RU2013123720A - Моноклональные антитела против белка rgm a и их применение - Google Patents

Моноклональные антитела против белка rgm a и их применение Download PDF

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RU2013123720A
RU2013123720A RU2013123720/10A RU2013123720A RU2013123720A RU 2013123720 A RU2013123720 A RU 2013123720A RU 2013123720/10 A RU2013123720/10 A RU 2013123720/10A RU 2013123720 A RU2013123720 A RU 2013123720A RU 2013123720 A RU2013123720 A RU 2013123720A
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rgm
binding
cdr
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Бернхард К. МЮЛЛЕР
Мартин Шмидт
Ив Х. Барлоу
Мэри Р. ЛЕДДИ
Чунг-минг ХСИЕХ
Филип Д. БАРДУЭЛЛ
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Эбботт Гмбх Унд Ко.Кг
Эбботт Лэборетриз
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Abstract

1. Выделенное моноклональное антитело, содержащее антигенсвязующий домен, где указанное антитело способно связывать эпитоп молекулы RGM, указанный антигенсвязующий домен содержит по меньшей мере два набора CDR вариабельного домена, где указанные по меньшей мере два набора CDR вариабельного домена представляют собой набор VH 8D1 и набор VL 8D1, где наборы CDR вариабельного домена состоят из:2. Антитело по п. 1, содержащее набор вариабельного домена, где по меньшей мере одни из указанных трех CDR является модифицированной аминокислотной последовательностью CDR с последовательностью, которая по меньшей мере на 50% идентична исходной последовательности, где указанное антитело способно связываться с эпитопом молекулы RGM.3. Антитело по любому из предыдущих пунктов, дополнительно содержащее акцепторную каркасную область человека, где указанная акцепторная каркасная область человека содержит по меньшей мере одну аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO:15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 и 33.4. Антитело по п. 1 или 2, которое представляет собой антитело 8D1.5. Антигенсвязующий фрагмент выделенного моноклонального антитела по любому из пп. 1-4.6. Выделенная нуклеиновая кислота, кодирующая молекулу антитела по любому из пп. 1-5.7. Вектор, содержащий выделенную нуклеиновую кислоту по п. 6.8. Клетка-хозяин, содержащая вектор по п. 7.9. Способ получения белка, способного связываться с RGM, включающий культивирование клетки-хозяина по п. 8 в культуральной среде в условиях, подходящих для получения связывающего белка, способного связываться с RGM.10. Фармацевтическая композиция для лечения заболевания, в котором акт

Claims (13)

1. Выделенное моноклональное антитело, содержащее антигенсвязующий домен, где указанное антитело способно связывать эпитоп молекулы RGM, указанный антигенсвязующий домен содержит по меньшей мере два набора CDR вариабельного домена, где указанные по меньшей мере два набора CDR вариабельного домена представляют собой набор VH 8D1 и набор VL 8D1, где наборы CDR вариабельного домена состоят из:
набор VH 8D1     VH 8D1 CDR-H1 остатки 31-35 SEQ ID NO:55 SEQ ID NO:63 VH 8D1 CDR-H2 остатки 50-66 SEQ ID NO:55 SEQ ID NO:64 VH 8D1 CDR-H3 остатки 97-110 SEQ ID NO:55 SEQ ID NO:65 Набор VL 8D1     VL 8D1 CDR-L1 остатки 24-34 SEQ ID NO:56 SEQ ID NO:66 VL 8D1 CDR-L2 остатки 50-56 SEQ ID NO:56 SEQ ID NO:67 VL 8D1 CDR-L3 остатки 89-97 SEQ ID NO:57 SEQ ID NO:68
2. Антитело по п. 1, содержащее набор вариабельного домена, где по меньшей мере одни из указанных трех CDR является модифицированной аминокислотной последовательностью CDR с последовательностью, которая по меньшей мере на 50% идентична исходной последовательности, где указанное антитело способно связываться с эпитопом молекулы RGM.
3. Антитело по любому из предыдущих пунктов, дополнительно содержащее акцепторную каркасную область человека, где указанная акцепторная каркасная область человека содержит по меньшей мере одну аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO:15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 и 33.
4. Антитело по п. 1 или 2, которое представляет собой антитело 8D1.
5. Антигенсвязующий фрагмент выделенного моноклонального антитела по любому из пп. 1-4.
6. Выделенная нуклеиновая кислота, кодирующая молекулу антитела по любому из пп. 1-5.
7. Вектор, содержащий выделенную нуклеиновую кислоту по п. 6.
8. Клетка-хозяин, содержащая вектор по п. 7.
9. Способ получения белка, способного связываться с RGM, включающий культивирование клетки-хозяина по п. 8 в культуральной среде в условиях, подходящих для получения связывающего белка, способного связываться с RGM.
10. Фармацевтическая композиция для лечения заболевания, в котором активность RGM A оказывает негативное воздействие, содержащая терапевтически эффективное количество антитела по любому из пп. 1-5, и фармацевтически приемлемый носитель.
11. Применение антитела по любому из пп. 1-5 для получения лекарственного средства, используемого для снижения связывания hRGM A с костным морфогентическим белком-2 и костным морофгенетическим белком-4 (BMP-2 и BMP-4) у больного.
12. Применение продукта по любому из пп. 1-5 для получения лекарственного средства для снижения активности RGM A у больного, страдающего заболеванием, при котором активность RGM A является патологической.
13. Применение по п. 12, где заболевание включает неврологические заболевания, выбранные из группы, включающей боковой амиотрофический склероз, повреждение плечевого сплетения, повреждение головного мозга, в том числе травматическое повреждение головного мозга, церебральный паралич, болезнь Гийена-Барре, лейкодистрофию, рассеянный склероз, поствакцинальный полиомиелит, расщелину позвоночника, повреждение спинного мозга, спинально-мышечную атрофию, спинальные опухоли, инсульт, поперечный миелит; деменцию, сенильную деменцию, когнитивные нарушения умеренной степени, деменцию, связанную с болезнью Альцгеймера, хорею Хантингтона, позднюю дискинезию, гиперкинезий, мании, болезнь Паркинсона, синдром Стила-Ричардсона, синдром Дауна, тяжелую псевдопаралитическую миастению, травму нерва, сосудистый амилоидоз, кровоизлияние в головной мозг I степени с амилоидозом, воспаление головного мозга, острое нарушение со спутанностью сознания, боковой амиотрофический склероз, глаукому и болезнь Альцгеймера.
RU2013123720/10A 2008-02-29 2013-05-23 Моноклональные антитела против белка rgm a и их применение RU2013123720A (ru)

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