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1. 发明授权

US11987614B2 Polymeric forms of H-NOX proteins 有权
公开(公告)号：US11987614B2
公开(公告)日：2024-05-21
申请号：US17397577
申请日：2021-08-09
申请人： Omniox, Inc.
发明人： Gregory Kapp , Laura Serwer , Natacha Le Moan , Stephen P. L. Cary
IPC分类号： C07H21/00 , A61K38/16 , A61K38/41 , A61K45/06 , A61N5/10 , C07K14/795 , G01N33/53 , G01N33/574 , A61K38/00
CPC分类号： C07K14/795 , A61K38/164 , A61K38/41 , A61K45/06 , A61N5/10 , G01N33/53 , G01N33/57407 , A61K38/00 , A61N2005/1098 , C07K2319/21 , G01N2800/52 , Y02A50/30
摘要： The invention provides polymeric H-NOX proteins for the delivery of oxygen with longer circulation half-lives compared to monomeric H-NOX proteins. Polymeric H-NOX proteins extravasate into and preferentially accumulate in tumor tissue for sustained delivery of oxygen. The invention also provides the use of H-NOX proteins as radiosensitizers for the treatment of brain cancers.

2. 发明申请

US20150306183A1 FIVE-COORDINATE NEUROGLOBIN AND USE THEREOF AS A BLOOD SUBSTITUTE 审中-公开
标题翻译：作为血液替代品使用五种协调的神经营养因子及其使用
公开(公告)号：US20150306183A1
公开(公告)日：2015-10-29
申请号：US14795115
申请日：2015-07-09
申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education , Wake Forest University
发明人： Mark T. Gladwin , Daniel B. Kim-Shapiro , Mauro Tiso
IPC分类号： A61K38/41 , A61K45/06 , A61K9/00
CPC分类号： A61K38/41 , A61K9/0019 , A61K35/14 , A61K35/16 , A61K35/18 , A61K38/42 , A61K45/06 , Y02A50/387
摘要： Described herein is the finding that a mutant form of human neuroglobin (H64L) with a stable five-coordinate geometry reduces nitrite to nitric oxide approximately 2000-times faster than the wild type neuroglobin. Five-coordinate neuroglobin is also capable of binding and releasing oxygen. Based on these findings, the use of five-coordinate neuroglobin as a blood substitute is described herein. Particularly provided is a method of replacing blood and/or increasing oxygen delivery to tissues in a subject by administering to the subject a therapeutically effective amount of neuroglobin with a stable five-coordinate geometry. In some cases, five-coordinate neuroglobin is administered in combination with another therapeutic agent or composition, such as a second blood replacement product (for example, a hemoglobin-based oxygen carrier), a blood product (such as red blood cells, serum or plasma) or whole blood.
摘要翻译：这里描述的发现是具有稳定的五坐标几何形状的人类神经球蛋白（H64L）的突变形式将亚硝酸盐比野生型神经球蛋白的亚硝酸盐还原为大约2000倍的一氧化氮。五配位神经球蛋白也能够结合和释放氧气。基于这些发现，本文描述了使用五配位神经球蛋白作为血液代用品。特别提供的是通过向受试者施用具有稳定的五坐标几何形状的治疗有效量的神经球蛋白来替代血液和/或增加对受试者组织的氧输送的方法。在一些情况下，五配位神经球蛋白与另一种治疗剂或组合物，例如第二种血液替代产品（例如，基于血红蛋白的氧载体），血液制品（例如红细胞，血清或血浆）或全血。

3. 发明授权

US09114109B2 Five-coordinate neuroglobin and use thereof as a blood substitute 有权
标题翻译：五配位神经球蛋白及其作为血液代用品
公开(公告)号：US09114109B2
公开(公告)日：2015-08-25
申请号：US12817085
申请日：2010-06-16
申请人： Mark T. Gladwin , Daniel B. Kim-Shapiro , Mauro Tiso
发明人： Mark T. Gladwin , Daniel B. Kim-Shapiro , Mauro Tiso
IPC分类号： A61K35/16 , A61K35/18 , A61K35/42 , A61K35/14 , A61K38/42
CPC分类号： A61K38/41 , A61K9/0019 , A61K35/14 , A61K35/16 , A61K35/18 , A61K38/42 , A61K45/06 , Y02A50/387
摘要： Described herein is the finding that a mutant form of human neuroglobin (H64L) with a stable five-coordinate geometry reduces nitrite to nitric oxide approximately 2000-times faster than the wild type neuroglobin. Five-coordinate neuroglobin is also capable of binding and releasing oxygen. Based on these findings, the use of five-coordinate neuroglobin as a blood substitute is described herein. Particularly provided is a method of replacing blood and/or increasing oxygen delivery to tissues in a subject by administering to the subject a therapeutically effective amount of neuroglobin with a stable five-coordinate geometry. In some cases, five-coordinate neuroglobin is administered in combination with another therapeutic agent or composition, such as a second blood replacement product (for example, a hemoglobin-based oxygen carrier), a blood product (such as red blood cells, serum or plasma) or whole blood.
摘要翻译：这里描述的发现是具有稳定的五坐标几何形状的人类神经球蛋白（H64L）的突变形式将亚硝酸盐比野生型神经球蛋白的亚硝酸盐还原为大约2000倍的一氧化氮。五配位神经球蛋白也能够结合和释放氧气。基于这些发现，本文描述了使用五配位神经球蛋白作为血液代用品。特别提供的是通过向受试者施用具有稳定的五坐标几何形状的治疗有效量的神经球蛋白来替代血液和/或增加对受试者组织的氧输送的方法。在一些情况下，五配位神经球蛋白与另一种治疗剂或组合物，例如第二种血液替代产品（例如，基于血红蛋白的氧载体），血液制品（例如红细胞，血清或血浆）或全血。

