JP6400082B2 - 「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 - Google Patents
「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 Download PDFInfo
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- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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| PL2931738T3 (pl) | 2012-12-13 | 2019-07-31 | Aduro Biotech, Inc. | Kompozycje zawierające cykliczne dinukleotydy purynowe o zdefiniowanej stereochemii i sposoby ich otrzymywania i zastosowania |
| WO2014179335A1 (en) * | 2013-04-29 | 2014-11-06 | Memorial Sloan Kettering Cancer Center | Compositions and methods for altering second messenger signaling |
| WO2014179760A1 (en) | 2013-05-03 | 2014-11-06 | The Regents Of The University Of California | Cyclic di-nucleotide induction of type i interferon |
| US9549944B2 (en) | 2013-05-18 | 2017-01-24 | Aduro Biotech, Inc. | Compositions and methods for inhibiting “stimulator of interferon gene”—dependent signalling |
| RS59500B1 (sr) | 2013-05-18 | 2019-12-31 | Aduro Biotech Inc | Sastavi i metode za aktiviranje signaliziranja koje je zavisno od „stimulatora gena za interferon“ |
| EP3027227A4 (en) | 2013-07-31 | 2018-05-23 | Memorial Sloan Kettering Cancer Center | Sting crystals and modulators |
| MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| TWI716362B (zh) | 2014-10-14 | 2021-01-21 | 瑞士商諾華公司 | 針對ｐｄ－ｌ１之抗體分子及其用途 |
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| 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 |
| 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 |
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| CN116003593A (zh) | 2016-01-11 | 2023-04-25 | 苏黎世大学 | 针对人白介素-2的免疫刺激性人源化单克隆抗体及其融合蛋白 |
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| DE102016113714A1 (de) | 2016-07-26 | 2018-02-01 | Rosa Karl | Transfektionsverfahren mit nicht-viralen Genliefersystemen |
| US10414747B2 (en) | 2016-10-04 | 2019-09-17 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene compounds as sting agonists |
| WO2018100558A2 (en) | 2016-12-01 | 2018-06-07 | Takeda Pharmaceutical Company Limited | Cyclic dinucleotide |
| WO2018118665A1 (en) * | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Cyclic dinucleotide sting agonists for cancer treatment |
| US11492367B2 (en) | 2017-01-27 | 2022-11-08 | Janssen Biotech, Inc. | Cyclic dinucleotides as sting agonists |
| US11021511B2 (en) | 2017-01-27 | 2021-06-01 | Janssen Biotech, Inc. | Cyclic dinucleotides as sting agonists |
| JP2020514321A (ja) | 2017-02-01 | 2020-05-21 | モデルナティーエックス， インコーポレイテッド | 活性化がん遺伝子変異ペプチドをコードする免疫調節治療ｍＲＮＡ組成物 |
| CA3053568A1 (en) | 2017-02-21 | 2018-08-30 | Board Of Regents, The University Of Texas System | Cyclic dinucleotides as agonists of stimulator of interferon gene dependent signalling |
| US11466047B2 (en) | 2017-05-12 | 2022-10-11 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
| CN118307674A (zh) | 2017-06-22 | 2024-07-09 | 诺华股份有限公司 | 针对cd73的抗体分子及其用途 |
| WO2018237173A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| US11285131B2 (en) | 2017-08-04 | 2022-03-29 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene STING agonists for cancer treatment |
| US11312772B2 (en) | 2017-08-04 | 2022-04-26 | Merck Sharp & Dohme Corp. | Combinations of PD-1 antagonists and benzo [b] thiophene STING agonists for cancer treatment |
| ES2904317T3 (es) * | 2017-08-31 | 2022-04-04 | Bristol Myers Squibb Co | Dinucleótidos cíclicos como agentes anticancerosos |
| US10947263B2 (en) * | 2017-08-31 | 2021-03-16 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
