KR20120057588A - 가변 속도 방출 링커를 포함하는 폴리알 약물 접합체 - Google Patents
가변 속도 방출 링커를 포함하는 폴리알 약물 접합체 Download PDFInfo
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- KR20120057588A KR20120057588A KR1020117031373A KR20117031373A KR20120057588A KR 20120057588 A KR20120057588 A KR 20120057588A KR 1020117031373 A KR1020117031373 A KR 1020117031373A KR 20117031373 A KR20117031373 A KR 20117031373A KR 20120057588 A KR20120057588 A KR 20120057588A
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- cancer
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| US8349308B2 (en) * | 2010-03-26 | 2013-01-08 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
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| US8815226B2 (en) | 2011-06-10 | 2014-08-26 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
| RU2617402C2 (ru) | 2011-06-10 | 2017-04-25 | Мерсана Терапьютикс, Инк. | Конъюгаты белок-полимер-лекарственное средство |
| AU2012332588B2 (en) | 2011-11-01 | 2017-09-07 | Bionomics, Inc. | Methods of blocking cancer stem cell growth |
| CN104024236A (zh) * | 2011-12-23 | 2014-09-03 | 摩萨那医疗公司 | 烟曲霉素衍生物-phf结合物的药物配制品 |
| EP2928503B1 (en) | 2012-12-10 | 2019-02-20 | Mersana Therapeutics, Inc. | Conjugates of auristatin compounds |
| AU2013359506B2 (en) * | 2012-12-10 | 2018-05-24 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
| WO2014093640A1 (en) | 2012-12-12 | 2014-06-19 | Mersana Therapeutics,Inc. | Hydroxy-polmer-drug-protein conjugates |
| MY174813A (en) | 2013-03-15 | 2020-05-16 | Zymeworks Inc | Cytotoxic and anti-mitotic compounds, and methods of using the same |
| CA2925132C (en) | 2013-10-04 | 2021-11-30 | Prolynx Llc | Slow-release conjugates of sn-38 |
| CA2926586C (en) | 2013-10-11 | 2020-04-07 | Mersana Therapeutics, Inc. | Polymeric scaffold based on phf for targeted drug delivery |
| WO2015054669A1 (en) | 2013-10-11 | 2015-04-16 | Asana Biosciences, Llc | Protein-polymer-drug conjugates |
| CA2935077C (en) | 2013-12-27 | 2022-03-15 | Geoffrey C. Winters | Sulfonamide-containing linkage systems for drug conjugates |
| CA2960899C (en) | 2014-09-17 | 2021-08-17 | Zymeworks Inc. | Cytotoxic and anti-mitotic compounds, and methods of using the same |
| WO2016070089A2 (en) | 2014-10-31 | 2016-05-06 | Abbvie Biotherapeutics Inc. | Anti-cs1 antibodies and antibody drug conjugates |
| MX2017006167A (es) | 2014-11-12 | 2018-03-23 | Siamab Therapeutics Inc | Compuestos que interactúan con glicanos y métodos de uso. |
| EP3230282A1 (en) | 2014-12-09 | 2017-10-18 | AbbVie Inc. | Bcl xl inhibitory compounds having low cell permeability and antibody drug conjugates including the same |
| CN113209306A (zh) | 2014-12-09 | 2021-08-06 | 艾伯维公司 | 具有细胞渗透性的bcl-xl抑制剂的抗体药物缀合物 |
| CN108350078A (zh) | 2015-11-03 | 2018-07-31 | 默克专利股份公司 | 用于提高肿瘤选择性和抑制的双特异性抗体及其用途 |
| CN116217729A (zh) | 2015-11-12 | 2023-06-06 | 思进公司 | 聚糖相互作用化合物及使用方法 |
