RU2362780C2 - Nogo-a-нейтрализующие иммуноглобулины для лечения неврологических заболеваний - Google Patents
Nogo-a-нейтрализующие иммуноглобулины для лечения неврологических заболеваний Download PDFInfo
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- 208000012902 Nervous system disease Diseases 0.000 title claims abstract 9
- 208000025966 Neurological disease Diseases 0.000 title claims abstract 7
- 108060003951 Immunoglobulin Proteins 0.000 title 1
- 102000018358 immunoglobulin Human genes 0.000 title 1
- 229940072221 immunoglobulins Drugs 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims abstract 4
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 230000003472 neutralizing effect Effects 0.000 claims abstract 3
- 230000028600 axonogenesis Effects 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 239000012634 fragment Substances 0.000 claims 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 208000006011 Stroke Diseases 0.000 claims 2
- 230000004936 stimulating effect Effects 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
- 210000003050 axon Anatomy 0.000 claims 1
- 230000018109 developmental process Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 208000020431 spinal cord injury Diseases 0.000 claims 1
- 230000009529 traumatic brain injury Effects 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000014511 neuron projection development Effects 0.000 abstract 1
- 238000006386 neutralization reaction Methods 0.000 abstract 1
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- 230000000638 stimulation Effects 0.000 abstract 1
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Abstract
Настоящее изобретение относится к иммунологии и биотехнологии. Предложены варианты нейтрализующих антител или их функциональных аналогов против NOGO-A человека, каждый из которых характеризуется набором специфических CDR. Описана фармацевтическая композиция для нейтрализации NOGO-A человека. Раскрыты варианты использования антител или их функциональных аналогов в изготовлении лекарственного средства для лечения и/или профилактики неврологических заболеваний/расстройств. Описан способ стимуляции роста аксонов с использованием антител по изобретению. Использование изобретения обеспечивает нейтрализующие антитела с высокой аффинностью к NOGO-A человека, с KD порядка 10-9 М, что может найти дальнейшее применение в медицине для активирования роста нейритов. 7 н. и 10 з.п. ф-лы, 45 ил., 14 табл.
Description
Claims (17)
1. Антитело или его функциональный фрагмент, содержащие каждый из следующих CDR:
CDR легкой цепи: SEQ ID NO: 1, 2 и 3;
CDR тяжелой цепи: SEQ ID NO: 4, 5 и 6,
или аналог такого антитела, которые связываются с NOGO-A человека и нейтрализуют его.
CDR легкой цепи: SEQ ID NO: 1, 2 и 3;
CDR тяжелой цепи: SEQ ID NO: 4, 5 и 6,
или аналог такого антитела, которые связываются с NOGO-A человека и нейтрализуют его.
2. Антитело или его функциональный фрагмент, содержащие каждый из следующих CDR:
CDR легкой цепи: SEQ ID NO: 7, 8 и 9;
CDR тяжелой цепи: SEQ ID NO: 10, 11 и 12,
или аналог такого антитела, которые связываются с NOGO-A человека и нейтрализуют его.
CDR легкой цепи: SEQ ID NO: 7, 8 и 9;
CDR тяжелой цепи: SEQ ID NO: 10, 11 и 12,
или аналог такого антитела, которые связываются с NOGO-A человека и нейтрализуют его.
3. Антитело или его функциональный фрагмент, содержащие каждый из следующих CDR:
CDR легкой цепи: SEQ ID NO: 13, 14 и 15;
CDR тяжелой цепи: SEQ ID NO: 16, 17 и 18,
или аналог такого антитела, которые связываются с NOGO-A человека и нейтрализуют его.
CDR легкой цепи: SEQ ID NO: 13, 14 и 15;
CDR тяжелой цепи: SEQ ID NO: 16, 17 и 18,
или аналог такого антитела, которые связываются с NOGO-A человека и нейтрализуют его.
4. Антитело по пп.1, 2 или 3, которое представляет собой моноклональное антитело.
5. Антитело по п.4, которое представляет собой гуманизированное или химерное антитело.
6. Антитело по п.1, где вариабельная область тяжелой цепи содержит последовательность аминокислот, определенную в SEQ ID NO: 37.
7. Антитело по п.2, где вариабельная область тяжелой цепи содержит последовательность аминокислот, определенную в SEQ ID NO: 38.
8. Антитело по п.3, где вариабельная область тяжелой цепи содержит последовательность аминокислот, определенную в SEQ ID NO: 39.
9. Антитело по п.1 или 6, где вариабельная область легкой цепи содержит последовательность аминокислот, определенную в SEQ ID NO: 40.
10. Антитело по п.2 или 7, где вариабельная область легкой цепи содержит последовательность аминокислот, определенную в SEQ ID NO: 41.
