JP2007501612A - Ｎｏｇｏ受容体アンタゴニスト - Google Patents
Ｎｏｇｏ受容体アンタゴニスト Download PDFInfo
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| WO2006124627A2 (en) * | 2005-05-12 | 2006-11-23 | Biogen Idec Ma Inc. | Methods of treating conditions involving neuronal degeneration |
| US7893032B2 (en) | 2005-07-07 | 2011-02-22 | Yale University | NgR variants and compositions thereof for suppressing axonal growth inhibition |
| BRPI0613387A2 (pt) | 2005-07-08 | 2011-01-11 | Biogen Idec Inc | anticorpo isolado ou fragmento de ligação de antìgeno deste e o seu uso, polinucleotìdeo isolado, composição, vetor, célula hospedeira, anticorpo anti-sp35 e método para a produção do mesmo, polipeptìdeo isolado, método in vitro para redução da inibição do crescimento axonal e método in vitro para inibição do crescimento do colapso do cone |
| WO2007039256A2 (de) | 2005-09-30 | 2007-04-12 | Abbott Gmbh & Co. Kg | Bindungsdomänen von proteinen der repulsive guidance molecule (rgm) proteinfamilie und funktionale fragmente davon sowie deren verwendung |
| JP5829373B2 (ja) | 2006-01-27 | 2015-12-09 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ｎｏｇｏレセプターアンタゴニスト |
| EP2068866A4 (en) | 2006-07-24 | 2010-04-07 | Biogen Idec Inc | METHODS FOR PROMOTING MYELINIZATION, NEURONAL SURVIVAL AND DIFFERENTIATION OF OLIGODENDROCYTES BY ADMINISTERING SP35 OR TRKA ANTAGONISTS |
| WO2008036858A2 (en) | 2006-09-20 | 2008-03-27 | The Board Of Regents Of The University Of Texas System | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
| EP2700410A1 (en) | 2006-11-21 | 2014-02-26 | Abbott Laboratories | Neutralizing monoclonal antibodies against the Nogo-66 receptor (NGR) and uses thereof |
| WO2009094459A1 (en) | 2008-01-22 | 2009-07-30 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
| US8962803B2 (en) | 2008-02-29 | 2015-02-24 | AbbVie Deutschland GmbH & Co. KG | Antibodies against the RGM A protein and uses thereof |
| US8058406B2 (en) | 2008-07-09 | 2011-11-15 | Biogen Idec Ma Inc. | Composition comprising antibodies to LINGO or fragments thereof |
| CA2780069C (en) | 2009-12-08 | 2018-07-17 | Abbott Gmbh & Co. Kg | Monoclonal antibodies against the rgm a protein for use in the treatment of retinal nerve fiber layer degeneration |
| MX391536B (es) | 2012-01-27 | 2025-03-21 | Abbvie Deutschland | Composicion y metodo para el diagnostico y tratamiento de enfermedades asociadas con la degeneracion de neuritas. |
| JP2015518829A (ja) | 2012-05-14 | 2015-07-06 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | 運動ニューロンに関する状態の処置のためのｌｉｎｇｏ−２アンタゴニスト |
| HK1246810A1 (zh) | 2015-01-08 | 2018-09-14 | Biogen Ma Inc. | Lingo-1对抗药及用於治疗脱髓鞘疾病的用途 |
| CN110488007A (zh) * | 2019-09-26 | 2019-11-22 | 天津华科泰生物技术有限公司 | 一种快速检测神经胶质纤维酸性蛋白的免疫层析检测卡及其制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6475753B1 (en) * | 1998-06-16 | 2002-11-05 | Human Genome Sciences, Inc. | 94 Human Secreted Proteins |
| WO2003035687A1 (en) * | 2001-10-22 | 2003-05-01 | Novartis Ag | Nogo receptor homologues and their use |
-
2004
- 2004-01-30 BR BRPI0413426-5A patent/BRPI0413426A/pt not_active IP Right Cessation
- 2004-01-30 WO PCT/US2004/002702 patent/WO2005016955A2/en not_active Ceased
- 2004-01-30 CN CNA2004800294122A patent/CN1926147A/zh active Pending
- 2004-01-30 CA CA002535007A patent/CA2535007A1/en not_active Abandoned
- 2004-01-30 PL PL380274A patent/PL380274A1/pl not_active Application Discontinuation
- 2004-01-30 JP JP2006522535A patent/JP2007501612A/ja active Pending
- 2004-01-30 EP EP04707073A patent/EP1660517A4/en not_active Withdrawn
- 2004-01-30 MX MXPA06001444A patent/MXPA06001444A/es unknown
- 2004-01-30 AU AU2004264405A patent/AU2004264405A1/en not_active Abandoned
-
2006
- 2006-03-06 NO NO20061081A patent/NO20061081L/no not_active Application Discontinuation
- 2006-03-07 IS IS8339A patent/IS8339A/is unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6475753B1 (en) * | 1998-06-16 | 2002-11-05 | Human Genome Sciences, Inc. | 94 Human Secreted Proteins |
| WO2003035687A1 (en) * | 2001-10-22 | 2003-05-01 | Novartis Ag | Nogo receptor homologues and their use |
Also Published As
| Publication number | Publication date |
|---|---|
| PL380274A1 (pl) | 2007-01-22 |
| CN1926147A (zh) | 2007-03-07 |
| WO2005016955A3 (en) | 2006-07-20 |
| EP1660517A4 (en) | 2006-10-04 |
| WO2005016955A2 (en) | 2005-02-24 |
| AU2004264405A1 (en) | 2005-02-24 |
| CA2535007A1 (en) | 2005-02-24 |
| MXPA06001444A (es) | 2006-05-15 |
| EP1660517A2 (en) | 2006-05-31 |
| NO20061081L (no) | 2006-04-18 |
| IS8339A (is) | 2006-03-07 |
| BRPI0413426A (pt) | 2006-10-17 |
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