及其制备方法 |
| UY36391A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido1), sus métodos de síntesis y composiciones farmacèuticas que las contienen |
| WO2016073738A2 (en) | 2014-11-05 | 2016-05-12 | Flexus Biosciences, Inc. | Immunoregulatory agents |
| UY36390A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen |
| US10525035B2 (en) | 2014-12-18 | 2020-01-07 | Lankenau Institute For Medical Research | Methods and compositions for the treatment of retinopathy and other ocular diseases |
| WO2016123573A1 (en) | 2015-01-30 | 2016-08-04 | President And Fellows Of Harvard College | Peritumoral and intratumoral materials for cancer therapy |
| KR102394917B1 (ko) | 2015-03-04 | 2022-05-09 | 길리애드 사이언시즈, 인코포레이티드 | 톨 유사 수용체 조정제 화합물 |
| WO2016147144A1 (en) * | 2015-03-17 | 2016-09-22 | Pfizer Inc. | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| CN106660974B (zh) * | 2015-03-31 | 2019-08-30 | 江苏恒瑞医药股份有限公司 | 含氨磺酰基的1,2,5-噁二唑类衍生物、其制备方法及其在医药上的应用 |
| EP3280736A1 (en) | 2015-04-07 | 2018-02-14 | F. Hoffmann-La Roche AG | Antigen binding complex having agonistic activity and methods of use |
| AU2016250976B2 (en) | 2015-04-21 | 2020-02-27 | Jiangsu Hengrui Medicine Co., Ltd. | Imidazo isoindole derivative, preparation method therefor and medical use thereof |
| MA44594B1 (fr) | 2015-05-29 | 2020-09-30 | Memorial Sloan Kettering Cancer Center | Anticorps anti-ctla-4 et méthodes d'utilisation de ceux-ci |
| US9891882B2 (en) * | 2015-06-01 | 2018-02-13 | Nagravision S.A. | Methods and systems for conveying encrypted data to a communication device |
| KR20180025888A (ko) | 2015-06-08 | 2018-03-09 | 제넨테크, 인크. | 항-ox40 항체 및 pd-1 축 결합 길항제를 사용하여 암을 치료하는 방법 |
| HK1252272A1 (zh) | 2015-06-08 | 2019-05-24 | 豪夫迈‧罗氏有限公司 | 使用抗ox40抗体治疗癌症的方法 |
| EP3317287B1 (en) * | 2015-07-02 | 2019-07-31 | GlaxoSmithKline Intellectual Property Development Limited | Inhibitors of indoleamine 2,3-dioxygenase |
| US20180271861A1 (en) * | 2015-07-14 | 2018-09-27 | Kyowa Hakko Kirin Co., Ltd. | Therapeutic agent for a tumor comprising an ido inhibitor administered in combination with an antibody |
| CN116196426A (zh) | 2015-07-16 | 2023-06-02 | 百欧肯治疗有限公司 | 治疗癌症的组合物及方法 |
| MX2018001014A (es) | 2015-07-24 | 2018-05-23 | Newlink Genetics Corp | Sales y profarmacos de 1-metil-d-triptofano. |
| WO2017024996A1 (zh) * | 2015-08-07 | 2017-02-16 | 江苏恒瑞医药股份有限公司 | 羟基脒类衍生物、其制备方法及其在医药上的应用 |
| JP2018525412A (ja) | 2015-08-26 | 2018-09-06 | ギリアード サイエンシーズ， インコーポレイテッド | 重水素化トール様受容体調節因子 |
| WO2017040790A1 (en) | 2015-09-01 | 2017-03-09 | Agenus Inc. | Anti-pd-1 antibodies and methods of use thereof |
| CN107396498B (zh) | 2015-09-14 | 2019-07-23 | 昂宝电子（上海）有限公司 | 用于发光二极管照明系统中的电流调节的系统和方法 |
| CN106565696B (zh) * | 2015-10-09 | 2020-07-28 | 江苏恒瑞医药股份有限公司 | 噁二唑类衍生物、其制备方法及其在医药上的应用 |
| AU2016349501B2 (en) * | 2015-11-04 | 2022-07-21 | Incyte Corporation | Pharmaceutical compositions and methods for indoleamine 2,3-dioxygenase inhibition and indications therefor |
| WO2017080934A1 (en) | 2015-11-09 | 2017-05-18 | F. Hoffmann-La Roche Ag | Screening assay to identify id01 and/or tdo modulators |
| AU2016364889B2 (en) | 2015-12-02 | 2024-01-04 | Agenus Inc. | Antibodies and methods of use thereof |
| EP3389783B1 (en) * | 2015-12-15 | 2024-07-03 | Merck Sharp & Dohme LLC | Novel compounds as indoleamine 2,3-dioxygenase inhibitors |
| CN106883193B (zh) * | 2015-12-15 | 2021-10-15 | 上海翰森生物医药科技有限公司 | 吲哚胺2,3-双加氧酶抑制剂及其制备方法与应用 |
| AU2017208848A1 (en) | 2016-01-19 | 2018-07-12 | Pfizer Inc. | Cancer vaccines |
| US9624185B1 (en) * | 2016-01-20 | 2017-04-18 | Yong Xu | Method for preparing IDO inhibitor epacadostat |
| CN105646389B (zh) * | 2016-01-28 | 2019-06-28 | 中国科学院上海有机化学研究所 | 一种作为吲哚胺-2,3-双加氧酶抑制剂的氨基磺酸脂及其制备方法和用途 |
| EP3416725A1 (en) | 2016-02-19 | 2018-12-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of obesity |
| CN108602786B (zh) * | 2016-02-25 | 2019-04-23 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的噁二唑类化合物及包含该化合物的组合物及其用途 |