| CA3006596A1 (en) | 2015-11-30 | 2017-06-08 | Abbvie Inc. | Anti-hulrrc15 antibody drug conjugates and methods for their use |
| AU2016365117A1 (en) | 2015-11-30 | 2018-05-31 | Abbvie Biotherapeutics Inc. | Anti-huLRRC15 antibody drug conjugates and methods for their use |
| AU2017239038B2 (en) | 2016-03-22 | 2024-06-27 | Bionomics Inc | Administration of an anti-LGR5 monoclonal antibody |
| RS60663B1 (sr) | 2016-05-17 | 2020-09-30 | Abbvie Biotherapeutics Inc | Konjugati anti-cmet antitelo-lek i metodi za njihovu primenu |
| CA3026434A1 (en) * | 2016-06-03 | 2017-12-07 | Novacyte, Inc. | Polymer linkers and their uses |
| CN109963870B (zh) | 2016-06-08 | 2023-07-28 | 艾伯维公司 | 抗b7-h3抗体和抗体药物偶联物 |
| CN109562168A (zh) | 2016-06-08 | 2019-04-02 | 艾伯维公司 | 抗cd98抗体及抗体药物偶联物 |
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| CN116173232A (zh) | 2016-06-08 | 2023-05-30 | 艾伯维公司 | 抗cd98抗体及抗体药物偶联物 |
| EP3468616A1 (en) | 2016-06-08 | 2019-04-17 | AbbVie Inc. | Anti-egfr antibody drug conjugates |
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| BR112018075639A2 (pt) | 2016-06-08 | 2019-04-09 | Abbvie Inc. | conjugados de anticorpo fármaco anti-egfr |
| WO2017214339A1 (en) | 2016-06-08 | 2017-12-14 | Abbvie Inc. | Anti-b7-h3 antibodies and antibody drug conjugates |
| CA3027044A1 (en) | 2016-06-08 | 2017-12-14 | Abbvie Inc. | Anti-b7-h3 antibodies and antibody drug conjugates |
| WO2018004338A1 (en) | 2016-06-27 | 2018-01-04 | Tagworks Pharmaceuticals B.V. | Cleavable tetrazine used in bio-orthogonal drug activation |
| DK3512882T3 (da) | 2016-09-14 | 2021-05-31 | Merck Patent Gmbh | Anti-c-met-antistoffer og antistoflægemiddelkonjugater deraf til effektiv tumorinhibering |
| CA3041254A1 (en) | 2016-10-19 | 2018-04-26 | Invenra Inc. | Antibody constructs |
| US11401330B2 (en) | 2016-11-17 | 2022-08-02 | Seagen Inc. | Glycan-interacting compounds and methods of use |
| US11135307B2 (en) | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
| KR102312222B1 (ko) | 2016-12-22 | 2021-10-12 | 우니베르시따 델리 스투디 만냐 그레챠 카탄차로 | Cd43의 독특한 시알로글리코실화된 암-연관 에피토프를 표적으로 하는 모노클로날 항체 |
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| US10772971B2 (en) | 2017-06-22 | 2020-09-15 | Mersana Therpeutics, Inc. | Methods of producing drug-carrying polymer scaffolds and protein-polymer-drug conjugates |
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| CN113365664A (zh) | 2018-10-29 | 2021-09-07 | 梅尔莎纳医疗公司 | 具有含肽接头的半胱氨酸工程化的抗体-药物缀合物 |
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| US12037378B2 (en) | 2019-05-21 | 2024-07-16 | Novartis Ag | Variant CD58 domains and uses thereof |
| IL289094A (en) | 2019-06-17 | 2022-02-01 | Tagworks Pharmaceuticals B V | Tetrazines for increasing the speed and yield of the "click release" reaction |
| JP7784899B2 (ja) | 2019-06-17 | 2025-12-12 | タグワークス ファーマシューティカルス ビー.ブイ. | 高速で且つ効率的なクリック放出の為の化合物 |
| CN114585651A (zh) | 2019-08-08 | 2022-06-03 | 再生元制药公司 | 新型抗原结合分子形式 |
