KR20120080611A - 효능 있는 접합체 및 친수성 링커 - Google Patents

효능 있는 접합체 및 친수성 링커 Download PDF

Info

Publication number
KR20120080611A
KR20120080611A KR1020127010084A KR20127010084A KR20120080611A KR 20120080611 A KR20120080611 A KR 20120080611A KR 1020127010084 A KR1020127010084 A KR 1020127010084A KR 20127010084 A KR20127010084 A KR 20127010084A KR 20120080611 A KR20120080611 A KR 20120080611A
Authority
KR
South Korea
Prior art keywords
cell
antibody
bond
maytansinoid
formula
Prior art date
Application number
KR1020127010084A
Other languages
English (en)
Korean (ko)
Inventor
라제바 싱
샤론 디. 윌헬름
라비 브이.제이. 체리
Original Assignee
이뮤노젠 아이엔씨
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 이뮤노젠 아이엔씨 filed Critical 이뮤노젠 아이엔씨
Publication of KR20120080611A publication Critical patent/KR20120080611A/ko

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Transplantation (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
KR1020127010084A 2009-10-06 2009-10-06 효능 있는 접합체 및 친수성 링커 KR20120080611A (ko)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2009/059620 WO2010126551A1 (en) 2009-04-30 2009-10-06 Potent conjugates and hydrophilic linkers

Publications (1)

Publication Number Publication Date
KR20120080611A true KR20120080611A (ko) 2012-07-17

Family

ID=46467238

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020127010084A KR20120080611A (ko) 2009-10-06 2009-10-06 효능 있는 접합체 및 친수성 링커

Country Status (7)

