RU2451523C2 - Упакованные иммуностимулирующей нуклеиновой кислотой частицы, предназначенные для лечения гиперчувствительности - Google Patents

Упакованные иммуностимулирующей нуклеиновой кислотой частицы, предназначенные для лечения гиперчувствительности Download PDF

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RU2451523C2
RU2451523C2 RU2008128136/15A RU2008128136A RU2451523C2 RU 2451523 C2 RU2451523 C2 RU 2451523C2 RU 2008128136/15 A RU2008128136/15 A RU 2008128136/15A RU 2008128136 A RU2008128136 A RU 2008128136A RU 2451523 C2 RU2451523 C2 RU 2451523C2
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composition according
bacteriophage
allergy
composition
animal
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RU2008128136A (ru
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Вольфганг РЕННЕР (CH)
Вольфганг РЕННЕР
Мартин БАХМАНН (CH)
Мартин БАХМАНН
Индулис СИЕЛЕНС (LV)
Индулис СИЕЛЕНС
Конрад КЁСТЕР (DE)
Конрад КЁСТЕР
Клаус ДИТМАЙЕР (CH)
Клаус ДИТМАЙЕР
Зебастиан ФУКС (DE)
Зебастиан ФУКС
Ваня МАНОЛОВА (CH)
Ваня МАНОЛОВА
Патрик МАУРЕР (CH)
Патрик МАУРЕР
Пауль ПУМПЕНС (LV)
Пауль ПУМПЕНС
Регина РЕНХОФА (LV)
Регина РЕНХОФА
Ален ТИССО (CH)
Ален ТИССО
Зоу Ю (Ch)
Зоу Ю
Карл ПРОБА (CH)
Карл ПРОБА
Маттиас КИНЦЛЕР (CH)
Маттиас КИНЦЛЕР
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Цитос Биотехнологи Аг
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Abstract

Группа изобретений относится к области медицины и касается упакованных иммуностимулирующей нуклеиновой кислотой частиц, предназначенных для лечения гиперчувствительности, которая является аллергией. Сущность изобретений включает композиции, содержащие вирусоподобную частицу, упакованную иммуностимулирующими нуклеиновыми кислотами, при этом вирусоподобная частица представляет собой вирусоподобную частицу РНКового бактериофага, упакованную иммуностимулирующей нуклеиновой кислотой, содержащей неметилированный CpG олигонуклеотид. Композиции, предлагаемые в изобретениях, наиболее целесообразно применять для лечения диффузного нейродерматита, астмы и опосредуемой IgE аллергии (аллергии типа I), прежде всего аллергии на пыльцу и аллергии на домашнюю пыль. Преимущество изобретений заключается в создании средства для лечения гиперчувствительности, преимущественно аллергии. 3 н. и 21 з.п.ф-лы, 39 пр., 32 табл., 6 ил.

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Claims (24)

