AU2013271375B2 - Compositions and methods for cancer immunotherapy - Google Patents
Compositions and methods for cancer immunotherapy Download PDFInfo
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- AU2013271375B2 AU2013271375B2 AU2013271375A AU2013271375A AU2013271375B2 AU 2013271375 B2 AU2013271375 B2 AU 2013271375B2 AU 2013271375 A AU2013271375 A AU 2013271375A AU 2013271375 A AU2013271375 A AU 2013271375A AU 2013271375 B2 AU2013271375 B2 AU 2013271375B2
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| EA201590396A1 (ru) | 2012-12-13 | 2015-12-30 | Адуро Биотек, Инк. | Композиция, содержащая циклические пуриновые динуклеотиды с определенной стереохимией, и способ ее получения и применения |
| MX365661B (es) * | 2012-12-19 | 2019-06-10 | Univ Texas | Activacion farmaceutica de una senda de señalizacion de di-nucleotido ciclico de mamifero. |
| CA2908154C (en) | 2013-04-29 | 2023-11-28 | 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 |
| 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“ |
| 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 |
| AU2014280133B2 (en) * | 2013-06-14 | 2016-12-15 | Intervet International B.V. | Pharmaceutical compositions comprising a GPG oligodeoxynucleotide and cyclic di-GMP |
| WO2015017652A1 (en) | 2013-07-31 | 2015-02-05 | Memorial Sloan-Kettering Cancer Center | Sting crystals and modulators |
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| 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 |
| ES2692226T3 (es) | 2014-06-04 | 2018-11-30 | Glaxosmithkline Intellectual Property Development Limited | Dinucleótidos cíclicos como moduladores de STING |
| CA2958771A1 (en) * | 2014-09-08 | 2016-03-17 | Dana-Farber Cancer Institute, Inc. | Methods of treating cancer |
| US10010607B2 (en) | 2014-09-16 | 2018-07-03 | Institut Curie | Method for preparing viral particles with cyclic dinucleotide and use of said particles for inducing immune response |
| EP3215182B1 (en) * | 2014-11-05 | 2023-01-04 | The Regents of The University of California | Combination immunotherapy |
| US11058758B2 (en) | 2014-11-20 | 2021-07-13 | National Institutes Of Biomedical Innovation, Health And Nutrition | TH1-inducing adjuvant comprising combination of different nucleic acid adjuvants, and use of same |
| US20170340658A1 (en) * | 2014-12-16 | 2017-11-30 | Invivogen | Combined use of a chemotherapeutic agent and a cyclic dinucleotide for cancer treatment |
| ES2764178T3 (es) | 2014-12-16 | 2020-06-02 | Kayla Therapeutics | Dinucleótidos cíclicos fluorados para inducción de citocinas |
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| SG11201806623VA (en) | 2015-02-11 | 2018-09-27 | Univ Johns Hopkins | Bacteria over-expressing c-di-amp and therapeutic methods |
| KR102873947B1 (ko) * | 2015-05-07 | 2025-10-22 | 베이롤 칼리지 오브 메드신 | 수지상 세포 면역요법 |
| GEP20207182B (en) | 2015-08-13 | 2020-11-25 | Merck Sharp & Dohme | Cyclic di-nucleotide compounds as sting agonists |
| US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| CN106540255A (zh) * | 2015-09-18 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | 环二核苷酸cGAMP联合贝伐珠单抗在抗肿瘤中的应用 |
| CN106540254A (zh) * | 2015-09-22 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | 环二核苷酸cGAMP及其衍生物是潜在免疫佐剂 |
| CN106540253A (zh) * | 2015-09-24 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | cGAMP及其衍生物在制备抗肿瘤疫苗中的应用 |
| 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 |
