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1. 发明申请

WO2004005550A3 METHOD OF SCREENING FOR ANTIDIABETIC AGENTS 审中-公开
标题翻译：抗生素代谢筛选方法
公开(公告)号：WO2004005550A3
公开(公告)日：2004-04-15
申请号：PCT/JP0308523
申请日：2003-07-04
申请人： FUJISAWA PHARMACEUTICAL CO , FUJIMURA TAKAO , SAKUMA HIROYUKI , KIMURA CHIAKI , OE TOMOYA , ARAMORI ICHIRO
发明人： FUJIMURA TAKAO , SAKUMA HIROYUKI , KIMURA CHIAKI , OE TOMOYA , ARAMORI ICHIRO
IPC分类号： A61P3/08 , G01N33/50 , G01N33/68 , G01N33/92
CPC分类号： G01N33/5044 , G01N33/5008 , G01N33/5023 , G01N33/6872 , G01N33/92 , G01N2333/70567 , G01N2800/042
摘要： A method of screening for an antidiabetic agent that lowers blood glucose level without inducing obesity and/or insulin resistance, is provided. The method comprises measuring the expression level of a nuclear peroxisome proliferator-activated receptor g (PPARg)-induced adipogenic gene in mature adipocytes in the presence of a test compound or a PPARg full agonist and selecting a compound that results in an expression level significantly lower than that measured using the PPARg full agonist. The method may further comprise the same steps except for using differentiating adipocytes to select a compound that results in an expression level comparable to or higher than that measured using the PPARg full agonist. A kit used for the above screening method, a compound obtainable by the screening method, a pharmaceutical composition containing such a compound, and a method lowering the blood glucose level without causing obesity and/or insulin resistance using the compound, are also provided.
摘要翻译：提供了筛选降低血糖水平而不诱导肥胖和/或胰岛素抵抗的抗糖尿病药的方法。该方法包括在受试化合物或PPARg全激动剂的存在下测量成熟脂肪细胞中核过氧化物酶体增殖物激活受体g（PPARg）诱导的脂肪形成基因的表达水平，并选择导致表达水平显着降低的化合物比使用PPARg全激动剂测量的。该方法可以进一步包括相同的步骤，除了使用分化脂肪细胞来选择导致与使用PPARg全激动剂测量的表达水平相当或更高的表达水平的化合物。还提供了用于上述筛选方法的试剂盒，通过筛选方法获得的化合物，含有这种化合物的药物组合物，以及使用该化合物降低血糖水平而不引起肥胖和/或胰岛素抵抗的方法。

2. 发明专利

JPH0898686A VARIANT TYPE CEPHALOSPORIN C ACYLASE AND ITS PRODUCTION 失效
公开(公告)号：JPH0898686A
公开(公告)日：1996-04-16
申请号：JP23927294
申请日：1994-10-03
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： SAITO YOSHIMASA , FUJIMURA TAKAO , ISHII YOSHINORI
IPC分类号： C12N15/09 , C12N1/21 , C12N9/80 , C12P35/06 , C12R1/19
摘要： PURPOSE: To obtain the subject new enzyme having a specific amino acid sequence as a form of a precursor before processing into α-subunit and β-subunit in a host cell and capable of decomposing cephalosporin C into 7- aminocephalosporanic acid. CONSTITUTION: This cephalosporin C acylase is a new variant type enzyme in which an amino acid sequence as a precursor form before processing into α-subunit and β-subunit in a host cell is expressed by formula I (A1-169 is same amino acid sequence as an amino acid sequence from Thr1 to Phe169 of natural cephalosporin C acylase; A171-773 is same amino acid sequence as an amino acid sequence from Len171 to Ala773 of natural cephalosporin C acylase; X1 is an amino acid other than Lys) and hydrolyzes cephalosporin C of formula II (R1 is a cetoxy, OH, H; R2 is a carboxy acyl) to 7-aminocephalosporanic acid of formula III. The cephalosporin C acylase is obtained by manifesting a gene in which 170th amino acid of natural type enzyme gene is changed in the host cell.