| JP7785669B2 (ja) | 2019-11-05 | 2025-12-15 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | N末端scFv多重特異性結合分子 |
| JP2023509760A (ja) | 2020-01-08 | 2023-03-09 | シンシス セラピューティクス,インコーポレイテッド | Alk5阻害剤複合体およびその使用 |
| JP2023516080A (ja) | 2020-03-06 | 2023-04-17 | ジーオー セラピューティクス,インコーポレイテッド | 抗グリコcd44抗体およびその使用 |
| US20230128499A1 (en) | 2020-03-27 | 2023-04-27 | Novartis Ag | Bispecific combination therapy for treating proliferative diseases and autoimmune diseases |
| US11028132B1 (en) | 2020-04-07 | 2021-06-08 | Yitzhak Rosen | Half-life optimized linker composition |
| AR124681A1 (es) | 2021-01-20 | 2023-04-26 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
| US20250326855A1 (en) | 2021-03-05 | 2025-10-23 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
| KR20240107093A (ko) | 2021-08-05 | 2024-07-08 | 고 테라퓨틱스, 인크. | 항-글리코-muc4 항체 및 그의 용도 |
| JP2024536722A (ja) | 2021-09-03 | 2024-10-08 | ジーオー セラピューティクス,インコーポレイテッド | 抗グリコcmet抗体およびその使用 |
| US20250066498A1 (en) | 2021-09-03 | 2025-02-27 | Go Therapeutics, Inc. | Anti-glyco-lamp1 antibodies and their uses |
| JP2024532537A (ja) | 2021-09-06 | 2024-09-05 | ヴェラクサ バイオテック ゲーエムベーハー | 真核生物における遺伝暗号の拡張のための新規アミノアシルtRNA合成酵素変異体 |
| EP4186529B1 (en) | 2021-11-25 | 2025-07-09 | Veraxa Biotech GmbH | Improved antibody-payload conjugates (apcs) prepared by site-specific conjugation utilizing genetic code expansion |
| JP2024543916A (ja) | 2021-11-25 | 2024-11-26 | ヴェラクサ バイオテック ゲーエムベーハー | 遺伝暗号拡張を利用した部位特異的結合によって調製された改良された抗体ペイロード複合体(apc) |
| CA3239713A1 (en) | 2021-12-08 | 2023-06-15 | Edward A. LEMKE | Hydrophilic tetrazine-functionalized payloads for preparation of targeting conjugates |
| IL314951B2 (en) | 2022-02-15 | 2025-07-01 | Tagworks Pharmaceuticals B V | Masked il12 protein |
| KR20250049568A (ko) | 2022-07-15 | 2025-04-11 | 페온 테라퓨틱스 리미티드 | Cdcp1에 결합하는 항체 약물 접합체 및 이의 용도 |
| WO2024080872A1 (en) | 2022-10-12 | 2024-04-18 | Tagworks Pharmaceuticals B.V. | Strained bicyclononenes |
| AU2024207469A1 (en) | 2023-01-13 | 2025-08-28 | Regeneron Pharmaceuticals, Inc. | Fgfr3 binding molecules and methods of use thereof |
| CN120569216A (zh) | 2023-01-20 | 2025-08-29 | 巴斯夫欧洲公司 | 稳定型生物聚合物组合物、其制造和用途 |
| CN121100004A (zh) | 2023-03-10 | 2025-12-09 | 泰克沃尔科斯制药有限公司 | 具有改进的t-连接子的反式-环辛烯 |
| WO2024258967A1 (en) | 2023-06-13 | 2024-12-19 | Synthis Therapeutics, Inc. | Anti-cd5 antibodies and their uses |
| WO2025021929A1 (en) | 2023-07-27 | 2025-01-30 | Veraxa Biotech Gmbh | Hydrophilic trans-cyclooctene (hytco) compounds, constructs and conjugates containing the same |
| WO2025056807A1 (en) | 2023-09-15 | 2025-03-20 | Basf Se | Stabilized biopolymer composition, their manufacture and use |
| WO2025078841A2 (en) | 2023-10-11 | 2025-04-17 | Antikor Biopharma Limited | Antibodies, conjugates, and uses thereof |
| WO2025149667A1 (en) | 2024-01-12 | 2025-07-17 | Pheon Therapeutics Ltd | Antibody drug conjugates and uses thereof |
