RU2016124731A - Рецептор-направленные конструкции и их применение - Google Patents
Рецептор-направленные конструкции и их применение Download PDFInfo
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- RU2016124731A RU2016124731A RU2016124731A RU2016124731A RU2016124731A RU 2016124731 A RU2016124731 A RU 2016124731A RU 2016124731 A RU2016124731 A RU 2016124731A RU 2016124731 A RU2016124731 A RU 2016124731A RU 2016124731 A RU2016124731 A RU 2016124731A
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- drug delivery
- cancer
- targeted drug
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Classifications
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Claims (53)
1. Молекула для адресной доставки лекарственного средства, содержащая:
лигаид, который направленно связывается с молекулой клеточной поверхности;
домен, обеспечивающий проникновение через клеточную мембрану; и
домен, связывающий молекулярный груз.
2. Молекула для адресной доставки лекарственного средства по п. 1, дополнительно содержащая терапевтическое средство.
3. Молекула для адресной доставки лекарственного средства по п. 2, отличающаяся тем, что терапевтическое средство формирует комплекс с доменом, связывающим молекулярный груз.
4. Молекула для адресной доставки лекарственного средства по п. 3, отличающаяся тем, что комплекс является ковалентным или нековалентным.
5. Молекула для адресной доставки лекарственного средства по п. 1, отличающаяся тем, что молекула для адресной доставки лекарственного средства представляет собой наночастицу, имеющую диаметр от около 5 нм и до около 50 нм.
6. Молекула для адресной доставки лекарственного средства по п. 1, отличающаяся тем, что молекула клеточной поверхности представляет собой белок, углеводный фрагмент, присоединенный к белку или их комбинацию.
7. Молекула для адресной доставки лекарственного средства по п. 1, отличающаяся тем, что молекула клеточной поверхности представляет собой рецептор, а лиганд направленно связывается с рецептором на раковой клетке.
8. Молекула для адресной доставки лекарственного средства по п. 7, отличающаяся тем, что раковая клетка представляет собой любую одну или более из клетки злокачественной опухоли легких, почек, печени, желудка, молочной железы, толстого кишечника, желудочно-кишечного тракта, яичников, немелкоклеточной карциномы легких или злокачественной опухоли головного мозга.
9. Молекула для адресной доставки лекарственного средства по п. 7, отличающаяся тем, что рецептор выбран из группы, состоящей из c-Met, HER2, HER3, CD4 и CD20.
10. Молекула для адресной доставки лекарственного средства по п. 7, отличающаяся тем, что лиганд выбран из группы, состоящей из белка, белкового фрагмента, полипептида, олигопептида, антитела, фрагмента антитела и малой органической молекулы.
11. Молекула для адресной доставки лекарственного средства по п. 7, отличающаяся тем. что лиганд выбран из группы, состоящей из фактора роста гепатоцитов (HGF), интерналина В, бактериального белка инвазина (Inv) и пептида, имеющего последовательность, изложенную в SEQ ID NO: 5.
12. Молекула для адресной доставки лекарственного средства по п. 1, отличающаяся тем, что домен, обеспечивающий проникновение через клеточную мембрану, представляет собой белок, являющийся основанием пентона, или его фрагмент, полученный из аденовируса.
13. Молекула для адресной доставки лекарственного средства по п. 1, отличающаяся тем, что домен, связывающий молекулярный груз, представляет собой декализиновый мотив.
14. Молекула для адресной доставки лекарственного средства по п. 2, отличающаяся тем, что терапевтическое средство представляет собой любое одно или более из алкилирующих средств, антиметаболитов, противоопухолевых антибиотиков, ингибиторов митоза, кортикостероидов, цитотоксических средств или их комбинаций.
15. Молекула для адресной доставки лекарственного средства по п. 2, отличающаяся тем, что терапевтическое средство выбрано из группы, состоящей из белка, белкового фрагмента, полипептида, олигопептида, нуклеиновой кислоты, дезоксирибонуклеиновой кислоты (ДНК), рибонуклеиновой кислоты (РНК), мРНК, тРНК, рРНК, онРНК, миРНК и малой органической молекулы.
16. Молекула для адресной доставки лекарственного средства по п. 2, отличающаяся тем, что терапевтическое средство выбрано из группы, состоящей из соединений коррола, треосульфана, трофосфамида, винбластина, паклитаксела, доцетаксола, доксорубицина, эпирубицина, этопозида, камптотецина, топотекана, иринотекана, тенипозида, криснатола, митомицина, метотрексата, микофеноловой кислоты, гидроксимочевины, 5-фторурацила, доксифлуридина, цитозин-арабинозида, меркаптопурина, тиогуанина, 2'-дезокси-5-фторуридина, глицината афидиколина, пиразолоимидазола, галихондрина, колхицина и ризоксина, или их комбинации.
17. Фармацевтическая композиция, содержащая:
молекулу для адресной доставки лекарственного средства, содержащую:
лиганд, мишенью которого является рецептор на клеточной поверхности;
домен, обеспечивающий проникновение через клеточную мембрану; и
домен, связывающий молекулярный груз; и
фармацевтически приемлемый носитель.
