CA2680535C - Binding ligand linked drug delivery conjugates of tubulysins - Google Patents

Binding ligand linked drug delivery conjugates of tubulysins Download PDF

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Publication number
CA2680535C
CA2680535C CA2680535A CA2680535A CA2680535C CA 2680535 C CA2680535 C CA 2680535C CA 2680535 A CA2680535 A CA 2680535A CA 2680535 A CA2680535 A CA 2680535A CA 2680535 C CA2680535 C CA 2680535C
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CA
Canada
Prior art keywords
alkyl
drug delivery
pharmaceutically acceptable
acceptable salt
aryl
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.)
Expired - Fee Related
Application number
CA2680535A
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English (en)
French (fr)
Other versions
CA2680535A1 (en
Inventor
Iontcho Radoslavov Vlahov
Christopher Paul Leamon
Yu Wang
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 CA2680535A1 publication Critical patent/CA2680535A1/en
Application granted granted Critical
Publication of CA2680535C publication Critical patent/CA2680535C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (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)
CA2680535A 2007-03-14 2008-03-13 Binding ligand linked drug delivery conjugates of tubulysins Expired - Fee Related CA2680535C (en)

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

Publications (2)

Publication Number Publication Date
CA2680535A1 CA2680535A1 (en) 2008-09-18
CA2680535C true CA2680535C (en) 2016-09-20

Family

ID=39588060

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2680535A Expired - Fee Related CA2680535C (en) 2007-03-14 2008-03-13 Binding ligand linked drug delivery conjugates of tubulysins

Country Status (9)

Country Link
US (3) US9555139B2 (OSRAM)
EP (3) EP2481427A1 (OSRAM)
JP (2) JP5829793B2 (OSRAM)
CN (3) CN104127878A (OSRAM)
AU (1) AU2008224988A1 (OSRAM)
CA (1) CA2680535C (OSRAM)
IL (1) IL200857A (OSRAM)
NZ (2) NZ580132A (OSRAM)
WO (1) WO2008112873A2 (OSRAM)

Families Citing this family (71)

