KR20170072244A - 관문 억제제를 가지는 tlr9 효능제를 이용한 암 치료 - Google Patents
관문 억제제를 가지는 tlr9 효능제를 이용한 암 치료 Download PDFInfo
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- KR20170072244A KR20170072244A KR1020177012557A KR20177012557A KR20170072244A KR 20170072244 A KR20170072244 A KR 20170072244A KR 1020177012557 A KR1020177012557 A KR 1020177012557A KR 20177012557 A KR20177012557 A KR 20177012557A KR 20170072244 A KR20170072244 A KR 20170072244A
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| MA45123A (fr) | 2016-05-27 | 2019-04-10 | Agenus Inc | Anticorps anti-tim-3 et leurs méthodes d'utilisation |
| WO2018039629A2 (en) | 2016-08-25 | 2018-03-01 | Northwestern University | Micellar spherical nucleic acids from thermoresponsive, traceless templates |
| KR102557336B1 (ko) | 2016-09-13 | 2023-07-18 | 노쓰 캐롤라이나 스테이트 유니버시티 | 혈소판 조성물 및 치료제의 전달 방법 |
| WO2018053242A1 (en) * | 2016-09-15 | 2018-03-22 | Idera Pharmaceuticals, Inc. | Immune modulation with tlr9 agonists for cancer treatment |
| WO2018067943A1 (en) * | 2016-10-07 | 2018-04-12 | Abraxis Bioscience, Llc | Methods of treating biliary tract cancer |
| CA3037380A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
| MA46770A (fr) | 2016-11-09 | 2019-09-18 | Agenus Inc | Anticorps anti-ox40, anticorps anti-gitr, et leurs procédés d'utilisation |
| US20180271996A1 (en) | 2017-02-28 | 2018-09-27 | Mersana Therapeutics, Inc. | Combination therapies of her2-targeted antibody-drug conjugates |
| ES2953575T3 (es) | 2017-03-23 | 2023-11-14 | QBiotics Pty Ltd | Terapia de combinación para el tratamiento o la prevención de tumores |
| US11696954B2 (en) | 2017-04-28 | 2023-07-11 | Exicure Operating Company | Synthesis of spherical nucleic acids using lipophilic moieties |
| CN109893654B (zh) * | 2017-12-11 | 2021-07-27 | 江苏恒瑞医药股份有限公司 | Vegfr抑制剂治疗肿瘤的方法 |
| EP3823669A1 (en) * | 2017-12-18 | 2021-05-26 | Debiopharm International SA | Combination of an agonist anti-pd-1 antibody with a gnrh agonist or antagonist to treat cancer |
| TW202011959A (zh) | 2018-04-14 | 2020-04-01 | 美商戴納瓦克斯技術公司 | 用於治療癌症之包括CpG-C 型寡核苷酸及組蛋白去乙醯酶抑制劑之組合 |
| EP3566718A1 (en) | 2018-05-07 | 2019-11-13 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz | A pharmazeutical combination (treg depleting agent, checkpoint inhibitor, tlr9 agonist) for use in the treatment of cancer |
| FI3846824T3 (fi) * | 2018-09-07 | 2025-09-25 | Massachusetts Gen Hospital | Koostumuksia ja menetelmiä immuunitarkistuspisteen estämiseen |
| WO2020063858A1 (zh) * | 2018-09-29 | 2020-04-02 | 江苏恒瑞医药股份有限公司 | Tlr激动剂与免疫检查点抑制剂联合在制备治疗肿瘤的药物中的用途 |
| US20210340544A1 (en) * | 2018-10-18 | 2021-11-04 | Idera Pharmaceuticals, Inc. | Tlr9 modulators for treating cancer |
| WO2020128893A1 (en) * | 2018-12-21 | 2020-06-25 | Pfizer Inc. | Combination treatments of cancer comprising a tlr agonist |
| CN111057762B (zh) * | 2019-11-28 | 2022-11-08 | 中国人民解放军陆军军医大学第一附属医院 | 检测基因在制备检测食管鳞癌对顺铂敏感性的制剂中的用途 |
| CN116406276A (zh) * | 2020-09-22 | 2023-07-07 | 特萨乐斯生命科学公司 | 使用toll样受体激动剂的癌症疗法 |
| US11898147B2 (en) * | 2021-09-06 | 2024-02-13 | National Health Research Institutes | CpG-oligodeoxynucleotide compounds in combination with immune modulators for cancer immunotherapy |
