公开(公告)号：US08163700B2

公开(公告)日：2012-04-24

申请号：US12945683

申请日：2010-11-12

申请人： Marie T. Filbin ,  Marco Domeniconi ,  Zixuan Cao

发明人： Marie T. Filbin ,  Marco Domeniconi ,  Zixuan Cao

IPC分类号： A61K38/04 ,  A61K38/08 ,  A61K38/16

CPC分类号： C07K14/70503

摘要： The present invention relates generally to products, compositions and methods useful for promoting neural repair and regeneration. The products and compositions of this invention include myelin-associated glycoprotein (MAG) derivatives that are inhibitors of endogenous MAG (e.g., mutant MAG proteins) and Nogo Receptor (NgR) binding inhibitors that are peptides derived from MAG, Nogo and OMgp that can bind to NgR and block NgR signaling. Peptides that can bind and activate NgR signaling are also provided. Inhibitory MAG derivatives and NgR binding inhibitors are useful for blocking the inhibition of neural regeneration mediated by proteins such as MAG, Nogo and/or OMgp in the nervous system. These inhibitors are also useful for treating neural degeneration associated with injuries, disorders or diseases.

摘要翻译： 本发明一般涉及可用于促进神经修复和再生的产品，组合物和方法。 本发明的产品和组合物包括作为内源性MAG抑制剂（例如，突变MAG蛋白）和Nogo受体（NgR）结合抑制剂的髓鞘相关糖蛋白（MAG）衍生物，其是衍生自MAG，Nogo和OMgp的肽，其可以结合 到NgR并阻断NgR信号。 还提供了可以结合和激活NgR信号传导的肽。 抑制性MAG衍生物和NgR结合抑制剂可用于阻断由神经系统中的蛋白质如MAG，Nogo和/或OMgp介导的神经再生的抑制。 这些抑制剂也可用于治疗与损伤，疾病或疾病相关的神经变性。

公开(公告)号：US20100056604A1

公开(公告)日：2010-03-04

申请号：US12604743

申请日：2009-10-23

申请人： Marie T. Filbin ,  Elena Nikulina

发明人： Marie T. Filbin ,  Elena Nikulina

IPC分类号： A61K31/40

CPC分类号： A61K31/4015 ,  A61K31/00

摘要： The invention relates to the novel identification of inhibitors of phosphodiesterase type 4 (“PDE4”) as agents which can reverse inhibition of neural regeneration in the mammalian central and peripheral nervous system. The invention provides compositions and methods using agents that can reverse the inhibitory effects on neural regeneration by regulating PDE4 expression. A composition comprising at least one PDE4 inhibitor in an amount effective to inhibit PDE4 activity in a neuron when administered to an animal is provided. Methods for regulating (e.g., promoting) neural growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with disorders or diseases, comprising the step of administering to an animal a composition comprising a therapeutically effective amount of an agent which inhibits phosphodiesterase IV activity in a neuron are provided.

摘要翻译： 本发明涉及磷酸二酯酶4型（“PDE4”）抑制剂的新鉴定，其可以逆转哺乳动物中枢和周围神经系统神经再生的抑制作用。 本发明提供使用可通过调节PDE4表达来逆转对神经再生的抑制作用的试剂的组合物和方法。 提供了包含至少一种PDE4抑制剂的组合物，其以有效抑制对动物施用的神经元中的PDE4活性的量。 用于调节（例如，促进）神经系统中的神经生长或再生的方法，治疗神经组织或神经元的损伤或损伤的方法，以及用于治疗与疾病或疾病相关的神经变性的方法，包括向动物施用 提供了包含治疗有效量的抑制神经元中磷酸二酯酶IV活性的试剂的组合物。

公开(公告)号：US08673594B2

公开(公告)日：2014-03-18

申请号：US12613310

申请日：2009-11-05

申请人： Marie T. Filbin ,  Rajiv R. Ratan

发明人： Marie T. Filbin ,  Rajiv R. Ratan

IPC分类号： C12P21/04 ,  C12N5/071

CPC分类号： A61K31/7076 ,  A61K31/00 ,  A61K31/5575 ,  A61K38/185 ,  A61K38/50 ,  A61K48/00 ,  G01N33/5008 ,  G01N33/5026 ,  G01N33/5058 ,  G01N2333/475

摘要： This invention relates to the novel identification of arginase as an enzymatic activity which can reverse inhibition of neuronal regeneration in the central and peripheral nervous system. Assays to monitor the effects of various agents on arginase expression and thus on neuronal regeneration and repair and to identify agents which will block or promote the inhibitory effects on neuronal outgrowth are provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of myelin on neural regeneration by affecting arginase activity or putrescine and derivative polyamine levels in a neuron. Methods for regulating and for promoting (or repressing) neuronal growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with conditions, disorders or diseases, comprising the step of administering at least one of the compositions according to this invention, are provided.

