CN101678124A - 结合配体连接的微管溶素递药缀合物 - Google Patents

结合配体连接的微管溶素递药缀合物 Download PDF

Info

Publication number
CN101678124A
CN101678124A CN200880015901A CN200880015901A CN101678124A CN 101678124 A CN101678124 A CN 101678124A CN 200880015901 A CN200880015901 A CN 200880015901A CN 200880015901 A CN200880015901 A CN 200880015901A CN 101678124 A CN101678124 A CN 101678124A
Authority
CN
China
Prior art keywords
group
alkyl
drug delivery
aryl
delivery conjugates
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.)
Pending
Application number
CN200880015901A
Other languages
English (en)
Chinese (zh)
Inventor
I·R·弗拉霍夫
C·P·利蒙
王羽
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.)
Endocyte Inc
Original Assignee
Endocyte Inc
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 Endocyte Inc filed Critical Endocyte Inc
Publication of CN101678124A publication Critical patent/CN101678124A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • 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
    • A61K47/54—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 compound
    • A61K47/55—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 compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • 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
    • A61K47/54—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 compound
    • A61K47/55—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 compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/551—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 compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN200880015901A 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物 Pending CN101678124A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US89490107P 2007-03-14 2007-03-14
US60/894,901 2007-03-14
US91155107P 2007-04-13 2007-04-13
US60/911,551 2007-04-13
PCT/US2008/056824 WO2008112873A2 (en) 2007-03-14 2008-03-13 Binding ligand linked drug delivery conjugates of tubulysins

Related Child Applications (2)

Application Number Title Priority Date Filing Date
CN201410195784.8A Division CN104127878A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物
CN201410195870.9A Division CN103948937A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物

Publications (1)

Publication Number Publication Date
CN101678124A true CN101678124A (zh) 2010-03-24

Family

ID=39588060

Family Applications (3)

Application Number Title Priority Date Filing Date
CN200880015901A Pending CN101678124A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物
CN201410195784.8A Pending CN104127878A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物
CN201410195870.9A Pending CN103948937A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物

Family Applications After (2)

Application Number Title Priority Date Filing Date
CN201410195784.8A Pending CN104127878A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物
CN201410195870.9A Pending CN103948937A (zh) 2007-03-14 2008-03-13 结合配体连接的微管溶素递药缀合物

Country Status (9)

