MY194058A - Cyclic dinucleotides for treating conditions associated with sting activity such as cancer - Google Patents
Cyclic dinucleotides for treating conditions associated with sting activity such as cancerInfo
- Publication number
- MY194058A MY194058A MYPI2018702369A MYPI2018702369A MY194058A MY 194058 A MY194058 A MY 194058A MY PI2018702369 A MYPI2018702369 A MY PI2018702369A MY PI2018702369 A MYPI2018702369 A MY PI2018702369A MY 194058 A MY194058 A MY 194058A
- Authority
- MY
- Malaysia
- Prior art keywords
- cancer
- conditions associated
- treating conditions
- cyclic dinucleotides
- sting activity
- Prior art date
Links
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07H21/02—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Endocrinology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662277273P | 2016-01-11 | 2016-01-11 | |
| US201662436759P | 2016-12-20 | 2016-12-20 | |
| PCT/US2017/013066 WO2017123669A1 (en) | 2016-01-11 | 2017-01-11 | Cyclic dinucleotides for treating conditions associated with sting activity such as cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MY194058A true MY194058A (en) | 2022-11-10 |
Family
ID=58010371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MYPI2018702369A MY194058A (en) | 2016-01-11 | 2017-01-11 | Cyclic dinucleotides for treating conditions associated with sting activity such as cancer |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US10604542B2 (enExample) |
| EP (1) | EP3402801B1 (enExample) |
| JP (1) | JP6867395B2 (enExample) |
| KR (2) | KR20250049441A (enExample) |
| CN (1) | CN109451740B (enExample) |
| AU (1) | AU2017207757B2 (enExample) |
| BR (1) | BR112018013808A2 (enExample) |
| CA (1) | CA3011528A1 (enExample) |
| CL (1) | CL2018001870A1 (enExample) |
| CO (1) | CO2018008196A2 (enExample) |
| DK (1) | DK3402801T3 (enExample) |
| EA (1) | EA036421B1 (enExample) |
| ES (1) | ES3046957T3 (enExample) |
| FI (1) | FI3402801T3 (enExample) |
| HR (1) | HRP20251050T1 (enExample) |
| IL (1) | IL260427B (enExample) |
| LT (1) | LT3402801T (enExample) |
| MX (1) | MX2018008266A (enExample) |
| MY (1) | MY194058A (enExample) |
| PE (1) | PE20181330A1 (enExample) |
| PL (1) | PL3402801T3 (enExample) |
| PT (1) | PT3402801T (enExample) |
| RS (1) | RS67188B1 (enExample) |
| SG (1) | SG11201805888SA (enExample) |
| SI (1) | SI3402801T1 (enExample) |
| SM (1) | SMT202500412T1 (enExample) |
| WO (1) | WO2017123669A1 (enExample) |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112017018908A2 (pt) | 2015-03-10 | 2018-04-17 | Aduro Biotech, Inc. | composições e métodos para ativar a sinalização dependente do "estimulador do gene de interferon |
| CN108137641B (zh) | 2015-08-13 | 2022-04-01 | 默沙东公司 | 作为sting激动剂的环状双核苷酸化合物 |
| US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| PT3402801T (pt) * | 2016-01-11 | 2025-10-23 | Innate Tumor Immunity Inc | Dinucleótidos cíclicos para o tratamento de condições associadas à atividade de sting, tal como cancro |
| HUE060396T2 (hu) | 2016-03-18 | 2023-02-28 | Immune Sensor Llc | Ciklikus DI-nukleotid vegyületek és azok felhasználási módszerei |
| EP3507367A4 (en) | 2016-07-05 | 2020-03-25 | Aduro BioTech, Inc. | CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF |
