RU2018108353A - Комбинация, включающая иммуностимулирующие олигонуклеотиды - Google Patents

Комбинация, включающая иммуностимулирующие олигонуклеотиды Download PDF

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RU2018108353A
RU2018108353A RU2018108353A RU2018108353A RU2018108353A RU 2018108353 A RU2018108353 A RU 2018108353A RU 2018108353 A RU2018108353 A RU 2018108353A RU 2018108353 A RU2018108353 A RU 2018108353A RU 2018108353 A RU2018108353 A RU 2018108353A
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Маттьяс ШРОФФ
Мануэль Шмидт
Керстин КАПП
Альфредо ЦУРЛО
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Мологен Аг
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Claims (28)

1. Комбинация, включающая следующие компоненты:
а. первую группу, включающую химическое соединение или молекулу, связывающиеся по меньшей мере с одной из молекул из группы: ПКГ-1, ПКГ-L1, ОХ40, TIM-3, LAG3, CD137 (4-1ВВ) и влияющую на их функцию Т-клеточных регуляторов; а также
б. вторую группу, включающую некодирующую последовательность дезоксирибонуклеиновых кислот, в которую для лечения вирусных инфекций входит, по меньшей мере, один мотив последовательности N1N2CGN3N4, где N означает нуклеотид, содержащий А, С, Т или G; С - дезоксицитидин; G - дезоксигуанозин; А - дезоксиаденозин; а Т - дезокситимидин.
2. Комбинация, по п. 1, где N1N2 представляет собой элемент групп GT, GG, GA, AT и АА, a N3N4 представляет собой элемент групп СТ, TG и ТТ.
3. Комбинация по любому из пп. 1-2, где некодирующая последовательность дезоксирибонуклеиновых кислот может быть представлена в следующих видах: линейная последовательность с незамкнутой с двух сторон цепью; линейная последовательность с незамкнутой двойной цепью с одной стороны и одноцепочечной шпилькой с другой; гантелеобразный конструкт, частично одноцепочечный, с ковалентно замкнутой цепью дезоксирибонуклеиновых кислот.
4. Комбинация по любому из пп. 1-2, где регуляторы Т-клеток включают ингибиторы контрольных точек иммунной системы и сопутствующие стимулирующие молекулы иммунной системы.
5. Комбинация по любому из пп. 1-2, содержащая по меньшей мере три мотива последовательности N1N2CGN3N4.
6. Комбинация по любому из пп. 1-2, где линейная некодирующая последовательность с неразветвленной цепью дезоксирибонуклеиновых кислот включает по меньшей мере один нуклеотид в L-образной конформации.
7. Комбинация по любому из пп. 1-2, где один из пяти концевых нуклеотидов, расположенных на 5'- и/или 3'-конце одиночной цепи ДНК с линейной некодирующей последовательностью дезоксирибонуклеиновых кислот с неразветвленной цепью, находится в L-образной конформации.
8. Комбинация по любому из пп. 1-2, включающая по меньшей мере одну из следующих последовательностей:
а. GTTCCTGGAG ACGTTCTTAG GAACGTTCTC CTTGACGTTG GAGAGAAC (идент. № последовательности: 1), или
б. ACCTTCCTTG TACTAACGTT GCCTCAAGGA AGGTTGATCT TCATAACGTT GCCTAGATCA (идент. № последовательности: 2), или
в. AACGTTCTTCGGGG CGTT (идент. № последовательности: 3), или
г. AGGTGGTAAC CCCTAGGGGT TACCACCTTC ATCGTCGTTT TGTCGTTTTG TCGTTCTT (идент. № последовательности: 4).
9. Комбинация по любому из пп. 1-2, где некодирующая последовательность дезоксирибонуклеиновых кислот имеет длину от 40 до 200 нуклеотидов.
10. Комбинация, по п. 9, где последовательность с) является частью последовательности CCTAGGGGTT АССАССТТСА TTGGAAAACG TTCTTCGGGG CGTTCTTAGG TGGTAACC CCTAGGGGTT АССАССТТСА TTGGAAAACG TTCTTCGGGG CGTTCTTAGG TGGTAACC (идент. № последовательности: 5).
11. Комбинация по любому из пп. 1-2, где некодирующая последовательность дезоксирибонуклеиновых кислот имеет длину от 48 до 116 нуклеотидов.
12. Комбинация по любому из пп. 1-2, где вышеуказанный мотив последовательности N1N2CGN3N4 является частью одноцепочечного участка.
13. Комбинация по любому из пп. 1-2, где молекула, связанная с Т-клеточными регуляторами, представляет собой антитело.
14. Комбинация по любому из пп. 1-2, компоненты обеих групп представлены в твердой, жидкой или газообразной форме, а вводимая доза составляет 15 мг/кг веса максимально.
15. Способ, включающий этап введения компонентов комбинации, представленной в любом из пп. 1-13 формулы изобретения, одновременно, с чередованием или последовательно.
16. Способ по п. 15, где некодирующую последовательность дезоксирибонуклеиновых кислот используют до химического вещества или молекулы для влияния на Т-клеточные регуляторы.
17. Применение комбинации по любому из пп. 1-13 в качестве лекарственного средства.
18. Применение комбинации, по любому из пп. 1-13, для лечения рака, аутоиммунного заболевания или воспаления.
19. Применение комбинации, по п. 17, где соединения комбинации вводят одновременно, с чередованием или последовательно.
20. Применение комбинации, по любому из пп. 1-13, для изготовления фармкомпозиции на основе комбинации.
21. Применение комбинации, по п. 19, в которой фармацевтическое вещество высвобождает соединения комбинации одновременно, с чередованием или последовательно.
22. Применение комбинации, по любому из пп. 1-13, в качестве адъюванта при терапевтической или профилактической вакцинации.
RU2018108353A 2015-09-09 2016-09-09 Комбинация, включающая иммуностимулирующие олигонуклеотиды RU2766693C2 (ru)

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LU92821A LU92821B1 (en) 2015-09-09 2015-09-09 Combination comprising immunostimulatory oligonucleotides
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PCT/EP2016/071314 WO2017042336A1 (en) 2015-09-09 2016-09-09 Combination comprising immunostimulatory oligonucleotides

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WO2018053401A1 (en) 2016-09-19 2018-03-22 Celgene Corporation Methods of treating vitiligo using pd-1 binding proteins
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