公开(公告)号：EP0955313A4

公开(公告)日：2001-11-07

申请号：EP96910198

申请日：1996-04-19

申请人： HOECHST MARION ROUSSEL LTD

发明人： MAKISHIMA FUSAO ,  TAKAMATSU HIROYUKI ,  MIKI HIDEO ,  KAWAI SHINJI ,  KIMURA MICHIO ,  MATSUMOTO TOMOAKI ,  KATSUURA MIEKO ,  ENOMOTO KOICHI ,  SATOH YUSUKE

IPC分类号： A61K38/00 ,  C07K14/51 ,  C12N1/21 ,  C12N15/12 ,  A61K38/17 ,  C12P21/02

CPC分类号： C07K14/51 ,  A61K38/00 ,  Y10S514/801

摘要： A protein comprising an amino acid sequence represented by SEQ ID NO: 1 in the Sequence Listing and originating in human MP52 and the dimer of this protein. This dimer protein can be obtained by constructing a plasmid containing a DNA wherein a codon encoding methionine is added to the 5' end of a DNA sequence encoding the above-mentioned aminoacid sequence, transforming Escherichia coli by this plasmid, incubating the E. coli transformant, solubilizing and purifying the obtained inclusion body to thereby give a monomer protein, and then renaturing the obtained monomer protein into the dimer followed by purification. This dimer protein is useful in the treatment of cartilage and bone diseases.

摘要翻译： 一种蛋白质，其包含序列表中SEQ ID NO：1所示的氨基酸序列，并且源自人MP52和该蛋白质的二聚体。 该二聚体蛋白质可通过构建含有DNA的质粒来获得，其中在编码上述氨基酸序列的DNA序列的5'末端添加编码甲硫氨酸的密码子，用该质粒转化大肠杆菌，将大肠杆菌转化体 ，将得到的包涵体溶解并纯化，由此得到单体蛋白质，然后将获得的单体蛋白质复性成二聚体，然后纯化。 该二聚体蛋白质可用于治疗软骨和骨骼疾病。

公开(公告)号：EP0866125A4

公开(公告)日：2001-10-10

申请号：EP96925064

申请日：1996-07-24

申请人： HOECHST MARION ROUSSEL LTD

发明人： KIMURA MICHIO ,  MATSUMOTO TOMOAKI ,  TAKAHASHI MIKIKO ,  KAWAI SHINJI ,  FUJINO YUKIO

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61P3/00 ,  A61P19/10 ,  A61P43/00 ,  C07K14/47 ,  C07K14/51 ,  C12N5/10 ,  C12N15/12 ,  C12P21/02 ,  C12R1/91 ,  A61K38/17

CPC分类号： C07K14/51 ,  A61K38/00

摘要： A protein named HMW human MP52 which is produced in CHO cells and has the amino acid sequence represented by SEQ ID NO:1 in the Sequence Listing; a process for producing HMW human MP52; and a medicinal composition comprising HMW human MP52 as the active ingredient. Because of having the effect of promoting bone induction, HMW human MP52 is usable in the treatment or prevention of bone diseases, etc.

公开(公告)号：EP0949335A1

公开(公告)日：1999-10-13

申请号：EP97950371.1

申请日：1997-12-24

申请人： Hoechst Marion Roussel, Ltd.

发明人： HONDA, Jun, c/o Hoechst Marion Roussel Ltd. ,  ANDOU, Hidetoshi, c/o Hoechst Marion Roussel Ltd. ,  SUGIMOTO, Shunjiro, c/o Hoechst Marion Roussel Ltd

IPC分类号： C12P21/02 ,  C07K14/51 ,  C12N15/09

CPC分类号： C07K14/51

摘要： The present invention relates to a process for the production of purified dimeric bone morphogenetic factors. Purified dimeric bone morphogenetic factor can be produced by subjecting an inclusion body of a bone morphogenetic factor produced by means of a genetic engineering technology to the following steps a) - e) in order;

a) treating an inclusion body of a bone morphogenetic factor with a denaturing agent to obtain a solubilized monomer,
b) treating the solubilized monomer with a refolding solution to obtain a dimeric bone morphogenetic factor,
c) treating the dimeric bone morphogenetic factor by ultrafiltration and substitution of solvent,
d) subjecting the dimeric bone morphogenetic factor in solvent thus substituted to isoelectric precipitation, and
e) subjecting the dimeric bone morphogenetic factor thus isoelectrically precipitated to reverse-phase chromatography.

摘要翻译： 本发明涉及一种生产纯化的二聚体骨形态发生因子的方法。 纯化的二聚体骨形态发生因子可以通过使遗传工程技术产生的骨形态发生因子的包涵体按照以下步骤a）-e）进行制备： a）用变性剂处理骨形态发生因子的包涵体以获得溶解的单体，b）用重折叠溶液处理溶解的单体以获得二聚骨形态发生因子，c）通过超滤处理二聚体骨形态发生因子，和 取代溶剂，d）将二聚体骨形态发生因子置于溶剂中，从而代替等电点沉淀，e）使二聚体骨形态发生因子进行等电沉淀以进行反相色谱。

