公开(公告)号：EP1445249A1

公开(公告)日：2004-08-11

申请号：EP02781763.4

申请日：2002-11-13

申请人： TOYAMA CHEMICAL CO., LTD. ,  Hirono, Shuichi ,  Shiozawa, Shunichi

发明人： CHAKI, Hisaaki ,  KOTSUBO, Hironori ,  TANAKA, Tadashi ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC分类号： C07C59/90 ,  C07C69/734 ,  C07C69/76 ,  C07C205/34 ,  C07C219/32 ,  C07C255/54 ,  C07C255/37 ,  C07C271/64 ,  C07C235/42 ,  C07C311/29 ,  C07C311/51 ,  C07C311/53 ,  C07C317/22 ,  C07C323/19 ,  A61K31/192

CPC分类号： C07C235/42 ,  A61K31/192 ,  C07C59/90 ,  C07C65/34 ,  C07C65/40 ,  C07C69/738 ,  C07C69/76 ,  C07C69/88 ,  C07C69/94 ,  C07C205/34 ,  C07C217/76 ,  C07C255/54 ,  C07C259/10 ,  C07C271/64 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/18

摘要： A benzophenone derivative represented by the following formula:
wherein

R 1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R 2 represents, for example, a carboxyl group optionally protected with alkyl;
R 3 represents, for example, an optionally protected hydroxyl group; R 4 represents, for example, an optionally substituted cycloalkyloxy group; and R 5 represents, for example, a hydrogen atom,
   or a salt thereof has anti-arthritic activity, inhibits bone destruction caused by arthritis, and provides high safety and excellent pharmacokinetics and thus is useful as therapeutic agent for arthritis. These compounds have inhibitory effect on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression of AP-1 is involved.

公开(公告)号：EP1471143A1

公开(公告)日：2004-10-27

申请号：EP03700501.4

申请日：2003-01-08

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KOMAI, Koichiro ,  NAKATSUKASA, Mikiko

IPC分类号： C12N15/12 ,  C07K14/515 ,  C12Q1/68 ,  G01N33/566 ,  A61K45/00 ,  A61K38/17 ,  A61K48/00 ,  A61P29/00

CPC分类号： G01N33/564 ,  C07K14/47 ,  C07K14/4713 ,  C12Q1/6883 ,  C12Q2600/156 ,  G01N2800/102

摘要： An gene was identified as a RA disease susceptibility gene on Human Chromosome 8, the gene coding a protein that has an amino acid sequence shown in SEQ. ID NO.1 and that has such mutation that glycine is inserted as a 269th amino acid in the sequence. Moreover, it was found that mutation of the gene and the protein relate to onset of RA. Achieved is a method of evaluating with high accuracy the onset or onset possibility of RA by using the mutation.

摘要翻译： 编码具有498个氨基酸（S1）的完全限定序列的血管生成素-1蛋白质的类风湿关节炎疾病敏感性基因（I）是在269位具有甘氨酸插入变异的说明书中给出的新的。 包括以下独立权利要求：（1）由（S1）组成的蛋白质（II）和序列269位置处的甘氨酸插入变异; （2）确定类风湿关节炎的发病; （3）通过检测（I）或（II）的存在或不存在或通过使用确定试剂盒来确定类风湿性关节炎的发作; （4）治疗类风湿关节炎; 和（5）用于治疗具有（II）的患者类风湿性关节炎的治疗药物。 活动：抗风湿; 抗关节炎。 没有给出生物数据。 作用机制：促血管生成素-1蛋白激动剂; 基因治疗。

公开(公告)号：EP1164190A1

公开(公告)日：2001-12-19

申请号：EP00909754.4

申请日：2000-03-21

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KOMAI, Koichiro

IPC分类号： C12N15/12 ,  C12Q1/68 ,  C07K14/47 ,  C07K16/18

CPC分类号： C07K14/4713

摘要： As a disease gene for rheumatoid arthritis present in human chromosome X and a method of diagnosing rheumatoid arthritis, a disease gene, which is a mutant of protooncogene Dbl transcribing an mRNA that encodes the cDNA of which the sequence from the 2679th to 2952nd bases is shown in SEQ ID NO: 1, which disease gene transcribes an mRNA encoding the cDNA of which the region from the 20th to 274th bases in SEQ ID NO: 1 is substituted with the sequence of SEQ ID NO: 2, and a method for diagnosing rheuma toid arthritis by detecting the mRNA of the above-described gene or its expression product in a biological specimen, is provided.

