EA033456B1 - Конъюгаты антитело-лекарственное средство, содержащие пептидомиметические линкеры - Google Patents

Конъюгаты антитело-лекарственное средство, содержащие пептидомиметические линкеры

Info

Publication number
EA033456B1
EA033456B1 EA201691059A EA201691059A EA033456B1 EA 033456 B1 EA033456 B1 EA 033456B1 EA 201691059 A EA201691059 A EA 201691059A EA 201691059 A EA201691059 A EA 201691059A EA 033456 B1 EA033456 B1 EA 033456B1
Authority
EA
Eurasian Patent Office
Prior art keywords
antibody
drug conjugates
peptidomimetic
linkers
conjugates
Prior art date
Application number
EA201691059A
Other languages
English (en)
Russian (ru)
Other versions
EA201691059A1 (ru
Inventor
John Flygare
Janet Gunzner-Toste
Thomas Pillow
Brian Safina
Vishal Verma
Binqing Wei
Guiling Zhao
Leanna Staben
Philip Wilson Howard
Luke Masterson
Original Assignee
Genentech Inc
Medimmune Ltd
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 Genentech Inc, Medimmune Ltd filed Critical Genentech Inc
Publication of EA201691059A1 publication Critical patent/EA201691059A1/ru
Publication of EA033456B1 publication Critical patent/EA033456B1/ru

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/55131,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/55171,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05Dipeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68035Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6849Medicinal 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 receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • A61K47/6867Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • A61K47/6869Medicinal 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 the reproductive system: ovaria, uterus, testes, prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6889Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2851Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3061Blood cells
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3069Reproductive system, e.g. ovaria, uterus, testes, prostate
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3076Immunoglobulins [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 against structure-related tumour-associated moieties
    • C07K16/3092Immunoglobulins [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 against structure-related tumour-associated moieties against tumour-associated mucins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51Complete heavy chain or Fd fragment, i.e. VH + CH1
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515Complete light chain, i.e. VL + CL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Reproductive Health (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pregnancy & Childbirth (AREA)
  • Gynecology & Obstetrics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EA201691059A 2013-12-16 2014-12-16 Конъюгаты антитело-лекарственное средство, содержащие пептидомиметические линкеры EA033456B1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361916675P 2013-12-16 2013-12-16
PCT/US2014/070493 WO2015095124A1 (en) 2013-12-16 2014-12-16 Peptidomimetic compounds and antibody-drug conjugates thereof

Publications (2)

Publication Number Publication Date
EA201691059A1 EA201691059A1 (ru) 2016-11-30
EA033456B1 true EA033456B1 (ru) 2019-10-31

Family

ID=52273598

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201691059A EA033456B1 (ru) 2013-12-16 2014-12-16 Конъюгаты антитело-лекарственное средство, содержащие пептидомиметические линкеры

Country Status (13)

Country Link
US (2) US10533058B2 (enExample)
EP (1) EP3082872B1 (enExample)
JP (2) JP6681838B2 (enExample)
KR (2) KR102405762B1 (enExample)
CN (1) CN105848685B (enExample)
BR (1) BR112016014126B1 (enExample)
CA (1) CA2931798C (enExample)
EA (1) EA033456B1 (enExample)
HK (1) HK1222577A1 (enExample)
MX (1) MX381017B (enExample)
NZ (1) NZ720743A (enExample)
WO (1) WO2015095124A1 (enExample)
ZA (1) ZA201603697B (enExample)

