公开(公告)号：US4945046A

公开(公告)日：1990-07-31

申请号：US57143

申请日：1987-06-03

申请人： Hajime Horii ,  Haruhide Kawabe ,  Hirofumi Arimura ,  Hiromichi Mukai ,  Kaoru Kobayashi ,  Muneo Tsujikawa ,  Masayuki Nishida ,  Tadakazu Suyama

发明人： Hajime Horii ,  Haruhide Kawabe ,  Hirofumi Arimura ,  Hiromichi Mukai ,  Kaoru Kobayashi ,  Muneo Tsujikawa ,  Masayuki Nishida ,  Tadakazu Suyama

IPC分类号： C07K14/02 ,  C12N15/81

CPC分类号： C07K14/005 ,  C12N15/81 ,  C12N2730/10122

摘要： A method of producing a heterologous protein in yeast is disclosed, which comprises transforming a yeast Saccharomyces cerevisiae with recombinant DNA comprising a promoter selected from the group consisting of a yeast promoter or a hybrid promoter derived from a yeast promoter, particularly a hybrid promoter containing the enhancer region of SV40 virus, and a gene coding for a heterologous protein such as HBsAg and Pre S-HBsAg, particularly full length Pre S-HBsAg culturing, the resulting transformed cells to express the gene coding the heterologous protein, and isolating the heterologous protein from the cultured medium. GAP-DH and PH05 promoters and miniaturized ones can be used as the yeast promoter. The expression of the full length Pre S-HBsAg is carried out in the same expression system as that for 2nd or 3rd Pre S-ABsAg.

摘要翻译： 公开了一种在酵母中产生异源蛋白质的方法，其包括用包含启动子的重组DNA转化酵母酿酒酵母，所述启动子选自酵母启动子或源自酵母启动子的杂合启动子，特别是含有 SV40病毒的增强子区和编码异源蛋白如HBsAg和Pre S-HBsAg的基因，特别是全长Pre S-HBsAg培养，所得转化细胞表达编码异源蛋白的基因，并分离异源蛋白 从培养基中。 GAP-DH和PH05启动子和小型化可用作酵母启动子。 全长前S-HBsAg的表达在与第2或第3前S-ABsAg相同的表达系统中进行。

公开(公告)号：US5021339A

公开(公告)日：1991-06-04

申请号：US397347

申请日：1989-08-24

申请人： Hiromichi Mukai ,  Hajime Horii ,  Muneo Tsujikawa ,  Haruhide Kawabe ,  Hirofumi Arimura ,  Tadakazu Suyama

发明人： Hiromichi Mukai ,  Hajime Horii ,  Muneo Tsujikawa ,  Haruhide Kawabe ,  Hirofumi Arimura ,  Tadakazu Suyama

IPC分类号： C07K14/02 ,  C12N15/81

CPC分类号： C07K14/005 ,  C12N15/81 ,  C12N2730/10122

摘要： A DNA sequence of the yeast glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) promoter and a process for preparing a heterologous protein utilizing said DNA sequence as a promoter are disclosed, said GAP-DH promoter comprising a region upstream of an initiator codon of the GAP-DH protein up to -164 bp as a minimum unit. Since the GAP-DH promoter is small in size, a physiologically active substance can be expressed in yeasts effectively and recombination of DNA can be simplified.

摘要翻译： 公开了酵母甘油醛-3-磷酸脱氢酶（GAP-DH）启动子的DNA序列和利用所述DNA序列作为启动子制备异源蛋白质的方法，所述GAP-DH启动子包含上游的起始密码子 最高达-164 bp的GAP-DH蛋白作为最小单位。 由于GAP-DH启动子的大小小，所以能够有效地在酵母中表达生理活性物质，可以简化DNA的重组。

公开(公告)号：US5453264A

公开(公告)日：1995-09-26

申请号：US204164

申请日：1994-03-03

申请人： Fumio Mori ,  Tadashi Okano ,  Kazuki Murakami ,  Masakazu Shintome ,  Hiromichi Mukai ,  Ikuko Miyagi ,  Takashi Imagawa ,  Sang-Won Kim ,  Taro Marukawa ,  Takahiro Kozuka

发明人： Fumio Mori ,  Tadashi Okano ,  Kazuki Murakami ,  Masakazu Shintome ,  Hiromichi Mukai ,  Ikuko Miyagi ,  Takashi Imagawa ,  Sang-Won Kim ,  Taro Marukawa ,  Takahiro Kozuka

IPC分类号： A61K49/06 ,  C07C229/16 ,  C07C237/04 ,  A61K49/00 ,  A61K31/295 ,  A61K31/32

CPC分类号： C07C229/16 ,  A61K49/06 ,  C07C237/04 ,  Y10T436/24

摘要： A compound of the following formula ##STR1## wherein m is an integer of 1 to 3, R.sub.1 and R.sub.2 are the same or different and each is hydrogen atom or lower alkyl, and R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are the same or different and each is hydroxy or a ##STR2## (wherein n is 0 or 1, X is --NH-- or --O--, Y is alkylene, A is hydrogen atom, lower alkyl, lower alkoxy, halogen atom or trifluoromethyl, and B is alkyl or alkenyl), with the proviso that two or three of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are hydroxyl groups and that when two of them are hydroxyl groups, the cases where R.sub.3 and R.sub.5 are hydroxy, and R.sub.4 and R.sub.6 are hydroxy are excluded; a complex compound comprising said compound and a metallic atom; and a diagnostic agent containing said complex compound. The above compound is useful as a chelating agent and the complex compound comprising said compound and a metallic atom exhibits superior characteristics as a contrast medium for image diagnosis.

