BRPI0716812A2 - Pro drogas polimericas direcionadas contendo ligantes multifuncionais - Google Patents
Pro drogas polimericas direcionadas contendo ligantes multifuncionais Download PDFInfo
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- BRPI0716812A2 BRPI0716812A2 BRPI0716812-8A BRPI0716812A BRPI0716812A2 BR PI0716812 A2 BRPI0716812 A2 BR PI0716812A2 BR PI0716812 A BRPI0716812 A BR PI0716812A BR PI0716812 A2 BRPI0716812 A2 BR PI0716812A2
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- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84494306P | 2006-09-15 | 2006-09-15 | |
| US60/844,943 | 2006-09-15 | ||
| PCT/US2007/078600 WO2008034124A2 (fr) | 2006-09-15 | 2007-09-15 | Promédicaments polymères ciblés contenant des segments de liaison multifonctionnels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0716812A2 true BRPI0716812A2 (pt) | 2013-11-05 |
Family
ID=39184644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0716812-8A BRPI0716812A2 (pt) | 2006-09-15 | 2007-09-15 | Pro drogas polimericas direcionadas contendo ligantes multifuncionais |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP2073820A4 (fr) |
| JP (1) | JP2010503708A (fr) |
| KR (1) | KR20090057383A (fr) |
| CN (1) | CN101541332A (fr) |
| AU (1) | AU2007296056B2 (fr) |
| BR (1) | BRPI0716812A2 (fr) |
| CA (1) | CA2662981A1 (fr) |
| IL (1) | IL197517A0 (fr) |
| MX (1) | MX2009002855A (fr) |
| RU (1) | RU2009114154A (fr) |
| WO (1) | WO2008034124A2 (fr) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101688244B (zh) | 2007-04-20 | 2013-05-08 | 希格马托罕见疾病公司 | 稳定的重组腺苷脱氨酶 |
| EP2307032A4 (fr) * | 2008-05-22 | 2014-08-20 | Univ Ramot | Nouveaux conjugués de polymères sur lesquels sont fixés un agent thérapeutiquement actif et une fraction ciblant l'angiogenèse et utilisations de ces conjugués pour traiter des maladies liées à l'angiogenèse |
| WO2009141823A2 (fr) | 2008-05-22 | 2009-11-26 | Ramot At Tel Aviv University Ltd. | Conjugués d'un polymère, d'un bisphosphonate et d'un agent anti-angiogenèse et leurs utilisations dans le traitement et la surveillance de maladies concernant les os |
| US20110105413A1 (en) * | 2008-05-23 | 2011-05-05 | Enzon Pharmaceuticals, Inc. | Polymeric systems containing intracellular releasable disulfide linker for the delivery of oligonucleotides |
| CN102112493B (zh) | 2008-07-23 | 2015-04-01 | 韩美科学株式会社 | 包含具有三个官能性末端的非肽基聚合物的多肽复合物 |
| WO2010057154A1 (fr) * | 2008-11-17 | 2010-05-20 | Enzon Pharmaceuticals, Inc. | Conjugués libérables pour systèmes d'administration d'acides nucléiques |
| CA2742838A1 (fr) * | 2008-11-17 | 2010-05-20 | Enzon Pharmaceuticals, Inc. | Lipides-polymeres liberables pour systemes de delivrance d'acides nucleiques |
| US20130030359A1 (en) * | 2010-01-22 | 2013-01-31 | Ascendis Pharma A/S | Dipeptide-based prodrug linkers for aromatic amine-containing drugs |
| US20130018010A1 (en) * | 2010-04-16 | 2013-01-17 | Enzon Pharmaceuticals, Inc. | Polymeric conjugates of adenine nucleoside analogs |
| WO2011155501A1 (fr) | 2010-06-11 | 2011-12-15 | 独立行政法人科学技術振興機構 | Particules multimères pharmaceutiques et leur procédé de fabrication |
| US9028880B2 (en) * | 2010-11-30 | 2015-05-12 | The Board Of Trustees Of The University Of Illinois | Silica nanoparticle agent conjugates |
| CN103045720B (zh) * | 2011-10-17 | 2014-08-20 | 格诺思博生物科技(上海)有限公司 | 检测病源细胞的靶向性分子及其应用 |
| IN2014MN01819A (fr) | 2012-03-05 | 2015-07-03 | Univ Ramot | |
| CN102746316B (zh) * | 2012-06-26 | 2015-04-15 | 济南精合医药科技有限公司 | 用于抗肿瘤药物的间硝基芳甲氧基喜树碱缺氧激活前药 |
| CN102731518B (zh) * | 2012-06-26 | 2014-12-03 | 济南精合医药科技有限公司 | 用于抗肿瘤药物的邻硝基芳甲氧基喜树碱缺氧激活前药 |
| KR102320753B1 (ko) * | 2013-10-04 | 2021-11-02 | 프로린크스 엘엘시 | Sn-38 서방성 컨쥬게이트 |
| CN105764503A (zh) | 2013-10-15 | 2016-07-13 | 西雅图基因公司 | 用于改善配体-药物偶联物药代动力学的peg化的药物-接头 |
| GB201414098D0 (en) * | 2014-08-08 | 2014-09-24 | Illumina Cambridge Ltd | Modified nucleotide linkers |
| JP2017534612A (ja) | 2014-10-14 | 2017-11-24 | ポリセリックス・リミテッド | Pegの部分を含めた脱離基を含む試薬を用いるペプチド又はタンパク質のコンジュゲーションのための方法 |
| CN107073131B (zh) * | 2014-10-24 | 2021-05-25 | 宝力泰锐克斯有限公司 | 缀合物和缀合试剂 |
| JP6570034B2 (ja) * | 2014-11-26 | 2019-09-04 | 日本化薬株式会社 | 新規なグルタミン酸誘導体およびその用途 |
| CN105641708A (zh) * | 2014-12-04 | 2016-06-08 | 上海中医药大学附属普陀医院 | 多肽修饰的聚(甲基丙烯酸寡聚乙二醇酯-co-蟾毒灵)纳米制剂及其制备方法 |
| US11571480B2 (en) * | 2015-08-11 | 2023-02-07 | Coherent Biopharma I, Limited | Multi-ligand drug conjugates and uses thereof |
| CN107029242A (zh) | 2015-11-03 | 2017-08-11 | 财团法人工业技术研究院 | 抗体药物复合物及其制造方法 |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| KR20180090290A (ko) | 2015-12-04 | 2018-08-10 | 시애틀 지네틱스, 인크. | 사차화 튜불리신 화합물들의 컨쥬게이트들 |
| EP3433278A4 (fr) | 2016-03-25 | 2019-11-06 | Seattle Genetics, Inc. | Procédé de préparation de lieurs de médicaments pégylés et leurs intermédiaires |
| CN107375288B (zh) * | 2016-05-16 | 2019-08-23 | 博瑞生物医药(苏州)股份有限公司 | 多臂的聚合靶向抗癌偶联物 |
| CN106265683A (zh) * | 2016-09-14 | 2017-01-04 | 江南大学 | 一种具有穿膜靶向特性的致病菌生物膜新型抑制剂的制备方法 |
| US11135307B2 (en) * | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
| US11730822B2 (en) | 2017-03-24 | 2023-08-22 | Seagen Inc. | Process for the preparation of glucuronide drug-linkers and intermediates thereof |
| EP3613792B1 (fr) * | 2017-04-21 | 2021-02-24 | Bright Gene Bio-Medical Technology Co., Ltd. | Conjugué anticancéreux ciblé à bras multiples |
| JP7231147B2 (ja) * | 2017-06-29 | 2023-03-01 | 国立大学法人東海国立大学機構 | Rna導入試薬及びその利用 |
| CA3082165A1 (fr) * | 2017-11-30 | 2019-06-06 | Seattle Genetics, Inc. | Procede pour la preparation de composes coupleurs de medicaments |
| IL319417A (en) | 2018-01-08 | 2025-05-01 | Regeneron Pharma | Steroids and their anti-inflammatory properties |
| EP3737383A4 (fr) | 2018-01-12 | 2021-12-15 | Prolynx LLC | Traitement synergique du cancer |
| KR102141124B1 (ko) * | 2018-01-30 | 2020-08-04 | (주)바이오니아 | 이중 가닥 miRNA를 포함하는 이중나선 올리고뉴클레오타이드 구조체 및 이의 용도 |
| US20220047713A1 (en) * | 2018-04-02 | 2022-02-17 | Jenkem Technology Co., Ltd. (Beijing) | Cell-penetrating peptide-multiarm pol yethylene glycol-drug conjugate having targeting property and application thereof |
| KR20210084546A (ko) * | 2018-10-29 | 2021-07-07 | 메르사나 테라퓨틱스, 인코포레이티드 | 펩티드 함유 링커를 갖는 시스테인 조작된 항체-약물 접합체 |
| CN116920115A (zh) * | 2018-12-17 | 2023-10-24 | 荣昌生物制药(烟台)股份有限公司 | 一种用于抗体药物偶联物的连接子及其应用 |
| US11739166B2 (en) | 2020-07-02 | 2023-08-29 | Davol Inc. | Reactive polysaccharide-based hemostatic agent |
| US12161777B2 (en) | 2020-07-02 | 2024-12-10 | Davol Inc. | Flowable hemostatic suspension |
| US20240115713A1 (en) * | 2020-07-28 | 2024-04-11 | Chongqing Upgra Biotechnology Co., Ltd. | Polyethylene glycol conjugate drug, and preparation method therefor and use thereof |
| WO2022022354A1 (fr) * | 2020-07-28 | 2022-02-03 | 重庆阿普格雷生物科技有限公司 | Agent synergiste de médicament conjugué au polyéthylène glycol, son procédé de préparation et son utilisation |
| EP4267210A1 (fr) | 2020-12-28 | 2023-11-01 | Davol Inc. | Matériaux hémostatiques pulvérulents secs réactifs comprenant une protéine et un agent de réticulation à base de polyéthylène glycol modifié multifonctionnalisé |
| CN115209922A (zh) * | 2021-01-28 | 2022-10-18 | 南京桦冠生物技术有限公司 | 缀合物及其用途 |
| WO2023138682A1 (fr) * | 2022-01-24 | 2023-07-27 | 北京桦冠生物技术有限公司 | Conjugué et son utilisation |
| WO2025139993A1 (fr) * | 2023-12-29 | 2025-07-03 | 四川科伦博泰生物医药股份有限公司 | Conjugué anticorps-médicament, composition pharmaceutique associée et utilisation associée |
| CN118994301B (zh) * | 2024-08-13 | 2025-04-01 | 广州医科大学 | 一种中药小分子偶联化合物及其在耐药性肿瘤中的应用 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2626654B2 (ja) * | 1990-03-31 | 1997-07-02 | 科学技術振興事業団 | 標的指向性高分子医薬化合物及びその中間体 |
| US5643575A (en) * | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US7011812B1 (en) * | 1996-05-03 | 2006-03-14 | Immunomedics, Inc. | Targeted combination immunotherapy of cancer and infectious diseases |
| US6331289B1 (en) * | 1996-10-28 | 2001-12-18 | Nycomed Imaging As | Targeted diagnostic/therapeutic agents having more than one different vectors |
| AU7266898A (en) * | 1997-04-30 | 1998-11-24 | Enzon, Inc. | Single-chain antigen-binding proteins capable of glycosylation, production and uses thereof |
| US5965119A (en) * | 1997-12-30 | 1999-10-12 | Enzon, Inc. | Trialkyl-lock-facilitated polymeric prodrugs of amino-containing bioactive agents |
| US7060479B2 (en) * | 1999-12-08 | 2006-06-13 | Serono Genetics Institute, S.A. | Full-length human cDNAs encoding potentially secreted proteins |
| US6251382B1 (en) * | 1998-04-17 | 2001-06-26 | Enzon, Inc. | Biodegradable high molecular weight polymeric linkers and their conjugates |
| US6153655A (en) * | 1998-04-17 | 2000-11-28 | Enzon, Inc. | Terminally-branched polymeric linkers and polymeric conjugates containing the same |