| CN107176933B (zh) * | 2016-03-09 | 2020-10-09 | 中国科学院上海有机化学研究所 | 一种含氮烷基化和芳基化亚砜亚胺的吲哚胺-2,3-双加氧酶抑制剂 |
| CN107304191B (zh) * | 2016-04-20 | 2023-09-29 | 上海翰森生物医药科技有限公司 | 吲哚胺2,3-双加氧酶抑制剂及其制备方法与应用 |
| WO2017181849A1 (zh) * | 2016-04-20 | 2017-10-26 | 江苏豪森药业集团有限公司 | 吲哚胺2,3-双加氧酶抑制剂及其制备方法与应用 |
| BR112018071602B1 (pt) * | 2016-04-29 | 2024-02-27 | Iomet Pharma Ltd. | Compostos de imidazopiridina substituídos, sua composição e seus usos como inibidores da indolamina 2,3-dioxigenase e/ou triptofano-2,3- dioxigenase |
| CN109348714A (zh) | 2016-05-04 | 2019-02-15 | 百时美施贵宝公司 | 吲哚胺2,3-双加氧酶的抑制剂及其使用方法 |
| BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
| KR102366813B1 (ko) | 2016-05-27 | 2022-02-24 | 아게누스 인코포레이티드 | 항-tim-3 항체 및 이의 사용 방법 |
| MX2018014377A (es) | 2016-05-27 | 2019-03-14 | Gilead Sciences Inc | Metodos para tratar infecciones por virus de hepatitis b usando inhibidores de proteina no estructural 5a (ns5a), proteina no estructural 5b (ns5b) o proteina no estructural 3 (ns3). |
| AR108586A1 (es) | 2016-06-10 | 2018-09-05 | Lilly Co Eli | Compuestos de 2,3-dihidro-1h-indol |
| CN106109472A (zh) * | 2016-06-13 | 2016-11-16 | 中山大学 | 氯氮卓作为吲哚胺2,3-双加氧酶-1抑制剂的用途 |
| CA3032544A1 (en) * | 2016-08-02 | 2018-02-08 | Shandong Luye Pharmaceutical Co., Ltd. | Ido1 inhibitor and preparation method and application thereof |
| US11046776B2 (en) | 2016-08-05 | 2021-06-29 | Genentech, Inc. | Multivalent and multiepitopic antibodies having agonistic activity and methods of use |
| WO2018039430A1 (en) * | 2016-08-24 | 2018-03-01 | H. Lee Moffitt Cancer Center & Research Institute, Inc. | Radiofluorinated carboximidamides as ido targeting pet tracer for cancer imaging |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| US11351164B2 (en) | 2016-08-26 | 2022-06-07 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
| PT3507276T (pt) | 2016-09-02 | 2022-01-11 | Gilead Sciences Inc | Compostos moduladores do recetor de tipo toll |
| WO2018045150A1 (en) | 2016-09-02 | 2018-03-08 | Gilead Sciences, Inc. | 4,6-diamino-pyrido[3,2-d]pyrimidine derivaties as toll like receptor modulators |
| EP4268838A3 (en) | 2016-09-19 | 2023-12-27 | University Of South Florida | Method of targeting oncolytic viruses to tumors |
| CA3037380A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
| AU2017343780B2 (en) | 2016-10-13 | 2023-08-31 | Juno Therapeutics, Inc. | Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators |
| MA46535A (fr) | 2016-10-14 | 2019-08-21 | Prec Biosciences Inc | Méganucléases modifiées spécifiques de séquences de reconnaissance dans le génome du virus de l'hépatite b |
| WO2018072697A1 (zh) * | 2016-10-17 | 2018-04-26 | 上海医药集团股份有限公司 | 含噁二唑环化合物、制备方法、中间体、组合物及应用 |
| EP3532091A2 (en) | 2016-10-29 | 2019-09-04 | H. Hoffnabb-La Roche Ag | Anti-mic antibidies and methods of use |
| UY37466A (es) | 2016-11-03 | 2018-01-31 | Phenex Discovery Verwaltungs Gmbh | N-hidroxiamidinheterociclos sustituidos como moduladores de la indolamina 2,3-dioxigenasa |
| EP3538152A4 (en) | 2016-11-09 | 2020-09-30 | Agenus Inc. | ANTI-OX40 ANTIBODIES, ANTI-GITR ANTIBODIES, AND PROCESSES FOR USE |
| EP3544965A4 (en) * | 2016-11-28 | 2020-05-20 | Shanghai Fochon Pharmaceutical Co., Ltd. | Sulfoximine, sulfonimidamide, sulfondiimine and diimidosulfonamide compounds as inhibitors of indoleamine 2, 3-dioxygenase |
| BR112019011582A2 (pt) | 2016-12-07 | 2019-10-22 | Agenus Inc. | anticorpos e métodos de utilização dos mesmos |
| IL307242A (en) | 2016-12-07 | 2023-11-01 | Agenus Inc | Anti-CTLA-4 antibodies and methods of using them |
| CN108218807A (zh) * | 2016-12-22 | 2018-06-29 | 上海长森药业有限公司 | 一种作为吲哚胺-2,3-双加氧酶抑制剂的砜脒及其制备方法和用途 |
| PE20191541A1 (es) | 2016-12-22 | 2019-10-23 | Calithera Biosciences Inc | Composiciones y metodos para inhibir la accion de la arginasa |
| MA47265A (fr) | 2017-01-13 | 2019-11-20 | Agenus Inc | Récepteurs de lymphocytes t qui se lient à ny-eso-1 et méthodes d'utilisation de ces derniers |