* 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
TWI367096B (en) 2003-01-27 2012-07-01 Endocyte Inc Vitamin-receptor binding drug delivery conjugates and pharmaceutical compositions
AU2004283246B2 (en) 2003-10-14 2009-07-23 Baxalta GmbH Vitamin K epoxide recycling polypeptide VKORC1, a therapeutic target of coumarin and their derivatives
EP1789391B1 (en) 2004-07-23 2017-06-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
US8044200B2 (en) * 2005-03-16 2011-10-25 Endocyte, Inc. Synthesis and purification of pteroic acid and conjugates thereof
EP2382995A3 (en) * 2005-08-19 2013-09-25 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
CA2617660C (en) * 2005-08-19 2014-03-25 Endocyte, Inc. Multi-drug ligand conjugates
US20100104626A1 (en) 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
WO2008112873A2 (en) 2007-03-14 2008-09-18 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
WO2009002993A1 (en) * 2007-06-25 2008-12-31 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
EP3388086B1 (en) 2007-08-17 2020-10-07 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
JP2011500835A (ja) 2007-10-25 2011-01-06 エンドサイト，インコーポレイテッド チューブリシン類および調製プロセス
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
CA2785373A1 (en) * 2009-12-23 2011-06-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
MY197016A (en) * 2010-02-24 2023-05-20 Immunogen Inc Folate receptor 1 antibodies and immunoconjugates and uses thereof
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
CA2807511A1 (en) 2010-08-06 2012-02-09 Endocyte, Inc. Processes for preparing tubulysins
JP5926374B2 (ja) 2011-06-10 2016-05-25 メルサナ セラピューティクス，インコーポレイティド タンパク質−高分子−薬剤コンジュゲート
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
EP2846838B1 (en) * 2012-05-07 2017-05-03 Nitto Denko Corporation Polymer conjugates with a linker
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
KR102434075B1 (ko) 2012-05-17 2022-08-19 익스텐드 바이오사이언시즈, 인크. 개선된 약물 전달용 캐리어
ES2939836T3 (es) 2012-07-12 2023-04-27 Hangzhou Dac Biotech Co Ltd Conjugados de moléculas de unión celular con agentes citotóxicos
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
MX2015004757A (es) 2012-10-16 2015-07-17 Endocyte Inc Conjugados de suministro de farmacos que contienen aminoacidos no naturales y metodo para usarlos.
KR20150104092A (ko) * 2012-11-15 2015-09-14 엔도사이트, 인코포레이티드 Psma 발현 세포에 의해 야기되는 질병을 치료하기 위한 컨쥬게이트
CN105849086B (zh) 2012-11-24 2018-07-31 杭州多禧生物科技有限公司 亲水性链接体及其在药物分子和细胞结合分子共轭反应上的应用
AU2013359506B2 (en) 2012-12-10 2018-05-24 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
EP2931316B1 (en) 2012-12-12 2019-02-20 Mersana Therapeutics, Inc. Hydroxyl-polymer-drug-protein conjugates
PT2956173T (pt) 2013-02-14 2017-06-26 Bristol Myers Squibb Co Compostos de tubulisina, métodos de produção e utilização
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
SI4095130T1 (sl) 2013-10-18 2024-05-31 Novartis Ag Označeni zaviralci za prostato specifičnega membranskega antigena (PSMA), njihova uporaba kot kontrastna sredstva in farmacevtska sredstva za zdravljenje raka prostate
AU2014348601A1 (en) 2013-11-14 2016-05-26 Endocyte, Inc. Compounds for positron emission tomography
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
GB201402006D0 (en) 2014-02-06 2014-03-26 Oncomatryx Biopharma S L Antibody-drug conjugates and immunotoxins
GB201402009D0 (en) * 2014-02-06 2014-03-26 Oncomatryx Biopharma S L Antibody-drug conjugates and immunotoxins
CN114262344A (zh) 2014-02-28 2022-04-01 杭州多禧生物科技有限公司 带电荷链接体及其在共轭反应上的应用
WO2015183988A1 (en) * 2014-05-28 2015-12-03 Stealth Peptides International, Inc. Therapeutic compositions including therapeutic small molecules and uses thereof
US9585934B2 (en) 2014-10-22 2017-03-07 Extend Biosciences, Inc. Therapeutic vitamin D conjugates
US9789197B2 (en) 2014-10-22 2017-10-17 Extend Biosciences, Inc. RNAi vitamin D conjugates
WO2016065052A1 (en) 2014-10-22 2016-04-28 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
CN105641707B (zh) * 2014-11-11 2020-11-24 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
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
CA2991973C (en) 2015-07-12 2021-12-07 Suzhou M-Conj Biotech Co., Ltd. Bridge linkers for conjugation of a cell-binding molecule
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
TWI852735B (zh) * 2015-12-04 2024-08-11 美商思進公司 四級胺化妥布賴森(tubulysin)化合物之結合物
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
CN114191428B (zh) 2016-03-02 2024-09-24 卫材研究发展管理有限公司 基于艾日布林的抗体-药物偶联物和使用方法
NZ752394A (en) 2016-11-14 2021-07-30 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