Country Link
US (3) US9555139B2 (enExample)
EP (3) EP2481427A1 (enExample)
JP (2) JP5829793B2 (enExample)
CN (3) CN101678124A (enExample)
AU (1) AU2008224988A1 (enExample)
CA (1) CA2680535C (enExample)
IL (1) IL200857A (enExample)
NZ (2) NZ599239A (enExample)
WO (1) WO2008112873A2 (enExample)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014009774A1 (en) * 2012-07-12 2014-01-16 Hangzhou Dac Biotech Co., Ltd Conjugates of cell binding molecules with cytotoxic agents
CN104640572A (zh) * 2012-05-15 2015-05-20 索伦托医疗有限公司(美国) 药物偶联物,偶联方法,及其用途
CN105641707A (zh) * 2014-11-11 2016-06-08 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
CN108042811A (zh) * 2012-11-15 2018-05-18 恩多塞特公司 用于治疗由psma表达细胞引起的疾病的共轭物
CN109316605A (zh) * 2014-01-20 2019-02-12 博瑞生物医药（苏州）股份有限公司 叶酸受体结合配体-药物偶联物
WO2019127607A1 (en) * 2017-12-31 2019-07-04 Hangzhou Dac Biotech Co. Ltd A conjugate of a tubulysin analog with branched linkers
CN110234357A (zh) * 2016-11-23 2019-09-13 梅尔莎纳医疗公司 用于抗体-药物缀合物的含肽接头
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1389209B1 (en) * 2001-04-24 2009-04-08 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
AR042942A1 (es) * 2003-01-27 2005-07-06 Endocyte Inc Conjugados de administracion de drogas de union de receptores de vitaminas
DE602004026897D1 (de) 2003-10-14 2010-06-10 Baxter Healthcare Sa Vkorc1 (vitamin k epoxide recycling polypeptide), ein therapeutisches ziel für coumarin und deren derivate
EP1789391B1 (en) 2004-07-23 2017-06-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
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
WO2007022493A2 (en) * 2005-08-19 2007-02-22 Endocyte, Inc. Ligand conjugates of vinca alkaloids, analogs, and derivatives
CN103893778A (zh) * 2005-08-19 2014-07-02 恩多塞特公司 多药物配体缀合物
WO2008101231A2 (en) 2007-02-16 2008-08-21 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
JP5829793B2 (ja) 2007-03-14 2015-12-09 エンドサイト・インコーポレイテッドＥｎｄｏｃｙｔｅ， Ｉｎｃ． 結合性リガンドが結合したツブリシンの薬剤送達結合体
WO2011079227A1 (en) * 2009-12-23 2011-06-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
WO2009002993A1 (en) 2007-06-25 2008-12-31 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
PT2187965T (pt) 2007-08-17 2020-01-17 Purdue Research Foundation Conjugados ligando-ligante de ligação a psma e métodos para utilização
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
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
WO2011069116A1 (en) * 2009-12-04 2011-06-09 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
TWI796132B (zh) * 2010-02-24 2023-03-11 美商免疫遺傳股份有限公司 葉酸受體１抗體類和免疫共軛物類及彼等之用途
US9951324B2 (en) 2010-02-25 2018-04-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
EP2409983A1 (en) * 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
MX2013001402A (es) 2010-08-06 2013-08-29 Endocyte Inc Proceso para preparar tubulisinas.
RU2617402C2 (ru) 2011-06-10 2017-04-25 Мерсана Терапьютикс, Инк. Конъюгаты белок-полимер-лекарственное средство
WO2013126797A1 (en) 2012-02-24 2013-08-29 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
CN104736179B (zh) * 2012-05-07 2017-09-26 日东电工株式会社 具有接头的聚合物缀合物
AU2013263349B2 (en) 2012-05-17 2016-09-08 Extend Biosciences, Inc Carriers for improved drug delivery
EP2708243A1 (en) 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
EP2908818A4 (en) 2012-10-16 2016-07-13 Endocyte Inc CONJUGATES OF DRUG DELIVERY CONTAINING ARTIFICIAL AMINO ACIDS AND METHODS OF USE
JP6133431B2 (ja) 2012-11-24 2017-05-24 ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． 親水性連結体及び薬物分子と細胞結合分子との共役反応における親水性連結体の使用
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
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
JP2016514157A (ja) * 2013-03-14 2016-05-19 アルバニー モレキュラー リサーチ， インコーポレイテッド リガンド−治療薬コンジュゲートおよびケイ素ベースのリンカー
AU2014336638C1 (en) 2013-10-18 2020-09-17 Novartis Ag Labeled inhibitors of prostate specific membrane antigen (PSMA), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
EP4541378A3 (en) 2013-11-14 2025-07-30 Endocyte, Inc. Compounds for positron emission tomography
GB201402009D0 (en) * 2014-02-06 2014-03-26 Oncomatryx Biopharma S L Antibody-drug conjugates and immunotoxins
GB201402006D0 (en) * 2014-02-06 2014-03-26 Oncomatryx Biopharma S L Antibody-drug conjugates and immunotoxins
PT3122757T (pt) 2014-02-28 2023-11-03 Hangzhou Dac Biotech Co Ltd Ligantes carregados e as suas utilizações em conjugação
WO2015183988A1 (en) * 2014-05-28 2015-12-03 Stealth Peptides International, Inc. Therapeutic compositions including therapeutic small molecules and uses thereof
WO2016065042A1 (en) 2014-10-22 2016-04-28 Extend Biosciences, Inc. Therapeutic vitamin d conjugates
US9789197B2 (en) 2014-10-22 2017-10-17 Extend Biosciences, Inc. RNAi vitamin D conjugates
US9616109B2 (en) 2014-10-22 2017-04-11 Extend Biosciences, Inc. Insulin vitamin D conjugates
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
WO2016089879A1 (en) * 2014-12-01 2016-06-09 Endocyte, Inc. Conjugates of garftase inhibitors
US10188759B2 (en) 2015-01-07 2019-01-29 Endocyte, Inc. Conjugates for imaging
AU2015242213A1 (en) 2015-07-12 2018-03-08 Hangzhou Dac Biotech Co., Ltd Bridge linkers for conjugation of cell-binding molecules
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
CN108367043A (zh) * 2015-12-04 2018-08-03 西雅图基因公司 季铵化的微管溶素化合物的缀合物
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
SMT202100416T1 (it) 2016-03-02 2021-09-14 Eisai R&D Man Co Ltd Coniugati anticorpo-farmaco a base di eribulina e metodi di uso
KR20220147720A (ko) 2016-11-14 2022-11-03 항저우 디에이씨 바이오테크 씨오, 엘티디 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용
JP6585650B2 (ja) * 2017-03-23 2019-10-02 ハンヂョウ ディーエイシー バイオテック カンパニー リミテッド 細胞毒性剤と細胞結合受容体との共役体
CN112368024A (zh) 2018-04-17 2021-02-12 恩多塞特公司 治疗癌症的方法
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
TWI753252B (zh) * 2019-05-03 2022-01-21 中國大陸商杭州多禧生物科技有限公司 含支鏈連接體的Ｔｕｂｕｌｙｓｉｎ同系物偶聯物
JP7604397B2 (ja) 2019-05-20 2024-12-23 エンドサイト・インコーポレイテッド Ｐｓｍａコンジュゲートの調製方法
JP6842127B2 (ja) * 2019-05-22 2021-03-17 ハンヂョウ ディーエイシー バイオテック カンパニー リミテッド 細胞毒性剤と細胞結合受容体との共役体
PH12021553156A1 (en) 2019-06-29 2022-07-25 Hangzhou Dac Biotech Co Ltd Conjugates of tubulysin derivatives and cell binding molecules and methods of making
EP3862023A1 (en) 2020-02-05 2021-08-11 Hangzhou DAC Biotech Co, Ltd Conjugates of cell-binding molecules with cytotoxic agents
JP7044419B2 (ja) * 2021-02-04 2022-03-30 ハンヂョウ ディーエイシー バイオテック カンパニー リミテッド 細胞毒性剤と細胞結合受容体との共役体
EP4426727A2 (en) 2021-11-03 2024-09-11 Hangzhou Dac Biotech Co., Ltd. Specific conjugation of an antibody
EP4593867A2 (en) 2022-09-30 2025-08-06 Extend Biosciences, Inc. Long-acting parathyroid hormone

