DK2931738T3 - COMPOSITIONS INCLUDING CYCLIC PURINDINUCLEOTIDES WITH DEFINED STEREOCHEMISTRY AND METHODS FOR PREPARING AND USING THEREOF - Google Patents
COMPOSITIONS INCLUDING CYCLIC PURINDINUCLEOTIDES WITH DEFINED STEREOCHEMISTRY AND METHODS FOR PREPARING AND USING THEREOF Download PDFInfo
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Classifications
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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
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
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- A61K39/02—Bacterial antigens
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- A61K39/385—Haptens or antigens, bound to carriers
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/213—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Landscapes
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
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| US201261737006P | 2012-12-13 | 2012-12-13 | |
| US201361790514P | 2013-03-15 | 2013-03-15 | |
| PCT/US2013/075189 WO2014093936A1 (en) | 2012-12-13 | 2013-12-13 | Compositions comprising cyclic purine dinucleotides having defined stereochemistries and methods for their preparation and use |
Publications (1)
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| DK2931738T3 true DK2931738T3 (en) | 2019-04-15 |
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| CA2813751C (en) | 2010-10-06 | 2019-11-12 | President And Fellows Of Harvard College | Injectable, pore-forming hydrogels for materials-based cell therapies |
| CN104507538B (zh) | 2012-06-08 | 2018-04-06 | 艾杜罗生物科技公司 | 癌症免疫疗法的组合物和方法 |
| SG11201502796RA (en) | 2012-12-13 | 2015-05-28 | Aduro Biotech Inc | Compositions comprising cyclic purine dinucleotides having defined stereochemistries and methods for their preparation and use |
| WO2014099824A1 (en) | 2012-12-19 | 2014-06-26 | Board Of Regents, The University Of Texas System | Pharmaceutical targeting of a mammalian cyclic di-nucleotide signaling pathway |
| CA2908154C (en) | 2013-04-29 | 2023-11-28 | Memorial Sloan Kettering Cancer Center | Compositions and methods for altering second messenger signaling |
| JP2016518140A (ja) * | 2013-05-03 | 2016-06-23 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｉ型インターフェロンの環状ジヌクレオチド誘導法 |
| CN105188373B (zh) * | 2013-05-18 | 2017-09-22 | 艾杜罗生物科技公司 | 抑制“干扰素基因刺激蛋白”依赖性信号传导的组合物和方法 |
| US9549944B2 (en) | 2013-05-18 | 2017-01-24 | Aduro Biotech, Inc. | Compositions and methods for inhibiting “stimulator of interferon gene”—dependent signalling |
| CU24377B1 (es) | 2013-05-18 | 2018-12-05 | Aduro Biotech Inc | Dinucléotidos de purina cíclicos y composiciones de los mismos útiles para inducir la producción de interferón de tipo i dependientes de sting |
| US10176292B2 (en) | 2013-07-31 | 2019-01-08 | Memorial Sloan-Kettering Cancer Center | STING crystals and modulators |
| JP2016538344A (ja) * | 2013-11-19 | 2016-12-08 | ザ・ユニバーシティ・オブ・シカゴＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃｈｉｃａｇｏ | 癌処置としてのｓｔｉｎｇアゴニストの使用 |
| CN103908468B (zh) * | 2014-04-21 | 2017-02-08 | 上海捌加壹医药科技有限公司 | 环二核苷酸cGAMP在制备抗肿瘤药物中的应用 |
| US10682400B2 (en) | 2014-04-30 | 2020-06-16 | President And Fellows Of Harvard College | Combination vaccine devices and methods of killing cancer cells |
| KR20170015353A (ko) | 2014-06-04 | 2017-02-08 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Ｓｔｉｎｇ의 조절제로서 사이클릭 디뉴클레오타이드 |
| WO2016079899A1 (ja) * | 2014-11-20 | 2016-05-26 | 国立研究開発法人医薬基盤・健康・栄養研究所 | 異なる核酸アジュバントの組み合わせによる、新規Ｔｈ１誘導性アジュバントおよびその用途 |
| CN107148424B (zh) | 2014-12-16 | 2021-01-08 | 凯拉治疗股份公司 | 用于诱导细胞因子的环状二核苷酸 |
| GB201501462D0 (en) | 2015-01-29 | 2015-03-18 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CA3013713C (en) | 2015-02-11 | 2025-09-09 | Univ Johns Hopkins | Bacteria over-expressing c-di-amp and therapeutic methods |
| JP6692826B2 (ja) * | 2015-03-10 | 2020-05-13 | アドゥロ バイオテック，インク． | 「インターフェロン遺伝子刺激因子」依存性シグナル伝達の活性化のための組成物及び方法 |
| US10738095B2 (en) | 2015-06-03 | 2020-08-11 | The Medical College Of Wisconsin, Inc. | Engineered CCL20 locked dimer polypeptide |
