RU2005104113A - Использование уреазы для угнетения роста раковых клеток - Google Patents

Использование уреазы для угнетения роста раковых клеток Download PDF

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RU2005104113A
RU2005104113A RU2005104113/15A RU2005104113A RU2005104113A RU 2005104113 A RU2005104113 A RU 2005104113A RU 2005104113/15 A RU2005104113/15 A RU 2005104113/15A RU 2005104113 A RU2005104113 A RU 2005104113A RU 2005104113 A RU2005104113 A RU 2005104113A
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composition
urease
tumor
group
composition according
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RU2005104113/15A
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RU2326691C2 (ru
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Герман ЧАО (CA)
Герман ЧАО
Вах ВОНГ (CA)
Вах Вонг
Дональд СЕГАЛ (CA)
Дональд Сегал
Джерри МАКЭЛРОЙ (CA)
Джерри МАКЭЛРОЙ
Джон ДОЧЕРТИ (CA)
Джон Дочерти
Джоди ДИКСТЕЙН (CA)
Джоди Дикстейн
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Хеликс Биофарма Корп. (Ca)
Хеликс Биофарма Корп.
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
    • 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
    • A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/66—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 a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • Nanotechnology (AREA)
  • Organic Chemistry (AREA)
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  • General Engineering & Computer Science (AREA)
  • Crystallography & Structural Chemistry (AREA)
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  • Oncology (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
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Claims (17)

1. Фармацевтическая композиция, предназначенная для использования при ингибировании роста опухолевых клеток у млекопитающего-субъекта, включающая
фермент уреазу химический фрагмент, ассоциированный с ферментом уреазой и эффективно усиливающий доставку фермента к опухолевым клеткам при введении композиции субъекту, и фармацевтический носитель.
2. Композиция по п.1, в которой указанный химический фрагмент включает гидрофильный полимер, (i) конъюгированный с ферментом уреазой, (ii) выбранный из группы, состоящей из полиэтиленгликоля, поливинилпирролидона, поливинилметилового эфира, полигидроксипропилметакриламида, полигидроксипропилметакрилата, полигидроксиэтилакрилата, полиметакриламида, полидиметилакриламида, полиметилоксазолина, полиэтилоксазолина, гидроксиэтилоксазолина, полигидроксипропилоксазолина, полиаспартамида и гидрофильных производных целлюлозы, и (iii) присутствующий в количестве, позволяющем эффективно увеличить время нахождения в кровообращении или уменьшить антигенность указанной композиции по сравнению с нативной уреазой.
3. Композиция по п.2, в которой указанный гидрофильный полимер представляет собой полиэтиленгликоль, имеющий молекулярный вес от примерно 1000 до 10000 Д.
4. Композиция по п.1 или 2, в которой указанный химический фрагмент представляет собой нацеливающий фрагмент, присоединенный к указанному ферменту уреазе, и выбранный из группы, состоящей из антитела к противоопухолевому антигену, анти-DCG антитела, и лиганда, способного специфически связываться с поверхностными рецепторами опухолевых клеток.
5. Композиция по п.4, в которой указанный нацеливающий фрагмент является полипептидом, и указанная композиция представляет собой гибридный белок, состоящий из нацеливающего фрагмента и фермента уреазы.
6. Композиция по п.4, в которой указанная уреаза включает, на своем С- или N-конце, первый спиралеобразующий пептид, характеризующийся выбранным зарядом и способностью взаимодействовать со вторым, противоположно заряженным спиралеобразующим пептидом, с образованием стабильного α-спирального биспирального гетеродимера; и указанный химический фрагмент включает нацеливающий фрагмент, содержащий указанный второй спиралеобразующий пептид.
7. Композиция по п.1, в которой указанный химический фрагмент включает везикулы, содержащие фермент уреазу в инкапсулированной форме.
8. Композиция по п.7, в которой указанные везикулы представляют собой липосомы, имеющие большое время циркуляции в крови благодаря наличию наружного покрытия из полиэтиленгликольных цепей, и размеры, позволяющие им экстравазировать в участки опухоли при внутривенном введении композиции.
9. Композиция по п.7, в которой указанные везикулы представляют собой липосомы, имеющие поверхностно-связанные нацеливающие фрагменты, выбранные из группы, состоящей из антитела к противоопухолевому антигену, анти-hCG антитела и лигандов, способных специфически связываться с поверхностными рецепторами опухолевых клеток.
10. Композиция по п.7, дополнительно включающая агент, инкапсулированный в указанных липосомах, и выбранный из группы, состоящей из мочевины, терапевтически активного противоопухолевого агента и агента визуализации.
11. Композиция по п.1, в которой указанная уреаза представляет собой растительную или бактериальную уреазу.
12. Композиция по п.1, дополнительно включающая слабоосновное противоопухолевое соединение, эффективность которого снижается в градиенте более высокого внутриклеточного/более низкого внеклеточного значений рН в солидной опухоли.
13. Композиция по п.12, в которой противоопухолевое соединение выбирают из группы, состоящей из доксорубицина, даунорубицина, митоксантрона, эпирубицина, митомицина, блеомицина, алкалоидов барвинка (Vinca), таких как винбластин и винкристин, алкилирующих агентов, таких как циклофосфамид и мехлорэтамина гидрохлорид, и противоопухолевых производных пурина и пиримидина.
14. Использование фермента уреазы в производстве лекарственного средства для лечения или диагностики опухоли у млекопитающего-субъекта, получающего лечение слабоосновным противоопухолевым соединением, эффективность которого снижается в градиенте более высокого внутриклеточного/более низкого внеклеточного значений рН в солидной опухоли.
15. Использование по п.14, в котором фермент уреаза присоединен к нацеливающему фрагменту, выбранному из группы, состоящей из антитела к противоопухолевому антигену, анти-hCG антитела и лигандов, способных специфически связываться с поверхностными рецепторами опухолевых клеток.
16. Использование по п.14, в котором указанное противоопухолевое соединение выбирают из группы, состоящей из доксорубицина, даунорубицина, митоксантрона, эпирубицина, митомицина, блеомицина, алкалоидов барвинка (Vinca), таких как винбластин и винкристин, алкилирующих агентов, таких как циклофосфамид и мехлорэтамина гидрохлорид, и противоопухолевых производных пурина и пиримидина.
17. Композиция для генной терапии, предназначенная для использования при ингибировании роста опухолевых клеток у млекопитающего-субъекта, включающая нацеливающий вектор, эффективно обеспечивающий при введении субъекту селективную трансфекцию опухолевых клеток, и переносимую в указанном векторе рекомбинантную последовательность нуклеиновой кислоты, обеспечивающую продуцирование мРНК уреазы в подвергнутых трансфекции опухолевых клетках.
RU2005104113/15A 2002-07-18 2003-07-16 Использование уреазы для ингибирования роста раковых клеток RU2326691C2 (ru)

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JP (4) JP2006501196A (ru)
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