Country Link
EP (1) EP2486023A4 (ja)
JP (1) JP2013506709A (ja)
KR (1) KR20120080611A (ja)
CN (1) CN102596922A (ja)
IL (1) IL219020A0 (ja)
IN (1) IN2012DN02780A (ja)
WO (1) WO2010126551A1 (ja)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101984053B1 (ko) 2009-02-05 2019-05-30 이뮤노젠 아이엔씨 신규한 벤조디아제핀 유도체
RS59389B1 (sr) 2010-03-12 2019-11-29 Debiopharm Int Sa Cd37-vezujući molekuli i njihovi imunokonjugati
CA2816426A1 (en) * 2010-11-17 2012-06-07 Genentech, Inc. Alaninyl maytansinol antibody conjugates
WO2012086857A1 (ko) * 2010-12-21 2012-06-28 (주)파낙스이엠 광역학 진단 또는 치료를 위한 결합체 및 이의 제조방법
WO2012112708A1 (en) 2011-02-15 2012-08-23 Immunogen, Inc. Cytotoxic benzodiazepine derivatives and methods of preparation
KR20140031883A (ko) * 2011-04-01 2014-03-13 이뮤노젠 아이엔씨 Cd37-결합 분자 및 그의 면역콘주게이트
AU2012340686A1 (en) * 2011-11-21 2014-06-19 Immunogen, Inc. Method of treatment of tumors that are resistant to EGFR therapies by EGFR antibody cytotoxic agent conjugate
US9353150B2 (en) 2012-12-04 2016-05-31 Massachusetts Institute Of Technology Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment
CN103044677A (zh) * 2012-12-28 2013-04-17 上海景宇生物科技有限公司 一种异端基遥爪聚乙二醇及其制备方法
CN103083652B (zh) * 2013-02-06 2016-08-10 中国科学院过程工程研究所 一种以异型双功能试剂为连接桥的脑膜炎多糖结合疫苗及其制备方法
US9415118B2 (en) * 2013-03-13 2016-08-16 Novartis Ag Antibody drug conjugates
US9498532B2 (en) * 2013-03-13 2016-11-22 Novartis Ag Antibody drug conjugates
BR112015022585B1 (pt) 2013-03-15 2023-04-04 Regeneron Pharmaceuticals, Inc Composto, composição farmacêutica, conjugado droga-anticorpo, e, uso dos mesmos
CN103254311B (zh) * 2013-05-09 2015-05-13 齐鲁制药有限公司 一种制备抗体-美登素类生物碱药物偶联物的方法
US10208125B2 (en) 2013-07-15 2019-02-19 University of Pittsburgh—of the Commonwealth System of Higher Education Anti-mucin 1 binding agents and uses thereof
MX2016001541A (es) * 2013-08-02 2016-08-18 Sanofi Sa Uso de anticuerpo inmunoconjugado anti-muc1 maitansinoide para el tratamiento de tumores solidos.
AU2014311361B2 (en) 2013-08-26 2018-11-29 Regeneron Pharmaceuticals, Inc. Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses
CN103483357B (zh) * 2013-10-12 2015-11-18 齐鲁制药有限公司 一种抗体-美登素偶联物的中间体新晶型及其制备方法
WO2015057699A2 (en) 2013-10-15 2015-04-23 Seattle Genetics, Inc. Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
WO2015113476A1 (zh) * 2014-01-29 2015-08-06 上海恒瑞医药有限公司 配体-细胞毒性药物偶联物、其制备方法及其应用
GB201402009D0 (en) * 2014-02-06 2014-03-26 Oncomatryx Biopharma S L Antibody-drug conjugates and immunotoxins
US10550190B2 (en) * 2014-04-04 2020-02-04 Merck Sharp & Dohme Corp. Phosphate based linkers for intracellular delivery of drug conjugates
KR20170040249A (ko) * 2014-08-12 2017-04-12 노파르티스 아게 항-cdh6 항체 약물 접합체
PT3271329T (pt) 2015-03-19 2021-10-25 Hangzhou Dac Biotech Co Ltd Novos ligantes hidrofílicos e conjugados ligando-fármaco dos mesmos
WO2016167798A1 (en) * 2015-04-17 2016-10-20 Northwestern University Phosphatidylethanolamine-specific probes
CA2986437A1 (en) 2015-06-08 2016-12-15 Debiopharm International, S.A. Anti-cd37 immunoconjugate and anti-cd20 antibody combinations
CN113087763A (zh) 2015-07-21 2021-07-09 伊缪诺金公司 制备细胞毒性苯并二氮杂䓬衍生物的方法
WO2017040247A1 (en) 2015-08-28 2017-03-09 Immunogen, Inc. Antibodies and assays for detection of cd37
CA3006000A1 (en) 2015-12-04 2017-06-08 Seattle Genetics, Inc. Conjugates of quaternized tubulysin compounds
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
CN105435241A (zh) * 2015-12-10 2016-03-30 浙江大学 一种iRGD-抗癌药物偶联物及其制备方法和应用
MA43094B1 (fr) 2016-01-25 2020-10-28 Regeneron Pharma Dérivés de maytansinoïde, leurs conjugués, et procédés d'utilisation
MA43835A (fr) 2016-03-25 2018-11-28 Seattle Genetics Inc Procédé de préparation de lieurs de médicaments pégylés et leurs intermédiaires
US10918627B2 (en) 2016-05-11 2021-02-16 Massachusetts Institute Of Technology Convergent and enantioselective total synthesis of Communesin analogs
GB201615725D0 (en) 2016-09-15 2016-11-02 Polytherics Ltd Novel cytotoxic agents and conjugates thereof
EA201990781A9 (ru) * 2016-09-23 2019-11-27 Анти-steap2 антитела, конъюгаты антитело-лекарственное средство и биспецифические антигенсвязывающие молекулы, которые связывают steap2 и cd3, и их применение
EP3535297B1 (en) 2016-11-02 2022-08-10 Debiopharm International, S.A. Methods for improving anti-cd37 immunoconjugate therapy
AU2018237683A1 (en) 2017-03-24 2019-10-31 Seagen Inc. Process for the preparation of glucuronide drug-linkers and intermediates thereof
US11932650B2 (en) 2017-05-11 2024-03-19 Massachusetts Institute Of Technology Potent agelastatin derivatives as modulators for cancer invasion and metastasis
US10646585B2 (en) 2017-09-15 2020-05-12 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and ligand-drug conjugates thereof
US10640508B2 (en) 2017-10-13 2020-05-05 Massachusetts Institute Of Technology Diazene directed modular synthesis of compounds with quaternary carbon centers
BR112020006901A2 (pt) * 2017-11-01 2020-10-13 Arrowhead Pharmaceuticals, Inc. ligantes de integrina e usos dos mesmos
AU2019294510A1 (en) * 2018-06-26 2021-01-21 Immunogen, Inc. Immunoconjugates targeting ADAM9 and methods of use thereof
WO2020247054A1 (en) 2019-06-05 2020-12-10 Massachusetts Institute Of Technology Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof

Family Cites Families (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4307016A (en) 1978-03-24 1981-12-22 Takeda Chemical Industries, Ltd. Demethyl maytansinoids
US4563304A (en) 1981-02-27 1986-01-07 Pharmacia Fine Chemicals Ab Pyridine compounds modifying proteins, polypeptides or polysaccharides
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
PT1696031E (pt) 1991-12-02 2010-06-25 Medical Res Council Produção de auto-anticorpos a partir de reportórios de segmentos de anticorpo e exibidos em fagos
CA2076465C (en) 1992-03-25 2002-11-26 Ravi V. J. Chari Cell binding agent conjugates of analogues and derivatives of cc-1065
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
GB9320575D0 (en) 1993-10-06 1993-11-24 Amp Gmbh Coaxial connector having improved locking mechanism
IL111748A0 (en) 1993-12-03 1995-01-24 Zeneca Ltd Proteins
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
US6355780B1 (en) 1995-02-22 2002-03-12 Yeda Research And Development Co. Ltd. Antibodies to the death domain motifs of regulatory proteins
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US6680311B1 (en) 1996-08-30 2004-01-20 Eli Lilly And Company Cryptophycin compounds
FR2763066B1 (fr) 1997-05-08 2001-01-05 Agency Ind Science Techn Nouveau compose d'ester aromatique et materiau optique non lineaire de second ordre qui en est produit
WO1999006587A2 (en) 1997-08-01 1999-02-11 Morphosys Ag Novel method and phage for the identification of nucleic acid sequences encoding members of a multimeric (poly)peptide complex
US7115396B2 (en) 1998-12-10 2006-10-03 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
US7303749B1 (en) 1999-10-01 2007-12-04 Immunogen Inc. Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
AU765588C (en) 1999-11-24 2004-12-16 Immunogen, Inc. Cytotoxic agents comprising taxanes and their therapeutic use
JP2003531821A (ja) 1999-12-29 2003-10-28 イムノージェン インコーポレーテッド 改変型ドキソルビシンおよびダウノルビシンを含む細胞傷害性薬剤ならびにその治療上の使用
US6956036B1 (en) 2000-03-17 2005-10-18 Alcon, Inc. 6-hydroxy-indazole derivatives for treating glaucoma
US6596503B1 (en) 2000-08-18 2003-07-22 East Carolina University Monoclonal antibody DS6, tumor-associated antigen CA6, and methods of use thereof
US6333410B1 (en) 2000-08-18 2001-12-25 Immunogen, Inc. Process for the preparation and purification of thiol-containing maytansinoids
US6747021B2 (en) 2000-10-02 2004-06-08 Eli Lilly And Company Cryptophycin compound
WO2002030356A2 (en) 2000-10-13 2002-04-18 The University Of Mississipi Synthesis of epothilones and relates analogs
US7767802B2 (en) 2001-01-09 2010-08-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
US6441163B1 (en) 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US6560782B2 (en) 2001-06-11 2003-05-13 Playtex Products, Inc. Antimicrobial glove and method of making same
US20060159838A1 (en) 2005-01-14 2006-07-20 Cabot Corporation Controlling ink migration during the formation of printable electronic features
US6716821B2 (en) * 2001-12-21 2004-04-06 Immunogen Inc. Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same
DE10202419A1 (de) 2002-01-22 2003-08-07 Ribopharma Ag Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
US6534660B1 (en) 2002-04-05 2003-03-18 Immunogen, Inc. CC-1065 analog synthesis
US6596757B1 (en) 2002-05-14 2003-07-22 Immunogen Inc. Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use
AU2003253048A1 (en) 2002-07-09 2004-01-23 Morphochem Aktiengellschaft Fur Kombinatorische Chemie Tubulysin conjugates
ES2556641T3 (es) 2002-07-31 2016-01-19 Seattle Genetics, Inc. Conjugados de fármacos y su uso para tratar cáncer, una enfermedad autoinmune o una enfermedad infecciosa
DE60336149D1 (de) 2002-08-16 2011-04-07 Immunogen Inc Vernetzer mit hoher reaktivität und löslichkeit und ihre verwendung bei der herstellung von konjugaten für die gezielte abgabe von kleinmolekularen arzneimitteln
ES2539627T3 (es) 2002-11-07 2015-07-02 Immunogen, Inc. Anticuerpos anti-CD33 y método para el tratamiento de leucemia mieloide aguda usando los mismos
EP1620544B1 (en) 2003-04-17 2018-09-19 Alnylam Pharmaceuticals Inc. MODIFIED iRNA AGENTS
US8088387B2 (en) * 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
SI1651162T1 (sl) * 2003-05-20 2016-02-29 Immunogen, Inc. Izboljšani citotoksični agenti, ki vsebujejo nove majtanzinoide
US7276497B2 (en) * 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
US7595306B2 (en) 2003-06-09 2009-09-29 Alnylam Pharmaceuticals Inc Method of treating neurodegenerative disease
EP1633770B1 (en) 2003-06-13 2015-04-29 Alnylam Europe AG Double-stranded ribonucleic acid with increased effectiveness in an organism
JP4584987B2 (ja) 2004-04-30 2010-11-24 アルニラム ファーマスーティカルズ インコーポレイテッド Ｃ５修飾ピリミジンを含むオリゴヌクレオチド
AU2005249490B2 (en) * 2004-06-01 2010-07-29 Genentech, Inc. Antibody drug conjugates and methods
US7615618B2 (en) 2004-06-30 2009-11-10 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a non-phosphate backbone linkage
WO2006093526A2 (en) 2004-07-21 2006-09-08 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a modified or non-natural nucleobase
JP4193771B2 (ja) 2004-07-27 2008-12-10 セイコーエプソン株式会社 階調電圧発生回路及び駆動回路
US7632932B2 (en) 2004-08-04 2009-12-15 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
AU2004224925C1 (en) 2004-08-30 2011-07-21 Biotest Ag Immunoconjugates targeting syndecan-1 expressing cells and use thereof
PL1791565T3 (pl) * 2004-09-23 2016-10-31 Modyfikowane cysteiną przeciwciała i koniugaty
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
PL1819359T3 (pl) 2004-12-09 2015-08-31 Janssen Biotech Inc Immunokoniugaty skierowane przeciw integrynie, metody ich wytwarzania oraz ich zastosowanie
US7301019B2 (en) 2005-01-21 2007-11-27 Immunogen, Inc. Method for the preparation of maytansinoid esters
US20070213292A1 (en) 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
WO2007062466A1 (en) 2005-11-29 2007-06-07 The University Of Sydney Demibodies: dimerisation-activated therapeutic agents
US7897568B2 (en) 2006-03-03 2011-03-01 Vinay K. Singh Compositions for treatment of cancer
MX2008015132A (es) * 2006-05-30 2008-12-10 Genentech Inc Anticuerpos e inmunoconjugados y sus usos.
AU2007262666B2 (en) 2006-06-22 2013-09-12 Walter And Eliza Hall Institute Of Medical Research Structure of the insulin receptor ectodomain
JP2010533495A (ja) * 2007-07-16 2010-10-28 ジェネンテック， インコーポレイテッド ヒト化ＣＤ７９ｂ抗体およびイムノコンジュゲートならびにそれらの使用
KR20100137585A (ko) * 2008-04-30 2010-12-30 이뮤노젠 아이엔씨 강력한 복합체 및 친수성 링커

