Patents by Inventor Michael Tymianski
Michael Tymianski has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11878044Abstract: 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.Type: GrantFiled: February 17, 2021Date of Patent: January 23, 2024Assignee: NoNO Inc.Inventor: Michael Tymianski
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Publication number: 20230285504Abstract: 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.Type: ApplicationFiled: February 19, 2021Publication date: September 14, 2023Inventor: Michael TYMIANSKI
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Publication number: 20230139826Abstract: The peptide inhibitor of PSD-95, Tat-NR2B9c, is cleaved by the serum protease, plasmin, inducible by thrombolytic agents. Conversely, Tat-NR2B9c has no detrimental effect on the activity of a thrombolytic agent. Inactivation of Tat-NR2B9c by thrombolytic agents can be reduced or avoided by several approaches including spacing the administration of the respective agents to avoid substantial overlap in plasma residence between Tat-NR2B9c and plasmin, using mechanical instead of thrombolytic reperfusion or using active agent that inhibits PSD-95 not subject to cleavage by plasmin, e.g., D-amino acid variants of Tat-NR2B9c.Type: ApplicationFiled: February 19, 2021Publication date: May 4, 2023Inventors: Michael TYMIANSKI, Jonathan David GARMAN
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Publication number: 20220175879Abstract: 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.Type: ApplicationFiled: November 11, 2021Publication date: June 9, 2022Applicant: NoNO Inc.Inventor: Michael Tymianski
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Patent number: 11338015Abstract: 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.Type: GrantFiled: April 11, 2019Date of Patent: May 24, 2022Assignee: NoNO Inc.Inventor: Michael Tymianski
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Publication number: 20210308209Abstract: 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.Type: ApplicationFiled: February 17, 2021Publication date: October 7, 2021Applicant: NoNO Inc.Inventor: Michael Tymianski
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Patent number: 10967041Abstract: 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.Type: GrantFiled: August 1, 2018Date of Patent: April 6, 2021Assignee: NoNO Inc.Inventor: Michael Tymianski
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Publication number: 20200222492Abstract: 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.Type: ApplicationFiled: September 21, 2019Publication date: July 16, 2020Applicant: NoNO Inc.Inventor: Michael Tymianski
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Publication number: 20200121755Abstract: 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.Type: ApplicationFiled: April 11, 2019Publication date: April 23, 2020Applicant: NoNO, Inc.Inventors: Michael Tymianski, Jonathan David Garman
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Patent number: 10300110Abstract: 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.Type: GrantFiled: December 10, 2015Date of Patent: May 28, 2019Assignee: NoNO, Inc.Inventors: Michael Tymianski, Jonathan David Garman
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Publication number: 20190091283Abstract: 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.Type: ApplicationFiled: August 1, 2018Publication date: March 28, 2019Inventor: Michael Tymianski
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Publication number: 20190038760Abstract: 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.Type: ApplicationFiled: July 12, 2018Publication date: February 7, 2019Inventors: Michael Tymianski, Jonathan David Garman, Hong Cui
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Publication number: 20180369319Abstract: 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.Type: ApplicationFiled: April 18, 2018Publication date: December 27, 2018Inventor: Michael Tymianski
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Patent number: 10064910Abstract: The invention provides a combination treatment for ischemia conditions in or otherwise affecting the CNS, such as stroke. The treatment invoices administration of a PSD-95 inhibitor and performing reperfusion therapy (e.g. by administration of tPA). Administration 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.Type: GrantFiled: June 23, 2012Date of Patent: September 4, 2018Assignee: NoNO Inc.Inventor: Michael Tymianski
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Patent number: 10046060Abstract: 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.Type: GrantFiled: August 24, 2016Date of Patent: August 14, 2018Assignee: NoNO INC.Inventors: Michael Tymianski, Jonathan David Garman, Hong Cui
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Publication number: 20170239316Abstract: 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.Type: ApplicationFiled: October 12, 2016Publication date: August 24, 2017Inventor: Michael Tymianski
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Patent number: 9629892Abstract: The invention provides methods of treatment or prophylaxis of damaging effects of penetrative injury to the brain or other part of the central nervous system. The methods are based in part on results in a rodent model of penetrative ballistic injury showing that an inhibitor of PDF-95 NMDAR interaction is effective in inhibiting neurological deficits resulting from such injury. The methods are useful for treating subjects having or at risk of penetrative brain injury, including subjects who have been shot in the head or at risk of such injury (e.g., military or law enforcement personnel).Type: GrantFiled: August 12, 2011Date of Patent: April 25, 2017Assignee: NoNO Inc.Inventors: Michael Tymianski, Peter S. Lu, Jonathan David Garman
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Patent number: 9610323Abstract: The invention provides animal models and clinical trials for assessing agents for potential use in treating and effecting prophylaxis stroke and other neurological diseases, particularly those mediated at least in part by excitoxitity. The invention also provides preferred dosage and infusion regimes and pharmaceutical compositions for clinical application of such agents.Type: GrantFiled: January 14, 2015Date of Patent: April 4, 2017Assignee: NoNO INC.Inventors: Michael Tymianski, Jonathan David Garman
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Publication number: 20170043030Abstract: 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.Type: ApplicationFiled: August 24, 2016Publication date: February 16, 2017Inventors: Michael Tymianski, Jonathan David Garman, Hong Cui
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Patent number: 9566284Abstract: This invention relates to methods of screening for modulators of mammalian cell injury cause by TRPM7 gene and protein activity, compounds that modulate TRPM7 gene and protein activity and methods of treatment of mammalian cell injury using modulators of TRPM7 gene and protein activity.Type: GrantFiled: November 26, 2013Date of Patent: February 14, 2017Assignee: NONO Inc.Inventors: Xiujun Sun, Michael Tymianski, Jonathan David Garman