18. Способ лечения злокачественной опухоли у субъекта, который в этом нуждается, включающий:
идентификацию субъекта, который нуждается в лечении;
обеспечение композиции, содержащей молекулу для адресной доставки
лекарственного средства по п. 1;
и
введение субъекту эффективного количества композиции для лечения злокачественной опухоли у субъекта.
19. Способ по п. 18, отличающийся тем, что злокачественная опухоль выбрана из группы, состоящей из лейкоза, миеломы, В-клеточных лимфом (лимфомы Ходжкина и/или неходжкинские лимфомы), злокачественной опухоли головного мозга, злокачественной опухоли молочной железы, злокачественной опухоли толстого кишечника, злокачественной опухоли легких, гепатоцеллюлярной карциномы, злокачественной опухоли почки, злокачественной опухоли желудочно-кишечного тракта, злокачественной опухоли поджелудочной железы, злокачественной опухоли шейки матки, злокачественной опухоли яичников, злокачественной опухоли печени, злокачественной опухоли мочевого пузыря, злокачественной опухоли мочевыводящих путей, злокачественной опухоли щитовидной железы, злокачественной опухоли почек, карциномы, меланомы, злокачественной опухоли головы и шеи, злокачественной опухоли головного мозга, злокачественной опухоли предстательной железы, андрогензависимой злокачественной опухоли предстательной железы и андрогеннезависимой злокачественной опухоли предстательной железы.
20. Способ по п. 18, отличающийся тем, что лиганд представляет собой интерналин В или его фрагмент, домен, обеспечивающий проникновение через клеточную мембрану, представляет собой белок, являющийся основанием пептона, или его фрагмент, и домен, связывающий молекулярный груз, представляет собой декализиновый мотив.
21. Способ по п. 18, отличающийся тем, что композиция дополнительно содержит цитотоксическое средство.
22. Способ по п. 18, отличающийся тем, что цитотоксическое средство выбрано из группы, состоящей из соединений коррола, треосульфана, трофосфамида, винбластина, паклитаксела, доцетаксола, доксорубицина, эпирубицина, этопозида, камптотецина, топотекана, иринотекана, тенипозида, криснатола, митомицина, метотрексата, микофеноловой кислоты, гидроксимочевины, 5-фторурацила, доксифлуридина, цитозин-арабинозида, меркаптопурина, тиогуанина, 2'-дезокси-5-фторуридина, глицината афидиколина, пиразолоимидазола, галихондрина, колхицина и ризоксина, или их комбинации.
23. Способ но п. 18, дополнительно включающий применение дополнительных терапевтических воздействий.
24. Способ по п. 18, отличающийся тем, что композицию и дополнительные терапевтические воздействия применяют одновременно или последовательно.
25. Способ по п. 18, отличающийся тем, что дополнительные терапевтические воздействия представляют собой любое одно или более из оперативного вмешательства, облучения, иммунотерапии, вакцинации или их комбинаций.
26. Способ подавления прогрессирования злокачественной опухоли у субъекта, который в этом нуждается, включающий:
идентификацию субъекта, который нуждается в лечении;
обеспечение композиции, содержащей молекулу для адресной доставки лекарственного средства по п. 1;
и
введение субъекту эффективного количества композиции для подавления прогрессирования злокачественной опухоли у субъекта.
27. Способ предотвращения метастазирования злокачественной опухоли у субъекта, который в этом нуждается, включающий:
идентификацию субъекта, который нуждается в лечении;
обеспечение композиции, содержащей молекулу для адресной доставки лекарственного средства по п. 1;
и
введение субъекту эффективного количества композиции для предотвращения метастазирования злокачественной опухоли у субъекта.
28. Способ адресной доставки терапевтического соединения в головной мозг субъекта, который в этом нуждается, включающий:
идентификацию субъекта, который нуждается в лечении;
обеспечение композиции, содержащей молекулу для адресной доставки лекарственного средства по п. 1;
и
введение субъекту эффективного количества композиции.
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WO2009009441A2 (en) | 2007-07-06 | 2009-01-15 | Cedars-Sinai Medical Center | Self-assembling complex for targeting chemical agents to cells |
WO2010085665A2 (en) | 2009-01-23 | 2010-07-29 | Cedars-Sinai Medical Center | Targeted delivery system |
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US20160331840A1 (en) | 2016-11-17 |
CA2935404A1 (en) | 2015-07-23 |
WO2015109264A1 (en) | 2015-07-23 |
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IL246668A0 (en) | 2016-08-31 |
US20220362389A1 (en) | 2022-11-17 |
CN106413738A (zh) | 2017-02-15 |
KR102434541B1 (ko) | 2022-08-19 |
BR112016016202A2 (pt) | 2017-09-19 |
ZA201605237B (en) | 2019-04-24 |
AU2020203434A1 (en) | 2020-06-11 |
JP6608370B2 (ja) | 2019-11-20 |
JP2017508724A (ja) | 2017-03-30 |
RU2016124731A3 (ru) | 2018-09-18 |
EP3096773A1 (en) | 2016-11-30 |
RU2682335C2 (ru) | 2019-03-19 |
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