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1.发明申请Polynucleotide Participating In Rheumatoid Arthritis And Utilization Of The Same 有权多核苷酸参与类风湿关节炎及其利用公开(公告)号：US20090035752A1
公开(公告)日：2009-02-05
申请号：US10590823
申请日：2004-11-25
CPC分类号： C12Q1/6883 , C12Q2600/154 , C12Q2600/158
摘要： Analysis is made on the DNA methylation of the region (including a promoter region) upstream from the translation initiation point of a rheumatoid arthritis-associated gene DR3 in human genome. As a result, it is found out that an allele-specific methylation occurs in a CpG sequence located about −380 to −180 bp upstream from translation initiation point (ATG) of the gene DR3. It is further found out that the CpG sequences downstream therefrom of the genes DR3 originating in healthy subjects are all in the unmethylated state, while methylated and unmethylated sequences are both observed in the genes DR3 originating in RA patients.
摘要翻译： 对人类基因组中类风湿性关节炎相关基因DR3的翻译起始点上游的区域（包括启动子区域）的DNA甲基化进行分析。 结果发现等位基因特异性甲基化发生在位于基因DR3的翻译起始点（ATG）上游约-380至-180bp的CpG序列中。 进一步发现源自健康受试者的基因DR3下游的CpG序列都处于非甲基化状态，而在来自RA患者的基因DR3中都观察到甲基化和未甲基化的序列。
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公开(公告)号：US07741030B2
公开(公告)日：2010-06-22
申请号：US10590823
申请日：2004-11-25
CPC分类号： C12Q1/6883 , C12Q2600/154 , C12Q2600/158
摘要： Analysis is made on the DNA methylation of the region (including a promoter region) upstream from the translation initiation point of a rheumatoid arthritis-associated gene DR3 in human genome. As a result, it is found out that an allele-specific methylation occurs in a CpG sequence located about −380 to −180 bp upstream from translation initiation point (ATG) of the gene DR3. It is further found out that the CpG sequences downstream therefrom of the genes DR3 originating in healthy subjects are all in the unmethylated state, while methylated and unmethylated sequences are both observed in the genes DR3 originating in RA patients.
摘要翻译： 对人类基因组中类风湿性关节炎相关基因DR3的翻译起始点上游的区域（包括启动子区域）的DNA甲基化进行分析。 结果发现等位基因特异性甲基化发生在位于基因DR3的翻译起始点（ATG）上游约-380至-180bp的CpG序列中。 进一步发现源自健康受试者的基因DR3下游的CpG序列都处于非甲基化状态，而在来自RA患者的基因DR3中都观察到甲基化和未甲基化的序列。
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公开(公告)号：US20120046326A1
公开(公告)日：2012-02-23
申请号：US13287375
申请日：2011-11-02
IPC分类号： A61K31/423 , A61P19/10
CPC分类号： C07D261/20 , A61K31/423
摘要： Pharmaceutical agents characterized by containing benzophenone derivatives represented by the general formula: wherein the each substituent is as defined in the specification, or salts thereof have suppressive effect on RANKL production, suppressive effect on OPG reduction and inhibitory effects on differentiation/activation of osteoclasts, and are extremely useful for treating, for example therapy and/or prevention, of various diseases in which differentiation/activation of osteoclast are involved, such as osteoporosis.
摘要翻译： 其特征在于含有以下通式表示的二苯甲酮衍生物：其中各取代基如说明书中所定义，或其盐对RANKL产生具有抑制作用，对OPG降低的抑制作用以及对破骨细胞分化/活化的抑制作用，以及 对于治疗和/或预防涉及破骨细胞分化/活化的各种疾病如骨质疏松症是非常有用的。
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4.发明授权Disease susceptibility gene for rheumatoid arthritis, protein thereof, evaluation method and evaluation kit for evaluating onset possibility of rheumatoid arthritis by using those, and remedy and curing medicine for rheumatoid arthritis 有权用于类风湿关节炎的疾病易感基因，其蛋白质，评估方法和用于评估类风湿性关节炎发作可能性的评价试剂盒，以及用于治疗类风湿性关节炎药物公开(公告)号：US07615341B2
公开(公告)日：2009-11-10
申请号：US10501259
申请日：2003-01-08
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： 在人染色体8上将基因鉴定为RA疾病易感基因，编码具有SEQ ID NO：1所示氨基酸序列的蛋白质的基因。 证件号码。 1，并且具有这样的突变，甘氨酸作为序列中的第269个氨基酸被插入。 此外，发现基因和蛋白质的突变与RA的发病有关。 实现是通过使用突变以高精度评估RA的发作或发作可能性的方法。
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公开(公告)号：US07615538B2
公开(公告)日：2009-11-10
申请号：US10440256
申请日：2003-05-19
申请人： Shunichi Shiozawa
发明人： Shunichi Shiozawa
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/13
摘要： The invention provides a method for therapy of rheumatoid arthritis, which comprises administering double-stranded oligonucleotide comprising the nucleotide sequence of 5′-TGAGTCA-3′ to a patient who suffers rheumatoid arthritis.