摘要翻译： 下式的化合物，其中m为1〜3的整数，R 1和R 2相同或不同，各自为氢原子或低级烷基，R 3，R 4，R 5和R 6相同或不同， （其中n为0或1，X为-NH-或-O-，Y为亚烷基，A为氢原子，低级烷基，低级烷氧基，卤素原子或三氟甲基，B为烷基 或烯基），条件是R3，R4，R5和R6中的两个或三个为羟基，当两个或三个为羟基时，排除R3和R5为羟基，R4和R6为羟基的情况; 包含所述化合物和金属原子的络合物; 和含有所述复合化合物的诊断剂。 上述化合物可用作螯合剂，并且包含所述化合物和金属原子的络合物表现出作为图像诊断的造影剂的优异特性。

公开(公告)号：US06926884B2

公开(公告)日：2005-08-09

申请号：US10220610

申请日：2001-03-02

申请人： Yasuo Ikeda ,  Hiroshi Saito ,  Hiromichi Mukai ,  Yoshiyuki Mori ,  Mitsuru Murata

发明人： Yasuo Ikeda ,  Hiroshi Saito ,  Hiromichi Mukai ,  Yoshiyuki Mori ,  Mitsuru Murata

IPC分类号： A61K38/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/14 ,  A61K51/08 ,  A61P7/02 ,  A61P7/04 ,  A61P9/00 ,  A61P29/00 ,  C07K14/705 ,  A61K38/14 ,  A61K47/34 ,  C07K14/475

CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K47/544 ,  A61K47/60 ,  A61K47/64 ,  A61K47/6911 ,  A61K49/0002 ,  A61K49/085 ,  A61K49/14

摘要： The present invention provides a conjugate wherein GP (glycoprotein) Ib and a lipid are bonded via polyalkylene oxide. The present invention also provides a complex (GPIb lipid complex) containing this conjugate and a free lipid. The GPIb lipid complex is expected to have a potential for practical application in a wide range, as a platelet substitute, a pharmaceutical agent for the prophylaxis or treatment of angiopathy, vascular damage and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent thereof. Moreover, the GPIb lipid complex of the present invention is also superior in retention property in blood, which enables continuous expression of a pharmacological action. The conjugate of the present invention is highly utilizable as an active ingredient of the GPIb lipid complex of the present invention.

摘要翻译： 本发明提供了通过聚环氧烷键合GP（糖蛋白）1b和脂质的结合物。 本发明还提供了含有该缀合物和游离脂质的复合物（GPIb脂质复合物）。 预期GPIb脂质复合物在广泛范围内具有实际应用的潜力，作为血小板替代物，用于预防或治疗血管病，血管损伤和血栓形成的药剂，对vWF缺乏症的诊断等，生物 或医用试剂，用于筛选血小板聚集抑制剂或抗血栓形成的试剂等。 本发明的GPIb脂质复合物也可用作诊断血管损伤或血栓形成的位置，或其治疗剂。 此外，本发明的GPIb脂质复合物在血液中的保留性也优异，能够连续表达药理作用。 本发明的缀合物作为本发明的GPIb脂质复合物的活性成分是高度可利用的。

公开(公告)号：US5575986A

公开(公告)日：1996-11-19

申请号：US423451

申请日：1995-04-19

申请人： Fumio Mori ,  Tadashi Okano ,  Kazuki Murakami ,  Masakazu Shintome ,  Hiromichi Mukai ,  Ikuko Miyagi ,  Takashi Imagawa ,  Sang-Won Kim ,  Taro Marukawa ,  Takahiro Kozuka

发明人： Fumio Mori ,  Tadashi Okano ,  Kazuki Murakami ,  Masakazu Shintome ,  Hiromichi Mukai ,  Ikuko Miyagi ,  Takashi Imagawa ,  Sang-Won Kim ,  Taro Marukawa ,  Takahiro Kozuka

IPC分类号： A61K49/06 ,  C07C229/16 ,  C07C237/04 ,  A61K49/00 ,  A61K31/295 ,  A61K31/32

CPC分类号： C07C229/16 ,  A61K49/06 ,  C07C237/04 ,  Y10T436/24

摘要： A compound of the following formula ##STR1## wherein m is an integer of 1 to 3, R.sub.1 and R.sub.2 are the same or different and each is hydrogen atom or lower alkyl, and R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are the same or different and each is hydroxy or a group of the formula ##STR2## (wherein n is 0 or 1, X is --NH-- or --O--, Y is alkylene, A is hydrogen atom, lower alkyl, lower alkoxy, halogen atom or trifluoromethyl, and B is alkyl or alkenyl), with the proviso that two or three of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are hydroxyl groups and that when two of them are hydroxyl groups, the cases where R.sub.3 and R.sub.5 are hydroxy, and R.sub.4 and R.sub.6 are hydroxy are excluded; a complex compound comprising said compound and a metallic atom; and a diagnostic agent containing said complex compound. The above compound is useful as a chelating agent and the complex compound comprising said compound and a metallic atom exhibits superior characteristics as a contrast medium for image diagnosis.

摘要翻译： 下式的化合物，其中m为1〜3的整数，R 1和R 2相同或不同，各自为氢原子或低级烷基，R 3，R 4，R 5和R 6相同或不同， （其中n为0或1，X为-NH-或-O-，Y为亚烷基，A为氢原子，低级烷基，低级烷氧基，卤原子或三氟甲基） 并且B是烷基或烯基），条件是R3，R4，R5和R6中的两个或三个是羟基，当其中两个是羟基时，其中R3和R5是羟基，R4和R6是 羟基被排除; 包含所述化合物和金属原子的络合物; 和含有所述复合化合物的诊断剂。 上述化合物可用作螯合剂，并且包含所述化合物和金属原子的络合物表现出作为图像诊断的造影剂的优异特性。