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    Recombinant human serum albumin, process for producing the same and pharmaceutical preparation containing the same
    1.
    发明授权
    Recombinant human serum albumin, process for producing the same and pharmaceutical preparation containing the same 失效
    重组人血清白蛋白，其制备方法和含有其的药物制剂

    公开(公告)号：US5986062A

    公开(公告)日：1999-11-16

    申请号：US538471

    申请日：1995-10-03

    申请人： Takao Ohmura ,  Akinori Sumi ,  Wataru Ohtani ,  Naoto Furuhata ,  Kazuya Takeshima ,  Kaeko Kamide ,  Munehiro Noda ,  Masahide Kondo ,  Syoichi Ishikawa ,  Kazuhiro Oohara ,  Kazumasa Yokoyama ,  Nagatoshi Fujiwara

    发明人： Takao Ohmura ,  Akinori Sumi ,  Wataru Ohtani ,  Naoto Furuhata ,  Kazuya Takeshima ,  Kaeko Kamide ,  Munehiro Noda ,  Masahide Kondo ,  Syoichi Ishikawa ,  Kazuhiro Oohara ,  Kazumasa Yokoyama ,  Nagatoshi Fujiwara

    IPC分类号： A61K38/00 ,  C07K14/765

    CPC分类号： C07K14/765 ,  A61K2039/545 ,  A61K38/00

    摘要： Human serum albumin obtained by gene manipulation techniques can be purified by a combination of specified steps in which a culture supernatant obtained from a human serum albumin-producing host is subjected to ultrafiltration, heat treatment, acid treatment and another ultrafiltration, followed by subsequent treatments with a cation exchanger, a hydrophobic chromatography carrier and an anion exchanger, and by salting-out to thereby obtain a pure form of human serum albumin which contains substantially no proteinous and polysaccharide contaminants, which is formulated into a pharmaceutical preparation. The thus obtained human serum albumin can further be purified by treating recombinant human serum albumin with a hydrophobic chromatography carrier at pH of 2 to 5 and a salt concentration of 0.4 to 1 and exposing the carrier to a pH of 6 to 8 and a salt concentration of 0.01 to 0.3 M, or treating the culture supernatant with boric acid or a salt thereof at pH 8 to 11 for 1 to 10 hours and recovering the supernatant. This process makes it possible to effeciently purify recombinant human serum albumin and to provide substantially pure human serum albumin which does not contain producer host-related substances and other contaminants and is sufficiently free from coloration.

    摘要翻译： 通过基因操作技术获得的人血清白蛋白可以通过特定步骤的组合来纯化，其中将得自人血清白蛋白的宿主的培养上清液进行超滤，热处理，酸处理和另一次超滤，然后用 阳离子交换剂，疏水性色谱载体和阴离子交换剂，并通过盐析，从而获得纯的形式的人血清白蛋白，其基本上不含有配制成药物制剂的蛋白质和多糖污染物。 由此获得的人血清白蛋白可以进一步通过用pH为2至5和盐浓度为0.4至1的疏水色谱载体处理重组人血清白蛋白并将载体暴露于pH6至8和盐浓度 为0.01〜0.3M，或用硼酸或其盐在pH8〜11处理培养上清1〜10小时，回收上清液。 该方法使得可以有效地纯化重组人血清白蛋白并提供基本上纯的人血清白蛋白，其不含生产者宿主相关物质和其它污染物，并且没有着色。

    Method for decoloring human serum albumin
    3.
    发明授权
    Method for decoloring human serum albumin 失效
    人血清白蛋白脱色方法

    公开(公告)号：US5710253A

    公开(公告)日：1998-01-20

    申请号：US358302

    申请日：1994-12-19

    申请人： Wataru Ohtani ,  Naoto Furuhata ,  Akinori Sumi ,  Munehiro Noda ,  Takao Ohmura

    发明人： Wataru Ohtani ,  Naoto Furuhata ,  Akinori Sumi ,  Munehiro Noda ,  Takao Ohmura

    IPC分类号： C12P21/00 ,  A61K38/16 ,  A61P7/00 ,  C07K1/14 ,  C07K1/20 ,  C07K14/76 ,  C07K14/765 ,  C12N15/00 ,  C12R1/84 ,  C07K1/36 ,  A61K38/38 ,  C07K1/16

    CPC分类号： C07K14/765

    摘要： A method for decoloring a recombinant human serum albumin by treating the albumin with a reducing agent is disclosed. Also, a method for decoloring a recombinant human serum albumin by treating the albumin with a method removing free polysaccharides with a cation exchanger followed by heat treatment is disclosed. The present invention provides a recombinant human serum albumin, coloring of which is fully suppressed by preventing binding of certain coloring components, which are contained in the raw materials or contaminants secreted by a microorganism, to human serum albumin so as not to cause coloring of the human serum albumin.