Family Cites Families (217)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2515483A (en) * 1946-08-10 1950-07-18 Merck & Co Inc Diacylated pteroic acid and process for preparing same
US2816110A (en) * 1956-11-23 1957-12-10 Merck & Co Inc Methods for the production of substituted pteridines
US3392173A (en) * 1964-03-09 1968-07-09 Lilly Co Eli Novel acyl derivatives of desacetyl-vincaleukoblastine and processes for their preparation
US3387001A (en) * 1964-10-19 1968-06-04 Lilly Co Eli Novel aminoacyl esters of desacetyl vincaleukoblastine
US3641109A (en) 1968-09-04 1972-02-08 Carl D Emerson Alkyl and aryl esters of polyhalo-dithio alcohols
US3632622A (en) 1969-04-01 1972-01-04 Chevron Res Polyhaloalkylpolythioalkyl sulfite esters
US3618608A (en) 1970-02-16 1971-11-09 Mary E Brink Diaper with fastener
US3617608A (en) 1970-04-15 1971-11-02 Repco Products Corp Underground electrical conductor housing for accommodating a transformer
US4203898A (en) * 1977-08-29 1980-05-20 Eli Lilly And Company Amide derivatives of VLB, leurosidine, leurocristine and related dimeric alkaloids
US4166810A (en) * 1978-04-20 1979-09-04 Eli Lilly And Company Derivatives of 4-desacetyl VLB C-3 carboxyhydrazide
US4337339A (en) * 1979-04-30 1982-06-29 Baker Instruments Corp. Process for preparation of folic acid derivatives
US4639456A (en) 1980-06-10 1987-01-27 Omnichem S.A. Vinblastin-23-oyl amino acid derivatives
US4316885A (en) 1980-08-25 1982-02-23 Ayerst, Mckenna And Harrison, Inc. Acyl derivatives of rapamycin
US4713249A (en) 1981-11-12 1987-12-15 Schroeder Ulf Crystallized carbohydrate matrix for biologically active substances, a process of preparing said matrix, and the use thereof
US5140104A (en) * 1982-03-09 1992-08-18 Cytogen Corporation Amine derivatives of folic acid analogs
DE116208T1 (de) 1982-12-07 1985-02-28 Kyowa Hakko Kogyo Co., Ltd., Tokio/Tokyo Mitomycin-analoge.
EP0124502B1 (fr) 1983-04-29 1991-06-12 OMNICHEM Société anonyme Nouveaux conjugués de la vinblastine et de ses dérivés, procédé pour leur préparation et compositions pharmaceutiques contenant ces conjugués
US4866180A (en) * 1984-02-24 1989-09-12 Bristol-Myers Company Amino disulfide thiol exchange products
GB8413849D0 (en) 1984-05-31 1984-07-04 Amersham Int Plc Nmr contrast agents
JPS60255789A (ja) 1984-06-01 1985-12-17 Kyowa Hakko Kogyo Co Ltd マイトマイシン誘導体，その製造法および抗腫瘍剤
US5266333A (en) 1985-03-06 1993-11-30 American Cyanamid Company Water dispersible and water soluble carbohydrate polymer compositions for parenteral administration of growth hormone
US4650803A (en) 1985-12-06 1987-03-17 University Of Kansas Prodrugs of rapamycin
US4801688A (en) * 1986-05-27 1989-01-31 Eli Lilly And Company Hydrazone immunoglobulin conjugates
IL82579A0 (en) 1986-05-27 1987-11-30 Lilly Co Eli Immunoglobulin conjugates
DE3750846T2 (de) 1986-08-29 1995-05-11 Kyowa Hakko Kogyo Kk Mitomycin-derivate.
US5094849A (en) * 1988-08-08 1992-03-10 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized vinca analogs via simple organic linkers
US5006652A (en) * 1988-08-08 1991-04-09 Eli Lilly And Company Intermediates for antibody-vinca drug conjugates
US5108921A (en) * 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5688488A (en) * 1989-04-03 1997-11-18 Purdue Research Foundation Composition and method for tumor imaging
WO1990012095A1 (en) 1989-04-03 1990-10-18 Purdue Research Foundation Method for enhancing transmembrane transport of exogenous molecules
AU634314B2 (en) 1989-11-13 1993-02-18 Green Cross Corporation, The Chimeric mouse-human a10 antibody with specificity to a human tumor cell antigen
US5627165A (en) 1990-06-13 1997-05-06 Drug Innovation & Design, Inc. Phosphorous prodrugs and therapeutic delivery systems using same
US5998603A (en) * 1994-09-29 1999-12-07 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analogs, and oligomers thereof
DE69132925T2 (de) 1990-08-29 2002-10-10 Centre Hospitalier Regional De Nantes, Nantes An stabile proteinkernstruktur gebundene proteinpolyliganden
US5130307A (en) 1990-09-28 1992-07-14 American Home Products Corporation Aminoesters of rapamycin
US5221670A (en) 1990-09-19 1993-06-22 American Home Products Corporation Rapamycin esters
US5378696A (en) 1990-09-19 1995-01-03 American Home Products Corporation Rapamycin esters
US5233036A (en) 1990-10-16 1993-08-03 American Home Products Corporation Rapamycin alkoxyesters
US5120842A (en) 1991-04-01 1992-06-09 American Home Products Corporation Silyl ethers of rapamycin
US5100883A (en) 1991-04-08 1992-03-31 American Home Products Corporation Fluorinated esters of rapamycin
US5194447A (en) 1992-02-18 1993-03-16 American Home Products Corporation Sulfonylcarbamates of rapamycin
US5118678A (en) 1991-04-17 1992-06-02 American Home Products Corporation Carbamates of rapamycin
US5138051A (en) 1991-08-07 1992-08-11 American Home Products Corporation Rapamycin analogs as immunosuppressants and antifungals
US5118677A (en) 1991-05-20 1992-06-02 American Home Products Corporation Amide esters of rapamycin
US5169851A (en) 1991-08-07 1992-12-08 American Home Products Corporation Rapamycin analog as immunosuppressants and antifungals
US6335434B1 (en) * 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US5151413A (en) 1991-11-06 1992-09-29 American Home Products Corporation Rapamycin acetals as immunosuppressant and antifungal agents
US5159079A (en) * 1991-12-20 1992-10-27 Eli Lilly And Company 2-piperidones as intermediates for 5-deaza-10-oxo- and 5-deaza-10-thio-5,6,7,8-tetrahydrofolic acids
US6004555A (en) * 1992-03-05 1999-12-21 Board Of Regents, The University Of Texas System Methods for the specific coagulation of vasculature
US6022966A (en) 1993-11-22 2000-02-08 Neorx Corporation Pretargeting methods and compounds
US5302584A (en) 1992-10-13 1994-04-12 American Home Products Corporation Carbamates of rapamycin