3. 发明专利

JPH07313161A 7-BETA-(-(4-CARBOXYBUTANAMIDO)-CEPHALOSPORANIC ACID ACYLASE AND ITS PRODUCTION 失效
公开(公告)号：JPH07313161A
公开(公告)日：1995-12-05
申请号：JP11006694
申请日：1994-05-24
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： SAITO YOSHIMASA , FUJIMURA TAKAO , ISHII YOSHINORI , TAKANORI HITOSHI
IPC分类号： C12N15/09 , C12N1/21 , C12N9/80 , C12R1/19
摘要： PURPOSE:To obtain the subject acylase useful for producing 7- aminocephalosporanic acid which is an intermediate for semisynthetic cephem- based antibiotics. CONSTITUTION:This 7-beta-(4-carboxybutanamido)-cephalosporanic acid acylase has an amino acid sequence in which a part of the N-terminal sequence in a natural type 7-beta-(4-carboxybutanamido)-cephalosporanic acid is substituted with Met-Leu-Ala-Glu-Pro-Thr, Met-Phe-Pro-Thr, Met-Phe-Tyr-Phe-Glu-Pro-Thr, Met-Phe-Tyr-Phe-Leu-A a-Glu-Pro-Thr or Met-Tyr-Tyr-Phe-Pro-Thr. The 7-beta-(4- carboxybutanamido)-cephalosporanic acid acylase is obtained by culturing a host cell transformed with an expression vector containing a DNA capable of coding the 7-beta-(4-carboxybutanamido)-cephalosporanic acid acylase in a culture medium.

4. 发明专利

JPH06225761A NEW MUTANT GAMMA-GLUTAMYL TRANSPEPTIDASE 失效
公开(公告)号：JPH06225761A
公开(公告)日：1994-08-16
申请号：JP1892693
申请日：1993-02-05
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： NIWA MINEO , FUJIMURA TAKAO , SAITO YOSHIMASA
IPC分类号： C12N9/10 , C12N15/09 , C12N15/54 , C12R1/19
摘要： PURPOSE:To provide a new and high active mutant gamma-glutamyl transpeptidase which is useful as an enzyme producing gamma-glutamyldopa of vasodilative activity by replacing the Lys at a specific site in gamma-glutamyl transpeptidase of Escherichia coli with another amino acid. CONSTITUTION:The cDNA including the gene encoding natural gamma-glutamyl transpeptidase isolated from Escherichia coli by the usual cloning is subjected to enzymatic treatment with restriction enzyme, alkali phosphatase, nucleotide kinase, DNA kinase and DNA polymerase to form a mutant DNA encoding E.c. natural y glutamyl transpeptidase in which the Lys at 332 position from the N-terminus is replaced with another amino acid. Then, the DNA is incorporated into the expression vector and introduced into the host cells for transformation. Finally, the cells are cultured to produce the new mutant gamma-glutamyl transpeptidase of high activity.

5. 发明专利

AU2003292680A1 METHOD OF SELECTING NOVEL IMMUNOSUPPRESSANT 未知
公开(公告)号：AU2003292680A1
公开(公告)日：2004-07-29
申请号：AU2003292680
申请日：2003-12-26
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： MATSUOKA HIDEAKI , FUJIMURA TAKAO , HAYASHI MASAKO , ARAMORI ICHIRO
IPC分类号： A61P37/06 , A61P43/00 , C12Q1/34 , G01N33/573 , C12N15/09 , C12N9/14 , C12Q1/68 , C12Q1/02 , A61K45/00
摘要： The present invention provides a method of selecting an IL-2 production inhibitor and/or an immunocyte proliferation inhibitor having low GATA-1 production inhibitory activity, which comprises measuring the HDAC4 and/or HDAC8 inhibitory activity of a test substance, and a method of selecting an immunosuppressant having low thrombocytopenic activity, which comprises measuring the HDAC4 and/or HDAC8 inhibitory activity of a test HDAC inhibitor.

6. 发明专利

HU9601151D0 A NEW CEPHALOSPORIN C ACYLASE 未知
公开(公告)号：HU9601151D0
公开(公告)日：1996-06-28
申请号：HU9601151
申请日：1994-10-26
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： FUJIMURA TAKAO , ISHII YOSHINORI , NIWA MINEO , NOGUCHI YUJI , SAITO YOSHIMASA
IPC分类号： C12N15/09 , C12N1/21 , C12N9/14 , C12N9/80 , C12N15/55 , C12P35/02 , C12R1/19
摘要： PCT No. PCT/JP94/01799 Sec. 371 Date May 1, 1996 Sec. 102(e) Date May 1, 1996 PCT Filed Oct. 26, 1994 PCT Pub. No. WO95/12680 PCT Pub. Date May 11, 1995A mutant CC acylase wherein at least one amino acid at the Ala49, Met164, Ser166, Met174, Glu358, Met465, Met506, or Met750 position of the amino acid sequence of the native CC acylase is replaced by a different amino acid, a DNA coding therefor, an expression vector containing the said DNA, a microorganism transformed with the said expression vector, the production of the CC acylase by culturing the said transformant, and use thereof for the production of a compound. The mutant CC acylase of the invention has desirable properties in terms of enzymatic potency, alteration of pH profile, efficiency of processing, and the like.

