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    Chemically modified hemoglobin as an effective, stable, non-immunogenic red blood cell substitute
    1.
    发明授权
    Chemically modified hemoglobin as an effective, stable, non-immunogenic red blood cell substitute 失效
    化学修饰的血红蛋白作为有效，稳定，非免疫原性的红细胞替代品

    公开(公告)号：US5386014A

    公开(公告)日：1995-01-31

    申请号：US888039

    申请日：1992-05-22

    申请人： Kwang Nho ,  Shmuel Zalipsky ,  Frank Davis

    发明人： Kwang Nho ,  Shmuel Zalipsky ,  Frank Davis

    IPC分类号： A61K38/00 ,  A61K47/48 ,  C07K14/805 ,  C07K17/06 ,  C07K13/00 ,  C07K17/08

    CPC分类号： A61K47/48215 ,  A61K47/48307 ,  C07K14/805 ,  C07K17/06 ,  A61K38/00 ,  Y10S530/815

    摘要： The present invention relates to chemically modified hemoglobin produced by a novel and efficient method in which stroma-free hemoglobin is first effectively deoxygenated and reduced and then conjugated with a polyalkylene oxide such as polyethylene glycol (PEG) under conditions which maintain the structural integrity of the heme oxygen binding site. In specific, preferred embodiments of the invention, the deoxygenation and reduction is performed under an inert atmosphere by the amino acid cysteine. In additional specific, preferred embodiments, the structural integrity of the heme oxygen binding site is maintained by a high anionic concentration in the reaction mixture. In further preferred specific emodiments of the invention, the polyalkylene oxide is polyethylene glycol; in still further preferred specific embodiments of the invention, the polyalkylene oxide is linked to hemoglobin via a urethane (carbamate) linkage.The novel PEG-modified hemoglobin compounds of the invention exhibit superior oxygen transport capabilities, extended half-life, and importantly, low immunogenicity.

    摘要翻译： 本发明涉及通过新颖有效的方法制备的化学修饰的血红蛋白，其中无基质血红蛋白首先被有效地脱氧和还原，然后在保持结构完整性的条件下与聚环氧烷如聚乙二醇（PEG）缀合 血红素氧气结合位点。 在本发明的具体的优选实施方案中，通过氨基酸半胱氨酸在惰性气氛下进行脱氧和还原。 在另外具体的优选实施方案中，通过反应混合物中的高阴离子浓度维持血红素氧结合位点的结构完整性。 在本发明的进一步优选的具体实施方案中，聚环氧烷是聚乙二醇; 在本发明的进一步优选的具体实施方案中，聚环氧烷通过氨基甲酸酯（氨基甲酸酯）连接与血红蛋白连接。 本发明的新型PEG修饰的血红蛋白化合物表现出优异的氧输送能力，延长的半衰期，并且重要的是低的免疫原性。

    Monofunctional polyethylene glycol aldehydes
    2.
    发明授权
    Monofunctional polyethylene glycol aldehydes 失效
    单官能聚乙二醇醛

    公开(公告)号：US06916962B2

    公开(公告)日：2005-07-12

    申请号：US10431294

    申请日：2003-05-07

    申请人： Perry Rosen ,  Kwang Nho

    发明人： Perry Rosen ,  Kwang Nho

    IPC分类号： C08G65/324 ,  C08G65/329 ,  C08G65/331 ,  C08G65/333 ,  C07C47/02 ,  C07K16/00 ,  C08G63/48

    CPC分类号： C08G65/33396 ,  C08G65/324 ,  C08G65/329 ,  C08G65/331 ,  C08L2203/02

    摘要： The present invention provides novel monofunctional polyethylene glycol aldehydes for the pegylation of therapeutically active proteins. The pegylated protein conjugates that are produced, retain a substantial portion of their therapeutic activity and are less immunogenic than the protein from which the conjugate is derived. New syntheses for preparing such aldehydes are described.

    摘要翻译： 本发明提供用于治疗活性蛋白质聚乙二醇化的新型单官能聚乙二醇醛。 产生的聚乙二醇化的蛋白质缀合物保留了其治疗活性的相当大部分，并且与衍生缀合物的蛋白质相比具有较少的免疫原性。 描述了用于制备这种醛的新合成。

    Preparation method of peg-maleimide derivatives
    3.
    发明授权
    Preparation method of peg-maleimide derivatives 失效
    聚马来酰亚胺衍生物的制备方法

    公开(公告)号：US06828401B2

    公开(公告)日：2004-12-07

    申请号：US10697409

    申请日：2003-10-29

    申请人： Kwang Nho ,  Changmin Hyun ,  Junghun Lee ,  Youngkyoung Pak

    发明人： Kwang Nho ,  Changmin Hyun ,  Junghun Lee ,  Youngkyoung Pak

    IPC分类号： C08F11612

    CPC分类号： C08G73/12 ,  C08G65/33337

    摘要： The present invention relates to novel synthetic methods for PEG-maleimide derivatives, specifically, novel synthetic methods for PEG-maleimide. The final products thereof are useful as a pegylation reagent in the field of bioengineering and the medicinal field or the preparation of medical appliances and by conjugating with certain moieties or specific domains of polysaccharides and biological proteins such as antibodies as a bio-compatible or bio-degradable polymer.