| US6214330B1 (en) * | 1998-07-13 | 2001-04-10 | Enzon, Inc. | Coumarin and related aromatic-based polymeric prodrugs |
| US6777387B2 (en) * | 2000-03-31 | 2004-08-17 | Enzon Pharmaceuticals, Inc. | Terminally-branched polymeric linkers containing extension moieties and polymeric conjugates containing the same |
| MXPA03007392A (es) * | 2001-02-20 | 2003-12-04 | Enzon Inc | Enlazantes polimericos ramificados terminalmente y conjugados polimericos que contienen los mismos. |
| US7091186B2 (en) * | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| CN100475269C (zh) * | 2002-03-05 | 2009-04-08 | 北京键凯科技有限公司 | 亲水性聚合物-谷氨酸寡肽与药物分子的结合物、包含该结合物的组合物及用途 |
| ITMI20020951A1 (it) * | 2002-05-06 | 2003-11-06 | Univ Degli Studi Trieste | Derivati multifunzionali del polietilenglicole loro preparazione ed impiego |
| US7122189B2 (en) * | 2002-08-13 | 2006-10-17 | Enzon, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| US7595304B2 (en) * | 2003-04-13 | 2009-09-29 | Enzon Pharmaceuticals, Inc. | Polymeric oligonucleotide prodrugs |
| US20040228831A1 (en) * | 2003-05-15 | 2004-11-18 | Belinka Benjamin A. | Polymeric conjugates for tissue activated drug delivery |
| GB0411186D0 (en) * | 2004-05-19 | 2004-06-23 | Celltech R&D Ltd | Biological products |
| US7365127B2 (en) * | 2005-02-04 | 2008-04-29 | Enzon Pharmaceuticals, Inc. | Process for the preparation of polymer conjugates |
| WO2006088248A1 (fr) * | 2005-02-18 | 2006-08-24 | Nof Corporation | Derive de polyoxyalkylene |
-
2007
- 2007-09-15 WO PCT/US2007/078600 patent/WO2008034124A2/fr not_active Ceased
- 2007-09-15 RU RU2009114154/15A patent/RU2009114154A/ru not_active Application Discontinuation
- 2007-09-15 MX MX2009002855A patent/MX2009002855A/es unknown
- 2007-09-15 BR BRPI0716812-8A patent/BRPI0716812A2/pt not_active Application Discontinuation
- 2007-09-15 CN CNA2007800425870A patent/CN101541332A/zh active Pending
- 2007-09-15 KR KR1020097005134A patent/KR20090057383A/ko not_active Withdrawn
- 2007-09-15 EP EP07842578.2A patent/EP2073820A4/fr not_active Withdrawn
- 2007-09-15 AU AU2007296056A patent/AU2007296056B2/en not_active Expired - Fee Related
- 2007-09-15 CA CA002662981A patent/CA2662981A1/fr not_active Abandoned
- 2007-09-15 JP JP2009528519A patent/JP2010503708A/ja active Pending
-
2009
- 2009-03-10 IL IL197517A patent/IL197517A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2009114154A (ru) | 2010-10-20 |
| IL197517A0 (en) | 2009-12-24 |
| AU2007296056B2 (en) | 2012-09-13 |
| WO2008034124A2 (fr) | 2008-03-20 |
| KR20090057383A (ko) | 2009-06-05 |
| AU2007296056A1 (en) | 2008-03-20 |
| EP2073820A4 (fr) | 2014-07-16 |
| MX2009002855A (es) | 2009-03-30 |
| JP2010503708A (ja) | 2010-02-04 |
| EP2073820A2 (fr) | 2009-07-01 |
| CA2662981A1 (fr) | 2008-03-20 |
| WO2008034124A3 (fr) | 2008-08-07 |
| CN101541332A (zh) | 2009-09-23 |
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