| MX363780B (es) | 2015-12-03 | 2019-04-03 | Glaxosmithkline Ip Dev Ltd | Dinucleótidos de purina cíclica como moduladores del estimulador de los genes de interferón. |
| SMT202500412T1 (it) | 2016-01-11 | 2025-11-10 | Innate Tumor Immunity Inc | Dinucleotidi ciclici per il trattamento di condizioni associate all’attività di sting quali il cancro |
| CN106544319A (zh) * | 2016-01-24 | 2017-03-29 | 聊城市奥润生物医药科技有限公司 | 一种用于刺激树突状细胞成熟的组合物及其用于刺激树突状细胞成熟的方法 |
| CN108779473A (zh) | 2016-03-16 | 2018-11-09 | 法国居里学院 | 用于制备具有环二核苷酸的病毒颗粒的方法和所述颗粒用于治疗癌症的用途 |
| 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 |
| JOP20170083B1 (ar) | 2016-04-07 | 2022-03-14 | Glaxosmithkline Ip Dev Ltd | أميدات هتيروسيكلية مفيدة كمعدلات بروتين |
| WO2017175156A1 (en) | 2016-04-07 | 2017-10-12 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators |
| WO2017186711A1 (en) | 2016-04-25 | 2017-11-02 | Invivogen | Novel complexes of immunostimulatory compounds, and uses thereof |
| EP3481402A4 (en) | 2016-07-06 | 2020-01-22 | Sperovie Biosciences, Inc. | CONNECTIONS, COMPOSITIONS AND METHODS FOR TREATING A DISEASE |
| BR112019004042A2 (pt) * | 2016-08-30 | 2019-05-28 | Dana-Farber Cancer Institute, Inc. | composições de liberação de fármaco e usos das mesmas |
| EA037513B1 (ru) * | 2016-09-17 | 2021-04-06 | ИММЬЮН СЕНСОР, ЭлЭлСи | Циклические динуклеотидные соединения и способы их применения |
| TN2020000158A1 (en) | 2016-10-04 | 2022-04-04 | Merck Sharp & Dohme | BENZO[b]THIOPHENE COMPOUNDS AS STING AGONISTS |
| JOP20170192A1 (ar) | 2016-12-01 | 2019-01-30 | Takeda Pharmaceuticals Co | داي نوكليوتيد حلقي |
| KR101889181B1 (ko) * | 2016-12-19 | 2018-08-16 | 주식회사 포스코 | 굽힘성 및 신장플랜지성이 우수한 고장력강 및 이의 제조방법 |
| CA3047579A1 (en) * | 2016-12-22 | 2018-06-28 | Mavupharma, Inc. | Compositions and methods of enhancing or augmenting type i ifn production |
| EA201991804A1 (ru) | 2017-02-01 | 2020-02-07 | МОДЕРНАТиЭкс, ИНК. | ИММУНОМОДУЛИРУЮЩИЕ ТЕРАПЕВТИЧЕСКИЕ КОМПОЗИЦИИ мРНК, КОДИРУЮЩЕЙ ПЕПТИДЫ С АКТИВИРУЮЩЕЙ ОНКОГЕННОЙ МУТАЦИЕЙ |
| US20200055883A1 (en) | 2017-02-17 | 2020-02-20 | Eisai R&D Management Co., Ltd. | Cyclic di-nucleotides derivative for the treatment of cancer |
| US10933078B2 (en) | 2017-02-21 | 2021-03-02 | Board Of Regents, The University Of Texas System | Cyclic dinucleotides as agonists of stimulator of interferon gene dependent signalling |
| 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 |
| WO2018208667A1 (en) | 2017-05-12 | 2018-11-15 | Merck Sharp & Dohme Corp. | Cyclic di-nucleotide compounds as sting agonists |
| KR20200028392A (ko) * | 2017-06-12 | 2020-03-16 | 유니버시티 오브 마이애미 | 질환의 치료를 위한 sting-의존성 활성화제 |
| US11969499B2 (en) | 2017-06-16 | 2024-04-30 | William Marsh Rice University | Hydrogel delivery of sting immunotherapy for treatment cancer |
| JP2020529421A (ja) | 2017-08-04 | 2020-10-08 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | がんの処置のためのＰＤ−１アンタゴニストおよびベンゾ［ｂ］チオフェンＳＴＩＮＧアゴニストの組み合わせ |
| CA3071538A1 (en) | 2017-08-04 | 2019-02-07 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene sting agonists for cancer treatment |
| WO2019046511A1 (en) | 2017-08-31 | 2019-03-07 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISEASE |
| WO2019051489A1 (en) | 2017-09-11 | 2019-03-14 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS OF TREATING DISEASE |
| WO2019051488A1 (en) | 2017-09-11 | 2019-03-14 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS OF TREATING DISEASE |