    摘要翻译： 公开了通过用还原剂处理白蛋白来使重组人血清白蛋白脱色的方法。 另外，公开了一种通过用阳离子交换剂随后热处理除去游离多糖的方法处理白蛋白来对重组人血清白蛋白进行脱色的方法。 本发明提供一种重组人血清白蛋白，通过防止原料中含有的某些着色成分或微生物分泌的污染物与人血清白蛋白结合，使其着色得到完全抑制，从而不引起 人血清白蛋白。

    Process for purifying recombinant human serum albumin
    5.
    发明授权
    Process for purifying recombinant human serum albumin 有权
    重组人血清白蛋白纯化方法

    公开(公告)号：US06617133B1

    公开(公告)日：2003-09-09

    申请号：US09317214

    申请日：1999-05-24

    申请人： Munehiro Noda ,  Akinori Sumi ,  Takao Ohmura ,  Kazumasa Yokoyama

    发明人： Munehiro Noda ,  Akinori Sumi ,  Takao Ohmura ,  Kazumasa Yokoyama

    IPC分类号： C12P2100

    CPC分类号： C07K14/765

    摘要： The invention provides a process for purifying recombinant human serum albumin (rHSA) by heating a-culture medium containing rHSA and the rHSA-producing host cells, feeding said heated solution upwardly into a fluidized bed in which adsorbent particles are suspended to effect contacting with the adsorbent particles and then recovering the adsorbed fraction containing the rHSA, and a composition comprising rHSA which shows a A350/A280 ratio of below 0.015, when formulated into a 25% solution of said albumin.

    摘要翻译： 本发明提供了通过加热含有rHSA和产生rHSA的宿主细胞的培养基来纯化重组人血清白蛋白（rHSA）的方法，将所述加热溶液向上加入流化床中，其中吸附剂颗粒悬浮以实现与 吸附剂颗粒，然后回收含有rHSA的吸附级分，以及包含rHSA的组合物，其在配制成所述白蛋白的25％溶液时显示A350 / A280比率低于0.015。

    Process for purifying recombinant human serum albumin
    6.
    发明授权
    Process for purifying recombinant human serum albumin 失效
    重组人血清白蛋白纯化方法

    公开(公告)号：US5962649A

    公开(公告)日：1999-10-05

    申请号：US522089

    申请日：1995-08-31

    申请人： Munehiro Noda ,  Akinori Sumi ,  Takao Ohmura ,  Kazumasa Yokoyama

    发明人： Munehiro Noda ,  Akinori Sumi ,  Takao Ohmura ,  Kazumasa Yokoyama

    IPC分类号： C07K14/765 ,  C07K1/16

    CPC分类号： C07K14/765

    摘要： The invention provides a process for purifying recombinant human serum albumin (rHSA) by heating a culture medium containing rHSA and the rHSA-producing host cello, feeding said heated solution upwardly into a fluidized bed in which adsorbent particles are suspended to effect contacting with the adsorbent particles and then recovering the adsorbed fraction containing the rHSA, and a composition comprising rHSA which shows a A35D/A280 ratio of below 0.015, when formulated into a 25% solution of said albumin.

    摘要翻译： 本发明提供了通过加热含有rHSA和产生rHSA的宿主大肠杆菌的培养基来纯化重组人血清白蛋白（rHSA）的方法，将所述加热溶液向上加入到流化床中，其中吸附剂颗粒悬浮以与吸附剂接触 颗粒，然后回收含有rHSA的吸附级分，以及包含rHSA的组合物，其在配制成所述白蛋白的25％溶液时显示A35D / A280比率低于0.015。

    Plasma fraction purification
    7.
    发明授权
    Plasma fraction purification 失效
    血浆级分纯化