| JP2020506895A (ja) | 2017-01-17 | 2020-03-05 | ボード オブ レジェンツ, ザ ユニバーシティ オブ テキサス システムBoard Of Regents, The University Of Texas System | インドールアミン２，３−ジオキシゲナーゼおよび／またはトリプトファンジオキシゲナーゼの阻害剤として有用な化合物 |
| TWI714820B (zh) | 2017-01-31 | 2021-01-01 | 美商基利科學股份有限公司 | 替諾福韋艾拉酚胺(tenofovir alafenamide)之晶型 |
| JOP20180008A1 (ar) | 2017-02-02 | 2019-01-30 | Gilead Sciences Inc | مركبات لعلاج إصابة بعدوى فيروس الالتهاب الكبدي b |
| CN110461326A (zh) * | 2017-03-29 | 2019-11-15 | 默沙东公司 | 作为吲哚胺2,3-双加氧酶(ido)抑制剂的新型经取代n’-羟基甲脒基-1,2,5-噁二唑化合物 |
| WO2018187479A1 (en) | 2017-04-04 | 2018-10-11 | Case Western Reserve University | Method of modulating ribonucleotide reductase |
| CN108689958B (zh) * | 2017-04-05 | 2021-09-17 | 南京华威医药科技集团有限公司 | 一种含有肼基的吲哚胺2,3-双加氧化酶抑制剂 |
| CN106967005B (zh) * | 2017-04-07 | 2019-07-16 | 上海肇钰医药科技有限公司 | 一种能抑制ido的化合物、其制备方法及其用途 |
| WO2018191502A2 (en) | 2017-04-13 | 2018-10-18 | Agenus Inc. | Anti-cd137 antibodies and methods of use thereof |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| CN108794423B (zh) * | 2017-04-27 | 2022-07-19 | 鲁南制药集团股份有限公司 | 亚氨脲衍生物 |
| RS64576B1 (sr) | 2017-05-01 | 2023-10-31 | Agenus Inc | Anti-tigit antitela i postupci njihove primene |
| CN109081818B (zh) * | 2017-06-14 | 2022-04-22 | 南京华威医药科技集团有限公司 | 新型吲哚胺2,3-双加氧化酶抑制剂 |
| CN109111438B (zh) * | 2017-06-26 | 2021-11-02 | 正大天晴药业集团股份有限公司 | 用于ido抑制剂的脒类化合物 |
| EP3651792A1 (en) | 2017-07-11 | 2020-05-20 | Pfizer Inc | Immunogenic compositions comprising cea muc1 and tert |
| US12227567B2 (en) | 2017-07-25 | 2025-02-18 | Truebinding, Inc. | Treating cancer by blocking the interaction of TIM-3 and its ligand |
| EP3668880B1 (en) | 2017-08-17 | 2021-10-06 | Idorsia Pharmaceuticals Ltd | Inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase |
| CN107311956A (zh) * | 2017-08-22 | 2017-11-03 | 合肥圣迪利克医药科技有限公司 | 一种艾卡跺司他合成方法 |
| SG11202001319QA (en) | 2017-09-04 | 2020-03-30 | Agenus Inc | T cell receptors that bind to mixed lineage leukemia (mll)-specific phosphopeptides and methods of use thereof |
| EP3681491A4 (en) | 2017-09-11 | 2021-06-30 | Atossa Therapeutics, Inc. | Methods for making and using endoxifen |
| CN108863976B (zh) * | 2017-09-11 | 2022-09-16 | 郑州泰基鸿诺医药股份有限公司 | 用作ido调节剂的化合物及其应用 |
| US20200261414A1 (en) | 2017-09-14 | 2020-08-20 | Lankenau Institute For Medical Research | Methods and compositions for the treatment of cancer |
| WO2019057104A1 (zh) * | 2017-09-20 | 2019-03-28 | 上海翰森生物医药科技有限公司 | 一种双加氧酶抑制剂的盐及其制备方法和用途 |
| CN109897011B (zh) * | 2017-12-08 | 2023-10-31 | 上海华汇拓医药科技有限公司 | 一类ido抑制剂及其应用 |
| CN109928922A (zh) * | 2017-12-18 | 2019-06-25 | 成都华健未来科技有限公司 | 一类环己烷类化合物 |
| AU2018392213B2 (en) | 2017-12-20 | 2021-03-04 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3' cyclic dinucleotides with phosphonate bond activating the STING adaptor protein |
| WO2019123339A1 (en) | 2017-12-20 | 2019-06-27 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| CN109942565B (zh) | 2017-12-20 | 2021-03-26 | 海创药业股份有限公司 | 一种吲哚胺-2,3-双加氧酶抑制剂及其制备方法和用途 |
| CN111587116A (zh) | 2018-01-05 | 2020-08-25 | 迪克纳制药公司 | 降低β-连环蛋白和IDO表达以加强免疫疗法 |
| JP7217279B2 (ja) | 2018-01-15 | 2023-02-02 | イドーシア ファーマシューティカルズ リミテッド | インドールアミン ２，３－ジオキシゲナーゼ及び／又はトリプトファン ２，３－ジオキシゲナーゼの阻害剤 |
| CN108586378B (zh) | 2018-01-22 | 2020-06-19 | 南京华威医药科技集团有限公司 | 吲哚胺2,3-双加氧化酶抑制剂及其制备方法和用途 |
| CN110066253B (zh) * | 2018-01-24 | 2023-06-23 | 江苏柯菲平医药股份有限公司 | 1,2,5-噁二唑类衍生物，其制备方法及其在医药中的应用 |
| US11369589B2 (en) | 2018-01-24 | 2022-06-28 | Nanjing Carephar Shenghui Pharmaceutical Co., Ltd. | Modulator of indoleamine 2,3-dioxygenase, preparation method and use thereof |
| CN110577501A (zh) * | 2018-06-07 | 2019-12-17 | 江苏柯菲平医药股份有限公司 | 吲哚胺2,3-双加氧酶调节剂，其制备方法及用途 |
| ES2939493T3 (es) * | 2018-02-02 | 2023-04-24 | Hinova Pharmaceuticals Inc | Inhibidor de la indoleamina-2,3-dioxigenasa, procedimiento de preparación del mismo y uso del mismo |
| CN108101899B (zh) * | 2018-02-11 | 2021-01-26 | 中国药科大学 | IDO1抑制剂Epacadostat中间体的制备方法 |
