AU2010279674B2 - Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof - Google Patents

Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof Download PDF

Info

Publication number
AU2010279674B2
AU2010279674B2 AU2010279674A AU2010279674A AU2010279674B2 AU 2010279674 B2 AU2010279674 B2 AU 2010279674B2 AU 2010279674 A AU2010279674 A AU 2010279674A AU 2010279674 A AU2010279674 A AU 2010279674A AU 2010279674 B2 AU2010279674 B2 AU 2010279674B2
Authority
AU
Australia
Prior art keywords
substituted
unsubstituted
alkyl
compound
alkenyl
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.)
Ceased
Application number
AU2010279674A
Other languages
English (en)
Other versions
AU2010279674A1 (en
Inventor
Heng Cheng
Qiang Cong
Sanjeev Gangwar
Qian Zhang
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.)
ER Squibb and Sons LLC
Original Assignee
ER Squibb and Sons LLC
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 ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC
Publication of AU2010279674A1 publication Critical patent/AU2010279674A1/en
Assigned to MEDAREX, L.L.C. reassignment MEDAREX, L.L.C. Amend patent request/document other than specification (104) Assignors: MEDAREX, INC.
Assigned to E. R. SQUIBB & SONS, L.L.C. reassignment E. R. SQUIBB & SONS, L.L.C. Alteration of Name(s) of Applicant(s) under S113 Assignors: MEDAREX, L.L.C.
Application granted granted Critical
Publication of AU2010279674B2 publication Critical patent/AU2010279674B2/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • 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
    • 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
    • A61K47/6817—Toxins
    • A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
    • C07C229/14—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of carbon skeletons containing rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
    • C07C229/16—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • 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
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • 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
    • C07K5/10—Tetrapeptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)
AU2010279674A 2009-08-03 2010-08-02 Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof Ceased AU2010279674B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US23093209P 2009-08-03 2009-08-03
US61/230,932 2009-08-03
US23288309P 2009-08-11 2009-08-11
US61/232,883 2009-08-11
PCT/US2010/044078 WO2011017249A1 (en) 2009-08-03 2010-08-02 Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof

Publications (2)

Publication Number Publication Date
AU2010279674A1 AU2010279674A1 (en) 2012-02-23
AU2010279674B2 true AU2010279674B2 (en) 2015-05-07

Family

ID=42782224

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2010279674A Ceased AU2010279674B2 (en) 2009-08-03 2010-08-02 Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof

Country Status (28)

Country Link
US (6) US8394922B2 (enExample)
EP (1) EP2461830B1 (enExample)
JP (1) JP5859964B2 (enExample)
KR (1) KR101759359B1 (enExample)
CN (2) CN102725001B (enExample)
AR (1) AR077701A1 (enExample)
AU (1) AU2010279674B2 (enExample)
BR (1) BR112012002615A2 (enExample)
CA (1) CA2770042C (enExample)
CL (1) CL2012000302A1 (enExample)
CO (1) CO6501196A2 (enExample)
DK (1) DK2461830T3 (enExample)
EA (1) EA022288B1 (enExample)
ES (1) ES2525351T3 (enExample)
HR (1) HRP20140976T1 (enExample)
HU (1) HUE026997T2 (enExample)
IL (1) IL217717A (enExample)
IN (1) IN2012DN00860A (enExample)
MX (1) MX2012001665A (enExample)
NZ (1) NZ597985A (enExample)
PE (1) PE20121087A1 (enExample)
PL (1) PL2461830T3 (enExample)
PT (1) PT2461830E (enExample)
SG (2) SG178095A1 (enExample)
SI (1) SI2461830T1 (enExample)
SM (1) SMT201400183B (enExample)
TW (1) TWI469794B (enExample)
WO (1) WO2011017249A1 (enExample)