4. 发明授权

US11654161B2 Compositions and methods for neuralgenesis 有权
公开(公告)号：US11654161B2
公开(公告)日：2023-05-23
申请号：US16700750
申请日：2019-12-02
申请人： The Johns Hopkins University
发明人： Thomas Hartung , David Pamies , Helena T. Hogberg
IPC分类号： A61K35/30 , A61K38/41 , C12N5/074 , G01N33/68 , G01N33/50 , C12N5/00 , G01N33/58
CPC分类号： A61K35/30 , A61K38/41 , C12N5/0062 , C12N5/0696 , G01N33/50 , G01N33/58 , G01N33/6893 , C12N2501/11 , C12N2501/115 , C12N2501/13 , C12N2501/22
摘要： The present invention relates to novel compositions and methods to produce 3D organ equivalents of the brain (i.e. “mini-brains”). The invention also relates to methods of using human induced pluripotent stem cells, a combination of growth and other soluble factors and gyratory shaking. Cells from healthy or diseased donors or animals can be used to allow testing different genetic backgrounds. The model can be further enhanced by using genetically modified cells, adding micro-glia or their precursors or indicator cells (e.g. with reporter genes or tracers) as well as adding endothelial cells to form a blood-brain-barrier.

5. 发明申请

US20150290214A1 METHOD OF TREATMENT OF DISEASE 有权
标题翻译：治疗疾病的方法
公开(公告)号：US20150290214A1
公开(公告)日：2015-10-15
申请号：US14438413
申请日：2013-10-24
申请人： Zeev GROSS , Adi HABER , Itzchak ANGEL , TECHNION RESEARCH AND DEVELOPMENT FOUNDATION LTD.
发明人： Zeev Gross , Adi Haber , Itzchak Angel
IPC分类号： A61K31/555
CPC分类号： A61K31/555 , A61K31/409 , A61K38/41 , C07D487/22
摘要： An embodiment of the invention provides a use of an effective amount of a transition metal complex of a corrole, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof for treating a disease of the eye and/or the kidney in a subject suffering from diabetes. An embodiment of the invention further provides a use of a transition metal complex of a corrole, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof for lowering serum glucose and serum triglyceride levels in a subject suffering from diabetes.
摘要翻译：本发明的一个实施方案提供了有效量的角role的过渡金属络合物，其旋光异构体或其药学上可接受的盐在治疗患有眼睛和/或肾脏的受试者的眼睛和/或肾脏疾病中的用途糖尿病。本发明的一个实施方案进一步提供了用于降低患有糖尿病的受试者的血清葡萄糖和血清甘油三酯水平的糠醛，其旋光异构体或其药学上可接受的盐的过渡金属络合物的用途。

6. 发明授权

US08252281B2 Methods for the treatment of sepsis and sepsis-associated cardiac dysfunction 有权
标题翻译：治疗败血症和败血症相关心脏功能障碍的方法
公开(公告)号：US08252281B2
公开(公告)日：2012-08-28
申请号：US11816230
申请日：2006-02-14
申请人： Richard J. Levy , Clifford S. Deutschman
发明人： Richard J. Levy , Clifford S. Deutschman
IPC分类号： A61K38/43 , C12P21/06 , C07K1/00
CPC分类号： A61K38/41
摘要： Methods for the treatment of sepsis related cardiac dysfunction are disclosed.
摘要翻译：公开了治疗败血症相关心脏功能障碍的方法。

