IN2012DN00860A - - Google Patents

Download PDF

Info

Publication number
IN2012DN00860A
IN2012DN00860A IN860DEN2012A IN2012DN00860A IN 2012DN00860 A IN2012DN00860 A IN 2012DN00860A IN 860DEN2012 A IN860DEN2012 A IN 860DEN2012A IN 2012DN00860 A IN2012DN00860 A IN 2012DN00860A
Authority
IN
India
Prior art keywords
ligand
conjugated
antibody
optionally
formula
Prior art date
Application number
Inventor
Heng Cheng
Qiang Cong
Sanjeev Gangwar
Qian Zhang
Original Assignee
Medarex 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 Medarex Inc filed Critical Medarex Inc
Publication of IN2012DN00860A publication Critical patent/IN2012DN00860A/en

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)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (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)

Abstract

Antiproliferative compounds having a structure represented by formula (II), where n, R1, R2, R3, R4, and R5 are as defined herein, can be used to treat tumors, optionally when conjugated to a ligand such as an antibody:
IN860DEN2012 2009-08-03 2010-08-02 IN2012DN00860A (en)

Applications Claiming Priority (3)

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

Publications (1)

Publication Number Publication Date
IN2012DN00860A true IN2012DN00860A (en) 2015-07-10

Family

ID=42782224

Family Applications (1)

Application Number Title Priority Date Filing Date
IN860DEN2012 IN2012DN00860A (en) 2009-08-03 2010-08-02

Country Status (28)

Country Link
US (6) US8394922B2 (en)
EP (1) EP2461830B1 (en)
JP (1) JP5859964B2 (en)
KR (1) KR101759359B1 (en)
CN (2) CN102725001B (en)
AR (1) AR077701A1 (en)
AU (1) AU2010279674B2 (en)
BR (1) BR112012002615A2 (en)
CA (1) CA2770042C (en)
CL (1) CL2012000302A1 (en)
CO (1) CO6501196A2 (en)
DK (1) DK2461830T3 (en)
EA (1) EA022288B1 (en)
ES (1) ES2525351T3 (en)
HR (1) HRP20140976T1 (en)
HU (1) HUE026997T2 (en)
IL (1) IL217717A (en)
IN (1) IN2012DN00860A (en)
MX (1) MX2012001665A (en)
NZ (1) NZ597985A (en)
PE (1) PE20121087A1 (en)
PL (1) PL2461830T3 (en)
PT (1) PT2461830E (en)
SG (2) SG10201503332XA (en)
SI (1) SI2461830T1 (en)
SM (1) SMT201400183B (en)
TW (1) TWI469794B (en)
WO (1) WO2011017249A1 (en)