| SI3752501T1 (sl) | 2018-02-13 | 2023-08-31 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| JP7050165B2 (ja) | 2018-02-26 | 2022-04-07 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｂｖ複製阻害剤としての置換ピロリジン化合物 |
| EP3774883A1 (en) | 2018-04-05 | 2021-02-17 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | ２，２，─環二核苷酸 |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
| US20190314324A1 (en) | 2018-04-13 | 2019-10-17 | The University Of Chicago | Combination of micheliolide derivatives or nanoparticles with ionizing radiation and checkpoint inhibitors for cancer therapy |
| CA3093130C (en) | 2018-04-19 | 2023-10-17 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| CN112218883A (zh) | 2018-04-26 | 2021-01-12 | 艾吉纳斯公司 | 热休克蛋白结合肽组合物及其使用方法 |
| CN110407765B (zh) * | 2018-04-28 | 2022-12-06 | 上海挚盟医药科技有限公司 | 1,2,5-噁二唑类衍生物、其制备方法及其在医药上的应用 |
| TW202014193A (zh) | 2018-05-03 | 2020-04-16 | 捷克科學院有機化學與生物化學研究所 | 包含碳環核苷酸之2’3’－環二核苷酸 |
| GB201809050D0 (en) | 2018-06-01 | 2018-07-18 | E Therapeutics Plc | Modulators of tryptophan catabolism |
| SI3820572T1 (sl) | 2018-07-13 | 2023-12-29 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| US11046649B2 (en) | 2018-07-17 | 2021-06-29 | Board Of Regents, The University Of Texas System | Compounds useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| CN109180603A (zh) * | 2018-10-10 | 2019-01-11 | 中国药科大学 | Epacadostat关键中间体的制备方法 |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ， インコーポレイテッド | Ｐｄ－１／ｐｄ－ｌ１阻害剤 |
| TWI721624B (zh) | 2018-10-31 | 2021-03-11 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
| CA3117556A1 (en) | 2018-10-31 | 2020-05-07 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds as hpk1 inhibitors |
| CN111617078B (zh) * | 2019-02-28 | 2023-02-03 | 四川科伦博泰生物医药股份有限公司 | 用于疾病治疗和/或预防的药物组合物、方法及其用途 |
| JP7350871B2 (ja) | 2019-03-07 | 2023-09-26 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール，ヴイ．ヴイ．アイ． | ２’３’－環状ジヌクレオチドおよびそのプロドラッグ |
| EP3935065A1 (en) | 2019-03-07 | 2022-01-12 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| WO2020178770A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI751517B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| EP3972695A1 (en) | 2019-05-23 | 2022-03-30 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
| CA3140708A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
| CN114245807B (zh) | 2019-06-25 | 2025-05-02 | 吉利德科学公司 | Flt3l-fc融合蛋白和使用方法 |
| JP7662204B2 (ja) | 2019-07-03 | 2025-04-15 | アトッサ・セラピューティクス・インコーポレイテッド | エンドキシフェンの徐放性組成物 |
| CN110204537B (zh) * | 2019-07-10 | 2021-10-08 | 盛世泰科生物医药技术(苏州)有限公司 | 一种用作吲哚胺2，3-双加氧酶的抑制剂的1，2，5-噁二唑衍生物 |
| EP3997083A1 (en) | 2019-07-11 | 2022-05-18 | Idorsia Pharmaceuticals Ltd | Inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase |
| US20220257619A1 (en) | 2019-07-18 | 2022-08-18 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| AU2020319875A1 (en) | 2019-08-01 | 2022-02-17 | Incyte Corporation | A dosing regimen for an IDO inhibitor |
| EP4017476A1 (en) | 2019-08-19 | 2022-06-29 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| WO2021042019A1 (en) | 2019-08-30 | 2021-03-04 | Agenus Inc. | Anti-cd96 antibodies and methods of use thereof |
| TWI755055B (zh) * | 2019-09-18 | 2022-02-11 | 台灣神隆股份有限公司 | 用於製備惡拉戈利鈉及其中間體的方法 |
| MY208114A (en) | 2019-09-30 | 2025-04-16 | Gilead Sciences Inc | Hbv vaccines and methods treating hbv |
| EP4041402A1 (en) | 2019-11-12 | 2022-08-17 | Nammi Therapeutics, Inc. | Formulated and/or co-formulated liposome compositions containing ido antagonist prodrugs useful in the treatment of cancer and methods thereof |
| CN116057068A (zh) | 2019-12-06 | 2023-05-02 | 精密生物科学公司 | 对乙型肝炎病毒基因组中的识别序列具有特异性的优化的工程化大范围核酸酶 |
| CN113045655A (zh) | 2019-12-27 | 2021-06-29 | 高诚生物医药(香港)有限公司 | 抗ox40抗体及其用途 |
| WO2021188959A1 (en) | 2020-03-20 | 2021-09-23 | Gilead Sciences, Inc. | Prodrugs of 4'-c-substituted-2-halo-2'-deoxyadenosine nucleosides and methods of making and using the same |
