公开(公告)号：US4694074A

公开(公告)日：1987-09-15

申请号：US792081

申请日：1985-10-28

申请人： Yahiro Uemura ,  Takao Ohmura ,  Akimasa Ohmizu ,  Akinori Sumi ,  Wataru Ohtani ,  Yoshitaka Sakanishi ,  Hiroshi Morise ,  Hirofumi Arimura ,  Tadakazu Suyama

发明人： Yahiro Uemura ,  Takao Ohmura ,  Akimasa Ohmizu ,  Akinori Sumi ,  Wataru Ohtani ,  Yoshitaka Sakanishi ,  Hiroshi Morise ,  Hirofumi Arimura ,  Tadakazu Suyama

IPC分类号： C12N15/09 ,  A61K39/29 ,  A61P1/16 ,  C07K1/16 ,  C07K1/22 ,  C07K14/005 ,  C07K14/02 ,  C07K14/195 ,  C07K14/435 ,  C12N5/00 ,  C12N15/00 ,  C12P21/00 ,  C12P21/08 ,  C07K3/18 ,  C07K3/28

CPC分类号： C07K14/005 ,  C12N2730/10122 ,  Y10S530/806 ,  Y10S530/808

摘要： A process for the purification of HBsAg is disclosed, which comprises adsorbing specifically on a carrier, in the presence of an inorganic salt in an amount of 5 to 25 W/V %, an HBsAg obtained by gene engineering.

摘要翻译： 公开了一种用于纯化HBsAg的方法，其包括在载体上以5至25W / V％的无机盐存在下特异性吸附通过基因工程获得的HBsAg。

公开(公告)号：US5132404A

公开(公告)日：1992-07-21

申请号：US584023

申请日：1990-09-18

申请人： Wataru Ohtani ,  Akinori Sumi ,  Takao Ohmura ,  Yahiro Uemura

发明人： Wataru Ohtani ,  Akinori Sumi ,  Takao Ohmura ,  Yahiro Uemura

IPC分类号： C12N1/16 ,  C07K14/435 ,  C07K14/76 ,  C07K14/765 ,  C12N15/09 ,  C12N15/14 ,  C12P21/00 ,  C12P21/02 ,  C12R1/865

CPC分类号： C07K14/765

摘要： A method of purifying human serum albumin which comprises subjecting human serum albumin-containing solution to heat treatment of about 50.degree.-70.degree. C. for 1-5 hours in the presence of acetyltryptophan and/or an organic carboxylic acid with 6-12 carbon atoms or a salt thereof.

公开(公告)号：US5440018A

公开(公告)日：1995-08-08

申请号：US36387

申请日：1993-03-24

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

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

IPC分类号： A61K38/00 ,  C07K1/14 ,  C07K14/765 ,  C12N15/14 ,  A61K38/38 ,  C07K1/16 ,  C07K1/36

CPC分类号： C07K14/765 ,  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. 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。 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。

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。

公开(公告)号：US5369020A

公开(公告)日：1994-11-29

申请号：US031823

申请日：1993-03-16

申请人： Akinori Sumi ,  Wataru Ohtani ,  Naoto Furuhata ,  Kazuya Takeshima ,  Kaeko Kamide ,  Takao Ohmura ,  Kazumasa Yokoyama

发明人： Akinori Sumi ,  Wataru Ohtani ,  Naoto Furuhata ,  Kazuya Takeshima ,  Kaeko Kamide ,  Takao Ohmura ,  Kazumasa Yokoyama

IPC分类号： A61K38/16 ,  A61P7/00 ,  B01D15/00 ,  C07K14/765 ,  C12N1/15 ,  C12N1/19 ,  C12N15/09 ,  C12N15/14 ,  C12P21/00 ,  C12P21/02 ,  C12R1/84 ,  C12R1/865 ,  C12P1/02

CPC分类号： C12P21/02 ,  C07K14/765

摘要： A method for suppressing coloring of human serum albumin expressed by genetic engineering, which comprises culture and/or purification in the presence of an amine compound selected from the group consisting of alkylamines, diamines, guanidines, benzamidines, basic amino acids, and aminophenylacetic acids. According to the present invention, coloring of HSA expressed by genetic engineering can be suppressed to from one-half to one-tenth of that without treatment for coloring suppression. In addition, HSA can be recovered in high yields, and the treatment of the invention does not affect the inherent properties of HSA.

摘要翻译： 一种用于抑制由遗传工程表达的人血清白蛋白着色的方法，其包括在选自烷基胺，二胺，胍胺，苯甲脒，碱性氨基酸和氨基苯基乙酸的胺化合物存在下培养和/或纯化。 根据本发明，通过遗传工程表达的HSA的着色可以抑制在不进行着色抑制处理的情况下的一半到十分之一。 另外，HSA可以以高收率回收，本发明的处理不影响HSA的固有特性。

公开(公告)号：US5521287A

公开(公告)日：1996-05-28

申请号：US202130

申请日：1994-02-25

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 ,  A61K38/38 ,  C07K1/16 ,  C07K1/36

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.

