RU2016123839A - Новые модуляторы и способы их применения - Google Patents
Новые модуляторы и способы их применения Download PDFInfo
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- RU2016123839A RU2016123839A RU2016123839A RU2016123839A RU2016123839A RU 2016123839 A RU2016123839 A RU 2016123839A RU 2016123839 A RU2016123839 A RU 2016123839A RU 2016123839 A RU2016123839 A RU 2016123839A RU 2016123839 A RU2016123839 A RU 2016123839A
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- seq
- modulator according
- efna modulator
- amino acid
- variable region
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
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- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
- A61K47/6455—Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
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Claims (25)
1. Выделенный модулятор EFNA (эфрина А).
2. Выделенный модулятор EFNA по п. 1, содержащий антагонист EFNA.
3. Выделенный модулятор EFNA по п. 1, содержащий антитело или его иммунореактивный фрагмент.
4. Выделенный модулятор EFNA по п. 3, где антитело или его иммунореактивный фрагмент включает моноклональное антитело.
5. Выделенный модулятор EFNA по п. 4, где моноклональное антитело выбрано из группы, состоящей из химерных антител, CDR-привитых антител, гуманизированных антител и человеческих антител.
6. Выделенный модулятор EFNA по п. 4, где указанное моноклональное антитело включает нейтрализующее антитело.
7. Выделенный модулятор EFNA по п. 4, где указанное моноклональное антитело включает интернализованное антитело.
8. Выделенный модулятор EFNA по п. 4, где указанное моноклональное антитело включает истощающее антитело.
9. Выделенный модулятор EFNA по п. 4, где указанное моноклональное антитело включает антитело, которое вступает в ассоциацию с EFNA4.
10. Выделенный модулятор EFNA по п. 9, где указанное моноклональное антитело содержит вариабельную область легкой цепи, имеющую три области, определяющие комплементарность, и вариабельную область тяжелой цепи, имеющую три области, определяющие комплементарность, где области тяжелой и легкой цепи, определяющие комплементарность, содержат области, определяющие комплементарность, представленные на Фиг. 7А.
11. Выделенный модулятор EFNA по п. 9, где указанное моноклональное антитело содержит вариабельную область легкой цепи и вариабельную область тяжелой цепи, где указанная вариабельная область легкой цепи содержит аминокислотную последовательность, имеющую по меньшей мере 60%-ную идентичность с аминокислотной последовательностью, выбранной из группы, состоящей из аминокислотных последовательностей, представленнных в SEQ ID NO: 99, SEQ ID NO: 103, SEQ ID NO: 107, SEQ ID NO: 111, SEQ ID NO: 115, SEQ ID NO: 119, SEQ ID NO: 123, SEQ ID NO: 127, SEQ ID NO: 131, SEQ ID NO: 135, SEQ ID NO: 139, SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 151, SEQ ID NO: 155, SEQ ID NO: 159 и SEQ ID NO: 163, и где указанная вариабельная область тяжелой цепи содержит аминокислотную последовательность, имеющую по меньшей мере 60%-ную идентичность с аминокислотной последовательностью, выбранной из группы, состоящей из аминокислотных последовательностей, представленных в SEQ ID NO: 97, SEQ ID NO: 101, SEQ ID NO: 105, SEQ ID NO: 109, SEQ ID NO: 113, SEQ ID NO: 117, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 129, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 145, SEQ ID NO: 149, SEQ ID NO: 153, SEQ ID NO: 157 и SEQ ID NO: 161.
12. Выделенный модулятор EFNA по п. 9, 10 или 11, дополнительно содержащий цитотоксический агент.
13. Нуклеиновая кислота, кодирующая аминокислотную вариабельную область тяжелой цепи или аминокислотную вариабельную область легкой цепи по п. 11.
14. Вектор, содержащий нуклеиновую кислоту по п. 13.
15. Клетка-хозяин, содержащая вектор по п. 14.
16. Выделенный модулятор EFNA по п. 1, содержащий аминокислотную последовательность, представленную в SEQ ID NO: 2, или ее фрагмент.
17. Выделенный модулятор EFNA по п. 16, где модулятор EFNA дополнительно содержит по меньшей мере часть константной области иммуноглобулина.
18. Выделенный модулятор EFNA по п. 1, где указанный модулятор снижает частоту появления опухоль-инициирующих клеток при введении нуждающемуся в этом субъекту.
19. Выделенный модулятор EFNA по п. 18, где снижение частоты появления определяли, используя проточный цитометрический анализ поверхностных маркеров опухолевых клеток, которыми, как известно, обогащены опухоль-инициирующие клетки.
20. Выделенный модулятор EFNA по п. 18, где снижение частоты появления определяли, используя иммуногистохимическое обнаружение поверхностных маркеров опухолевых клеток, которыми, как известно, обогащены опухоль-инициирующие клетки.
21. Выделенный модулятор EFNA по п. 18, где указанные опухоль-инициирующие клетки включают клетки, поддерживающие опухоль.
22. Выделенный модулятор EFNA по п. 1, дополнительно содержащий цитотоксический агент.
23. Выделенный модулятор EFNA по п. 1, где указанный модулятор EFNA содержит пан-модулятор EFNA.
24. Фармацевтическая композиция, содержащая выделенный модулятор EFNA по п. 1.
25. Выделенный модулятор EFNA4.
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