TW202235438A - 能夠調節配體結合活性的配體結合分子 - Google Patents
能夠調節配體結合活性的配體結合分子 Download PDFInfo
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| KR102533814B1 (ko) | 2016-11-28 | 2023-05-19 | 추가이 세이야쿠 가부시키가이샤 | 리간드 결합 활성을 조정 가능한 리간드 결합 분자 |
| KR20240018673A (ko) | 2016-11-28 | 2024-02-13 | 추가이 세이야쿠 가부시키가이샤 | 항원 결합 도메인 및 운반 부분을 포함하는 폴리펩티드 |
| TWI818934B (zh) | 2017-11-28 | 2023-10-21 | 日商中外製藥股份有限公司 | 可調整配體結合活性的配體結合分子 |
| JP7482630B2 (ja) | 2017-11-28 | 2024-05-14 | 中外製薬株式会社 | 抗原結合ドメインおよび運搬部分を含むポリペプチド |
| EP3794022A1 (en) * | 2018-05-14 | 2021-03-24 | Werewolf Therapeutics, Inc. | Activatable cytokine polypeptides and methods of use thereof |
| JP7414736B2 (ja) | 2018-05-30 | 2024-01-16 | 中外製薬株式会社 | アグリカン結合ドメインおよび運搬部分を含むポリペプチド |
| US20210253672A1 (en) * | 2018-05-30 | 2021-08-19 | Chugai Seiyaku Kabushiki Kaisha | Ligand-binding molecule containing single domain antibody |
| JP2021530243A (ja) * | 2018-07-25 | 2021-11-11 | アスクジーン・ファーマ・インコーポレイテッドAskGene Pharma, Inc. | 新規il−21プロドラッグおよびそれを使用する方法 |
| US20220048966A1 (en) * | 2018-09-28 | 2022-02-17 | Pierre Fabre Medicament | New immunocytokines for the treatment of cancer |
| CN120022352A (zh) | 2018-10-22 | 2025-05-23 | 联邦高等教育系统匹兹堡大学 | Cxcr3的可切割激活剂及其使用方法 |
| WO2020116498A1 (ja) * | 2018-12-04 | 2020-06-11 | 中外製薬株式会社 | Cxcr3リガンド |
| CN113905757A (zh) | 2019-06-05 | 2022-01-07 | 中外制药株式会社 | 抗体切割位点结合分子 |
| WO2020246567A1 (ja) * | 2019-06-05 | 2020-12-10 | 中外製薬株式会社 | プロテアーゼ基質、及びプロテアーゼ切断配列を含むポリペプチド |
| WO2020252264A1 (en) | 2019-06-12 | 2020-12-17 | AskGene Pharma, Inc. | Novel il-15 prodrugs and methods of use thereof |
| EP4021927A1 (en) * | 2019-08-29 | 2022-07-06 | Antagonis Biotherapeutics GmbH | T-cell mobilizing cxcl10 mutant with increased glycosaminoglycan binding affinity |
| WO2021149697A1 (en) * | 2020-01-20 | 2021-07-29 | Chugai Seiyaku Kabushiki Kaisha | Ligand-binding fusion proteins |
| EP3889183A1 (en) * | 2020-04-01 | 2021-10-06 | Pierre Fabre Medicament | A protein complex comprising an immunocytokine |
| EP4373862A1 (en) * | 2021-07-19 | 2024-05-29 | Chugai Seiyaku Kabushiki Kaisha | Protease-mediated target specific cytokine delivery using fusion polypeptide |
| WO2023120643A1 (ja) | 2021-12-23 | 2023-06-29 | 中外製薬株式会社 | Cxcr3発現細胞遊走活性が増強したcxcr3リガンド。 |
| CN120112547A (zh) | 2022-11-16 | 2025-06-06 | 瑞泽恩制药公司 | 包含膜结合il-12和蛋白酶可裂解接头的嵌合蛋白 |
Family Cites Families (109)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| DK0585287T3 (da) | 1990-07-10 | 2000-04-17 | Cambridge Antibody Tech | Fremgangsmåde til fremstilling af specifikke bindingsparelementer |
| AU8507191A (en) | 1990-08-29 | 1992-03-30 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| EP0605522B1 (en) | 1991-09-23 | 1999-06-23 | Medical Research Council | Methods for the production of humanized antibodies |
| ES2341666T3 (es) | 1991-12-02 | 2010-06-24 | Medimmune Limited | Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos. |