Families Citing this family (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
ES2623057T3 (es) 2010-04-15 2017-07-10 Medimmune Limited Pirrolobenzodiazepinas usadas para tratar enfermedades proliferativas
CN103068405A (zh) 2010-04-15 2013-04-24 西雅图基因公司 靶向吡咯并苯并二氮杂卓结合物
CN103987718A (zh) 2011-09-20 2014-08-13 斯皮罗根有限公司 作为非对称二聚体pbd化合物用于内含在靶向结合物中的吡咯并苯并二氮杂卓
CN103998449A (zh) 2011-10-14 2014-08-20 斯皮罗根有限公司 吡咯并苯并二氮杂卓
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
CN103998450B (zh) 2011-10-14 2017-03-08 麦迪穆有限责任公司 吡咯并苯并二氮杂卓
CA2850375C (en) 2011-10-14 2019-07-02 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
CA2885305C (en) 2012-10-12 2019-11-12 Spirogen Sarl Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
CN104703630A (zh) 2012-10-12 2015-06-10 斯皮罗根有限公司 吡咯并苯并二氮杂卓及其结合物
RS58921B1 (sr) 2012-10-12 2019-08-30 Medimmune Ltd Pirolobenzodiazepini i njihovi konjugati
WO2014096368A1 (en) 2012-12-21 2014-06-26 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
JP6527466B2 (ja) 2012-12-21 2019-06-05 メドイミューン・リミテッドMedImmune Limited 増殖性疾患および自己免疫疾患の治療に使用するための非対称ピロロベンゾジアゼピンニ量体
NZ710746A (en) 2013-03-13 2018-11-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
WO2014159981A2 (en) 2013-03-13 2014-10-02 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
EA201691023A1 (ru) 2013-12-16 2016-10-31 Дженентек, Инк. Пептидомиметические соединения и их конъюгаты антитела с лекарственным средством
JP6681838B2 (ja) * 2013-12-16 2020-04-15 ジェネンテック, インコーポレイテッド ペプチド模倣薬化合物及びその抗体−薬剤複合体
JP6671292B2 (ja) 2013-12-16 2020-03-25 ジェネンテック, インコーポレイテッド ペプチド模倣化合物及びその抗体−薬物コンジュゲート
CN106687141A (zh) 2014-09-10 2017-05-17 麦迪穆有限责任公司 吡咯并苯并二氮杂卓及其缀合物
EP3191520B1 (en) 2014-09-12 2020-01-01 Genentech, Inc. Anti-cll-1 antibodies and immunoconjugates
PL3191135T3 (pl) 2014-09-12 2021-01-25 Genentech, Inc. Przeciwciała i immunokoniugaty anty-HER2
JP2017531620A (ja) 2014-09-12 2017-10-26 ジェネンテック, インコーポレイテッド システイン操作抗体及びコンジュゲート
GB201416112D0 (en) 2014-09-12 2014-10-29 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
KR20170101895A (ko) 2014-11-25 2017-09-06 에이디씨 테라퓨틱스 에스에이 피롤로벤조디아제핀-항체 접합체
EP3226908A1 (en) * 2014-12-03 2017-10-11 F.Hoffmann-La Roche Ag Anti-staphylococcus aureus antibody rifamycin conjugates and uses thereof
EP3226909A1 (en) * 2014-12-03 2017-10-11 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
AR104987A1 (es) 2015-06-15 2017-08-30 Genentech Inc Inmunoconjugados anticuerpo-fármaco unidos por enlazadores no peptídicos
TW201718647A (zh) 2015-06-16 2017-06-01 建南德克公司 抗-cll-1抗體及使用方法
GB201513607D0 (en) * 2015-07-31 2015-09-16 Feingold Jay M Pyrrolobenzodiazepine-antibody conjugates
MA43345A (fr) 2015-10-02 2018-08-08 Hoffmann La Roche Conjugués anticorps-médicaments de pyrrolobenzodiazépine et méthodes d'utilisation
GB201601431D0 (en) 2016-01-26 2016-03-09 Medimmune Ltd Pyrrolobenzodiazepines
GB201602359D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
GB201602356D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
WO2017201132A2 (en) 2016-05-18 2017-11-23 Mersana Therapeutics, Inc. Pyrrolobenzodiazepines and conjugates thereof
CN109152843A (zh) 2016-05-20 2019-01-04 豪夫迈·罗氏有限公司 Protac抗体缀合物及其使用方法
EP3465221B1 (en) 2016-05-27 2020-07-22 H. Hoffnabb-La Roche Ag Bioanalytical method for the characterization of site-specific antibody-drug conjugates
JP7043425B2 (ja) 2016-06-06 2022-03-29 ジェネンテック, インコーポレイテッド シルベストロール抗体-薬物コンジュゲート及び使用方法
JP7049276B2 (ja) 2016-06-24 2022-04-06 メルサナ セラピューティクス インコーポレイテッド ピロロベンゾジアゼピンおよびその結合体
