HRP20220123T1 - Citotoksični i antimitotički spojevi, te postupci njihove uporabe - Google Patents

Citotoksični i antimitotički spojevi, te postupci njihove uporabe Download PDF

Info

Publication number
HRP20220123T1
HRP20220123T1 HRP20220123TT HRP20220123T HRP20220123T1 HR P20220123 T1 HRP20220123 T1 HR P20220123T1 HR P20220123T T HRP20220123T T HR P20220123TT HR P20220123 T HRP20220123 T HR P20220123T HR P20220123 T1 HRP20220123 T1 HR P20220123T1
Authority
HR
Croatia
Prior art keywords
alkyl
amino
aryl
cycloalkyl
thio
Prior art date
Application number
HRP20220123TT
Other languages
English (en)
Inventor
Geoffrey C. Winters
James R. RICH
Graham Albert Edwin GARNETT
Alexander Laurence MANDEL
Tom Han Hsiao HSIEH
Elyse Marie Josee Bourque
Stuart Daniel Barnscher
Original Assignee
Zymeworks 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 Zymeworks Inc. filed Critical Zymeworks Inc.
Publication of HRP20220123T1 publication Critical patent/HRP20220123T1/hr

Links

Classifications

    • 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
    • A61K38/05—Dipeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • 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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • 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
    • 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
    • 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
    • A61K47/6813—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6855—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from breast cancer cell
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6867—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of a blood cancer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
    • C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
    • C07D207/448—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • C07K5/0205—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)3-C(=0)-, e.g. statine or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/02—Linear peptides containing at least one abnormal peptide link
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L25/00—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof
    • H01L25/16—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof the devices being of types provided for in two or more different main groups of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. forming hybrid circuits
    • H01L25/162—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof the devices being of types provided for in two or more different main groups of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. forming hybrid circuits the devices being mounted on two or more different substrates
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L25/00—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof
    • H01L25/16—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof the devices being of types provided for in two or more different main groups of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. forming hybrid circuits
    • H01L25/167—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof the devices being of types provided for in two or more different main groups of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. forming hybrid circuits comprising optoelectronic devices, e.g. LED, photodiodes
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
    • H10K59/00—Integrated devices, or assemblies of multiple devices, comprising at least one organic light-emitting element covered by group H10K50/00
    • H10K59/10—OLED displays
    • H10K59/12—Active-matrix OLED [AMOLED] displays
    • H10K59/131—Interconnections, e.g. wiring lines or terminals
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
    • H10K59/00—Integrated devices, or assemblies of multiple devices, comprising at least one organic light-emitting element covered by group H10K50/00
    • H10K59/10—OLED displays
    • H10K59/18—Tiled displays
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
    • H10K71/00—Manufacture or treatment specially adapted for the organic devices covered by this subclass
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
    • H10K77/00—Constructional details of devices covered by this subclass and not covered by groups H10K10/80, H10K30/80, H10K50/80 or H10K59/80
    • H10K77/10—Substrates, e.g. flexible substrates
    • H10K77/111—Flexible substrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
    • H10K59/00—Integrated devices, or assemblies of multiple devices, comprising at least one organic light-emitting element covered by group H10K50/00
    • H10K59/10—OLED displays
    • H10K59/12—Active-matrix OLED [AMOLED] displays
    • H10K59/1201—Manufacture or treatment

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Cell Biology (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Computer Hardware Design (AREA)
  • Power Engineering (AREA)
  • Manufacturing & Machinery (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)

Claims (26)