| TW201927771A (zh) | 2017-10-05 | 2019-07-16 | 英商葛蘭素史密斯克藍智慧財產發展有限公司 | 可作為蛋白質調節劑之雜環醯胺及其使用方法 |
| BR112020006780A2 (pt) | 2017-10-05 | 2020-10-06 | Glaxosmithkline Intellectual Property Development Limited | moduladores do estimulador de genes do interferon (sting) |
| CN107619438B (zh) * | 2017-10-11 | 2021-12-03 | 广州云启科技有限公司 | 新型环二核苷酸受体及其激动剂或抑制剂筛选的方法和试剂盒 |
| CN109694397B (zh) * | 2017-10-23 | 2021-08-31 | 上海弘翊生物科技有限公司 | 环状二核苷酸化合物、其制备方法和应用 |
| PE20210156A1 (es) | 2017-11-10 | 2021-01-26 | Takeda Pharmaceuticals Co | Compuestos moduladores de sting y metodos de elaboracion y uso |
| US11685761B2 (en) | 2017-12-20 | 2023-06-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| WO2019123340A1 (en) | 2017-12-20 | 2019-06-27 | 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 |
| CN112118866A (zh) | 2018-03-23 | 2020-12-22 | 科迪亚克生物科学公司 | 包含sting激动剂的细胞外囊泡 |
| 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 |
| WO2019195658A1 (en) | 2018-04-05 | 2019-10-10 | Dana-Farber Cancer Institute, Inc. | Sting levels as a biomarker for cancer immunotherapy |
| 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 |
| 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 |
| 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 |
| 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 |
| EP3820477A4 (en) | 2018-07-10 | 2022-07-13 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATMENT OF DISEASES |
| KR102783784B1 (ko) | 2018-08-16 | 2025-03-21 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 화합물의 염 및 이의 결정 |
| MA53438A (fr) | 2018-08-24 | 2021-09-15 | Codiak Biosciences Inc | Vésicules extracellulaires ciblant des cellules dendritiques et utilisations associées |
| WO2020093040A1 (en) * | 2018-11-02 | 2020-05-07 | The Regents Of The University Of California | Methods to diagnose and treat cancer using non-human nucleic acids |
| WO2020178768A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| CN113543851B (zh) | 2019-03-07 | 2025-03-18 | 捷克共和国有机化学与生物化学研究所 | 2’3’-环二核苷酸及其前药 |
| US20220143061A1 (en) | 2019-03-07 | 2022-05-12 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| JP2022525924A (ja) | 2019-03-21 | 2022-05-20 | 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 | 細胞外小胞コンジュゲート及びその使用 |
| SG11202109702QA (en) | 2019-03-21 | 2021-10-28 | Codiak Biosciences Inc | Extracellular vesicles for vaccine delivery |
| 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 |
| EP3962493A2 (en) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity/level of irf or sting or of treating cancer, comprising the administration of a sting modulator and/or purinergic receptor modulator or postcellular signaling factor |
| WO2020227421A1 (en) | 2019-05-09 | 2020-11-12 | Aligos Therapeutics, Inc. | Modified cyclic dinucleoside compounds as sting modulators |
| US20220251200A1 (en) | 2019-07-03 | 2022-08-11 | Codiak Biosciences, Inc. | Extracellular vesicles targeting t cells and uses thereof |
| GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| CN114981256B (zh) * | 2019-08-21 | 2024-11-08 | 斯克里普斯研究学院 | 干扰素基因刺激物sting的单环激动剂 |
| WO2021041532A1 (en) | 2019-08-26 | 2021-03-04 | Dana-Farber Cancer Institute, Inc. | Use of heparin to promote type 1 interferon signaling |
| US20230241089A1 (en) | 2019-09-25 | 2023-08-03 | Codiak Biosciences, Inc. | Sting agonist comprising exosomes for treating neuroimmunological disorders |