Families Citing this family (90)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5149620B2 (en) 2004-07-23 2013-02-20 エンドサイト，インコーポレイテッド Bivalent linker and conjugate thereof
NZ580132A (en) 2007-03-14 2012-11-30 Endocyte Inc Binding ligand linked drug delivery conjugates of tubulysins to vitamins
CN104383553A (en) 2007-06-25 2015-03-04 恩多塞特公司 Conjugates containing hydrophilic spacer linkers
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US9193763B2 (en) 2007-08-17 2015-11-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
IT1394860B1 (en) * 2009-07-22 2012-07-20 Kemotech S R L PHARMACEUTICAL COMPOUNDS
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
SG185428A1 (en) 2010-06-08 2012-12-28 Genentech Inc Cysteine engineered antibodies and conjugates
ES2656167T5 (en) * 2011-03-16 2021-03-26 Hoffmann La Roche Ion exchange chromatography with improved selectivity for the separation of monomers, aggregates and polypeptide fragments by modulating the mobile phase
CA2837840C (en) 2011-06-10 2020-08-04 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
US10080805B2 (en) 2012-02-24 2018-09-25 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
EP3925627A1 (en) * 2012-05-15 2021-12-22 Concortis Biosystems, Corp Drug-conjugates and uses thereof
EP3210627B1 (en) * 2012-07-12 2022-12-21 Hangzhou Dac Biotech Co., Ltd Conjugates of cell binding molecules with cytotoxic agents
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
EP2708243A1 (en) 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
JP2015536323A (en) 2012-10-16 2015-12-21 エンドサイト・インコーポレイテッドＥｎｄｏｃｙｔｅ， Ｉｎｃ． Drug delivery conjugates comprising unnatural amino acids and methods of use
AU2013344778C1 (en) 2012-11-15 2024-06-27 Endocyte, Inc. Conjugates for treating diseases caused by PSMA expressing cells
AU2012395148B2 (en) 2012-11-24 2016-10-27 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
CA2892863C (en) 2012-12-10 2022-03-15 Mersana Therapeutics, Inc. Polymeric scaffold based on phf for targeted drug delivery
EP2931316B1 (en) 2012-12-12 2019-02-20 Mersana Therapeutics, Inc. Hydroxyl-polymer-drug-protein conjugates
LT2956173T (en) 2013-02-14 2017-06-26 Bristol-Myers Squibb Company Tubulysin compounds, methods of making and use
US20140249315A1 (en) * 2013-03-01 2014-09-04 Endocyte, Inc. Processes for preparing tubulysins
US9522876B2 (en) 2013-03-15 2016-12-20 Zymeworks Inc. Cytotoxic and anti-mitotic compounds, and methods of using the same
JP6171435B2 (en) * 2013-03-18 2017-08-02 富士通株式会社 Semiconductor device and manufacturing method thereof, power supply device, and high-frequency amplifier
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
EP3456700A1 (en) 2013-10-18 2019-03-20 Deutsches Krebsforschungszentrum Labeled inhibitors of prostate specific membrane antigen (psma), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
CN105849568B (en) 2013-11-14 2018-05-04 恩多塞特公司 Compounds for Positron Emission Tomography
WO2015074792A1 (en) 2013-11-25 2015-05-28 Ontochem Gmbh Method for diagnosing g-protein coupled receptor-related diseases
SG11201605260VA (en) 2013-12-27 2016-07-28 Zymeworks Inc Var2csa-drug conjugates