| EP0746609A4 (en) | 1991-12-17 | 1997-12-17 | Genpharm Int | NON-HUMAN TRANSGENIC ANIMALS CAPABLE OF PRODUCING HETEROLOGOUS ANTIBODIES |
| DE69333823T2 (de) | 1992-03-24 | 2006-05-04 | Cambridge Antibody Technology Ltd., Melbourn | Verfahren zur herstellung von gliedern von spezifischen bindungspaaren |
| NZ255101A (en) | 1992-07-24 | 1997-08-22 | Cell Genesys Inc | A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor |
| JPH08509612A (ja) | 1993-04-26 | 1996-10-15 | ジェンファーム インターナショナル インコーポレイテッド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
| GB9313509D0 (en) | 1993-06-30 | 1993-08-11 | Medical Res Council | Chemisynthetic libraries |
| FR2707189B1 (fr) | 1993-07-09 | 1995-10-13 | Gradient Ass | Procédé de traitement de résidus de combustion et installation de mise en Óoeuvre dudit procédé. |
| JPH09506508A (ja) | 1993-12-03 | 1997-06-30 | メディカル リサーチ カウンシル | 組換え結合タンパク質およびペプチド |
| HU221385B1 (en) | 1994-07-13 | 2002-09-28 | Chugai Pharmaceutical Co Ltd | Reconstituted human antibody against human interleukin-8 |
| EP0822830B1 (en) | 1995-04-27 | 2008-04-02 | Amgen Fremont Inc. | Human anti-IL-8 antibodies, derived from immunized xenomice |
| EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
| WO2006069036A2 (en) | 2004-12-21 | 2006-06-29 | Centocor, Inc. | Anti-il-12 antibodies, epitopes, compositions, methods and uses |
| JP5291279B2 (ja) | 2000-09-08 | 2013-09-18 | ウニヴェルジテート・チューリッヒ | 反復モジュールを含む反復タンパク質の集合体 |
| JP2004526419A (ja) | 2000-10-16 | 2004-09-02 | フィロス インク. | 抗体模倣物および他の結合タンパク質のためのタンパク質骨格 |
| US20030157561A1 (en) | 2001-11-19 | 2003-08-21 | Kolkman Joost A. | Combinatorial libraries of monomer domains |
| PT2208784E (pt) | 2001-06-22 | 2013-04-03 | Chugai Pharmaceutical Co Ltd | Inibidores da proliferação celular contendo um anticorpo anti-glipicano 3 |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| CN1665932B (zh) | 2002-04-30 | 2010-12-15 | 株式会社载体研究所 | 具有修饰的蛋白酶依赖向性的载体 |
| AU2003242024A1 (en) | 2002-06-05 | 2003-12-22 | Chugai Seiyaku Kabushiki Kaisha | Method of constructing antibody |
| AU2003265866A1 (en) | 2002-09-03 | 2004-03-29 | Vit Lauermann | Targeted release |
| AU2002328429A1 (en) | 2002-09-04 | 2004-03-29 | Chugai Seiyaku Kabushiki Kaisha | CONSTRUCTION OF ANTIBODY USING MRL/lpr MOUSE |
| AU2004284090A1 (en) | 2003-10-24 | 2005-05-06 | Avidia, Inc. | LDL receptor class A and EGF domain monomers and multimers |
| JP2005168328A (ja) | 2003-12-08 | 2005-06-30 | Hokkaido Univ | シグナル伝達活性を有する細胞質蛋白質の活性制御方法 |
| US20050191293A1 (en) | 2003-12-10 | 2005-09-01 | Shrikant Deshpande | IP-10 antibodies and their uses |
| WO2005110453A2 (en) | 2004-04-12 | 2005-11-24 | Catalyst Biosciences, Inc. | Cleavage of vegf and vegf receptor by wildtype and mutant mt-sp1 |
| EP2216046B1 (en) | 2004-07-09 | 2014-03-12 | Chugai Seiyaku Kabushiki Kaisha | Anti-glypican 3 antibody |
