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1. 发明授权

US5827693A Expression of recombinant hemoglobin and hemoglobin variants in yeast 失效
标题翻译：酵母中重组血红蛋白和血红蛋白变体的表达
公开(公告)号：US5827693A
公开(公告)日：1998-10-27
申请号：US484686
申请日：1995-06-07
申请人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
发明人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
IPC分类号： A61K38/00 , C07K14/805 , C12N15/81 , C12P21/06 , C12N15/00 , C12N1/14
CPC分类号： C12N15/81 , C07K14/805 , A61K38/00
摘要： The invention is directed to a substantially pure mammalian globin chain or heme-binding fragment thereof. The invention is further directed to recombinant DNA vectors capable of expressing at least one globin chain or substantially homologous variant thereof in yeast. The invention also relates to methods for expressing at least one globin chain or substantially homologous variant thereof in yeast. Expressed alpha-like globin and beta-like globin chains or variants thereof may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. Additionally, expressed gamma-globin chains may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. The invention also relates to methods for expressing hemoglobin or variants thereof in yeast where the heme is produced by the yeast and ligated to globins to form hemoglobin in vivo. The hemoglobin produced by the methods of the present invention may be used in applications requiring a physiological oxygen carrier such as in blood substitute solutions and as in plasma expanders or in applications requiring a physiological oxygen carrier.
摘要翻译：本发明涉及基本上纯的哺乳动物球蛋白链或其血红素结合片段。本发明还涉及能够在酵母中表达至少一种珠蛋白链或基本上同源的变体的重组DNA载体。本发明还涉及用于在酵母中表达至少一种珠蛋白链或基本上同源的变体的方法。表达的α样球蛋白和β样球蛋白链或其变体可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。此外，表达的γ-珠蛋白链可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。本发明还涉及在酵母中表达血红蛋白或其变体的方法，其中血红素由酵母产生并与球蛋白结合以在体内形成血红蛋白。通过本发明的方法产生的血红蛋白可以用于需要生理氧载体的应用中，例如在血液替代溶液中，以及在等离子体扩张器中或在需要生理氧载体的应用中。

2. 发明授权

US06172039B2 Expression of recombinant hemoglobin and hemoglobin variants in yeast 失效
标题翻译：酵母中重组血红蛋白和血红蛋白变体的表达
公开(公告)号：US06172039B2
公开(公告)日：2001-01-09
申请号：US08463160
申请日：1995-06-05
申请人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
发明人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
IPC分类号： C07K14805
CPC分类号： C12N15/81 , A61K38/00 , C07K14/805 , Y02A50/473
摘要： The invention is directed to a substantially pure mammalian globin chain or heme-binding fragment thereof. The invention is further directed to recombinant DNA vectors capable of expressing at least one globin chain or substantially homologous variant thereof in yeast. The invention also relates to methods for expressing at least one globin chain or substantially homologous variant thereof in yeast. Expressed alpha-like globin and beta-like globin chains or variants thereof may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. Additionally, expressed gamma-globin chains may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. The invention also relates to methods for expressing hemoglobin or variants thereof in yeast where the heme is produced by the yeast and ligated to globins to form hemoglobin in vivo. The hemoglobin produced by the methods of the present invention may be used in applications requiring a physiological oxygen carrier such as in blood substitute solutions and as in plasma expanders or in applications requiring a physiological oxygen carrier.
摘要翻译：本发明涉及基本上纯的哺乳动物球蛋白链或其血红素结合片段。本发明还涉及能够在酵母中表达至少一种珠蛋白链或基本上同源的变体的重组DNA载体。本发明还涉及用于在酵母中表达至少一种珠蛋白链或基本上同源的变体的方法。表达的α样球蛋白和β样球蛋白链或其变体可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。此外，表达的γ-珠蛋白链可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。本发明还涉及在酵母中表达血红蛋白或其变体的方法，其中血红素由酵母产生并与球蛋白结合以在体内形成血红蛋白。通过本发明的方法产生的血红蛋白可以用于需要生理氧载体的应用中，例如在血液替代溶液中，以及在等离子体扩张器中或在需要生理氧载体的应用中。