| JP7270608B2 (ja) | 2017-08-31 | 2023-05-10 | エフ－スター・セラピューティクス・インコーポレイテッド | 化合物、組成物、及び疾患の治療方法 |
| US11427610B2 (en) * | 2017-10-16 | 2022-08-30 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
| EP3700933A1 (en) | 2017-10-25 | 2020-09-02 | Novartis AG | Antibodies targeting cd32b and methods of use thereof |
| JP7195317B2 (ja) | 2017-11-10 | 2022-12-23 | 武田薬品工業株式会社 | Ｓｔｉｎｇ調節剤化合物、ならびに製造及び使用する方法 |
| CN111511754B (zh) | 2017-12-20 | 2023-09-12 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的2’3’环状二核苷酸 |
| US10966999B2 (en) | 2017-12-20 | 2021-04-06 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| EP3727401A4 (en) | 2017-12-20 | 2022-04-06 | Merck Sharp & Dohme Corp. | CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS |
| SG11202008636YA (en) | 2018-03-23 | 2020-10-29 | Codiak Biosciences Inc | Extracellular vesicles comprising sting-agonist |
| US10793557B2 (en) | 2018-04-03 | 2020-10-06 | Merck Sharp & Dohme Corp. | Sting agonist compounds |
| US11702430B2 (en) | 2018-04-03 | 2023-07-18 | Merck Sharp & Dohme Llc | Aza-benzothiophene compounds as STING agonists |
| 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 |
| 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 |
| US20210214459A1 (en) | 2018-05-31 | 2021-07-15 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| EP3841112A1 (en) | 2018-08-24 | 2021-06-30 | Codiak BioSciences, Inc. | Extracellular vesicles targeting dendritic cells and uses thereof |
| KR102567590B1 (ko) | 2018-09-06 | 2023-08-17 | 다이이찌 산쿄 가부시키가이샤 | 신규 고리형 디뉴클레오티드 유도체 및 그 항체 약물 콘쥬게이트 |
| AU2019344398B2 (en) | 2018-09-21 | 2022-09-22 | Shanghai De Novo Pharmatech Co., Ltd. | Cyclic dinucleotide analogue, pharmaceutical composition thereof, and application |
| CN114080232A (zh) | 2019-03-21 | 2022-02-22 | 科迪亚克生物科学公司 | 用于疫苗递送的细胞外囊泡 |
| KR20210141554A (ko) | 2019-03-21 | 2021-11-23 | 코디악 바이오사이언시즈, 인크. | 세포외 소포 접합체 및 이의 용도 |
| US12281109B2 (en) | 2019-04-04 | 2025-04-22 | Merck Sharp & Dohme Llc | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
| 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 |
| US20220251200A1 (en) | 2019-07-03 | 2022-08-11 | Codiak Biosciences, Inc. | Extracellular vesicles targeting t cells and uses thereof |
| AU2020310853A1 (en) | 2019-07-05 | 2022-01-27 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| CA3149482A1 (en) | 2019-08-02 | 2021-02-11 | Mersana Therapeutics, Inc. | Bis-[n-((5-carbamoyl)-1h-benzo[d]imidazol-2-yl)-pyrazol-5-carboxamide] derivatives and related compounds as sting (stimulator of interferon genes) agonists for the treatment of cancer |
| CA3152478A1 (en) | 2019-09-25 | 2021-04-01 | Codiak Biosciences, Inc. | Extracellular vesicle compositions |
| EP4034247A1 (en) | 2019-09-25 | 2022-08-03 | Codiak BioSciences, Inc. | Sting agonist comprising exosomes for treating neuroimmunological disorders |
| US20230103726A1 (en) | 2019-09-25 | 2023-04-06 | Codiak Biosciences, Inc. | Methods of producing extracellular vesicles |
| US20220395465A1 (en) | 2019-09-25 | 2022-12-15 | Codiak Biosciences, Inc. | Sting agonist comprising exosomes combined with il-12 displaying exosomes for treating a tumour |
| WO2021113679A1 (en) | 2019-12-06 | 2021-06-10 | Mersana Therapeutics, Inc. | Dimeric compounds as sting agonists |
| CA3168368A1 (en) | 2020-03-06 | 2021-09-10 | Masayuki Ishizaki | Antibody-drug conjugate including novel cyclic dinucleotide derivative |
| WO2021184017A1 (en) | 2020-03-13 | 2021-09-16 | Codiak Biosciences, Inc. | Extracellular vesicles for treating neurological disorders |