| EP2418278A3 (en) | 2005-05-09 | 2012-07-04 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| US7666817B2 (en) | 2005-08-31 | 2010-02-23 | The Regents Of The University Of California | Cellular libraries of peptide sequences (CLiPS) and methods of using the same |
| JP2009519011A (ja) | 2005-12-01 | 2009-05-14 | ドマンティス リミテッド | インターロイキン1受容体1型に結合する非競合ドメイン抗体フォーマット |
| EA200801166A1 (ru) | 2005-12-01 | 2008-12-30 | Домантис Лимитед | Форматы конкурентного доменного антитела, которые связываются с рецептором интерлейкина 1 первого типа |
| TWI417301B (zh) | 2006-02-21 | 2013-12-01 | Wyeth Corp | 對抗人類介白素-22(il-22)之抗體及其用途 |
| TWI369402B (en) | 2006-07-05 | 2012-08-01 | Catalyst Biosciences Inc | Protease screening methods and proteases identified thereby |
| WO2008016854A2 (en) | 2006-08-02 | 2008-02-07 | The Uab Research Foundation | Methods and compositions related to soluble monoclonal variable lymphocyte receptors of defined antigen specificity |
| AU2007285695B2 (en) | 2006-08-18 | 2012-05-24 | Ablynx N.V. | Amino acid sequences directed against IL-6R and polypeptides comprising the same for the treatment of diseases and disorders associated with IL-6-mediated signalling |
| EP2139919A2 (en) | 2007-02-28 | 2010-01-06 | Novimmune Sa | Human anti-ip-10 antibodies and uses thereof |
| CA2688434A1 (en) | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| KR101799337B1 (ko) | 2007-06-21 | 2017-12-20 | 마크로제닉스, 인크. | 공유결합형 디아바디 및 이것의 사용 |
| ES2628395T3 (es) | 2007-08-15 | 2017-08-02 | Bayer Pharma Aktiengesellschaft | Anticuerpo regulado por proteasa |
| CA3128656A1 (en) | 2007-08-22 | 2009-02-26 | The Regents Of The University Of California | Activatable binding polypeptides and methods of identification and use thereof |
| AU2016213702C1 (en) | 2007-08-22 | 2018-11-29 | Cytomx Therapeutics, Inc. | Activatable binding polypeptides and methods of identification and use thereof |
| CN102482347B (zh) | 2009-01-12 | 2017-04-26 | 希托马克斯医疗有限责任公司 | 修饰抗体组合物及其制备和使用方法 |
| MX2011010681A (es) | 2009-04-10 | 2012-01-20 | Ablynx Nv | Secuencias mejoradas de aminoacidos dirigidas contra il-6r y polipeptidos que comprenden el mismo para el tratamiento de enfermedades y trastornos relacionados con il-6r. |
| JP2011026294A (ja) | 2009-06-26 | 2011-02-10 | Canon Inc | 化合物 |
| ES2534085T3 (es) | 2009-08-17 | 2015-04-17 | Roche Glycart Ag | Inmunoconjugados dirigidos |
| US8734774B2 (en) | 2010-04-02 | 2014-05-27 | University Of Rochester | Protease activated cytokines |
| US9193791B2 (en) | 2010-08-03 | 2015-11-24 | City Of Hope | Development of masked therapeutic antibodies to limit off-target effects |
| RU2013110876A (ru) | 2010-08-24 | 2014-09-27 | Рош Гликарт Аг | Активируемые биспецифические антитела |
| WO2012028697A1 (en) | 2010-09-01 | 2012-03-08 | Eth Zürich, Institute Of Molecular Biology And Biophysics | Affinity purification system based on donor strand complementation |
| JP6130307B2 (ja) | 2011-03-17 | 2017-05-17 | ザ ユニバーシティ オブ バーミンガム | 再指向性免疫療法 |