ES2916722T3 (en) 2013-12-27 2022-07-05 Zymeworks Inc Sulfonamide-containing linkage systems for drug conjugates
ES2843537T3 (en) 2014-01-28 2021-07-19 Tube Pharmaceuticals Gmbh Cytotoxic tubulysin compounds and conjugates thereof
FI3122757T3 (en) 2014-02-28 2023-10-10 Hangzhou Dac Biotech Co Ltd Charged linkers and their uses for conjugation
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
UY36075A (en) * 2014-04-11 2015-10-30 Medimmune Llc TUBULISINE DERIVATIVES
CN106456799B (en) * 2014-06-03 2020-05-22 江苏佳瑞生物技术有限公司 Peptide-drug conjugates
EP3184540A4 (en) 2014-08-22 2018-03-21 Yafei Shanghai Biolog Medicine Science& Technology Specifically activated micromolecular target coupling body in tumor microenvironment and use thereof
CN104262455B (en) * 2014-08-22 2017-05-03 亚飞（上海）生物医药科技有限公司 Tumor microenvironment targeted activation docetaxel derivatives, preparation thereof and uses of the derivatives
HRP20241124T1 (en) * 2014-09-11 2024-11-22 Seagen Inc. TARGETED DELIVERY OF MEDICINAL SUBSTANCES CONTAINING TERTIARY AMINE
TW201625688A (en) 2014-09-12 2016-07-16 建南德克公司 Cysteine engineered antibodies and conjugates
EP3194421B1 (en) 2014-09-17 2021-11-03 Zymeworks Inc. Cytotoxic and anti-mitotic compounds, and methods of using the same
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
PL3221346T3 (en) 2014-11-21 2021-03-08 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
TWI711630B (en) 2014-11-21 2020-12-01 美商必治妥美雅史谷比公司 Antibodies against cd73 and uses thereof
WO2016086021A1 (en) 2014-11-25 2016-06-02 Bristol-Myers Squibb Company Novel pd-l1 binding polypeptides for imaging
US10188759B2 (en) 2015-01-07 2019-01-29 Endocyte, Inc. Conjugates for imaging
EA201791896A1 (en) 2015-02-25 2018-02-28 Уильям Марш Райс Юниверсити DESATECOXITUBULIZIN H AND ITS ANALOGUES
ES2736106T3 (en) 2015-03-10 2019-12-26 Bristol Myers Squibb Co Antibodies that can be conjugated by transglutaminase and conjugates produced from them
EA035412B1 (en) 2015-05-29 2020-06-10 Бристол-Майерс Сквибб Компани ANTIBODIES TO OX40 AND THEIR APPLICATION
EP3319936B1 (en) 2015-07-12 2025-12-17 Hangzhou Dac Biotech Co., Ltd. Bridge linkers for conjugation of cell-binding molecules
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
EP3353198B1 (en) 2015-09-23 2020-06-17 Bristol-Myers Squibb Company Glypican-3binding fibronectin based scafflold molecules
TWI678364B (en) * 2015-09-24 2019-12-01 南韓商Ｌｇ化學股份有限公司 Compound and organic light emitting device comprising the same
CN107029242A (en) 2015-11-03 2017-08-11 财团法人工业技术研究院 Antibody drug complex and method for producing same
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
TWI852735B (en) 2015-12-04 2024-08-11 美商思進公司 Conjugates of quaternized tubulysin compounds
US20180362619A1 (en) 2015-12-21 2018-12-20 Bristol-Myers Squibb Company Variant antibodies for site-specific conjugation
WO2017134547A1 (en) 2016-02-01 2017-08-10 Pfizer Inc. Tubulysin analogs and methods for their preparation
CA3016187A1 (en) 2016-03-04 2017-09-08 Bristol-Myers Squibb Company Combination therapy with anti-cd73 antibodies