| US20240099973A1 (en) | 2019-09-25 | 2024-03-28 | Lonza Sales Ag | Extracellular vesicle compositions |
| EP4034276A1 (en) | 2019-09-25 | 2022-08-03 | Codiak BioSciences, Inc. | Methods of producing extracellular vesicles |
| EP4034150A1 (en) | 2019-09-25 | 2022-08-03 | Codiak BioSciences, Inc. | Sting agonist comprising exosomes combined with il-12 displaying exosomes for treating a tumour |
| EP4075980B1 (en) | 2019-12-18 | 2025-07-23 | Stinginn LLC | Substituted 1,2, 4-triazoles and methods of use |
| JP7662644B2 (ja) | 2019-12-18 | 2025-04-15 | シーティーエックスティー・ピーティーワイ・リミテッド | 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 |
| WO2021184017A1 (en) | 2020-03-13 | 2021-09-16 | Codiak Biosciences, Inc. | Extracellular vesicles for treating neurological disorders |
| AU2021236763A1 (en) | 2020-03-20 | 2022-10-06 | Lonza Sales Ag | Extracellular vesicles for therapy |
| KR20230002680A (ko) * | 2020-04-15 | 2023-01-05 | 스태튼스 세룸 인스티튜트 | 병원성 감염의 예방 또는 조기 치료 용도의 리포솜 조성물 |
| US20230149560A1 (en) | 2020-04-20 | 2023-05-18 | Massachusetts Institute Of Technology | Lipid compositions for delivery of sting agonist compounds and uses thereof |
| US11897888B1 (en) | 2020-04-30 | 2024-02-13 | Stinginn Llc | Small molecular inhibitors of sting signaling compositions and methods of use |
| WO2021237100A1 (en) | 2020-05-21 | 2021-11-25 | Codiak Biosciences, Inc. | Methods of targeting extracellular vesicles to lung |
| JP7072604B2 (ja) * | 2020-06-23 | 2022-05-20 | アンスティテュ・クリー | 環状ジヌクレオチドを含むウイルス粒子を調製する方法及びがんを治療するための前記粒子の使用 |
| CN111956797B (zh) * | 2020-07-10 | 2022-05-13 | 清华大学 | 新型疫苗佐剂及其在新冠肺炎疫苗和其他疫苗中的应用 |
| 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 |
| EP4240488A1 (en) | 2020-11-09 | 2023-09-13 | Takeda Pharmaceutical Company Limited | Antibody drug conjugates |
| WO2022118043A1 (en) * | 2020-12-03 | 2022-06-09 | Enara Bio Limited | Novel protein-ligand complex |
| US20240423927A1 (en) | 2021-04-20 | 2024-12-26 | Institut Curie | Compositions and methods for use in immunotherapy |
| EP4326321A1 (en) | 2021-04-20 | 2024-02-28 | Institut Curie | Compositions and methods for use in immunotherapy |
| WO2023056468A1 (en) | 2021-09-30 | 2023-04-06 | Codiak Biosciences, Inc. | Extracellular vesicle comprising cholesterol tagged sting-agonist |
| WO2024086799A2 (en) * | 2022-10-20 | 2024-04-25 | Northwestern University | Lipid nanoparticles and methods of using the same for treating cell proliferative diseases and disorders |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5637483A (en) * | 1991-10-04 | 1997-06-10 | Whitehead Institute For Biomedical Research | Irradiated tumor cell vaccine engineered to express GM-CSF |
| US20070281897A1 (en) * | 2004-03-15 | 2007-12-06 | Karaolis David K | Method for stimulating the immune, inflammatory or neuroprotective response |
| WO2011136828A1 (en) * | 2010-04-27 | 2011-11-03 | The Johns Hopkins University | Immunogenic compositions and methods for treating neoplasia |
Family Cites Families (53)
| 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 |
| 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 |
| EP1053301B1 (en) | 1998-02-02 | 2004-04-21 | The Johns Hopkins University School Of Medicine | A universal immunomodulatory cytokine-expressing bystander cell line and related compositions and methods of manufacture and use |
| KR100455814B1 (ko) | 1999-02-15 | 2004-11-06 | 니뽄 신야쿠 가부시키가이샤 | 단쇄화 폴리뉴클레오티드 및 그 제법 |
| US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
| AU5717400A (en) | 1999-06-14 | 2001-01-02 | Cancer Research Ventures Limited | Cancer therapy |
| US6635677B2 (en) * | 1999-08-13 | 2003-10-21 | Case Western Reserve University | Methoxyamine combinations in the treatment of cancer |
| EP1320602A2 (en) | 2000-09-21 | 2003-06-25 | The Regents Of The University Of California | Spas-1 cancer antigen |
| WO2002059575A2 (en) | 2001-01-23 | 2002-08-01 | The Trustees Of Princeton University, Princeton University | Method and apparatus for analysis of biological solutions |
| 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 |
| US20040197312A1 (en) * | 2003-04-02 | 2004-10-07 | Marina Moskalenko | Cytokine-expressing cellular vaccine combinations |
| US8367716B2 (en) | 2003-07-28 | 2013-02-05 | Karaolis David K R | Method for attentuating virulence of microbial pathogens and for inhibiting microbial biofilm formation |
| AU2004281834A1 (en) | 2003-10-15 | 2005-04-28 | Cerus Corporation | Listeria-based EphA2 vaccines |
| CA2542804A1 (en) | 2003-10-24 | 2005-05-06 | Alza Corporation | Preparation of lipid particles |
| EP1740192B1 (en) | 2004-03-15 | 2012-06-13 | David K. R. Karaolis | Cyclic dinucleotide for stimulating the immune of inflammatory response |
| CA2607579A1 (en) | 2005-05-06 | 2006-11-23 | 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 |
| CA2631931C (en) | 2005-12-01 | 2014-04-29 | Pronai Therapeutics, Inc. | Cancer therapies and pharmaceutical compositions used therein |
| CA2662335A1 (en) | 2006-09-05 | 2008-03-13 | Valeria Ossovskaya | Methods for designing parp inhibitors and uses thereof |
| WO2009133560A1 (en) | 2008-04-29 | 2009-11-05 | Smart Assays | Non-hydrolyzable and permeable cyclic bis-[nucleotide monophosphate] derivatives and uses thereof |
| JP2011529708A (ja) | 2008-08-04 | 2011-12-15 | ユニバーシティ オブ マイアミ | 自然免疫応答の調節因子ｓｔｉｎｇ（インターフェロン遺伝子の刺激因子） |
| 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 |
| EP2376107B1 (en) | 2008-12-09 | 2014-05-21 | Coley Pharmaceutical Group, Inc. | Immunostimulatory oligonucleotides |
| US8765171B2 (en) | 2009-03-09 | 2014-07-01 | The Regents Of The University Of California | 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 |
| HRP20161585T1 (hr) | 2009-06-05 | 2016-12-30 | Infectious Disease Research Institute | Sintetski glukopiranozilni lipidi kao adjuvansi i cjepivni pripravci koji ih sadrže |
| EP2448954A1 (en) | 2009-07-01 | 2012-05-09 | 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 |
| WO2011119492A2 (en) | 2010-03-22 | 2011-09-29 | Massachusetts Institute Of Technology | Methods and compositions related to the measurement of material properties |
| 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 |
| PT2640842T (pt) | 2010-11-17 | 2018-10-12 | Providence Health & Services Oregon D/B/A Providence Portland Medical Center | Métodos e composições para induzir uma resposta imune a egfrviii |
| US9061048B2 (en) | 2010-12-15 | 2015-06-23 | The Regents Of The University Of California | Cyclic di-AMP induction of type I interferon |
| US8772474B2 (en) | 2010-12-22 | 2014-07-08 | Alios Biopharma, Inc. | Cyclic nucleotide analogs |
| US9880084B2 (en) | 2011-04-15 | 2018-01-30 | The University Of British Columbia | Apparatus for separation of particles |
| WO2013086331A1 (en) | 2011-12-07 | 2013-06-13 | President And Fellows Of Harvard College | High efficiency di-nucleotide cyclase |