| JP2023518414A (ja) | 2020-03-20 | 2023-05-01 | コディアック バイオサイエンシーズ， インコーポレイテッド | 治療のための細胞外小胞 |
| WO2021202984A1 (en) | 2020-04-02 | 2021-10-07 | Mersana Therapeutics, Inc. | Antibody drug conjugates comprising sting agonists |
| WO2021206158A1 (ja) | 2020-04-10 | 2021-10-14 | 小野薬品工業株式会社 | がん治療方法 |
| JP2023533111A (ja) | 2020-05-15 | 2023-08-02 | イミューンセンサー セラピューティクス、インコーポレイテッド | 免疫チェックポイント阻害剤とのｓｔｉｎｇアゴニスト併用治療 |
| WO2021237100A1 (en) | 2020-05-21 | 2021-11-25 | Codiak Biosciences, Inc. | Methods of targeting extracellular vesicles to lung |
| EP4295917A3 (en) | 2020-08-07 | 2024-02-28 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| TW202227479A (zh) | 2020-09-02 | 2022-07-16 | 日商第一三共股份有限公司 | 新穎內－β－Ｎ－乙醯葡萄糖胺苷酶 |
| WO2022066883A1 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Extracellular vesicles comprising kras antigens and uses thereof |
| WO2022066898A2 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Methods of producing extracellular vesicles |
| EP4228681A1 (en) | 2020-10-14 | 2023-08-23 | Boehringer Ingelheim International GmbH | Combination of a sting agonist and a complex comprising a cell penetrating peptide, a cargo and a tlr peptide agonist |
| AU2021363267A1 (en) * | 2020-10-20 | 2023-06-22 | Tyligand Bioscience (Shanghai) Limited | Multifunctional cyclic dinucleotide and use thereof |
| JP7397996B2 (ja) | 2020-11-09 | 2023-12-13 | 武田薬品工業株式会社 | 抗体薬物コンジュゲート |
| TW202241454A (zh) | 2021-02-01 | 2022-11-01 | 日商第一三共股份有限公司 | 抗體－免疫賦活化劑共軛物之新穎製造方法 |
| AU2022315305A1 (en) | 2021-07-23 | 2024-02-01 | Immunesensor Therapeutics, Inc. | Sting agonist combination treatments with cytokines |
| WO2023056468A1 (en) | 2021-09-30 | 2023-04-06 | Codiak Biosciences, Inc. | Extracellular vesicle comprising cholesterol tagged sting-agonist |
| WO2023154799A1 (en) | 2022-02-14 | 2023-08-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Combination immunotherapy for treating cancer |
| US20250207169A1 (en) | 2022-03-02 | 2025-06-26 | Daiichi Sankyo Company, Limited | METHOD FOR PRODUCING Fc-CONTAINING MOLECULE |
| AU2023336004A1 (en) | 2022-08-29 | 2025-03-06 | Daiichi Sankyo Company, Limited | Antibody-drug conjugate including mutant fc region |
| GB202304385D0 (en) | 2023-03-24 | 2023-05-10 | Prostate Cancer Res | Combinatorial IL-15 therapy |
| CN116253766B (zh) * | 2023-03-27 | 2024-08-27 | 瑞阳（上海）新药研发有限公司 | 一种环二核苷酸2’,3’-cGAMP的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004275696B2 (en) * | 2003-07-28 | 2010-02-18 | Karagen Pharmaceuticals, Inc. | Method for attenuating virulence of microbial pathogens and for inhibiting microbial biofilm formation |
| JP2007533647A (ja) * | 2003-10-24 | 2007-11-22 | アルザ・コーポレーシヨン | 脂質粒子の調製 |
| 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 |
| US20120178710A1 (en) * | 2009-07-01 | 2012-07-12 | Rutgers, The State University Of New Jersey | Synthesis of cyclic diguanosine monophosphate and thiophosphate analogs thereof |
| US9061048B2 (en) * | 2010-12-15 | 2015-06-23 | The Regents Of The University Of California | Cyclic di-AMP induction of type I interferon |
| 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 |
| PL2931738T3 (pl) * | 2012-12-13 | 2019-07-31 | Aduro Biotech, Inc. | Kompozycje zawierające cykliczne dinukleotydy purynowe o zdefiniowanej stereochemii i sposoby ich otrzymywania i zastosowania |
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| WO2014189806A1 (en) | 2014-11-27 |
| JP2016531842A (ja) | 2016-10-13 |
| CN105188373A (zh) | 2015-12-23 |
| EP2996472A1 (en) | 2016-03-23 |
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