| US11571462B2 (en) | 2015-06-03 | 2023-02-07 | The Medical College Of Wisconsin, Inc. | Engineered CCL20 locked dimer polypeptide |
| BR112018002757A8 (pt) | 2015-08-13 | 2023-04-11 | Merck Sharp & Dohme | Composto, composição farmacêutica, e, métodos para induzir uma resposta imune, para induzir uma produção de interferon tipo i e para tratamento de um distúrbio |
| US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| WO2017040790A1 (en) | 2015-09-01 | 2017-03-09 | Agenus Inc. | Anti-pd-1 antibodies and methods of use thereof |
| CN105367617A (zh) * | 2015-09-25 | 2016-03-02 | 武汉品生科技有限公司 | 一种基于环二腺核苷酸的衍生物、tat多肽及其在一型干扰素小分子中抑制剂的应用 |
| AU2016343993A1 (en) * | 2015-10-28 | 2018-05-10 | Aduro Biotech, Inc. | Compositions and methods for activating "stimulator of interferon gene"-dependent signalling |
| CN106539813B (zh) * | 2015-11-30 | 2019-12-03 | 杭州星鳌生物科技有限公司 | 干扰素刺激基因(sting)激活剂在抗炎症中的应用 |
| JP6411676B2 (ja) * | 2015-12-03 | 2018-10-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｓｔｉｎｇの調節因子としての環状プリンジヌクレオチド |
| CN106554416B (zh) * | 2015-12-09 | 2019-03-15 | 聊城市奥润生物医药科技有限公司 | 一种抗pd-l1人源化单克隆抗体联合干扰素基因刺激蛋白（sting）激动剂在抗肿瘤中的应用 |
| CN106539814A (zh) * | 2015-12-09 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | 干扰素基因刺激蛋白（sting）激动剂在抗类风湿性关节炎等疾病中的应用 |
| CN106540260A (zh) * | 2015-12-09 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | 干扰素基因刺激蛋白（sting）激动剂在抗阿尔兹海默症中的应用 |
| US20180369268A1 (en) * | 2015-12-16 | 2018-12-27 | Aduro Biotech, Inc. | Methods for identifying inhibitors of "stimulator of interferon gene"- dependent interferon production |
| CA3008641A1 (en) | 2015-12-16 | 2017-06-22 | Gritstone Oncology, Inc. | Neoantigen identification, manufacture, and use |
| KR20250049441A (ko) * | 2016-01-11 | 2025-04-11 | 인네이트 튜머 이뮤니티, 인코포레이티드 | Sting 활성과 연관된 상태 예컨대 암의 치료를 위한 시클릭 디뉴클레오티드 |
| KR20180114946A (ko) * | 2016-03-02 | 2018-10-19 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 면역요법을 위한 sting 활성화 나노백신 |
| NZ746112A (en) | 2016-03-18 | 2023-01-27 | Immune Sensor Llc | Cyclic di-nucleotide compounds and methods of use |
| CN106539757A (zh) * | 2016-03-20 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | 环二核苷酸cGAMP-脂质体在抗肿瘤中的应用 |
| RU2018137389A (ru) | 2016-04-07 | 2020-05-12 | Глаксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Гетероциклические амиды, полезные в качестве модуляторов |
| ES2921855T3 (es) | 2016-04-07 | 2022-09-01 | Glaxosmithkline Ip Dev Ltd | Amidas heterocíclicas útiles como moduladores de proteínas |
| EP3448393A1 (en) | 2016-04-25 | 2019-03-06 | Invivogen | Novel complexes of immunostimulatory compounds, and uses thereof |
| US10696985B1 (en) | 2016-06-06 | 2020-06-30 | Vanderbilt University | Reversibly crosslinked endosomolytic polymer vesicles for cytosolic drug delivery |
| US11098077B2 (en) | 2016-07-05 | 2021-08-24 | Chinook Therapeutics, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
| AU2017293781B2 (en) * | 2016-07-06 | 2022-12-22 | Invox Pharma Limited | Compounds, compositions, and methods for the treatment of disease |
| WO2018013924A1 (en) | 2016-07-15 | 2018-01-18 | Massachusetts Institute Of Technology | Synthetic nanoparticles for delivery of immunomodulatory compounds |
| DE102016113714A1 (de) | 2016-07-26 | 2018-02-01 | Rosa Karl | Transfektionsverfahren mit nicht-viralen Genliefersystemen |
| NL2017267B1 (en) | 2016-07-29 | 2018-02-01 | Aduro Biotech Holdings Europe B V | Anti-pd-1 antibodies |
| JP7274214B2 (ja) | 2016-08-02 | 2023-05-16 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 免疫応答を調節するための生体材料 |
| NL2017270B1 (en) | 2016-08-02 | 2018-02-09 | Aduro Biotech Holdings Europe B V | New anti-hCTLA-4 antibodies |
| KR102497742B1 (ko) | 2016-08-30 | 2023-02-10 | 다나-파버 캔서 인스티튜트 인크. | 약물 전달 조성물 및 그의 용도 |
| WO2018053508A1 (en) * | 2016-09-19 | 2018-03-22 | The University Of North Carolina At Chapel Hill | Methods and compositions for inducing an immune response |
| US10537590B2 (en) | 2016-09-30 | 2020-01-21 | Boehringer Ingelheim International Gmbh | Cyclic dinucleotide compounds |
| EP3523287B1 (en) | 2016-10-04 | 2021-09-01 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene compounds as sting agonists |