摘要翻译： 作为人类染色体X中存在的类风湿关节炎的疾病基因和诊断类风湿性关节炎的方法，显示了一种疾病基因，其是表达编码第2679位至第2952位碱基序列的cDNA的mRNA的原癌基因Dbl的突变体 在SEQ ID NO：1中，哪个疾病基因转录成编码SEQ ID NO：1中第20位至第274位碱基的cDNA的mRNA被SEQ ID NO：2的序列取代，以及用于诊断风湿病的方法 提供了通过检测生物样本中上述基因或其表达产物的mRNA的关节炎。

公开(公告)号：EP1164190B1

公开(公告)日：2011-06-29

申请号：EP00909754.4

申请日：2000-03-21

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KOMAI, Koichiro

IPC分类号： C12N15/12 ,  C12Q1/68 ,  C07K14/47 ,  C07K16/18

CPC分类号： C07K14/4713

摘要： A rheumatoid arthritis gene occurring in human X chromosome which is a variant sequence of a proto-oncogene Dbl gene transcribing an mRNA encoding a cDNA the sequence of the bases at the 2679- to 2952-positions of which is represented by SEQ ID NO:1, characterized by transcribing an mRNA encoding a cDNA wherein the region of the bases from the 19- to 274-positions of SEQ ID NO:1 has been substituted by the sequence represented by SEQ ID NO:2; and a method for diagnosing rheumatoid arthritis characterized by detecting the occurrence of mRNA of the above-described gene or its expression product in a biological sample.

公开(公告)号：EP1335021A1

公开(公告)日：2003-08-13

申请号：EP01978865.2

申请日：2001-10-24

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KONISHI, Yoshitake

IPC分类号： C12N15/12 ,  C07K14/47 ,  C12Q1/68 ,  G01N33/50 ,  A61K38/17 ,  A61K48/00

CPC分类号： C12Q1/6883 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4713 ,  C07K14/70539 ,  C12Q2600/156

摘要： Mutations in a genome associating in rheumatoid arthritis (RA) are found in human DR3 genomic DNA having the base sequence represented by SEQ ID NO:1. The invention provides a genome having such mutations, transcripts thereof, a method of highly accurately evaluating the RA onset or the RA onset possibility by using the mutations thereof, an evaluation kit therefor, and a therapeutic method and remedies for RA.

摘要翻译： 在基因组中在类风湿关节炎（RA）相关联的突变在具有由SEQ ID NO：1所示的碱基序列的人类基因组DR3 DNA中发现 本发明提供具有突变检查基因组，转录物，高度精确地设定的评价发病RA或通过使用突变体，到评估板为此在RA发病可能性和治疗方法和补救措施RA的方法。

公开(公告)号：EP1384777B1

公开(公告)日：2009-05-27

申请号：EP02713262.0

申请日：2002-03-29

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KOMAI, Koichiro ,  YAGI, Hirofumi ,  MATSUURA, Nao

IPC分类号： C12N15/09 ,  C12Q1/68 ,  G01N33/566 ,  G01N33/50

CPC分类号： C12Q1/6883 ,  C12Q2600/156

摘要： Genomic DNAs derived from the genomic DNA represented by SEQ ID NO:1 by at least one of the following variations; a method of diagnosing human rheumatoid arthritis by using these variations; a method of judging the onset risk thereof; and a diagnostic kit for detecting the same: (1) substitution of cytosine (c) at the 1987-position into thymine (t); (2) substitution of thymine (t) at the 3664-position into guanine (g); and (3) substitution of adenine (a) at the 3769-position into cytosine (c).

公开(公告)号：EP1471143B1

公开(公告)日：2008-02-27

申请号：EP03700501.4

申请日：2003-01-08

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KOMAI, Koichiro ,  NAKATSUKASA, Mikiko

IPC分类号： C07K14/515 ,  C12Q1/68 ,  A61K45/00 ,  A61K38/17 ,  A61K48/00

CPC分类号： G01N33/564 ,  C07K14/47 ,  C07K14/4713 ,  C12Q1/6883 ,  C12Q2600/156 ,  G01N2800/102

摘要： A gene comprising the amino acid represented by SEQ ID NO:1 and having a glycine insertion mutation as the 269th amino acid in the sequence is identified as an RA disease sensitive gene on human 8th chromosome. Moreover, it is clarified that the mutation in this gene and its protein relates to the onset of RA so as to establish a method of highly accurately judging the onset of RA or the onset risk thereof, etc.

