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2. 发明申请

WO2008006103A2 NOGO RECEPTOR FUNCTIONAL MOTIFS, PEPTIDE MIMETICS, AND MUTATED FUNCTIONAL MOTIFS RELATED THERETO, AND METHODS OF USING THE SAME 审中-公开
标题翻译： NOGO受体功能运动，肽类物质和与之相关的突变功能运动物质及其使用方法
公开(公告)号：WO2008006103A2
公开(公告)日：2008-01-10
申请号：PCT/US2007073063
申请日：2007-07-09
申请人： WYETH CORP , KING S COLLEGE LONDON , WOOD ANDREW , KATZ ALAN , GAO YING , BATES BRIAN G , DOHERTY PATRICK , WILLIAMS GARETH
发明人： WOOD ANDREW , KATZ ALAN , GAO YING , BATES BRIAN G , DOHERTY PATRICK , WILLIAMS GARETH
IPC分类号： C07K14/705 , A61K38/17 , G01N33/68
CPC分类号： C07K14/705 , A61K38/00 , G01N33/6872 , G01N2500/04
摘要： The present invention provides novel isolated and purified polynucleotides and polypeptides related to functional motifs of the Nogo receptor 1 (NgR1) (e.g., the binding pocket on the side surface of NgR1, functional motifs comprising the amino acid sequence of FRG, etc.) and use of peptides mimicking these functional motifs as antagonists to NgR1 ligands, e.g., myelin-associated glycoprotein, oligodendrocyte myelin glycoprotein, Nogo- A, Nogo-66, GTIb, an antibody to Nogo receptor, an antibody to GTIb, an antibody to p75 neurotrophin receptor, and an antibody to Lingo- 1, etc. The invention also provides antibodies to the mimetic peptide antagonists. The present invention is further directed to novel therapeutics and therapeutic targets and to methods of screening and assessing test compounds for treatments requiring axonal regeneration, i.e., reversal of the effects of NgR1 ligand binding to the NgR1 (i.e., producing inhibition of axonal growth). The present invention also is directed to novel methods for treating disorders arising from inhibition of axonal growth mediated by the binding of NgRl ligands to the NgRl. Further, the invention is directed to methods of treating a subject with a neurodegenerative disorder, including, but not limited to, Parkinson's disease, Alzheimer's disease, progressive supranuclear palsy, multiple sclerosis, multiple system atrophy, corticobasal degeneration, Huntington's disease, dementia with Lewy bodies, spinocerebellar ataxia, stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, epilepsy, and senile dementia, comprising, e.g., antagonizing NgR1.
摘要翻译：本发明提供与Nogo受体1（NgR1）的功能基序相关的新型分离和纯化的多核苷酸和多肽（例如，NgR1侧表面的结合口袋，包含FRG的氨基酸序列的功能基序等）和使用模仿这些功能基序的肽作为NgR1配体的拮抗剂，例如髓磷脂相关糖蛋白，少突胶质细胞髓鞘糖蛋白，Nogo- A，Nogo-66，GTIb，Nogo受体的抗体，GTIb的抗体，p75神经营养蛋白的抗体受体和针对Ling-1的抗体等。本发明还提供了针对模拟肽拮抗剂的抗体。本发明进一步涉及新的治疗和治疗靶标，以及筛选和评估需要轴突再生的治疗的试验化合物的方法，即逆转NgR1配体结合NgR1的作用（即产生轴突生长的抑制）。本发明还涉及用于治疗由NgR1配体与NgR1结合介导的轴突生长抑制引起的疾病的新方法。此外，本发明涉及用神经退行性疾病治疗受试者的方法，包括但不限于帕金森氏病，阿尔茨海默氏病，进行性核上性麻痹，多发性硬化，多系统萎缩，皮质基底膜变性，亨廷顿病，路易氏痴呆身体，脊髓小脑性共济失调，中风，脊髓创伤，创伤性脑损伤，多发性痴呆，癫痫和老年性痴呆，包括例如拮抗NgR1。

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