JP7050770B2 (ja) 2016-10-05 2022-04-08 エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト 抗体薬物コンジュゲートの調製方法
GB201617466D0 (en) 2016-10-14 2016-11-30 Medimmune Ltd Pyrrolobenzodiazepine conjugates
SI3544636T1 (sl) 2017-02-08 2021-08-31 Adc Therapeutics Sa Konjugati pirolobenzodiazepin-protitelo
GB201702031D0 (en) 2017-02-08 2017-03-22 Medlmmune Ltd Pyrrolobenzodiazepine-antibody conjugates
HRP20221063T1 (hr) 2017-04-18 2022-11-11 Medimmune Limited Konjugati pirolobenzodiazepina
JP7220203B2 (ja) 2017-08-18 2023-02-09 メドイミューン・リミテッド ピロロベンゾジアゼピン複合体
MX2020003125A (es) 2017-09-29 2020-10-01 Daiichi Sankyo Co Ltd Conjugado de anticuerpo-derivado de pirrolobenzodiazepina.
US11638760B2 (en) 2017-11-27 2023-05-02 Mersana Therapeutics, Inc. Pyrrolobenzodiazepine antibody conjugates
TW201929908A (zh) 2017-12-21 2019-08-01 美商梅爾莎納醫療公司 吡咯并苯并二氮呯抗體共軛物
GB201803342D0 (en) 2018-03-01 2018-04-18 Medimmune Ltd Methods
GB201806022D0 (en) 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
CN111018857B (zh) * 2018-10-09 2023-06-02 嘉兴优博生物技术有限公司 靶向蛋白酶降解平台(ted)
IL282441B2 (en) 2018-10-24 2025-07-01 Hoffmann La Roche Conjugated chemical inducers of degradation and methods of use
WO2020100954A1 (ja) 2018-11-14 2020-05-22 第一三共株式会社 抗cdh6抗体-ピロロベンゾジアゼピン誘導体コンジュゲート
US12209180B2 (en) 2018-11-20 2025-01-28 Regeneron Pharmaceuticals, Inc. Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof for use as LXR agonists
WO2020123275A1 (en) 2018-12-10 2020-06-18 Genentech, Inc. Photocrosslinking peptides for site specific conjugation to fc-containing proteins
EP3915973A4 (en) * 2019-01-23 2023-02-01 ABTIS Co., Ltd. COMPOUND FOR THE PRODUCTION OF AN ANTIBODY-PAYLOAD CONJUGATE AND ITS USE
WO2020180158A1 (ko) * 2019-03-07 2020-09-10 에이비엘바이오 주식회사 항체-약물 접합체 및 이의 용도
CN113631560B (zh) 2019-03-15 2025-02-18 麦迪穆有限责任公司 氮杂环丁烷并苯并二氮杂䓬二聚体和用于治疗癌症的包含它们的缀合物
KR20210141630A (ko) 2019-03-25 2021-11-23 다이이찌 산쿄 가부시키가이샤 항 her2 항체-피롤로벤조디아제핀 유도체 콘주게이트
TWI856078B (zh) 2019-03-25 2024-09-21 日商第一三共股份有限公司 抗體–吡咯并苯二氮呯衍生物結合物、其製造方法及其用途
CA3139180A1 (en) 2019-03-27 2020-10-01 Daiichi Sankyo Company, Limited Combination of antibody-pyrrolobenzodiazepine derivative conjugate and parp inhibitor
US20240123081A1 (en) 2019-10-25 2024-04-18 Medimmune, Llc Branched moiety for use in conjugates
IL299860A (en) 2020-07-21 2023-03-01 Genentech Inc Antibody-conjugated chemical factors for the discharge of BRM and their methods
CN116113641A (zh) 2020-09-02 2023-05-12 第一三共株式会社 新型内-β-N-乙酰氨基葡萄糖苷酶
US20230372528A1 (en) 2020-10-16 2023-11-23 University Of Georgia Research Foundation, Inc. Glycoconjugates
KR20230146521A (ko) 2021-01-13 2023-10-19 메모리얼 슬로안 케터링 캔서 센터 항체-피롤로벤조디아제핀 유도체 접합체
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
IL312728A (en) 2021-11-30 2024-07-01 Daiichi Sankyo Co Ltd Protease-cleavable masked antibodies
AR128330A1 (es) 2022-01-26 2024-04-17 Genentech Inc Inductores químicos de degradación conjugados con anticuerpo y métodos de estos
AR128331A1 (es) 2022-01-26 2024-04-17 Genentech Inc Inductores químicos de degradación conjugados con anticuerpos y métodos de estos
CA3251410A1 (en) 2022-02-09 2025-07-08 Daiichi Sankyo Co Ltd Masked antibody sensitive to the environment and its use
WO2023167238A1 (ja) 2022-03-02 2023-09-07 第一三共株式会社 Fc含有分子の製造方法
EP4637833A2 (en) 2022-12-23 2025-10-29 Genentech, Inc. Cereblon degrader conjugates, and uses thereof
WO2025096716A1 (en) 2023-11-01 2025-05-08 Incyte Corporation Anti-mutant calreticulin (calr) antibody-drug conjugates and uses thereof
KR102786374B1 (ko) 2024-11-08 2025-03-24 노인균 조명 매립이 가능한 걸레받이

