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1. 发明授权

US07462757B2 Animal with gene hypoexpression 失效
标题翻译：动物与基因低表达
公开(公告)号：US07462757B2
公开(公告)日：2008-12-09
申请号：US10478466
申请日：2002-05-21
申请人： Tomoko Satomi , Ryuichi Tozawa , Mitsugu Nakata , Yoshitaka Yasuhara , Yoshio Taniyama
发明人： Tomoko Satomi , Ryuichi Tozawa , Mitsugu Nakata , Yoshitaka Yasuhara , Yoshio Taniyama
IPC分类号： A01K67/00 , A01K67/027 , G01N33/00
CPC分类号： C12N15/907 , A01K2217/075 , C12N2517/02
摘要： The present invention relates to non-human animal embryonic stem cells in which a lecithin:cholesterol acyltransferase-like lysophospholipase endogenous gene is inactivated; non-human animals deficient in expression of LLPL gene; methods of screening for prophylactics and/or therapeutic drug using the cells or the animals; and prophylactics and/or therapeutic drug obtainable by the screening.The non-human animal ES cells of the invention in which their LLPL gene is inactivated are very useful in creating non-human animals deficient in expression of LLPL gene. The LLPL expression deficient non-human animals of the invention can be disease models for such diseases caused by insufficiency of the biological activities of LLPL since the animals lack various biological activities inducible by LLPL. Therefore, the animals of the invention are useful in screening for prophylactics and/or therapeutic drug for various diseases resulting from LLPL deficiency, as well as in elucidating the causes of LLPL-related diseases and examining therapeutic methods for such diseases. The screening methods of the invention are capable of efficiently screening for prophylactics and/or therapeutic drug for various diseases resulting from LLPL deficiency.
摘要翻译：本发明涉及非人动物胚胎干细胞，其中卵磷脂：胆固醇酰基转移酶样溶血磷脂酶内源基因失活; 非人类动物缺乏LLPL基因的表达; 使用细胞或动物筛选预防和/或治疗药物的方法; 以及通过筛选可获得的预防和/或治疗药物。其LLPL基因失活的本发明的非人动物ES细胞非常有用于产生缺乏LLPL基因表达的非人动物。本发明的LLPL表达缺陷型非人动物可以是LLPL生物活性不足引起的疾病的疾病模型，因为动物缺乏由LLPL诱导的各种生物活性。因此，本发明的动物可用于筛选由LLPL缺乏引起的各种疾病的预防和/或治疗药物，以及阐明LLPL相关疾病的原因并检查这些疾病的治疗方法。本发明的筛选方法能够有效筛选由LLPL缺乏引起的各种疾病的预防和/或治疗药物。

2. 发明授权

US07309693B2 Preventives and remedies for pulmonary hypertension 有权
标题翻译：肺动脉高压的预防和补救措施
公开(公告)号：US07309693B2
公开(公告)日：2007-12-18
申请号：US10276971
申请日：2001-05-25
申请人： Kensuke Egashira , Yoshikazu Yonemitsu , Katsuo Sueishi , Yasuhiro Ikeda , Yoshiyuki Inada
发明人： Kensuke Egashira , Yoshikazu Yonemitsu , Katsuo Sueishi , Yasuhiro Ikeda , Yoshiyuki Inada
IPC分类号： A61K31/70 , A01N43/04 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C07K16/24 , A61K31/711 , A61K38/195 , A61K2039/505
摘要： The present invention provides a prophylactic and/or therapeutic agent for pulmonary hypertension, comprising an antagonistic mutein of MCP-1 or a salt thereof, a DNA molecule comprising a nucleotide sequence encoding the antagonistic mutein of MCP-1, or a neutralizing antibody against MCP-1. The antagonistic mutein of MCP-1 or a salt thereof, the DNA molecule having a nucleotide sequence encoding the antagonistic mutein of MCP-1, or the neutralizing antibody against MCP-1 has hypotensive activity, and thus is useful as a pharmaceutical agent for preventing and/or treating pulmonary hypertension (primary pulmonary hypertension, in particular).
摘要翻译：本发明提供了一种肺动脉高压的预防和/或治疗剂，其包含MCP-1的拮抗性突变蛋白或其盐，包含编码MCP-1的拮抗性突变蛋白的核苷酸序列的DNA分子或针对MCP的中和抗体 -1。 MCP-1或其盐的拮抗性突变蛋白，具有编码MCP-1的拮抗性突变蛋白的核苷酸序列的DNA分子或针对MCP-1的中和抗体具有降血压活性，因此可用作预防药物和/或治疗肺动脉高压（特别是原发性肺动脉高压）。