| JP7100227B2 (ja) | 2016-07-06 | 2022-07-13 | エフ－スター・セラピューティクス・インコーポレイテッド | 疾患の治療のための化合物、組成物、および方法 |
| EP3922279B8 (en) | 2016-08-30 | 2025-02-12 | Dana-Farber Cancer Institute, Inc. | Drug delivery compositions and uses thereof |
| RS62410B1 (sr) | 2016-10-04 | 2021-10-29 | Merck Sharp & Dohme | Benzo[b]tiofenska jedinjenja kao agonisti sting |
| JOP20170192A1 (ar) | 2016-12-01 | 2019-01-30 | Takeda Pharmaceuticals Co | داي نوكليوتيد حلقي |
| US20200055883A1 (en) | 2017-02-17 | 2020-02-20 | Eisai R&D Management Co., Ltd. | Cyclic di-nucleotides derivative for the treatment of cancer |
| TW202430219A (zh) | 2017-04-13 | 2024-08-01 | 荷蘭商賽羅帕公司 | 抗-SIRPα 抗體 |
| US11466047B2 (en) | 2017-05-12 | 2022-10-11 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
| US11259980B2 (en) | 2017-07-31 | 2022-03-01 | Arizona Board Of Regents On Behalf Of Arizona State University | Soft inflatable exosuit for knee rehabilitation |
| MA49773A (fr) | 2017-08-04 | 2021-04-21 | Merck Sharp & Dohme | Combinaisons d'antagonistes de pd-1 et d'agonistes de sting benzo[b |
| CA3071538A1 (en) | 2017-08-04 | 2019-02-07 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene sting agonists for cancer treatment |
| AU2018323053A1 (en) | 2017-08-30 | 2020-03-19 | Beijing Xuanyi Pharmasciences Co., Ltd | Cyclic di-nucleotides as stimulator of interferon genes modulators |
| EP3676277A1 (en) * | 2017-08-31 | 2020-07-08 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
| EP3675859A4 (en) | 2017-08-31 | 2021-06-30 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF A DISEASE |
| WO2019051488A1 (en) | 2017-09-11 | 2019-03-14 | Sperovie Biosciences, Inc. | COMPOUNDS, COMPOSITIONS AND METHODS OF TREATING DISEASE |
| US11707531B2 (en) | 2017-09-11 | 2023-07-25 | F-star Therapeutics, Inc. | Compounds, compositions, and methods for the treatment of disease |
| EA202090719A1 (ru) | 2017-09-14 | 2020-07-01 | Янссен Байофарма, Инк. | Модифицированные нуклеозидные амидофосфиты |
| WO2019074887A1 (en) * | 2017-10-10 | 2019-04-18 | Bristol-Myers Squibb Company | CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS |
| WO2019084060A1 (en) | 2017-10-24 | 2019-05-02 | Silverback Therapeutics, Inc. | CONJUGATES AND METHODS OF USE FOR THE SELECTIVE DELIVERY OF IMMUNOMODULATORY AGENTS |
| KR20200098511A (ko) | 2017-11-10 | 2020-08-20 | 다케다 야쿠힌 고교 가부시키가이샤 | Sting 조절제 화합물, 및 제조 및 사용 방법 |
| 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 |
| WO2019125974A1 (en) | 2017-12-20 | 2019-06-27 | Merck Sharp & Dohme Corp. | Cyclic di-nucleotide compounds as sting agonists |
| 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 |
| EP3505527A1 (en) * | 2017-12-29 | 2019-07-03 | Invivogen | Cyclic dinucleotides for cytokine induction |
| US10519187B2 (en) * | 2018-02-13 | 2019-12-31 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
| JP7250808B2 (ja) * | 2018-03-08 | 2023-04-03 | ブリストル－マイヤーズ スクイブ カンパニー | 抗がん剤としての環状ジヌクレオチド |
| WO2019180683A1 (en) | 2018-03-23 | 2019-09-26 | Takeda Pharmaceutical Company Limited | Sting modulator compounds with sulfamate linkages, and methods of making and using |
| US11702430B2 (en) | 2018-04-03 | 2023-07-18 | Merck Sharp & Dohme Llc | Aza-benzothiophene compounds as STING agonists |