    摘要翻译： 本发明涉及PEG-马来酰亚胺衍生物的新型合成方法，特别涉及PEG-马来酰亚胺的新型合成方法。 其最终产物可用作生物工程领域中的聚乙二醇化试剂和药用领域或医疗器具的制备，并且通过与多糖和生物蛋白质的某些部分或特定结构域（例如作为生物相容或生物相容性的抗体）结合， 可降解聚合物。

    Chemically modified hemoglobin as an effective, stable non-immunogenic red blood cell substitute
    7.
    发明授权
    Chemically modified hemoglobin as an effective, stable non-immunogenic red blood cell substitute 失效
    化学修饰的HEMOGLOBIN作为有效的，稳定的非免疫性红血球细胞替代物

    公开(公告)号：US5234903A

    公开(公告)日：1993-08-10

    申请号：US616129

    申请日：1990-11-20

    申请人： Kwang Nho ,  Shmuel Zalipsky ,  Frank Davis

    发明人： Kwang Nho ,  Shmuel Zalipsky ,  Frank Davis

    IPC分类号： A61K38/16 ,  A61K38/00 ,  A61K47/48 ,  C07K1/08 ,  C07K14/805 ,  C07K17/06

    CPC分类号： A61K47/48215 ,  A61K47/48307 ,  C07K14/805 ,  C07K17/06 ,  A61K38/00

    摘要： The present invention relates to chemically modified hemoglobin produced by a novel and efficient method in which stroma-free hemoglobin is first effectively deoxygenated and reduced and then conjugated with a polyalkylene oxide such as polyethylene glycol (PEG) under conditions which maintain the structural integrity of the heme oxygen binding site. In specific, preferred embodiments of the invention, the deoxygenation and reduction is performed under an inert atmosphere by the amino acid cysteine. In additional specific, preferred embodiments, the structural integrity of the heme oxygen binding site is maintained by a high anionic concentration in the reaction mixture. In further preferred specific embodiments of the invention, the polyalkylene oxide is polyethylene glycol; in still further preferred specific embodiments of the invention, the polyalkylene oxide is linked to hemoglobin via a urethane (carbamate) linkage.The novel PEG-modified hemoglobin compounds of the invention exhibit superior oxygen transport capabilities, extended half-life, and importantly, low immunogenicity.

    摘要翻译： 本发明涉及通过新颖有效的方法制备的化学修饰的血红蛋白，其中无基质血红蛋白首先被有效地脱氧和还原，然后在保持结构完整性的条件下与聚环氧烷如聚乙二醇（PEG）缀合 血红素氧气结合位点。 在本发明的具体的优选实施方案中，通过氨基酸半胱氨酸在惰性气氛下进行脱氧和还原。 在另外具体的优选实施方案中，通过反应混合物中的高阴离子浓度维持血红素氧结合位点的结构完整性。 在本发明的进一步优选的具体实施方案中，聚环氧烷是聚乙二醇; 在本发明的进一步优选的具体实施方案中，聚环氧烷通过氨基甲酸酯（氨基甲酸酯）连接与血红蛋白连接。 本发明的新型PEG修饰的血红蛋白化合物表现出优异的氧输送能力，延长的半衰期，并且重要的是低的免疫原性。

    Methylmaleimidyl polymer derivatives
    9.
    发明申请
    Methylmaleimidyl polymer derivatives 审中-公开
    甲基马来酰亚胺基聚合物衍生物

    公开(公告)号：US20070141021A1

    公开(公告)日：2007-06-21

    申请号：US11638997

    申请日：2006-12-13

    申请人： Perry Rosen ,  Kwang Nho

    发明人： Perry Rosen ,  Kwang Nho

    IPC分类号： A61K38/17 ,  C07K14/47 ,  C07D207/40

    CPC分类号： A61K38/063 ,  A61K47/60 ,  C07D207/40

    摘要： Novel N-2-methylmaleirnide pegylating reagents for the site specific pegylation of therapeutically active proteins and methods for such pegylation using said reagents.

    摘要翻译： 用于治疗活性蛋白质的位点特异性聚乙二醇化的新型N-2-甲基马来酰亚胺聚乙二醇化试剂和使用所述试剂进行此类聚乙二醇化的方法。

    Bifunctional polyethylene glycol derivatives
    10.
    发明授权
    Bifunctional polyethylene glycol derivatives 失效
    双功能聚乙二醇衍生物

    公开(公告)号：US07217845B2

    公开(公告)日：2007-05-15

    申请号：US10721013

    申请日：2003-11-21

    申请人： Perry Rosen ,  Kwang Nho

    发明人： Perry Rosen ,  Kwang Nho

    IPC分类号： C07C47/00 ,  C07C233/00 ,  C07C235/00 ,  C08F283/00

    CPC分类号： C08G65/33396 ,  A61K47/60 ,  C08G65/329 ,  C08G65/331 ,  C08L2203/02

    摘要： The present invention provides novel heterobifunctional and monobifunctional polyethylene glycol derivatives for the pegylation of therapeutically active proteins. The heterobifunctional PEGs which bear two different functional groups as well as the monobifunctional PEGs which contain two similar functional groups, may be used for cross-linking purposes. The cross-linking may be intramolecular between two areas within the same molecule or intermolecular between two separate molecules. The pegylated protein conjugates that are produced, retain a substantial portion of their therapeutic activity and are less immunogenic than the protein from which the conjugate is derived. New syntheses for preparing such bifunctional derivatives are described.

    摘要翻译： 本发明提供用于治疗活性蛋白质聚乙二醇化的新型异双功能和单官能聚乙二醇衍生物。 具有两个不同官能团的异双功能PEG以及含有两个相似官能团的单官能PEG可用于交联目的。 交联可以在相同分子内的两个区域之间或两个分开的分子之间的分子间分子内。 产生的聚乙二醇化的蛋白质缀合物保留了其治疗活性的相当大部分，并且与衍生缀合物的蛋白质相比具有较少的免疫原性。 描述了用于制备这种双官能衍生物的新合成。