11. Антитело по п.3 или 8, где вариабельная область легкой цепи содержит последовательность аминокислот, определенную в SEQ ID NO: 42.
12. Фармацевтическая композиция для нейтрализации NOGO-A человека, содержащая эффективное количество антитела против NOGO-A или его функционального фрагмента или аналога по любому из пп.1-11 вместе с фармацевтически приемлемым растворителем или носителем.
13. Применение антитела против NOGO-A или его функционального фрагмента или аналога по любому из пп.1-11 в изготовлении лекарства для лечения инсульта и других неврологических заболеваний/расстройств.
14. Применение антитела против NOGO-A или его функционального фрагмента или аналога по любому из пп.1-11 в изготовлении лекарства для ингибирования нейродегенерации и/или стимуляции функционального восстановления у пациента-человека, страдающего от инсульта или другого неврологического заболевания/расстройства или подверженного риску их развития.
15. Применение по любому из п.13 или 14, где другое неврологическое заболевание/расстройство выбрано из группы, состоящей из травматического повреждения головного мозга, повреждения спинного мозга, болезни Альцгеймера, лобно-височных деменций (таупатий), периферической невропатии, болезни Паркинсона, болезни Гентингтона и рассеянного склероза.
16. Способ стимуляции роста аксонов, включающий стадию приведения человеческого аксона в контакт с антителом против NOGO-A или его функциональным фрагментом или аналогом по любому из пп.1-11.
17. Способ по п.16, который является способом in vitro.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0329684.5 | 2003-12-22 | ||
| GB0329711.6 | 2003-12-22 | ||
| GB0329711A GB0329711D0 (en) | 2003-12-22 | 2003-12-22 | Antibodies |
| GB0329684A GB0329684D0 (en) | 2003-12-22 | 2003-12-22 | Method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2006123481A RU2006123481A (ru) | 2008-01-27 |
| RU2362780C2 true RU2362780C2 (ru) | 2009-07-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2006123481/13A RU2362780C2 (ru) | 2003-12-22 | 2004-12-20 | Nogo-a-нейтрализующие иммуноглобулины для лечения неврологических заболеваний |
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| Country | Link |
|---|---|
| US (4) | US7988964B2 (ru) |
| EP (3) | EP1706426A2 (ru) |
| JP (2) | JP2007537145A (ru) |
| KR (1) | KR101150548B1 (ru) |
| AR (1) | AR048912A1 (ru) |
| AT (1) | ATE440866T1 (ru) |
| AU (1) | AU2004303585B2 (ru) |
| BR (1) | BRPI0417959A (ru) |
| CA (1) | CA2549956C (ru) |
| CY (1) | CY1110530T1 (ru) |
| DE (1) | DE602004022871D1 (ru) |
| DK (1) | DK1711530T3 (ru) |
| ES (1) | ES2330444T3 (ru) |
| HR (1) | HRP20090527T1 (ru) |
| IL (1) | IL176206A (ru) |
| IS (1) | IS2739B (ru) |
| MA (1) | MA28289A1 (ru) |
| MX (1) | MXPA06007190A (ru) |
| MY (1) | MY144612A (ru) |
| NO (1) | NO20062767L (ru) |
| NZ (1) | NZ548013A (ru) |
| PL (1) | PL1711530T3 (ru) |
| PT (1) | PT1711530E (ru) |
| RU (1) | RU2362780C2 (ru) |
| SI (1) | SI1711530T1 (ru) |
| TW (1) | TWI329649B (ru) |
| WO (2) | WO2005061544A2 (ru) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8680239B2 (en) | 2000-12-22 | 2014-03-25 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. | Use of RGM and its modulators |
| US8906864B2 (en) | 2005-09-30 | 2014-12-09 | AbbVie Deutschland GmbH & Co. KG | Binding domains of proteins of the repulsive guidance molecule (RGM) protein family and functional fragments thereof, and their use |
| US9102722B2 (en) | 2012-01-27 | 2015-08-11 | AbbVie Deutschland GmbH & Co. KG | Composition and method for the diagnosis and treatment of diseases associated with neurite degeneration |
| US9175075B2 (en) | 2009-12-08 | 2015-11-03 | AbbVie Deutschland GmbH & Co. KG | Methods of treating retinal nerve fiber layer degeneration with monoclonal antibodies against a retinal guidance molecule (RGM) protein |
| US9605069B2 (en) | 2008-02-29 | 2017-03-28 | AbbVie Deutschland GmbH & Co. KG | Antibodies against the RGM a protein and uses thereof |