| WO2025174248A1 (en) | 2024-02-16 | 2025-08-21 | Tagworks Pharmaceuticals B.V. | Trans-cyclooctenes with "or gate" release |
| WO2025240335A1 (en) | 2024-05-13 | 2025-11-20 | Regeneron Pharmaceuticals, Inc. | Fgfr3 binding molecules and methods of use thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH26256A (en) | 1988-08-12 | 1992-04-01 | Fujisawa Pharmaceutical Co | Oxaspiro [2,5] octane derivative |
| US5811510A (en) | 1995-04-14 | 1998-09-22 | General Hospital Corporation | Biodegradable polyacetal polymers and methods for their formation and use |
| WO1998056372A1 (en) | 1997-06-09 | 1998-12-17 | Massachusetts Institute Of Technology | TYPE 2 METHIONINE AMINOPEPTIDASE (MetAP2) INHIBITORS AND USES THEROF |
| US20020103136A1 (en) * | 1998-03-05 | 2002-08-01 | Dong-Mei Feng | Conjugates useful in the treatment of prostate cancer |
| WO1999061432A1 (en) | 1998-05-12 | 1999-12-02 | Biochem Pharma Inc. | Fumagillin analogs and their use as angiogenesis inhibitors |
| US6603812B1 (en) | 1998-08-17 | 2003-08-05 | Linear Technology Corporation | Hardware implementation of a decimating finite impulse response filter |
| DE602004032553D1 (de) * | 2003-09-05 | 2011-06-16 | Gen Hospital Corp | Polyacetal-arzneimittelkonjugate als freisetzungssystem |
| US20060235161A1 (en) * | 2005-03-31 | 2006-10-19 | Jorge Heller | PEG-polyacetal and PEG-polyacetal-POE graft copolymers and pharmaceutical compositions |
| US20070019008A1 (en) | 2005-07-22 | 2007-01-25 | Xerox Corporation | Systems, methods, and programs for increasing print quality |
| NZ585547A (en) * | 2007-11-28 | 2012-12-21 | Mersana Therapeutics Inc | Biocompatible biodegradable fumagillin analog conjugates |
| WO2009121564A1 (en) * | 2008-03-31 | 2009-10-08 | Freie Universität Berlin | Drug conjugates with polyglycerols |
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- 2010-05-27 EP EP10781215.8A patent/EP2435053B1/en not_active Not-in-force
- 2010-05-27 AU AU2010254013A patent/AU2010254013A1/en not_active Abandoned
- 2010-05-27 WO PCT/US2010/036413 patent/WO2010138719A1/en not_active Ceased
- 2010-05-27 CA CA2762877A patent/CA2762877A1/en not_active Abandoned
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- 2010-05-27 CN CN2010800236442A patent/CN102448469A/zh active Pending
- 2010-05-27 KR KR1020117031373A patent/KR20120057588A/ko not_active Withdrawn
- 2010-05-28 TW TW099117180A patent/TW201102089A/zh unknown
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| WO2010138719A1 (en) | 2010-12-02 |
| EP2435053A4 (en) | 2016-03-16 |
| AR078510A1 (es) | 2011-11-16 |
| AU2010254013A1 (en) | 2011-11-24 |
| EP2435053A1 (en) | 2012-04-04 |
| US8524214B2 (en) | 2013-09-03 |
| IL216325A0 (en) | 2012-01-31 |
| CA2762877A1 (en) | 2010-12-02 |
| EP2435053B1 (en) | 2018-11-14 |
| JP2012528240A (ja) | 2012-11-12 |
| CN102448469A (zh) | 2012-05-09 |
| TW201102089A (en) | 2011-01-16 |
| US20100305149A1 (en) | 2010-12-02 |
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