Families Citing this family (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101098854B (zh) 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
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
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
BRPI0812970A2 (pt) 2007-06-25 2019-09-24 Endocyte Inc conjugados contendo espaçadores hidrofílicos
DK2187965T3 (da) 2007-08-17 2020-01-20 Purdue Research Foundation Psma-bindingsligand-linker-konjugater og fremgangsmåder til anvendelse
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
US9951324B2 (en) 2010-02-25 2018-04-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
CA3220104A1 (en) 2010-06-08 2011-12-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
HRP20180028T4 (hr) * 2011-03-16 2020-10-02 F. Hoffmann - La Roche Ag Kromatografija izmjene iona s poboljšanom selektivnošću za odvajanje polipeptidnih monomera, agregata i fragmenata modulacijom pokretne faze
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
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
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
HK1220626A1 (zh) 2013-03-15 2017-05-12 The Centre For Drug Research And Development 具细胞毒性和抗有丝分裂的化合物以及其使用方法
JP6171435B2 (ja) * 2013-03-18 2017-08-02 富士通株式会社 半導体装置及びその製造方法、電源装置、高周波増幅器
WO2014197866A1 (en) 2013-06-06 2014-12-11 Igenica Biotherapeutics, Inc. Modified antibodies and related compounds, compositions, and methods of use
WO2015057585A1 (en) * 2013-10-14 2015-04-23 Regents Of The University Of Minnesota Therapeutic compounds
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
WO2015074792A1 (en) 2013-11-25 2015-05-28 Ontochem Gmbh Method for diagnosing g-protein coupled receptor-related diseases
KR102384740B1 (ko) 2013-12-27 2022-04-07 자임워크스 인코포레이티드 약물 접합체를 위한 설폰아마이드-함유 연결 시스템
MX2016008448A (es) 2013-12-27 2017-01-09 Zymeworks Inc Conjugados de var2csa-farmaco.
WO2015113760A1 (en) * 2014-01-28 2015-08-06 Tube Pharmaceuticals Gmbh Cytotoxic tubulysin compounds for conjugation
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
WO2015135659A1 (en) 2014-03-14 2015-09-17 Ontochem Gmbh Receptor ligand linked cytotoxic molecules
SG11201607818WA (en) 2014-03-20 2016-10-28 Bristol Myers Squibb Co Stabilized fibronectin based scaffold molecules
CA2945318A1 (en) * 2014-04-11 2015-10-15 Medimmune, Llc Tubulysin derivatives
JP6539729B2 (ja) * 2014-06-03 2019-07-03 ジアリー・ファーマシューティカルズ・インコーポレイテッドＪｉａｒａｙ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． ペプチド−薬物複合体
CN104262455B (zh) * 2014-08-22 2017-05-03 亚飞（上海）生物医药科技有限公司 肿瘤微环境靶向激活的紫杉醇衍生物及其制备和用途
CN106715457B (zh) 2014-08-22 2021-09-28 亚飞（上海）生物医药科技有限公司 一种肿瘤微环境特异激活的小分子靶向偶联体及其用途
HRP20241124T1 (hr) 2014-09-11 2024-11-22 Seagen Inc. Ciljana isporuka lijekovitih tvari koje sadrže tercijarni amin
JP2017531620A (ja) 2014-09-12 2017-10-26 ジェネンテック， インコーポレイテッド システイン操作抗体及びコンジュゲート
ES2905569T3 (es) 2014-09-17 2022-04-11 Zymeworks Inc Compuestos citotóxicos y antimitóticos y métodos para utilizarlos
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
ES2826566T3 (es) 2014-11-21 2021-05-18 Bristol Myers Squibb Co Anticuerpos que comprenden regiones constantes pesadas modificadas
JP6805142B2 (ja) 2014-11-21 2020-12-23 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｃｄ７３に対する抗体およびその使用
JP6622814B2 (ja) 2014-11-25 2019-12-18 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ イメージングのための新規ｐｄ−ｌ１結合ポリペプチド
US10188759B2 (en) 2015-01-07 2019-01-29 Endocyte, Inc. Conjugates for imaging
KR20170137725A (ko) * 2015-02-25 2017-12-13 윌리엄 마쉬 라이스 유니버시티 데스아세톡시투불리신 h 및 이의 유사체
ES2736106T3 (es) 2015-03-10 2019-12-26 Bristol Myers Squibb Co Anticuerpos que se pueden conjugar mediante la transglutaminasa y conjugados producidos a partir de ellos
AU2016271111B2 (en) 2015-05-29 2022-04-28 Bristol-Myers Squibb Company Antibodies against OX40 and uses thereof