3. 发明申请

US20060275286A1 Antibody and use of the same 有权
标题翻译：抗体和使用相同
公开(公告)号：US20060275286A1
公开(公告)日：2006-12-07
申请号：US11498439
申请日：2006-08-02
申请人： Hirokazu Matsumoto , Yasuko Horikoshi , Chieko Kitada , Tetsuya Ohtaki
发明人： Hirokazu Matsumoto , Yasuko Horikoshi , Chieko Kitada , Tetsuya Ohtaki
IPC分类号： A61K39/395 , G01N33/53 , C12P21/04 , C12N5/06 , C07K16/26
CPC分类号： G01N33/689 , C07K16/18 , G01N33/6857 , G01N2800/368
摘要： The present invention aims at providing an antibody, by which metastin or its derivative can be quantified specifically with a high sensitivity, a method of detecting/quantifying metastin or its derivative using the antibody, and a diagnostic agent (e.g., a diagnostic for pregnancy) the same. Specifically, an antibody capable of specifically reacting with a partial peptide at the N-terminus or C-terminus of a polypeptide having the amino acid sequence represented by SEQ ID NO: 1 or its derivative, and a method of detecting/quantifying metastin or its derivative using the antibody as well as a diagnostic agent using the same.
摘要翻译：本发明的目的在于提供抗体，通过该抗体可以以高灵敏度特异性地定量分析蛋白或其衍生物，使用抗体检测/定量分析蛋白或其衍生物的方法，以及诊断剂（例如，怀孕诊断）一样。具体而言，能够与具有SEQ ID NO：1所示的氨基酸序列的多肽的N末端或C末端的部分肽特异性反应的抗体或其衍生物，以及检测/定量分析的方法衍生物以及使用该抗体的诊断剂。

4. 发明授权

US07144720B2 Protein and DNA thereof 失效
公开(公告)号：US07144720B2
公开(公告)日：2006-12-05
申请号：US11088999
申请日：2005-03-24
申请人： Koji Yoshimura , Yuichi Hikichi , Atsushi Nishimura
发明人： Koji Yoshimura , Yuichi Hikichi , Atsushi Nishimura
IPC分类号： C12N9/50 , C12N15/00 , C12N1/20 , C12Q1/68 , C07H21/04
CPC分类号： C12N9/6489 , A61K38/00 , C07K16/40 , G01N2500/00
摘要： The present invention relates to a novel protein belonging to an ADAM family, a partial peptide thereof or a salt thereof, a DNA encoding the protein, a recombinant vector comprising the DNA, a transformant, a method for producing the protein, a medicine comprising the protein or the DNA, an antibody against the protein, a method/kit for screening for a compound or a salt thereof which promotes or inhibits the protease activity or the extracellular metric degrading enzyme activity (preferably, the peptidoglycan degrading enzyme activity) of the protein, a compound obtained by the screening, and a medicine comprising the compound. The present protein and a DNA encoding it can be used, for example, as an agent for treating or preventing various diseases such as disc herniation, ischialgia, glomerular nephritis, diabetic nephropathy, hepatic fibrosis, pulmonary fibrosis or osteopetrosis. In addition, the present antibody can be used for quantitating the present protein in a test solution. Further, the present protein is useful as a reagent for screening for a compound which promotes or inhibits the protease activity of the present protein.

