DE10254439A1 - Tubulysine, Herstellungsverfahren und Tubulysin-Mittel - Google Patents

Tubulysine, Herstellungsverfahren und Tubulysin-Mittel Download PDF

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Publication number
DE10254439A1
DE10254439A1 DE10254439A DE10254439A DE10254439A1 DE 10254439 A1 DE10254439 A1 DE 10254439A1 DE 10254439 A DE10254439 A DE 10254439A DE 10254439 A DE10254439 A DE 10254439A DE 10254439 A1 DE10254439 A1 DE 10254439A1
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DE
Germany
Prior art keywords
alkyl
compound
alkenyl
general formula
type
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
DE10254439A
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German (de)
English (en)
Inventor
Gerhard Hoefle
Nicole Glaser
Heinrich Steinmetz
Thomas Leibold
Florenz Sasse
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Helmholtz Zentrum Fuer Infektionsforschung De GmbH
Original Assignee
Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Helmholtz Zentrum fuer Infektionsforschung HZI GmbH filed Critical Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
Priority to DE10254439A priority Critical patent/DE10254439A1/de
Priority to JP2004552485A priority patent/JP4620467B2/ja
Priority to US10/535,630 priority patent/US7754885B2/en
Priority to EP08018687A priority patent/EP2028185A1/de
Priority to AT03775204T priority patent/ATE412659T1/de
Priority to EP03775204A priority patent/EP1562979B1/de
Priority to AU2003283282A priority patent/AU2003283282A1/en
Priority to PCT/EP2003/011603 priority patent/WO2004046170A2/de
Priority to DE50310721T priority patent/DE50310721D1/de
Publication of DE10254439A1 publication Critical patent/DE10254439A1/de
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Plural Heterocyclic Compounds (AREA)
DE10254439A 2002-11-21 2002-11-21 Tubulysine, Herstellungsverfahren und Tubulysin-Mittel Withdrawn DE10254439A1 (de)

Priority Applications (9)

Application Number Priority Date Filing Date Title
DE10254439A DE10254439A1 (de) 2002-11-21 2002-11-21 Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
JP2004552485A JP4620467B2 (ja) 2002-11-21 2003-10-20 チューブライシン、その製造方法、及び、チューブライシン製剤
US10/535,630 US7754885B2 (en) 2002-11-21 2003-10-20 Tubulysins, method for producing the same and tubulysin preparations
EP08018687A EP2028185A1 (de) 2002-11-21 2003-10-20 Tubulysine und Tubulysin-Mittel
AT03775204T ATE412659T1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin- mittel
EP03775204A EP1562979B1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel
AU2003283282A AU2003283282A1 (en) 2002-11-21 2003-10-20 Tubulysins, method for producing the same and tubulysin preparations
PCT/EP2003/011603 WO2004046170A2 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel
DE50310721T DE50310721D1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE10254439A DE10254439A1 (de) 2002-11-21 2002-11-21 Tubulysine, Herstellungsverfahren und Tubulysin-Mittel

Publications (1)

Publication Number Publication Date
DE10254439A1 true DE10254439A1 (de) 2004-06-03

Family

ID=32240267

Family Applications (2)

Application Number Title Priority Date Filing Date
DE10254439A Withdrawn DE10254439A1 (de) 2002-11-21 2002-11-21 Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
DE50310721T Expired - Lifetime DE50310721D1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel

Family Applications After (1)

Application Number Title Priority Date Filing Date
DE50310721T Expired - Lifetime DE50310721D1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel

Country Status (7)

Country Link
US (1) US7754885B2 (https=)
EP (2) EP2028185A1 (https=)
JP (1) JP4620467B2 (https=)
AT (1) ATE412659T1 (https=)
AU (1) AU2003283282A1 (https=)
DE (2) DE10254439A1 (https=)
WO (1) WO2004046170A2 (https=)

Cited By (9)

* Cited by examiner, † Cited by third party
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EP2409983A1 (en) 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
WO2015127685A1 (en) 2014-02-28 2015-09-03 Hangzhou Dac Biotech Co., Ltd Charged linkers and their uses for conjugation
WO2015151081A2 (en) 2015-07-12 2015-10-08 Suzhou M-Conj Biotech Co., Ltd Bridge linkers for conjugation of a cell-binding molecule
EP3210627A1 (en) 2012-07-12 2017-08-30 Hangzhou Dac Biotech Co., Ltd Conjugates of cell binding molecules with cytotoxic agents
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
US10232051B2 (en) 2015-07-15 2019-03-19 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
WO2021000067A1 (zh) 2019-06-29 2021-01-07 杭州多禧生物科技有限公司 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法
EP3888691A1 (en) 2016-11-14 2021-10-06 Hangzhou Dac Biotech Co., Ltd. Conjugation linkers, cell binding molecule-drug conjugates containing the likers, methods of making and uses such conjugates with the linkers
WO2023078273A1 (en) 2021-11-03 2023-05-11 Hangzhou Dac Biotech Co., Ltd. Specific conjugation for an antibody-drug conjugate