| US11001605B2 (en) | 2016-10-07 | 2021-05-11 | Biolog Life Science Institute Gmbh & Co. Kg | Cyclic dinucleotides containing benzimidazole, method for the production of same, and use of same to activate stimulator of interferon genes (sting)-dependent signaling pathways |
| US10266558B2 (en) * | 2016-10-07 | 2019-04-23 | Alexandre Vasilievich Ivachtchenko | Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof |
| JOP20170192A1 (ar) | 2016-12-01 | 2019-01-30 | Takeda Pharmaceuticals Co | داي نوكليوتيد حلقي |
| BR112019011582A2 (pt) | 2016-12-07 | 2019-10-22 | Agenus Inc. | anticorpos e métodos de utilização dos mesmos |
| WO2018119117A1 (en) * | 2016-12-22 | 2018-06-28 | The Regents Of The University Of California | Methods of producing cyclic dinucleotides |
| JP2018131427A (ja) * | 2017-02-17 | 2018-08-23 | 国立研究開発法人理化学研究所 | 免疫細胞の制御技術 |
| US20200055883A1 (en) | 2017-02-17 | 2020-02-20 | Eisai R&D Management Co., Ltd. | Cyclic di-nucleotides derivative for the treatment of cancer |
| EP3585379A4 (en) | 2017-02-21 | 2020-12-02 | Board of Regents, The University of Texas System | CYCLIC DINUCLEOTIDES USED AS AGONISTS OF THE INTERFERON-DEPENDENT SIGNALING STIMULATOR |
| CN106928298B (zh) * | 2017-03-13 | 2021-10-22 | 杭州星鳌生物科技有限公司 | 环二核苷酸cGAMP衍生物的结构组成、制备方法及其在抗肿瘤中的应用 |
| JOP20190218A1 (ar) * | 2017-03-22 | 2019-09-22 | Boehringer Ingelheim Int | مركبات ثنائية النيوكليوتيدات حلقية معدلة |
| IL315837A (en) | 2017-04-13 | 2024-11-01 | Sairopa B V | Anti-SIRP-alpha antibodies |
| EP3610022A1 (en) | 2017-04-14 | 2020-02-19 | Tollnine, Inc. | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
| AR113224A1 (es) | 2017-04-28 | 2020-02-19 | Novartis Ag | Conjugados de anticuerpo que comprenden un agonista de sting |
| UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
| EP3621624B1 (en) | 2017-05-12 | 2023-08-30 | Merck Sharp & Dohme LLC | Cyclic di-nucleotide compounds as sting agonists |
| WO2018232217A1 (en) | 2017-06-16 | 2018-12-20 | William Marsh Rice University | Hydrogel delivery of sting immunotherapy for treatment of cancer |
| RU2020109328A (ru) | 2017-08-04 | 2021-09-06 | Мерк Шарп И Доум Корп. | Комбинации антагонистов pd-1 и бензо[b]тиофеновых агонистов sting для лечения рака |
| EP3661498A4 (en) | 2017-08-04 | 2021-04-21 | Merck Sharp & Dohme Corp. | BENZO [B] THIOPHEN STING ANTAGONISTS FOR CANCER TREATMENT |
| CA3073919A1 (en) | 2017-08-30 | 2019-03-07 | Beijing Xuanyi Pharmasciences Co., Ltd. | Cyclic di-nucleotides as stimulator of interferon genes modulators |
| WO2019046511A1 (en) | 2017-08-31 | 2019-03-07 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISEASE |
| WO2019051488A1 (en) | 2017-09-11 | 2019-03-14 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS OF TREATING DISEASE |
| WO2019051489A1 (en) | 2017-09-11 | 2019-03-14 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS OF TREATING DISEASE |
| CA3076337A1 (en) | 2017-09-19 | 2019-03-28 | Massachusetts Institute Of Technology | Compositions for chimeric antigen receptor t cell therapy and uses thereof |
| US11377440B2 (en) | 2017-10-05 | 2022-07-05 | Glaxosmithkline Intellectual Property Development Limited | Modulators of stimulator of interferon genes (STING) |
| US20210238172A1 (en) | 2017-10-05 | 2021-08-05 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators and methods of using the same |
| WO2019075112A1 (en) | 2017-10-10 | 2019-04-18 | Gritstone Oncology, Inc. | IDENTIFICATION OF NEO-ANTIGENS USING HOT POINTS |
| MX2020004858A (es) | 2017-11-10 | 2020-10-01 | Takeda Pharmaceuticals Co | Compuestos moduladores de sting y metodos de elaboracion y uso. |
| CN111936136B (zh) | 2017-11-14 | 2024-07-05 | 儿童医学中心公司 | 新咪唑并嘧啶化合物及其用途 |
| JP7382316B2 (ja) * | 2017-11-14 | 2023-11-16 | ザ チルドレンズ メディカル センター コーポレーション | ヒト免疫応答をモジュレートするためのイミダゾピリミジンの使用 |
| KR20200090855A (ko) | 2017-11-22 | 2020-07-29 | 그릿스톤 온콜로지, 인코포레이티드 | 신생항원에 대한 접합 에피토프 제시 감소 |
| 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 |
| US11685761B2 (en) | 2017-12-20 | 2023-06-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| 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 |