1. Spoj s Formulom I: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time što: R1 je odabran iz niza koji sadrži: amino-C1-C6 alkil, amino-aril, amino-C3-C7 cikloalkil, amino-heterociklil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između arila, aril-C1-C6 alkila, C1-C6 alkila, C1-C6 alkiltio, karboksila, karboksamida, C3-C7 cikloalkila, C3-C7 cikloalkil-C1-C6 alkila, gvanidino, halo, C1-C6 haloalkila, heterociklila, heterociklil-C1-C6 alkila, hidroksila, i tio; ili R1 je RaRbNCH(Rc)-; Ra je odabran iz niza koji sadrži: H i C1-C6 alkil; Rb je C1-C6 alkil; i Rc je Rd-C(CH3)2-; i Rd je odabran iz niza koji sadrži: H, aril, C3-C7 cikloalkil, i heteroaril, od kojih je svaki izborno supstituiran s jednim ili više supstituenata odabranih iz niza koji sadrži: C1-C4 aciltio, C2-C4 alkenil, C1-C4 alkil, C1-C4 alkilamino, C1-C4 alkiloksi, amino, amino-C1-C4 alkil, halo, C1-C4 haloalkil, hidroksil, hidroksi-C1-C4 alkil, i tio, pri čemu su C2-C4 alkenil, C1-C4 alkilamino i C1-C4 alkiloksi dalje izborno supstituirani s jednim supstituentom odabranim od C1-C4 alkilarila, hidroksila, i tio; ili Rb i Rc uzeti zajedno s atomima na koje su svaki vezani tvore heterociklildiil; R2 je odabran iz niza koji sadrži: C1-C6 alkil, aril, aril-C1-C6 alkil, C3-C7 cikloalkil, C3-C7 cikloalkil-C1-C6 alkil, heteroaril, heteroaril-C1-C6 alkil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-arila, amino-C3-C7 cikloalkila, arila, karboksamida, karboksila, cijano, C1-C6 haloacila, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila; i X je odsutan.
2. Spoj prema patentnom zahtjevu 1, naznačen time što R1 je odabran iz niza koji sadrži: amino-C1-C6 alkil, amino-aril, amino-C3-C7 cikloalkil, amino-heterociklil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih od C1-C6 alkila i halo.
3. Spoj prema patentnom zahtjevu 1, naznačen time što R1 je RaRbNCH(Rc)-.
4. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time što je R2 odabran iz niza koji sadrži: C2-C6 alkil, aril, aril-C1-C6 alkil, C4-C7 cikloalkil, C3-C7 cikloalkil-C1-C6 alkil, heteroaril, heteroaril-C1-C6 alkil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-aril, amino-C3-C7 cikloalkila, arila, karboksamida, karboksila, cijano, C1-C6 haloacila, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila.
5. Spoj prema patentnom zahtjevu 1 koji ima Formulu Ia: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time što: R2 je odabran iz niza koji sadrži: C1-C6 alkil, aril, aril-C1-C6 alkil, C3-C7 cikloalkil, C3-C7 cikloalkil-C1-C6 alkil, heteroaril, heteroaril-C1-C6 alkil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-aril, amino-C3-C7 cikloalkil, arila, karboksamida, karboksila, cijano, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila; i R4 i R5 su svaki neovisno odabrani između: H i C1-C6 alkila.
6. Spoj prema patentnom zahtjevu 1 koji ima Formulu Id: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time što: R2 je odabran iz niza koji sadrži: C1-C6 alkil, aril, aril-C1-C6 alkil, C3-C7 cikloalkil, C3-C7 cikloalkil-C1-C6 alkil, heteroaril, heteroaril-C1-C6 alkil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-arila, amino-C3-C7 cikloalkila, arila, karboksamida, karboksila, cijano, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila; i R4 i R5 su svaki neovisno odabrani između: H i C1-C6 alkila.
7. Spoj prema patentnom zahtjevu 5 ili 6, naznačen time što: R2 je odabran iz niza koji sadrži: C2-C6 alkil, aril, aril-C1-C6 alkil, C4-C7 cikloalkil, C3-C7 cikloalkil-C1-C6 alkil, heteroaril, heteroaril-C1-C6 alkil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-arila, amino-C3-C7 cikloalkila, arila, karboksamida, karboksila, cijano, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila.
8. Spoj prema bilo kojem od patentnih zahtjeva 5 do 7, naznačen time što R4 i R5 su svaki C1-C6 alkil.
9. Spoj prema bilo kojem od patentnih zahtjeva 5 do 7, naznačen time što R4 i R5 su svaki metil.
10. Spoj prema bilo kojem od patentnih zahtjeva 5 do 7, naznačen time što R4 je H, i R5 je C1-C6 alkil.
11. Spoj prema bilo kojem od patentnih zahtjeva 5 do 7, naznačen time što R4 je H, i R5 je metil.
12. Spoj prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time što je R2 odabran iz niza koji sadrži: aril, aril-C1-C6 alkil, heteroaril i heteroaril-C1-C6 alkil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-arila, amino-C3-C7 cikloalkila, arila, karboksamida, karboksila, cijano, C1-C6 haloacila, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila.