CN109620949A (en) * 2016-03-13 2019-04-16 曹帅 It is a kind of for treating the pharmaceutical composition of osteocarcinoma
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
JP2019518013A (en) 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 Antibody drug conjugates of tubulysin analogues with improved stability
US10106560B2 (en) 2016-06-16 2018-10-23 Bristol-Myers Squibb Company Process and intermediates for making tubulysin analogs
ES2902179T3 (en) 2016-08-19 2022-03-25 Bristol Myers Squibb Co 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
WO2018075842A1 (en) 2016-10-20 2018-04-26 Bristol-Myers Squibb Company Condensed benzodiazepine derivatives and conjugates made therefrom
AU2016429272A1 (en) 2016-11-14 2019-05-02 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
JP6585650B2 (en) * 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 Conjugates of cytotoxic agents and cell-bound receptors
US20200299400A1 (en) 2017-05-25 2020-09-24 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
WO2019108685A1 (en) * 2017-11-29 2019-06-06 William March Rice University Tubulysin analogues as anticancer agents and payloads for antibody-drug conjugates and methods of treatment therewith
KR20210003135A (en) 2018-04-17 2021-01-11 엔도사이트, 인코포레이티드 Cancer treatment method
WO2019209811A1 (en) 2018-04-24 2019-10-31 Bristol-Myers Squibb Company Macrocyclic toll-like receptor 7 (tlr7) agonists
SG11202011739SA (en) 2018-05-29 2020-12-30 Bristol Myers Squibb Co Modified self-immolating moieties for use in prodrugs and conjugates and methods of using and making
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 (en) 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 Antibodies containing modified heavy chain constant regions
KR102861586B1 (en) 2018-11-30 2025-09-17 브리스톨-마이어스 스큅 컴퍼니 Antibodies comprising a glutamine-containing light chain C-terminal extension, conjugates thereof, and methods and uses thereof
JP7514836B2 (en) 2018-12-12 2024-07-11 ブリストル－マイヤーズ スクイブ カンパニー Engineered antibodies for conjugation with transglutaminase, and conjugates, methods and uses thereof
CN118027137A (en) 2018-12-21 2024-05-14 里珍纳龙药品有限公司 Tubulysin and protein-tubulysin conjugates
JP7604397B2 (en) 2019-05-20 2024-12-23 エンドサイト・インコーポレイテッド Methods for preparing PSMA conjugates
JP6842127B2 (en) * 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 Conjugates of cytotoxic agents and cell-binding receptors
JP2022540395A (en) 2019-06-29 2022-09-15 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． Cell-binding molecule-tubulysin derivative conjugate and method for preparing the same
US20240377413A1 (en) 2019-09-16 2024-11-14 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
CN113387829B (en) * 2020-03-13 2023-04-07 凯特立斯（深圳）科技有限公司 Preparation method of shakubiqu
EP4171653A2 (en) * 2020-06-24 2023-05-03 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
JP7044419B2 (en) * 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 Conjugates of cytotoxic agents and cell-binding receptors
CN117980327A (en) 2021-11-03 2024-05-03 杭州多禧生物科技有限公司 Specific conjugation of antibodies