US11135307B2 (en) * 2016-11-23 2021-10-05 Mersana Therapeutics, Inc. Peptide-containing linkers for antibody-drug conjugates
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
US11998584B2 (en) 2017-12-31 2024-06-04 Hangzhou Dac Biotech Co., Ltd. Conjugate of a tubulysin analog with branched linkers
US12208102B2 (en) 2018-04-17 2025-01-28 Endocyte, Inc. Methods of treating cancer
CA3117050A1 (en) * 2018-10-29 2020-05-07 Mersana Therapeutics, Inc. Cysteine engineered antibody-drug conjugates with peptide-containing linkers
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
CN114096264B (zh) 2019-05-20 2025-03-14 因多塞特股份有限公司 制备psma缀合物的方法
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
EP3991752A4 (en) 2019-06-29 2023-03-29 Hangzhou Dac Biotech Co., Ltd CELL-BINDING MOLECULE-TUBULYSIN DERIVATIVE CONJUGATE AND METHOD FOR ITS PRODUCTION
CA3108168A1 (en) 2020-02-05 2021-08-05 Yue Zhang 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
KR20240095442A (ko) 2021-11-03 2024-06-25 항저우 디에이씨 바이오테크 씨오, 엘티디 항체의 특이적 접합
AU2023353057A1 (en) 2022-09-30 2025-05-01 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
EP0116208B1 (en) 1982-12-07 1988-03-30 Kyowa Hakko Kogyo Co., Ltd. Mitomycin analogues
ATE64396T1 (de) 1983-04-29 1991-06-15 Omnichem Sa Konjugierte vinblastin-verbindungen und ihre derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zusammensetzungen.
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
IL82579A0 (en) 1986-05-27 1987-11-30 Lilly Co Eli Immunoglobulin conjugates
US4801688A (en) 1986-05-27 1989-01-31 Eli Lilly And Company Hydrazone immunoglobulin conjugates
WO1988001622A1 (fr) 1986-08-29 1988-03-10 Kyowa Hakko Kogyo Kabusiki Kaisha Derives de mitomycine
US5006652A (en) 1988-08-08 1991-04-09 Eli Lilly And Company Intermediates for antibody-vinca drug conjugates
US5094849A (en) 1988-08-08 1992-03-10 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized vinca analogs via simple organic linkers
US5688488A (en) 1989-04-03 1997-11-18 Purdue Research Foundation Composition and method for tumor imaging
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
AU5356490A (en) 1989-04-03 1990-11-05 Purdue Research Foundation Method for enhancing transmembrane transport of exogenous molecules
KR910009284A (ko) 1989-11-13 1991-06-28 원본미기재 인체 종양 세포 항원에 특이적인 키메라형 생쥐-인체 a10 항체
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
JPH06502301A (ja) 1990-08-29 1994-03-17 サントル　オスピタリエ　レジオナル　デ　ナント 安定タンパク質コアに結合されたタンパク質ポリリガンド
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
US5130307A (en) 1990-09-28 1992-07-14 American Home Products Corporation Aminoesters of rapamycin
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
EP0710110B1 (en) 1993-04-23 2002-03-06 Abbott Laboratories Antibodies of ring opened rapamycins
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
US5385910A (en) 1993-11-22 1995-01-31 American Home Products Corporation Gem-distributed esters of rapamycin
US5385908A (en) 1993-11-22 1995-01-31 American Home Products Corporation Hindered 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
CA2253904A1 (en) 1996-05-03 1997-11-13 Immunomedics, Inc. Targeted combination immunotherapy of cancer
DE19621133A1 (de) 1996-05-24 1997-11-27 Boehringer Mannheim Gmbh Bestimmungsverfahren mit oligomerisierten Rezeptoren
US6315978B1 (en) 1996-08-27 2001-11-13 University Of Utah, Research Foundation Bioconjugates and delivery of bioactive agents
JP2000516961A (ja) 1996-08-30 2000-12-19 イーライ・リリー・アンド・カンパニー 非古典的ピロロ［２，３―ｄ］ピリミジン抗葉酸物質
WO1998010651A1 (en) 1996-09-12 1998-03-19 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
US6291673B1 (en) 1997-10-17 2001-09-18 Purdue Research Foundation Folic acid derivatives
GB9723669D0 (en) 1997-11-07 1998-01-07 Univ Aberdeen Skin penetration enhancing components
US6399638B1 (en) 1998-04-21 2002-06-04 Bristol-Myers Squibb Company 12,13-modified 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
CA2353593A1 (en) 1998-12-18 2000-06-22 Hadasit Medical Research Services & Development Ltd. Method of administering a compound to multi-drug resistant cells
US6291684B1 (en) 1999-03-29 2001-09-18 Bristol-Myers Squibb Company Process for the preparation of aziridinyl epothilones from oxiranyl epothilones
EP1880736A1 (en) 1999-04-23 2008-01-23 Alza Corporation Releasable linkage and composition 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
JP2003507438A (ja) 1999-08-24 2003-02-25 セルゲイト， インコーポレイテッド オリゴアルギニン部分を使用する上皮組織を横切るおよび上皮組織内への薬物送達の増強
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
AU765588C (en) 1999-11-24 2004-12-16 Immunogen, Inc. Cytotoxic agents comprising taxanes and their therapeutic use
