RU2007102287A - Антагонисты активности рецептора интерлейкина-21 - Google Patents
Антагонисты активности рецептора интерлейкина-21 Download PDFInfo
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- RU2007102287A RU2007102287A RU2007102287/13A RU2007102287A RU2007102287A RU 2007102287 A RU2007102287 A RU 2007102287A RU 2007102287/13 A RU2007102287/13 A RU 2007102287/13A RU 2007102287 A RU2007102287 A RU 2007102287A RU 2007102287 A RU2007102287 A RU 2007102287A
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- 239000005557 antagonist Substances 0.000 title claims 9
- 102000004527 Interleukin-21 Receptors Human genes 0.000 title 1
- 108010017411 Interleukin-21 Receptors Proteins 0.000 title 1
- 102000008640 interleukin-21 receptor activity proteins Human genes 0.000 claims 25
- 108040002099 interleukin-21 receptor activity proteins Proteins 0.000 claims 25
- 238000000034 method Methods 0.000 claims 25
- 239000012634 fragment Substances 0.000 claims 19
- 239000000427 antigen Substances 0.000 claims 11
- 102000036639 antigens Human genes 0.000 claims 11
- 108091007433 antigens Proteins 0.000 claims 11
- 241000124008 Mammalia Species 0.000 claims 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 9
- 206010052779 Transplant rejections Diseases 0.000 claims 8
- 208000024891 symptom Diseases 0.000 claims 7
- 201000010099 disease Diseases 0.000 claims 5
- 102000004169 proteins and genes Human genes 0.000 claims 5
- 108090000623 proteins and genes Proteins 0.000 claims 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 208000035475 disorder Diseases 0.000 claims 4
- 210000000056 organ Anatomy 0.000 claims 4
- 238000002054 transplantation Methods 0.000 claims 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 3
- 208000012657 Atopic disease Diseases 0.000 claims 3
- 108060003951 Immunoglobulin Proteins 0.000 claims 3
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims 3
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 3
- 208000012659 Joint disease Diseases 0.000 claims 3
- 208000006673 asthma Diseases 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 230000003176 fibrotic effect Effects 0.000 claims 3
- 102000018358 immunoglobulin Human genes 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 210000001519 tissue Anatomy 0.000 claims 3
- 201000004624 Dermatitis Diseases 0.000 claims 2
- 206010016654 Fibrosis Diseases 0.000 claims 2
- 201000009961 allergic asthma Diseases 0.000 claims 2
- 208000010668 atopic eczema Diseases 0.000 claims 2
- 230000004761 fibrosis Effects 0.000 claims 2
- 108020001507 fusion proteins Proteins 0.000 claims 2
- 102000037865 fusion proteins Human genes 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 208000011231 Crohn disease Diseases 0.000 claims 1
- 206010012438 Dermatitis atopic Diseases 0.000 claims 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 208000003456 Juvenile Arthritis Diseases 0.000 claims 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
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- 208000003782 Raynaud disease Diseases 0.000 claims 1
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- 150000001413 amino acids Chemical class 0.000 claims 1
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Claims (32)
1. Способ лечения, облегчения симптоматики или предотвращения аутоиммунного или воспалительного нарушения у млекопитающего, включающий введение указанному млекопитающему антагониста IL-21/IL-21R, выбранного из группы, включающей антитело к IL-21R, антитело к IL-21, антиген-связывающий фрагмент антитела к IL-21R, антигенсвязывающий фрагмент антитела к IL-21 и растворимый фрагмент IL-21R, в количестве, достаточном для лечения, облегчения симптоматики или предотвращения указанного нарушения.
2. Способ лечения, облегчения симптоматики или предотвращения нарушения, выбранного из группы, включающей заболевание суставов, атопическое нарушение, дыхательное заболевание, воспалительное заболевание кожи, воспалительное заболевание кишечника, фиброзное заболевание, системную красную волчанку, отторжение трансплантата и нарушение, связанное с отторжением трансплантата, у млекопитающего, включающий введение млекопитающему антагониста IL-21/IL-21R, выбранного из группы, включающей антитело к IL-21R, антитело к IL-21, антигенсвязывающий фрагмент антитела к IL-21R, антигенсвязывающий фрагмент антитела к IL-21 и растворимый фрагмент IL-21R, в количестве, достаточном для лечения, облегчения симптоматики или предотвращения указанного нарушения.
