RU2360923C2 - Новый лиганд рецептора цитокина zcytor17 - Google Patents

Новый лиганд рецептора цитокина zcytor17 Download PDF

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RU2360923C2
RU2360923C2 RU2004125165/13A RU2004125165A RU2360923C2 RU 2360923 C2 RU2360923 C2 RU 2360923C2 RU 2004125165/13 A RU2004125165/13 A RU 2004125165/13A RU 2004125165 A RU2004125165 A RU 2004125165A RU 2360923 C2 RU2360923 C2 RU 2360923C2
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seq
sequence
polypeptide
polynucleotide
amino acid
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RU2004125165/13A
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RU2004125165A (ru
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Синди А. СПРЕШЕР (US)
Синди А. СПРЕШЕР
Йозеф Л. КЕЙПЕР (US)
Йозеф Л. КЕЙПЕР
Мария М. ДАСОВИЧ (US)
Мария М. ДАСОВИЧ
Фрэнсис Дж. ГРАНТ (US)
Фрэнсис Дж. ГРАНТ
Анджела К. ХЭММОНД (US)
Анджела К. Хэммонд
Джулия Е. НОВАК (US)
Джулия Е. НОВАК
Джейн А. ГРОСС (US)
Джейн А. Гросс
Стейси Р. ДИЛЛОН (US)
Стейси Р. Диллон
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Займоджинетикс, Инк.
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Abstract

Настоящее изобретение относится к области биотехнологии. Предложен полипептид и соответствующий полинуклеотид zcytor17lig и молекулы антитела против zcytor17 человека. Zcytor17lig человека является новым цитокином. Настоящее изобретение относится также к способам получения белка, его применению для стимуляции иммунной реакции у млекопитающего. Описан способ получения антитела к указанному белку и соответствующие антитела. Указанные полипептиды можно использовать при осуществлении способов стимуляции иммунной системы, пролиферации и/или развития гемопоэтических клеток in vitro и in vivo. 14 н. и 3 з.п. ф-лы, 3 ил., 21 табл.

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Claims (19)