公开(公告)号：US5294699A

公开(公告)日：1994-03-15

申请号：US719443

申请日：1991-06-24

申请人： Takao Ohmura ,  Akinori Sumi ,  Wataru Ohtani ,  Naoto Fuluhata ,  Kaoru Kobayashi ,  Shinobu Kuwae ,  Hirotoshi Fukutsuka ,  Tomoshi Ohya ,  Hiroshi Morise

发明人： Takao Ohmura ,  Akinori Sumi ,  Wataru Ohtani ,  Naoto Fuluhata ,  Kaoru Kobayashi ,  Shinobu Kuwae ,  Hirotoshi Fukutsuka ,  Tomoshi Ohya ,  Hiroshi Morise

IPC分类号： A61K38/16 ,  A61K38/00 ,  B01D15/00 ,  B01D15/04 ,  C07K1/14 ,  C07K1/20 ,  C07K14/435 ,  C07K14/76 ,  C07K14/765 ,  C12N15/09 ,  C12N15/14 ,  C12N15/81 ,  C12P21/02 ,  C12R1/865 ,  C07K3/28 ,  A61K45/02

CPC分类号： C07K14/765 ,  C12N15/81 ,  A61K38/00 ,  C07K2319/02

摘要： A method of inhibiting the coloration of human serum albumin expressed by using the gene manipulation technology which method comprises separating coloring contaminants from said human serum albumin before said coloring contaminants bind to the human serum albumin.

摘要翻译： 通过使用基因操作技术抑制人血清白蛋白的着色的方法，该方法包括在所述着色污染物与人血清白蛋白结合之前从所述人血清白蛋白中分离着色污染物。

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。

公开(公告)号：US5334512A

公开(公告)日：1994-08-02

申请号：US854841

申请日：1992-03-20

申请人： Kaoru Kobayashi ,  Shinobu Kuwae ,  Tomoshi Ooya ,  Hirotoshi Fukutsuka ,  Akinori Sumi ,  Wataru Ohtani ,  Takao Ohmura ,  Kazumasa Yokoyama

发明人： Kaoru Kobayashi ,  Shinobu Kuwae ,  Tomoshi Ooya ,  Hirotoshi Fukutsuka ,  Akinori Sumi ,  Wataru Ohtani ,  Takao Ohmura ,  Kazumasa Yokoyama

IPC分类号： C07K14/765 ,  C12N1/16 ,  C12N1/19 ,  C12N15/09 ,  C12N15/14 ,  C12P21/00 ,  C12R1/84 ,  C12N1/38 ,  C12N15/81 ,  C12P21/02

CPC分类号： C07K14/765 ,  C12N1/16

摘要： A method for producing human serum albumin which comprises cultivating a human serum albumin-producing host prepared by genetic engineering, in a medium containing a fatty acid having 10 to 26 carbon atoms, or its salt, and a method for cultivating the host. HSA production can be greatly increased by the present invention.

摘要翻译： 一种生产人血清白蛋白的方法，包括在含有10-26个碳原子的脂肪酸的培养基或其盐中培养通过基因工程制备的人血清白蛋白生产宿主及其培养方法。 通过本发明可以大大增加HSA的生产。

公开(公告)号：US5612197A

公开(公告)日：1997-03-18

申请号：US442756

申请日：1995-05-17

申请人： Toyoo Ohda ,  Wataru Ohtani ,  Tomoshi Ohya ,  Shinobu Kuwae ,  Kenji Tomomitsu ,  Kaoru Kobayashi ,  Takao Ohmura

发明人： Toyoo Ohda ,  Wataru Ohtani ,  Tomoshi Ohya ,  Shinobu Kuwae ,  Kenji Tomomitsu ,  Kaoru Kobayashi ,  Takao Ohmura

IPC分类号： C12P21/00 ,  C07K14/765 ,  C12N1/19 ,  C12P21/02 ,  C12R1/84

CPC分类号： C12P21/02 ,  C07K14/765

摘要： A process for producing recombinant human serum albumin is disclosed, which comprises culturing a human serum albumin-producing host, prepared by gene manipulation techniques in a medium that contains an amino acid, preferably at least one amino acid selected from the group consisting of alanine, aspartic acid, glutamic acid, histidine, serine, tryptophan, valine, isoleucine, phenylalanine, cysteine and arginine, more preferably histidine. The process can significantly increase the yield of human serum albumin over that produced by known processes.

摘要翻译： 公开了一种生产重组人血清白蛋白的方法，其包括在含有氨基酸的培养基中培养产生人血清白蛋白的宿主，其通过基因操纵技术制备，优选至少一种选自丙氨酸， 天冬氨酸，谷氨酸，组氨酸，丝氨酸，色氨酸，缬氨酸，异亮氨酸，苯丙氨酸，半胱氨酸和精氨酸，更优选组氨酸。 该方法可以显着提高人血清白蛋白与已知方法产生的产量。