| KR20150004416A (ko) | 2012-04-30 | 2015-01-12 | 글렌 엔. 바버 | 면역 반응의 조절 |
| WO2013185052A1 (en) | 2012-06-08 | 2013-12-12 | Aduro Biotech | Compostions and methods for cancer immunotherapy |
| US9090646B2 (en) | 2012-12-05 | 2015-07-28 | Rutgers, The State University Of New Jersey | Biotinylated compounds |
| EA201590396A1 (ru) * | 2012-12-13 | 2015-12-30 | Адуро Биотек, Инк. | Композиция, содержащая циклические пуриновые динуклеотиды с определенной стереохимией, и способ ее получения и применения |
| MX365661B (es) | 2012-12-19 | 2019-06-10 | Univ Texas | Activacion farmaceutica de una senda de señalizacion de di-nucleotido ciclico de mamifero. |
| CA2908154C (en) | 2013-04-29 | 2023-11-28 | 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 |
| 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 |
| 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“ |
| WO2015017652A1 (en) | 2013-07-31 | 2015-02-05 | Memorial Sloan-Kettering Cancer Center | Sting crystals and modulators |
-
2013
- 2013-06-07 WO PCT/US2013/044744 patent/WO2013185052A1/en not_active Ceased
- 2013-06-07 EP EP13799826.6A patent/EP2858722B8/en not_active Not-in-force
- 2013-06-07 CN CN201380037917.2A patent/CN104507538B/zh not_active Expired - Fee Related
- 2013-06-07 JP JP2015516245A patent/JP6257607B2/ja not_active Expired - Fee Related
- 2013-06-07 IN IN2492MUN2014 patent/IN2014MN02492A/en unknown
- 2013-06-07 CA CA2876150A patent/CA2876150A1/en not_active Abandoned
- 2013-06-07 US US13/912,960 patent/US9770467B2/en active Active
- 2013-06-07 KR KR1020157000522A patent/KR20150022996A/ko not_active Ceased
- 2013-06-07 SG SG11201407875UA patent/SG11201407875UA/en unknown
- 2013-06-07 NZ NZ702392A patent/NZ702392A/en not_active IP Right Cessation
- 2013-06-07 AU AU2013271375A patent/AU2013271375B2/en not_active Ceased
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5637483A (en) * | 1991-10-04 | 1997-06-10 | Whitehead Institute For Biomedical Research | Irradiated tumor cell vaccine engineered to express GM-CSF |
| US20070281897A1 (en) * | 2004-03-15 | 2007-12-06 | Karaolis David K | Method for stimulating the immune, inflammatory or neuroprotective response |
| WO2011136828A1 (en) * | 2010-04-27 | 2011-11-03 | The Johns Hopkins University | Immunogenic compositions and methods for treating neoplasia |
Non-Patent Citations (1)
| Title |
|---|
| WOODWARD et al., "c-di-AMP Secreted by Intracellular Listeria monocytogenes Activates a Host Type I Interferon Response", (2010), Science, Vol. 328, No. 5986, Pages 1703-1705. * |
Also Published As
| Publication number | Publication date |
|---|---|
| US9770467B2 (en) | 2017-09-26 |
| EP2858722B1 (en) | 2017-12-13 |
| EP2858722A4 (en) | 2015-12-23 |
| SG11201407875UA (en) | 2014-12-30 |
| US20150010613A1 (en) | 2015-01-08 |
| NZ702392A (en) | 2017-03-31 |
| WO2013185052A1 (en) | 2013-12-12 |
| CN104507538B (zh) | 2018-04-06 |
| JP6257607B2 (ja) | 2018-01-10 |
| JP2015518901A (ja) | 2015-07-06 |
| KR20150022996A (ko) | 2015-03-04 |
| EP2858722A1 (en) | 2015-04-15 |
| AU2013271375A1 (en) | 2014-12-18 |
| EP2858722B8 (en) | 2018-02-21 |
| HK1204302A1 (en) | 2015-11-13 |
| CA2876150A1 (en) | 2013-12-12 |
| SG10201610251PA (en) | 2017-01-27 |
| IN2014MN02492A (enExample) | 2015-07-17 |
| CN104507538A (zh) | 2015-04-08 |
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