3. Способ по п.2, отличающийся тем, что антитело к IL-21R способно связываться с IL-21R, который содержит аминокислотную последовательность, по меньшей мере на 90% идентичную последовательности SEQ ID NO: 2, причем IL-21R способен связывать IL-21.
4. Способ по п.3, отличающийся тем, что указанное заболевание суставов выбрано из группы, включающей ревматоидный артрит, ювенальный ревматоидный артрит, остеоартрит, псориатический артрит и анкилозирующий спондилит.
5. Способ по п.4, отличающийся тем, что указанное заболевание суставов представляет собой ревматоидный артрит.
6. Способ по п.3, отличающийся тем, что указанное дыхательное заболевание представляет собой астму или хроническое обструктивное заболевание легких.
7. Способ по п.3, отличающийся тем, что указанное фиброзное заболевание выбрано из группы, включающей фиброз внутренних органов, фиброз кожи, фиброзное заболевание глаз, системный склероз, полиомиозит, дерматомиозит, эозинофильный фасцит, синдром Рейно, гломерулонефрит и назальный полипоз.
8. Способ по п.3, отличающийся тем, что указанное воспалительное заболевание кишечника выбрано из группы, включающей воспалительное заболевание кишечника, язвенный колит и болезнь Крона.
9. Способ по п.3, отличающийся тем, что указанное кожное воспалительное заболевание представляет собой псориаз.
10. Способ по п.3, отличающийся тем, что атопическое заболевание выбрано из группы, включающей аллергическую астму, атопический дерматит, крапивницу, экзему, аллергический ринит и аллергический энтерогастрит.
11. Способ по п.10, отличающийся тем, что указанное атопическое заболевание представляет собой аллергическую астму.
12. Способ по п.3, отличающийся тем, что указанное заболевание, связанное с отторжением трансплантата, представляет собой заболевание трансплантат против хозяина.
13. Способ по п.3, отличающийся тем, что указанное заболевание представляет собой отторжение трансплантата.
14. Способ по п.3, отличающийся тем, что указанное заболевание представляет собой системную красную волчанку.
15. Способ по п.2, отличающийся тем, что млекопитающее представляет собой человека.
16. Способ по п.2, отличающийся тем, что растворимый фрагмент IL-21R содержит внеклеточный домен IL-21R и Fc фрагмент иммуноглобулина.
17. Способ по п.16, отличающийся тем, что внеклеточный домен IL-21R содержит аминокислоты 1-235 SEQ ID NO: 2.
18. Способ по п.2, отличающийся тем, что растворимый фрагмент IL-21R содержит аминокислотную последовательность, по меньшей мере на 90% идентичную последовательности SEQ ID NO: 29.
19. Способ по п.2, отличающийся тем, что антагонист II-21/IL-21R представляет собой антитело к IL-21R или его антигенсвязывающий фрагмент.
20. Способ по п.2, отличающийся тем, что антагонист IL-21/IL-21R представляет собой антитело к IL-21 или его антигенсвязывающий фрагмент.
21. Гибридный белок, который содержит внеклеточный домен II-21R и Fc фрагмент иммуноглобулина, причем IL-21R имеет аминокислотную последовательность, по меньшей мере на 90% идентичную последовательности SEQ ID NO: 2, при этом указанный гибридный белок способен связывать IL-21.
22. Гибридный белок по п.21, который содержит аминокислотную последовательность, по меньшей мере на 90% идентичную последовательности SEQ ID NO: 29.
23. Вектор, который содержит нуклеотидную последовательность, кодирующую гибридный белок по п.21.
24. Рекомбинантная клетка-хозяин, которая содержит вектор по п.23.
25. Способ получения гибридного белка, включающий (а) культивирование рекомбинантной клетки хозяина по п.24 в условиях, при которых происходит экспрессия указанного гибридного белка; и (б) выделение гибридного белка.
26. Фармацевтическая композиция, содержащая антагонист IL-21/IL-21R и фармацевтически приемлемый носитель.
27. Фармацевтическая композиция по п.26, отличающаяся тем, что антагонист II-21/IL-21R выбран из группы, включающей антитело к IL-21R, антитело к IL-21, антигенсвязывающий фрагмент антитела к II-21R, антигенсвязывающий фрагмент антитела к IL-21 и растворимый фрагмент II-21R.
28. Фармацевтическая композиция по п.27, отличающаяся тем, что растворимый фрагмент IL-21R содержит внеклеточный домен IL-21R и Fc фрагмент иммуноглобулина.