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
EP3353198B1 (en) 2015-09-23 2020-06-17 Bristol-Myers Squibb Company Glypican-3binding fibronectin based scafflold molecules
WO2017052259A1 (ko) * 2015-09-24 2017-03-30 주식회사 엘지화학 화합물 및 이를 포함하는 유기 발광 소자
TWI660741B (zh) 2015-11-03 2019-06-01 財團法人工業技術研究院 抗體藥物複合物及其製造方法
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
US11229708B2 (en) 2015-12-04 2022-01-25 Seagen Inc. Conjugates of quaternized tubulysin compounds
EP3394096A1 (en) 2015-12-21 2018-10-31 Bristol-Myers Squibb Company Variant antibodies for site-specific conjugation
CA3012960A1 (en) 2016-02-01 2017-08-10 Pfizer Inc. Tubulysin analogs and methods for their preparation
AU2017228470A1 (en) 2016-03-04 2018-08-30 Bristol-Myers Squibb Company Combination therapy with anti-CD73 antibodies
CN105664134B (zh) * 2016-03-13 2019-04-26 浙江药苑生物科技有限公司 一种用于治疗骨癌的药物组合物
JP2019518013A (ja) 2016-05-10 2019-06-27 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 安定性が向上したツブリシン類似体の抗体薬物結合体
US20170326249A1 (en) 2016-05-10 2017-11-16 Bristol-Myers Squibb Company Antibody-drug conjugate of an anti-glypican-3 antibody and a tubulysin analog, preparation and uses
WO2017218724A1 (en) 2016-06-16 2017-12-21 Bristol-Myers Squibb Company Process and intermediates for making tubulysin analogs
WO2018035391A1 (en) 2016-08-19 2018-02-22 Bristol-Myers Squibb Company Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use
US20190218294A1 (en) 2016-09-09 2019-07-18 Bristol-Myers Squibb Company Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment
US10517958B2 (en) 2016-10-04 2019-12-31 Zymeworks Inc. Compositions and methods for the treatment of platinum-drug resistant cancer
US10398783B2 (en) 2016-10-20 2019-09-03 Bristol-Myers Squibb Company Antiproliferative compounds and conjugates made therefrom
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
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
MX2019013132A (es) 2017-05-25 2020-01-27 Bristol Myers Squibb Co Anticuerpos que comprenden regiones constantes pesadas modificadas.
US11274124B2 (en) 2017-11-29 2022-03-15 William Marsh Rice University Tubulysin analogues as anticancer agents and payloads for antibody-drug conjugates and methods of treatment therewith
MX2020010813A (es) 2018-04-17 2021-01-08 Endocyte Inc Metodos de tratamiento de cancer.
WO2019209811A1 (en) 2018-04-24 2019-10-31 Bristol-Myers Squibb Company Macrocyclic toll-like receptor 7 (tlr7) agonists
JP7458997B2 (ja) 2018-05-29 2024-04-01 ブリストル－マイヤーズ スクイブ カンパニー プロドラッグおよび複合体に使用する修飾自己切断部分ならびにその使用方法および製造方法
US11020490B2 (en) 2018-06-22 2021-06-01 Bristol-Myers Squibb Company Antibody-drug conjugate with a tubulysin analog warhead having a stabilized acetate group in the TUV subunit
JP2022513653A (ja) 2018-11-28 2022-02-09 ブリストル－マイヤーズ スクイブ カンパニー 修飾された重鎖定常領域を含む抗体
DK3886914T3 (da) 2018-11-30 2023-07-03 Bristol Myers Squibb Co Antistof omfattende en glutaminholdig letkæde-c-terminal forlængelse, konjugater deraf og fremgangsmåder samt anvendelser
WO2020123425A2 (en) 2018-12-12 2020-06-18 Bristol-Myers Squibb Company Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
WO2020132658A2 (en) 2018-12-21 2020-06-25 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
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
US20240377413A1 (en) 2019-09-16 2024-11-14 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
CN113387829B (zh) * 2020-03-13 2023-04-07 凯特立斯（深圳）科技有限公司 一种沙库必曲的制备方法
MX2022015769A (es) * 2020-06-24 2023-01-19 Regeneron Pharma Tubulisinas y conjugados de proteina-tubulisina.
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
WO2026080716A1 (en) * 2024-10-11 2026-04-16 Codeable Therapeutics, Incorporated Modified self-immolating moieties in antibody-drug conjugates