| CA3185040A1 (en) | 2020-05-26 | 2021-12-02 | Truebinding, Inc. | Methods of treating inflammatory diseases by blocking galectin-3 |
| BR112023002164A2 (pt) | 2020-08-07 | 2023-03-14 | Gilead Sciences Inc | Profármacos de análogos de nucleotídeos de fosfonamida e seu uso farmacêutico |
| WO2022064526A1 (en) * | 2020-09-25 | 2022-03-31 | Msn Laboratories Private Limited, R&D Center | Solid state forms of epacadostat and their processes for preparation thereof |
| TWI815194B (zh) | 2020-10-22 | 2023-09-11 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| US20240091202A1 (en) | 2021-03-05 | 2024-03-21 | Universität Basel | Compositions for the treatment of ebv associated diseases or conditions |
| EP4052705A1 (en) | 2021-03-05 | 2022-09-07 | Universität Basel Vizerektorat Forschung | Compositions for the treatment of ebv associated diseases or conditions |
| TW202348237A (zh) | 2021-05-13 | 2023-12-16 | 美商基利科學股份有限公司 | TLR8調節化合物及抗HBV siRNA療法之組合 |
| JP7686091B2 (ja) | 2021-06-23 | 2025-05-30 | ギリアード サイエンシーズ， インコーポレイテッド | ジアシルグリセロールキナーゼ調節化合物 |
| AU2022298639C1 (en) | 2021-06-23 | 2025-07-17 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CA3222277A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| EP4359389A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| GB202303250D0 (en) | 2023-03-06 | 2023-04-19 | King S College London | Method and compounds |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| US20250345389A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025240244A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies comprising bulevirtide and lonafarnib for use in the treatment of hepatitis d virus infection |
| CN119841748B (zh) * | 2025-03-21 | 2025-06-10 | 济南大学 | 一种对甲苯磺酰脲的制备方法 |
Family Cites Families (128)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3236855A (en) | 1964-01-17 | 1966-02-22 | Merck & Co Inc | Certain n-phenyl(thiazole-hydroxamidine) compounds and their preparation |
| US3354174A (en) | 1964-02-19 | 1967-11-21 | Sterling Drug Inc | 1-and 2-benzimidazolyl-lower-alkylamidoximes, amidines-, and guanidines |
| US3553228A (en) * | 1967-09-26 | 1971-01-05 | Colgate Palmolive Co | 3-substituted-4h(1)benzopyrano(3,4-d) isoxazoles |
| DE2040628A1 (de) | 1970-08-17 | 1972-02-24 | Fahlberg List Veb | Neue herbizide Mittel |
| US3948928A (en) * | 1972-03-17 | 1976-04-06 | Dainippon Pharmaceutical Co., Ltd. | 3-Substituted-1,2-benzisoxazoles and pharmaceutically acceptable acid addition salts thereof |
| JPS5621033B2 (enExample) | 1973-09-05 | 1981-05-16 | ||
| DE2640484A1 (de) * | 1975-09-11 | 1977-04-07 | Philagro Sa | Amidoxim-derivate, ihre herstellung und verwendung |
| FR2323683A1 (fr) | 1975-09-11 | 1977-04-08 | Philagro Sa | Nouveaux derives d'amidoximes, leur preparation et les compositions qui les contiennent |
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4323681A (en) * | 1980-09-29 | 1982-04-06 | American Home Products Corporation | 4-Amino-2-substituted-5-pyrimidinecarboxamidoximes and carbothioamides |
| US5156840A (en) | 1982-03-09 | 1992-10-20 | Cytogen Corporation | Amine-containing porphyrin derivatives |
| JPS58208275A (ja) | 1982-05-20 | 1983-12-03 | Lion Corp | ５−アミノ−ピラゾ−ル誘導体及び該化合物を含有する抗腫瘍剤 |
| DE3462259D1 (de) * | 1983-07-22 | 1987-03-05 | Bayer Ag | Substituted furazans |
| US4507485A (en) | 1984-01-23 | 1985-03-26 | Bristol-Myers Company | 3,4-Disubstituted-1,2,5-oxadiazoles having histamine H2 -receptor antagonist activity |
| JPS60193968A (ja) | 1984-03-13 | 1985-10-02 | Toyo Jozo Co Ltd | シクロペンテン環を有するイミダゾ−ルアミドオキシムおよびその製造法 |
| JPS6259283A (ja) | 1985-09-10 | 1987-03-14 | Kaken Pharmaceut Co Ltd | セフアロスポリン化合物 |
| US5057313A (en) | 1986-02-25 | 1991-10-15 | The Center For Molecular Medicine And Immunology | Diagnostic and therapeutic antibody conjugates |
| JPS6320710A (ja) | 1986-07-11 | 1988-01-28 | Matsushita Electric Ind Co Ltd | 薄膜磁気ヘツドの製造方法 |
| AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
