RU2018108353A - Комбинация, включающая иммуностимулирующие олигонуклеотиды - Google Patents
Комбинация, включающая иммуностимулирующие олигонуклеотиды Download PDFInfo
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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.
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PCT/EP2016/071314 WO2017042336A1 (en) | 2015-09-09 | 2016-09-09 | Combination comprising immunostimulatory oligonucleotides |
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JP6697384B2 (ja) | 2013-07-25 | 2020-05-20 | イグジキュア, インコーポレーテッドExicure, Inc. | 予防的および治療的使用のための免疫刺激剤としての球状の核酸ベース構築物 |
US11213593B2 (en) | 2014-11-21 | 2022-01-04 | Northwestern University | Sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
LU92821B1 (en) | 2015-09-09 | 2017-03-20 | Mologen Ag | Combination comprising immunostimulatory oligonucleotides |
GB2542425A (en) | 2015-09-21 | 2017-03-22 | Mologen Ag | Means for the treatment of HIV |
EA201890790A1 (ru) | 2015-09-29 | 2018-10-31 | Селджин Корпорейшн | Связывающие pd-1 белки и способы их применения |
WO2018039629A2 (en) | 2016-08-25 | 2018-03-01 | Northwestern University | Micellar spherical nucleic acids from thermoresponsive, traceless templates |
WO2018053405A1 (en) | 2016-09-19 | 2018-03-22 | Celgene Corporation | Methods of treating immune disorders using pd-1 binding proteins |
US10766958B2 (en) | 2016-09-19 | 2020-09-08 | Celgene Corporation | Methods of treating vitiligo using PD-1 binding antibodies |
EP3392345A1 (en) | 2017-04-22 | 2018-10-24 | Mologen AG | Biomarker for small cell lung cancer therapy |
US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
JP2020531555A (ja) * | 2017-08-31 | 2020-11-05 | モロゲン・アーゲー | 腫瘍微小環境のモジュレーションのためのtlr−9アゴニスト |
TW202011959A (zh) | 2018-04-14 | 2020-04-01 | 美商戴納瓦克斯技術公司 | 用於治療癌症之包括CpG-C 型寡核苷酸及組蛋白去乙醯酶抑制劑之組合 |
CN112007149A (zh) * | 2019-05-29 | 2020-12-01 | 思格(苏州)生物科技有限公司 | 一种新型复合免疫佐剂及其应用 |
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