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
    • 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
    • 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 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)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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 (enExample)
EP (3) EP2139523B1 (enExample)
JP (2) JP5829793B2 (enExample)
CN (3) CN104127878A (enExample)
AU (1) AU2008224988A1 (enExample)
CA (1) CA2680535C (enExample)
IL (1) IL200857A (enExample)
NZ (2) NZ580132A (enExample)
WO (1) WO2008112873A2 (enExample)

Families Citing this family (72)

* 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
US7601332B2 (en) * 2003-01-27 2009-10-13 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
EP2272951B1 (en) 2003-10-14 2014-07-23 Baxter International Inc. Vitamin k epoxide recycling polypeptide vkorc1, a therapeutic target of coumarin and their derivatives
CN101098854B (zh) 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
CN101175757B (zh) * 2005-03-16 2012-11-14 恩多塞特公司 蝶酸及其缀合物的合成和纯化
JP2009504783A (ja) * 2005-08-19 2009-02-05 エンドサイト，インコーポレイテッド ビンカアルカロイド、類似体および誘導体のリガンド結合体
RU2470668C2 (ru) * 2005-08-19 2012-12-27 Эндосайт, Инк. Конъюгаты лиганда с несколькими лекарственными средствами
US20100104626A1 (en) 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
CN104127878A (zh) 2007-03-14 2014-11-05 恩多塞特公司 结合配体连接的微管溶素递药缀合物
BRPI0812970A2 (pt) * 2007-06-25 2019-09-24 Endocyte Inc conjugados contendo espaçadores hidrofílicos
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
DK2187965T3 (da) 2007-08-17 2020-01-20 Purdue Research Foundation Psma-bindingsligand-linker-konjugater og fremgangsmåder til anvendelse
EP2209374B1 (en) 2007-10-25 2014-12-03 Endocyte, Inc. Tubulysins and processes for preparing
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
US20120258905A1 (en) * 2009-12-23 2012-10-11 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
CN105777907B (zh) * 2010-02-24 2020-03-17 伊缪诺金公司 叶酸受体1抗体与免疫缀合物以及其用途
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
US8889880B2 (en) 2010-08-06 2014-11-18 Endocyte, Inc. Processes for preparing tubulysins
EP2717916B1 (en) 2011-06-10 2017-03-08 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
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
US9078926B2 (en) * 2012-05-07 2015-07-14 Nitto Denko Corporation Polymer conjugates with a linker
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
MX349035B (es) 2012-05-17 2017-07-07 Extend Biosciences Inc Portadores para el suministro mejorado de farmaco.
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
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
EA201590622A1 (ru) * 2012-10-16 2015-10-30 Эндосайт, Инк. Конъюгаты для доставки лекарственного средства, содержащие не встречающиеся в природе аминокислоты, и способы применения
KR102318999B1 (ko) * 2012-11-15 2021-10-29 엔도사이트, 인코포레이티드 Psma 발현 세포에 의해 야기되는 질병을 치료하기 위한 컨쥬게이트
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
WO2014093394A1 (en) 2012-12-10 2014-06-19 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
US9872918B2 (en) 2012-12-12 2018-01-23 Mersana Therapeutics, Inc. Hydroxyl-polymer-drug-protein conjugates
DK2956173T3 (en) 2013-02-14 2017-07-17 Bristol Myers Squibb Co TUBULYSIS RELATIONSHIPS, METHODS OF PRODUCING AND USING THEREOF
US20140249315A1 (en) 2013-03-01 2014-09-04 Endocyte, Inc. Processes for preparing tubulysins
WO2014160305A1 (en) * 2013-03-14 2014-10-02 Albany Molecular Research, Inc. Ligand-therapeutic agent conjugates and silicon-based linkers
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
WO2015073678A1 (en) 2013-11-14 2015-05-21 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
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
JP6417421B2 (ja) 2014-02-28 2018-11-07 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． 荷電連結体及び共役体のためのその使用
WO2015183988A1 (en) * 2014-05-28 2015-12-03 Stealth Peptides International, Inc. Therapeutic compositions including therapeutic small molecules and uses thereof
WO2016065052A1 (en) 2014-10-22 2016-04-28 Extend Biosciences, Inc. Insulin vitamin d conjugates