7. 发明专利

AU2003245051A8 Method of screening for antidiabetic agents 未知
公开(公告)号：AU2003245051A8
公开(公告)日：2004-01-23
申请号：AU2003245051
申请日：2003-07-04
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： FUJIMURA TAKAO , ARAMORI ICHIRO , SAKUMA HIROYUKI , OE TOMOYA , KIMURA CHIAKI
IPC分类号： A61P3/08 , C12Q1/68 , G01N33/50 , G01N33/68 , G01N33/92

8. 发明专利

DE69430067D1 未知
公开(公告)号：DE69430067D1
公开(公告)日：2002-04-11
申请号：DE69430067
申请日：1994-10-26
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： NIWA MINEO , SAITO YOSHIMASA , FUJIMURA TAKAO , ISHII YOSHINORI , NOGUCHI YUJI
IPC分类号： C12N15/09 , C12N1/21 , C12N9/14 , C12N9/80 , C12N15/55 , C12P35/02 , C12R1/19 , C12N15/70
摘要： PCT No. PCT/JP94/01799 Sec. 371 Date May 1, 1996 Sec. 102(e) Date May 1, 1996 PCT Filed Oct. 26, 1994 PCT Pub. No. WO95/12680 PCT Pub. Date May 11, 1995A mutant CC acylase wherein at least one amino acid at the Ala49, Met164, Ser166, Met174, Glu358, Met465, Met506, or Met750 position of the amino acid sequence of the native CC acylase is replaced by a different amino acid, a DNA coding therefor, an expression vector containing the said DNA, a microorganism transformed with the said expression vector, the production of the CC acylase by culturing the said transformant, and use thereof for the production of a compound. The mutant CC acylase of the invention has desirable properties in terms of enzymatic potency, alteration of pH profile, efficiency of processing, and the like.

9. 发明专利

AT214098T 未知
公开(公告)号：AT214098T
公开(公告)日：2002-03-15
申请号：AT94931165
申请日：1994-10-26
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： NIWA MINEO , SAITO YOSHIMASA , FUJIMURA TAKAO , ISHII YOSHINORI , NOGUCHI YUJI
IPC分类号： C12N15/09 , C12N1/21 , C12N9/14 , C12N9/80 , C12N15/55 , C12P35/02 , C12R1/19 , C12N15/70
摘要： PCT No. PCT/JP94/01799 Sec. 371 Date May 1, 1996 Sec. 102(e) Date May 1, 1996 PCT Filed Oct. 26, 1994 PCT Pub. No. WO95/12680 PCT Pub. Date May 11, 1995A mutant CC acylase wherein at least one amino acid at the Ala49, Met164, Ser166, Met174, Glu358, Met465, Met506, or Met750 position of the amino acid sequence of the native CC acylase is replaced by a different amino acid, a DNA coding therefor, an expression vector containing the said DNA, a microorganism transformed with the said expression vector, the production of the CC acylase by culturing the said transformant, and use thereof for the production of a compound. The mutant CC acylase of the invention has desirable properties in terms of enzymatic potency, alteration of pH profile, efficiency of processing, and the like.

10. 发明专利

AU2003245051A1 METHOD OF SCREENING FOR ANTIDIABETIC AGENTS 未知
公开(公告)号：AU2003245051A1
公开(公告)日：2004-01-23
申请号：AU2003245051
申请日：2003-07-04
申请人： FUJISAWA PHARMACEUTICAL CO
发明人： SAKUMA HIROYUKI , KIMURA CHIAKI , OE TOMOYA , ARAMORI ICHIRO , FUJIMURA TAKAO
IPC分类号： A61P3/08 , C12Q1/68 , G01N33/50 , G01N33/68 , G01N33/92

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