RU2015104579A - Диагностические анализы и наборы для детекции фолатного рецептора 1 - Google Patents
Диагностические анализы и наборы для детекции фолатного рецептора 1 Download PDFInfo
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- 238000004458 analytical method Methods 0.000 title claims 3
- 238000001514 detection method Methods 0.000 title claims 2
- 102000010451 Folate receptor alpha Human genes 0.000 title 1
- 108050001931 Folate receptor alpha Proteins 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 claims abstract 28
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 28
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 28
- 239000000427 antigen Substances 0.000 claims abstract 23
- 102000036639 antigens Human genes 0.000 claims abstract 23
- 108091007433 antigens Proteins 0.000 claims abstract 23
- 239000012634 fragment Substances 0.000 claims abstract 23
- 102100035139 Folate receptor alpha Human genes 0.000 claims abstract 17
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 claims abstract 17
- 238000000034 method Methods 0.000 claims abstract 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 8
- 238000006467 substitution reaction Methods 0.000 claims abstract 4
- 241001529936 Murinae Species 0.000 claims abstract 2
- 102000039446 nucleic acids Human genes 0.000 claims abstract 2
- 108020004707 nucleic acids Proteins 0.000 claims abstract 2
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 5
- 238000002965 ELISA Methods 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 2
- 238000003018 immunoassay Methods 0.000 claims 2
- 238000002991 immunohistochemical analysis Methods 0.000 claims 2
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 210000004748 cultured cell Anatomy 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000004163 cytometry Methods 0.000 claims 1
- 238000000684 flow cytometry Methods 0.000 claims 1
- 238000010185 immunofluorescence analysis Methods 0.000 claims 1
- 238000001114 immunoprecipitation Methods 0.000 claims 1
- 238000003127 radioimmunoassay Methods 0.000 claims 1
- 238000001262 western blot Methods 0.000 claims 1
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Abstract
1. Антитело или его антиген-связывающий фрагмент, который специфически связывается с тем же эпитопом FOLR1, или конкурентно ингибирует связывание с FOLR1, что и антитело выбранное из группы, состоящей из:(a) антитела, содержащего полипептид SEQ ID NO: 25 и полипептид SEQ ID NO: 29;(b) антитела, содержащего полипептид SEQ ID NO: 26 и полипептид SEQ ID NO: 30;(c) антитела, содержащего полипептид SEQ ID NO: 27 и полипептид SEQ ID NO: 31; и(d) антитела, содержащего полипептид SEQ ID NO: 28 и полипептид SEQ ID NO: 32.2. Антитело или его антиген-связывающий фрагмент по п. 1, отличающиеся тем, что указанное антитело или его антиген-связывающий фрагмент содержит последовательности аминокислот, выбранные из группы, состоящей из:(a) SEQ ID NO: 1, 2 и 3 и SEQ ID NO: 13, 14 и 15;(b) SEQ ID NO: 4, 5 и 6 и SEQ ID NO: 16, 17 и 18;(c) SEQ ID NO: 7, 8 и 9 и SEQ ID NO: 19, 20 и 21;(d) SEQ ID NO: 10, 11 и 12 и SEQ ID NO: 22, 23 и 24; и(e) вариантов (a)-(d), содержащих 1, 2, 3 или 4 консервативные аминокислотные замены.3. Антитело или его антиген-связывающий фрагмент по п. 1, отличающиеся тем, что указанное антитело или его антиген-связывающий фрагмент содержит последовательности аминокислот, выбранные из группы, состоящей из:(a) SEQ ID NO: 25 и SEQ ID NO: 29;(b) SEQ ID NO: 26 и SEQ ID NO: 30;(c) SEQ ID NO: 27 и SEQ ID NO: 31; и(d) SEQ ID NO: 28 и SEQ ID NO: 32.4. Антитело или его антиген-связывающий фрагмент по любому из пп. 1-3, отличающиеся тем, что указанное антитело или его антиген-связывающий фрагмент является мышиным, не относящимся к человеку, гуманизированным, химерным, с измененной поверхностью или человеческим.5. Полипептид, который специфически связывает FOLR1, при этом указанный полипептид содержит последовательности, выбранные из группы, состоящей из:(a) SEQ ID NO: 1, 2 и 3 и SEQ ID NO: 13, 14 и 15;(b) SEQ ID NO: 4, 5 и 6 и SEQ ID NO: 16, 17 и 18;(c) SEQ ID NO: 7, 8 и 9 и SEQ ID NO: 19, 20 и 21;(d) SEQ ID NO: 10, 11 и 12 и SEQ ID NO: 22, 23 и 24; и(e) вариантов (a)-(d), содержащих 1, 2, 3 или 4 консервативные аминокислотные замены.6. Молекула нуклеиновой кислоты, кодирующая антитело, его антиген-связывающий фрагмент или полипептид по любому из пп. 1-5.7. Способ детекции белка FOLR1 в образце, включающий
Claims (17)
1. Антитело или его антиген-связывающий фрагмент, который специфически связывается с тем же эпитопом FOLR1, или конкурентно ингибирует связывание с FOLR1, что и антитело выбранное из группы, состоящей из:
(a) антитела, содержащего полипептид SEQ ID NO: 25 и полипептид SEQ ID NO: 29;
(b) антитела, содержащего полипептид SEQ ID NO: 26 и полипептид SEQ ID NO: 30;
(c) антитела, содержащего полипептид SEQ ID NO: 27 и полипептид SEQ ID NO: 31; и
(d) антитела, содержащего полипептид SEQ ID NO: 28 и полипептид SEQ ID NO: 32.