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011130598A1 (en) * 2010-04-15 2011-10-20 Spirogen Limited Pyrrolobenzodiazepines and conjugates thereof
WO2013041606A1 (en) * 2011-09-20 2013-03-28 Spirogen Sàrl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
WO2013055990A1 (en) * 2011-10-14 2013-04-18 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
WO2013053873A1 (en) * 2011-10-14 2013-04-18 Spirogen Sàrl Pyrrolobenzodiazepines
WO2013177055A2 (en) * 2012-05-21 2013-11-28 Genentech, Inc. ANTI-Ly6E ANTIBODIES AND IMMUNOCONJUGATES AND METHODS OF USE

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
BRPI0516284A (pt) 2004-09-23 2008-09-02 Genentech Inc anticorpo construìdo com cisteìna, método de selecionar anticorpos, compostos conjugados de droga-anticorpo, composição farmacêutica, método para matar ou inibir a proliferação de células de tumor, métodos de inibir a proliferação celular e o crescimento de células de tumor, artigo manufaturado e método para produzir um composto
US20100111856A1 (en) 2004-09-23 2010-05-06 Herman Gill Zirconium-radiolabeled, cysteine engineered antibody conjugates
AU2011265054B2 (en) 2010-06-08 2016-09-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
WO2012130765A1 (en) * 2011-03-29 2012-10-04 Bayer Materialscience Ag Use of an aqueous preparation for the coating of wood surfaces to achieve a natural-touch effect
WO2013055987A1 (en) 2011-10-14 2013-04-18 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2014057120A1 (en) * 2012-10-12 2014-04-17 Adc Therapeutics Sàrl Pyrrolobenzodiazepine-antibody conjugates
WO2014159981A2 (en) 2013-03-13 2014-10-02 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
CN105358573B (zh) 2013-05-31 2020-10-30 基因泰克公司 抗壁磷壁酸抗体和缀合物
US9803002B2 (en) 2013-05-31 2017-10-31 Genentench, Inc. Anti-wall teichoic antibodies and conjugates
CA2913011A1 (en) 2013-05-31 2014-12-04 Genentech, Inc. Anti-wall teichoic antibodies and conjugates
US20140356375A1 (en) 2013-05-31 2014-12-04 Genentech, Inc. Anti-wall teichoic antibodies and conjugates
US10442836B2 (en) 2013-08-12 2019-10-15 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1H-benzo[E]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
JP6671292B2 (ja) 2013-12-16 2020-03-25 ジェネンテック, インコーポレイテッド ペプチド模倣化合物及びその抗体−薬物コンジュゲート
JP6681838B2 (ja) * 2013-12-16 2020-04-15 ジェネンテック, インコーポレイテッド ペプチド模倣薬化合物及びその抗体−薬剤複合体
EA201691023A1 (ru) 2013-12-16 2016-10-31 Дженентек, Инк. Пептидомиметические соединения и их конъюгаты антитела с лекарственным средством
MX2016007578A (es) 2013-12-16 2016-10-03 Genentech Inc Compuestos de conjugado anticuerpo-farmaco dimerico de 1-(clorometil)-2,3-dihidro-1h-benzo [e] indol, y metodos de uso y tratamiento.
EP3191520B1 (en) 2014-09-12 2020-01-01 Genentech, Inc. Anti-cll-1 antibodies and immunoconjugates
JP2017531620A (ja) 2014-09-12 2017-10-26 ジェネンテック, インコーポレイテッド システイン操作抗体及びコンジュゲート
PE20170905A1 (es) 2014-09-17 2017-07-12 Genentech Inc Pirrolobenzodiazepinas y conjugados de anticuerpo-disulfuro de las mismas
EP3226909A1 (en) 2014-12-03 2017-10-11 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
EP3226908A1 (en) 2014-12-03 2017-10-11 F.Hoffmann-La Roche Ag Anti-staphylococcus aureus antibody rifamycin conjugates and uses thereof
RU2731055C2 (ru) 2014-12-03 2020-08-28 Дженентек, Инк. Конъюгаты антитела к staphylococcus aureus с рифамицином и их применение