US5258389A (en) 1992-11-09 1993-11-02 Merck & Co., Inc. O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives
US5260300A (en) 1992-11-19 1993-11-09 American Home Products Corporation Rapamycin carbonate esters as immuno-suppressant agents
US5583020A (en) 1992-11-24 1996-12-10 Ribozyme Pharmaceuticals, Inc. Permeability enhancers for negatively charged polynucleotides
AU686629B2 (en) * 1993-04-23 1998-02-12 Wyeth Rapamycin Conjugates and Antibodies
US7279561B1 (en) 1993-04-23 2007-10-09 Wyeth Anti-rapamycin monoclonal antibodies
US5562907A (en) 1993-05-14 1996-10-08 Arnon; Stephen S. Method to prevent side-effects and insensitivity to the therapeutic uses of toxins
US5391730A (en) 1993-10-08 1995-02-21 American Home Products Corporation Phosphorylcarbamates of rapamycin and oxime derivatives thereof
US5385908A (en) 1993-11-22 1995-01-31 American Home Products Corporation Hindered esters of rapamycin
US5385910A (en) 1993-11-22 1995-01-31 American Home Products Corporation Gem-distributed esters of rapamycin
US5385909A (en) 1993-11-22 1995-01-31 American Home Products Corporation Heterocyclic esters of rapamycin
US5389639A (en) 1993-12-29 1995-02-14 American Home Products Company Amino alkanoic esters of rapamycin
US5417982A (en) 1994-02-17 1995-05-23 Modi; Pankaj Controlled release of drugs or hormones in biodegradable polymer microspheres
IL112873A (en) * 1994-03-08 2005-03-20 Wyeth Corp Rapamycin-fkbp12 binding proteins, their isolation and their use
US6171859B1 (en) * 1994-03-30 2001-01-09 Mitokor Method of targeting conjugate molecules to mitochondria
US5362718A (en) 1994-04-18 1994-11-08 American Home Products Corporation Rapamycin hydroxyesters
US5463048A (en) 1994-06-14 1995-10-31 American Home Products Corporation Rapamycin amidino carbamates
US5491231A (en) 1994-11-28 1996-02-13 American Home Products Corporation Hindered N-oxide esters of rapamycin
US5547668A (en) * 1995-05-05 1996-08-20 The Board Of Trustees Of The University Of Illinois Conjugates of folate anti-effector cell antibodies
AUPN449295A0 (en) 1995-07-28 1995-08-24 Inner And Eastern Health Care Network, The Radioprotectors
US6207157B1 (en) * 1996-04-23 2001-03-27 The United States Of America As Represented By The Department Of Health And Human Services Conjugate vaccine for nontypeable Haemophilus influenzae
US6030941A (en) * 1996-05-01 2000-02-29 Avi Biopharma, Inc. Polymer composition for delivering substances in living organisms
JP2000510119A (ja) * 1996-05-03 2000-08-08 イムノメディクス，インコーポレイテッド ガンに対する標的コンビネーション免疫療法
DE19621133A1 (de) * 1996-05-24 1997-11-27 Boehringer Mannheim Gmbh Bestimmungsverfahren mit oligomerisierten Rezeptoren
WO1998008859A1 (en) 1996-08-27 1998-03-05 University Of Utah Research Foundation Bioconjugates and delivery of bioactive agents
CA2263907A1 (en) 1996-08-30 1998-03-05 Christopher Leighon Jordan Nonclassical pyrrolo[2,3-d]pyrimidine antifolates
EP0926955A4 (en) 1996-09-12 2003-05-07 Merck & Co Inc Conjugates useful in the treatment of prostate cancer
US6056973A (en) * 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
US6071532A (en) * 1996-10-15 2000-06-06 Emory University Synthesis of glycophospholipid and peptide-phospholipid conjugates and uses thereof
US6177404B1 (en) * 1996-10-15 2001-01-23 Merck & Co., Inc. Conjugates useful in the treatment of benign prostatic hyperplasia
WO1999020626A1 (en) 1997-10-17 1999-04-29 Purdue Research Foundation Folic acid derivatives
GB9723669D0 (en) * 1997-11-07 1998-01-07 Univ Aberdeen Skin penetration enhancing components
US6380395B1 (en) * 1998-04-21 2002-04-30 Bristol-Myers Squibb Company 12, 13-cyclopropane epothilone derivatives
US6093382A (en) * 1998-05-16 2000-07-25 Bracco Research Usa Inc. Metal complexes derivatized with folate for use in diagnostic and therapeutic applications
CA2330611A1 (en) 1998-05-22 1999-12-02 The Board Of Trustees Of The Leland Stanford Junior University Bifunctional molecules and therapies based thereon
JP2002532407A (ja) 1998-12-18 2002-10-02 アルザ・コーポレーション 多薬物耐性細胞に対する化合物の投与方法
US6291684B1 (en) * 1999-03-29 2001-09-18 Bristol-Myers Squibb Company Process for the preparation of aziridinyl epothilones from oxiranyl epothilones
US6342244B1 (en) * 1999-04-23 2002-01-29 Alza Corporation Releasable linkage and compositions containing same
AUPQ014799A0 (en) 1999-05-04 1999-05-27 Access Pharmaceuticals Australia Pty Limited Amplification of folate-mediated targeting to tumor cells using polymers
AUPQ071299A0 (en) 1999-06-02 1999-06-24 Access Pharmaceuticals Australia Pty Limited Vitamin directed dual targeting therapy
US6822086B1 (en) 1999-08-09 2004-11-23 The General Hospital Corporation Drug-carrier complexes and methods of use thereof
EP1210121A2 (en) 1999-08-24 2002-06-05 Cellgate Inc. Enhancing drug delivery across and into epithelial tissues using oligo arginine moieties
KR20020059618A (ko) * 1999-10-15 2002-07-13 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 이미지화제 및 항종양제로서 유용한 코발라민 콘쥬게이트
US7067111B1 (en) * 1999-10-25 2006-06-27 Board Of Regents, University Of Texas System Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging
PT1242401E (pt) 1999-11-24 2007-03-30 Immunogen Inc Agentes citotóxicos compreendendo taxanos e o seu uso terapêutico
AU2001256970C1 (en) * 2000-03-31 2008-07-03 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
US6670355B2 (en) * 2000-06-16 2003-12-30 Wyeth Method of treating cardiovascular disease
US6290929B1 (en) 2000-07-28 2001-09-18 The Procter & Gamble Company Cancer treatment
PT1318837E (pt) * 2000-08-11 2004-12-31 Wyeth Corp Metodo de tratamenton de carcinoma positivo a receptor de estrogenio
CA2421485A1 (en) * 2000-09-19 2002-03-28 Wyeth Water soluble rapamycin esters
US6399625B1 (en) * 2000-09-27 2002-06-04 Wyeth 1-oxorapamycins
US6399626B1 (en) * 2000-10-02 2002-06-04 Wyeth Hydroxyesters of 7-desmethylrapamycin
US6440991B1 (en) * 2000-10-02 2002-08-27 Wyeth Ethers of 7-desmethlrapamycin