13. Spoj prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time što je R2 odabran iz niza koji sadrži: aril i aril-C1-C6 alkil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: amino, amino-C1-C6 alkila i amino-C3-C7 cikloalkila.
14. Spoj prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time što je R2 odabran od: 4-aminobenzila, 4-(aminometil)benzila, 4-(aminometil)fenila, 4-aminofenila i benzila.
15. Spoj prema patentnom zahtjevu 1 naznačen time što je odabran od sljedećeg, ili njegove farmaceutski prihvatljive soli: [image] [image]
16. Spoj odabran od sljedećeg, ili njegova farmaceutski prihvatljiva sol: [image]
17. Pripravak s formulom II: (T)-(L)-(D) II naznačen time što je (T) ciljajući dio koji je sposoban vezati ciljnu stanicu, (L) je spona, a (D) je spoj prema bilo kojem od zahtjeva 1 do 15.
18. Pripravak prema patentnom zahtjevu 17, naznačen time što (L)-(D) ima jednu od slijedećih struktura: [image] [image] [image] [image] ili [image]
19. Pripravak s formulom III: (T)-(L1)-(D1) III naznačen time što: (T) je ciljajući dio koji je sposoban vezati ciljnu stanicu; (D1) je spoj prema patentnom zahtjevu 1 koji ima strukturu (IV): [image] pri čemu: R1 je odabran iz niza koji sadrži: amino-C1-C6 alkil, amino-aril, amino-C3-C7 cikloalkil, amino-heterociklil, i heterociklil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između arila, aril-C1-C6 alkila, C1-C6 alkila, C1-C6 alkiltio, karboksila, karboksamida, C3-C7 cikloalkila, C3-C7 cikloalkil-C1-C6 alkila, gvanidino, halo, C1-C6 haloalkila, heterociklila, heterociklil-C1-C6 alkila, hidroksila, i tio; ili R1 je RaRbNCH(Rc)-; Ra je odabran iz niza koji sadrži: H i C1-C6 alkil; Rb je C1-C6 alkil; i Rc je Rd-C(CH3)2-; i Rd je odabran iz niza koji sadrži: H, aril, C3-C7 cikloalkil, i heteroaril, od kojih je svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C4 aciltio, C2-C4 alkenila, C1-C4 alkila, C1-C4 alkilamino, C1-C4 alkiloksi, amino, amino-C1-C4 alkila, halo, C1-C4 haloalkila, hidroksila, hidroksi-C1-C4 alkila, i tio, pri čemu C2-C4 alkenil, C1-C4 alkilamino i C1-C4 alkiloksi su dalje izborno supstituirani s jednim supstituentom odabranim od C1-C4 alkilarila, hidroksila, i tio; ili Rb i Rc uzeti zajedno s atomima na koje su svaki vezani tvore heterociklildiil; X je odsutan; R2a je odabran iz niza koji sadrži: C2-C6 alkildiil, arildiil, C4-C7 cikloalkildiil, heteroarildiil, i heterociklildiil, svaki izborno supstituiran s jednim ili više supstituenata odabranih između: C1-C6 alkoksi, C1-C6 alkoksikarbonila, C1-C6 alkila, C1-C6 alkilamino, amino, amino-C1-C6 alkila, amino-arila, amino-C3-C7 cikloalkila, arila, karboksamida, karboksila, cijano, C1-C6 haloalkila, C1-C6 haloalkoksi, halo, hidroksila, nitro, tio, i tio-C1-C6 alkila; i (L1)-(T) ima strukturu (V): (AA)1-(AA)n-(L2)-(T) V pri čemu: -NH- skupina vezana na R2a u formuli IV tvori enzimsku cijepajuću peptidnu vezu (JPB) s (AA)1 u formuli V; svaki AA je neovisno aminokiselina; n je cijeli broj od 0 do 25, i (L2) je izborno preostali dio spone (L1), i pri čemu (AA)1-(AA)n, uzeti zajedno sadrže aminokiselinsku sekvencu sposobnu olakšati enzimsko cijepanje JPB.
20. Pripravak prema bilo kojem od patentnih zahtjeva 17 do 19, naznačen time što je (T) monoklonsko antitijelo ili fragment antitijela.
21. Pripravak prema patentnom zahtjevu 20, naznačen time što je antitijelo ili fragment antitijela bispecifično antitijelo ili fragment antitijela.
22. Pripravak prema patentnom zahtjevu 20 ili 21, naznačen time što antitijelo ili fragment antitijela specifično veže antigen stanice raka.
23. Pripravak prema patentnom zahtjevu 22, naznačen time što je antigen stanice raka HER2.
24. Farmaceutski pripravak naznačen time što sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 16 ili njegovu farmaceutski prihvatljivu sol, ili pripravak prema bilo kojem od zahtjeva 17 do 23, te farmaceutski prihvatljiv nosač, razrjeđivač ili pomoćnu tvar.
25. Spoj prema bilo kojem od patentnih zahtjeva 1 do 16, ili pripravak prema bilo kojem od zahtjeva 17 do 23, naznačen time što je za uporabu u terapiji.
26. Spoj ili pripravak za uporabu prema patentnom zahtjevu 25, naznačen time što je terapija liječenje raka.
HRP20220123TT 2014-09-17 2015-09-17 Citotoksični i antimitotički spojevi, te postupci njihove uporabe HRP20220123T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462051883P 2014-09-17 2014-09-17
EP15842388.9A EP3194421B1 (en) 2014-09-17 2015-09-17 Cytotoxic and anti-mitotic compounds, and methods of using the same
PCT/CA2015/050910 WO2016041082A1 (en) 2014-09-17 2015-09-17 Cytotoxic and anti-mitotic compounds, and methods of using the same