| JP2696342B2 (ja) | 1988-06-27 | 1998-01-14 | 日本曹達株式会社 | アミジン誘導体、その製造方法及び殺ダニ剤・農園芸用殺菌剤 |
| EP0352832B1 (en) | 1988-07-05 | 1992-05-06 | Akzo N.V. | Compounds with bronchodilator activity |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| JPH04297449A (ja) | 1991-03-27 | 1992-10-21 | Hokko Chem Ind Co Ltd | Ｎ−ヒドロキシベンジルグアニジン誘導体および農園芸用殺菌剤 |
| JPH05186458A (ja) | 1991-04-26 | 1993-07-27 | Japan Tobacco Inc | 新規なベンゾピラン誘導体 |
| FR2677019B1 (fr) * | 1991-05-27 | 1994-11-25 | Pf Medicament | Nouvelles piperidines disubstituees-1,4, leur preparation et leur application en therapeutique. |
| CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
| AU3178993A (en) | 1991-11-25 | 1993-06-28 | Enzon, Inc. | Multivalent antigen-binding proteins |
| US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
| US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| JP2709677B2 (ja) | 1992-06-19 | 1998-02-04 | 株式会社大塚製薬工場 | ホスホン酸ジエステル誘導体 |
| SI9200344B (sl) | 1992-11-26 | 1998-06-30 | Lek, | Postopek za pripravo amlodipin benzensulfonata |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| FR2720396B1 (fr) * | 1994-05-27 | 1996-06-28 | Adir | Nouveaux N-pyridyl carboxamides et dérivés leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US5731315A (en) | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
| AU725609C (en) | 1995-08-18 | 2002-01-03 | Morphosys Ag | Protein/(poly)peptide libraries |
| US5883102A (en) | 1995-10-17 | 1999-03-16 | Astra Pharmaceuticals Limited | Pharmaceutically active compounds |
| AU1730497A (en) | 1996-02-17 | 1997-09-02 | Agrevo Uk Limited | Fungicidal 1,2,4-oxadiazoles and analogues |
| US5955495A (en) | 1996-05-03 | 1999-09-21 | Hoffmann-La Roche Inc. | Method of treating diseases of the CNS |
| JPH11171702A (ja) | 1997-09-24 | 1999-06-29 | Takeda Chem Ind Ltd | 害虫防除方法 |
| AU1628699A (en) | 1997-12-05 | 1999-06-28 | Medical College Of Georgia Research Institute, Inc. | High-affinity tryptophan transporter |
| DE69822204T2 (de) | 1997-12-10 | 2005-02-17 | Dainippon Ink And Chemicals, Inc. | Oximderivate und sie enthaltende landwirtschaftliche chemikalien |
| WO1999062903A1 (en) | 1998-06-02 | 1999-12-09 | Takeda Chemical Industries, Ltd. | Oxadiazoline derivatives and their use as insecticides |
| CN1152031C (zh) | 1998-08-11 | 2004-06-02 | 诺瓦提斯公司 | 具有血管生成抑制活性的异喹啉衍生物 |
| FR2784678B1 (fr) | 1998-09-23 | 2002-11-29 | Sod Conseils Rech Applic | Nouveaux derives de n-(iminomethyl)amines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
| US6133031A (en) | 1999-08-19 | 2000-10-17 | Isis Pharmaceuticals Inc. | Antisense inhibition of focal adhesion kinase expression |
| DE60010988T2 (de) | 1999-03-03 | 2005-06-09 | Samjin Pharmaceutical Co., Ltd. | Piperazinderivate und verfahren zu ihrer herstellung |
| GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| SK14222001A3 (sk) | 1999-04-09 | 2002-07-02 | Basf Aktiengesellschaft | Prekurzory trombínových inhibítorov |
| WO2000071517A1 (en) | 1999-05-24 | 2000-11-30 | Mitsubishi Pharma Corporation | Phenoxypropylamine compounds |
| JP2001158785A (ja) | 1999-11-30 | 2001-06-12 | Takeda Chem Ind Ltd | 農薬組成物 |
| JP2001158786A (ja) | 1999-11-30 | 2001-06-12 | Takeda Chem Ind Ltd | 哺乳動物の外部寄生虫防除剤 |
| ATE376996T1 (de) * | 2000-01-13 | 2007-11-15 | Amgen Inc | Antibakterielle mittel |
| JP2001233861A (ja) | 2000-02-22 | 2001-08-28 | Ube Ind Ltd | ピラゾールオキシム化合物、その製法及び用途 |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| PL202623B1 (pl) | 2000-06-28 | 2009-07-31 | Smithkline Beecham Plc | Sposób wytwarzania drobno zmielonego preparatu substancji leczniczej, drobno zmielona substancja lecznicza wytworzona tym sposobem i zawierająca ją kompozycja farmaceutyczna |
| HU229403B1 (en) * | 2000-12-18 | 2013-12-30 | Actelion Pharmaceuticals Ltd | Novel sulfamides and their use as endothelin receptor antagonists |
| GB0108102D0 (en) | 2001-03-30 | 2001-05-23 | Pfizer Ltd | Compounds |