AU2002241524A1 (en) * 2000-11-28 2002-06-11 Wyeth Expression analysis of FKBP nucleic acids and polypeptides useful in the diagnosis and treatment of prostate cancer
US20020168737A1 (en) 2001-01-24 2002-11-14 Cornish Virginia W. Binding and catalysis screen for high throughput determination of protein function using chemical inducers of dimerization
AR036993A1 (es) * 2001-04-02 2004-10-20 Wyeth Corp Uso de agentes que modulan la interaccion entre pd-1 y sus ligandos en la submodulacion de respuestas inmunologicas
CA2442066C (en) * 2001-04-02 2005-11-01 Wyeth Pd-1, a receptor for b7-4, and uses therefor
EP1389209B1 (en) 2001-04-24 2009-04-08 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
RU2316349C2 (ru) 2001-05-02 2008-02-10 Пердью Рисерч Фаундейшн Лечение и диагностика заболеваний, опосредованных макрофагами
US7109165B2 (en) * 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
EP1392664A4 (en) * 2001-06-01 2005-01-26 Bristol Myers Squibb Co EPOTHILONE DERIVATIVES
US20040018203A1 (en) * 2001-06-08 2004-01-29 Ira Pastan Pegylation of linkers improves antitumor activity and reduces toxicity of immunoconjugates
UA77200C2 (en) * 2001-08-07 2006-11-15 Wyeth Corp Antineoplastic combination of cci-779 and bkb-569
EP1419153A1 (en) * 2001-08-22 2004-05-19 Wyeth Rapamycin dialdehydes
CA2455308A1 (en) * 2001-08-22 2003-03-06 Wyeth Rapamycin 29-enols
CA2461877A1 (en) * 2001-09-28 2003-04-10 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
GR1004163B (el) * 2001-11-01 2003-02-21 Πολυκυκλικα παραγωγα τροποποιησης των οπτικων ιδιοτητων και των ιδιοτητων αντοχης στο πλασμα των πολυμερων λιθογραφιας
JP2005520795A (ja) 2001-12-12 2005-07-14 コンフォーマ・セラピューティクス・コーポレイション Ｈｓｐ９０阻害活性を有するプリン類似体
US20030194409A1 (en) 2002-01-17 2003-10-16 Rothman James E. Conjugate heat shock protein-binding peptides
US8043602B2 (en) * 2002-02-07 2011-10-25 Endocyte, Inc. Folate targeted enhanced tumor and folate receptor positive tissue optical imaging technology
US7000695B2 (en) * 2002-05-02 2006-02-21 Halliburton Energy Services, Inc. Expanding wellbore junction
DK2260875T3 (da) * 2002-05-06 2014-06-30 Endocyte Inc Folatreceptor-targetede billeddannelsesmidler
US6596757B1 (en) * 2002-05-14 2003-07-22 Immunogen Inc. Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use
US7910594B2 (en) * 2002-05-15 2011-03-22 Endocyte, Inc. Vitamin-mitomycin conjugates
AU2003266233A1 (en) * 2002-07-09 2004-01-23 Morphochem Aktiengesellschaft Fur Kombinatorische Chemie Novel tubulysin analogues
US7776814B2 (en) 2002-07-09 2010-08-17 R&D-Biopharmaceuticals Gmbh Tubulysin conjugates
IL166039A0 (en) 2002-07-31 2006-01-15 Schering Ag New effector conjugates process for their production and their pharmaceutical use
DE10241152A1 (de) 2002-09-05 2004-03-18 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysin-Biosynthese-Gene
KR20120104412A (ko) 2002-09-06 2012-09-20 인설트 테라페틱스, 인코퍼레이티드 공유결합된 치료제 전달을 위한 사이클로덱스트린-기초 중합체
US20040047917A1 (en) 2002-09-06 2004-03-11 Stephen Wilson Drug delivery and targeting with vitamin B12 conjugates
WO2004032877A2 (en) * 2002-10-10 2004-04-22 Wyeth Compositions, organisms and methodologies employing a novel human kinase
AU2003286705A1 (en) 2002-10-24 2004-05-13 Research Corporation Technologies Functional mri agents for cancer imaging
JP2006516388A (ja) * 2002-11-21 2006-07-06 ワイス ループス腎炎の治療用組成物および方法
DE10254439A1 (de) * 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
AU2003288467A1 (en) 2002-12-13 2004-07-09 Immunomedics, Inc. Immunoconjugates with an intracellularly-cleavable linkage
AR042942A1 (es) * 2003-01-27 2005-07-06 Endocyte Inc Conjugados de administracion de drogas de union de receptores de vitaminas
AR042938A1 (es) * 2003-02-06 2005-07-06 Wyeth Corp Uso del cci-779 en el tratamiento de la fibrosis hepatica
WO2004084805A2 (en) 2003-03-19 2004-10-07 The J. David Gladstone Institutes Acetylated tat polypeptides and methods of use thereof
AU2004233092C9 (en) * 2003-04-17 2010-10-28 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
WO2004100983A2 (en) 2003-05-06 2004-11-25 Purdue Research Foundation, Inc. Treatment of lupus targeting the macrophages or the folate receptor
WO2004101803A2 (en) * 2003-05-12 2004-11-25 Wyeth Holdings Corporation Process for producing anticancer agent ll-d45042
RU2238200C1 (ru) * 2003-07-07 2004-10-20 Таланов Александр Васильевич Аппарат на воздушной подушке
AU2004259669A1 (en) * 2003-07-16 2005-02-03 Wyeth CCI-779 Isomer C
CA2532988A1 (en) * 2003-08-07 2005-02-24 Wyeth Regioselective synthesis of cci-779
JP2007519681A (ja) 2004-01-30 2007-07-19 バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト 新規なエフェクター複合体、それらを製造する方法およびそれらの薬学上の使用
US20060105975A1 (en) 2004-04-19 2006-05-18 Shannon Pendergrast Aptamer-mediated intracellular delivery of therapeutic oligonucleotides
WO2005112919A2 (en) * 2004-05-19 2005-12-01 Medarex, Inc. Self-immolative linkers and drug conjugates
WO2005115912A1 (ja) 2004-05-25 2005-12-08 Matsushita Electric Industrial Co., Ltd. 水素生成装置及びそれを用いた燃料電池システム
EP1789391B1 (en) 2004-07-23 2017-06-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
JP5192234B2 (ja) * 2004-08-10 2013-05-08 アルナイラム ファーマシューティカルズ， インコーポレイテッド 化学修飾オリゴヌクレオチド
TW200616604A (en) 2004-08-26 2006-06-01 Nicholas Piramal India Ltd Nitric oxide releasing prodrugs containing bio-cleavable linker
EP1812864A2 (en) 2004-10-07 2007-08-01 Emory University Multifunctional nanoparticles conjugates and their use
WO2007001457A2 (en) 2004-11-12 2007-01-04 Xencor, Inc. Antibodies operably linked to selected chemoattractants
US20110166319A1 (en) 2005-02-11 2011-07-07 Immunogen, Inc. Process for preparing purified drug conjugates
TW200640493A (en) 2005-02-16 2006-12-01 Insert Therapeutics Inc Cyclodextrin-based polymers for therapeutics delivery
US7312217B2 (en) 2005-03-11 2007-12-25 Syntrix Biosystems, Inc. Aminopterin dosage forms and methods for inflammatory disorders