Publications (1)

Publication Number Publication Date
HRP20220123T1 true HRP20220123T1 (hr) 2022-04-15

Family

ID=55454112

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20220123TT HRP20220123T1 (hr) 2014-09-17 2015-09-17 Citotoksični i antimitotički spojevi, te postupci njihove uporabe

Country Status (21)

Country Link
US (5) US9879086B2 (hr)
EP (2) EP3194421B1 (hr)
JP (2) JP6875273B2 (hr)
KR (2) KR102494557B1 (hr)
CN (2) CN107001415B (hr)
AU (2) AU2015318556C1 (hr)
BR (1) BR112017005126B1 (hr)
CA (1) CA2960899C (hr)
CY (1) CY1124933T1 (hr)
DK (1) DK3194421T3 (hr)
ES (1) ES2905569T3 (hr)
HR (1) HRP20220123T1 (hr)
HU (1) HUE057768T2 (hr)
IL (3) IL287645B2 (hr)
MX (1) MX2017003476A (hr)
PL (1) PL3194421T3 (hr)
PT (1) PT3194421T (hr)
RS (1) RS62860B1 (hr)
RU (1) RU2723651C2 (hr)
SG (1) SG11201702143PA (hr)
WO (1) WO2016041082A1 (hr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX368258B (es) 2013-03-15 2019-09-25 Zymeworks Inc Compuestos citotoxicos y antimitoticos y metodos de uso de los mismos.
CN106255513B (zh) * 2013-12-27 2022-01-14 酵活有限公司 用于药物偶联物的含磺酰胺连接系统
CA2935064C (en) 2013-12-27 2023-06-27 Zymeworks Inc. Var2csa-drug conjugates
IL287645B2 (en) 2014-09-17 2024-04-01 Zymeworks Bc Inc Cytotoxic and anti-mitotic compounds and methods for their use
US10517958B2 (en) 2016-10-04 2019-12-31 Zymeworks Inc. Compositions and methods for the treatment of platinum-drug resistant cancer
IL315325A (en) 2018-01-04 2024-10-01 Iconic Therapeutics Inc Anti-tissue-mediated antibodies, antibody-drug conjugates, and related methods
MX2020009469A (es) * 2018-03-13 2021-01-29 Zymeworks Inc Conjugados de anticuerpo y farmaco anti-her2 biparatopicos y metodos de uso.
KR20220029724A (ko) * 2019-07-03 2022-03-08 아이코닉 테라퓨틱스, 인코포레이티드 항-조직 인자 항체-약물 접합체 및 관련 방법
US12076400B2 (en) 2019-12-06 2024-09-03 Zymeworks Bc Inc. Methods of using a bispecific antigen-binding construct targeting HER2 in combination with CDK4/6 inhibitors for the treatment of breast cancer
CN112285361B (zh) * 2020-09-27 2023-12-05 中国人民解放军空军军医大学 排除抗-cd38单克隆抗体药物对抗人球蛋白检测干扰的试剂