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ATE427948T1 (de) 2001-04-24 2009-04-15 Purdue Research Foundation Folat-mimetika und deren folatrezeptorbindende konjugate
CA2484640C (en) * 2002-05-15 2012-01-17 Endocyte, Inc. Vitamin-mitomycin conjugates
DK1523493T3 (da) * 2002-07-09 2013-12-02 Alexander Doemling Nye tubulysinanaloge
WO2004069159A2 (en) 2003-01-27 2004-08-19 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
CN101098854B (zh) * 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
CN101175757B (zh) * 2005-03-16 2012-11-14 恩多塞特公司 蝶酸及其缀合物的合成和纯化
EP2382995A3 (en) * 2005-08-19 2013-09-25 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
BRPI0615354A2 (pt) * 2005-08-19 2011-05-17 Endocyte, Inc. conjugado de liberação de fármaco de ligação de receptor, composição farmacêutica que o compreende, bem como seu uso
US20100104626A1 (en) * 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
AU2008224988A1 (en) * 2007-03-14 2008-09-18 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
WO2008138561A1 (en) * 2007-05-10 2008-11-20 R & D Biopharmaceuticals Gmbh Tubulysine derivatives
CN101784565B (zh) 2007-06-25 2014-12-10 恩多塞特公司 含有亲水性间隔区接头的共轭物
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
EP2181101A2 (en) * 2007-07-20 2010-05-05 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysin d analogues
US8476451B2 (en) * 2007-07-20 2013-07-02 The Regents Of The University Of California Tubulysin D analogues
CN101909441B (zh) * 2007-10-25 2015-05-13 恩多塞特公司 微管蛋白抑制剂及其制备方法
EP2174947A1 (en) * 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
IT1394860B1 (it) * 2009-07-22 2012-07-20 Kemotech S R L Composti farmaceutici
US8394922B2 (en) 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
JP2013535220A (ja) 2010-08-06 2013-09-12 エンドサイト，インコーポレイテッド ツブリシンを調製するためのプロセス
WO2012171020A1 (en) 2011-06-10 2012-12-13 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
RU2014124984A (ru) * 2011-12-05 2016-01-27 Идженика Биотерапьютикс, Инк. Конъюгаты антитело-лекарственное средство и родственные соединения, композиции и способы
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US20140080175A1 (en) 2012-03-29 2014-03-20 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
CN104640572B (zh) 2012-05-15 2018-04-27 索伦托医疗有限公司 药物偶联物，偶联方法，及其用途
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
EP2708243A1 (en) 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
BR112015008365A2 (pt) 2012-10-16 2017-07-04 Endocyte Inc composto da fórmula b-l(d)x, ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto, composição de forma de dosagem unitária ou dose unitária, composição para tratar um câncer em um paciente, e método para tratar um câncer em um paciente
EA201590783A1 (ru) 2012-11-15 2015-11-30 Эндосайт, Инк. Конъюгаты для доставки лекарственных средств и способы лечения заболеваний, вызванных клетками, экспрессирующими psma
CA2892863C (en) 2012-12-10 2022-03-15 Mersana Therapeutics, Inc. Polymeric scaffold based on phf for targeted drug delivery
WO2014093640A1 (en) 2012-12-12 2014-06-19 Mersana Therapeutics,Inc. Hydroxy-polmer-drug-protein conjugates
LT2956173T (lt) 2013-02-14 2017-06-26 Bristol-Myers Squibb Company Tubulizino junginiai, gavimo ir panaudojimo būdai
US20140249315A1 (en) 2013-03-01 2014-09-04 Endocyte, Inc. Processes for preparing tubulysins
US10781259B2 (en) 2013-06-06 2020-09-22 Magenta Therapeutics, Inc. Modified antibodies and related compounds, compositions, and methods of use
NZ758049A (en) 2013-10-15 2024-03-22 Seagen Inc Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
AU2014337317A1 (en) 2013-10-15 2016-09-15 Sorrento Therapeutics Inc. Drug-conjugates with a targeting molecule and two different drugs
WO2015113760A1 (en) * 2014-01-28 2015-08-06 Tube Pharmaceuticals Gmbh Cytotoxic tubulysin compounds for conjugation
SG11201608192SA (en) 2014-04-11 2016-10-28 Medimmune Llc Bispecific her2 antibodies
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
CN112826940A (zh) * 2014-11-11 2021-05-25 杭州多禧生物科技有限公司 细胞毒素分子同细胞结合受体分子的共轭体
EP3250238B1 (en) 2015-01-28 2022-06-01 Sorrento Therapeutics, Inc. Antibody drug conjugates
MY192146A (en) 2015-11-10 2022-08-01 Medimmune Llc Binding molecules specific for asct2 and uses thereof
KR20180090290A (ko) 2015-12-04 2018-08-10 시애틀 지네틱스, 인크. 사차화 튜불리신 화합물들의 컨쥬게이트들
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
CN109843919A (zh) 2016-03-25 2019-06-04 西雅图基因公司 用于制备聚乙二醇化的药物-接头及其中间体的方法
KR102648564B1 (ko) 2017-03-24 2024-03-19 씨젠 인크. 글루쿠로니드 약물-링커의 제조 공정 및 그 중간물
MA51447A (fr) 2017-08-01 2020-06-10 Medimmune Llc Conjugué anticorps monoclonal-médicament dirigé contre bcma
US20220241377A1 (en) 2019-07-24 2022-08-04 Molgenie GmbH Receptor-targeting peptide-drug conjugates
BR112023004415A2 (pt) 2020-09-11 2023-05-09 Medimmune Ltd Moléculas terapêuticas de ligação a b7-h4
GB202117928D0 (en) 2021-12-11 2022-01-26 Cancer Research Tech Ltd Immunotherapy for cancer
EP4489859A1 (en) 2022-03-09 2025-01-15 Astrazeneca AB Binding molecules against fr alpha
CN120936382A (zh) 2023-02-16 2025-11-11 阿斯利康(瑞典)有限公司 采用治疗性结合分子治疗癌症的组合疗法