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
EP1864133B1 (en) 2005-03-30 2010-03-10 Purdue Research Foundation Method for breastcancer prognosis using cellular folate vitamin receptor quantification
EP1912677B1 (en) 2005-06-20 2013-10-02 Psma Development Company, L.L.C. PSMA antibody-drug conjugates
EP1904183B1 (en) * 2005-07-05 2014-10-15 Purdue Research Foundation Pharmaceutical composition for the treatment of osteoarthritis
KR20080080081A (ko) 2005-08-19 2008-09-02 네오스 테크놀로지스, 인크. 글리코페닐화 인자 ⅶ 및 인자 ⅶ에이
WO2007022493A2 (en) 2005-08-19 2007-02-22 Endocyte, Inc. Ligand conjugates of vinca alkaloids, analogs, and derivatives
CN103893778A (zh) 2005-08-19 2014-07-02 恩多塞特公司 多药物配体缀合物
NZ595430A (en) 2005-08-24 2013-05-31 Immunogen Inc Process for preparing maytansinoid antibody conjugates
CA2670355A1 (en) 2005-11-21 2008-04-24 Medivas, Llc Polymer particles for delivery of macromolecules and methods of use
AR062448A1 (es) * 2006-05-25 2008-11-12 Endocyte Inc Conjugados de analogos de aziridinil-epotilona y composiciones farmaceuticas que comprenden los mismos
CA2668197A1 (en) 2006-11-03 2008-05-15 Philip S. Low Ex vivo flow cytometry method and device
JP2010516625A (ja) 2007-01-24 2010-05-20 インサート セラピューティクス， インコーポレイテッド 制御された薬物送達のためのテザー基を有するポリマー−薬物コンジュゲート
EP3453405A1 (en) 2007-02-16 2019-03-13 Vergell Medical S.A. Dual acting prodrugs
WO2008101231A2 (en) 2007-02-16 2008-08-21 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
JP5829793B2 (ja) 2007-03-14 2015-12-09 エンドサイト・インコーポレイテッドＥｎｄｏｃｙｔｅ， Ｉｎｃ． 結合性リガンドが結合したツブリシンの薬剤送達結合体
CA2723671C (en) 2007-05-10 2018-06-19 R & D Biopharmaceuticals Gmbh Tubulysine derivatives
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
WO2011079227A1 (en) 2009-12-23 2011-06-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
WO2009002993A1 (en) 2007-06-25 2008-12-31 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
WO2009004720A1 (ja) * 2007-07-03 2009-01-08 Fujitsu Limited レベル低下検出装置、光増幅装置、およびレベル低下検出方法
US8476451B2 (en) 2007-07-20 2013-07-02 The Regents Of The University Of California Tubulysin D analogues
PT2187965T (pt) 2007-08-17 2020-01-17 Purdue Research Foundation Conjugados ligando-ligante de ligação a psma e métodos para utilização
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
CA2708171C (en) 2007-12-04 2018-02-27 Alnylam Pharmaceuticals, Inc. Folate conjugates
BRPI0911442A2 (pt) 2008-04-30 2019-03-12 Immunogen, Inc. conjugados potentes e ligantes hidrofílicos
US20100040669A1 (en) 2008-08-12 2010-02-18 Higuchi John W Non-Invasive Ocular Delivery of Rapamycin
JP5675619B2 (ja) 2008-09-17 2015-02-25 エンドサイト, インク.Endocyte, Inc. 葉酸拮抗薬の葉酸受容体結合性コンジュゲート
US20100074863A1 (en) 2008-09-17 2010-03-25 Yat Sun Or Anti-infective pyrrolidine derivatives and analogs
EP2174947A1 (en) 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
WO2010045598A2 (en) 2008-10-17 2010-04-22 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
US20120022245A1 (en) 2008-10-17 2012-01-26 Purdue Research Foundation Folate targeting of nucleotides
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
CN102648208B (zh) 2009-11-12 2016-04-27 R&D生技药品有限责任公司 微管蛋白抑制剂
EP2322537A1 (en) 2009-11-12 2011-05-18 R & D Biopharmaceuticals Gmbh Tubulin inhibitors
WO2011069116A1 (en) 2009-12-04 2011-06-09 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
CA2790577A1 (en) 2010-02-25 2011-09-01 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
TWI540136B (zh) 2010-04-15 2016-07-01 梅迪繆思有限公司 吡咯并苯并二氮呯及其共軛物
EP2409983A1 (en) 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
MX2013001402A (es) 2010-08-06 2013-08-29 Endocyte Inc Proceso para preparar tubulisinas.
CA2812543A1 (en) 2010-09-27 2012-04-12 Endocyte, Inc. Folate conjugates for treating inflammation of the eye
US20140243282A1 (en) 2010-12-31 2014-08-28 Satish Reddy Kallam Methods and compositions for designing novel conjugate therapeutics
AU2012236403B2 (en) 2011-03-29 2016-08-04 Immunogen, Inc. Process for manufacturing conjugates of improved homogeneity
RS58367B1 (sr) 2011-03-29 2019-03-29 Immunogen Inc Priprema konjugata antitela i majtanzinoida jednostepenim postupkom
JP6209159B2 (ja) 2011-06-21 2017-10-04 イミュノジェン・インコーポレーテッド ペプチドリンカーを有する新規メイタンシノイド誘導体およびその結合体
CA2857398A1 (en) 2011-12-05 2013-06-13 Igenica Biotherapeutics, Inc. Antibody-drug conjugates and related compounds, compositions, and methods
WO2013126797A1 (en) 2012-02-24 2013-08-29 Purdue Research Foundation Cholecystokinin b receptor targeting for imaging and therapy
US9629918B2 (en) 2012-02-29 2017-04-25 Purdue Research Foundation Folate receptor alpha binding ligands
US20140080175A1 (en) 2012-03-29 2014-03-20 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
JP6290187B2 (ja) 2012-05-11 2018-03-07 クランツ，アレクサンダー 癌の処置のためのタンパク質の部位特異的標識及び標的送達
US9981046B2 (en) 2012-05-15 2018-05-29 Concortis Biosystems, Corp., a wholly owned Subsidiary of Sorrento Therapeutics, Inc. Drug-conjugates, conjugation methods, and uses thereof
JP6117921B2 (ja) 2012-07-12 2017-04-19 ハンヂョウ ディーエイシー バイオテック カンパニー リミテッド 細胞毒性剤と細胞結合受容体との共役体
EP2708243A1 (en) 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
EP2908818A4 (en) 2012-10-16 2016-07-13 Endocyte Inc CONJUGATES OF DRUG DELIVERY CONTAINING ARTIFICIAL AMINO ACIDS AND METHODS OF USE
US20140107316A1 (en) 2012-10-16 2014-04-17 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
US9636413B2 (en) 2012-11-15 2017-05-02 Endocyte, Inc. Conjugates for treating diseases caused by PSMA expressing cells
JP6133431B2 (ja) 2012-11-24 2017-05-24 ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． 親水性連結体及び薬物分子と細胞結合分子との共役反応における親水性連結体の使用
AU2013364065B2 (en) 2012-12-21 2018-10-04 Altrubio Inc. Hydrophilic self-immolative linkers and conjugates thereof
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
CN104784699B (zh) 2014-01-20 2019-05-03 博瑞生物医药（苏州）股份有限公司 叶酸受体结合配体-药物偶联物