Family Cites Families (73)

* 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 (en) 1985-06-26 1992-08-01 Liposome Co Inc LIPOSOMAS COUPLING METHOD.
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5312335A (en) 1989-11-09 1994-05-17 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 (en) 1996-09-23 2009-05-14 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysins, methods for their production and agents containing them
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
CN102766210B (en) * 1999-08-24 2015-07-08 E.R.施贵宝&圣斯有限责任公司 Human CTLA-4 antibodies and uses thereof
DE10008089A1 (en) 2000-02-22 2001-10-31 Biotechnolog Forschung Gmbh Production of tubulysin compounds comprises multi-stage process including condensation of N-methylpipecolinoyl-isoleucine with substituted thiazole-4-carboxylic acid derivative
PE20020908A1 (en) * 2001-03-21 2002-10-26 Cell Therapeutics Inc RECOMBINANT PRODUCTION OF POLYANIONIC POLYMERS AND USE OF THE SAME
US7087600B2 (en) * 2001-05-31 2006-08-08 Medarex, Inc. Peptidyl prodrugs and linkers and stabilizers useful therefor
US7091186B2 (en) 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
JP4562395B2 (en) * 2002-01-09 2010-10-13 メダレックス， インク． Human monoclonal antibody against CD30
WO2004005326A2 (en) * 2002-07-09 2004-01-15 Morphochem Aktiengellschaft Fu Tubulysin conjugates
DK1523493T3 (en) * 2002-07-09 2013-12-02 Alexander Doemling New tubulysine analogues
DE10241152A1 (en) * 2002-09-05 2004-03-18 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysin biosynthesis genes
FR2845630B1 (en) * 2002-10-09 2005-09-30 Helitest Ags DEMASTICATING DEVICE, IN PARTICULAR FOR REFLECTING JOINTS IN AIRCRAFT TANK STRUCTURES AND CONTAINER INTERVENTION
DE10254439A1 (en) * 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysins, manufacturing processes and tubulysin agents
TW200510454A (en) 2003-04-15 2005-03-16 Smithkline Beecham Corp Conjugates comprising human IL-18 and substitution mutants thereof
JP4680902B2 (en) * 2003-07-22 2011-05-11 バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト RG1 antibody and use thereof
EP1718667B1 (en) 2004-02-23 2013-01-09 Genentech, Inc. Heterocyclic self-immolative linkers and conjugates
US7517903B2 (en) * 2004-05-19 2009-04-14 Medarex, Inc. Cytotoxic compounds and conjugates
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 (en) 2004-06-23 2006-01-26 Dömling, Alexander, Dr. Treatment of diseases (e.g. proliferative diseases of tumor cells, ophthalmic diseases and skin diseases) associated with angiogenesis comprises administration of carbamide compounds
ES2579805T3 (en) 2004-09-23 2016-08-16 Genentech, Inc. Antibodies and conjugates engineered with cysteine
MX2007009878A (en) * 2005-02-18 2007-10-03 Medarex Inc Human monoclonal antibodies to prostate specific membrane antigen (psma).
US7714016B2 (en) * 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
PL2161336T5 (en) 2005-05-09 2017-10-31 Ono Pharmaceutical Co 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
EP1899379B1 (en) * 2005-06-20 2018-04-11 E. R. Squibb & Sons, L.L.C. Cd19 antibodies and their uses
EP2374480A3 (en) * 2005-08-19 2013-05-01 Endocyte, Inc. Mutli-drug ligand conjugates
AU2006294554B2 (en) * 2005-09-26 2013-03-21 E. R. Squibb & Sons, L.L.C. Antibody-drug conjugates and methods of use
NZ566395A (en) * 2005-09-26 2012-03-30 Medarex Inc Human monoclonal antibodies to CD70
CN101365679B (en) * 2005-10-26 2012-11-14 梅达莱克斯公司 Methods and compounds for preparing cc-1065 analogs
CA2627190A1 (en) * 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
NZ568015A (en) * 2005-12-08 2012-03-30 Medarex Inc Human monoclonal antibodies to O8E
AU2006321841C1 (en) * 2005-12-08 2013-01-24 E. R. Squibb & Sons, L.L.C. Human monoclonal antibodies to protein tyrosine kinase 7 ( PTK7 ) and their use
EP2097097B1 (en) 2006-12-01 2018-05-30 E. R. Squibb & Sons, L.L.C. Antibodies, in particular human antibodies, that bind cd22 and uses thereof
AU2007333098A1 (en) 2006-12-14 2008-06-19 Medarex, Inc. Human antibodies that bind CD70 and uses thereof
UY30776A1 (en) * 2006-12-21 2008-07-03 Medarex Inc CD44 ANTIBODIES
TWI412367B (en) 2006-12-28 2013-10-21 梅達雷克斯有限責任公司 Chemical linker and cleavable substrate and conjugate thereof
US20080176958A1 (en) * 2007-01-24 2008-07-24 Insert Therapeutics, Inc. Cyclodextrin-based polymers for therapeutics delivery
KR20090122439A (en) * 2007-02-21 2009-11-30 메다렉스, 인코포레이티드 Chemical linkers and conjugates thereof having a single amino acid
WO2008106080A2 (en) * 2007-02-27 2008-09-04 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Synthesis of desacetoxytubulysin h and analogs thereof
NZ580132A (en) * 2007-03-14 2012-11-30 Endocyte Inc Binding ligand linked drug delivery conjugates of tubulysins to vitamins
EP2532673A3 (en) 2007-05-10 2014-01-08 R & D Biopharmaceuticals Gmbh Tubulysine derivatives
CN104383553A (en) 2007-06-25 2015-03-04 恩多塞特公司 Conjugates containing hydrophilic spacer linkers
US7387981B1 (en) 2007-06-28 2008-06-17 Lyondell Chemical Technology, L.P. Direct epoxidation catalyst and process
WO2009012958A2 (en) 2007-07-20 2009-01-29 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysin d analogues
US9193763B2 (en) 2007-08-17 2015-11-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
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
SI2195017T1 (en) 2007-10-01 2015-01-30 Bristol-Myers Squibb Company Human antibodies that bind mesothelin, and uses thereof
WO2009055562A1 (en) 2007-10-25 2009-04-30 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

