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：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：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：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。