5. 发明申请

US20050209213A1 Quinoline compound 失效
标题翻译：喹啉化合物
公开(公告)号：US20050209213A1
公开(公告)日：2005-09-22
申请号：US10493427
申请日：2002-10-24
申请人： Yuji Ishihara , Makoto Kamata , Shiro Takekawa , Nobuhiro Suzuki , Koki Kato
发明人： Yuji Ishihara , Makoto Kamata , Shiro Takekawa , Nobuhiro Suzuki , Koki Kato
IPC分类号： A61K31/4015 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K31/5377 , A61K31/55 , A61P3/04 , A61P5/04 , A61P25/22 , A61P25/24 , A61P43/00 , C07D215/38 , C07D401/06 , C07D401/12 , C07D405/12 , C07D409/12 , C07D471/04 , C07D413/02 , C07D41/02
CPC分类号： C07D401/06 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K31/5377 , A61K31/55 , C07D215/38 , C07D401/12 , C07D405/12 , C07D409/12 , C07D471/04
摘要： A compound, which has a melanin-concentrating hormone antagonistic action and useful as an agent for preventing or treating obesity, and which is represented by the formula: wherein Ar is a cyclic group optionally having substituent(s); X is a bond or a spacer having a main chain of 1 to 6 atoms; R1 and R2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 may form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s); Y is a divalent hydrocarbon group optionally having substituent(s) (except CO); R3 is a hydrogen atom or a hydrocarbon group optionally having substituent(s); and ring A and ring B may further have substituents, and when ring B further has a substituent, the substituent may be linked to R1 to form a ring, or a salt thereof, or a prodrug thereof, is provided.
摘要翻译：一种化合物，其具有黑色素浓集激素拮抗作用并且可用作预防或治疗肥胖症的药剂，并且其由下式表示：其中Ar是任选具有取代基的环状基团; X是具有1至6个原子的主链的键或间隔基; R 1和R 2相同或不同，各自为氢原子或任选具有取代基的烃基，或R 1〜 >和R 2可以与相邻的氮原子一起形成任选具有取代基的含氮杂环; Y是任选具有取代基（CO除外）的二价烃基; R 3是氢原子或任选具有取代基的烃基; 并且环A和环B可以进一步具有取代基，并且当环B还具有取代基时，取代基可以与R 1连接形成环，或其盐或其前药，被提供。

6. 发明授权

US06924300B2 Oxyiminoalkanoic acid derivatives 失效
公开(公告)号：US06924300B2
公开(公告)日：2005-08-02
申请号：US10331056
申请日：2002-12-27
申请人： Yu Momose , Hiroyuki Odaka , Hiroshi Imoto , Hiroyuki Kimura , Junichi Sakamoto
发明人： Yu Momose , Hiroyuki Odaka , Hiroshi Imoto , Hiroyuki Kimura , Junichi Sakamoto
IPC分类号： A61K31/195 , A61K31/235 , A61K31/42 , A61K31/421 , A61K31/422 , A61K31/4245 , A61K31/426 , A61K31/427 , A61K31/437 , A61K31/44 , A61K31/4402 , A61K31/4439 , A61K31/47 , A61K31/4704 , A61K31/4745 , A61K31/496 , A61K31/505 , A61P3/06 , A61P3/10 , A61P9/10 , A61P29/00 , A61P43/00 , C07D213/74 , C07D215/14 , C07D239/42 , C07D261/08 , C07D263/32 , C07D271/06 , C07D277/24 , C07D413/04 , C07D413/12 , C07D471/04 , C07D263/30 , C07D277/20
CPC分类号： C07D213/74 , A61K31/42 , A61K31/421 , A61K31/4245 , A61K31/426 , A61K31/427 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/4745 , A61K31/505 , C07D215/14 , C07D239/42 , C07D261/08 , C07D263/32 , C07D271/06 , C07D277/24 , C07D413/12 , C07D471/04
摘要： To provide a novel oxyiminoalkanoic acid derivative which has excellent hypoglycemic and hypolipidemic actions and which is used for the prevention or treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance and impaired glucose tolerance.A compound represented by the formula: wherein R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a bond, —CO—, —CH(OH)— or a group represented by —NR6— wherein R6 is a hydrogen atom or an optionally substituted alkyl group; n is an integer of 1 to 3; Y is an oxygen atom, a sulfur atom, —SO—, —SO2— or a group represented by —NR7— wherein R7 is a hydrogen atom or an optionally alkyl group; ring A is a benzene ring optionally having additional one to three substituents; p is an integer of 1 to 8; R2 is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; q is an integer of 0 to 6; m is 0 or 1; R3 is a hydroxy group, OR8 (R8 is an optionally substituted hydrocarbon group.) or NR9R10 (R9 and R10 are the same or different groups which are selected from a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted acyl group or R9 and R10 combine together to form a ring); R4 and R5 are the same or different groups which are selected from a hydrogen atom or an optionally substituted hydrocarbon group wherein R4 may form a ring with R2; provided that when R1 is a ethoxymethyl, a C1-3 alkyl, phenyl or p-methoxyphenyl and q=m=0, R3 is NR9R10; and provided that O-[2-chloro-4-(2-quinolylmethoxy)phenylmethyl]oxime and a methyl pyruvate of [2-chloro-4-(2-quinolylmethoxy)phenylmethyl]-2-iminoxypropionic acid are excluded; or a salt thereof.