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN104640572A (zh) * 2012-05-15 2015-05-20 索伦托医疗有限公司(美国) 药物偶联物,偶联方法,及其用途
US10501412B2 (en) 2012-07-12 2019-12-10 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
US10399941B2 (en) 2012-07-12 2019-09-03 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
WO2014009774A1 (en) * 2012-07-12 2014-01-16 Hangzhou Dac Biotech Co., Ltd Conjugates of cell binding molecules with cytotoxic agents
US11767294B2 (en) 2012-07-12 2023-09-26 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
US11834406B2 (en) 2012-07-12 2023-12-05 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
CN108042811A (zh) * 2012-11-15 2018-05-18 恩多塞特公司 用于治疗由psma表达细胞引起的疾病的共轭物
CN109316605A (zh) * 2014-01-20 2019-02-12 博瑞生物医药（苏州）股份有限公司 叶酸受体结合配体-药物偶联物
CN105641707A (zh) * 2014-11-11 2016-06-08 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
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
CN110234357A (zh) * 2016-11-23 2019-09-13 梅尔莎纳医疗公司 用于抗体-药物缀合物的含肽接头
WO2019127607A1 (en) * 2017-12-31 2019-07-04 Hangzhou Dac Biotech Co. Ltd A conjugate of a tubulysin analog with branched linkers
US11998584B2 (en) 2017-12-31 2024-06-04 Hangzhou Dac Biotech Co., Ltd. Conjugate of a tubulysin analog with branched linkers