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DE19638870B4 (de) * 1996-09-23 2009-05-14 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysine, Verfahren zu ihrer Gewinnung und sie enthaltende Mittel
DE10008089A1 (de) * 2000-02-22 2001-10-31 Biotechnolog Forschung Gmbh Syntheseverfahren zur Herstellung von Tubulysinen
DK1523493T3 (da) * 2002-07-09 2013-12-02 Alexander Doemling Nye tubulysinanaloge
US20100047841A1 (en) * 2007-02-27 2010-02-25 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Synthesis of desacetoxytubulysin h and analogs thereof

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012010287A1 (en) 2010-07-19 2012-01-26 Leibniz-Institut Für Pflanzenbiochemie Tubulysin analogues
EP2409983A1 (en) 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
US9371358B2 (en) 2010-07-19 2016-06-21 Leibniz-Institut fur Pflanzenbiochemie Tubulysin analogues
EP3348280A1 (en) 2012-07-12 2018-07-18 Hangzhou Dac Biotech Co., Ltd Conjugates of cell binding molecules with cytotoxic agents
EP3210627A1 (en) 2012-07-12 2017-08-30 Hangzhou Dac Biotech Co., Ltd Conjugates of cell binding molecules with cytotoxic agents
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
US10683314B2 (en) 2014-02-28 2020-06-16 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
US10464955B2 (en) 2014-02-28 2019-11-05 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
WO2015127685A1 (en) 2014-02-28 2015-09-03 Hangzhou Dac Biotech Co., Ltd Charged linkers and their uses for conjugation
US10696699B2 (en) 2014-02-28 2020-06-30 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
US10696700B2 (en) 2014-02-28 2020-06-30 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
WO2015151081A2 (en) 2015-07-12 2015-10-08 Suzhou M-Conj Biotech Co., Ltd Bridge linkers for conjugation of a cell-binding molecule
EP4678240A2 (en) 2015-07-12 2026-01-14 Hangzhou Dac Biotech Co., Ltd. Bridge linkers for conjugation of cell-binding molecules
US10232051B2 (en) 2015-07-15 2019-03-19 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
US10293055B2 (en) 2015-07-15 2019-05-21 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
US10328157B2 (en) 2015-07-15 2019-06-25 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
EP3888691A1 (en) 2016-11-14 2021-10-06 Hangzhou Dac Biotech Co., Ltd. Conjugation linkers, cell binding molecule-drug conjugates containing the likers, methods of making and uses such conjugates with the linkers
WO2021000067A1 (zh) 2019-06-29 2021-01-07 杭州多禧生物科技有限公司 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法
WO2023078273A1 (en) 2021-11-03 2023-05-11 Hangzhou Dac Biotech Co., Ltd. Specific conjugation for an antibody-drug conjugate

Also Published As

Publication number Publication date
ATE412659T1 (de) 2008-11-15
US20060128754A1 (en) 2006-06-15
AU2003283282A1 (en) 2004-06-15
WO2004046170A3 (de) 2004-07-01
WO2004046170A2 (de) 2004-06-03
AU2003283282A8 (en) 2004-06-15
JP2006518704A (ja) 2006-08-17
EP2028185A1 (de) 2009-02-25
EP1562979B1 (de) 2008-10-29
DE50310721D1 (de) 2008-12-11
EP1562979A2 (de) 2005-08-17
JP4620467B2 (ja) 2011-01-26
US7754885B2 (en) 2010-07-13

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Owner name: HELMHOLTZ-ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH, DE

8141 Disposal/no request for examination