| US12065649B2 (en) | 2018-01-09 | 2024-08-20 | Vanderbilt University | Pattern recognition receptor agonist prodrugs and methods of use thereof |
| US12220462B1 (en) | 2018-02-13 | 2025-02-11 | Abionyx Pharma Sa | Complexes for delivery of cyclic dinucleotides |
| WO2019161171A1 (en) * | 2018-02-16 | 2019-08-22 | Sperovie Biosciences, Inc. | Nanoparticle formulations of sting agonists |
| BR112020019089A2 (pt) | 2018-03-23 | 2020-12-29 | Codiak Biosciences, Inc. | Vesículas extracelulares compreendendo agonista de sting |
| JP2021519279A (ja) | 2018-03-27 | 2021-08-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 修飾環式ジヌクレオチド化合物 |
| CN111971291A (zh) | 2018-03-27 | 2020-11-20 | 勃林格殷格翰国际有限公司 | 用作sting激动剂的含有2-氮杂-次黄嘌呤或6h-吡唑并[1,5-d][1,2,4]三嗪-7-酮的环状二核苷酸化合物 |
| EP3774764A1 (en) | 2018-04-03 | 2021-02-17 | Merck Sharp&Dohme Corp. | Benzothiophenes and related compounds as sting agonists |
| US11702430B2 (en) | 2018-04-03 | 2023-07-18 | Merck Sharp & Dohme Llc | Aza-benzothiophene compounds as STING agonists |
| WO2019195658A1 (en) | 2018-04-05 | 2019-10-10 | Dana-Farber Cancer Institute, Inc. | Sting levels as a biomarker for cancer immunotherapy |
| 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 |
| 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 |
| GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
| WO2019227007A1 (en) | 2018-05-25 | 2019-11-28 | Incyte Corporation | Tricyclic heterocyclic compounds as sting activators |
| BR112020024605A2 (pt) | 2018-06-01 | 2021-04-06 | Eisai R&D Management Co., Ltd. | Métodos para o tratamento de câncer de bexiga |
| WO2020014127A1 (en) | 2018-07-10 | 2020-01-16 | Sperovie Biosciences, Inc. | Compounds, compositions, and methods for the treatment of disease |
| WO2020028566A1 (en) | 2018-07-31 | 2020-02-06 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
| WO2020028565A1 (en) | 2018-07-31 | 2020-02-06 | Incyte Corporation | Tricyclic heteraryl compounds as sting activators |
| KR20210040387A (ko) | 2018-08-03 | 2021-04-13 | 고쿠리츠다이가쿠호우진 도쿄다이가쿠 | 세포성 면역을 유도하는 경비 백신 |
| BR112021001349A2 (pt) | 2018-08-16 | 2021-04-20 | Eisai R&D Management Co., Ltd. | sais de compostos e cristais dos mesmos |
| EP3841112A1 (en) | 2018-08-24 | 2021-06-30 | Codiak BioSciences, Inc. | Extracellular vesicles targeting dendritic cells and uses thereof |
| LT3848054T (lt) | 2018-09-06 | 2025-03-25 | Daiichi Sankyo Company, Limited | Ciklinių dinukleotidų darinių antikūno ir vaisto konjugatai |
| WO2020059895A1 (ko) * | 2018-09-17 | 2020-03-26 | 주식회사 큐라티스 | 스팅 작용자를 포함하는 면역항원보강제 및 백신 조성물 |
| MX2021003207A (es) | 2018-09-21 | 2021-06-23 | Shanghai De Novo Pharmatech Co Ltd | Analogo de dinucleotido ciclico. composicion farmaceutica del mismo y su aplicacion. |
| US11110106B2 (en) | 2018-10-29 | 2021-09-07 | Venenum Biodesign, LLC | Sting agonists for treating bladder cancer and solid tumors |
| US11161864B2 (en) | 2018-10-29 | 2021-11-02 | Venenum Biodesign, LLC | Sting agonists |
| WO2020092633A1 (en) | 2018-10-30 | 2020-05-07 | Vanderbilt University | Graft copolymers, methods of forming graft copolymers, and methods of use thereof |
| EP3873938A1 (en) | 2018-10-31 | 2021-09-08 | Novartis AG | Dc-sign antibody conjugates comprising sting agonists |
| US11596692B1 (en) | 2018-11-21 | 2023-03-07 | Incyte Corporation | PD-L1/STING conjugates and methods of use |
| US12129267B2 (en) | 2019-01-07 | 2024-10-29 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
| EP3901161B1 (en) * | 2019-01-10 | 2025-01-22 | Shenzhen YING Biopharmaceutical Co., Ltd. | Cyclic dinucleotide prodrug molecule, preparation method therefor and application thereof |
| 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 |
| 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 |
| 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 |
| WO2020191369A1 (en) | 2019-03-21 | 2020-09-24 | Codiak Biosciences, Inc. | Process for preparing extracellular vesicles |
| KR20210141554A (ko) | 2019-03-21 | 2021-11-23 | 코디악 바이오사이언시즈, 인크. | 세포외 소포 접합체 및 이의 용도 |
