RU2349340C2 - Биспецифические антитела к erb-b и их применение для лечения опухолей - Google Patents
Биспецифические антитела к erb-b и их применение для лечения опухолей Download PDFInfo
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Abstract
Изобретение относится к медицине, а именно к иммунотерапии. Предложено биспецифическое антитело и его применение для лечения опухолей. Новое антитело обладает способностью связываться с EGF рецептором, причем содержит два антигенсвязывающих участка, которые связываются с различными эпитопами указанного рецептора, что обеспечивает более высокую занятость рецептора антителами при одинаковой дозе. Это дает возможность повысить плотность антитела на рецепторе и привести к значительному ингибированию роста опухоли и/или усилению апоптоза солидных опухолей или метастаз. 4 н. и 12 з.п. ф-лы.
Description
Claims (16)
1. Биспецифическое антитело, обладающее способностью связываться с EGF рецептором (EGFR), причем указанное антитело содержит первый антигенсвязывающий участок, который связывается с первым эпитопом указанного EGFR, и второй отличный антигенсвязывающий участок, который связывается со вторым эпитопом указанного EGFR, где указанный первый антигенсвязывающий участок происходит от гуманизированного, химерного или мышиного MAb 425, а указанный второй антигенсвязывающий участок происходит от гуманизированного, химерного или мышиного MAb 225, и каждый из указанных первых и вторых антигенсвязывающих участков связывается с различными эпитопами на одной и той же молекуле EGFR.
2. Биспецифическое антитело по п.1, в котором указанные различные эпитопы расположены в пределах связывающего домена естественного лиганда(ов) указанного EGF рецептора.
3. Биспецифическое антитело по п.1, в котором по крайней мере один указанный эпитоп расположен в пределах связывающего домена естественного лиганда(ов) указанного EGF рецептора.
4. Биспецифическое антитело по п.1, в котором первый или второй антигенсвязывающий участок связывается с эпитопом, расположенным в пределах связывающего домена естественного лиганда(ов) указанной молекулы EGF рецептора.
5. Биспецифическое антитело по п.1, в котором первый и второй антигенсвязывающий участок связывается с эпитопом, расположенным в пределах связывающего домена естественного лиганда(ов) указанной молекулы EGF рецептора.
6. Иммуноконъюгат, включающий биспецифическое антитело по п.1 или его фрагмент, слитый непосредственно или при помощи линкерной молекулы через С-концевую часть с цитокином.
7. Фармацевтическая композиция для лечения рака, которая содержит терапевтически эффективное количество биспецифического антитела по п.1 или его иммуноконъюгата по п.6, необязательно с фармацевтически приемлемым носителем, разбавителем или наполнителем.
8. Фармацевтическая композиция по п.7, которая дополнительно содержит моноспецифическое антитело к ErbB или его функционально активный фрагмент.
9. Фармацевтическая композиция по п.8, в которой указанное моноспецифическое антитело к ErbB или его функционально эффективный фрагмент выбрано из группы, включающей MAb 425, MAb 225, или MAb 4D5 (Herceptin®).
10. Фармацевтическая композиция по п.7, которая дополнительно содержит цитотоксическое средство.
11. Фармацевтическая композиция по п.10, в которой цитотоксическое средство представляет собой химиотерапевтическое средство.
12. Фармацевтическая композиция по п.11, в которой указанное химиотерапевтическое средство выбрано из любого соединения из группы, включающей цисплатин, доксорубицин, гемцитабин, доцетаксел, паклитаксел, блеомицин.
13. Фармацевтическая композиция по п.10, в которой указанное цитотоксическое средство представляет собой ингибитор рецептора ErbB, ингибитор рецептора VEGF, ингибитор тирозинкиназы, ингибитор протеинкиназы А, антиангиогенное средство, антигормональное средство или цитокин.
14. Фармацевтический набор для лечения рака, который содержит (i) первую упаковку, содержащую по меньшей мере биспецифическое антитело по п.1 или иммуноконъюгат по п.6; (ii) вторую упаковку, содержащую по меньшей мере моноспецифическое антитело к ErbB или его функционально активный фрагмент.
15. Фармацевтический набор по п.14, который дополнительно содержит третью упаковку, содержащую цитотоксическое средство.
16. Фармацевтический набор по п.15, в котором указанное цитотоксическое средство выбрано из любого соединения из группы, включающей цисплатин, доксорубицин, гемцитабин, доцетаксел, паклитаксел, блеомицин, ингибитор рецептора ErbB, ингибитор рецептора VEGF, ингибитор тирозинкиназы, ингибитор протеинкиназы А, антиангиогенное средство, антигормональное средство или цитокин.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02022390.5 | 2002-10-10 | ||
EP02022389 | 2002-10-10 | ||
EP02022390 | 2002-10-10 | ||
EP02022389.7 | 2002-10-10 |
Publications (2)
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RU2005114482A RU2005114482A (ru) | 2006-01-27 |
RU2349340C2 true RU2349340C2 (ru) | 2009-03-20 |
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Application Number | Title | Priority Date | Filing Date |
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RU2005114480A RU2354402C2 (ru) | 2002-10-10 | 2003-10-09 | ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, НАПРАВЛЕННЫЕ НА РЕЦЕПТОРЫ ErbB1 |
RU2005114482A RU2349340C2 (ru) | 2002-10-10 | 2003-10-09 | Биспецифические антитела к erb-b и их применение для лечения опухолей |
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RU2005114480A RU2354402C2 (ru) | 2002-10-10 | 2003-10-09 | ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, НАПРАВЛЕННЫЕ НА РЕЦЕПТОРЫ ErbB1 |
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US (2) | US7638125B2 (ru) |
EP (2) | EP1549345A1 (ru) |
JP (3) | JP5179702B2 (ru) |
KR (2) | KR20050057631A (ru) |
CN (1) | CN1703243B (ru) |
AU (2) | AU2003273964B2 (ru) |
BR (2) | BR0315117A (ru) |
CA (2) | CA2501818C (ru) |
CY (1) | CY1116167T1 (ru) |
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ES (1) | ES2533963T3 (ru) |
HK (2) | HK1081449A1 (ru) |
HU (1) | HUE025086T2 (ru) |
MX (2) | MXPA05003796A (ru) |
PL (2) | PL374586A1 (ru) |
PT (1) | PT1549344E (ru) |
RU (2) | RU2354402C2 (ru) |
SI (1) | SI1549344T1 (ru) |
WO (2) | WO2004032961A1 (ru) |
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