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
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
US11229708B2 (en) * 2015-12-04 2022-01-25 Seagen Inc. Conjugates of quaternized tubulysin compounds
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
MY199595A (en) 2016-03-02 2023-11-08 Eisai R&D Man Co Ltd Eribulin-based antibody-drug conjugates and methods of use
KR20220147719A (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
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
JP7262817B2 (ja) 2017-12-31 2023-04-24 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． 分岐連結体を備えたチューブリシン類縁体の共役体
MX2020010813A (es) 2018-04-17 2021-01-08 Endocyte Inc Metodos de tratamiento de 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
EP3972627A4 (en) 2019-05-20 2023-06-21 Endocyte, Inc. Methods for preparing psma conjugates
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
AU2019452577B2 (en) 2019-06-29 2023-08-24 Hangzhou Dac Biotech Co., Ltd. Cell-binding molecule-Tubulysin derivative conjugate and preparation method therefor
EP3862023A1 (en) 2020-02-05 2021-08-11 Hangzhou DAC Biotech Co, Ltd Conjugates of cell-binding molecules with cytotoxic agents
WO2022106629A1 (en) 2020-11-19 2022-05-27 Novartis Ag Synthesis of prostate specific membrane antigen (psma) ligands
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
CN117980327A (zh) 2021-11-03 2024-05-03 杭州多禧生物科技有限公司 抗体的特异性偶联
US12233115B2 (en) 2022-09-30 2025-02-25 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
GR81790B (enExample) 1983-04-29 1984-12-12 Omnichem Sa
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
US5103018A (en) 1986-08-26 1992-04-07 Kyowa Hakko Kogyo Kabushiki Kaisha Mitomycin derivatives
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
IL93982A0 (en) 1989-04-03 1991-01-31 Purdue Research Foundation Method for enhancing transmembrane transport of exogenous molecules
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
EP0457875A4 (en) 1989-11-13 1993-03-03 Xoma Corporation 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
EP0547163B1 (en) 1990-08-29 2002-02-06 Centre Hospitalier Regional De Nantes Protein polyligands joined to a stable protein core
US5130307A (en) 1990-09-28 1992-07-14 American Home Products Corporation Aminoesters of rapamycin
US5378696A (en) 1990-09-19 1995-01-03 American Home Products Corporation Rapamycin esters
US5221670A (en) 1990-09-19 1993-06-22 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
US5118678A (en) 1991-04-17 1992-06-02 American Home Products Corporation Carbamates of rapamycin
US5194447A (en) 1992-02-18 1993-03-16 American Home Products Corporation Sulfonylcarbamates 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
US7279561B1 (en) 1993-04-23 2007-10-09 Wyeth Anti-rapamycin monoclonal antibodies
EP1181938B1 (en) 1993-04-23 2007-11-14 Wyeth Rapamycin conjugates and 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
AU717020B2 (en) 1996-05-03 2000-03-16 Immunomedics Inc. Targeted combination immunotherapy of cancer
DE19621133A1 (de) 1996-05-24 1997-11-27 Boehringer Mannheim Gmbh Bestimmungsverfahren mit oligomerisierten Rezeptoren
CA2264592C (en) 1996-08-27 2012-02-21 University Of Utah Research Foundation Bioconjugates and delivery of bioactive agents
EP0923287A4 (en) 1996-08-30 2001-08-01 Lilly Co Eli NON-CLASSIC PYRROLO (2,3-D) PYRIMIDINE ANTIFOLATE
AU715632B2 (en) 1996-09-12 2000-02-03 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
US6372712B1 (en) 1998-05-22 2002-04-16 The Board Of Trustees Of The Leland Stanford Jr. University Synthetic bifunctional molecules containing a drug moiety and presenter protein ligand
WO2000035422A2 (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
HUP0201425A3 (en) 1999-04-23 2006-07-28 Hadasit Med Res Service Conjugate having a cleavable linkage for use in a liposome
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
WO2001013957A2 (en) 1999-08-24 2001-03-01 Cellgate, Inc. Enhancing drug delivery across and into epithelial tissues using oligo arginine moieties
WO2001028592A1 (en) 1999-10-15 2001-04-26 Mayo Foundation For Medical Education And Research Cobalamin conjugates useful as imaging agents and as antitumor agents