| AU2023232820A1 (en) | 2022-03-07 | 2024-09-05 | Mersana Therapeutics, Inc. | Antibody drug conjugates comprising sting agonists, combinations and methods of use |
Family Cites Families (103)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3512676A (en) * | 1967-08-07 | 1970-05-19 | Wsr Inc | Container end structure |
| US6355476B1 (en) | 1988-11-07 | 2002-03-12 | Advanced Research And Technologyinc | Nucleic acid encoding MIP-1α Lymphokine |
| US6303121B1 (en) | 1992-07-30 | 2001-10-16 | Advanced Research And Technology | Method of using human receptor protein 4-1BB |
| US6362325B1 (en) | 1988-11-07 | 2002-03-26 | Advanced Research And Technology Institute, Inc. | Murine 4-1BB gene |
| US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
| US5652355A (en) | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
| TW244371B (enExample) | 1992-07-23 | 1995-04-01 | Tri Clover Inc | |
| US6346614B1 (en) | 1992-07-23 | 2002-02-12 | Hybridon, Inc. | Hybrid oligonucleotide phosphorothioates |
| US6084067A (en) | 1993-07-26 | 2000-07-04 | Dana-Farber Cancer Institute | CTLA4/CD28 ligands and uses therefor |
| US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| US6051227A (en) | 1995-07-25 | 2000-04-18 | The Regents Of The University Of California, Office Of Technology Transfer | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| US5855887A (en) | 1995-07-25 | 1999-01-05 | The Regents Of The University Of California | Blockade of lymphocyte down-regulation associated with CTLA-4 signaling |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| US5912332A (en) | 1996-07-26 | 1999-06-15 | Hybridon, Inc. | Affinity-based purification of oligonucleotides using soluble multimeric oligonucleotides |
| US6113881A (en) | 1996-09-20 | 2000-09-05 | Helene Curtis, Inc. | Hair styling mousse compositions comprising carboxylated polyurethane resins |
| CA2268340A1 (en) | 1996-10-11 | 1998-04-23 | Bristol-Myers Squibb Company | Methods and compositions for immunomodulation |
| WO1998042752A1 (en) | 1997-03-21 | 1998-10-01 | Brigham And Women's Hospital Inc. | Immunotherapeutic ctla-4 binding peptides |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US7109003B2 (en) | 1998-12-23 | 2006-09-19 | Abgenix, Inc. | Methods for expressing and recovering human monoclonal antibodies to CTLA-4 |
| EE05627B1 (et) | 1998-12-23 | 2013-02-15 | Pfizer Inc. | CTLA-4 vastased inimese monoklonaalsed antikehad |
| WO2000037504A2 (en) | 1998-12-23 | 2000-06-29 | Pfizer Inc. | Human monoclonal antibodies to ctla-4 |
| FR2795937B1 (fr) | 1999-07-09 | 2001-09-14 | Air Liquide | Machine de croutage en ligne |
| EP1210428B1 (en) | 1999-08-23 | 2015-03-18 | Dana-Farber Cancer Institute, Inc. | Pd-1, a receptor for b7-4, and uses therefor |
| US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
| EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| US20040214783A1 (en) * | 2002-05-08 | 2004-10-28 | Terman David S. | Compositions and methods for treatment of neoplastic disease |
| DE19941311C1 (de) | 1999-08-31 | 2001-06-07 | Cryoelectra Ges Fuer Kryoelek | Bandfilter |
