EA201400046A1 - Удаление клеток-мишеней с помощью циркулирующих вирусспецифических цитотоксических т-клеток с использованием содержащих гкгс класса i комплексов - Google Patents

Удаление клеток-мишеней с помощью циркулирующих вирусспецифических цитотоксических т-клеток с использованием содержащих гкгс класса i комплексов

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EA201400046A1
EA201400046A1 EA201400046A EA201400046A EA201400046A1 EA 201400046 A1 EA201400046 A1 EA 201400046A1 EA 201400046 A EA201400046 A EA 201400046A EA 201400046 A EA201400046 A EA 201400046A EA 201400046 A1 EA201400046 A1 EA 201400046A1
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Prior art keywords
cells
complex
class
polypeptide
antibody
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EA201400046A
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English (en)
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Хендрик Кнётген
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Ф. Хоффманн-Ля Рош Аг
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Application filed by Ф. Хоффманн-Ля Рош Аг filed Critical Ф. Хоффманн-Ля Рош Аг
Publication of EA201400046A1 publication Critical patent/EA201400046A1/ru

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3023—Lung
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Wood Science & Technology (AREA)
  • Virology (AREA)
  • Toxicology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

В заявке описан комплекс, который содержит в качестве первого компонента выведенный из антитела компонент, который специфически связывается с антигеном-мишенью, и в качестве второго компонента выведенный из вируса пептид, связанный с белковым комплексом ГКГС класса. С помощью представленного в настоящем описании комплекса существующие вирусспецифические циркулирующие цитотоксические Т-клетки (Т-клетки памяти и/или эффекторные Т-клетки) индивидуума можно направлять к клеткам, экспрессирующим антиген-мишень, с которыми выведенный из антитела компонент комплекса специфически связывается, "маркируя" эти клетки комплексами ГКГС класса I, имитируя острую вирусную инфекцию. Так, одним из объектов изобретения является комплекс, отличающийся тем, что он содержит один слитый полипептид, который содержит в направлении от N- к С-концу либо (I) β2-микроглобулин и (II) внеклеточные домены α1, α2 и α3 молекулы ГКГС класса I, относительная частота встречаемости которой составляет менее 1%, либо (I) выведенный из вируса пептид, (II) β2-микроглобулин и (III) внеклеточные домены α1, α2 и α3 молекулы ГКГС класса I, относительная частота встречаемости которой составляет 1% или более, и две полипептидные цепи, которые связаны с помощью одного или нескольких дисульфидных мостиков, в котором первая связанная дисульфидными мостиками полипептидная цепь содержит в направлении от N- к С-концу (I) вариабельный домен легкой или тяжелой цепи иммуноглобулина, (II) константный домен легкой или тяжелой цепи иммуноглобулина и (III) полипептид шарнирной области цепи антитела, а вторая связанная дисульфидными мостиками полипептидная цепь содержит полипептид шарнирной области тяжелой цепи антитела,
EA201400046A 2011-06-22 2012-06-19 Удаление клеток-мишеней с помощью циркулирующих вирусспецифических цитотоксических т-клеток с использованием содержащих гкгс класса i комплексов EA201400046A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP11171027 2011-06-22
PCT/EP2012/061734 WO2012175508A1 (en) 2011-06-22 2012-06-19 Removal of target cells by circulating virus-specific cytotoxic t-cells using mhc class i comprising complexes

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US (4) US20130011394A1 (ru)
EP (1) EP2723773B1 (ru)
JP (2) JP6246711B2 (ru)
KR (1) KR102038155B1 (ru)
CN (2) CN110229235A (ru)
AR (1) AR086982A1 (ru)
AU (1) AU2012274127B2 (ru)
BR (1) BR112013029746B1 (ru)
CA (1) CA2835772C (ru)
CL (1) CL2013003634A1 (ru)
CO (1) CO6801646A2 (ru)
CR (1) CR20130609A (ru)
EA (1) EA201400046A1 (ru)
EC (1) ECSP13013098A (ru)
ES (1) ES2667864T3 (ru)
IL (1) IL229486B (ru)
MA (1) MA35604B1 (ru)
MX (1) MX354663B (ru)
PE (1) PE20141212A1 (ru)
PH (1) PH12013502499A1 (ru)
PL (1) PL2723773T3 (ru)
SG (1) SG195077A1 (ru)
TW (1) TWI563087B (ru)
WO (1) WO2012175508A1 (ru)

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