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
HK1049997B (en) 1999-11-24 2007-02-23 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
ATE278421T1 (de) 2000-08-11 2004-10-15 Wyeth Corp Verfahren zur behandlung eines östrogenrezeptor positives karzinoms
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
JP2004526425A (ja) 2000-11-28 2004-09-02 ワイス 前立腺癌の診断および治療に有用なｆｋｂｐ核酸およびポリペプチドの発現分析
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
US6800653B2 (en) 2001-06-01 2004-10-05 Bristol-Myers Squibb Compnay 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
US6680330B2 (en) 2001-08-22 2004-01-20 Wyeth Rapamycin dialdehydes
EP1419154B1 (en) 2001-08-22 2005-10-05 Wyeth Rapamycin 29-enols
DE60234782D1 (de) 2001-09-28 2010-01-28 Purdue Research Foundation Behandlungsverfahren mit liganden-immunogenkonjugaten
GR1004163B (el) 2001-11-01 2003-02-21 Πολυκυκλικα παραγωγα τροποποιησης των οπτικων ιδιοτητων και των ιδιοτητων αντοχης στο πλασμα των πολυμερων λιθογραφιας
EP1519735A4 (en) 2001-12-12 2006-01-11 Conforma Therapeutic Corp ASSAYS AND DEVICES 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
ES2438008T3 (es) 2002-05-06 2014-01-15 Endocyte, Inc. Agentes de formación de imágenes dirigidos a vitaminas
US6596757B1 (en) 2002-05-14 2003-07-22 Immunogen Inc. Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use
KR20040106547A (ko) 2002-05-15 2004-12-17 엔도사이트, 인코포레이티드 비타민-마이토마이신 공액체
EP1521769B1 (de) 2002-07-09 2015-09-09 Dömling, Alexander Tubulysinkonjugate
US7816377B2 (en) 2002-07-09 2010-10-19 R&D-Biopharmaceuticals Gmbh Tubulysin analogues
KR20050026033A (ko) 2002-07-31 2005-03-14 쉐링 악티엔게젤샤프트 신규 효과기 접합체, 그의 제조 방법 및 그의 약학적 용도
DE10241152A1 (de) 2002-09-05 2004-03-18 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysin-Biosynthese-Gene
KR20140070676A (ko) 2002-09-06 2014-06-10 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
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
DE10254439A1 (de) 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
US7060797B2 (en) 2002-11-21 2006-06-13 Wyeth Composition and method for treating lupus nephritis
CA2508831C (en) 2002-12-13 2012-05-01 Immunomedics, Inc. Immunoconjugates with an intracellularly-cleavable linkage
US7601332B2 (en) 2003-01-27 2009-10-13 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
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
EP2669377A3 (en) 2003-04-17 2015-10-14 Alnylam Pharmaceuticals Inc. Modified iRNA agents
EP1622646B1 (en) 2003-05-06 2012-08-08 Purdue Research Foundation 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
EP1646635A1 (en) 2003-07-16 2006-04-19 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
SI1718340T1 (sl) 2004-01-30 2008-04-30 Bayer Schering Pharma Ag Novi efektorski konjugati, postopek za njihovo proizvodnjo in njihova farmacevtska uporaba
WO2005111238A2 (en) 2004-04-19 2005-11-24 Archemix Corporation Aptamer-mediated intracellular delivery of therapeutic oligonucleotides
BRPI0510909A2 (pt) * 2004-05-19 2008-12-16 Medarex Inc composto de ligaÇço fÁrmaco-ligante citotàxico, formulaÇço farmacÊutica, mÉtodo para matar uma cÉlula e mÉtodo para retardar ou interromper o crescimento de tumor
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
CN101098854B (zh) 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
EP2990410A1 (en) 2004-08-10 2016-03-02 Alnylam Pharmaceuticals Inc. Chemically modified oligonucleotides
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
US7811572B2 (en) 2005-08-24 2010-10-12 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
DE602006012816D1 (de) 2005-03-30 2010-04-22 Endocyte Inc Tifizierung von zellulären folat vitamin rezeptoren
AU2006262231B2 (en) 2005-06-20 2013-01-24 Psma Development Company, Llc PSMA antibody-drug conjugates
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
JP2009504783A (ja) 2005-08-19 2009-02-05 エンドサイト，インコーポレイテッド ビンカアルカロイド、類似体および誘導体のリガンド結合体
RU2470668C2 (ru) 2005-08-19 2012-12-27 Эндосайт, Инк. Конъюгаты лиганда с несколькими лекарственными средствами
MX2008002395A (es) 2005-08-19 2008-03-18 Neose Technologies Inc Factor vii y factor viia glicopegilados.