| HK1047109A1 (zh) | 1999-10-15 | 2003-02-07 | University Of Massachusetts | 作为指定基因干预工具的rna干预轨迹基因 |
| JP2003520828A (ja) | 2000-01-27 | 2003-07-08 | ジェネティクス インスティテュート，エルエルシー | Ｃｔｌａ４（ｃｄ１５２）に対する抗体、これを含む結合体、およびその使用 |
| EP1309726B2 (en) | 2000-03-30 | 2018-10-03 | Whitehead Institute For Biomedical Research | Rna sequence-specific mediators of rna interference |
| RU2322500C2 (ru) | 2000-12-01 | 2008-04-20 | Макс-Планк-Гезелльшафт Цур Фердерунг Дер Виссеншафтен Е.Ф. | Малые молекулы рнк, опосредующие интерференцию рнк |
| AR036993A1 (es) | 2001-04-02 | 2004-10-20 | Wyeth Corp | Uso de agentes que modulan la interaccion entre pd-1 y sus ligandos en la submodulacion de respuestas inmunologicas |
| US20040241745A1 (en) | 2001-07-31 | 2004-12-02 | Tasuku Honjo | Substance specific to pd-1 |
| NZ536420A (en) | 2002-04-12 | 2008-04-30 | Medarex Inc | Methods of treatment using CTLA-4 antibodies |
| AU2003281200A1 (en) | 2002-07-03 | 2004-01-23 | Tasuku Honjo | Immunopotentiating compositions |
| US6887673B2 (en) | 2002-07-30 | 2005-05-03 | Bristol-Myers Squibb Company | Humanized antibodies against human 4-1BB |
| WO2004035607A2 (en) | 2002-10-17 | 2004-04-29 | Genmab A/S | Human monoclonal antibodies against cd20 |
| US8039443B2 (en) | 2002-11-21 | 2011-10-18 | Archemix Corporation | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
| CN101899114A (zh) | 2002-12-23 | 2010-12-01 | 惠氏公司 | 抗pd-1抗体及其用途 |
| EP1591527B1 (en) | 2003-01-23 | 2015-08-26 | Ono Pharmaceutical Co., Ltd. | Substance specific to human pd-1 |
| JP2006523226A (ja) | 2003-02-28 | 2006-10-12 | ザ ジョンズ ホプキンス ユニバーシティ | Ｔ細胞調節方法 |
| US20060246123A1 (en) | 2003-03-12 | 2006-11-02 | Eli Gilboa | Oligonucleotide mimetics |
| US20050250106A1 (en) | 2003-04-24 | 2005-11-10 | David Epstein | Gene knock-down by intracellular expression of aptamers |
| CN100482673C (zh) * | 2003-07-15 | 2009-04-29 | 艾德拉药物股份有限公司 | 使用免疫刺激性寡核苷酸和/或免疫子化合物结合细胞因子和/或化疗剂或放射治疗对免疫系统的协同刺激作用 |
| KR101126030B1 (ko) * | 2003-07-15 | 2012-03-19 | 이데라 파마슈티칼즈, 인코포레이티드 | 사이토킨 및/또는 화학치료제 또는 방사선 치료와 연계하여면역자극 올리고누클레오티드 및/또는 이뮤노머 화합물을이용하여 면역계를 공동 상승 자극시키는 방법 |
| US7288638B2 (en) | 2003-10-10 | 2007-10-30 | Bristol-Myers Squibb Company | Fully human antibodies against human 4-1BB |
| BRPI0509274A (pt) | 2004-03-26 | 2007-09-04 | Pfizer Prod Inc | usos de anticorpos anti-ctla-4 |
| HUE036894T2 (hu) * | 2004-06-15 | 2018-08-28 | Idera Pharmaceuticals Inc | Immunstimuláló oligonukleotid multimerek |
| EP1781083A4 (en) | 2004-06-18 | 2009-09-09 | Univ California | SEQUENCES OF BRASSICA INDEHISCENT1 |
| US8239749B2 (en) | 2004-06-25 | 2012-08-07 | Apple Inc. | Procedurally expressing graphic objects for web pages |
| EP1793858A4 (en) | 2004-09-08 | 2008-12-10 | Univ Ohio State Res Found | HUMAN MONOCLONAL ANTI-CTLA4 ANTIBODIES FOR CANCER TREATMENT |
| CN109485727A (zh) | 2005-05-09 | 2019-03-19 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及使用抗pd-1抗体来治疗癌症的方法 |
| EP3130350A1 (en) | 2005-06-08 | 2017-02-15 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (pd-1)pathway |
| KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
| CN101268101A (zh) * | 2005-07-07 | 2008-09-17 | 科利制药集团公司 | 用于癌症治疗的抗-CTLA-4抗体和含有CpG基序的合成寡脱氧核苷酸联合治疗 |
