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    Method of Reducing Injury to Mammalian Cells
    11.
    发明申请
    Method of Reducing Injury to Mammalian Cells 审中-公开

    公开(公告)号：US20200222492A1

    公开(公告)日：2020-07-16

    申请号：US16578318

    申请日：2019-09-21

    申请人： NoNO Inc.

    发明人： Michael Tymianski

    IPC分类号： A61K38/08 ,  A61K38/17

    摘要： A method of inhibiting the binding between N-methyl-D-aspartate receptors and neuronal proteins in a neuron is disclosed. The method comprises administering to the neuron an effective inhibiting amount of a peptide replacement agent for the NMDA receptor or neuronal protein interaction domain that effect said inhibition of the NMDA receptor- neuronal protein interaction. The method is of value in reducing the damaging effect of injury to mammalian cells. Postsynaptic density-95 protein (PSD-95) couples neuronal N-methyl-D-aspartate receptors (NMDARs) to pathways mediating excitotoxicity, ischemic and traumatic brain damage. This coupling was disrupted by transducing neurons with peptides that bind to modular domains on either side of the PSD-95/NMDAR interaction complex. This treatment attenuated downstream NMDAR signaling without blocking NMDAR activity, protected cultured cortical neurons from excitotoxic insults, dramatically reduced cerebral infarction volume in rats subjected to transient focal cerebral ischemia, and traumatic brain injury (TBI) in rats.

    COMBINATION THERAPY FOR ISCHEMIA
    12.
    发明申请
    COMBINATION THERAPY FOR ISCHEMIA 审中-公开

    公开(公告)号：US20190091283A1

    公开(公告)日：2019-03-28

    申请号：US16051971

    申请日：2018-08-01

    申请人： NONO INC.

    发明人： Michael Tymianski

    IPC分类号： A61K38/10 ,  A61K38/49 ,  A61K38/17

    摘要： The invention provides a combination treatment for ischemia conditions in or otherwise affecting the CNS, such as stroke. The treatment involves administration of a PSD-95 inhibitor and performing reperfusion therapy (e.g., by administration of tPA). Administering a PSD-95 inhibitor in combination with reperfusion therapy increases the efficacy of the reperfusion therapy and/or slows the decline in efficacy of reperfusion therapy with time after onset of ischemia thus extending the window in which reperfusion therapy can be administered.

    Method Of Reducing Injury To Mammalian Cells
    13.
    发明申请
    Method Of Reducing Injury To Mammalian Cells 审中-公开

    公开(公告)号：US20170239316A1

    公开(公告)日：2017-08-24

    申请号：US15292062

    申请日：2016-10-12

    申请人： NONO, INC.

    发明人： Michael Tymianski

    IPC分类号： A61K38/08

    CPC分类号： A61K38/08 ,  A61K38/1709

    摘要： A method of inhibiting the binding between N-methyl-D-aspartate receptors and neuronal proteins in a neuron is disclosed. The method comprises administering to the neuron an effective inhibiting amount of a peptide replacement agent for the NMDA receptor or neuronal protein interaction domain that effect said inhibition of the NMDA receptor-neuronal protein interaction. The method is of value in reducing the damaging effect of injury to mammalian cells. Postsynaptic density-95 protein (PSD-95) couples neuronal N-methyl-D-aspartate receptors (NMDARs) to pathways mediating excitotoxicity, ischemic and traumatic brain damage. This coupling was disrupted by transducing neurons with peptides that bind to modular domains on either side of the PSD-95NMDAR interaction complex. This treatment attenuated downstream NMDAR signaling without blocking NMDAR activity, protected cultured cortical neurons from excitotoxic insults, dramatically reduced cerebral infarction volume in rats subjected to transient focal cerebral ischemia, and traumatic brain injury (TBI) in rats.

    CO-ADMINISTRATION OF AN AGENT LINKED TO AN INTERNALIZATION PEPTIDE WITH AN ANTI-INFLAMMATORY
    14.
    发明申请
    CO-ADMINISTRATION OF AN AGENT LINKED TO AN INTERNALIZATION PEPTIDE WITH AN ANTI-INFLAMMATORY 审中-公开
    连接到具有抗炎症的内化肽的药剂的联合给药

    公开(公告)号：US20150126460A1

    公开(公告)日：2015-05-07

    申请号：US14585028

    申请日：2014-12-29

    申请人： NoNO Inc.

    发明人： Michael Tymianski ,  Jonathan David Garman ,  Hong Cui

    IPC分类号： A61K47/48 ,  A61K38/10 ,  A61K31/277 ,  A61K38/08

    CPC分类号： A61K47/64 ,  A61K31/275 ,  A61K31/277 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  A61K47/645 ,  C07K16/1072 ,  C07K2319/10 ,  A61K2300/00

    摘要： The invention provides methods of delivering pharmacologic agents linked to an internalization peptide, in which an inflammatory response inducible by the internalization peptide is inhibited by co-administration of an anti-inflammatory or by linking the internalization peptide to biotin or similar molecule. Such methods are premised in part on the results described in the examples whereby administration of a pharmacological agent linked to tat at high dosages is closely followed by an inflammatory response, which includes mast cell degranulation, histamine release and the typical sequelae of histamine release, such as redness, heat, swelling, and hypotension.

    摘要翻译： 本发明提供了递送与内化肽连接的药理学试剂的方法，其中通过共同给予抗炎剂或通过将内化肽与生物素或类似分子连接来抑制内化肽诱导的炎症反应。 这些方法部分地基于实施例中描述的结果，其中以高剂量施用与tat连接的药剂紧随其后是炎性反应，其包括肥大细胞脱粒，组胺释放和组胺释放的典型后遗症，例如 作为发红，发热，肿胀和低血压。

    THERAPY FOR SUBARACHNOID HEMORRHAGE AND ISCHEMIA
    19.
    发明申请
    THERAPY FOR SUBARACHNOID HEMORRHAGE AND ISCHEMIA 审中-公开
    治疗子宫内膜异位症和异位症

    公开(公告)号：US20160228499A1

    公开(公告)日：2016-08-11

    申请号：US14965694

    申请日：2015-12-10

    申请人： NoNO Inc.

    发明人： Michael Tymianski

    IPC分类号： A61K38/16 ,  C12N7/00 ,  A61K49/00

    CPC分类号： A61K38/162 ,  A61K38/00 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  A61K49/00 ,  C07K14/47 ,  C07K14/70571 ,  C07K2319/10 ,  C12N7/00 ,  C12N2740/16311 ,  C12N2740/16322 ,  C12N2740/16371 ,  G01N33/6893 ,  G01N2800/2871

    摘要： The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefitting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

    摘要翻译： 该应用程序提供来自在经历血管内修复动脉瘤或以其他方式影响CNS的受试者中的PSD-95抑制剂的临床试验的数据。 受试者是否在进行血管内手术之前是否将动脉瘤破裂分层。 如果受试者存活，破裂与更高的死亡率或增加的衰弱有关。 该试验提供证据显示，在进行血管内手术前有和无动脉瘤破裂的受试者。 令人惊讶的是，受病理学和神经认知结果判断的治疗受益最大的受试者是动脉瘤破裂引起蛛网膜下腔出血的受试者。 这些数据构成了PSD-95抑制剂不仅在缺血性和出血性中风中有益，而且对出血或影响CNS，特别是蛛网膜下腔出血的形式有益。

    ND2 PEPTIDES AND METHODS OF TREATING NEUROLOGICAL DISEASE
    20.
    发明申请
    ND2 PEPTIDES AND METHODS OF TREATING NEUROLOGICAL DISEASE 有权
    ND2肽和治疗神经病的方法

    公开(公告)号：US20140274906A1

    公开(公告)日：2014-09-18

    申请号：US13842848

    申请日：2013-03-15

    申请人： NONO INC.

    发明人： Michael Tymianski ,  Rongwen Li ,  Jonathan David Garman

    IPC分类号： C07K14/00 ,  C07K7/06

    CPC分类号： C07K14/00 ,  A61K38/00 ,  C07K7/06 ,  C07K2319/10 ,  C07K2319/22 ,  C07K2319/23 ,  C12N9/0036 ,  C12Y106/05003

    摘要： The invention is based in part on identifying a core region of ND2 responsible for interacting with Src to within residues 289-321 of ND2 and more particularly residues 307-321 or 310-321 of ND2. Peptides including, overlapping or from within this region can be used to inhibit ND2 interaction with Src Inhibition of this interaction is useful for treatment or prophylaxis of neurological diseases and disorders, pain and cancer.

    摘要翻译： 本发明部分地基于鉴定负责与Src相互作用的ND2的核心区域在ND2的残基289-321内，更具体地说是ND2的残基307-321或310-321。 包括，重叠或来自该区域的肽可用于抑制ND2与Src的相互作用抑制该相互作用可用于治疗或预防神经疾病和病症，疼痛和癌症。