7. 发明授权

US06849738B2 Processes for the production of thienopyrimidine derivatives 失效
标题翻译：噻吩并嘧啶衍生物的制备方法
公开(公告)号：US06849738B2
公开(公告)日：2005-02-01
申请号：US10220233
申请日：2001-02-27
申请人： Koichiro Fukuoka , Hiroaki Yamamoto , Kazuhiro Kimura , Junichi Kawakami , Shokyo Miki
发明人： Koichiro Fukuoka , Hiroaki Yamamoto , Kazuhiro Kimura , Junichi Kawakami , Shokyo Miki
IPC分类号： C07D333/38 , C07D495/04
CPC分类号： C07D495/04 , C07D333/38
摘要： The present invention provides a process for producing an intermediate for thienopyrimidine derivatives having the GnRH antagonistic activity at an industrial large scale.The process for production of the present invention relates to a process for producing a compound represented by the formula (III): wherein respective symbols have the same meanings as those described below, or a salt thereof, which comprises subjecting a compound represented by the formula (I): wherein R1 denotes hydrogen, nitro, halogen, phthalimido, mono- or di-(alkylcarbonyl)amino or alkoxy, or a salt thereof, to an acid halogenating reaction, which is successively reacted with malonic acid ester and magnesium alkoxide, treated with an acid, and reacted with sulfur and a compound represented by the formula: NCCH2COOR2 [wherein R2 denotes alkyl or aryl], or a salt thereof, in the presence of primary amine. According to the process of production of the present invention, thienopyrimidine derivatives having the GnRH antagonistic activity can be produced effectively and at an industrial large scale by a high yield and simple method.
摘要翻译：本发明提供了一种在工业上大规模生产具有GnRH拮抗活性的噻吩并嘧啶衍生物的中间体的方法。本发明的制备方法涉及一种由式（III）表示的化合物的制备方法：其中各自符号具有与下述相同的含义或其盐，其包括使由式（I）表示的化合物：其中R 1表示氢，硝基，卤素，苯二甲酰亚氨基，单 - 或二 - （烷基羰基）氨基或烷氧基或其盐与酸卤化反应反应，该酸卤化反应与丙酸和烷氧基镁连续反应，用酸处理，并与硫和式NCCH 2 COOR 2表示的化合物反应[其中 R 2表示烷基或芳基]或其盐，在伯胺的存在下。根据本发明的制造方法，可以通过高产率和简单的方法有效地以工业规模生产具有GnRH拮抗活性的噻吩并嘧啶衍生物。

8. 发明申请

US20040209919A1 Stabilized pharmaceutical composition 审中-公开
标题翻译：稳定的药物组合物
公开(公告)号：US20040209919A1
公开(公告)日：2004-10-21
申请号：US10835442
申请日：2004-04-28
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD.
发明人： Tadashi Makino , Tetsuro Tabata , Shin-Ichiro Hirai
IPC分类号： A61K031/4439 , A61K033/00
CPC分类号： C07D401/12 , A61K9/1611 , A61K9/2009 , A61K9/5026 , A61K9/5078 , A61K31/44 , A61K31/4439 , A61K47/02 , Y10S514/951
摘要： The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula 1 wherein R1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R3 and R5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.
摘要翻译：本发明的药物组合物，其包含下式的苯并咪唑化合物其中R 1是氢，烷基，卤素，氰基，羧基，烷酰氧基，烷氧羰基烷基，氨基甲酰基，氨基甲酰基烷基，羟基，烷氧基，羟基烷基，三氟甲基，酰基，氨基甲酰氧基，硝基，酰氧基，芳基，芳氧基，烷硫基或烷基亚磺酰基，R 2是氢，烷基，酰基，烷氧羰基，氨基甲酰基，烷基氨基甲酰基，二烷基氨基甲酰基，烷基羰基甲基，烷氧基羰基甲基或烷基磺酰基，R 3和R 5相同或不同的，各自为氢，烷基，烷氧基或烷氧基烷氧基，R 4为氢，烷基，可任选氟化的烷氧基或烷氧基烷氧基，m为0至4的整数，以及碱性无机盐稳定剂，身体稳定镁和钙碱性无机盐稳定剂是特别有用的。