| AU2006306521B2 (en) * | 2005-10-21 | 2011-12-22 | Medical College Of Georgia Research Institute, Inc. | The induction of indoleamine 2,3-dioxygenase in dendritic cells by TLR ligands and uses thereof |
| WO2007052058A1 (en) * | 2005-11-04 | 2007-05-10 | Novartis Vaccines And Diagnostics Srl | Influenza vaccines including combinations of particulate adjuvants and immunopotentiators |
| CA2632940A1 (en) * | 2005-12-20 | 2007-07-05 | Idera Pharmaceuticals, Inc. | Immunostimulatory activity of palindromic immune modulatory oligonucleotides (imo tm) contiaining different lengths of palindromic segments |
| JP6092497B2 (ja) | 2006-03-30 | 2017-03-08 | ユニバーシティー オブ カリフォルニア | 抗ｃｔｌａ−４抗体の限局性分泌のための方法および組成物 |
| US20080031887A1 (en) * | 2006-06-30 | 2008-02-07 | Joseph Lustgarten | Conjugates for inducing targeted immune responses and methods of making and using same |
| CN101104640A (zh) | 2006-07-10 | 2008-01-16 | 苏州大学 | 抗人pd-l1单克隆抗体制备及应用 |
| JP2008066402A (ja) | 2006-09-05 | 2008-03-21 | Fujifilm Corp | 撮像素子および撮像装置 |
| WO2008073959A2 (en) * | 2006-12-12 | 2008-06-19 | Idera Pharmaceuticals, Inc. | Synthetic agonists of tlr9 |
| WO2008100562A2 (en) * | 2007-02-14 | 2008-08-21 | Medical College Of Georgia Research Institute, Inc. | Indoleamine 2,3-dioxygenase, pd-1/pd-l pathways, and ctla4 pathways in the activation of regulatory t cells |
| EP1987839A1 (en) | 2007-04-30 | 2008-11-05 | I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
| NZ600758A (en) | 2007-06-18 | 2013-09-27 | Merck Sharp & Dohme | Antibodies to human programmed death receptor pd-1 |
| KR20090010580A (ko) | 2007-07-24 | 2009-01-30 | 조용식 | 페트용 토이렛 |
| CA2693266C (en) * | 2007-08-01 | 2015-06-30 | Idera Pharmaceuticals, Inc. | Novel synthetic agonists of tlr9 |
| EP2212350B1 (en) | 2007-10-26 | 2013-08-28 | Governing Council of the University of Toronto | Treating chronic viral infection by targetting TIM-3 |
| US20120129870A1 (en) | 2007-12-17 | 2012-05-24 | Wenying Chai | Piperazinyl derivatives useful as modulators of the neuropeptide y2 receptor |
| US8263073B2 (en) | 2008-02-04 | 2012-09-11 | Medarex, Inc. | Anti-CTLA-4 antibodies with reduced blocking of binding of CTLA-4 to B7 and uses thereof |
| GB2457346B (en) | 2008-02-12 | 2012-03-28 | Scott Cutters Uk Ltd | Cutting tools |
| EP2307050A4 (en) | 2008-07-04 | 2012-07-25 | Ono Pharmaceutical Co | USE OF A EFFECTIVENESS MARKER TO OPTIMIZE THE THERAPEUTIC EFFECTIVENESS OF AN ANTI-HUMAN PD-1 ANTIBODY ON CANCERS |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| EP2342228B1 (en) | 2008-09-12 | 2017-09-06 | Oxford University Innovation Limited | Pd-1 specific antibodies and uses thereof |
| ES2592216T3 (es) | 2008-09-26 | 2016-11-28 | Dana-Farber Cancer Institute, Inc. | Anticuerpos anti-PD-1, PD-L1 y PD-L2 humanos y sus usos |
| WO2010077634A1 (en) | 2008-12-09 | 2010-07-08 | Genentech, Inc. | Anti-pd-l1 antibodies and their use to enhance t-cell function |
| US8741295B2 (en) | 2009-02-09 | 2014-06-03 | Universite De La Mediterranee | PD-1 antibodies and PD-L1 antibodies and uses thereof |
| US8605955B2 (en) | 2009-06-29 | 2013-12-10 | DigitalOptics Corporation Europe Limited | Methods and apparatuses for half-face detection |