7. 发明申请

US20100323029A1 FIVE-COORDINATE NEUROGLOBIN AND USE THEREOF AS A BLOOD SUBSTITUTE 有权
标题翻译：作为血液替代品使用五种协调的神经营养因子及其使用
公开(公告)号：US20100323029A1
公开(公告)日：2010-12-23
申请号：US12817085
申请日：2010-06-16
申请人： Mark T. Gladwin , Daniel B. Kim-Shapiro , Mauro Tiso
发明人： Mark T. Gladwin , Daniel B. Kim-Shapiro , Mauro Tiso
IPC分类号： A61K38/41 , A61K35/14 , A61K35/16 , A61K35/18 , A61P7/06 , A61P7/08 , A61P7/00 , A61P9/10 , A61P17/02 , A61P9/12
CPC分类号： A61K38/41 , A61K9/0019 , A61K35/14 , A61K35/16 , A61K35/18 , A61K38/42 , A61K45/06 , Y02A50/387
摘要： Described herein is the finding that a mutant form of human neuroglobin (H64L) with a stable five-coordinate geometry reduces nitrite to nitric oxide approximately 2000-times faster than the wild type neuroglobin. Five-coordinate neuroglobin is also capable of binding and releasing oxygen. Based on these findings, the use of five-coordinate neuroglobin as a blood substitute is described herein. Particularly provided is a method of replacing blood and/or increasing oxygen delivery to tissues in a subject by administering to the subject a therapeutically effective amount of neuroglobin with a stable five-coordinate geometry. In some cases, five-coordinate neuroglobin is administered in combination with another therapeutic agent or composition, such as a second blood replacement product (for example, a hemoglobin-based oxygen carrier), a blood product (such as red blood cells, serum or plasma) or whole blood.
摘要翻译：这里描述的发现是具有稳定的五坐标几何形状的人类神经球蛋白（H64L）的突变形式将亚硝酸盐比野生型神经球蛋白的亚硝酸盐还原为大约2000倍的一氧化氮。五配位神经球蛋白也能够结合和释放氧气。基于这些发现，本文描述了使用五配位神经球蛋白作为血液代用品。特别提供的是通过向受试者施用具有稳定的五坐标几何形状的治疗有效量的神经球蛋白来替代血液和/或增加对受试者组织的氧输送的方法。在一些情况下，五配位神经球蛋白与另一种治疗剂或组合物，例如第二种血液替代产品（例如，基于血红蛋白的氧载体），血液制品（例如红细胞，血清或血浆）或全血。

8. 发明申请

US20050208151A1 Treatment of rheumatoid arthritis with FLIP antagonists 审中-公开
标题翻译：用FLIP拮抗剂治疗类风湿关节炎
公开(公告)号：US20050208151A1
公开(公告)日：2005-09-22
申请号：US10980145
申请日：2004-11-01
申请人： Vincent Hurez , Saroja Ramanujan , Lisl Shoda , Leif Wennerberg , Seth Michelson , Nadine Defranoux
发明人： Vincent Hurez , Saroja Ramanujan , Lisl Shoda , Leif Wennerberg , Seth Michelson , Nadine Defranoux
IPC分类号： A61K31/16 , A61K31/19 , A61K31/277 , A61K31/407 , A61K31/52 , A61K31/704 , A61K31/7072 , A61K33/24 , A61K38/16 , A61K38/17 , A61K38/21 , A61K38/41 , A61K45/00 , A61K48/00 , C12Q1/00 , G01N33/50 , G01N33/564
CPC分类号： G01N33/564 , A61K31/52 , A61K38/162 , A61K38/1709 , A61K38/215 , A61K38/41 , G01N2800/102
摘要： The invention encompasses novel methods of treating rheumatoid arthritis and its symptoms and novel methods of identifying and screening for drugs useful in the treatment of rheumatoid arthritis and its clinical symptoms. Targeted manipulation of a computer model of a human rheumatic joint provided the surprising result that decreasing the activity of FLIP, an inhibitor of apoptosis, by at least 25% has a significant impact on the pathophysiology of rheumatoid arthritis. Inhibition of the activity of FLIP by at least 25% is predicted to alleviate the symptoms of rheumatoid arthritis.
摘要翻译：本发明包括治疗类风湿性关节炎及其症状的新方法及其鉴定和筛选用于治疗类风湿性关节炎及其临床症状的药物的新方法。人类风湿关节的计算机模型的目标操纵提供令人惊奇的结果，即将凋亡抑制剂FLIP的活性降低至少25％，对类风湿性关节炎的病理生理学具有显着影响。 FLIP活性抑制至少25％被预测为减轻类风湿性关节炎的症状。

9. 发明公开

US20240083979A1 COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARBOXYHEMOGLOBINEMIA 审中-公开
公开(公告)号：US20240083979A1
公开(公告)日：2024-03-14
申请号：US18504534
申请日：2023-11-08
申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education
发明人： Mark T. Gladwin , Jesus Tejero Bravo
IPC分类号： C07K14/795 , A61K9/00 , A61K38/41
CPC分类号： C07K14/795 , A61K9/0019 , A61K38/41 , A61K38/00
摘要： Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.

10. 发明授权

US11845785B2 Compositions and methods for the treatment of carboxyhemoglobinemia 有权
公开(公告)号：US11845785B2
公开(公告)日：2023-12-19
申请号：US16951529
申请日：2020-11-18
申请人： University of Pittsburgh—Of the Commonwealth System of Higher Education
发明人： Mark T. Gladwin , Jesus Tejero Bravo
IPC分类号： C07K14/795 , A61K38/41 , A61K9/00 , A61K38/00
CPC分类号： C07K14/795 , A61K9/0019 , A61K38/41 , A61K38/00
摘要： Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.

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