9. 发明申请

US20040044223A1 Benzimidazole derivatives, their production and use 失效
标题翻译：苯并咪唑衍生物，其生产和使用
公开(公告)号：US20040044223A1
公开(公告)日：2004-03-04
申请号：US10612984
申请日：2003-07-07
申请人： Takeda Chemical Industries, Ltd.
发明人： Takehiko Naka , Kohei Nishikawa , Takeshi Kato
IPC分类号： C07D43/02
CPC分类号： C07D235/02 , C07D235/26 , C07D235/28 , C07D235/30 , C07D403/04 , C07D403/10 , C07D405/14
摘要： A method for producing a compound represented by the formula: 1 wherein the ring A is a benzene ring which may be substituted in addition to the Rnull group; R1 is hydrogen or an optionally substituted hydrocarbon residue; X is a direct bond or a spacer having an atomic length or two or less between the phenylene group and the phenyl group; Y is nullOnull, nullS(O)m- or nullN(R4)null wherein m is an integer of 0, 1 or 2 and R4 is hydrogen or an optionally substituted alkyl group; Rnull is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or a group convertible thereinto; n is an integer of 1 or 2; or a salt thereof, which comprises deprotecting a compound represented by the formula: 2 wherein R is triphenylmethyl, 2-tetrahydropyranyl, methoxymethyl or ethoxy methyl, the other symbols as defined above; or a salt thereof.
摘要翻译：一种制备由下式表示的化合物的方法：其中环A是除R'基之外可被取代的苯环; R 1是氢或任选取代的烃残基; X是在亚苯基和苯基之间具有原子长度或者两个或更少的直接键或间隔子; Y是-O - ， - S（O）m - 或-N（R 4） - ，其中m是0,1或2的整数，R 4是氢或任选取代的烷基; R'是羧基，其酯，其酰胺或能够形成阴离子的基团或可转化的基团; n为1或2的整数; 其包括使由下式表示的化合物脱保护：其中R是三苯甲基，2-四氢吡喃基，甲氧基甲基或乙氧基甲基，其它符号如上定义; 或其盐。

10. 发明申请

US20030133941A1 Method of separating protective components of bordetella pertussis 审中-公开
标题翻译：分离百日咳博德特氏菌保护成分的方法
公开(公告)号：US20030133941A1
公开(公告)日：2003-07-17
申请号：US10206989
申请日：2002-07-30
申请人： Takeda Chemical Industries, Ltd.
发明人： Akihiro Suehara , Eiji Yamamoto , Shigeo Fujii
IPC分类号： A61K039/02 , C07K014/235
CPC分类号： C07K14/235 , A61K39/00
摘要： To provide a method of efficiently separate protective components of Bordetella pertussis On the basis of differences in adsorbability to calcium phosphate gel formed by adding calcium ions to a Bordetella pertussis culture in the presence of excess phosphate ions, protective components of Bordetella pertussis are separated from the Bordetella pertussis culture. Traditionally, protective components of Bordetella pertussis have been separated using different purification methods for the respective components. According to the present invention, the use of the same means of purification for all subject components makes it possible to purify each component with high efficiency and high recovery rate, an aspect very advantageous for industrial production. It is also possible to efficiently produce an improved purified pertussis component vaccine comprising an effective combination of pertussis filamentous hemagglutinin (FHA), pertactin (PRN, 69K-OMP), pertussis fimbriae (FIM) and pertussis toxin (PT).
摘要翻译：提供一种有效分离百日咳博德特氏菌保护成分的方法根据在过量磷酸根离子存在下向百日咳杆菌培养物中加入钙离子而形成的磷酸钙凝胶的吸附性差异，将百日咳博德特氏菌的保护成分从博德特氏菌百日咳培养。传统上，百日咳博德特氏菌的保护性成分已经使用各种成分的不同纯化方法进行分离。根据本发明，对于所有被摄体成分使用相同的纯化方法使得可以以高效率和高回收率净化每种组分，这对于工业生产非常有利。还可以有效地制备改进的纯化的百日咳组分疫苗，其包括百日咳丝状血凝素（FHA），百日咳杆菌（PRN，69K-OMP），百日咳菌毛（FIM）和百日咳毒素（PT））的有效组合。

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