| JP5409275B2 (ja) | 2009-11-06 | 2014-02-05 | アズビル株式会社 | 監視制御システム |
| EP2533779A4 (en) * | 2010-02-09 | 2013-08-21 | Georgia Health Sciences University Res Inst Inc | ALPHA-METHYL-TRYPTOPHANE AS INHIBITORS OF INDOLEAMINE DIOXYGENASE |
| TW201134488A (en) | 2010-03-11 | 2011-10-16 | Ucb Pharma Sa | PD-1 antibodies |
| EP2545078A1 (en) | 2010-03-11 | 2013-01-16 | UCB Pharma, S.A. | Pd-1 antibody |
| CA2792561C (en) | 2010-04-06 | 2021-10-26 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of cd274/pd-l1 gene |
| KR102315754B1 (ko) * | 2010-05-14 | 2021-10-22 | 더 제너럴 하스피톨 코포레이션 | 종양 특이적 신생항원을 확인하는 조성물 및 방법 |
| US9163087B2 (en) | 2010-06-18 | 2015-10-20 | The Brigham And Women's Hospital, Inc. | Bi-specific antibodies against TIM-3 and PD-1 for immunotherapy in chronic immune conditions |
| FR2963448A1 (fr) | 2010-07-29 | 2012-02-03 | Sagem Defense Securite | Procede et systeme d'analyse de donnees de vol enregistrees au cours d'un vol d'un avion. |
| GB201103955D0 (en) | 2011-03-09 | 2011-04-20 | Antitope Ltd | Antibodies |
| PL2699264T3 (pl) | 2011-04-20 | 2018-08-31 | Medimmune, Llc | Przeciwciała i inne cząsteczki wiążące B7-H1 i PD-1 |
| US8841418B2 (en) | 2011-07-01 | 2014-09-23 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to TIM3 |
| US20130018499A1 (en) | 2011-07-12 | 2013-01-17 | The Boeing Company | Producibility analysis during engineering design of composite parts |
| AR087405A1 (es) | 2011-08-01 | 2014-03-19 | Genentech Inc | Metodos para tratar el cancer por el uso de antagonistas de union al eje pd-1 e inhibidores de mek |
| WO2013022091A1 (ja) | 2011-08-11 | 2013-02-14 | 小野薬品工業株式会社 | Ｐｄ－１アゴニストからなる自己免疫疾患治療剤 |
| BR112014009526B8 (pt) | 2011-10-17 | 2023-01-17 | Herlev Hospital | Composição de vacina compreendendo pd-l1, kit de partes compreendendo tal composição e uso dos mesmos para tratar ou prevenir câncer |
| EP2785375B1 (en) | 2011-11-28 | 2020-07-22 | Merck Patent GmbH | Anti-pd-l1 antibodies and uses thereof |
| CN104159911A (zh) | 2012-03-07 | 2014-11-19 | 奥瑞基尼探索技术有限公司 | 作为免疫调节剂的模拟肽化合物 |
| CN104736168B (zh) | 2012-05-31 | 2018-09-21 | 索伦托治疗有限公司 | 与pd-l1结合的抗原结合蛋白 |
| AU2013308595C1 (en) | 2012-08-30 | 2019-01-17 | Amgen Inc. | A method for treating melanoma using a herpes simplex virus and an immune checkpoint inhibitor |
| CN105163754B (zh) * | 2012-09-20 | 2018-01-05 | 王荣福 | 前列腺特异性肿瘤抗原及其用途 |
| US9308236B2 (en) | 2013-03-15 | 2016-04-12 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
| ES2987696T3 (es) * | 2015-05-29 | 2024-11-15 | Dynavax Tech Corp | Agonista polinucleotídico del receptor de tipo toll 9 para el tratamiento del cáncer de pulmón |
| MX2017015308A (es) | 2015-05-29 | 2018-07-06 | Merck Sharp & Dohme | Combinacion de un antagonista de pd-1 y un oligonucleotido tipo cpg-c para tratar cancer. |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220004588A (ko) * | 2020-07-03 | 2022-01-11 | 주식회사 레모넥스 | Rna 및 이를 포함하는 핵산 전달체 |
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| JP6991857B2 (ja) | 2022-01-13 |
| CA2964155A1 (en) | 2016-04-14 |
| AU2015330731A1 (en) | 2017-05-04 |
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