摘要翻译： 本发明提供了一种治疗类风湿性关节炎的方法，其包括向患有类风湿性关节炎的患者施用包含5'-TGAGTCA-3'的核苷酸序列的双链寡核苷酸。
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公开(公告)号：US07314888B1
公开(公告)日：2008-01-01
申请号：US09830559
申请日：1999-11-05
申请人： Hisaaki Chaki , Tadakazu Takakura , Keiichi Tsuchida , Hironori Kotsubo , Yukihiko Aikawa , Shuichi Hirono , Shunichi Shiozawa
发明人： Hisaaki Chaki , Tadakazu Takakura , Keiichi Tsuchida , Hironori Kotsubo , Yukihiko Aikawa , Shuichi Hirono , Shunichi Shiozawa
IPC分类号： A61K31/18 , A61K31/19 , A61K31/195 , A61K31/235
CPC分类号： C07D207/333 , A61K38/00 , C07C59/64 , C07C59/84 , C07C65/24 , C07C65/34 , C07C65/36 , C07C65/38 , C07C65/40 , C07C69/738 , C07C69/94 , C07C229/34 , C07C233/01 , C07C233/47 , C07C235/20 , C07C235/84 , C07C251/32 , C07C251/48 , C07C251/60 , C07C255/49 , C07C275/24 , C07C311/06 , C07C311/51 , C07D207/08 , C07D209/42 , C07D235/26 , C07D277/60 , C07K7/06 , C07K7/64 , Y02P20/55
摘要： A compound or a salt thereof having the atom corresponding to N3 and the two or more atoms selected from N1, N2, N4 and N5, said atoms constitute the pharmacophore represented by the following formula: and inhibits the activity of transcription factor AP-1 and is useful as an agent for preventing and treating the diseases into which over expression of AP-1 participates and as an AP-1 inhibitor.
摘要翻译： 具有对应于N 3的原子的化合物或其盐和选自N 1，N 2，N 2的两个或多个原子， 所述原子构成由下式表示的药效团：并且抑制转录因子AP-1的活性，并且可用作预防和治疗转录因子 AP-1过表达的疾病和作为AP-1抑制剂的疾病。
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公开(公告)号：US20050113400A1
公开(公告)日：2005-05-26
申请号：US10493223
申请日：2002-11-13
申请人： Hisaaki Chaki , Hironori Kotsubo , Tadashi Tanaka , Yukihiko Aikawa , Shuichi Hirono , Shunichi Shiozawa
发明人： Hisaaki Chaki , Hironori Kotsubo , Tadashi Tanaka , Yukihiko Aikawa , Shuichi Hirono , Shunichi Shiozawa
IPC分类号： A61K31/192 , C07C59/90 , C07C65/34 , C07C65/40 , C07C69/738 , C07C69/76 , C07C69/88 , C07C69/94 , C07C205/34 , C07C217/76 , C07C235/42 , C07C255/54 , C07C259/10 , C07C271/64 , A61K31/44 , A61K31/277 , A61K31/40 , C07C65/30 , C07C255/56
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 R1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R2 represents, for example, a carboxyl group optionally protected with alkyl; R3 represents, for example, an optionally protected hydroxyl group; R4 represents, for example, an optionally substituted cycloalkyloxy group; and R5 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.