1. Композиция, предназначенная для применения в способе лечения гиперчувствительности у животного, где указанная гиперчувствительность является аллергией, и эта композиция содержит, практически состоит или состоит из:
(а) частицы, где частица представляет собой вирусоподобную частицу, в которой вирусоподобная частица представляет собой вирусоподобную частицу РНКового бактериофага; и
(б) иммуностимулирующей нуклеиновой кислоты, в которой иммуностимулирующая нуклеиновая кислота представляет собой содержащий неметилированный CpG олигонуклеотид;
где частица упакована с иммуностимулирующей нуклеиновой кислотой и где композицию вводят животному без аллергена или экстракта аллергена.
2. Композиция по п.1, в которой вирусоподобная частица содержит или в другом варианте практически состоит, в другом варианте состоит из оболочечных белков или их фрагментов РНКового бактериофага.
3. Композиция по п.2, в которой РНКовый бактериофаг выбран из группы, содержащей:
(а) бактериофаг Qβ;
(б) бактериофаг R17;
(в) бактериофаг fr;
(г) бактериофаг GA;
(д) бактериофаг SP;
(е) бактериофаг MS2;
(ж) бактериофаг M11;
(з) бактериофаг МХ1;
(и) бактериофаг NL95;
(к) бактериофаг f2;
(л) бактериофаг РР7 и
(м) бактериофаг АР205.
4. Композиция по п.2, в которой РНКовый бактериофаг представляет собой Qβ.
5. Композиция по п.2, где указанный белок оболочки имеет аминокислотную последовательность, представленную в SEQ ID NO:3.
6. Композиция по п.1, в которой содержащий неметилированный CpG олигонуклеотид содержит палиндромную последовательность, причем предпочтительно CpG-мотив содержащего неметилированный CpG олигонуклеотида является частью палиндромной последовательности, и предпочтительно указанная палиндромная последовательность представляет собой GACGATCGTC (SEQ ID NO:28).
7. Композиция по п.6, в которой палиндромная последовательность фланкирована на ее 5'-конце и на ее 3'-конце гуанозиновыми остатками, причем предпочтительно указанная палиндромная последовательность фланкирована на ее 5'-конце по меньшей мере 3 и максимум 15 гуанозиновыми остатками, и в которой палиндромная последовательность фланкирована на ее 3'-конце по меньшей мере 3 и максимум 15 гуанозиновыми остатками.
8. Композиция по п.1, в которой содержащий неметилированный CpG олигонуклеотид содержит или в другом варианте состоит из последовательности, выбранной из группы, включающей:
(а) «G6-6» GGGGGGGACGATCGTCGGGGGG (SEQ ID NO:32);
(б) «G7-7» GGGGGGGGACGATCGTCGGGGGGG (SEQ ID NO:33);
(в) «G8-8» GGGGGGGGGACGATCGTCGGGGGGGG (SEQ ID NO:25);
(г) «G9-9» GGGGGGGGGGACGATCGTCGGGGGGGGG (SEQ ID NO:26) и
(д) «G10» GGGGGGGGGGGACGATCGTCGGGGGGGGGG (SEQ ID NO:27).
9. Композиция по п.1, в которой содержащий неметилированный CpG олигонуклеотид содержит или в другом варианте практически состоит или в другом варианте состоит из последовательности GGGGGGGGGGGACGATCGTCGGGGGGGGGG (SEQ ID NO:27).
10. Композиция по п.5, в которой содержащий неметилированный CpG олигонуклеотид состоит из последовательности GGGGGGGGG GACGATCGTCGGGGGGGGGG (SEQ ID NO:27).
11. Композиция по п.1, в которой содержащий неметилированный CpG олигонуклеотид состоит только из связанных фосфодиэфирной связью нуклеотидов.
12. Композиция по п.1, в которой неметилированный CpG олигонуклеотид не доступен для гидролиза ДНКазой.
13. Композиция по п.1, в которой неметилированный CpG олигонуклеотид, содержит олигонуклеотид, содержащий из последовательности
GGGGGGGGGGGACGATCGTCGGGGGGGGGG (SEQ ID NO:27), причем указанный содержащий неметилированный CpG олигонуклеотид состоит только из связанных фосфодиэфирной связью нуклеотидов.
14. Композиция по п.1, где указанная аллергия представляет собой опосредуемую IgE аллергию.
15. Композиция по п.1, где гиперчувствительность представляет собой астму, причем предпочтительно указанная астма представляет собой опосредуемую IgE астму.
16. Композиция по п.1, где гиперчувствительность представляет собой дерматит, причем предпочтительно указанный дерматит представляет собой диффузный нейродерматит.
17. Композиция по п.1, где гиперчувствительность представляет собой опосредуемую IgE аллергию на встречающийся в естественных условиях аллерген, причем предпочтительно указанная опосредуемая IgE аллергия выбрана из группы, включающей:
(а) аллергию на пыльцу (сенная лихорадка);
(б) аллергию на домашнюю пыль;
(в) пищевую аллергию;
(г) аллергию на лекарственные средства;
(д) аллергию на яд насекомых, предпочтительно аллергию на пчелиный яд и
(е) аллергию на животных, предпочтительно аллергию на кошек.
18. Композиция по п.1, где животное представляет собой человека.
19. Композиция по п.1, где композиция не содержит аллерген или экстракт аллергена.
20. Фармацевтическая композиция, которая содержит, практически состоит или состоит из:
(а) композиции по одному из пп.1-19 и
(б) адъюванта, предпочтительно содержащего алюминий, адъюванта, наиболее предпочтительно альгидрогеля.
21. Способ лечения гиперчувствительности у животного, где указанная гиперчувствительность является аллергией, заключающийся в том, что вводят животному композицию по одному из пп.1-19.
22. Способ по п.21, где композицию вводят животному подкожно, внутримышечно, внутривенно, интраназально или непосредственно в лимфатический узел.
23. Способ по п.21, в котором животное представляет собой млекопитающее, предпочтительно человека.
24. Способ по п.21, в котором композицию вводят животному и в котором введение композиции животному осуществляют таким образом, чтобы не вводить аллерген или экстракт аллергена животному в течение по меньшей мере одной недели до и по меньшей мере одной недели после введения композиции животному.
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