1. Выделенный полипептид, содержащий последовательность аминокислотных остатков, выбранных из группы
(a) полипептида, приведенного в последовательности SEQ ID NO:2 от остатка 38 (Val) до остатка 152 (Leu);
(b) полипептида, приведенного в последовательности SEQ ID NO:2 от остатка 27 (Leu) до остатка 164 (Thr);
(c) полипептида, приведенного в последовательности SEQ ID NO:2 от остатка 24 (Ser) до остатка 164 (Thr); и
(d) полипептида, приведенного в последовательности SEQ ID NO:2 от остатка 1 (Met) до остатка 164 (Thr),
причем указанный полипептид связывается с рецептором zcytor17 человека.
2. Выделенный полипептид по п.1, где аминокислотные остатки 72, 133 и 147 являются цистеином.
3. Выделенный полипептид по п.1, который связывается с рецептором zcytor17, показанным в SEQ ID NO:5 или SEQ ID NO:71.
4. Экспрессирующий вектор, содержащий следующие функционально связанные элементы:
(а) промотор транскрипции;
(b) сегмент ДНК, кодирующий полипептид, который связывается с рецептором zcytor17 человека, содержащий аминокислотные остатки с 38 (Val) по 152 (Leu) SEQ ID NO:2; и
(c) терминатор транскрипции.
5. Культивируемая клетка, содержащая экспрессирующий вектор по п.4.
6. Способ получения полипептида, который включает в себя
культивирование клетки по п.5 в условиях, обеспечивающих экспрессию сегмента ДНК, и выделение полипептида, кодируемого указанным сегментом ДНК.
7. Способ стимуляции иммунной реакции у млекопитающего, предусматривающий стадию введения композиции, содержащей полипептид zcytor17lig, охарактеризованный в п.1, в приемлемом фармацевтическом носителе.
8. Способ обнаружения РНК zcytor17lig человека в биологическом образце, который включает в себя стадии
(a) контактирования зонда нуклеиновой кислоты zcytor17lig в условиях гибридизации либо (i) с молекулами испытуемой РНК, выделенными из биологического образца, либо (ii) с молекулами нуклеиновой кислоты, синтезированными из выделенных молекул РНК, при этом указанный зонд имеет нуклеотидную последовательность, содержащую часть нуклеотидной последовательности молекулы нуклеиновой кислоты, кодирующей полипептид, который связывается с рецептором zcytor17 человека, содержащий аминокислотные остатки с 38 (Val) по 152 (Leu) SEQ ID NO:2, или ее комплемент; и
(b) обнаружение образовавшихся гибридов зонда нуклеиновой кислоты и либо молекул испытуемой РНК, либо молекул синтезированной нуклеиновой кислоты;
при этом наличие гибридов указывает на присутствие РНК zcytor17lig человека в биологическом образце.
9. Способ обнаружения воспаления у пациента, включающий в себя
получение у пациента тканевого или биологического образца;
мечение полинуклеотида, содержащего по меньшей мере 14 смежных нуклеотидов последовательности SEQ ID NO:1 или комплемента последовательности SEQ ID NO:1, где полинуклеотид содержит полинуклеотид, выбранный из группы, состоящей из
(a) полинуклеотида, приведенного в последовательности SEQ ID NO:1 от нуклеотида 139 до нуклеотида 483;
(b) полинуклеотида, приведенного в последовательности SEQ ID NO:1 от нуклеотида 106 до нуклеотида 519;
(c) полинуклеотида, приведенного в последовательности SEQ ID NO:1 от нуклеотида 97 до нуклеотида 519; и
(d) полинуклеотида, приведенного в последовательности SEQ ID NO:1 от нуклеотида 28 до нуклеотида 519;
инкубацию тканевого или биологического образца в условиях, обеспечивающих гибридизацию полинуклеотида с комплементарной полинуклеотидной последовательностью;
визуализацию меченого полинуклеотида в тканевом или биологическом образце; и
сравнение уровня гибридизации меченого полинуклеотида в тканевом или биологическом образце, взятом у пациента, с нормальным контрольным тканевым или биологическим образцом;
при этом увеличение гибридизации меченого полинуклеотида в тканевом или биологическом образце пациента по сравнению с нормальным контрольным тканевым или биологическим образцом указывает на наличие воспаления у пациента.
10. Выделенный полипептид, связывающийся с рецептором zcytor17 человека, с одной или несколькими аминокислотными заменами, аминоконцевым метиониновым остатком, линкерным пептидом или аффинной меткой, содержащий последовательность аминокислотных остатков, выбранных из группы
(a) остатков от 38 (Val) до 152 (Leu) полипептида, приведенного в последовательности SEQ ID NO:2;
(b) остатков от 27 (Leu) до 164 (Thr) полипептида, приведенного в последовательности SEQ ID NO:2;
(c) остатков от 24 (Ser) до 164 (Thr) полипептида, приведенного в последовательности SEQ ID NO:2; и
(d) остатков от 1 (Met) до 164 (Thr) полипептида, приведенного в последовательности SEQ ID NO:2.
11. Выделенный полипептид, который связывается с рецептором zcytor17 человека, состоящий из последовательности аминокислотных остатков, выбранных из группы, состоящей из
(a) остатков от 38 (Val) до 152 (Leu) полипептида, приведенного в последовательности SEQ ID NO:2;
(b) остатков от 27 (Leu) до 164 (Thr) полипептида, приведенного в последовательности SEQ ID NO:2;
(c) остатков от 24 (Ser) до 164 (Thr) полипептида, приведенного в последовательности SEQ ID NO:2; и
(d) остатков от 1 (Met) до 164 (Thr) полипептида, приведенного в последовательности SEQ ID NO:2.
12. Выделенная молекула полинуклеотида, кодирующая полипептид по любому из пп.1, 2, 3, 10 или 11.
13. Выделенная молекула полинуклеотида по п.12, в которой нуклеотиды выбраны из группы
(a) нуклеотидов от 139 до 483 полинуклеотида, приведенного в последовательности SEQ ID NO:1;
(b) нуклеотидов от 106 до 519 полинуклеотида, приведенного в последовательности SEQ ID NO:1;
(c) нуклеотидов от 97 до 519 полинуклеотида, приведенного в последовательности SEQ ID NO:1; и
(d) нуклеотидов от 28 до 519 полинуклеотида, приведенного в последовательности SEQ ID NO:1;
14. Способ получения антитела против полипептида zcytor17lig, который включает в себя
инокуляцию животного адъювантом и полипептидом из группы
(a) полипептида, состоящего из аминокислот 38-152 аминокислотной последовательности SEQ ID NO:2;
(b) полипептида, состоящего из аминокислот 24-164 аминокислотной последовательности SEQ ID NO:2;
(c) полипептида, содержащего аминокислотную последовательность SEQ ID NO:2 от аминокислоты 27 до аминокислоты 164; и
выделение указанного антитела из организма животного.
15. Антитело, полученное способом по п.14, которое связывается с полипептидом zcytor17lig человека, состоящим из аминокислот 38-152 аминокислотной последовательности SEQ ID NO:2.
16. Антитело, полученное способом по п.14, которое связывается с полипептидом zcytor17lig человека, состоящим из аминокислот 24-164 аминокислотной последовательности SEQ ID NO:2.
17. Антитело, полученное способом по п.14, которое связывается с полипептидом zcytor17lig человека, состоящим из аминокислот 27-164 аминокислотной последовательности SEQ ID NO:2.
Приоритет по пунктам:
19.12.2002 - 1(а), 1(с), 1(d), 2-12, 13(a), 13(b), 13(d), 14-17;
25.04.2002 - 1(b), 13(с).
RU2004125165/13A 2002-01-18 2003-01-21 Новый лиганд рецептора цитокина zcytor17 RU2360923C2 (ru)

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