3. 发明授权

US06350729B1 Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein 失效
标题翻译：用含铁血红蛋白抑制一氧化氮介导的低血压和败血性休克
公开(公告)号：US06350729B1
公开(公告)日：2002-02-26
申请号：US09615353
申请日：2000-07-13
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K3842
CPC分类号： A61K38/42 , Y02A50/411
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

4. 发明授权

US5900403A Use of iron hemoprotein for treating pathogenic syndrome caused by nitric oxide overproduction 失效
标题翻译：使用铁血蛋白治疗由一氧化氮过量产生引起的致病综合征
公开(公告)号：US5900403A
公开(公告)日：1999-05-04
申请号：US942632
申请日：1997-10-02
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also direction to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明也是治疗败血性休克的方法。

5. 发明授权

US5674836A Treatment of septic shock with iron-containing hemoprotein 失效
标题翻译：用含铁血红蛋白治疗败血性休克
公开(公告)号：US5674836A
公开(公告)日：1997-10-07
申请号：US184255
申请日：1994-01-18
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

6. 发明授权

US6103690A Prevention or inhibition of pathogenic syndromes caused by nitric oxide overproduction using iron-containing hemoprotein 失效
标题翻译：使用含铁血红蛋白预防或抑制由一氧化氮过量产生引起的致病综合征
公开(公告)号：US6103690A
公开(公告)日：2000-08-15
申请号：US204392
申请日：1998-12-02
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

7. 发明授权

US5296466A Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein 失效
标题翻译：用含铁血红蛋白抑制一氧化氮介导的低血压和败血性休克
公开(公告)号：US5296466A
公开(公告)日：1994-03-22
申请号：US838603
申请日：1992-02-19
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12 , A61K37/02
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

8. 发明授权

US07329543B2 Red blood cells loaded with S-nitrosothiol and uses therefor 有权
标题翻译：装有S-亚硝基硫醇的红细胞并用于此
公开(公告)号：US07329543B2
公开(公告)日：2008-02-12
申请号：US11179349
申请日：2005-07-12
申请人： Jonathan S. Stamler , Joseph Bonaventura , John R. Pawloski , Timothy J. McMahon
发明人： Jonathan S. Stamler , Joseph Bonaventura , John R. Pawloski , Timothy J. McMahon
IPC分类号： C12N5/06
CPC分类号： A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K33/00 , A61K38/1816 , A61K47/54 , A61K47/6445 , A61K47/6901 , C07K14/00 , G01N21/631 , G01N21/76 , G01N33/721
摘要： Red blood cells can be loaded with low molecular weight nitrosylating agents, such as S-nitrosothiols, to act as a delivery system for NO+ groups to tissues. Loaded red blood cells can be used in methods of therapy for conditions which are characterized by abnormal O2 metabolism of tissues, oxygen-related toxicity, abnormal vascular tone, abnormal red blood cell adhesion, or abnormal O2 delivery by red blood cells. Such treatment of red blood cells can be extended to in vivo therapies, with the object to achieve an increase in the ratio of red blood cell S-nitrosothiol to hemoglobin.
摘要翻译：红细胞可以装载低分子量亚硝酰化剂，如S-亚硝基硫醇，作为组织的NO + +组的递送系统。加载的红细胞可以用于治疗方法，其特征在于组织的异常O 2代谢，氧相关毒性，异常血管紧张度，异常红细胞粘附或异常的O < 通过红细胞递送SUB> 2 。红细胞的这种治疗可以延伸到体内治疗，其目的是实现红细胞S-亚硝基硫醇与血红蛋白的比例的增加。

