RU2007133108A - АНТИТЕЛА, СВЯЗЫВАЮЩИЕСЯ С EphA2, И МЕТОДЫ ИХ ИСПОЛЬЗОВАНИЯ - Google Patents

АНТИТЕЛА, СВЯЗЫВАЮЩИЕСЯ С EphA2, И МЕТОДЫ ИХ ИСПОЛЬЗОВАНИЯ Download PDF

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RU2007133108A
RU2007133108A RU2007133108/13A RU2007133108A RU2007133108A RU 2007133108 A RU2007133108 A RU 2007133108A RU 2007133108/13 A RU2007133108/13 A RU 2007133108/13A RU 2007133108 A RU2007133108 A RU 2007133108A RU 2007133108 A RU2007133108 A RU 2007133108A
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epha2
immunoglobulin
binding fragment
antigen
pta
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RU2007133108/13A
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Дженни П. МЭЗЕР (US)
Дженни П. МЭЗЕР
Пенелопи Е. РОБЕРТС (US)
Пенелопи Е. РОБЕРТС
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Рэйвен Байотекнолоджиз, Инк. (Us)
Рэйвен Байотекнолоджиз, Инк.
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • 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
    • A61K47/6811Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817Toxins
    • A61K47/6819Plant toxins
    • A61K47/6825Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin
    • 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
    • A61K47/6891Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6897Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • C07K16/2866Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/42Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77Internalization into the cell

Claims (23)

1. По существу, очищенный иммуноглобулин или его антигенсвязывающий компонент, представляющий собой антитело SPL1, LUCA19, SG5 или LUCA40.
2. По существу, очищенный иммуноглобулин или его антигенсвязывающий компонент, который преимущественно связывается с EphA2 и обладает, по меньшей мере, одной из следующих характеристик SPL1, LUCA19, SG5 или LUCA40:
a. способность связываться с EphA2 на раковой клетке;
b. способность связываться с частью EphA2, которая открыта на поверхности живой раковой клетки in vitro или in vivo;
c. способность препятствовать пролиферации опухолевых клеток, не повышая содержания фосфотирозина в EphA2;
d. способность доставлять терапевтический агент или поддающийся выявлению маркер к раковой клетке, экспрессирующей EphA2; и
e. способность доставлять терапевтический агент или поддающийся выявлению маркер внутрь раковой клетки, экспрессирующей EphA2.
3. Выделенная последовательность нуклеиновой кислоты, кодирующая иммуноглобулин или его антигенсвязывающий фрагмент по п.1.
4. Нуклеиновая кислота по п.3, которая функционально связана промотором.
5. Нуклеиновая кислота по п.4, где промотор и нуклеиновая кислота заключены в экспрессирующем векторе.
6. Нуклеиновая кислота по п.3, кодирующая иммуноглобулин, который представляет собой моноклональное антитело.
7. Клеточная линия, трансфицированная, трансформированная или инфицированная вектором, который содержит нуклеиновую кислоту по п.3.
8. Способ получения, по существу, очищенного иммуноглобулина или его антигенсвязывающего фрагмента, включающий стадии:
a. выращивания клеточной линии, трансформированной нуклеиновой кислотой по п.3, в таких условиях, когда экспрессируется иммуноглобулин или антигенсвязывающий фрагмент; и
b. сбора экспрессированного иммуноглобулина или фрагмента.
9. Способ по п.8, где клеточная линия представляет собой гибридому.
10. Способ по п.9, где гибридома представляет собой гибридому ATCC № PTA-5070, PTA-6056 или PTA-6059 либо гибридому SG3.15B4.1F9.
11. Способ по п.8, где иммуноглобулин представляет собой моноклональное антитело.
12. Фармацевтическая композиция, содержащая эффективную дозу очищенного иммуноглобулина или антигенсвязывающего фрагмента по п.1 вместе с фармацевтически приемлемым носителем.
13. Гибридома, депонированная в американской коллекции типовых культур и имеющая инвентарный номер PTA-5070, PTA-6056 или PTA-6059 либо гибридома SG3.15B4.1F9 (PTA-XXXX).
14. Антитело, которое продуцировано гибридомой, депонированной в американской коллекции типовых культур и имеющей инвентарный номер PTA-5070, PTA-6056 или PTA-6059 либо гибридомой SG3.15B4.1F9 (PTA-XXXX).
15. Иммуноглобулин или его антигенсвязывающий фрагмент по п.1, который гуманизирован.
16. Иммуноглобулин или его антигенсвязывающий фрагмент по п.1, который химеризирован.
17. Иммуноглобулин или его антигенсвязывающий фрагмент по п.1, который представляет собой антитело человека.
18. Иммуноглобулин или его антигенсвязывающий фрагмент по п.1, который представляет собой дериват.
19. Фармацевтическая композиция по п.12, в которой указанный очищенный иммуноглобулин или антигенсвязывающий фрагмент представляет собой LUCA19, LUCA40, SG5 или SPL1.
20. Фармацевтическая композиция по п.12, в которой указанный очищенный иммуноглобулин или антигенсвязывающий фрагмент конкурирует с антителами LUCA19, LUCA40, SG5 или SPL1 за связывание с антигеном EphA2.
21. Фармацевтическая композиция по п.12, в которой очищенный иммуноглобулин или антигенсвязывающий фрагмент гуманизирован.
22. Фармацевтическая композиция по п.12, в которой очищенный иммуноглобулин или антигенсвязывающий фрагмент химеризирован.
23. Способ лечения рака у нуждающегося в этом больного, где указанный способ включает введение указанному больному терапевтически эффективного количества антитела против-EphA2, которое специфически связывается с антигеном EphA2 и обладает, по меньшей мере, одной из следующих характеристик SPL1, LUCA19, SG5 или LUCA40:
a. способность связываться с EphA2 на раковой клетке;
b. способность связываться с частью EphA2, которая открыта на поверхности живой раковой клетки in vitro или in vivo;
c. способность препятствовать пролиферации опухолевых клеток, не повышая содержания фосфотирозина в EphA2;
d. способность доставлять терапевтический агент или поддающийся выявлению маркер к раковой клетке, экспрессирующей EphA2; и
e. способность доставлять терапевтический агент или поддающийся выявлению маркер внутрь раковой клетки, экспрессирующей EphA2.
RU2007133108/13A 2005-02-04 2006-02-06 АНТИТЕЛА, СВЯЗЫВАЮЩИЕСЯ С EphA2, И МЕТОДЫ ИХ ИСПОЛЬЗОВАНИЯ RU2007133108A (ru)

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US (3) US7569672B2 (ru)
EP (1) EP1846450B1 (ru)
JP (1) JP5342145B2 (ru)
KR (1) KR101363252B1 (ru)
CN (2) CN104059150B (ru)
AT (1) ATE551367T1 (ru)
AU (1) AU2006210460B2 (ru)
BR (1) BRPI0607450A2 (ru)
CA (1) CA2597198C (ru)
CR (1) CR9332A (ru)
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IL (1) IL184803A (ru)
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