Family Cites Families (140)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2036891B (en) 1978-12-05 1983-05-05 Windsor Smith C Change speed gear
CA1213229A (en) 1982-04-12 1986-10-28 Gary S. David Antibodies having dual specificities, their preparation and uses therefor
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
JPS6147500A (ja) 1984-08-15 1986-03-07 Res Dev Corp Of Japan キメラモノクロ−ナル抗体及びその製造法
EP0173494A3 (en) 1984-08-27 1987-11-25 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by dna splicing and expression
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
JPS61134325A (ja) 1984-12-04 1986-06-21 Teijin Ltd ハイブリツド抗体遺伝子の発現方法
CA1282069C (en) 1985-09-12 1991-03-26 Damon L. Meyer Antibody complexes of hapten-modified diagnostic or therapeutic agents
AU606320B2 (en) 1985-11-01 1991-02-07 International Genetic Engineering, Inc. Modular assembly of antibody genes, antibodies prepared thereby and use
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US5053394A (en) 1988-09-21 1991-10-01 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
FI102355B1 (fi) 1988-02-11 1998-11-30 Bristol Myers Squibb Co Menetelmä yhdistävän välikappaleen omaavien antrasykliini-immunokonjugaattien valmistamiseksi
US5094849A (en) 1988-08-08 1992-03-10 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized vinca analogs via simple organic linkers
US5028697A (en) 1988-08-08 1991-07-02 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized methotrexate analogs via simple organic linkers
US5006652A (en) 1988-08-08 1991-04-09 Eli Lilly And Company Intermediates for antibody-vinca drug conjugates
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5137877B1 (en) 1990-05-14 1996-01-30 Bristol Myers Squibb Co Bifunctional linking compounds conjugates and methods for their production
GB9017024D0 (en) 1990-08-03 1990-09-19 Erba Carlo Spa New linker for bioactive agents
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
ATE158021T1 (de) 1990-08-29 1997-09-15 Genpharm Int Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
US5622929A (en) 1992-01-23 1997-04-22 Bristol-Myers Squibb Company Thioether conjugates
WO1994004690A1 (en) 1992-08-17 1994-03-03 Genentech, Inc. Bispecific immunoadhesins
US6569834B1 (en) 1992-12-03 2003-05-27 George R. Pettit Elucidation and synthesis of antineoplastic tetrapeptide w-aminoalkyl-amides
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
HUT72067A (en) 1992-12-16 1996-03-28 Basf Ag Dolostatin analog
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
US5556623A (en) 1993-03-30 1996-09-17 Eli Lilly And Company Antibody-drug conjugates
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
AU689131B2 (en) 1993-10-01 1998-03-26 Teikoku Hormone Mfg. Co., Ltd. Novel peptide derivative
US5599902A (en) 1994-11-10 1997-02-04 Arizona Board Of Regents Acting On Behalf Of Arizona State University Cancer inhibitory peptides
US5663149A (en) 1994-12-13 1997-09-02 Arizona Board Of Regents Acting On Behalf Of Arizona State University Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides
GB9508195D0 (en) 1995-04-20 1995-06-07 Univ British Columbia Novel biologically active compounds and compositions,their use and derivation
JP3871713B2 (ja) 1995-05-10 2007-01-24 協和醗酵工業株式会社 新規毒素複合体
EP0904107B1 (en) 1996-03-18 2004-10-20 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
US6759509B1 (en) 1996-11-05 2004-07-06 Bristol-Myers Squibb Company Branched peptide linkers
CA2225325A1 (en) 1997-12-19 1999-06-19 The University Of British Columbia Hemiasterlin analogs
US8097648B2 (en) 1998-06-17 2012-01-17 Eisai R&D Management Co., Ltd. Methods and compositions for use in treating cancer
KR100440643B1 (ko) 1999-01-28 2004-07-21 쥬가이 세이야쿠 가부시키가이샤 치환 페네틸아민 유도체
US6468522B1 (en) 1999-07-22 2002-10-22 University Of Medicine And Dentistry Of New Jersey Controlled release of thioamide moiety-containing therapeutic agents
US6323315B1 (en) 1999-09-10 2001-11-27 Basf Aktiengesellschaft Dolastatin peptides
US6756037B2 (en) 2000-03-31 2004-06-29 Enzon, Inc. Polymer conjugates of biologically active agents and extension moieties for facilitating conjugation of biologically active agents to polymeric terminal groups
TWI245034B (en) 2000-07-24 2005-12-11 Matsushita Electric Ind Co Ltd Capacitor
US6884869B2 (en) 2001-04-30 2005-04-26 Seattle Genetics, Inc. Pentapeptide compounds and uses related thereto
WO2003026577A2 (en) 2001-09-24 2003-04-03 Seattle Genetics, Inc. P-amidobenzylethers in drug delivery agents
US6716821B2 (en) 2001-12-21 2004-04-06 Immunogen Inc. Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same
WO2003072754A2 (en) 2002-02-27 2003-09-04 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Conjugates of ligand, linker and cytotoxic agent and related compositions and methods of use