Also Published As

Publication number Publication date
US8772542B2 (en) 2014-07-08
BR112012002615A2 (en) 2020-11-03
CA2770042C (en) 2017-02-28
US9226974B2 (en) 2016-01-05
US8772543B2 (en) 2014-07-08
HUE026997T2 (en) 2016-08-29
IL217717A (en) 2017-06-29
EA022288B1 (en) 2015-12-30
CN102725001A (en) 2012-10-10
PE20121087A1 (en) 2012-08-17
SG10201503332XA (en) 2015-06-29
PT2461830E (en) 2014-12-11
US20130189256A1 (en) 2013-07-25
CN104592351A (en) 2015-05-06
PL2461830T3 (en) 2015-03-31
US9580467B2 (en) 2017-02-28
CO6501196A2 (en) 2012-08-15
JP5859964B2 (en) 2016-02-16
AU2010279674B2 (en) 2015-05-07
US20160060294A1 (en) 2016-03-03
EA201270242A1 (en) 2012-07-30
SI2461830T1 (en) 2015-01-30
AR077701A1 (en) 2011-09-14
SMT201400183B (en) 2015-01-15
KR20120047998A (en) 2012-05-14
SG178095A1 (en) 2012-03-29
US20140323690A1 (en) 2014-10-30
AU2010279674A1 (en) 2012-02-23
CN102725001B (en) 2015-01-14
US20110027274A1 (en) 2011-02-03
WO2011017249A1 (en) 2011-02-10
EP2461830A1 (en) 2012-06-13
TW201106976A (en) 2011-03-01
CA2770042A1 (en) 2011-02-10
IL217717A0 (en) 2012-03-29
TWI469794B (en) 2015-01-21
US8394922B2 (en) 2013-03-12
US20130204033A1 (en) 2013-08-08
NZ597985A (en) 2013-08-30
KR101759359B1 (en) 2017-07-18
HRP20140976T1 (en) 2015-01-02
MX2012001665A (en) 2012-03-26
CL2012000302A1 (en) 2012-07-20
HK1164751A1 (en) 2012-09-28
US20130197259A1 (en) 2013-08-01
DK2461830T3 (en) 2015-01-12
US8802632B2 (en) 2014-08-12
EP2461830B1 (en) 2014-09-24
ES2525351T3 (en) 2014-12-22
JP2013501055A (en) 2013-01-10

Similar Documents

Publication Publication Date Title
NZ597985A (en) Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
MX341524B (en) Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates.
NZ705394A (en) Antibody-drug conjugate
MX2012008141A (en) Compounds and methods.
MX341133B (en) Compounds and methods.
MY156319A (en) Spiroheterocyclic n-oxypiperidines as pesticides
EA201170168A1 (en) COMPLEX (MINERAL-AMINO ACID) - POLYSACCHARIDE
TW200940681A (en) Novel organic electroluminescent compounds and organic electroluminescent device using the same
MX2010004493A (en) Tropane compounds.
EA201200102A1 (en) COMPOUNDS APPLICABLE AS A MEDICINE
TW200940683A (en) Novel organic electroluminescent compounds and organic electroluminescent device using the same
IN2015MN00135A (en)
MX2013008560A (en) Method for preparing 2-aminobenzamide derivatives.
EA201170154A1 (en) DERIVATIVES OF PYRIDINOPIRIDINONES, METHOD OF THEIR RECEPTION AND APPLICATION IN THERAPY
PH12012501813A1 (en) Iap bir domain binding compounds
MA32647B1 (en) Pyrrole compounds
NZ597570A (en) N1-acyl-5-fluoropyrimidinone derivatives
MX2014004920A (en) Novel pyrazine derivatives.
MX2012007835A (en) 2,5,7-substituted oxazolopyrimidine derivatives.
MX2012014796A (en) Process for preparing 4-hydroxypyridines.
MX2012012523A (en) Anticancer steroidal lactones unsaturated in position 7 (8).
MX2012005155A (en) Quinazoline compounds.
EA201270237A1 (en) Method of producing 1-benzyl-3-hydroxymethyl-1H-indazole and its derivatives and necessary intermediate compounds containing magnetic
EA201300792A1 (en) CHEMICAL COMPOUNDS
MX361998B (en) Method for producing 4-haloalkyl -3-mercapto-substituted 2-hydroxy-benzoic acid derivatives.