| US7115639B2 (en) | 2001-06-18 | 2006-10-03 | Applied Research Systems Ars Holding N.V. | Pyrrolidine oxadiazole- and thiadiazole oxime derivatives being oxytocin receptor antagonists |
| AU2002337142B2 (en) | 2001-09-19 | 2007-10-11 | Aventis Pharma S.A. | Indolizines as kinase protein inhibitors |
| TWI302836B (en) | 2001-10-30 | 2008-11-11 | Novartis Ag | Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity |
| KR20060111716A (ko) | 2002-01-22 | 2006-10-27 | 워너-램버트 캄파니 엘엘씨 | 2-(피리딘-2-일아미노)-피리도[2,3-ｄ]피리미딘-7-온 |
| AU2003218989A1 (en) | 2002-02-19 | 2003-09-09 | Pharmacia Italia S.P.A. | Tricyclic pyrazole derivatives, process for their preparation and their use as antitumor agents |
| ES2276048T3 (es) * | 2002-03-05 | 2007-06-16 | Eli Lilly And Company | Derivados de purina como inhibidores de cinasa. |
| GB0208224D0 (en) | 2002-04-10 | 2002-05-22 | Celltech R&D Ltd | Chemical compounds |
| US20030194803A1 (en) | 2002-04-12 | 2003-10-16 | Mellor Andrew L. | Antigen-presenting cell populations and their use as reagents for enhancing or reducing immune tolerance |
| ZA200408711B (en) | 2002-05-28 | 2006-10-25 | Dimensional Pharamaceuticals I | Novel thiophene amidines, composition thereof, and methods of treating complement-mediated diseases and conditions |
| PE20040522A1 (es) | 2002-05-29 | 2004-09-28 | Novartis Ag | Derivados de diarilurea dependientes de la cinasa de proteina |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| US7157462B2 (en) | 2002-09-24 | 2007-01-02 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
| US7015321B2 (en) | 2002-10-12 | 2006-03-21 | The Scripps Research Institute | Synthesis of non-symmetrical sulfamides using burgess-type reagents |
| AR042052A1 (es) | 2002-11-15 | 2005-06-08 | Vertex Pharma | Diaminotriazoles utiles como inhibidores de proteinquinasas |
| UA80767C2 (en) | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| AU2004204494B2 (en) | 2003-01-09 | 2011-09-29 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
| EP1585767A2 (en) | 2003-01-16 | 2005-10-19 | Genentech, Inc. | Synthetic antibody phage libraries |
| WO2004072266A2 (en) | 2003-02-13 | 2004-08-26 | Kalobios Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
| GB0305929D0 (en) | 2003-03-14 | 2003-04-23 | Novartis Ag | Organic compounds |
| EP1606285A4 (en) | 2003-03-27 | 2009-03-18 | Lankenau Inst Medical Res | NEW IDO HEMMER AND APPLICATION PROCEDURES |
| US7598287B2 (en) | 2003-04-01 | 2009-10-06 | Medical College Of Georgia Research Institute, Inc. | Use of inhibitors of indoleamine-2,3-dioxygenase in combination with other therapeutic modalities |
| KR20120090094A (ko) | 2003-06-13 | 2012-08-16 | 바이오겐 아이덱 엠에이 인코포레이티드 | 아글리코실 항-ｃｄ154(ｃｄ40 리간드) 항체 및 이의 용도 |
| ATE536353T1 (de) | 2003-08-20 | 2011-12-15 | Vertex Pharma | 2-(4-amino-1,2,5-oxadiazol-4-yl)-imidazol- verbindungen als protein kinase inhibitoren |
| NZ545776A (en) | 2003-08-22 | 2009-05-31 | Biogen Idec Inc | Improved antibodies having altered effector function and methods for making the same |
| PE20050952A1 (es) | 2003-09-24 | 2005-12-19 | Novartis Ag | Derivados de isoquinolina como inhibidores de b-raf |
| DE10348022A1 (de) | 2003-10-15 | 2005-05-25 | Imtm Gmbh | Neue Dipeptidylpeptidase IV-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen |
| DE10348023A1 (de) * | 2003-10-15 | 2005-05-19 | Imtm Gmbh | Neue Alanyl-Aminopeptidasen-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen |
| BRPI0511978A (pt) | 2004-06-10 | 2008-01-22 | Irm Llc | compostos e composições como inibidores de proteìnas quinases |
| JP4970946B2 (ja) | 2004-09-08 | 2012-07-11 | 田辺三菱製薬株式会社 | モルホリン化合物 |
| JP2008520612A (ja) | 2004-11-24 | 2008-06-19 | ノバルティス アクチエンゲゼルシャフト | ＪＡＫ阻害剤およびＢｃｒ−Ａｂｌ、Ｆｌｔ−３、ＦＡＫまたはＲＡＦキナーゼ阻害剤のうち少なくとも１個の組合せ |
| US8193359B2 (en) | 2004-12-24 | 2012-06-05 | Prosidion Limited | G-protein coupled receptor agonists |
| US7429667B2 (en) * | 2005-01-20 | 2008-09-30 | Ardea Biosciences, Inc. | Phenylamino isothiazole carboxamidines as MEK inhibitors |
