CN113905767A - 无痕连接体及其蛋白质偶联物 - Google Patents
无痕连接体及其蛋白质偶联物 Download PDFInfo
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- CN113905767A CN113905767A CN202080019317.3A CN202080019317A CN113905767A CN 113905767 A CN113905767 A CN 113905767A CN 202080019317 A CN202080019317 A CN 202080019317A CN 113905767 A CN113905767 A CN 113905767A
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7330101B2 (ja) | 2016-11-08 | 2023-08-21 | レゲネロン ファーマシューティカルス,インコーポレーテッド | ステロイド及びそのタンパク質コンジュゲート |
CN110944718A (zh) | 2017-05-18 | 2020-03-31 | 里珍纳龙药品有限公司 | 环糊精蛋白质药物偶联物 |
BR112020022400A2 (pt) | 2018-05-09 | 2021-02-02 | Regeneron Pharmaceuticals, Inc. | anticorpos anti-msr1 e métodos de uso dos mesmos |
US11806405B1 (en) | 2021-07-19 | 2023-11-07 | Zeno Management, Inc. | Immunoconjugates and methods |
WO2023079362A1 (en) * | 2021-11-03 | 2023-05-11 | Ripple Therapeutics Corporation | Processable compositions and use for the same |
US20230287138A1 (en) | 2022-01-12 | 2023-09-14 | Regneron Pharmaceuticals, Inc. | Protein-drug conjugates comprising camptothecin analogs and methods of use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105517577A (zh) * | 2013-06-21 | 2016-04-20 | 先天制药公司 | 多肽的酶促偶联 |
CN106163559A (zh) * | 2014-04-10 | 2016-11-23 | 第三共株式会社 | 抗her3抗体‑药物偶联物 |
CN112004557A (zh) * | 2018-01-08 | 2020-11-27 | 里珍纳龙药品有限公司 | 类固醇类化合物及其抗体偶联物 |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US20070258987A1 (en) | 2000-11-28 | 2007-11-08 | Seattle Genetics, Inc. | Recombinant Anti-Cd30 Antibodies and Uses Thereof |
TW200539855A (en) | 2004-03-15 | 2005-12-16 | Wyeth Corp | Calicheamicin conjugates |
BRPI0510883B8 (pt) | 2004-06-01 | 2021-05-25 | Genentech Inc | composto conjugado de droga e anticorpo, composição farmacêutica, método de fabricação de composto conjugado de droga e anticorpo e usos de uma formulação, de um conjugado de droga e anticorpo e um agente quimioterapêutico e de uma combinação |
JP2008521828A (ja) | 2004-11-29 | 2008-06-26 | シアトル ジェネティックス, インコーポレイテッド | 操作された抗体およびイムノコンジュゲート |
US7750116B1 (en) | 2006-02-18 | 2010-07-06 | Seattle Genetics, Inc. | Antibody drug conjugate metabolites |
WO2008122039A2 (en) | 2007-04-02 | 2008-10-09 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Selenocysteine mediated hybrid antibody molecules |
EP2167963B1 (en) | 2007-05-23 | 2019-04-17 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
BRPI0911442A2 (pt) | 2008-04-30 | 2019-03-12 | Immunogen, Inc. | conjugados potentes e ligantes hidrofílicos |
KR101000067B1 (ko) | 2008-12-30 | 2010-12-10 | 엘지전자 주식회사 | 고효율 태양전지용 레이저 소성장치 및 고효율 태양전지 제조방법 |
US20130028917A1 (en) | 2010-04-15 | 2013-01-31 | Spirogen Developments Sàrl | Pyrrolobenzodiazepines and conjugates thereof |
WO2012005982A2 (en) | 2010-07-06 | 2012-01-12 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Reporter for rna polymerase ii termination |
EP2714685B1 (en) | 2011-05-27 | 2016-10-19 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acid linked dolastatin derivatives |
