RU2012153978A - Связывающие комплект аптамеры и средства против с5, пригодные для лечения глазных нарушений - Google Patents

Связывающие комплект аптамеры и средства против с5, пригодные для лечения глазных нарушений Download PDF

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RU2012153978A
RU2012153978A RU2012153978/15A RU2012153978A RU2012153978A RU 2012153978 A RU2012153978 A RU 2012153978A RU 2012153978/15 A RU2012153978/15 A RU 2012153978/15A RU 2012153978 A RU2012153978 A RU 2012153978A RU 2012153978 A RU2012153978 A RU 2012153978A
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macular degeneration
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Дэвид ЭПШТЕЙН
Джефф С. КУРЦ
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АРКЕМИКС Эл Эл Си
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
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    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/16—Aptamers
    • C—CHEMISTRY; METALLURGY
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    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Abstract

1. Способ лечения, стабилизации и/или профилактики глазного нарушения, при этом способ включает введение терапевтически эффективного количества средства против С5 в комбинации со средством против PDGF субъекту, нуждающемуся в этом, причем средство против С5 является пегилированным или непегилированным аптамером, который связывается с С5 комплементом.2. Способ по п.1, где пегилированный или непегилированный аптамер имеет последовательность выбранную из: SEQ ID NO: с 1 по 69, 75, 76, 81, 91, 95 и 96.3. Способ по п.1, где пегилированный или непегилированный аптамер имеет последовательность SEQ ID NO:4, SEQ ID NO:5 или SEQ ID NO:67.4. Способ по п.1, где средство против С5 представляет собой пегилированный аптамер имеющий структуру, указанную ниже или ее соль:гдеуказывает на линкергде fC и fU=2' - фторнуклеотиды, и mG и mA=2' - OMe-нуклеотиды и все другие нуклеотиды являются 2'-ОН, и 3Т указывает на инвертированный дезокситимидин.5. Способ по п.4, где линкер представляет собой алкильный линкер.6. Способ по п.5, где алкильный линкер содержит от 2 до 18 последовательно расположенных групп СН.7. Способ по п.1, где средство против С5 представляет собой пегилированный аптамер имеющий структуру, указанную ниже:гдегде fC и fU=2' - фторнуклеотиды, и mG и mA=2' - ОМе-нуклеотиды и все другие нуклеотиды являются 2'-ОН, и где 3Т указывает на инвертированный дезокситимидин.8. Способ по любому из предшествующих пунктов, где глазное нарушение представляет собой дегенерацию желтого пятна или диабетическую ретинопатию.9. Способ по п.8, где дегенерация желтого пятна представляет собой возрастную дегенерацию желтого пятна (AMD).10. Способ по п.9, где возрастная дегенерация желтого пятна (AMD) представляет собо

Claims (21)

1. Способ лечения, стабилизации и/или профилактики глазного нарушения, при этом способ включает введение терапевтически эффективного количества средства против С5 в комбинации со средством против PDGF субъекту, нуждающемуся в этом, причем средство против С5 является пегилированным или непегилированным аптамером, который связывается с С5 комплементом.
2. Способ по п.1, где пегилированный или непегилированный аптамер имеет последовательность выбранную из: SEQ ID NO: с 1 по 69, 75, 76, 81, 91, 95 и 96.
3. Способ по п.1, где пегилированный или непегилированный аптамер имеет последовательность SEQ ID NO:4, SEQ ID NO:5 или SEQ ID NO:67.
4. Способ по п.1, где средство против С5 представляет собой пегилированный аптамер имеющий структуру, указанную ниже или ее соль:
Figure 00000001
где
Figure 00000002
указывает на линкер
Figure 00000003
где fC и fU=2' - фторнуклеотиды, и mG и mA=2' - OMe-нуклеотиды и все другие нуклеотиды являются 2'-ОН, и 3Т указывает на инвертированный дезокситимидин.
5. Способ по п.4, где линкер представляет собой алкильный линкер.
6. Способ по п.5, где алкильный линкер содержит от 2 до 18 последовательно расположенных групп СН2.
7. Способ по п.1, где средство против С5 представляет собой пегилированный аптамер имеющий структуру, указанную ниже:
Figure 00000004
где
Figure 00000003
где fC и fU=2' - фторнуклеотиды, и mG и mA=2' - ОМе-нуклеотиды и все другие нуклеотиды являются 2'-ОН, и где 3Т указывает на инвертированный дезокситимидин.
8. Способ по любому из предшествующих пунктов, где глазное нарушение представляет собой дегенерацию желтого пятна или диабетическую ретинопатию.
9. Способ по п.8, где дегенерация желтого пятна представляет собой возрастную дегенерацию желтого пятна (AMD).
10. Способ по п.9, где возрастная дегенерация желтого пятна (AMD) представляет собой AMD неэкссудативного типа или AMD экссудативного типа.
11. Способ по п.1, где средство против С5 доставляют внутриглазным введением.
12. Способ по п.1, где средство против С5 доставляют введением в стекловидное тело.
13. Способ по п.1, где средство против С5 доставляют посредством окологлазного введения.
14. Способ по п.1, где средство против С5 подлежащее введению, содержится в составе с замедленным действием.
15. Способ по п.1, где субъектом является человек.
16. Способ по п.1, где средство против PDGF выбрано из группы, состоящей из молекулы нуклеиновой кислоты, аптамера, антисмысловой молекулы, молекулы RNAi, белка, пептида, циклического пептида, антитела или фрагмента антитела, сахара, полимера и низкомолекулярного соединения.
17. Способ по п.1, где средство против С5 и средство против PDGF вводятся субъекту, нуждающемуся в этом, в количестве эффективном для стабилизации глазного нарушения, снижения симптома глазного нарушения или профилактики симптома глазного нарушения.
18. Способ по п.1, где средство против С5 и средство против PDGF вводят по существу одновременно.
19. Способ по п.1, где средство против С5 и средство против PDGF присутствуют в одной композиции.
20. Способ по п.1, где средство против С5 и средство против PDGP присутствуют в разных композициях.
21. Способ по п.1, где средство против С5 и средство против PDGF вводят последовательно.
RU2012153978/15A 2006-03-08 2012-12-13 Связывающие комплект аптамеры и средства против с5, пригодные для лечения глазных нарушений RU2012153978A (ru)

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