Also Published As

Publication number Publication date
IL200857A0 (en) 2010-05-17
EP2489372A3 (en) 2013-01-02
WO2008112873A2 (en) 2008-09-18
JP5829793B2 (ja) 2015-12-09
CN104127878A (zh) 2014-11-05
JP2014169320A (ja) 2014-09-18
EP2139523B1 (en) 2014-10-22
EP2139523A2 (en) 2010-01-06
US20100048490A1 (en) 2010-02-25
JP2010521485A (ja) 2010-06-24
AU2008224988A1 (en) 2008-09-18
CA2680535A1 (en) 2008-09-18
NZ599239A (en) 2013-10-25
EP2481427A1 (en) 2012-08-01
NZ580132A (en) 2012-11-30
US9555139B2 (en) 2017-01-31
CN103948937A (zh) 2014-07-30
IL200857A (en) 2017-09-28
US20170327537A1 (en) 2017-11-16
CA2680535C (en) 2016-09-20
EP2489372A2 (en) 2012-08-22
WO2008112873A3 (en) 2009-09-11
US20140066594A1 (en) 2014-03-06

Similar Documents

Publication Publication Date Title
US9555139B2 (en) Binding ligand linked drug delivery conjugates of tubulysins
CN101784565B (zh) 含有亲水性间隔区接头的共轭物
RU2470668C2 (ru) Конъюгаты лиганда с несколькими лекарственными средствами
EP2382995A2 (en) Ligand conjugates of Vinca alkaloids, analogs and derivatives
AU2013203147A1 (en) Binding ligand linked drug delivery conjugates of tubulysins
AU2016204030A1 (en) Binding ligand linked drug delivery conjugates of tubulysins
HK1174857A (en) Binding ligand linked drug delivery conjugates of tubulysins
AU2013204293A1 (en) Multi-drug ligand conjugates

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C12 Rejection of a patent application after its publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20100324