| KR20220004035A (ko) | 2019-03-21 | 2022-01-11 | 코디악 바이오사이언시즈, 인크. | 백신 전달을 위한 세포외 소포 |
| WO2020205688A1 (en) | 2019-04-04 | 2020-10-08 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
| TW202104214A (zh) | 2019-04-05 | 2021-02-01 | 英商葛蘭素史密斯克藍智慧財產發展有限公司 | 化合物 |
| WO2020227159A2 (en) * | 2019-05-03 | 2020-11-12 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity |
| JP7621974B2 (ja) | 2019-05-09 | 2025-01-27 | アリゴス セラピューティクス インコーポレイテッド | Ｓｔｉｎｇモジュレータとしての修飾環状ジヌクレオシド化合物 |
| IL287938B2 (en) | 2019-05-10 | 2025-07-01 | Takeda Pharmaceuticals Co | Antibody-drug conjugates |
| EP3994158A1 (en) | 2019-07-03 | 2022-05-11 | Codiak BioSciences, Inc. | Extracellular vesicles targeting t cells and uses thereof |
| GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| TW202120500A (zh) | 2019-08-02 | 2021-06-01 | 美商梅爾莎納醫療公司 | 干擾素基因刺激蛋白（ｓｔｉｎｇ）激動劑化合物及用途 |
| US12098212B2 (en) | 2019-08-12 | 2024-09-24 | Purinomia Biotech, Inc. | Methods and compositions for promoting and potentiating T-cell mediated immune responses through ADCC targeting of CD39 expressing cells |
| WO2021041532A1 (en) | 2019-08-26 | 2021-03-04 | Dana-Farber Cancer Institute, Inc. | Use of heparin to promote type 1 interferon signaling |
| EP3785719A1 (en) * | 2019-08-28 | 2021-03-03 | Helmholtz-Zentrum für Infektionsforschung GmbH | New use of cyclic dinucleotides |
| KR20220092654A (ko) | 2019-09-25 | 2022-07-01 | 코디악 바이오사이언시즈, 인크. | 세포외 소포 조성물 |
| WO2021062290A1 (en) | 2019-09-25 | 2021-04-01 | Codiak Biosciences, Inc. | Methods of producing extracellular vesicles |
| CA3152488A1 (en) | 2019-09-25 | 2021-04-01 | Codiak Biosciences, Inc. | Combination therapy using extracellular vesicles |
| US20230241089A1 (en) | 2019-09-25 | 2023-08-03 | Codiak Biosciences, Inc. | Sting agonist comprising exosomes for treating neuroimmunological disorders |
| WO2021074695A1 (en) | 2019-10-16 | 2021-04-22 | Avacta Life Sciences Limited | PD-L1 INHIBITOR - TGFβ INHIBITOR BISPECIFIC DRUG MOIETIES. |
| EP4069683A1 (en) | 2019-12-06 | 2022-10-12 | Mersana Therapeutics, Inc. | Dimeric compounds as sting agonists |
| CN114981265B (zh) | 2019-12-18 | 2025-01-03 | Ctxt私人有限公司 | 化合物 |
| US12251449B2 (en) | 2019-12-19 | 2025-03-18 | William Marsh Rice University | Synthetic multidomain peptide biomaterials that inhibit inducible nitric oxide synthase |
| WO2021126281A1 (en) | 2019-12-20 | 2021-06-24 | Nammi Therapeutics, Inc. | Formulated and/or co-formulated liposome compositions containing toll-like receptor ("tlr") agonist prodrugs useful in the treatment of cancer and methods thereof |
| US11179473B2 (en) | 2020-02-21 | 2021-11-23 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
| IL295759A (en) | 2020-02-28 | 2022-10-01 | Tallac Therapeutics Inc | Transglutaminase mediated coupling |
| IL296124A (en) | 2020-03-06 | 2022-11-01 | Daiichi Sankyo Co Ltd | Antibody-drug conjugate including novel cyclic dinucleotide derivative |
| EP4117717A1 (en) | 2020-03-13 | 2023-01-18 | Codiak BioSciences, Inc. | Extracellular vesicles for treating neurological disorders |
| AU2021236763A1 (en) | 2020-03-20 | 2022-10-06 | Lonza Sales Ag | Extracellular vesicles for therapy |
| BR122022020762A2 (pt) | 2020-04-02 | 2023-04-11 | Mersana Therapeutics, Inc | Conjugados de anticorpo-fármaco compreendendo agonistas de sting, seu uso e composição |
| JPWO2021206158A1 (enExample) | 2020-04-10 | 2021-10-14 | ||
| WO2021216572A1 (en) | 2020-04-20 | 2021-10-28 | Massachusetts Institute Of Technology | Lipid compositions for delivery of sting agonist compounds and uses thereof |
| WO2021221783A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Methods for identifying chimeric antigen receptor-targeting ligands and uses thereof |
| WO2021221782A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Chimeric antigen receptor-targeting ligands and uses thereof |
| IL298019A (en) | 2020-05-13 | 2023-01-01 | Massachusetts Inst Technology | Compositions of polymeric microdevices and their use in cancer immunotherapy |
| WO2021237100A1 (en) | 2020-05-21 | 2021-11-25 | Codiak Biosciences, Inc. | Methods of targeting extracellular vesicles to lung |