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008138561A1 (en) * 2007-05-10 2008-11-20 R & D Biopharmaceuticals Gmbh Tubulysine derivatives

Family Cites Families (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981001145A1 (en) 1979-10-18 1981-04-30 Univ Illinois Hydrolytic enzyme-activatible pro-drugs
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US5144011A (en) 1981-06-26 1992-09-01 Boston University Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers
US4631190A (en) 1981-06-26 1986-12-23 Shen Wei C Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
US4698420A (en) 1985-02-25 1987-10-06 Xoma Corporation Antibody hybrid molecules and process for their preparation
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (es) 1985-06-26 1992-08-01 Liposome Co Inc Metodo para acoplamiento de liposomas.
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
TW420681B (en) 1995-12-08 2001-02-01 Lederle Japan Ltd Carbapenem-3-carboxylic acid ester derivatives
DE19638870B4 (de) 1996-09-23 2009-05-14 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysine, Verfahren zu ihrer Gewinnung und sie enthaltende Mittel
US7214487B2 (en) 1998-06-26 2007-05-08 Sunesis Pharmaceuticals, Inc. Methods for identifying compounds that modulate enzymatic activities by employing covalently bonded target-extender complexes with ligand candidates
NZ517202A (en) 1999-08-24 2004-05-28 Medarex Inc Human CTLA-4 antibodies and their uses
DE10008089A1 (de) 2000-02-22 2001-10-31 Biotechnolog Forschung Gmbh Syntheseverfahren zur Herstellung von Tubulysinen
US20020169125A1 (en) 2001-03-21 2002-11-14 Cell Therapeutics, Inc. Recombinant production of polyanionic polymers and uses thereof
KR20030033007A (ko) 2001-05-31 2003-04-26 코울터 파머수티컬, 인코포레이티드 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제
US7091186B2 (en) 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
EP1471938A4 (en) 2002-01-09 2008-03-05 Medarex Inc HUMAN MONOCLONAL ANTIBODIES AGAINST CD30
US7816377B2 (en) 2002-07-09 2010-10-19 R&D-Biopharmaceuticals Gmbh Tubulysin analogues
EP1521769B1 (de) 2002-07-09 2015-09-09 Dömling, Alexander Tubulysinkonjugate
DE10241152A1 (de) 2002-09-05 2004-03-18 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysin-Biosynthese-Gene
FR2845630B1 (fr) * 2002-10-09 2005-09-30 Helitest Ags Dispositif de demasticage, notamment pour la refection de joints dans des structures de reservoirs d'aeronefs et container d'intervention
DE10254439A1 (de) * 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
EP1613274B1 (en) 2003-04-15 2010-03-03 GlaxoSmithKline LLC Human il-18 substitution mutants and their conjugates
PE20050712A1 (es) 2003-07-22 2005-11-02 Schering Ag Anticuerpos rg1
CA2556752C (en) 2004-02-23 2016-02-02 Genentech, Inc. Heterocyclic self-immolative linkers and conjugates
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
US7691962B2 (en) 2004-05-19 2010-04-06 Medarex, Inc. Chemical linkers and conjugates thereof
US7541330B2 (en) 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
DE102004030227A1 (de) 2004-06-23 2006-01-26 Dömling, Alexander, Dr. Wirkstoffe mit antiangiogenetischen Eigenschaften
TR201808537T4 (tr) 2004-09-23 2018-07-23 Genentech Inc Sistein değiştirilmiş antikorlar ve konjugatlar.
ES2386366T3 (es) 2005-02-18 2012-08-17 Medarex, Inc. Anticuerpo monoclonal humano contra el antígeno de membrana específico de la próstata (PSMA)
US7714016B2 (en) 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
EP3530736A3 (en) 2005-05-09 2019-11-06 ONO Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics
WO2007002223A2 (en) 2005-06-20 2007-01-04 Medarex, Inc. Cd19 antibodies and their uses
RU2470668C2 (ru) 2005-08-19 2012-12-27 Эндосайт, Инк. Конъюгаты лиганда с несколькими лекарственными средствами
EA016577B1 (ru) 2005-09-26 2012-06-29 Медарекс, Инк. Конъюгаты антитело-лекарство и их применение
EP1934261B1 (en) 2005-09-26 2014-10-29 Medarex, L.L.C. Human monoclonal antibodies to cd70
BRPI0619331A2 (pt) 2005-10-26 2011-09-27 Medarex Inc método para fazer um composto para preparar um análogo de cbi cc-1065, método para preparar um análogo de cbi cc-1065 e composto
WO2007059404A2 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
NZ569236A (en) 2005-12-08 2012-06-29 Medarex Inc Human monoclonal antibodies to protein tyrosine kinase 7 (PTK7) and their use
US8609816B2 (en) 2005-12-08 2013-12-17 Medarex, L.L.C. Human monoclonal antibodies to O8E
SG177168A1 (en) 2006-12-01 2012-01-30 Medarex Inc Human antibodies that bind cd22 and uses thereof
US20100150950A1 (en) 2006-12-14 2010-06-17 Medarex, Inc. Human antibodies that bind cd70 and uses thereof
UY30776A1 (es) 2006-12-21 2008-07-03 Medarex Inc Anticuerpos cd44
TWI412367B (zh) 2006-12-28 2013-10-21 梅達雷克斯有限責任公司 化學鏈接劑與可裂解基質以及其之綴合物
US20080176958A1 (en) 2007-01-24 2008-07-24 Insert Therapeutics, Inc. Cyclodextrin-based polymers for therapeutics delivery
JP2010519310A (ja) 2007-02-21 2010-06-03 メダレックス インコーポレイテッド 単一のアミノ酸を有する化学リンカーおよびその複合体
US20100047841A1 (en) 2007-02-27 2010-02-25 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Synthesis of desacetoxytubulysin h and analogs thereof
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
US7387981B1 (en) 2007-06-28 2008-06-17 Lyondell Chemical Technology, L.P. Direct epoxidation catalyst and process
EP2181101A2 (en) 2007-07-20 2010-05-05 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysin d analogues
DK2187965T3 (da) 2007-08-17 2020-01-20 Purdue Research Foundation Psma-bindingsligand-linker-konjugater og fremgangsmåder til anvendelse
EP2185188B1 (en) 2007-08-22 2014-08-06 Medarex, L.L.C. Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions
HRP20150074T1 (hr) 2007-10-01 2015-03-13 Bristol-Myers Squibb Company Humana antitijela koja se vežu za mezotelin i njihove uporabe
EP2209374B1 (en) 2007-10-25 2014-12-03 Endocyte, Inc. Tubulysins and processes for preparing
EP2174947A1 (en) * 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008138561A1 (en) * 2007-05-10 2008-11-20 R & D Biopharmaceuticals Gmbh Tubulysine derivatives