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011130598A1 (en) * 2010-04-15 2011-10-20 Spirogen Limited Pyrrolobenzodiazepines and conjugates thereof
WO2013041606A1 (en) * 2011-09-20 2013-03-28 Spirogen Sàrl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
WO2013055990A1 (en) * 2011-10-14 2013-04-18 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
WO2013053873A1 (en) * 2011-10-14 2013-04-18 Spirogen Sàrl Pyrrolobenzodiazepines
WO2013177055A2 (en) * 2012-05-21 2013-11-28 Genentech, Inc. ANTI-Ly6E ANTIBODIES AND IMMUNOCONJUGATES AND METHODS OF USE

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NOLTING B: "Linker technologies for antibody-drug conjugates", ANTIBODY-DRUG CONJUGATES, NEW YORK [U.A.] : HUMANA PRESS, C2013, US, vol. 1045, 1 January 2013 (2013-01-01), US, pages 71 - 100, XP008169796, ISBN: 978-1-62703-540-8, doi:10.1007/978-1-62703-541-5-5 *

Also Published As

Publication number Publication date
KR102337414B1 (ko) 2021-12-10
KR20210129700A (ko) 2021-10-28
US20160310611A1 (en) 2016-10-27
WO2015095124A1 (en) 2015-06-25
JP6681838B2 (ja) 2020-04-15
JP2017503009A (ja) 2017-01-26
BR112016014126A2 (pt) 2017-12-19
MX2016007851A (es) 2016-09-07
CN105848685A (zh) 2016-08-10
BR112016014126B1 (pt) 2023-02-14
US10533058B2 (en) 2020-01-14
EP3082872B1 (en) 2020-12-09
US20200157240A1 (en) 2020-05-21
ZA201603697B (en) 2019-10-30
MX381017B (es) 2025-03-12
US11692043B2 (en) 2023-07-04
EP3082872A1 (en) 2016-10-26
CN105848685B (zh) 2020-09-22
CA2931798C (en) 2023-06-27
HK1225319A1 (en) 2017-09-08
CA2931798A1 (en) 2015-06-25
JP2020045370A (ja) 2020-03-26
HK1222577A1 (zh) 2017-07-07
EA201691059A1 (ru) 2016-11-30
KR102405762B1 (ko) 2022-06-07
NZ720743A (en) 2021-12-24
KR20160110379A (ko) 2016-09-21

Similar Documents

Publication Publication Date Title
EA033456B1 (ru) Конъюгаты антитело-лекарственное средство, содержащие пептидомиметические линкеры
PH12016501171A1 (en) Peptidomimetic compounds and antibody-drug conjugates thereof
CY1119616T1 (el) Συζευγματα ανθρωπινου αντισωματος-φαρμακου κατα του ιστικου παραγοντα
BR112012026213A8 (pt) Compostos de pirrolobenzodiazepinas, conjugado das mesmas, composição farmacêutica compreendendo o conjugado e uso do mesmo para o tratamento de uma doença proliferativa
NZ710746A (en) Pyrrolobenzodiazepines and conjugates thereof
TW201129382A (en) Antibody formulation and therapeutic regimens
NZ741261A (en) Pyrrolobenzodiazepine antibody drug conjugates and methods of use
MX340090B (es) Analogos de spliceostatina.
UA111341C2 (uk) Аматоксиновий кон'югат з покращеними лінкерами
NZ710729A (en) Amatoxin derivatives
NZ725131A (en) Tubulysin derivatives
EA201890272A1 (ru) Axl-специфические конъюгаты антитело-лекарственное средство для лечения рака
PH12017500023A1 (en) Targeted conjugates and particles and formulations thereof
PH12015500940A1 (en) Bruton`s tyrosine kinase inhibitors
BR112014026730A2 (pt) conjugados fármaco-ligante de dr5
MX2014009757A (es) Derivados de isoindolina, composiciones farmaceuticas que los contienen y su uso en terapia.
UA115517C2 (uk) Кон'югат антитіло-лікарський засіб (adc), який зв'язується з білком 161p2f10b
EA201590622A1 (ru) Конъюгаты для доставки лекарственного средства, содержащие не встречающиеся в природе аминокислоты, и способы применения
IN2012MN02591A (enExample)
BR112013006651A2 (pt) composição e cocristal de aprepitante l-prolina
WO2013173096A3 (en) Conjugates of huperzine and analogs thereof
UA115307C2 (uk) Застосування лікарського засобу, що містить рекомбінантний лектин омели для лікування раку шкіри
TN2012000256A1 (en) Therapeutic use of protein-polymer conjugates
EA201992775A2 (ru) Конъюгаты антител человека против тканевого фактора с лекарственными препаратами

Legal Events

Date Code Title Description
MM4A Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)

Designated state(s): AM AZ BY KZ KG TJ TM