| RU2774446C2 (ru) * | 2016-06-08 | 2022-06-21 | Сучжоу Коннект Биофармасьютикалс, Лтд | Антитело для специфического связывания с рецептором интерлейкина 4 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0228832D0 (en) * | 2002-12-10 | 2003-01-15 | Novartis Ag | Organic compound |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| GB0321997D0 (en) * | 2003-09-19 | 2003-10-22 | Novartis Ag | Organic compound |
| CA2549956C (en) * | 2003-12-22 | 2016-04-12 | Glaxo Group Limited | Immunoglobulins |
| WO2007003421A2 (en) * | 2005-07-05 | 2007-01-11 | Glaxo Group Limited | Humanised antibodies specific for nogo-a and pharmaceutical uses thereof |
| PL1976877T5 (pl) * | 2005-11-30 | 2017-09-29 | Abbvie Inc | Przeciwciała monoklonalne przeciwko białku amyloidu beta oraz ich zastosowania |
| CN117903302A (zh) | 2005-11-30 | 2024-04-19 | Abbvie 公司 | 抗-Aβ球聚体抗体,其相关产品,生产所述抗体的方法,所述抗体的应用以及使用方法 |
| GB0525662D0 (en) | 2005-12-16 | 2006-01-25 | Glaxo Group Ltd | Immunoglobulins |
| US8663635B2 (en) | 2006-03-21 | 2014-03-04 | The Regents Of The University Of California | N-cadherin: target for cancer diagnosis and therapy |
| WO2008002594A2 (en) * | 2006-06-27 | 2008-01-03 | Neuroprotection For Life Corp. | Neuronal circuit-dependent neuroprotection by interaction between nicotinic receptors |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| WO2008070780A1 (en) * | 2006-12-07 | 2008-06-12 | Novartis Ag | Antagonist antibodies against ephb3 |
| EP2486928A1 (en) * | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
| WO2009026117A2 (en) * | 2007-08-16 | 2009-02-26 | Glaxo Group Limited | Novel compounds |
| ES2425768T3 (es) | 2007-11-02 | 2013-10-17 | Novartis Ag | Moléculas de unión a nogo-a mejoradas y uso farmacéutico de las mismas |
| AU2009231570A1 (en) * | 2008-04-04 | 2009-10-08 | The Regents Of The University Of California | Novel antibodies against cancer target block tumor growth, angiogenesis and metastasis |
| JP2011527317A (ja) * | 2008-07-11 | 2011-10-27 | グラクソ グループ リミテッド | Nogo−aアンタゴニストによる筋萎縮性側索硬化症の治療 |
| US10266585B2 (en) | 2009-08-28 | 2019-04-23 | The Board Of Regents Of The Univerity Of Texas System | Methods of treating brain injury |
| US9125846B2 (en) | 2010-10-15 | 2015-09-08 | The Board Of Regents Of The University Of Texas System | Antibodies that bind amyloid oligomers |
| MX360403B (es) | 2010-04-15 | 2018-10-31 | Abbvie Inc | Proteinas de union a amiloide beta. |
| US8828390B2 (en) | 2010-07-09 | 2014-09-09 | Universitat Zurich | Uses of NOGO-A inhibitors and related methods |
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| US8680239B2 (en) | 2000-12-22 | 2014-03-25 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. | Use of RGM and its modulators |
| US8906864B2 (en) | 2005-09-30 | 2014-12-09 | AbbVie Deutschland GmbH & Co. KG | Binding domains of proteins of the repulsive guidance molecule (RGM) protein family and functional fragments thereof, and their use |
| US9605069B2 (en) | 2008-02-29 | 2017-03-28 | AbbVie Deutschland GmbH & Co. KG | Antibodies against the RGM a protein and uses thereof |
| US9175075B2 (en) | 2009-12-08 | 2015-11-03 | AbbVie Deutschland GmbH & Co. KG | Methods of treating retinal nerve fiber layer degeneration with monoclonal antibodies against a retinal guidance molecule (RGM) protein |
| US9102722B2 (en) | 2012-01-27 | 2015-08-11 | AbbVie Deutschland GmbH & Co. KG | Composition and method for the diagnosis and treatment of diseases associated with neurite degeneration |
| US9365643B2 (en) | 2012-01-27 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Antibodies that bind to repulsive guidance molecule A (RGMA) |
| US10106602B2 (en) | 2012-01-27 | 2018-10-23 | AbbVie Deutschland GmbH & Co. KG | Isolated monoclonal anti-repulsive guidance molecule A antibodies and uses thereof |
| RU2774446C2 (ru) * | 2016-06-08 | 2022-06-21 | Сучжоу Коннект Биофармасьютикалс, Лтд | Антитело для специфического связывания с рецептором интерлейкина 4 |
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