29. Способ трансплантации/пересадки органа, ткани, клетки или группы клеток млекопитающему, включающий стадии:
(а) введения млекопитающему антагониста IL-21/IL-21R, выбранного из группы, включающей антитело к IL-21R, антитело к IL-21, антигенсвязывающий фрагмент антитела к IL-21R, антиген - связывающий фрагмент антитела к IL-21 и растворимый фрагмент IL-21R, в количестве, достаточном для снижения риска отторжения трансплантата; и
(б) трансплантации/пересадки органа, ткани, клетки или группы клеток указанному млекопитающему, при этом стадию трансплантация/пересадки (б) осуществляют либо перед, либо совместно, либо после стадии введения (а).
30. Способ по п.29, отличающийся тем, что трансплантируемые/пересаживаемые орган, ткань, клетка или группа клеток выбраны из группы, включающей сердце, почки, печень, легкое, поджелудочную железу, костный мозг, хрящ, роговицу, нервную ткань и их клетки.
31. Способ лечения, предотвращения или облегчения симптоматики отторжения трансплантата у млекопитающего-реципиента трансплантата, включающий (а) обнаружение симптома отторжения трансплантата у реципиента трансплантата и
(б) введение реципиенту трансплантата антагониста IL-21/IL-21R, выбранного из группы, включающей антитело к IL-21R, антитело к IL-21, антигенсвязывающий фрагмент антитела к IL-21R, антигенсвязывающий фрагмента антитела к IL-21 и растворимый фрагмент IL-21R.
32. Способ по п.31, отличающийся тем, что симптом отторжения трансплантата выбран из группы, включающей воспаление, ухудшение функционирования органа, признаки отторжения в биопсии и фиброз.
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2005
- 2005-08-05 EP EP05857905A patent/EP1773394A2/en not_active Withdrawn
- 2005-08-05 US US11/197,488 patent/US20060039902A1/en not_active Abandoned
- 2005-08-05 KR KR1020077002877A patent/KR20070057789A/ko not_active Application Discontinuation
- 2005-08-05 CA CA002574848A patent/CA2574848A1/en not_active Abandoned
- 2005-08-05 BR BRPI0514138-9A patent/BRPI0514138A/pt not_active IP Right Cessation
- 2005-08-05 AR ARP050103287A patent/AR051071A1/es unknown
- 2005-08-05 AU AU2005332996A patent/AU2005332996A1/en not_active Abandoned
- 2005-08-05 JP JP2007525033A patent/JP2008508885A/ja not_active Withdrawn
- 2005-08-05 MX MX2007001509A patent/MX2007001509A/es not_active Application Discontinuation
- 2005-08-05 RU RU2007102287/13A patent/RU2007102287A/ru not_active Application Discontinuation
- 2005-08-05 WO PCT/US2005/027912 patent/WO2006135385A2/en active Application Filing
- 2005-08-08 TW TW094126735A patent/TW200608995A/zh unknown
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2007
- 2007-01-29 IL IL181044A patent/IL181044A0/en unknown
- 2007-02-01 CR CR8891A patent/CR8891A/es not_active Application Discontinuation
- 2007-02-05 EC EC2007007226A patent/ECSP077226A/es unknown
- 2007-02-21 NO NO20070973A patent/NO20070973L/no not_active Application Discontinuation
- 2007-11-29 US US11/947,425 patent/US20080241098A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2599728C2 (ru) * | 2011-08-30 | 2016-10-10 | Абб Текнолоджи Аг | Сухой трансформатор |
Also Published As
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BRPI0514138A (pt) | 2008-05-27 |
EP1773394A2 (en) | 2007-04-18 |
WO2006135385A2 (en) | 2006-12-21 |
AU2005332996A1 (en) | 2006-12-21 |
CA2574848A1 (en) | 2006-12-21 |
ECSP077226A (es) | 2007-03-29 |
AR051071A1 (es) | 2006-12-20 |
MX2007001509A (es) | 2007-03-27 |
TW200608995A (en) | 2006-03-16 |
US20060039902A1 (en) | 2006-02-23 |
IL181044A0 (en) | 2007-07-04 |
CR8891A (es) | 2007-08-28 |
JP2008508885A (ja) | 2008-03-27 |
NO20070973L (no) | 2007-05-04 |
US20080241098A1 (en) | 2008-10-02 |
WO2006135385A3 (en) | 2007-02-22 |
KR20070057789A (ko) | 2007-06-07 |
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