2. Антитело или его антиген-связывающий фрагмент по п. 1, отличающиеся тем, что указанное антитело или его антиген-связывающий фрагмент содержит последовательности аминокислот, выбранные из группы, состоящей из:
(a) SEQ ID NO: 1, 2 и 3 и SEQ ID NO: 13, 14 и 15;
(b) SEQ ID NO: 4, 5 и 6 и SEQ ID NO: 16, 17 и 18;
(c) SEQ ID NO: 7, 8 и 9 и SEQ ID NO: 19, 20 и 21;
(d) SEQ ID NO: 10, 11 и 12 и SEQ ID NO: 22, 23 и 24; и
(e) вариантов (a)-(d), содержащих 1, 2, 3 или 4 консервативные аминокислотные замены.
3. Антитело или его антиген-связывающий фрагмент по п. 1, отличающиеся тем, что указанное антитело или его антиген-связывающий фрагмент содержит последовательности аминокислот, выбранные из группы, состоящей из:
(a) SEQ ID NO: 25 и SEQ ID NO: 29;
(b) SEQ ID NO: 26 и SEQ ID NO: 30;
(c) SEQ ID NO: 27 и SEQ ID NO: 31; и
(d) SEQ ID NO: 28 и SEQ ID NO: 32.
4. Антитело или его антиген-связывающий фрагмент по любому из пп. 1-3, отличающиеся тем, что указанное антитело или его антиген-связывающий фрагмент является мышиным, не относящимся к человеку, гуманизированным, химерным, с измененной поверхностью или человеческим.
5. Полипептид, который специфически связывает FOLR1, при этом указанный полипептид содержит последовательности, выбранные из группы, состоящей из:
(a) SEQ ID NO: 1, 2 и 3 и SEQ ID NO: 13, 14 и 15;
(b) SEQ ID NO: 4, 5 и 6 и SEQ ID NO: 16, 17 и 18;
(c) SEQ ID NO: 7, 8 и 9 и SEQ ID NO: 19, 20 и 21;
(d) SEQ ID NO: 10, 11 и 12 и SEQ ID NO: 22, 23 и 24; и
(e) вариантов (a)-(d), содержащих 1, 2, 3 или 4 консервативные аминокислотные замены.
6. Молекула нуклеиновой кислоты, кодирующая антитело, его антиген-связывающий фрагмент или полипептид по любому из пп. 1-5.
7. Способ детекции белка FOLR1 в образце, включающий контактирование указанного образца с антителом, его антиген-связывающим фрагментом или полипептидом по любому из пп. 1-5.
8. Способ по п. 7, отличающийся тем, что белок FOLR1 детектируют с помощью радиоиммуноанализа, вестерн-блоттинга, иммунофлуоресцентного анализа, иммуноферментного анализа, анализа иммунопреципитации, хемилюминесцентного анализа или иммуногистохимического анализа.
9. Способ по п. 8, отличающийся тем, что цитометрия представляет собой проточную цитометрию.
10. Способ по п. 7 или 8, отличающийся тем, что указанный белок FOLR1 представляет собой слущивающийся белок FOLR1.
11. Способ по п. 7 или 8, отличающийся тем, что белок FOLR1 детектируют в циркулирующих опухолевых клетках в указанном образце.
12. Способ по п. 8, отличающийся тем, что иммуноферментный анализ представляет собой твердофазный иммуноферментный анализ (ELISA).
13. Способ по п. 8, отличающийся тем, что белок FOLR1 детектируют с помощью иммуногистохимического анализа.
14. Клетка, продуцирующая антитело, его антиген-связывающий фрагмент по любому из пп. 1-4 или полипептид по п. 5.
15. Способ получения антитела, его антиген-связывающего фрагмента или полипептида по любому из пп. 1-5, включающий (а) культивирование клетки по п. 14; и (b) выделение указанного антитела, его антиген-связывающего фрагмента по любому из пп. 1-4 или полипептида по п. 5 из указанной культивированной клетки.
16. Набор для иммуноанализа для детекции белка FOLR1 в образце, указанный набор включает: (а) первый реагент, при этом первый реагент представляет собой антитело или его антиген-связывающий фрагмент по любому из пп. 1-4 или полипептид по п. 5, и (b) второй реагент, при этом второй реагент представляет собой реагент для детекции.
17. Способ лечения рака, включающий введение активного средства, содержащего антитело или его антиген-связывающий фрагмент, которое специфически связывается с FOLR1 у пациента с повышенными уровнями белка FOLR1, при этом повышеные уровни белка FOLR1 были измерены с помощью антитела, его антиген-связывающего фрагмента по любому из пп. 1-4 или полипептида по п. 5.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261695791P | 2012-08-31 | 2012-08-31 | |
US61/695,791 | 2012-08-31 | ||
US201361756254P | 2013-01-24 | 2013-01-24 | |
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