摘要翻译： 本发明涉及精氨酸酶作为酶活性的新鉴定，其可逆转中枢和周围神经系统中神经元再生的抑制。 测定各种试剂对精氨酸酶表达的影响，从而监测神经元再生和修复，并鉴定将阻断或促进对神经元生长的抑制作用的试剂。 本发明还涉及使用可以通过影响神经元中精氨酸酶活性或腐胺和衍生多胺水平来逆转髓鞘对神经再生的抑制作用的试剂的组合物和方法。 用于调节和（或抑制）神经系统中的神经元生长或再生的方法，用于治疗对神经组织或神经元的损伤或损伤的方法，以及用于治疗与病症，疾病或疾病相关的神经变性的方法，包括施用 提供至少一种根据本发明的组合物。

公开(公告)号：US08367615B2

公开(公告)日：2013-02-05

申请号：US12225639

申请日：2007-03-30

申请人： Marie T. Filbin ,  Sari S. Hannila

发明人： Marie T. Filbin ,  Sari S. Hannila

IPC分类号： A61K38/57

CPC分类号： A61K38/57

摘要： The present invention provides methods for stimulating neuronal survival, growth and regeneration by administering SLPIs to animals, such as humans. These methods can be used to treat a variety of neurological conditions such as neural injuries and degenerative diseases in subjects in need thereof.

摘要翻译： 本发明提供了通过对动物（例如人）施用SLPI来刺激神经元存活，生长和再生的方法。 这些方法可用于治疗有需要的受试者中的各种神经病症，例如神经损伤和退行性疾病。

公开(公告)号：US06399577B1

公开(公告)日：2002-06-04

申请号：US09769701

申请日：2001-01-25

申请人： Marie T. Filbin

发明人： Marie T. Filbin

IPC分类号： A61K3170

CPC分类号： A61K31/7016 ,  A61K38/1709 ,  C07K14/70503 ,  C07K2319/00

摘要： This invention relates to the novel identification of myelin-associated glycoprotein (“MAG”) as a potent inhibitor of neural regeneration. More particularly, this invention relates to compositions and methods useful for reversing inhibition of neural regeneration in the central and peripheral nervous system. Assays to monitor the effects of MAG on neural regeneration and to identify agents which will block or promote the inhibitory effects of MAG on neural outgrowth are provided. Screening methods for identifying such agents are also provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of MAG on neural regeneration. Methods for regulating and for promoting neural growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with disorders or diseases, comprising the step of administering at least one of the compositions according to this invention are provided.

摘要翻译： 本发明涉及髓鞘相关糖蛋白（“MAG”）作为神经再生的有效抑制剂的新鉴定。 更具体地，本发明涉及可用于逆转中枢和周围神经系统神经再生抑制的组合物和方法。 提供了监测MAG对神经再生的影响的测定，并且确定将阻断或促进MAG对神经生长的抑制作用的药剂。 还提供了用于鉴定这种试剂的筛选方法。 本发明还涉及使用能够逆转MAG对神经再生的抑制作用的试剂的组合物和方法。 用于调节和促进神经系统中的神经生长或再生的方法，治疗神经组织或神经元的损伤或损伤的方法，以及用于治疗与疾病或疾病相关的神经变性的方法，包括施用至少一种组合物 根据本发明。

公开(公告)号：US20110306061A1

公开(公告)日：2011-12-15

申请号：US12945683

申请日：2010-11-12

申请人： Marie T. Filbin ,  Marco Domeniconi ,  Zixuan Cao

发明人： Marie T. Filbin ,  Marco Domeniconi ,  Zixuan Cao

IPC分类号： G01N33/566 ,  C12N5/0793

CPC分类号： C07K14/70503

摘要： The present invention relates generally to products, compositions and methods useful for promoting neural repair and regeneration. The products and compositions of this invention include myelin-associated glycoprotein (MAG) derivatives that are inhibitors of endogenous MAG (e.g., mutant MAG proteins) and Nogo Receptor (NgR) binding inhibitors that are peptides derived from MAG, Nogo and OMgp that can bind to NgR and block NgR signaling. Peptides that can bind and activate NgR signaling are also provided. Inhibitory MAG derivatives and NgR binding inhibitors are useful for blocking the inhibition of neural regeneration mediated by proteins such as MAG, Nogo and/or OMgp in the nervous system. These inhibitors are also useful for treating neural degeneration associated with injuries, disorders or diseases.

