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11. 发明专利

DE69030539D1 未知
公开(公告)号：DE69030539D1
公开(公告)日：1997-05-28
申请号：DE69030539
申请日：1990-08-10
申请人： MITSUBISHI CHEM CORP
发明人： KITAMURA NAOMI , MIYAZAWA KEIJI , DAIKUHARA YASUSHI , TSUBOUCHI HIROHITO , NAKA DAIJI , TAKAHASHI KAZUHIRO , MATSUI RIE , YOSHIYAMA YOSHIKO , ISHII TAKEHISA
IPC分类号： A61K38/00 , C07K14/475 , C12N15/16 , C07K14/00 , C12P21/02 , C12N5/10 , A61K38/08
摘要： According to the present invention, there are provided hepatic parenchymal cell growth factor obtained by recombinant DNA technology, a gene coding for the factor, an expression vector capable of expressing the gene, a cell, in particular animal cell, transformed with the expression vector, and a process for producing the hepatic parenchymal cell growth factor.

12. 发明专利

AT152124T 未知
公开(公告)号：AT152124T
公开(公告)日：1997-05-15
申请号：AT90115397
申请日：1990-08-10
申请人： MITSUBISHI CHEM CORP
发明人： KITAMURA NAOMI , MIYAZAWA KEIJI , DAIKUHARA YASUSHI , TSUBOUCHI HIROHITO , NAKA DAIJI , TAKAHASHI KAZUHIRO , MATSUI RIE , YOSHIYAMA YOSHIKO , ISHII TAKEHISA
IPC分类号： A61K38/00 , C07K14/475 , C12N15/16 , C07K14/00 , C12P21/02 , C12N5/10 , A61K38/08
摘要： According to the present invention, there are provided hepatic parenchymal cell growth factor obtained by recombinant DNA technology, a gene coding for the factor, an expression vector capable of expressing the gene, a cell, in particular animal cell, transformed with the expression vector, and a process for producing the hepatic parenchymal cell growth factor.

13. 发明专利

JPH0827026A PREVENTING AND THERAPEUTIC AGENT FOR HEPATOPATHY 失效
公开(公告)号：JPH0827026A
公开(公告)日：1996-01-30
申请号：JP17120794
申请日：1994-07-22
申请人： MITSUBISHI CHEM CORP
发明人： DAIKUHARA YASUSHI , ARAGAKI NAOKATSU
IPC分类号： A61K38/22 , A61K38/46 , A61K38/48 , A61P1/16
摘要： PURPOSE:To obtain a preventing and therapeutic agent for hepatopathy, capable of increasing the amount of an active type HGF in a patient suffering from the hepatopathy and effectively used as an indirect medicine for the hepatopathy. CONSTITUTION:This preventing and therapeutic agent contains a protease capable of acting on an inactive type single-stranded human hepatocyte growth factor (hHGF) and inducing the hHGF into a double-stranded hHGF as an active ingredient. Serine protease is preferred as the protease and a blood coagulant factor XII, a tissue plasminogen activator, a urokinase, blood plasma kallikrein and an HGF activator are cited and the use of the HGF activator is especially preferred. The HGF activator is a protein having 34000Da molecular weight measured by the sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and an amino acid sequence represented by the formula and its precursor protein having 96000Da molecular weight. Acute hepatitis, fulminant hepatitis, chronic hepatitis and cirrhosis are cited as the hepatopathy to which the preventing and therapeutic agent is applied.

14. 发明专利

JP2577091B2 失效
公开(公告)号：JP2577091B2
公开(公告)日：1997-01-29
申请号：JP20944989
申请日：1989-08-11
申请人： MITSUBISHI CHEM CORP
发明人： KITAMURA NAOMI , MYAZAWA KEIJI , DAIKUHARA YASUSHI , TSUBOCHI HIROHITO , NAKA DAICHI , TAKAHASHI KAZUNOBU
IPC分类号： C12N15/09 , A61K38/22 , A61P1/16 , A61P43/00 , C07K1/22 , C07K14/475 , C12N1/21 , C12N15/12 , C12P21/02 , C12R1/19