US8815226B2 (en) | 2011-06-10 | 2014-08-26 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
WO2013053872A1 (en) | 2011-10-14 | 2013-04-18 | Spirogen Sàrl | Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines |
WO2013055990A1 (en) | 2011-10-14 | 2013-04-18 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
KR101891859B1 (ko) | 2011-10-14 | 2018-08-24 | 메디뮨 리미티드 | 피롤로벤조디아제핀 |
CN103997893B (zh) | 2011-10-14 | 2019-04-12 | 西雅图基因公司 | 吡咯并苯并二氮杂卓和靶向结合物 |
WO2013068874A1 (en) | 2011-11-11 | 2013-05-16 | Pfizer Inc. | Antibody-drug conjugates |
CN110201186A (zh) | 2012-10-23 | 2019-09-06 | 西纳福克斯股份有限公司 | 经修饰的抗体、抗体-缀合物及其制备方法 |
TWI641620B (zh) | 2013-08-21 | 2018-11-21 | 再生元醫藥公司 | 抗-prlr抗體及其用途 |
CA3025377A1 (en) * | 2016-06-02 | 2017-12-07 | Abbvie Inc. | Glucocorticoid receptor agonist and immunoconjugates thereof |
CA3037732A1 (en) | 2016-09-23 | 2018-03-29 | Regeneron Pharmaceuticals, Inc. | Anti-steap2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind steap2 and cd3, and uses thereof |
EA201900562A1 (ru) * | 2017-05-18 | 2020-05-12 | Регенерон Фармасьютикалз, Инк. | Бис-октагидрофенантрена карбоксамиды и их белковые конъюгаты |
CN110944718A (zh) * | 2017-05-18 | 2020-03-31 | 里珍纳龙药品有限公司 | 环糊精蛋白质药物偶联物 |
WO2019034176A1 (zh) * | 2017-08-18 | 2019-02-21 | 四川百利药业有限责任公司 | 一种喜树碱-抗体偶联物 |
WO2019034177A1 (zh) * | 2017-08-18 | 2019-02-21 | 四川百利药业有限责任公司 | 具有两种不同药物的抗体药物偶联物 |
CN112135542B (zh) | 2018-05-08 | 2022-08-16 | 耐克创新有限合伙公司 | 与聚烯烃板的结合以及由其形成的鞋类物品 |
BR112020022400A2 (pt) | 2018-05-09 | 2021-02-02 | Regeneron Pharmaceuticals, Inc. | anticorpos anti-msr1 e métodos de uso dos mesmos |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105517577A (zh) * | 2013-06-21 | 2016-04-20 | 先天制药公司 | 多肽的酶促偶联 |
CN106163559A (zh) * | 2014-04-10 | 2016-11-23 | 第三共株式会社 | 抗her3抗体‑药物偶联物 |
CN112004557A (zh) * | 2018-01-08 | 2020-11-27 | 里珍纳龙药品有限公司 | 类固醇类化合物及其抗体偶联物 |
Non-Patent Citations (1)
Title |
---|
JEFFREY C. KERN等: ""Novel Phosphate Modified Cathepsin B Linkers: Improving Aqueous Solubility and Enhancing Payload Scope of ADCs"", 《BIOCONJUGATE CHEM》, vol. 27, 31 December 2016 (2016-12-31), pages 2081 - 2088, XP055557206, DOI: 10.1021/acs.bioconjchem.6b00337 * |
Cited By (1)
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WO2023143351A1 (zh) * | 2022-01-29 | 2023-08-03 | 上海盛迪医药有限公司 | 糖皮质激素的药物偶联物 |
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WO2020146541A3 (en) | 2020-08-13 |
CA3125998A1 (en) | 2020-07-16 |
EP3908323A2 (en) | 2021-11-17 |
MX2021008114A (es) | 2021-08-05 |
MA59295A1 (fr) | 2023-07-31 |
BR112021013464A2 (pt) | 2021-09-21 |
KR20210114008A (ko) | 2021-09-17 |
WO2020146541A2 (en) | 2020-07-16 |
AU2020205662A1 (en) | 2021-07-22 |
IL284673A (en) | 2021-08-31 |
MA53772B1 (fr) | 2023-08-31 |
SG11202107212QA (en) | 2021-07-29 |
JP2022517767A (ja) | 2022-03-10 |
MA53772A1 (fr) | 2022-10-31 |
CL2021001790A1 (es) | 2022-07-01 |
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