| CN107936121B (zh) | 2011-05-16 | 2022-01-14 | 埃泰美德(香港)有限公司 | 多特异性fab融合蛋白及其使用方法 |
| TW201326209A (zh) | 2011-09-30 | 2013-07-01 | Chugai Pharmaceutical Co Ltd | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
| GB201203442D0 (en) | 2012-02-28 | 2012-04-11 | Univ Birmingham | Immunotherapeutic molecules and uses |
| JP6283017B2 (ja) | 2012-03-30 | 2018-02-21 | バイエル・ヘルスケア・エルエルシーBayer HealthCare LLC | プロテアーゼ制御抗体 |
| ES2670668T3 (es) | 2012-04-06 | 2018-05-31 | Omeros Corporation | Composiciones y métodos para inhibir la MASP-1 y/o la MASP-3 para el tratamiento de la hemoglobinuria nocturna paroxísmica |
| JP6178846B2 (ja) | 2012-05-22 | 2017-08-09 | ライフ テクノロジーズ エーエス | 組み換え抗体組成物およびその使用方法 |
| EP2863948B1 (en) | 2012-06-22 | 2018-10-24 | Cytomx Therapeutics Inc. | Anti-jagged 1/jagged 2 cross-reactive antibodies, activatable anti-jagged antibodies and methods of use thereof |
| WO2014052462A2 (en) | 2012-09-25 | 2014-04-03 | Cytomx Therapeutics, Inc. | Activatable antibodies that bind interleukin-6 receptor and methods of use thereof |
| JP6453208B2 (ja) | 2013-02-15 | 2019-01-16 | 国立大学法人京都工芸繊維大学 | 抗体のリフォールディング方法、リフォールディングされた抗体の製造方法、リフォールディングされた抗体、及びこれらの利用 |
| US20150087810A1 (en) | 2013-09-25 | 2015-03-26 | Cytomx Therapeutics, Inc. | Matrix Metalloproteinase Substrates And Other Cleavable Moieties And Methods Of Use Thereof |
| US9540440B2 (en) | 2013-10-30 | 2017-01-10 | Cytomx Therapeutics, Inc. | Activatable antibodies that bind epidermal growth factor receptor and methods of use thereof |
| WO2015089283A1 (en) | 2013-12-11 | 2015-06-18 | Cytomx Therapeutics, Inc. | Antibodies that bind activatable antibodies and methods of use thereof |
| BR112016017649B1 (pt) | 2014-01-31 | 2024-01-30 | Cytomx Therapeutics, Inc | Polipeptídeo isolado compreendendo substratos de matriptase e de ativador do plasminogênio u e outras porções cliváveis, composição farmacêutica compreendendo o dito polipeptídeo, bem como métodos para produzir e fabricar um polipeptídeo isolado compreendendo uma porção clivável e uso da composição farmacêutica e quantidade terapeuticamente eficaz da dita composição no tratamento de um distúrbio ou doença |
| MX2016010174A (es) | 2014-02-06 | 2016-11-15 | Hoffmann La Roche | Proteinas de fusion de interleucina-10 y usos de las mismas. |
| WO2016014974A2 (en) | 2014-07-25 | 2016-01-28 | Cytomx Therapeutics, Inc. | Anti-cd3 antibodies, activatable anti-cd3 antibodies, multispecific anti-cd3 antibodies, multispecific activatable anti-cd3 antibodies, and methods of using the same |
| GB201413357D0 (en) | 2014-07-28 | 2014-09-10 | Philogen Spa | Antibodies for treatment and diagnosis |
| JP2017529853A (ja) | 2014-09-25 | 2017-10-12 | アムジエン・インコーポレーテツド | プロテアーゼにより活性化可能な二重特異性タンパク質 |
| CA2964968A1 (en) | 2014-11-11 | 2016-05-19 | Amunix Operating Inc. | Targeted xten conjugate compositions and methods of making same |