15. 发明专利

JPH1183854A ANTIBODY AGAINST HEPATOCELL GROWTH FACTOR AND HEPATOCELL GROWTH FACTOR MEASURING METHOD 失效
公开(公告)号：JPH1183854A
公开(公告)日：1999-03-26
申请号：JP24820297
申请日：1997-09-12
申请人： OTSUKA PHARMA CO LTD , MITSUBISHI CHEM CORP
发明人： DAIKUHARA YASUSHI , ONISHI TOMOKAZU , ISHIKAWA EIJI , HASHIDA SEIICHI
IPC分类号： G01N33/53 , G01N33/531 , G01N33/576 , G01N33/577
摘要： PROBLEM TO BE SOLVED: To provide a highly sensitive immunological measuring method of hepatocell growth factor(HGF), and an antibody used therefor and a preparing method for the antibody by obtaining the antibody linked to HGF from the vitellus of oviposited egg of a bird after charging HGF to the bird as the immunogen. SOLUTION: HGF is charged to a bird together with an adjuvant. For the inoculation a hypodermic injection is desirable. For the introjection of antibody per one injection, 0.01-10 mg or so is desirable. Since the oviposition of a specific antibody is made in the vitellus of egg of bird within a few weeks, the vitellus is separated from the egg subjected to the immunity, and lipoprotain and lipid are removed therefrom. The removement is subjected to treatment of organic solvent such as diethylether. The anti-HGF antibody value of the obtained solution is measured and one having a higher antibody value is selected. Saturated ammonium sulfate solution is added to this delipoprotein-delipid solution to perform salting-out sedimentation. Otherwise polymer such as polyethylene glycole is added thereto to coaggulate the antibody. Then, a centrifugal process is applied thereto and the antibody is dissolved with plysiological phosphoric buffering solution. Accordingly, a roughly prepared antibody is obtained.

16. 发明专利

JPH0835968A DIAGNOSIS METHOD FOR HEPATIC DISEASE 失效
公开(公告)号：JPH0835968A
公开(公告)日：1996-02-06
申请号：JP19210594
申请日：1994-07-22
申请人： MITSUBISHI CHEM CORP
发明人： DAIKUHARA YASUSHI , ARAGAKI NAOTOSHI , ISHII TAKEHISA , SATO MASANORI
IPC分类号： G01N33/53 , A61K39/395 , G01N33/576
摘要： PURPOSE:To make it possible to find hepatic disease in the early period by detecting the single-stranded human hepatocyte growth factor of the inactive type in human body fluid. CONSTITUTION:The single-stranded human hepatocyte growth factor of the inactive type (HGF) contained in human body fluid, e.g. blood, plasma, lymph, sweat, urine or the like, is detected by using antibody. The single-stranded HGF is the precursor of double-stranded HGF (active type). In this detection, any of the following methods is used: only the single-stranded HGF is specificaly detected; or the total sum of the single-stranded HGF and the double-stranded HGF is detected and the double-stranded HGF is subtracted. The antibodies for the single-stranded HGF and the double-stranded HGF are used for both methods. As the antibody, any of polyclonal antibody and monoclonal antibody can be used. The antibody is marked with enzyme such as, e.g. horseradish peroxidase and provided for enzyme immunoassay. The single-stranded HGF is not present in a healthy person and presents only in patients of acute, chronic, fluminant hepatitis, cirrhosis or the like. Therefore, the hepatic disease can be found at the early period.

17. 发明专利

JPH1156382A GENE CODING FOR HEPATOCYTE PROLIFERATION FACTOR 失效
公开(公告)号：JPH1156382A
公开(公告)日：1999-03-02
申请号：JP19459698
申请日：1998-07-09
申请人： MITSUBISHI CHEM CORP
发明人： KITAMURA NAOMI , MIYAZAWA KEIJI , DAIKUHARA YASUSHI , TSUBOUCHI HIROHITO , NAKA DAICHI , TAKAHASHI KAZUNOBU
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61P1/00 , A61P1/16 , C07K14/47 , C07K14/52 , C12N1/21 , C12N5/10 , C12P21/02 , C12R1/19 , C12R1/91
摘要： PROBLEM TO BE SOLVED: To provide the subject new gene composed of a gene coding for a hepatocyte proliferation factor, having a specific amino acid sequence and usable e.g. for the production of the proliferation factor useful as a liver regeneration promoter, liver function improver, hepatitis treating agent, hepatocirrhosis suppressing agent, etc. SOLUTION: This new gene coding for a hepatocyte proliferation factor is expressed by the sequence from the 30th glutamic acid to the 728th serine of the amino acid sequence expressed by the formula. The gene is useful e.g. for the production of a hepatocyte proliferation factor having possibility to be usable as a hepatic disease treating agent such as a liver regeneration promoter, a liver function improver, a hepatitis treating agent, a hepatocirrhosis suppressing agent, etc. The gene can be produced by screening a λ-phage cDNA library originated from human placenta by plaque hybridization method using a probe consisting of an oligonucleotide produced from a base sequence estimated from an amino acid sequence constituting a part of the hepatocyte proliferation factor.