Also Published As

Publication number Publication date
CN102596922A (zh) 2012-07-18
WO2010126551A1 (en) 2010-11-04
EP2486023A4 (en) 2014-05-07
IL219020A0 (en) 2012-06-28
IN2012DN02780A (ja) 2015-09-18
JP2013506709A (ja) 2013-02-28
EP2486023A1 (en) 2012-08-15

Similar Documents

Publication Publication Date Title
JP5980989B2 (ja) 有効なコンジュゲートおよび親水性リンカー
KR20120080611A (ko) 효능 있는 접합체 및 친수성 링커
CN111087471B (zh) Trop2阳性疾病治疗的化合物及方法
JP2013506709A5 (ja)
KR101343676B1 (ko) 메이탠시노이드 화합물
TWI757759B (zh) 細胞毒性苯并二氮呯衍生物
US9737616B2 (en) Compounds and methods for the treatment of ERB B2/NEU positive diseases
US20130323268A1 (en) Cytotoxic agents comprising new ansamitocin derivatives
WO2014094355A1 (en) Compounds and methods for the treatment of egfr positive diseases
US20140178411A1 (en) Compounds and methods for the treatment of cd20 positive diseases
KR20140107418A (ko) 접합체 안정성을 개선하기 위한 n-하이드록시숙신이미드의 용도

Legal Events

Date Code Title Description
WITN Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid