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1. 发明授权

US11911438B2 Chloride salt of TAT-NR2B9C 有权
公开(公告)号：US11911438B2
公开(公告)日：2024-02-27
申请号：US17545995
申请日：2021-12-08
申请人： NONO INC.
发明人： Jonathan David Garman
IPC分类号： A61K38/10 , A61K47/64 , C07K7/08 , C07K19/00 , A61K38/16 , A61K9/19 , C07K14/705 , C07K7/06 , C07K14/16 , A61K9/00 , A61K47/12 , A61K47/18 , A61K47/26 , C07K14/005 , A61K38/00
CPC分类号： A61K38/162 , A61K9/0019 , A61K9/19 , A61K38/10 , A61K47/12 , A61K47/183 , A61K47/26 , A61K47/645 , C07K7/06 , C07K7/08 , C07K14/005 , C07K14/16 , C07K14/163 , C07K14/705 , C07K19/00 , A61K38/00 , C07K2319/10 , C12N2740/16322
摘要： The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c, as chloride salts. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. The chloride salt of TAT-NR2B9c shows improved stability compared with the acetate salt form of prior formulations. Formulations of the chloride salt of TAT-NR2B9c are stable at ambient temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

2. 发明公开

US20230285504A1 INHIBITION OF REPERFUSION INJURY WITH A PSD-95 INHIBITOR 审中-公开
公开(公告)号：US20230285504A1
公开(公告)日：2023-09-14
申请号：US17800883
申请日：2021-02-19
申请人： NONO INC.
发明人： Michael TYMIANSKI
IPC分类号： A61K38/10 , A61K38/48 , A61P25/28 , A61P7/02 , A61P9/10
CPC分类号： A61K38/10 , A61K38/482 , A61P25/28 , A61P7/02 , A61P9/10
摘要： The peptide inhibitor of PSD-95, Tat-NR2B9c, and related peptides can inhibit reperfusion injury when administered before blood flow is restored. This role is in addition to the role of active agent that inhibits PSD-95 inhibiting damage resulting from ischemia and resulting excitotoxicity. The relative timing of administering an active agent that inhibits PSD-95 and reperfusion by thrombolytic agents is additionally influenced by degradation of plasmin-sensitive active agent that inhibits PSD-95 by plasmin induced by thrombolytic agents if the active agent that inhibits PSD-95 and plasmin are co-resident in the plasma. Plasmin-degradation can be reduced or avoided and the benefit of inhibiting reperfusion injury obtained by administering an active agent that inhibits PSD-95 before restoration of blood flow by reperfusion, preferably at least 10, 15, 20, 22, 25, 30, 40, 50 or 60 minutes before restoration of blood flow by reperfusion.

3. 发明授权

US11338015B2 Therapy for subarachnoid hemorrhage and ischemia 有权
公开(公告)号：US11338015B2
公开(公告)日：2022-05-24
申请号：US16381757
申请日：2019-04-11
申请人： NoNO, Inc.
发明人： Michael Tymianski
IPC分类号： A61K38/16 , A61K38/10 , A61K45/06 , A61K49/00 , A61K38/08 , G01N33/68 , C07K14/705 , C07K14/47 , C12N7/00 , A61K38/00
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.

4. 发明授权

US10967041B2 Combination therapy for ischemia 有权
公开(公告)号：US10967041B2
公开(公告)日：2021-04-06
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.

5. 发明授权

US10300110B2 Therapy for subarachnoid hemorrhage and ischemia 有权
公开(公告)号：US10300110B2
公开(公告)日：2019-05-28
申请号：US14965694
申请日：2015-12-10
申请人： NoNO Inc.
发明人： Michael Tymianski , Jonathan David Garman
IPC分类号： G01N33/68 , A61K38/16 , A61K38/10 , A61K45/06 , A61K49/00 , A61K38/08 , C07K14/705 , C07K14/47 , C12N7/00 , A61K38/00
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 benefiting 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.

6. 发明授权

US10206973B2 Chloride salt of TAT-NR2B9c 有权
公开(公告)号：US10206973B2
公开(公告)日：2019-02-19
申请号：US15313940
申请日：2015-05-28
申请人： NoNO Inc.
发明人： Jonathan David Garman
IPC分类号： A61K38/10 , A61K38/16 , A61K9/19 , C07K14/705 , C07K7/06 , C07K7/08 , C07K19/00 , C07K14/16 , A61K9/00 , A61K47/12 , A61K47/18 , A61K47/26 , C07K14/005 , A61K38/00
摘要： The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c, as chloride salts. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. The chloride salt of TAT-NR2B9c shows improved stability compared with the acetate salt form of prior formulations. Formulations of the chloride salt of TAT-NR2B9c are stable at ambient temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

7. 发明申请

US20140323406A1 METHOD AND COMPOSITIONS FOR TREATING STROKE WITH FEVER 审中-公开
标题翻译：用于处理吹风的方法和组合物
公开(公告)号：US20140323406A1
公开(公告)日：2014-10-30
申请号：US14175861
申请日：2014-02-07
申请人： NONO INC.
发明人： Michael Tymianksi
IPC分类号： A61K38/08 , G01N33/50
CPC分类号： A61K38/08 , A61K38/07 , A61K38/177 , G01N33/5088 , G01N2500/02 , G01N2800/042 , G01N2800/2871
摘要： The invention provides methods of treating stroke and related conditions exacerbated by fever and/or hyperglycemi by administering peptides or peptidomimetics that inhibit binding of NMDAR 2B to PSD-95 to a patient.
摘要翻译：本发明提供了通过施用抑制NMDAR 2B与PSD-95结合的患者的肽或肽模拟物来治疗由发烧和/或高血糖加重的中风和相关病症的方法。

8. 发明授权

US11878044B2 Combination therapy for ischemia 有权
公开(公告)号：US11878044B2
公开(公告)日：2024-01-23
申请号：US17177970
申请日：2021-02-17
申请人： NoNO Inc.
发明人： Michael Tymianski
IPC分类号： A61K38/10 , A61K38/49 , A61K38/17
CPC分类号： A61K38/10 , A61K38/1787 , A61K38/49 , A61K38/1787 , A61K2300/00 , A61K38/49 , A61K2300/00
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.

9. 发明申请

US20190175689A1 CHLORIDE SALT OF TAT-NR2B9C 审中-公开
公开(公告)号：US20190175689A1
公开(公告)日：2019-06-13
申请号：US16128423
申请日：2018-09-11
申请人： NONO INC.
发明人： Jonathan David Garman
IPC分类号： A61K38/16 , C07K14/005 , A61K9/00 , A61K38/10 , C07K14/16 , C07K19/00 , C07K7/08 , C07K7/06 , C07K14/705 , A61K9/19 , A61K47/26 , A61K47/18 , A61K47/12
摘要： The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c, as chloride salts. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. The chloride salt of TAT-NR2B9c shows improved stability compared with the acetate salt form of prior formulations. Formulations of the chloride salt of TAT-NR2B9c are stable at ambient temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

10. 发明申请

US20180369319A1 Method of Reducing Injury to Mammalian Cells 审中-公开
公开(公告)号：US20180369319A1
公开(公告)日：2018-12-27
申请号：US15956563
申请日：2018-04-18
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.

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