摘要翻译： 本发明一般涉及可用于促进神经修复和再生的产品，组合物和方法。 本发明的产品和组合物包括作为内源性MAG抑制剂（例如，突变MAG蛋白）和Nogo受体（NgR）结合抑制剂的髓鞘相关糖蛋白（MAG）衍生物，其是衍生自MAG，Nogo和OMgp的肽，其可以结合 到NgR并阻断NgR信号。 还提供了可以结合和激活NgR信号传导的肽。 抑制性MAG衍生物和NgR结合抑制剂可用于阻断由神经系统中的蛋白质如MAG，Nogo和/或OMgp介导的神经再生的抑制。 这些抑制剂也可用于治疗与损伤，疾病或疾病相关的神经变性。

公开(公告)号：US07842666B2

公开(公告)日：2010-11-30

申请号：US10327213

申请日：2002-12-20

申请人： Marie T. Filbin ,  Marco Domeniconi ,  Zixuan Cao

发明人： Marie T. Filbin ,  Marco Domeniconi ,  Zixuan Cao

IPC分类号： A61K38/17 ,  A61K38/08 ,  A61K38/04 ,  C07K7/06 ,  C07K14/47

CPC分类号： C07K14/70503

摘要： The present invention relates generally to products, compositions and methods useful for promoting neural repair and regeneration. The products and compositions of this invention include myelin-associated glycoprotein (MAG) derivatives that are inhibitors of endogenous MAG (e.g., mutant MAG proteins) and Nogo Receptor (NgR) binding inhibitors that are peptides derived from MAG, Nogo and OMgp that can bind to NgR and block NgR signaling. Peptides that can bind and activate NgR signaling are also provided. Inhibitory MAG derivatives and NgR binding inhibitors are useful for blocking the inhibition of neural regeneration mediated by proteins such as MAG, Nogo and/or OMgp in the nervous system. These inhibitors are also useful for treating neural degeneration associated with injuries, disorders or diseases.

摘要翻译： 本发明一般涉及可用于促进神经修复和再生的产品，组合物和方法。 本发明的产品和组合物包括作为内源性MAG抑制剂（例如，突变MAG蛋白）和Nogo受体（NgR）结合抑制剂的髓鞘相关糖蛋白（MAG）衍生物，其是衍生自MAG，Nogo和OMgp的肽，其可以结合 到NgR并阻断NgR信号。 还提供了可以结合和激活NgR信号传导的肽。 抑制性MAG衍生物和NgR结合抑制剂可用于阻断由神经系统中的蛋白质如MAG，Nogo和/或OMgp介导的神经再生的抑制。 这些抑制剂也可用于治疗与损伤，疾病或疾病相关的神经变性。

公开(公告)号：US06203792B1

公开(公告)日：2001-03-20

申请号：US09305721

申请日：1999-05-05

申请人： Marie T. Filbin

发明人： Marie T. Filbin

IPC分类号： A61K39395

CPC分类号： A61K31/7016 ,  A61K38/1709 ,  C07K14/70503 ,  C07K2319/00

摘要： This invention relates to the novel identification of myelin-associated glycoprotein (“MAG”) as a potent inhibitor of neural regeneration. More particularly, this invention relates to compositions and methods useful for reversing inhibition of neural regeneration in the central and peripheral nervous system. Assays to monitor the effects of MAG on neural regeneration and to identify agents which will block or promote the inhibitory effects of MAG on neural outgrowth are provided. Screening methods for identifying such agents are also provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of MAG on neural regeneration. Methods for regulating and for promoting neural growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with disorders or diseases, comprising the step of administering at least one of the compositions according to this invention are provided.