| EP3774764A1 (en) | 2018-04-03 | 2021-02-17 | Merck Sharp&Dohme Corp. | Benzothiophenes and related 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 |
| MA52754A (fr) | 2018-05-25 | 2021-04-14 | Incyte Corp | Composés hétérocycliques tricycliques en tant qu'activateurs de sting |
| WO2020014127A1 (en) | 2018-07-10 | 2020-01-16 | Sperovie Biosciences, Inc. | Compounds, compositions, and methods for the treatment of disease |
| TW202030199A (zh) * | 2018-07-17 | 2020-08-16 | 美商健生生物科技公司 | 作為ｓｔｉｎｇ促效劑之環狀二核苷酸 |
| WO2020028565A1 (en) | 2018-07-31 | 2020-02-06 | Incyte Corporation | Tricyclic heteraryl compounds as sting activators |
| WO2020028566A1 (en) | 2018-07-31 | 2020-02-06 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
| CA3099904A1 (en) | 2018-08-16 | 2020-02-20 | Eisai R&D Management Co., Ltd. | Salts of compounds and crystals thereof |
| PT3848054T (pt) | 2018-09-06 | 2025-04-03 | Daiichi Sankyo Co Ltd | Conjugados anticorpo-fármaco de derivados de dinucleótidos cíclicos |
| KR20210081332A (ko) | 2018-09-12 | 2021-07-01 | 실버백 테라퓨틱스, 인크. | 면역 자극성 접합체를 사용한 질환의 치료를 위한 조성물 |
| BR112021005208A2 (pt) | 2018-09-21 | 2021-06-08 | Shanghai De Novo Pharmatech Co., Ltd. | análogo de dinucleotídeo cíclico, composição farmacêutica do mesmo, e aplicação |
| WO2020092127A1 (en) | 2018-10-29 | 2020-05-07 | Venenum Biodesign, LLC | Novel sting agonists |
| US11110106B2 (en) | 2018-10-29 | 2021-09-07 | Venenum Biodesign, LLC | Sting agonists for treating bladder cancer and solid tumors |
| WO2020089815A1 (en) | 2018-10-31 | 2020-05-07 | Novartis Ag | Antibody conjugates comprising sting agonist |
| US11596692B1 (en) | 2018-11-21 | 2023-03-07 | Incyte Corporation | PD-L1/STING conjugates and methods of use |
| MX2021006498A (es) * | 2018-12-04 | 2021-07-06 | Bristol Myers Squibb Co | Proceso para la preparacion de un dinucleotido ciclico. |
| US12129267B2 (en) | 2019-01-07 | 2024-10-29 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
| CN113423713A (zh) * | 2019-02-05 | 2021-09-21 | 百时美施贵宝公司 | 1,2,5-三-o-苯甲酰基-3-二苄基氨基-3-脱氧核糖作为生产3′-氨基-3′-脱氧腺苷和3′-氨基-3′-脱氧鸟苷的中间体及其受保护的衍生物的合成 |
| CN114173824A (zh) | 2019-05-10 | 2022-03-11 | 武田药品工业株式会社 | 抗体药物缀合物 |
| CA3145889A1 (en) | 2019-07-05 | 2021-01-14 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| WO2021013234A1 (en) * | 2019-07-25 | 2021-01-28 | Beigene, Ltd. | Cyclic dinucleotides as sting agonists |
| WO2021067644A1 (en) | 2019-10-01 | 2021-04-08 | Silverback Therapeutics, Inc. | Combination therapy with immune stimulatory conjugates |
| JP7787514B2 (ja) | 2019-12-26 | 2025-12-17 | 国立大学法人東海国立大学機構 | ポリヌクレオチド及び医薬組成物 |
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| KR20220151630A (ko) | 2020-03-06 | 2022-11-15 | 다이이찌 산쿄 가부시키가이샤 | 신규 고리형 디뉴클레오티드 유도체를 포함하는 항체 약물 컨쥬게이트 |
| JPWO2021206158A1 (enExample) | 2020-04-10 | 2021-10-14 | ||
| EP4138852A4 (en) * | 2020-04-21 | 2024-05-15 | Duke University | COMPOSITIONS AND METHODS FOR TREATING PAIN |
| US20230226218A1 (en) | 2020-05-11 | 2023-07-20 | Erytech Pharma | Red Cell Extracellular Vesicles (RCEVs) Containing Cargoes and Methods of Use and Production Thereof |
| CA3183993A1 (en) | 2020-07-01 | 2022-01-06 | Peter R. Baum | Anti-asgr1 antibody conjugates and uses thereof |