| MA41374A (fr) | 2015-01-20 | 2017-11-28 | Cytomx Therapeutics Inc | Substrats clivables par métalloprotéase matricielle et clivables par sérine protéase et procédés d'utilisation de ceux-ci |
| WO2016149201A2 (en) | 2015-03-13 | 2016-09-22 | Cytomx Therapeutics, Inc. | Anti-pdl1 antibodies, activatable anti-pdl1 antibodies, and methods of use thereof |
| EP3778640A1 (en) | 2015-05-01 | 2021-02-17 | Genentech, Inc. | Masked anti-cd3 antibodies and methods of use |
| CN107849133B (zh) | 2015-05-04 | 2022-08-23 | 西托姆克斯治疗公司 | 抗cd166抗体、可活化抗cd166抗体及其使用方法 |
| US10233244B2 (en) | 2015-05-04 | 2019-03-19 | Cytomx Therapeutics, Inc. | Anti-ITGA3 antibodies, activatable anti-ITGA3 antibodies, and methods of use thereof |
| SG10201913762QA (en) | 2015-05-04 | 2020-03-30 | Cytomx Therapeutics Inc | Anti-cd71 antibodies, activatable anti-cd71 antibodies, and methods of use thereof |
| US11400157B2 (en) | 2015-05-13 | 2022-08-02 | Chugai Seiyaku Kabushiki Kaisha | Multiple antigen binding molecular fusion, pharmaceutical composition, method for identifying linear epitope, and method for preparing multiple antigen binding molecular fusion |
| WO2017025698A1 (en) | 2015-08-11 | 2017-02-16 | Queen Mary University Of London | Bispecific, cleavable antibodies |
| BR112018016281A2 (pt) | 2016-03-22 | 2019-01-02 | F. Hoffmann-La Roche Ag | molécula biespecífica ativadora de célula t ativável por protease, polipeptídeo idiotipo-específico, composição farmacêutica, usos da molécula biespecífica e método de tratamento de uma doença em um indivíduo |
| JP7461741B2 (ja) | 2016-06-20 | 2024-04-04 | カイマブ・リミテッド | 抗pd-l1およびil-2サイトカイン |
| CA3042679A1 (en) | 2016-11-03 | 2018-05-11 | Bristol-Myers Squibb Company | Activatable anti-ctla-4 antibodies and uses thereof |
| KR102533814B1 (ko) | 2016-11-28 | 2023-05-19 | 추가이 세이야쿠 가부시키가이샤 | 리간드 결합 활성을 조정 가능한 리간드 결합 분자 |
| KR20240018673A (ko) | 2016-11-28 | 2024-02-13 | 추가이 세이야쿠 가부시키가이샤 | 항원 결합 도메인 및 운반 부분을 포함하는 폴리펩티드 |
| CA3046432A1 (en) | 2016-12-13 | 2018-06-21 | Astellas Pharma Inc. | Anti-human cd73 antibody |
| AU2018277310B2 (en) | 2017-06-02 | 2024-07-11 | Ablynx Nv | Aggrecan binding immunoglobulins |
| JP7249961B2 (ja) | 2017-06-02 | 2023-03-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Adamts5、mmp13およびアグリカンに結合するポリペプチド |
| AU2018297248A1 (en) | 2017-07-03 | 2020-02-20 | Torque Therapeutics, Inc. | Fusion molecules targeting immune regulatory cells and uses thereof |
| US20190038935A1 (en) | 2017-08-07 | 2019-02-07 | Timofey Ignatyev | Exercise game and apparatus employing color-changing base locations |
| CN107602706B (zh) | 2017-10-16 | 2020-12-04 | 湖北大学 | 一种切割效率增强的hrv 3c蛋白酶底物突变体及其应用 |
| TWI818934B (zh) | 2017-11-28 | 2023-10-21 | 日商中外製藥股份有限公司 | 可調整配體結合活性的配體結合分子 |
| JP7482630B2 (ja) | 2017-11-28 | 2024-05-14 | 中外製薬株式会社 | 抗原結合ドメインおよび運搬部分を含むポリペプチド |
| KR102020131B1 (ko) | 2017-12-29 | 2019-09-09 | 박성원 | 광경화성 조성물 및 이를 이용하여 제조된 성형품 |
| CA3115461A1 (en) | 2018-03-09 | 2019-09-12 | AskGene Pharma, Inc. | Novel cytokine prodrugs |