US7064211B2 (en) 2002-03-22 2006-06-20 Eisai Co., Ltd. Hemiasterlin derivatives and uses thereof
AU2003228354B8 (en) 2002-03-22 2010-03-04 Eisai R&D Management Co., Ltd. Hemiasterlin derivatives and uses thereof in the treatment of cancer
WO2003090678A2 (en) 2002-04-23 2003-11-06 Ohio State University Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin
ITMI20021391A1 (it) 2002-06-25 2003-12-29 Nicox Sa Nitroderivati di inibitori della cicloossigenasi-2
US20050180972A1 (en) 2002-07-31 2005-08-18 Wahl Alan F. Anti-CD20 antibody-drug conjugates for the treatment of cancer and immune disorders
US7659241B2 (en) 2002-07-31 2010-02-09 Seattle Genetics, Inc. Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease
US7087229B2 (en) 2003-05-30 2006-08-08 Enzon Pharmaceuticals, Inc. Releasable polymeric conjugates based on aliphatic biodegradable linkers
US7122189B2 (en) 2002-08-13 2006-10-17 Enzon, Inc. Releasable polymeric conjugates based on aliphatic biodegradable linkers
AU2003259163B2 (en) 2002-08-16 2008-07-03 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
US20040121965A1 (en) 2002-09-20 2004-06-24 Wyeth Holdings Corporation Method of treating resistant tumors
KR20050054951A (ko) 2002-09-20 2005-06-10 와이어쓰 홀딩스 코포레이션 튜불린 억제제의 합성에 유용한 중간체의 합성방법
JP2006507322A (ja) 2002-11-14 2006-03-02 シンタルガ・ビーブイ 多重自己脱離放出スペーサーとして構築されたプロドラッグ
US20070026478A1 (en) 2002-11-21 2007-02-01 Wyeth Hemiasterlin affinity probes and their uses
US7332164B2 (en) 2003-03-21 2008-02-19 Enzon Pharmaceuticals, Inc. Heterobifunctional polymeric bioconjugates
US7390910B2 (en) 2003-08-08 2008-06-24 Wyeth Compounds for treating tumors
US7576206B2 (en) 2003-08-14 2009-08-18 Cephalon, Inc. Proteasome inhibitors and methods of using the same
NZ546417A (en) 2003-09-15 2009-09-25 Univ British Columbia Ceratamines A and B, and analogues, syntheses and pharmaceutical compositions thereof
DE602004025834D1 (de) 2003-10-22 2010-04-15 Univ Johns Hopkins Die behandlung von tumoren
BR122018071808B8 (pt) 2003-11-06 2020-06-30 Seattle Genetics Inc conjugado
US7078562B2 (en) 2004-01-19 2006-07-18 Mitsubishi Gas Chemical Company, Inc. Adamantane derivatives and resin compositions using the same as raw material
US20050175619A1 (en) 2004-02-05 2005-08-11 Robert Duffy Methods of producing antibody conjugates
JP5064037B2 (ja) * 2004-02-23 2012-10-31 ジェネンテック， インコーポレイテッド 複素環式自壊的リンカーおよび結合体
JP4806680B2 (ja) 2004-05-19 2011-11-02 メダレックス インコーポレイテッド 自己犠牲リンカー及び薬剤複合体
WO2006027711A2 (en) 2004-08-26 2006-03-16 Nicholas Piramal India Limited Prodrugs and codrugs containing bio- cleavable disulfide linkers
CN101039701A (zh) 2004-08-26 2007-09-19 尼古拉斯皮拉马尔印度有限公司 含有生物可裂解二硫化物连接物的前药和共药
JP2008519863A (ja) 2004-11-12 2008-06-12 シアトル ジェネティクス インコーポレイティッド Ｎ末端にアミノ安息香酸単位を有するオーリスタチン
CA2587589A1 (en) 2004-11-29 2006-06-22 Seattle Genetics, Inc. Engineered antibodies and immunoconjugates
AR054183A1 (es) 2004-12-22 2007-06-06 Astrazeneca Ab Derivados de piridincarboxamida y su uso como agentes anticancerigenos. procesos de obtencion y composiciones farmaceuticas.
US7714016B2 (en) 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
CA2614436C (en) 2005-07-07 2016-05-17 Seattle Genetics, Inc. Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus
WO2007008848A2 (en) 2005-07-07 2007-01-18 Seattle Genetics, Inc. Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus
PT3248613T (pt) 2005-07-18 2022-03-16 Seagen Inc Conjugados de ligante de fármaco e beta-glucuronida
AU2006277117B2 (en) 2005-08-05 2013-01-10 Syntarga B.V. Triazole-containing releasable linkers and conjugates comprising the same
AU2006294554B2 (en) 2005-09-26 2013-03-21 E. R. Squibb & Sons, L.L.C. Antibody-drug conjugates and methods of use
CA2627190A1 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
WO2007103288A2 (en) 2006-03-02 2007-09-13 Seattle Genetics, Inc. Engineered antibody drug conjugates
US8367065B2 (en) 2006-09-15 2013-02-05 Enzon Pharmaceuticals, Inc. Targeted polymeric prodrugs containing multifunctional linkers
TWI412367B (zh) 2006-12-28 2013-10-21 Medarex Llc 化學鏈接劑與可裂解基質以及其之綴合物
EP2121667B1 (en) 2007-02-21 2016-06-08 E. R. Squibb & Sons, L.L.C. Chemical linkers with single amino acids and conjugates thereof
MX2010003916A (es) 2007-10-10 2010-05-05 Novartis Ag Espiro-pirrolidinas y su uso contra infeccion por el virus de hepatitis c (hcv) y por el virus de inmunodeficiencia humana (vih).
US20090155289A1 (en) 2007-11-01 2009-06-18 Steve Roberts Furin-cleavable peptide linkers for drug-ligand conjugates
CN101932598B (zh) 2008-01-30 2016-12-21 皮里斯股份公司 具有对人c-met受体酪氨酸激酶的亲和性的泪脂质运载蛋白的突变蛋白及其获得方法
US8609105B2 (en) 2008-03-18 2013-12-17 Seattle Genetics, Inc. Auristatin drug linker conjugates