US20070134332A1 (en) 2005-11-21 2007-06-14 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
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
US20080176958A1 (en) 2007-01-24 2008-07-24 Insert Therapeutics, Inc. Cyclodextrin-based polymers for therapeutics delivery
AU2008214801B2 (en) 2007-02-16 2014-02-27 Ktb Tumorforschungsgesellschaft Mbh Dual acting prodrugs
US20100104626A1 (en) 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
CN104127878A (zh) 2007-03-14 2014-11-05 恩多塞特公司 结合配体连接的微管溶素递药缀合物
EP2148886B1 (en) 2007-05-10 2014-02-19 R & D Biopharmaceuticals Gmbh Tubulysine derivatives
BRPI0812970A2 (pt) 2007-06-25 2019-09-24 Endocyte Inc conjugados contendo espaçadores hidrofílicos
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
DK2187965T3 (da) 2007-08-17 2020-01-20 Purdue Research Foundation Psma-bindingsligand-linker-konjugater og fremgangsmåder til anvendelse
EP2209374B1 (en) 2007-10-25 2014-12-03 Endocyte, Inc. Tubulysins and processes for preparing
US8507455B2 (en) 2007-12-04 2013-08-13 Alnylam Pharmaceuticals, Inc. Folate conjugates
UA108598C2 (xx) 2008-04-30 2015-05-25 Високоефективні кон'югати та гідрофільні зшиваючі агенти (лінкери)
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
US20110288152A1 (en) 2008-10-17 2011-11-24 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
WO2011057805A1 (en) 2009-11-12 2011-05-19 R&D Biopharmaceuticals Gmbh Tubulin inhibitors
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
US20120258905A1 (en) 2009-12-23 2012-10-11 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
CA2790577A1 (en) 2010-02-25 2011-09-01 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
PT2528625E (pt) 2010-04-15 2013-10-17 Spirogen Sarl Pirrolobenzodiazepinas e conjugados das mesmas
EP2409983A1 (en) 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
US8889880B2 (en) 2010-08-06 2014-11-18 Endocyte, Inc. Processes for preparing tubulysins
US20130203680A1 (en) 2010-09-27 2013-08-08 Endocyte, Inc. Folate conjugates for treating inflammation of the eye
WO2012090104A1 (en) 2010-12-31 2012-07-05 Kareus Therapeutics, Sa Methods and compositions for designing novel conjugate therapeutics
EA033468B1 (ru) 2011-03-29 2019-10-31 Immunogen Inc Способы получения конъюгата "антитело-майтансиноид"
KR20140019415A (ko) 2011-03-29 2014-02-14 이뮤노젠 아이엔씨 향상된 균질성의 접합체를 제조하기 위한 방법
WO2012177837A2 (en) 2011-06-21 2012-12-27 Immunogen, Inc. Novel maytansinoid derivatives with peptide linker and conjugates thereof
BR112014013526A8 (pt) 2011-12-05 2017-06-13 Igenica Biotherapeutics Inc conjugados de anticorpo-fármaco e compostos, composições e métodos relacionados
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
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
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
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
EP2708243A1 (en) 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
US20140107316A1 (en) 2012-10-16 2014-04-17 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
EA201590622A1 (ru) 2012-10-16 2015-10-30 Эндосайт, Инк. Конъюгаты для доставки лекарственного средства, содержащие не встречающиеся в природе аминокислоты, и способы применения
KR102318999B1 (ko) 2012-11-15 2021-10-29 엔도사이트, 인코포레이티드 Psma 발현 세포에 의해 야기되는 질병을 치료하기 위한 컨쥬게이트
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
KR20210132742A (ko) 2012-12-21 2021-11-04 알트루바이오 인코퍼레이티드 친수성 자기-희생 링커 및 그것의 포합체
DK2956173T3 (en) 2013-02-14 2017-07-17 Bristol Myers Squibb Co TUBULYSIS RELATIONSHIPS, METHODS OF PRODUCING AND USING THEREOF
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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