RU2010139886A - Моноклональные антитела против белка rgm а и их применение - Google Patents
Моноклональные антитела против белка rgm а и их применение Download PDFInfo
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Abstract
1. Связывающий белок, который диссоциирует из RGM A человека со значением KD, равным 1×10-7 M или менее, и константой скорости koff, равной 1×10-2с-1 или менее, причем обе константы определяют способом резонанса поверхностных плазмонов. ! 2. Связывающий белок, который связывается с RGM A человека и нейтрализует активность, ингибирующую разрастание нейритов RGM A человека, как определено стандартным анализом in vitro. ! 3. Связывающий белок, содержащий антиген-связывающий домен, причем указанный связывающий белок способен связывать эпитоп молекулы RGM, причем указанный антиген-связывающий домен содержит по меньшей мере один CDR, содержащий аминокислотную последовательность, выбранную из группы, состоящей из: ! GTTPDY (SEQ ID NO: 59), FQATHDPLT (SEQ ID NO: 62), ARRNEYYGSSFFDY (SEQ ID NO: 65), LQGYIPPRT (SEQ ID NO: 68), и ! модифицированных аминокислотных последовательностей CDR, последовательность которых по меньшей мере на 50% идентична одной из указанных последовательностей. ! 4. Конструкция антитела, содержащая связывающий белок, описанный в любом из предыдущих пунктов, причем указанная конструкция антитела дополнительно содержит линкерный полипептид или константный домен иммуноглобулина. ! 5. Конъюгат антитела, содержащий конструкцию антитела, описанную в п.4, причем указанный конъюгат антитела дополнительно содержит средство, выбранное из группы, состоящей из: молекулы иммуноадгезии, средства визуализации, терапевтического средства и цитотоксического средства. ! 6. Выделенная нуклеиновая кислота, кодирующая аминокислотную последовательность связывающего белка по любому из пп.1-3. !7. Выделенная нуклеиновая кислота, кодирующая аминокислотную последовательность к
Claims (22)
1. Связывающий белок, который диссоциирует из RGM A человека со значением KD, равным 1×10-7 M или менее, и константой скорости koff, равной 1×10-2с-1 или менее, причем обе константы определяют способом резонанса поверхностных плазмонов.
2. Связывающий белок, который связывается с RGM A человека и нейтрализует активность, ингибирующую разрастание нейритов RGM A человека, как определено стандартным анализом in vitro.
3. Связывающий белок, содержащий антиген-связывающий домен, причем указанный связывающий белок способен связывать эпитоп молекулы RGM, причем указанный антиген-связывающий домен содержит по меньшей мере один CDR, содержащий аминокислотную последовательность, выбранную из группы, состоящей из:
модифицированных аминокислотных последовательностей CDR, последовательность которых по меньшей мере на 50% идентична одной из указанных последовательностей.
4. Конструкция антитела, содержащая связывающий белок, описанный в любом из предыдущих пунктов, причем указанная конструкция антитела дополнительно содержит линкерный полипептид или константный домен иммуноглобулина.
5. Конъюгат антитела, содержащий конструкцию антитела, описанную в п.4, причем указанный конъюгат антитела дополнительно содержит средство, выбранное из группы, состоящей из: молекулы иммуноадгезии, средства визуализации, терапевтического средства и цитотоксического средства.
6. Выделенная нуклеиновая кислота, кодирующая аминокислотную последовательность связывающего белка по любому из пп.1-3.
7. Выделенная нуклеиновая кислота, кодирующая аминокислотную последовательность конструкции антитела по п.4.
8. Выделенная нуклеиновая кислота, кодирующая аминокислотную последовательность конъюгата антитела по п.5.
9. Вектор, содержащий выделенную нуклеиновую кислоту по любому из п.7 или 8.
10. Клетка-хозяин, содержащая вектор по п.9.
11. Способ получения белка, способного связывать RGM, предусматривающий культивирование клетки-хозяина по п.10 в культуральной среде при условиях, достаточных для продуцирования связывающего белка, способного связывать RGM.
12. Белок, полученный в соответствии со способом по п.11.
13. Композиция для высвобождения связывающего белка, причем указанная композиция содержит
(a) композицию, где указанная композиция содержит кристаллизованный белок-продукт, по п.5, и ингредиент; и
(b) по меньшей мере один полимерный носитель.
14. Способ лечения млекопитающего, предусматривающий стадию введения этому млекопитающему эффективного количества композиции по п.13.
15. Фармацевтическая композиция, содержащая продукт по п.1 и фармацевтически приемлемый носитель.
16. Способ уменьшения активности RGM A человека, предусматривающий контактирование RGM A человека с продуктом по п.1, так что активность RGM A человека уменьшается.
17. Способ уменьшения связывания hRGM A с рецептором Неогенином у индивида, при необходимости, предусматривающий стадию введения индивиду продукта по п.1.
18. Способ уменьшения связывания hRGM A с морфогенетическим белком кости 2 и морфогенетическим белком кости 4 (BMP-2 и BMP-4) у индивида, при необходимости, предусматривающий стадию введения индивиду продукта по п.1.
19. Способ лечения индивида от нарушения, ассоциированного с активностью RGM A, предусматривающий стадию введения продукта по п.1, отдельно или в комбинации с другими терапевтическими средствами.
20. Способ уменьшения активности RGM A у индивида, страдающего от нарушения, при котором активность RGM A оказывает негативное воздействие, предусматривающий введение индивиду продукта по п.1, отдельно или в комбинации с другими терапевтическими средствами.
21. Способ по п.20, где нарушение включает неврологические заболевания, выбранные из группы, состоящей из бокового амиотрофического склероза, повреждения плечевого сплетения, повреждения головного мозга, в том числе травматического повреждения головного мозга, церебрального паралича, болезни Гийена-Барре, лейкодистрофий, рассеянного склероза, поствакцинального полиомиелита, расщелины позвоночника, повреждения спинного мозга, спинально-мышечной атрофии, спинальных опухолей, инсульта, поперечного миелита; деменции, сенильной деменции, легкого когнитивного нарушения, связанной с болезнью Альцгеймера деменции, хореи Хантингтона, поздней дискинезии, гиперкинезий, маний, болезни Паркинсона, синдрома Стила-Ричардсона, синдрома Дауна, тяжелой псевдопаралитической миастении, травмы нерва, сосудистого амилоидоза, кровоизлияния I в головной мозг с амилоидозом, воспаления головного мозга, острого нарушения со спутанностью сознания, бокового амиотрофического склероза, глаукомы и болезни Альцгеймера.
22. Выделенный CDR связывающего белка, определенного в п.1.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3270708P | 2008-02-29 | 2008-02-29 | |
US61/032,707 | 2008-02-29 | ||
US9074308P | 2008-08-21 | 2008-08-21 | |
US61/090,743 | 2008-08-21 | ||
PCT/EP2009/001437 WO2009106356A1 (en) | 2008-02-29 | 2009-02-27 | Monoclonal antibodies against the rgm a protein and uses thereof |
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