US8236319B2 (en) 2008-04-30 2012-08-07 Immunogen, Inc. Cross-linkers and their uses
EP2276506A4 (en) 2008-04-30 2014-05-07 Immunogen Inc EFFICIENT CONJUGATES AND HYDROPHILIC BINDER
ES2906344T3 (es) 2008-06-27 2022-04-18 Merus Nv Animal murino transgénico productor de anticuerpos
GB2461546B (en) 2008-07-02 2010-07-07 Argen X Bv Antigen binding polypeptides
AU2009275358C1 (en) 2008-07-21 2015-09-24 Polytherics Limited Novel reagents and method for conjugating biological molecules
WO2010033240A2 (en) 2008-09-19 2010-03-25 Nektar Therapeutics Carbohydrate-based drug delivery polymers and conjugates thereof
PL2865387T3 (pl) 2008-11-21 2019-12-31 Københavns Universitet (University Of Copenhagen) Pobudzenie odpowiedzi odpornościowej
US20110182850A1 (en) 2009-04-10 2011-07-28 Trixi Brandl Organic compounds and their uses
KR20120057588A (ko) 2009-05-28 2012-06-05 메르사나 테라퓨틱스, 인코포레이티드 가변 속도 방출 링커를 포함하는 폴리알 약물 접합체
US8394922B2 (en) 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
CA2770866C (en) * 2009-08-28 2017-10-10 Arena Pharmaceuticals, Inc. Cannabinoid receptor modulators
ES2532866T3 (es) 2009-09-25 2015-04-01 Astellas Pharma Inc. Compuesto amida sustituida
JP2013523098A (ja) 2010-03-29 2013-06-17 ザイムワークス，インコーポレイテッド 強化又は抑制されたエフェクター機能を有する抗体
PT2560993T (pt) 2010-04-20 2024-09-16 Genmab As Proteínas contendo anticorpo heterodimérico fc e métodos para a produção das mesmas
ES2528956T3 (es) * 2010-06-10 2015-02-13 Seattle Genetics, Inc. Nuevos derivados de auristatina y su uso
WO2012032080A1 (en) 2010-09-07 2012-03-15 F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H Stabilised human fc
KR101769654B1 (ko) 2010-09-24 2017-08-18 아스텔라스세이야쿠 가부시키가이샤 치환 아미드 화합물
WO2012113847A1 (en) 2011-02-25 2012-08-30 Lonza Ltd Branched linker for protein drug conjugates
JP6101638B2 (ja) 2011-03-03 2017-03-22 ザイムワークス，インコーポレイテッド 多価ヘテロマルチマー足場設計及び構築物
WO2012123957A1 (en) 2011-03-16 2012-09-20 Council Of Scientific & Industrial Research Oligopeptides and process for preparation thereof
CA2831307A1 (en) * 2011-03-30 2012-10-04 Arizona Board Of Regents, For And On Behalf Of, Arizona State Universi Auristatin tyramine phosphate salts and auristatin aminoquinoline derivatives and prodrugs thereof
RU2610336C2 (ru) 2011-04-21 2017-02-09 Сиэтл Дженетикс, Инк. Новые конъюгаты связывающее соединение - активное соединение (adc) и их применение
EA201391756A1 (ru) 2011-05-27 2014-05-30 Амбркс, Инк. Композиции, содержащие, способы, включающие, и применение производных доластатина, связанных с неприродными аминокислотами
WO2012171020A1 (en) 2011-06-10 2012-12-13 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
UA117901C2 (uk) 2011-07-06 2018-10-25 Ґенмаб Б.В. Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування
US20130190248A1 (en) 2011-07-26 2013-07-25 Agensys, Inc. Substituted peptide analogs
WO2013068874A1 (en) 2011-11-11 2013-05-16 Pfizer Inc. Antibody-drug conjugates
JP6192233B2 (ja) 2011-11-17 2017-09-06 ファイザー・インク 細胞毒性ペプチドおよびその抗体薬物コンジュゲート
EP2812024B1 (en) 2012-02-09 2018-04-11 Var2 Pharmaceuticals ApS Targeting of chondroitin sulfate glycans
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
US10800856B2 (en) 2012-06-07 2020-10-13 Ambrx, Inc. Prostate-specific membrane antigen antibody drug conjugates
US9599265B2 (en) * 2012-06-15 2017-03-21 Stephen B. Maguire Multiple plate quick disconnect sandwich fitting
EP2861262B1 (en) 2012-06-19 2018-11-28 Ambrx, Inc. Anti-cd70 antibody drug conjugates
CA2880896C (en) 2012-06-26 2021-11-16 Del Mar Pharmaceuticals Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof
WO2014080251A1 (en) 2012-11-24 2014-05-30 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
SG10201705150RA (en) 2012-12-21 2017-07-28 Bioalliance Cv Hydrophilic self-immolative linkers and conjugates thereof
MX368258B (es) 2013-03-15 2019-09-25 Zymeworks Inc Compuestos citotoxicos y antimitoticos y metodos de uso de los mismos.
WO2015041635A1 (en) * 2013-09-17 2015-03-26 Halliburton Energy Services, Inc. Constant velocity device for downhole power generation
WO2015057876A1 (en) 2013-10-15 2015-04-23 Sorrento Therapeutics Inc. Drug-conjugates with a targeting molecule and two different drugs
MX2016007865A (es) 2013-12-17 2017-01-11 Novartis Ag Peptidos citotoxicos y conjugados de los mismos.
CN106255513B (zh) * 2013-12-27 2022-01-14 酵活有限公司 用于药物偶联物的含磺酰胺连接系统
CA2935064C (en) 2013-12-27 2023-06-27 Zymeworks Inc. Var2csa-drug conjugates
IL287645B2 (en) 2014-09-17 2024-04-01 Zymeworks Bc Inc Cytotoxic and anti-mitotic compounds and methods for their use
ES2918425T3 (es) 2015-01-28 2022-07-15 Sorrento Therapeutics Inc Conjugados de anticuerpo-fármaco
US10975112B2 (en) 2015-06-16 2021-04-13 Hangzhou Dac Biotech Co., Ltd. Linkers for conjugation of cell-binding molecules