| JP4361545B2 (ja) * | 2005-05-09 | 2009-11-11 | 小野薬品工業株式会社 | ＰｒｏｇｒａｍｍｅｄＤｅａｔｈ１（ＰＤ−１）に対するヒトモノクローナル抗体および抗ＰＤ−１抗体単独または他の免疫療法と併用した癌治療方法 |
| DK2559690T3 (en) | 2005-05-10 | 2016-04-25 | Incyte Holdings Corp | Modulators of indoleamine 2,3-dioxygenase and methods of use thereof |
| WO2006133417A1 (en) | 2005-06-07 | 2006-12-14 | Valeant Pharmaceuticals International | Phenylamino isothiazole carboxamidines as mek inhibitors |
| CN101252957A (zh) | 2005-06-30 | 2008-08-27 | 人类起源公司 | 使用胎盘源胶原生物纤维的鼓膜修复 |
| DE102005060466A1 (de) | 2005-12-17 | 2007-06-28 | Bayer Cropscience Ag | Carboxamide |
| ES2540561T3 (es) | 2005-12-20 | 2015-07-10 | Incyte Corporation | N-hidroxiamidinoheterociclos como moduladores de indolamina 2,3-dioxigenasa |
| WO2007095050A2 (en) * | 2006-02-09 | 2007-08-23 | Incyte Corporation | N-hydroxyguanidines as modulators of indoleamine 2,3-dioxygenase |
| JP4297449B2 (ja) | 2006-05-12 | 2009-07-15 | 株式会社サクラクレパス | 墨汁 |
| US20080119491A1 (en) * | 2006-09-19 | 2008-05-22 | Incyte Corporation | Amidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| WO2008036652A2 (en) * | 2006-09-19 | 2008-03-27 | Incyte Corporation | Amidines as modulators of indoleamine 2,3-dioxygenase |
| US20080125470A1 (en) | 2006-09-19 | 2008-05-29 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| CL2007002650A1 (es) | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
| US20080182882A1 (en) * | 2006-11-08 | 2008-07-31 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| CN101679297B (zh) | 2006-12-08 | 2012-01-11 | 埃克塞利希斯股份有限公司 | Lxr和fxr调节剂 |
| CL2008000066A1 (es) * | 2007-01-12 | 2008-08-01 | Smithkline Beecham Corp | Compuestos derivados de (5-hidroxi-3-oxo-2,3-dihidropiridazina-4-carbonil)glicina, inhibidores de hif prolil hidroxilasas; procedimiento de preparacion; composicion farmaceutica que comprende a dichos compuestos; y su uso en el tratamiento de la anem |
| CA2709202C (en) | 2007-12-19 | 2013-04-23 | Amgen Inc. | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
| AU2008345225A1 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| NZ590268A (en) | 2008-07-08 | 2012-11-30 | Incyte Corp | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
| PA8852901A1 (es) | 2008-12-22 | 2010-07-27 | Lilly Co Eli | Inhibidores de proteina cinasa |
| UY33227A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
| MX379532B (es) | 2010-10-25 | 2025-03-10 | G1 Therapeutics Inc | Inhibidores de cdk. |
| KR20160035613A (ko) | 2011-03-23 | 2016-03-31 | 암젠 인크 | Cdk 4/6 및 flt3의 융합된 트리사이클릭 이중 저해제 |
| WO2014066834A1 (en) | 2012-10-26 | 2014-05-01 | The University Of Chicago | Synergistic combination of immunologic inhibitors for the treatment of cancer |
| CR20160252A (es) | 2013-11-08 | 2016-09-19 | Incyte Holdings Corp | Proceso para la sintesis de un inhibidor de indolamina 2,3-dioxigenasa |
| MX390904B (es) | 2014-02-04 | 2025-03-21 | Incyte Corp | Combinación de un antagonista de muerte programada-1 y un inhibidor de indolamina 2,3-dioxigenasa 1 para el tratamiento del cáncer. |
| JP2017535528A (ja) | 2014-10-03 | 2017-11-30 | ノバルティス アーゲー | 組み合わせ治療 |
| IL287916B2 (en) | 2015-07-30 | 2023-09-01 | Macrogenics Inc | Molecules that bind pd-1 and methods of using them |
| US10292951B2 (en) | 2015-09-01 | 2019-05-21 | First Wave Bio, Inc. | Methods and compositions for treating conditions associated with an abnormal inflammatory responses |
| AU2016349501B2 (en) | 2015-11-04 | 2022-07-21 | Incyte Corporation | Pharmaceutical compositions and methods for indoleamine 2,3-dioxygenase inhibition and indications therefor |
| JP2018020710A (ja) | 2016-08-05 | 2018-02-08 | 三井造船株式会社 | 船舶用舵及び船舶 |
| CN111587116A (zh) | 2018-01-05 | 2020-08-25 | 迪克纳制药公司 | 降低β-连环蛋白和IDO表达以加强免疫疗法 |
| AU2020319875A1 (en) | 2019-08-01 | 2022-02-17 | Incyte Corporation | A dosing regimen for an IDO inhibitor |
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