| CN116209678A (zh) | 2020-07-01 | 2023-06-02 | 安尔士制药公司 | 抗asgr1抗体缀合物及其用途 |
| CN116113641A (zh) | 2020-09-02 | 2023-05-12 | 第一三共株式会社 | 新型内－β－N－乙酰氨基葡萄糖苷酶 |
| WO2022066934A2 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Process for preparing extracellular vesicles |
| US20240241020A1 (en) | 2020-09-23 | 2024-07-18 | Lonza Sales Ag | Process for preparing extracellular vesicles |
| WO2022066883A1 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Extracellular vesicles comprising kras antigens and uses thereof |
| CA3192470A1 (en) | 2020-09-23 | 2022-03-31 | Tim SOOS | Methods of producing extracellular vesicles |
| WO2022079175A1 (en) | 2020-10-14 | 2022-04-21 | Boehringer Ingelheim International Gmbh | Combination of a sting agonist and a complex comprising a cell penetrating peptide, a cargo and a tlr peptide agonist |
| WO2022083584A1 (zh) * | 2020-10-20 | 2022-04-28 | 泰励生物科技（上海）有限公司 | 多功能环二核苷酸及其用途 |
| TW202233251A (zh) | 2020-11-09 | 2022-09-01 | 日商武田藥品工業股份有限公司 | 抗體藥物綴合物 |
| CN116981479A (zh) | 2020-12-17 | 2023-10-31 | 塔夫茨大学信托人 | Fap激活的放射治疗诊断法以及与之相关的用途 |
| EP4032545A1 (en) * | 2021-01-26 | 2022-07-27 | Medizinische Hochschule Hannover | Immunogenic composition and vaccine containing chlamydia ssp. surface antigens and its use |
| EP4326321A1 (en) | 2021-04-20 | 2024-02-28 | Institut Curie | Compositions and methods for use in immunotherapy |
| WO2022223619A1 (en) | 2021-04-20 | 2022-10-27 | Institut Curie | Compositions and methods for use in immunotherapy |
| WO2022234003A1 (en) | 2021-05-07 | 2022-11-10 | Avacta Life Sciences Limited | Cd33 binding polypeptides with stefin a protein |
| WO2023056468A1 (en) | 2021-09-30 | 2023-04-06 | Codiak Biosciences, Inc. | Extracellular vesicle comprising cholesterol tagged sting-agonist |
| US20250243277A1 (en) | 2021-10-07 | 2025-07-31 | Avacta Life Sciences Limited | Pd-l1 binding affimers |
| WO2023167238A1 (ja) | 2022-03-02 | 2023-09-07 | 第一三共株式会社 | Ｆｃ含有分子の製造方法 |
| JP2025509191A (ja) | 2022-03-04 | 2025-04-11 | マサチューセッツ インスティテュート オブ テクノロジー | 経粘膜性の両親媒性物質－タンパク質コンジュゲートワクチン |
| WO2023218243A1 (en) | 2022-05-12 | 2023-11-16 | Avacta Life Sciences Limited | Lag-3/pd-l1 binding fusion proteins |
| WO2024036275A1 (en) * | 2022-08-10 | 2024-02-15 | Aldevron Llc | Methods for producing cyclic dinucleotides |
| EP4582106A1 (en) | 2022-08-29 | 2025-07-09 | Daiichi Sankyo Company, Limited | Antibody-drug conjugate including mutant fc region |
| CN115381936A (zh) * | 2022-08-29 | 2022-11-25 | 福建师范大学 | 一种猴痘病毒疫苗 |
| WO2024199359A1 (zh) * | 2023-03-28 | 2024-10-03 | 江苏瑞科生物技术股份有限公司 | 包含环二核苷酸分子的脂质体佐剂系统及其制备方法 |
| WO2024211577A1 (en) | 2023-04-05 | 2024-10-10 | Massachusetts Institute Of Technology | Hybrid polymeric systems and methods of use thereof |
| CN116392585A (zh) * | 2023-04-06 | 2023-07-07 | 中山大学孙逸仙纪念医院 | 一种肿瘤疫苗佐剂及其应用 |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9110808D0 (en) | 1991-05-17 | 1991-07-10 | Retroscreen Ltd | Aids vaccine and method for its production |
| GB2257704B (en) * | 1991-07-18 | 1995-03-01 | Erba Carlo Spa | Cyclic oligonucleotides phosphorothioates |
| US5904920A (en) | 1991-10-04 | 1999-05-18 | Whitehead Institute For Biomedical Research | Regulation of systemic immune responses utilizing cytokines and antigens |
| US5637483A (en) | 1991-10-04 | 1997-06-10 | Whitehead Institute For Biomedical Research | Irradiated tumor cell vaccine engineered to express GM-CSF |
| IT1262895B (it) | 1992-03-02 | 1996-07-22 | Proteina estratta da ceppi citotossici di helicobacter pylori, gene che la esprime, uso della proteina come vaccino o diagnostico. | |
| US5635160A (en) | 1995-06-07 | 1997-06-03 | The University Of North Carolina At Chapel Hill | Dinucleotides useful for the treatment of cystic fibrosis and for hydrating mucus secretions |
| US6033674A (en) | 1995-12-28 | 2000-03-07 | Johns Hopkins University School Of Medicine | Method of treating cancer with a tumor cell line having modified cytokine expression |
| US6277368B1 (en) | 1996-07-25 | 2001-08-21 | The Regents Of The University Of California | Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokine |
| KR20010074426A (ko) | 1998-02-02 | 2001-08-04 | 추후제출 | 만능 면역조절 사이토킨-발현 방관자 세포주 및 관련조성물 및 제조방법 및 사용방법 |
| WO2000047601A1 (en) | 1999-02-15 | 2000-08-17 | Nippon Shinyaku Co. Ltd. | Shortened-chain polynucleotides and process for the preparation thereof |
| US6558670B1 (en) * | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
| WO2002024739A2 (en) | 2000-09-21 | 2002-03-28 | The Regents Of The University Of California | Spas-1 cancer antigen |
| AU2002244337B2 (en) * | 2000-10-18 | 2005-08-11 | Glaxosmithkline Biologicals S.A. | Vaccines |
| US7279883B2 (en) | 2001-01-23 | 2007-10-09 | Lydia L. Sohn | Particle analyzer and methods for use thereof |
| TW200303759A (en) | 2001-11-27 | 2003-09-16 | Schering Corp | Methods for treating cancer |
| AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| CA2533873A1 (en) | 2003-07-28 | 2005-04-07 | David K.R. Karaolis | Method for attenuating virulence of microbial pathogens and for inhibiting microbial biofilm formation |
| KR20060130038A (ko) | 2003-10-15 | 2006-12-18 | 메디뮨 인코포레이티드 | 리스테리아에 의거한 ＥｐｈＡ２ 백신 |
| US20050175683A1 (en) * | 2003-10-24 | 2005-08-11 | Yuanpeng Zhang | Preparation of lipid particles |
| AU2005222626B2 (en) * | 2004-03-15 | 2010-05-20 | Karagen Pharmaceuticals, Inc. | A method for inhibiting cancer cell proliferation or increasing cancer cell apoptosis |
| US7592326B2 (en) * | 2004-03-15 | 2009-09-22 | Karaolis David K R | Method for stimulating the immune, inflammatory or neuroprotective response |
| EP1888790A2 (en) | 2005-05-06 | 2008-02-20 | The Regents of the University of California | Microfluidic system for identifying or sizing individual particles passing through a channel |
| US20070059683A1 (en) | 2005-09-15 | 2007-03-15 | Tom Barber | Veterinary diagnostic system |
| EP1782826A1 (en) * | 2005-11-08 | 2007-05-09 | GBF Gesellschaft für Biotechnologische Forschung mbH | PQS and c-diGMP and its conjugates as adjuvants and their uses in pharmaceutical compositions |
| US20090324587A1 (en) | 2005-12-01 | 2009-12-31 | Neal Clifford Goodwin | Cancer Therapies and Pharmaceutical Compositions Used Therein |
| EP2049665A2 (en) | 2006-07-28 | 2009-04-22 | Applera Corporation | Dinucleotide mrna cap analogs |
| EP2059802A4 (en) | 2006-09-05 | 2010-09-08 | Bipar Sciences Inc | METHODS FOR DESIGNING PARP INHIBITORS AND USES THEREOF |
| TWI444384B (zh) * | 2008-02-20 | 2014-07-11 | Gilead Sciences Inc | 核苷酸類似物及其在治療惡性腫瘤上的用途 |
| WO2010017248A2 (en) | 2008-08-04 | 2010-02-11 | University Of Miami | Sting (stimulator of interferon genes), a regulator of innate immune responses |
| US8840881B2 (en) | 2008-08-28 | 2014-09-23 | Aduro Gvax Inc. | Methods and compositions for treating prostate cancer or inducing a humoral immune response against prostate cancer |
| MY160201A (en) * | 2008-12-09 | 2017-02-28 | Coley Pharm Group Inc | Immunostimulatory oligonucleotides |
| CA2754896C (en) | 2009-03-09 | 2017-11-28 | Molecular Express, Inc. | Methods and compositions for liposomal formulation of antigens and uses thereof |
| US8414630B2 (en) | 2009-03-10 | 2013-04-09 | Marc Evan Richelsoph | Active bone screw |
| LT2437753T (lt) | 2009-06-05 | 2016-12-12 | Infectious Disease Research Institute | Sintetiniai gliukopiranozillipidų adjuvantai ir juos turinčios vakcinų kompozicijos |
| WO2011003025A1 (en) * | 2009-07-01 | 2011-01-06 | Rutgers, The State University Of New Jersey | Synthesis of cyclic diguanosine monophosphate and thiophosphate analogs thereof |
| US8771933B2 (en) | 2009-10-06 | 2014-07-08 | Massachusetts Institute Of Technology | Continuous-flow deformability-based cell separation |
| EP2513309A2 (en) * | 2009-12-18 | 2012-10-24 | Novartis AG | Organic compositions to treat hsf1-related diseases |
| EP2361911A1 (en) * | 2010-02-18 | 2011-08-31 | GenKyoTex SA | Pyrazolo piperidine derivatives as NADPH oxidase inhibitors |
| US20110287948A1 (en) | 2010-03-22 | 2011-11-24 | Massachusetts Institute Of Technology | Measurement of material properties and related methods and compositions based on cytoadherence |