| US20230256109A1 (en) | 2020-08-07 | 2023-08-17 | Tambo, Inc. | Trans-Cyclooctene Bioorthogonal Agents and Uses in Cancer and Immunotherapy |
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| JP2023545466A (ja) * | 2020-10-15 | 2023-10-30 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 免疫応答を調節することができる、金属イオンと会合したｓｔｉｎｇアゴニストの結晶多形体 |
| KR102466750B1 (ko) * | 2020-10-23 | 2022-11-15 | 아주대학교산학협력단 | 인돌리진 유도체를 유효성분으로 포함하는 인터페론 유전자 자극제 조성물 |
| US20230390409A1 (en) | 2020-10-30 | 2023-12-07 | Avacta Life Sciences Limited | Fap-activated serum extended half-life therapeutic conjugates |
| IL302390A (en) | 2020-11-09 | 2023-06-01 | Takeda Pharmaceuticals Co | Drug antibody conjugates |
| WO2023277168A1 (ja) | 2021-06-30 | 2023-01-05 | 協和キリン株式会社 | ポリヌクレオチド及び医薬組成物 |
| IL315341A (en) | 2022-03-02 | 2024-10-01 | Daiichi Sankyo Co Ltd | METHOD FOR PRODUCING Fc-CONTAINING MOLECULE |
| EP4582106A1 (en) | 2022-08-29 | 2025-07-09 | Daiichi Sankyo Company, Limited | Antibody-drug conjugate including mutant fc region |
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|---|---|---|---|---|
| US7927613B2 (en) | 2002-02-15 | 2011-04-19 | University Of South Florida | Pharmaceutical co-crystal compositions |
| BR0312442A (pt) | 2002-06-20 | 2005-05-10 | Nippon Suisan Kaisha Ltd | Pró-droga, utilização medicinal desta e processo para produzir a mesma |
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| HK1223794A1 (zh) | 2013-10-21 | 2017-08-11 | 德雷克塞尔大学 | 治疗慢性乙型肝炎病毒感染的sting激动剂的用途 |
| US20160287623A1 (en) | 2013-11-19 | 2016-10-06 | The University Of Chicago | Use of sting agonist as cancer treatment |
| US20150144176A1 (en) | 2013-11-22 | 2015-05-28 | Massachusetts Institute Of Technology | Photovoltaic power balancing and differential power processing |
| US9315523B2 (en) | 2013-12-06 | 2016-04-19 | Rutgers, The State University Of New Jersey | Cyclic dinucleosides |
| US10450341B2 (en) | 2014-06-04 | 2019-10-22 | Glaxosmithkline Intellectual Property Development Limited | Cyclic di-nucleotides as modulators of STING |
| PL3233882T3 (pl) | 2014-12-16 | 2020-04-30 | Kayla Therapeutics | Fluorowane cykliczne dinukleotydy do indukcji cytokin |
| WO2016096577A1 (en) | 2014-12-16 | 2016-06-23 | Invivogen | Combined use of a chemotherapeutic agent and a cyclic dinucleotide for cancer treatment |
| GB201501462D0 (en) | 2015-01-29 | 2015-03-18 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| BR112017018908A2 (pt) | 2015-03-10 | 2018-04-17 | Aduro Biotech, Inc. | composições e métodos para ativar a sinalização dependente do "estimulador do gene de interferon |
| CN108137641B (zh) | 2015-08-13 | 2022-04-01 | 默沙东公司 | 作为sting激动剂的环状双核苷酸化合物 |
| RU2020113165A (ru) | 2015-12-03 | 2020-06-09 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Циклические пуриновые динуклеотиды в качестве модуляторов sting |
| PT3402801T (pt) * | 2016-01-11 | 2025-10-23 | Innate Tumor Immunity Inc | Dinucleótidos cíclicos para o tratamento de condições associadas à atividade de sting, tal como cancro |
| HUE060396T2 (hu) | 2016-03-18 | 2023-02-28 | Immune Sensor Llc | Ciklikus DI-nukleotid vegyületek és azok felhasználási módszerei |
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