    公开(公告)号：US5219995A

    公开(公告)日：1993-06-15

    申请号：US913590

    申请日：1992-07-14

    申请人： Steven W. Herring ,  Yahiro Uemura ,  Munehiro Noda ,  Kenneth T. Shitanishi

    发明人： Steven W. Herring ,  Yahiro Uemura ,  Munehiro Noda ,  Kenneth T. Shitanishi

    IPC分类号： A61K38/43 ,  C07K1/18 ,  C07K1/22 ,  C07K1/30 ,  C07K14/435 ,  C07K14/745 ,  C12N9/64 ,  C12N9/74

    CPC分类号： C12N9/6429 ,  C07K14/745 ,  C12N9/6432 ,  C12Y304/21005 ,  C12Y304/21006

    摘要： The present invention describes a process for activating Factor II to Factor II.sub.a by incubating Factor II in the presence of Factor V, Factor X.sub.a, phospholipids, and calcium ions. Each of the factors is prepared from a single impure protein fraction which includes Factors II, V and X. The Factor II, V and X purification procedure comprises the steps of DEAE ligand chromatography and precipitation by the addition of barium chloride. Factor V is recovered from the barium chloride supernatant, and Factors II and X are contained in the barium chloride precipitate. The barium chloride precipitate is dissolved in an aqueous solution and is applied to a chromatographic resin coupled with a ligand which binds Factor X and Factor II weakly or not at all. Factor II is recovered from the fraction, which remains unbound or weakly bound to the Factor X binding ligand. Factor X.sub.a is prepared by recovering Factor X from the ligand during the Factor II preparation procedure and activating the Factor X to Factor X.sub.a by specific proteolytic cleavage.

    摘要翻译： 本发明描述了通过在因子V，因子Xa，磷脂和钙离子的存在下孵育因子II来激活因子II至因子IIa的方法。 因子II，V和X的纯化程序包括DEAE配体层析和加入氯化钡沉淀的步骤。 因子V从氯化钡上清液中回收，因子II和X包含在氯化钡沉淀中。 将氯化钡沉淀物溶解在水溶液中，并施加到与限制因子X和因子II的配体偶联的色谱树脂上或完全不结合。 因子II从部分回收，其保持未结合或弱结合于因子X结合配体。 因子Xa通过在因子II制备过程中从配体中回收因子X并通过特异性蛋白水解切割活化因子X至因子Xa来制备。

    Antibody and use thereof
    8.
    发明授权
    Antibody and use thereof 有权
    抗体及其用途

    公开(公告)号：US08445649B2

    公开(公告)日：2013-05-21

    申请号：US12734359

    申请日：2008-10-29

    申请人： Minako Hoshi ,  Michio Sato ,  Shoji Ideno ,  Koji Naito ,  Satoshi Horie ,  Munehiro Noda ,  Hajime Horii

    发明人： Minako Hoshi ,  Michio Sato ,  Shoji Ideno ,  Koji Naito ,  Satoshi Horie ,  Munehiro Noda ,  Hajime Horii

    IPC分类号： C07K16/18 ,  C12P21/08

    CPC分类号： C07K16/18 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/6896 ,  G01N2800/2821

    摘要： An antibody provided by the present invention has a low reactivity with amyloid precursor proteins, and has a higher reactivity with amylospheroids than with amyloid β fibrils or monomeric amyloid β-proteins. According to the present invention, an antibody is provided that has a higher reactivity with amylospheroids than with amyloid precursor proteins, and has any one or more of the following properties: (i) a higher activity with amylospheroids than with amyloid β fibrils; (ii) a higher reactivity with amylospheroids than with monomeric amyloid β-proteins; and (iii) an activity of inhibiting neuronal cell death induced by amylospheroids.

    摘要翻译： 由本发明提供的抗体与淀粉样蛋白前体蛋白具有低反应性，并且与淀粉样蛋白β原纤维或单体淀粉样β-蛋白具有比淀粉样蛋白球体更高的反应性。 根据本发明，提供了与淀粉样蛋白前体蛋白具有比淀粉样前体蛋白更高的反应性的抗体，并且具有以下特性中的任何一种或多种：（i）与淀粉样蛋白β原纤维相比，淀粉样蛋白球体的活性更高; （ii）与淀粉样β蛋白相比，淀粉样蛋白球体的反应性更高; 和（iii）抑制淀粉样蛋白球体诱导的神经元细胞死亡的活性。