DZ3332A1 (fr) 2000-03-31 2001-10-11 Purdue Research Foundation Methode de traitement a l'aide de conjugues ligand-immunogene
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
JP2004509898A (ja) 2000-09-19 2004-04-02 ワイス 水溶性ラパマイシンエステル
US6399625B1 (en) 2000-09-27 2002-06-04 Wyeth 1-oxorapamycins
US6440991B1 (en) 2000-10-02 2002-08-27 Wyeth Ethers of 7-desmethlrapamycin
US6399626B1 (en) 2000-10-02 2002-06-04 Wyeth Hydroxyesters of 7-desmethylrapamycin
MXPA03004688A (es) 2000-11-28 2003-09-05 Wyeth Corp Analisis de expresion de acidos nucleicos y polipeptidos fkbp utiles en diagnostico.
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
EP2388590A1 (en) 2001-04-02 2011-11-23 Dana Farber Cancer Institute PD-1, a receptor for B7-4, and uses thereof
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
EP1389209B1 (en) 2001-04-24 2009-04-08 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
IL158532A0 (en) 2001-05-02 2004-05-12 Purdue Research Foundation Treatment and diagnosis of macrophage mediated disease
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
JP2004532888A (ja) 2001-06-01 2004-10-28 ブリストル−マイヤーズ　スクイブ　カンパニー エポチロン誘導体
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
BR0211986A (pt) 2001-08-22 2004-09-28 Wyeth Corp 29-enóis de rapamicina
BR0211905A (pt) 2001-08-22 2004-09-21 Wyeth Corp Dialdeìdos de rapamicina
EP2168598A1 (en) 2001-09-28 2010-03-31 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
CA2468202A1 (en) 2001-12-12 2003-06-19 Conforma Therapeutics Corporation Assays and implements for determining and modulating hsp90 binding activity
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
CA2484345C (en) 2002-05-06 2015-09-29 Endocyte, Inc. Folate-targeted imaging agents
US6596757B1 (en) 2002-05-14 2003-07-22 Immunogen Inc. Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use
EP1504010B1 (en) 2002-05-15 2009-03-25 Endocyte, Inc. Vitamin-mitomycin conjugates
WO2004005327A1 (de) 2002-07-09 2004-01-15 Morphochem Ag Komb Chemie Neue tubulysinanaloga
US7776814B2 (en) 2002-07-09 2010-08-17 R&D-Biopharmaceuticals Gmbh Tubulysin conjugates
EP1524979A2 (en) 2002-07-31 2005-04-27 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
US20040047917A1 (en) 2002-09-06 2004-03-11 Stephen Wilson Drug delivery and targeting with vitamin B12 conjugates
KR101268258B1 (ko) 2002-09-06 2013-05-31 인설트 테라페틱스, 인코퍼레이티드 공유결합된 치료제 전달을 위한 사이클로덱스트린-기초 중합체
US7122361B2 (en) 2002-10-10 2006-10-17 Wyeth Compositions employing a novel human kinase
EP1558137A2 (en) 2002-10-24 2005-08-03 Research Corporation Technologies Functional mri agents for cancer imaging
WO2004048521A2 (en) 2002-11-21 2004-06-10 Wyeth Composition and method for treating lupus nephritis
DE10254439A1 (de) 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
CA2508831C (en) 2002-12-13 2012-05-01 Immunomedics, Inc. Immunoconjugates with an intracellularly-cleavable linkage
TWI367096B (en) * 2003-01-27 2012-07-01 Endocyte Inc Vitamin-receptor binding drug delivery conjugates and pharmaceutical compositions
AR042938A1 (es) 2003-02-06 2005-07-06 Wyeth Corp Uso del cci-779 en el tratamiento de la fibrosis hepatica
US7482016B2 (en) 2003-03-19 2009-01-27 The J. David Gladstone Institutes Immunogenic compositions comprising HIV-1 acetylated Tat polypeptides
CA2522637C (en) 2003-04-17 2014-01-21 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
JP4227649B2 (ja) 2003-08-07 2009-02-18 ワイス Ｃｃｉ−７７９の位置選択的合成
DK1718340T3 (da) 2004-01-30 2008-03-03 Bayer Schering Pharma Ag Nye effektorkonjugater, fremgangsmåde til deres fremstilling og deres farmaceutiske anvendelse
EP1737879B1 (en) 2004-04-19 2012-10-10 Archemix LLC Aptamer-mediated intracellular delivery of therapeutic oligonucleotides
CA2564076C (en) * 2004-05-19 2014-02-18 Medarex, Inc. Chemical linkers and conjugates thereof
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
CA2576233C (en) 2004-08-10 2016-03-15 Alnylam Pharmaceuticals, Inc. Conjugate comprising an antagomir and a ligand
TW200616604A (en) 2004-08-26 2006-06-01 Nicholas Piramal India Ltd Nitric oxide releasing prodrugs containing bio-cleavable linker
CA2583389A1 (en) 2004-10-07 2006-04-20 Emory University Multifunctional nanoparticles conjugates and their use
US20060222653A1 (en) 2004-11-12 2006-10-05 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
US8044200B2 (en) 2005-03-16 2011-10-25 Endocyte, Inc. Synthesis and purification of pteroic acid and conjugates thereof
RU2007139912A (ru) 2005-03-30 2009-05-10 Пердью Рисерч Фаундейшн (Us) Способ прогнозирования течения рака на основе количественного анализа клеточного рецептора витамина фолата