摘要翻译： 由下式表示的二苯甲酮衍生物：其中R 1表示例如任选取代的杂环基或取代的苯基; Z表示例如亚烷基; R 2表示例如任选被烷基保护的羧基; R 3表示例如任选保护的羟基; R 4表示例如任选取代的环烷氧基; R 5表示例如氢原子或其盐具有抗关节炎活性，抑制由关节炎引起的骨破坏，并且提供高安全性和优异的药代动力学，因此可用作治疗剂 用于关节炎。 这些化合物对AP-1活性具有抑制作用，可用作涉及AP-1过度表达的疾病的预防或治疗剂。
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8.发明授权Method of utilization of combination of benzophenone derivative or salt thereof and immunosuppressing agent, and pharmaceutical composition comprising these components 有权二苯甲酮衍生物或其盐与免疫抑制剂的组合的利用方法以及包含这些成分的药物组合物公开(公告)号：US09066977B2
公开(公告)日：2015-06-30
申请号：US12989029
申请日：2009-04-20
申请人： Yukihiko Aikawa , Shunichi Shiozawa
发明人： Yukihiko Aikawa , Shunichi Shiozawa
IPC分类号： A61K45/06 , A61K31/194 , A61K31/42 , A61K31/423 , A61K31/519 , A61K31/5377 , A61K31/573
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, R1 represents an optionally substituted heterocyclic group, a substituted phenyl group or the like; Z represents an alkylene group or the like; R2 represents a carboxyl group, which may be protected by an alkyl group, or the like; R3 represents an optionally protected hydroxyl group or the like; R4 represents an optionally substituted cycloalkyloxy group or the like; and R5 represents a hydrogen atom or the like.)
摘要翻译： 公开了通式（I）表示的二苯甲酮衍生物或其盐和一种或多种免疫抑制剂的组合用途，以及含有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。 用途和组合物可用于治疗或预防自身免疫性疾病等。 （式中，R 1表示可以具有取代基的杂环基，取代苯基等; Z表示亚烷基等; R2表示可被烷基保护的羧基等; R3 表示任选保护的羟基等; R 4表示任选取代的环烷基氧基等; R 5表示氢原子等。
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9.发明申请METHOD OF UTILIZATION OF COMBINATION OF BENZOPHENONE DERIVATIVE OR SALT THEREOF AND IMMUNOSUPPRESSING AGENT, AND PHARMACEUTICAL COMPOSITION COMPRISING THESE COMPONENTS 有权使用苯并噻唑衍生物或其盐及其免疫抑制剂的组合方法以及包含这些组分的药物组合物公开(公告)号：US20110039813A1
公开(公告)日：2011-02-17
申请号：US12989029
申请日：2009-04-20
申请人： Yukihiko Aikawa , Shunichi Shiozawa
发明人： Yukihiko Aikawa , Shunichi Shiozawa
IPC分类号： A61K31/573 , A61K31/423 , A61K31/5375 , A61K31/192 , A61K31/42 , A61K31/519 , A61P37/02 , A61P19/02
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, R1 represents an optionally substituted heterocyclic group, a substituted phenyl group or the like; Z represents an alkylene group or the like; R2 represents a carboxyl group, which may be protected by an alkyl group, or the like; R3 represents an optionally protected hydroxyl group or the like; R4 represents an optionally substituted cycloalkyloxy group or the like; and R5 represents a hydrogen atom or the like.)
摘要翻译： 公开了通式（I）表示的二苯甲酮衍生物或其盐和一种或多种免疫抑制剂的组合用途，以及含有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。 用途和组合物可用于治疗或预防自身免疫性疾病等。 （式中，R 1表示可以具有取代基的杂环基，取代苯基等; Z表示亚烷基等; R2表示可被烷基保护的羧基等; R3 表示任选保护的羟基等; R 4表示任选取代的环烷基氧基等; R 5表示氢原子等。
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公开(公告)号：US06623924B1
公开(公告)日：2003-09-23
申请号：US09423861
申请日：2000-01-31
申请人： Shunichi Shiozawa
发明人： Shunichi Shiozawa
IPC分类号： C12Q168
CPC分类号： C12Q1/6883 , C07K14/4713 , C12Q2600/156
摘要： The application provides genes causative of rheumatoid arthritis, which are located within ±1 centimorgan from DNA sequences to which the microsatellite markers D1S214, D1S253, D8S556, DXS1001, DXS1047, DXS1205, DXS1227 and/or DXS1232 are hybridized: a method for diagnosing rheumatoid arthritis, including amplifying the genomic DNA of a subject by PCR using at least one of the microsatellite markers as primer and comparing the PCR products thereof with the PCR products prepared in the same manner using the genomic DNA of a normal control; and a method for identifying the causative factors of rheumatoid arthritis including the same as described above.
摘要翻译： 该应用提供了类风湿性关节炎的基因，其位于与微卫星标记物D1S214，D1S253，D8S556，DXS1001，DXS1047，DXS1205，DXS1227和/或DXS1232杂交的DNA序列的±1厘摩尔以下：用于诊断类风湿性关节炎的方法 包括使用至少一个微卫星标记作为引物通过PCR扩增受试者的基因组DNA，并将其PCR产物与使用正常对照的基因组DNA以相同方式制备的PCR产物进行比较; 以及用于鉴定包括与上述相同的类风湿性关节炎的致病因子的方法。
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