9. 发明授权

US06916471B2 Red blood cells loaded with S-nitrosothiol and uses therefor 失效
标题翻译：装有S-亚硝基硫醇的红细胞并用于此
公开(公告)号：US06916471B2
公开(公告)日：2005-07-12
申请号：US10045603
申请日：2001-10-23
申请人： Jonathan S. Stamler , Joseph Bonaventura , John R. Pawloski , Timothy J. McMahon
发明人： Jonathan S. Stamler , Joseph Bonaventura , John R. Pawloski , Timothy J. McMahon
IPC分类号： A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K35/18 , A61K38/00 , A61K38/42 , A61K47/48 , C07K14/00 , G01N21/63 , G01N21/76 , G01N33/72 , C12N5/06
CPC分类号： A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K33/00 , A61K38/1816 , A61K47/54 , A61K47/6445 , A61K47/6901 , C07K14/00 , G01N21/631 , G01N21/76 , G01N33/721
摘要： Red blood cells can be loaded with low molecular weight nitrosylating agents, such as S-nitrosothiols, to act as a delivery system for NO+ groups to tissues. Loaded red blood cells can be used in methods of therapy for conditions which are characterized by abnormal O2 metabolism of tissues, oxygen-related toxicity, abnormal vascular tone, abnormal red blood cell adhesion, or abnormal O2 delivery by red blood cells. Such treatment of red blood cells can be extended to in vivo therapies, with the object to achieve an increase in the ratio of red blood cell S-nitrosothiol to hemoglobin.
摘要翻译：红细胞可以装载低分子量亚硝酰化剂，如S-亚硝基硫醇，作为组织的NO + +组的递送系统。加载的红细胞可以用于治疗方法，其特征在于组织的异常O 2代谢，氧相关毒性，异常血管紧张度，异常红细胞粘附或异常的O < 通过红细胞递送SUB> 2 。红细胞的这种治疗可以延伸到体内治疗，其目的是实现红细胞S-亚硝基硫醇与血红蛋白的比例的增加。

10. 发明授权

US5082642A Method for catalyzing oxidation/reduction reactions of simple molecules 失效
标题翻译：催化简单分子的氧化/还原反应的方法
公开(公告)号：US5082642A
公开(公告)日：1992-01-21
申请号：US607634
申请日：1990-10-31
申请人： David Bickar , Celia Bonaventura , Joseph Bonaventura
发明人： David Bickar , Celia Bonaventura , Joseph Bonaventura
IPC分类号： C01B21/087 , C01B21/22 , C01B21/36 , C01B31/18 , C01B31/20 , C01B31/26
CPC分类号： C01B21/36 , C01B31/18 , C01B31/20 , C01B31/262 , C01B31/267
摘要： This invention relates to a method for catalyzing the reactionsQZ+H.sub.2 X?QZX (1)andQZX?QZ+H.sub.2 X (2)whereinQ=C or N;Z=O or S;X=O, S, NH or NR;R=C.sub.1 to C.sub.8 alkyl which may be linear, branched or cyclized,which comprises:contacting at least one polydentate nitrogen-containing chelating agent complexed with a metal atom with the reactants of one of said reactions, wherein said contacting takes place in the presence of a means for oxidizing when reaction (1) is catalyzed and in the presence of a means for reducing when reaction (2) is catalyzed. A particular reaction is the conversion of NO to NO.sub.2 using water and supported porphines, hemes, phthalocyanines, ethioporphrins sirohemes, particularly heme and heme compounds or derivatives such as methemoglobin, myoglobin, or hemin.
摘要翻译：本发明涉及催化反应QZ + H2X→QZX（1）和QZX→QZ + H2X（2）的方法，其中Q = C或N; Z = O或S; X = O，S，NH或NR; R = C1至C8烷基，其可以是直链，支链或环化的，其包括：使与金属原子络合的至少一种多齿含氮螯合剂与所述反应之一的反应物接触，其中所述接触在存在下进行当催化反应（1）时和在反应（2）被催化时还原反应的手段的存在下，氧化的手段。特别的反应是使用水和负载的卟吩，海马，酞菁，乙孢子卟啉，特别是血红素和血红素化合物或衍生物如高铁血红蛋白，肌红蛋白或血红素，将NO转化为NO2。

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