| CN102199183B (zh) | 2010-03-26 | 2013-12-18 | 北京大学 | 环二鸟苷酸及其类似物和制备方法 |
| CA2798074A1 (en) | 2010-04-27 | 2011-11-03 | The Johns Hopkins University | Immunogenic compositions and methods for treating neoplasia |
| US8450293B2 (en) | 2010-08-10 | 2013-05-28 | Rutgers, The State University Of New Jersey | Synthesis and characterization of C8 analogs of c-di-GMP |
| HRP20181343T1 (hr) | 2010-11-17 | 2018-10-19 | Aduro Biotech, Inc. | Postupci i pripravci za induciranje imunosnog odgovora na egfrviii |
| US9061048B2 (en) | 2010-12-15 | 2015-06-23 | The Regents Of The University Of California | Cyclic di-AMP induction of type I interferon |
| EP2655392B1 (en) * | 2010-12-22 | 2018-04-18 | Alios Biopharma, Inc. | Cyclic nucleotide analogs |
| WO2012139209A1 (en) | 2011-04-15 | 2012-10-18 | The University Of British Columbia | Method and apparatus for separation of particles |
| WO2013086331A1 (en) | 2011-12-07 | 2013-06-13 | President And Fellows Of Harvard College | High efficiency di-nucleotide cyclase |
| EP2844756A4 (en) | 2012-04-30 | 2016-02-24 | Glen N Barber | MODULATION OF IMMUNE REACTIONS |
| CN104507538B (zh) | 2012-06-08 | 2018-04-06 | 艾杜罗生物科技公司 | 癌症免疫疗法的组合物和方法 |
| CN103566377A (zh) * | 2012-07-18 | 2014-02-12 | 上海博笛生物科技有限公司 | 癌症的靶向免疫治疗 |
| US9090646B2 (en) | 2012-12-05 | 2015-07-28 | Rutgers, The State University Of New Jersey | Biotinylated compounds |
| SG11201502796RA (en) | 2012-12-13 | 2015-05-28 | Aduro Biotech Inc | Compositions comprising cyclic purine dinucleotides having defined stereochemistries and methods for their preparation and use |
| WO2014099824A1 (en) | 2012-12-19 | 2014-06-26 | Board Of Regents, The University Of Texas System | Pharmaceutical targeting of a mammalian cyclic di-nucleotide signaling pathway |
| CA2908154C (en) | 2013-04-29 | 2023-11-28 | Memorial Sloan Kettering Cancer Center | Compositions and methods for altering second messenger signaling |
| JP2016518140A (ja) | 2013-05-03 | 2016-06-23 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｉ型インターフェロンの環状ジヌクレオチド誘導法 |
| CU24377B1 (es) * | 2013-05-18 | 2018-12-05 | Aduro Biotech Inc | Dinucléotidos de purina cíclicos y composiciones de los mismos útiles para inducir la producción de interferón de tipo i dependientes de sting |
| US9549944B2 (en) | 2013-05-18 | 2017-01-24 | Aduro Biotech, Inc. | Compositions and methods for inhibiting “stimulator of interferon gene”—dependent signalling |
| CN105188373B (zh) | 2013-05-18 | 2017-09-22 | 艾杜罗生物科技公司 | 抑制“干扰素基因刺激蛋白”依赖性信号传导的组合物和方法 |
| US10176292B2 (en) | 2013-07-31 | 2019-01-08 | Memorial Sloan-Kettering Cancer Center | STING crystals and modulators |
| KR20160065858A (ko) | 2013-10-21 | 2016-06-09 | 드렉셀유니버시티 | 만성 b형 간염 바이러스 감염을 치료하기 위한 스팅 효능제의 사용 |
| JP2016538344A (ja) | 2013-11-19 | 2016-12-08 | ザ・ユニバーシティ・オブ・シカゴＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃｈｉｃａｇｏ | 癌処置としてのｓｔｉｎｇアゴニストの使用 |
| WO2015074145A1 (en) | 2013-11-22 | 2015-05-28 | Brock University | Use of fluorinated cyclic dinucleotides as oral vaccine adjuvants |
| WO2015085565A1 (en) | 2013-12-13 | 2015-06-18 | Qualcomm Incorporated | Methods and apparatus for cell selection in a wireless communication system |
| WO2015108595A1 (en) | 2014-01-15 | 2015-07-23 | Nikolai Khodarev | Anti-tumor therapy |
| KR20170015353A (ko) | 2014-06-04 | 2017-02-08 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Ｓｔｉｎｇ의 조절제로서 사이클릭 디뉴클레오타이드 |
| CN107148424B (zh) | 2014-12-16 | 2021-01-08 | 凯拉治疗股份公司 | 用于诱导细胞因子的环状二核苷酸 |
| GB201501462D0 (en) | 2015-01-29 | 2015-03-18 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| JP6692826B2 (ja) * | 2015-03-10 | 2020-05-13 | アドゥロ バイオテック，インク． | 「インターフェロン遺伝子刺激因子」依存性シグナル伝達の活性化のための組成物及び方法 |
| BR112018002757A8 (pt) | 2015-08-13 | 2023-04-11 | Merck Sharp & Dohme | Composto, composição farmacêutica, e, métodos para induzir uma resposta imune, para induzir uma produção de interferon tipo i e para tratamento de um distúrbio |
| JP6411676B2 (ja) | 2015-12-03 | 2018-10-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｓｔｉｎｇの調節因子としての環状プリンジヌクレオチド |
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