Also Published As

Publication number Publication date
KR20120047998A (ko) 2012-05-14
IN2012DN00860A (enExample) 2015-07-10
IL217717A0 (en) 2012-03-29
BR112012002615A2 (pt) 2020-11-03
US20140323690A1 (en) 2014-10-30
US8772542B2 (en) 2014-07-08
ES2525351T3 (es) 2014-12-22
US20130189256A1 (en) 2013-07-25
CA2770042A1 (en) 2011-02-10
JP2013501055A (ja) 2013-01-10
EA022288B1 (ru) 2015-12-30
US8394922B2 (en) 2013-03-12
US20160060294A1 (en) 2016-03-03
CL2012000302A1 (es) 2012-07-20
CA2770042C (en) 2017-02-28
DK2461830T3 (en) 2015-01-12
HK1164751A1 (en) 2012-09-28
US8772543B2 (en) 2014-07-08
KR101759359B1 (ko) 2017-07-18
CN104592351A (zh) 2015-05-06
US9580467B2 (en) 2017-02-28
HUE026997T2 (en) 2016-08-29
AU2010279674A1 (en) 2012-02-23
AR077701A1 (es) 2011-09-14
US20130204033A1 (en) 2013-08-08
SG178095A1 (en) 2012-03-29
MX2012001665A (es) 2012-03-26
PT2461830E (pt) 2014-12-11
CO6501196A2 (es) 2012-08-15
IL217717A (en) 2017-06-29
EP2461830A1 (en) 2012-06-13
US20110027274A1 (en) 2011-02-03
TW201106976A (en) 2011-03-01
US8802632B2 (en) 2014-08-12
PL2461830T3 (pl) 2015-03-31
EP2461830B1 (en) 2014-09-24
WO2011017249A1 (en) 2011-02-10
US20130197259A1 (en) 2013-08-01
EA201270242A1 (ru) 2012-07-30
SMT201400183B (it) 2015-01-15
NZ597985A (en) 2013-08-30
PE20121087A1 (es) 2012-08-17
SI2461830T1 (sl) 2015-01-30
CN102725001B (zh) 2015-01-14
SG10201503332XA (en) 2015-06-29
HRP20140976T1 (hr) 2015-01-02
US9226974B2 (en) 2016-01-05
TWI469794B (zh) 2015-01-21
CN102725001A (zh) 2012-10-10
JP5859964B2 (ja) 2016-02-16

Similar Documents

Publication Publication Date Title
EP2461830B1 (en) Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
CA2900854C (en) Tubulysin compounds, methods of making and use
HK1164751B (en) Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
HK1212209B (en) Tubulysin compounds, methods of making and use

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)
MK14 Patent ceased section 143(a) (annual fees not paid) or expired