Also Published As

Publication number Publication date
IL275942A (en) 2020-08-31
IL287645B2 (en) 2024-04-01
US9879086B2 (en) 2018-01-30
DK3194421T3 (da) 2022-02-14
IL287645A (en) 2021-12-01
US20170247408A1 (en) 2017-08-31
JP6875273B2 (ja) 2021-05-19
KR102609034B1 (ko) 2023-12-01
AU2020230264B2 (en) 2022-05-19
CA2960899C (en) 2021-08-17
EP3194421A1 (en) 2017-07-26
EP3194421A4 (en) 2018-06-06
KR102494557B1 (ko) 2023-02-02
RU2017110069A3 (hr) 2019-03-12
US20160075735A1 (en) 2016-03-17
PL3194421T3 (pl) 2022-02-28
US11591405B2 (en) 2023-02-28
CN113416229A (zh) 2021-09-21
AU2015318556A1 (en) 2017-04-06
US20230317700A1 (en) 2023-10-05
JP2021121590A (ja) 2021-08-26
RU2017110069A (ru) 2018-10-17
MX2017003476A (es) 2017-08-02
CY1124933T1 (el) 2023-01-05
US20190345254A1 (en) 2019-11-14
CA2960899A1 (en) 2016-03-24
CN107001415B (zh) 2021-06-18
HUE057768T2 (hu) 2022-06-28
RU2723651C2 (ru) 2020-06-17
KR20170069227A (ko) 2017-06-20
RS62860B1 (sr) 2022-02-28
EP4029873A1 (en) 2022-07-20
BR112017005126B1 (pt) 2023-10-24
SG11201702143PA (en) 2017-04-27
BR112017005126A2 (pt) 2018-08-07
AU2015318556B2 (en) 2020-06-18
PT3194421T (pt) 2022-02-07
ES2905569T3 (es) 2022-04-11
JP2017533886A (ja) 2017-11-16
AU2020230264A1 (en) 2020-10-01
IL275942B (en) 2021-12-01
EP3194421B1 (en) 2021-11-03
US20180208667A1 (en) 2018-07-26
US20200207865A2 (en) 2020-07-02
US10450378B2 (en) 2019-10-22
JP7204083B2 (ja) 2023-01-16
AU2020230264C1 (en) 2022-09-22
WO2016041082A1 (en) 2016-03-24
IL251167A0 (en) 2017-04-30
IL287645B1 (en) 2023-12-01
AU2015318556C1 (en) 2021-01-07
KR20230020018A (ko) 2023-02-09
CN107001415A (zh) 2017-08-01
US10414822B2 (en) 2019-09-17

Similar Documents

Publication Publication Date Title
HRP20220123T1 (hr) Citotoksični i antimitotički spojevi, te postupci njihove uporabe
JP2017533886A5 (hr)
AR122902A2 (es) Compuestos terapéuticamente activos y sus métodos de preparación
PE20210414A1 (es) Compuestos inhibidores de rip1 y metodos para preparar y usar los mismos
AR094312A1 (es) Inhibidores del receptor del factor de crecimiento de fibroblastos
MX2020012217A (es) Porción de unión para activación condicional de moléculas de inmunoglobulina.
PE20141202A1 (es) Compuesto de ciclopropanoamina
JP2016508130A5 (hr)
BR112018002499A2 (pt) método de preparação de um composto da fórmula (a) ou um seu sal, solvato ou conjugado de aminoácido farmaceuticamente aceitável, composto produzido pelo método e composição farmacêutica
BR112018068278A2 (pt) derivado de 3-desóxi e suas composições farmacêuticas
AR123672A2 (es) Conjugados de anticuerpo fármaco
AR088175A1 (es) 3-pirimidin-4-il-oxazolidin-2-onas utiles para tratar cancer y composiciones farmaceuticas que las contienen
RU2016135922A (ru) Терапевтические соединения и композиции
BR112017012755A2 (pt) compostos de heteroarila de anel fundido e seu uso como inibidores de trk
JP2016506962A5 (hr)
EA201390723A1 (ru) Аминозамещенные производные бисфенилпентановой кислоты в качестве ингибиторов nep
AR050540A1 (es) Derivados de adamantilamida triciclica como inhibidores de deshidrogenasa 11- beta hidroxiesteroide
EA201101026A1 (ru) Ингибиторы бета-секретазы
AR088810A1 (es) Moduladores del receptor mas acoplado a la proteina g utiles en el tratamiento de trastornos cardiovasculares y composiciones farmaceuticas que los contienen
PE20140863A1 (es) Compuestos de benceno sustituidos con arilo o heteroarilo
EA201001724A1 (ru) Производные изоксазола и их применение в качестве потенциирующих средств для метаботропных глутаматных рецепторов
AR049300A1 (es) Compuestos triciclicos antagonistas de mglur1 como agentes terapeuticos
BR112015018509A2 (pt) compostos de imidazo piridina
EA201390969A1 (ru) Модуляторы глюкагонового рецептора
PE20080409A1 (es) Compuestos que modulan en el receptor cb2