PT1912677E (pt) 2005-06-20 2013-12-23 Psma Dev Company L L C Conjugados de anticorpos contra psma-fármaco
JP5175723B2 (ja) 2005-07-05 2013-04-03 パーデュー・リサーチ・ファウンデーション 単球介在性疾患を治療するための組成物の調製
CA2617660C (en) 2005-08-19 2014-03-25 Endocyte, Inc. Multi-drug ligand conjugates
EP2382995A3 (en) 2005-08-19 2013-09-25 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
EP1937719A4 (en) 2005-08-19 2010-11-24 Novo Nordisk As FACTOR VII AND GLYCOPEGYLE VIIA FACTOR
HRP20120794T1 (hr) 2005-08-24 2012-11-30 Immunogen, Inc. Postupak za pripremu proäśišä†enih konjugata lijeka
EP1957113A4 (en) 2005-11-21 2011-11-09 Medivas Llc POLYMER PARTICLES FOR THE OUTPUT OF MACROMOLECULES AND METHOD OF APPLICATION THEREFOR
PE20080102A1 (es) 2006-05-25 2008-02-11 Bristol Myers Squibb Co Conjugados de analogos de aziridinil-epotilona y composiciones farmaceuticas que comprenden los mismos
JP2010509570A (ja) 2006-11-03 2010-03-25 パーデュー・リサーチ・ファウンデーション エクスビボフローサイトメトリーの方法および装置
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
US20100104626A1 (en) 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
EP3453405A1 (en) 2007-02-16 2019-03-13 Vergell Medical S.A. Dual acting prodrugs
WO2008112873A2 (en) 2007-03-14 2008-09-18 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
US8980833B2 (en) 2007-05-10 2015-03-17 R&D-Biopharmaceuticals Gmbh Tubulysine derivatives
WO2009002993A1 (en) 2007-06-25 2008-12-31 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
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
EP3388086B1 (en) 2007-08-17 2020-10-07 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
JP2011500835A (ja) 2007-10-25 2011-01-06 エンドサイト，インコーポレイテッド チューブリシン類および調製プロセス
EP2231194B1 (en) 2007-12-04 2017-02-22 Alnylam Pharmaceuticals Inc. Folate-irna conjugates
AU2009243009B2 (en) 2008-04-30 2014-09-11 Immunogen, Inc Potent conjugates and hydrophilic linkers
US20100040669A1 (en) 2008-08-12 2010-02-18 Higuchi John W Non-Invasive Ocular Delivery of Rapamycin
US20100074863A1 (en) 2008-09-17 2010-03-25 Yat Sun Or Anti-infective pyrrolidine derivatives and analogs
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
EP2174947A1 (en) 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
WO2010045584A1 (en) 2008-10-17 2010-04-22 Endocyte, Inc. Folate targeting of nucleotides
US20110288152A1 (en) 2008-10-17 2011-11-24 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
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
ES2581207T3 (es) 2009-11-12 2016-09-02 Tube Pharmaceuticals Gmbh Inhibidores de la tubulina
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
CA2785373A1 (en) 2009-12-23 2011-06-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US20120322741A1 (en) 2010-02-25 2012-12-20 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
CA2807511A1 (en) 2010-08-06 2012-02-09 Endocyte, Inc. Processes for preparing tubulysins
WO2012047525A2 (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
CN103717262B (zh) 2011-03-29 2017-09-15 伊缪诺金公司 通过一步法制备类美登素抗体缀合物
AU2012236403B2 (en) 2011-03-29 2016-08-04 Immunogen, Inc. Process for manufacturing conjugates of improved homogeneity
WO2012177837A2 (en) 2011-06-21 2012-12-27 Immunogen, Inc. Novel maytansinoid derivatives with peptide linker and conjugates thereof
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
WO2013130776A1 (en) 2012-02-29 2013-09-06 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
US9545449B2 (en) 2012-05-11 2017-01-17 Advanced Proteone Therapeutics Inc. Site-specific labeling and targeted delivery of proteins for the treatment of cancer
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
ES2939836T3 (es) 2012-07-12 2023-04-27 Hangzhou Dac Biotech Co Ltd Conjugados de moléculas de unión celular con agentes citotóxicos
EP2708243A1 (en) 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
MX2015004757A (es) 2012-10-16 2015-07-17 Endocyte Inc Conjugados de suministro de farmacos que contienen aminoacidos no naturales y metodo para usarlos.
US20140107316A1 (en) 2012-10-16 2014-04-17 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
KR20150104092A (ko) 2012-11-15 2015-09-14 엔도사이트, 인코포레이티드 Psma 발현 세포에 의해 야기되는 질병을 치료하기 위한 컨쥬게이트
CN105849086B (zh) 2012-11-24 2018-07-31 杭州多禧生物科技有限公司 亲水性链接体及其在药物分子和细胞结合分子共轭反应上的应用
AU2013364065B2 (en) 2012-12-21 2018-10-04 Altrubio Inc. Hydrophilic self-immolative linkers and conjugates thereof
PT2956173T (pt) 2013-02-14 2017-06-26 Bristol Myers Squibb Co Compostos de tubulisina, métodos de produção e utilização
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

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