摘要翻译： 本发明涉及髓鞘相关糖蛋白（“MAG”）作为神经再生的有效抑制剂的新鉴定。 更具体地，本发明涉及可用于逆转中枢和周围神经系统神经再生抑制的组合物和方法。 提供了监测MAG对神经再生的影响的测定，并且确定将阻断或促进MAG对神经生长的抑制作用的药剂。 还提供了用于鉴定这种试剂的筛选方法。 本发明还涉及使用能够逆转MAG对神经再生的抑制作用的试剂的组合物和方法。 用于调节和促进神经系统中的神经生长或再生的方法，治疗神经组织或神经元的损伤或损伤的方法，以及用于治疗与疾病或疾病相关的神经变性的方法，包括施用至少一种组合物 根据本发明。

公开(公告)号：US08598315B2

公开(公告)日：2013-12-03

申请号：US12681243

申请日：2008-10-02

申请人： Marie T. Filbin ,  Sari S. Hannila

发明人： Marie T. Filbin ,  Sari S. Hannila

IPC分类号： A61K38/04 ,  A61K38/10 ,  C07K7/08

CPC分类号： A61K47/64 ,  A61K38/00 ,  Y02A50/411

摘要： This invention relates to novel protein transduction domains (PTDs) derived from secretory leukocyte protease inhibitor (SLPI). SLPI-derived PTDs are able to deliver cargo moieties in vivo and in vitro into the cytoplasm and nucleus of a host cell. The invention also relates to a transduction complex comprising one or more SLPI-derived PTDs linked or fused to one or more cargo moieties, which may comprise, for example, proteins, nucleic acids, lipids, carbohydrates, small molecules and other chemical compounds. The invention also relates to the manufacture of SLPI-derived PTDs, complexes comprising them; compositions comprising SLPI-derived PTDs or complexes; and utilization of SLPI-derived PTDs or complexes comprising them for therapeutic, diagnostic and research methods involving delivery of heterologous molecules across cellular membranes, and especially, across nuclear membranes.

摘要翻译： 本发明涉及从分泌白细胞蛋白酶抑制剂（SLPI）衍生的新型蛋白转导结构域（PTD）。 SLPI衍生的PTD能够将体内和体外的货物部分递送到宿主细胞的细胞质和细胞核中。 本发明还涉及包含与一个或多个货物部分连接或融合的一种或多种SLPI衍生的PTD的转导复合物，其可以包含例如蛋白质，核酸，脂质，碳水化合物，小分子和其它化合物。 本发明还涉及SLPI衍生的PTDs的制造，包含它们的复合物; 包含SLPI衍生的PTD或复合物的组合物; 以及利用包含它们的SLPI衍生的PTD或复合物用于治疗，诊断和研究方法，其涉及通过细胞膜，特别是穿过核膜递送异源分子。

公开(公告)号：US20130245070A1

公开(公告)日：2013-09-19

申请号：US13416885

申请日：2012-03-09

申请人： Rajiv R. Ratan ,  Marie T. Filbin

发明人： Rajiv R. Ratan ,  Marie T. Filbin

IPC分类号： A61K31/4439 ,  A61K31/085 ,  A61K31/36 ,  A61K31/352 ,  A61K31/4184 ,  A61K31/05 ,  A61K31/122

CPC分类号： A61K31/4439 ,  A61K31/05 ,  A61K31/085 ,  A61K31/122 ,  A61K31/352 ,  A61K31/36 ,  A61K31/4184 ,  A61K31/7048

摘要： The present invention relates to a method for enhancing arginase activity in a damaged or injured cell. In other aspects, the invention provides a method for treating a disorder that can be treated by enhancing arginase activity in a human in need thereof, the method comprising administering to the human an effective amount of a compound that enhances arginase activity. Such disorders include ischemia, hypoxia, neurodegenerative disease or condition, stroke or trauma of the nervous system. In yet another aspect, the invention provides methods for promoting regeneration of a neural cell in a human in need thereof.

摘要翻译： 本发明涉及一种增强损伤或损伤细胞中精氨酸酶活性的方法。 在其它方面，本发明提供了一种治疗可以通过增强有需要的人的精氨酸酶活性来治疗的病症的方法，所述方法包括给予人有效量的增强精氨酸酶活性的化合物。 这些疾病包括缺血，缺氧，神经变性疾病或病症，中风或神经系统的创伤。 另一方面，本发明提供了促进有需要的人中神经细胞再生的方法。