18. 发明专利

JPH111499A HEPATOCYTE GROWTH FACTOR 失效
公开(公告)号：JPH111499A
公开(公告)日：1999-01-06
申请号：JP19459798
申请日：1998-07-09
申请人： MITSUBISHI CHEM CORP
发明人： KITAMURA NAOMI , MIYAZAWA KEIJI , DAIKUHARA YASUSHI , TSUBOUCHI HIROHITO , NAKA DAICHI , TAKAHASHI KAZUNOBU
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61P1/00 , A61P1/16 , C07K14/52 , C12N1/21 , C12N5/00 , C12N5/10 , C12N15/00 , C12P21/02 , C12R1/19 , C12R1/91
摘要： PROBLEM TO BE SOLVED: To obtain the subject new factor useful for evaluating precise function and liver regeneration effect, etc., in liver damage in vitro, because the factor can be obtained in large amounts from a recombinant DNA technique and having possibility used as a liver-regenerating promoter, a liver function improver, hepatitis treating agent, liver cirrhosis suppressor, etc. SOLUTION: This hepatocyte growth factor is represented by a sequence ranging from 30th glutamic acid to 728th serine among amino acid sequence of the formula. The factor is obtained by decomposing, e.g. a hepatocyte growth factor (kHGF) purified from plasma of a patient attached by fulminant hepatitis with proteolytic enzyme, separating the produced peptide fragment, analyzing the amino acid sequence, screening a gene encoding kHGF from CDNA library, preferably placenta cDNA library by using an oligonucleotide prepared from a base sequence estimated from the amino acid sequence as a probe, inserting the gene into a plasmid to form a plasmid for expressing the protein and expressing kHGF to an animal cell, etc., transformed by the plasmid.

19. 发明专利

JPH09249697A HEPATOCYTIC GROWTH FACTOR 失效
公开(公告)号：JPH09249697A
公开(公告)日：1997-09-22
申请号：JP7191196
申请日：1996-03-27
申请人： MITSUBISHI CHEM CORP
发明人： KITAMURA NAOMI , MIYAZAWA KEIJI , DAIKUHARA YASUSHI , TSUBOUCHI HIROHITO , NAKA DAICHI , TAKAHASHI KAZUNOBU
IPC分类号： C12N15/09 , A61K38/00 , A61P1/16 , C07H21/04 , C07K14/52 , C07K19/00 , C12N1/21 , C12N5/00 , C12N5/10 , C12P21/02 , C12R1/19 , C12R1/91
摘要： PROBLEM TO BE SOLVED: To obtain a new hepatocytic growth factor, having a specific amino acid sequence, available in a large amount according to a recombinant DNA technique and useful as a therapeutic agent, etc., for hepatopathy such as a hepatic regeneration promoter, a hepatic function improver, a therapeutic agent for hepatitis or a suppressant for cirrhosis. SOLUTION: This new hepatic growth factor has an amino acid sequence represented by the formula and the possibility of providing a therapeutic agent, etc., for hepatopathy such as a hepatic regeneration promoter, a hepatic function improver, a therapeutic agent for hepatitis or a suppressant for cirrhosis. The hepatocytic growth factor is obtained in a large amount by screening a hepatic cDNA library derived from a human with probe, comprising a peptide fragment prepared by treating a human hepatic cell growth factor (hHGF) isolated from a blood plasma of a patient suffering from fulminant hepatitis with an Achromobacter protease I, etc., integrating the resultant gene capable of coding the hepatocytic growth factor into a vector and expressing the gene in the host cell.

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