| EP3794022A1 (en) | 2018-05-14 | 2021-03-24 | Werewolf Therapeutics, Inc. | Activatable cytokine polypeptides and methods of use thereof |
| JP7460609B2 (ja) | 2018-05-14 | 2024-04-02 | ウェアウルフ セラピューティクス, インコーポレイテッド | 活性化可能なインターロイキン-2ポリペプチド及びその使用方法 |
| JP7414736B2 (ja) | 2018-05-30 | 2024-01-16 | 中外製薬株式会社 | アグリカン結合ドメインおよび運搬部分を含むポリペプチド |
| EP3802831A4 (en) | 2018-05-30 | 2022-07-27 | Chugai Seiyaku Kabushiki Kaisha | Polypeptide comprising il-1r1 binding domain and carrying moiety |
| US20210253672A1 (en) | 2018-05-30 | 2021-08-19 | Chugai Seiyaku Kabushiki Kaisha | Ligand-binding molecule containing single domain antibody |
| US20210355219A1 (en) | 2018-09-21 | 2021-11-18 | Harpoon Therapeutics, Inc. | Conditionally activated target-binding molecules |
| EP3856764A4 (en) | 2018-09-27 | 2022-11-02 | Xilio Development, Inc. | MASKED CYTOKINE POLYPEPTIDES |
| SG11202103192RA (en) | 2018-10-03 | 2021-04-29 | Xencor Inc | Il-12 heterodimeric fc-fusion proteins |
| WO2020246567A1 (ja) | 2019-06-05 | 2020-12-10 | 中外製薬株式会社 | プロテアーゼ基質、及びプロテアーゼ切断配列を含むポリペプチド |
| CN113905757A (zh) | 2019-06-05 | 2022-01-07 | 中外制药株式会社 | 抗体切割位点结合分子 |
| BR112022001320A2 (pt) | 2019-07-25 | 2022-04-12 | Univ Chicago | Composições e métodos compreendendo agentes terapêuticos ativados por protease |
| WO2021149697A1 (en) | 2020-01-20 | 2021-07-29 | Chugai Seiyaku Kabushiki Kaisha | Ligand-binding fusion proteins |
| EP4373862A1 (en) | 2021-07-19 | 2024-05-29 | Chugai Seiyaku Kabushiki Kaisha | Protease-mediated target specific cytokine delivery using fusion polypeptide |
-
2017
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- 2024-12-24 JP JP2024226961A patent/JP2025041812A/ja active Pending
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| US12060654B2 (en) | 2024-08-13 |
| RU2019117223A (ru) | 2020-12-28 |
| US20250034756A1 (en) | 2025-01-30 |
| EP3546480A1 (en) | 2019-10-02 |
| JP2023075256A (ja) | 2023-05-30 |
| TWI776827B (zh) | 2022-09-11 |
| KR20230073346A (ko) | 2023-05-25 |
| KR102533814B1 (ko) | 2023-05-19 |
| US20200207846A1 (en) | 2020-07-02 |
| MX2024003513A (es) | 2024-04-08 |
| RU2019117223A3 (enExample) | 2021-02-18 |
| IL266827A (en) | 2019-08-29 |
| WO2018097308A1 (ja) | 2018-05-31 |
| JP7671794B2 (ja) | 2025-05-02 |
| JP2025041812A (ja) | 2025-03-26 |
| BR112019008265A2 (pt) | 2019-07-09 |
| MX2024003516A (es) | 2024-04-01 |
| KR20190087525A (ko) | 2019-07-24 |
| CA3039316A1 (en) | 2018-05-31 |
| JPWO2018097308A1 (ja) | 2019-10-17 |
| IL266827B2 (en) | 2025-04-01 |
| JP7626577B2 (ja) | 2025-02-07 |
| AU2017364818A1 (en) | 2019-05-23 |
| AU2017364818C1 (en) | 2025-05-15 |
| AU2017364818B2 (en) | 2024-11-21 |
| TW201833136A (zh) | 2018-09-16 |
| EP3546480A4 (en) | 2020-07-29 |
| CN110214151A (zh) | 2019-09-06 |
| IL266827B1 (en) | 2024-12-01 |
| MX2019005947A (es) | 2019-08-26 |
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