公开(公告)号：EP1384777A1

公开(公告)日：2004-01-28

申请号：EP02713262.0

申请日：2002-03-29

申请人： Shiozawa, Shunichi

发明人： SHIOZAWA, Shunichi ,  KOMAI, Koichiro ,  YAGI, Hirofumi ,  MATSUURA, Nao

IPC分类号： C12N15/09 ,  C12Q1/68 ,  G01N33/566 ,  G01N33/50

CPC分类号： C12Q1/6883 ,  C12Q2600/156

摘要： A genomic DNA involved in rheumatoid arthritis, a method of diagnosing rheumatoid arthritis or a method of judging onset risk of rheumatoid arthritis, and a diagnostic kit for diagnosing rheumatoid arthritis or judging onset risk of rheumatoid arthritis, which genomic DNA comprises at least one of the following mutations in genomic DNA consisting of the base sequence of SEQ ID NO: 1:

(1) substitution of thymine (t) for cytosine (c) at the position-1987;
(2) substitution of guanine (g) for thymine (t) at the position-3664; and
(3) substitution of cytosine (c) for adenine (a) at the position-3769.

摘要翻译： 在类风湿性关节炎中涉及的基因组DNA，诊断类风湿关节炎或判断类风湿性关节炎的发病风险的方法的方法，以及用于诊断类风湿性关节炎或判断类风湿性关节炎，哪些基因组DNA包含的所述至少一个的发病风险的诊断试剂盒 在基因组DNA以下突变由SEQ ID NO：1的碱基序列的1：（1）胸腺嘧啶（T），用于在位置1987胞嘧啶（c）的取代基; （2）鸟嘌呤（G），用于在位置3664胸腺嘧啶（T）取代; 和（3）的胞嘧啶（c）中为腺嘌呤的取代（a）在所述位置第三千七百六十九

公开(公告)号：EP1445249B1

公开(公告)日：2012-11-07

申请号：EP02781763.4

申请日：2002-11-13

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： CHAKI, Hisaaki ,  KOTSUBO, Hironori ,  TANAKA, Tadashi ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC分类号： C07C59/90 ,  C07C69/734 ,  C07C69/76 ,  C07C205/34 ,  C07C219/32 ,  C07C255/54 ,  C07C255/37 ,  C07C271/64 ,  C07C235/42 ,  C07C311/29 ,  C07C311/51 ,  C07D333/56 ,  C07D333/38 ,  C07D409/12 ,  C07D239/96 ,  C07D261/20 ,  A61K31/192 ,  A61P29/00

CPC分类号： C07C235/42 ,  A61K31/192 ,  C07C59/90 ,  C07C65/34 ,  C07C65/40 ,  C07C69/738 ,  C07C69/76 ,  C07C69/88 ,  C07C69/94 ,  C07C205/34 ,  C07C217/76 ,  C07C255/54 ,  C07C259/10 ,  C07C271/64 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/18

公开(公告)号：EP2266557A1

公开(公告)日：2010-12-29

申请号：EP09735250.4

申请日：2009-04-20

申请人： Toyama Chemical Co., Ltd.

发明人： AIKAWA, Yukihiko ,  SHIOZAWA, Shunichi

IPC分类号： A61K31/194 ,  A61K31/42 ,  A61K31/423 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/573 ,  A61K45/06 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00

CPC分类号： A61K45/06 ,  A61K31/194 ,  A61K31/42 ,  A61K31/423 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/573 ,  A61K2300/00

摘要： Disclosed are use of a benzophenone derivative represented by general formula (I) or a salt thereof and one or more immunosuppressing agents in combination, and a pharmaceutical composition containing the benzophenone derivative or a salt thereof and one or more immunosuppressing agents. The use and the composition are useful for treatment or prevention of autoimmune diseases and the like. (In the formula, R 1 represents an optionally substituted heterocyclic group, a substituted phenyl group or the like; Z represents an alkylene group or the like; R 2 represents a carboxyl group, which may be protected by an alkyl group, or the like; R 3 represents an optionally protected hydroxyl group or the like; R 4 represents an optionally substituted cycloalkyloxy group or the like; and R 5 represents a hydrogen atom or the like.)

摘要翻译： 本发明公开了使用或由通式（I）表示的二苯甲酮衍生物在组合它们的盐和一种或多种免疫抑制剂，以及含有该二苯甲酮衍生物或其盐和一种或多种免疫抑制剂的药物组合物。 的使用和该组合物是用于治疗或预防自身免疫性疾病的等是有用的。 （式中，R 1 darstellt到任选取代的杂环基，取代的苯基或类似物; Z darstellt在亚烷基等; R 2表示羧基基团，其可通过在烷基保护，或类似 ，R 3 darstellt到任选保护的羟基基团等; R 4 darstellt到任选取代的环烷氧基等;且R 5表示氢原子等）。