公开(公告)号：EP0867114A4

公开(公告)日：1999-06-09

申请号：EP96932037

申请日：1996-09-27

申请人： HOECHST MARION ROUSSEL LTD ,  OGAWA SHYOSO ,  IWAYA MAKOTO

发明人： OGAWA SHYOSO ,  IWAYA MAKOTO ,  SATOH MASAHIRO ,  TADA NORIHIRO

IPC分类号： A01K67/027 ,  C12N5/10 ,  C12N15/09 ,  C12N15/87 ,  C12N15/88

CPC分类号： A01K67/0275 ,  A01K2217/05 ,  C12N15/87 ,  C12N15/88

摘要： A method for preparing spermatozoa having an alien DNA of a mature male nonhuman vertebrate transduced thereinto which comprises injecting the alien DNA carried by a liposome for transduction into the testes of the animal thrice or more repeatedly and thus producing spermatozoa having the alien DNA transduced thereinto in the testes of the animal. A transgenic nonhuman vertebrate can be conveniently and efficiently produced by fertilizing an unfertilized egg with such a spermatozoon by natural crossing, artificial fertilization or external fertilization.

公开(公告)号：EP0884052A4

公开(公告)日：1999-05-06

申请号：EP96938460

申请日：1996-11-14

申请人： HOECHST MARION ROUSSEL LTD

发明人： SHIMURA TAKESADA ,  TORIYAMA SATSUKI

IPC分类号： C12N15/09 ,  A61F2/02 ,  A61F2/28 ,  A61F2/30 ,  A61K38/00 ,  A61K38/18 ,  A61K47/32 ,  A61K47/34 ,  A61L27/22 ,  A61P3/00 ,  A61P43/00 ,  C07K14/51 ,  C12P21/02 ,  C12R1/19 ,  A61B17/56 ,  A61M37/00

CPC分类号： A61L27/227 ,  A61F2/28 ,  A61F2/30756 ,  A61F2002/2817 ,  A61F2002/30062 ,  A61F2210/0004 ,  A61K38/1875 ,  C07K14/51

摘要： Cartilage/bone inducing materials for reparation which contain a bone inducer and polyoxyethylene polyoxypropylene glycol. In a particularly preferable example, the molecular weight of the polypropylene glycol constituting the polyoxyethylene polyoxypropylene glycol falls within the range of from about 1,500 to 4,000, the weight ratio of the ethylene oxide units falls within the range of from about 40 to 80 %/molecule, and the concentration of the polyoxyethylene polyoxypropylene glycol is about 10 to 50 % based on the aqueous solution. These materials are used in the cartilage/bone induction method without requiring any operation. Because of being composed of a bone inducer and a carrier which is easily absorbed in vivo, highly compatible with the bone inducer and undergoes reversible sol-gel change depending on the temperature, they can be highly applicable to fracture and bone-defective sites and thus exert excellent therapeutic effects.

公开(公告)号：EP0867114A1

公开(公告)日：1998-09-30

申请号：EP96932037.3

申请日：1996-09-27

申请人： Hoechst Marion Roussel, Ltd. ,  Ogawa, Shyoso ,  Iwaya, Makoto

发明人： OGAWA, Shyoso ,  IWAYA, Makoto ,  SATOH, Masahiro ,  TADA, Norihiro

IPC分类号： A01K67/027

CPC分类号： A01K67/0275 ,  A01K2217/05 ,  C12N15/87 ,  C12N15/88

摘要： A method for preparing a sperm containing an exogenous DNA, wherein the exogenous DNA together with liposome for the purpose of transduction of DNA into mammalian cells is injected repeating three times or more into a testis of a mature non-human vertebrate male and the sperm containing the exogenous DNA is produced in the testis of said male. It can be convenient and efficient to prepare a non-human transgenic vertebrate by mating a sperm containing an exogenous DNA with a female naturally, or mating an egg which has not yet been fertilized by artificial insemination or in vitro fertilization.

摘要翻译： 一种制备含有外源DNA的精子的方法，其中将外源DNA与脂质体一起用于将DNA转导入哺乳动物细胞的目的是注射重复三次或更多次的成熟非人类脊椎动物雄性睾丸和含有 在所述雄性的睾丸中产生外源DNA。 通过将含有外源DNA的精子与雌性天然配对，或者通过人工授精或体外受精来交配尚未受精的卵来制备非人转基因脊椎动物可以方便和有效。

公开(公告)号：EP0994093A1

公开(公告)日：2000-04-19

申请号：EP97922050.6

申请日：1997-05-14

申请人： Hoechst Marion Roussel, Ltd.

发明人： SAKAI, Kunikazu, Discovery Research Laboratories ,  SATOH, Yusuke, Discovery Research Laboratories ,  DOI, Kazuyuki, Information Technology Dept. ,  KITAMURA, Kazuyuki, Discovery Research Labs.

IPC分类号： C07C49/713 ,  C07C49/743 ,  C07C49/825 ,  C07C49/835 ,  C07C49/84 ,  A61K31/12

CPC分类号： C07C49/84 ,  C07C45/00 ,  C07C45/46 ,  C07C45/512 ,  C07C45/62 ,  C07C45/68 ,  C07C45/71 ,  C07C49/713 ,  C07C49/743 ,  C07C49/747 ,  C07C49/825 ,  C07C49/83 ,  C07C49/835

摘要： Compounds useful as preventive and therapeutic agents for bone and cartilage diseases; and drug compositions containing the same.
The compounds are polyhydroxyphenol derivatives of general formula (I) and quinone analogues derivative therefrom
(wherein R 1 is alkyl, optionally substituted benzyl, or optionally substituted aryl; R 2 is hydrogen, alkyl, alkenyl or optionally substituted benzyl; R 3 is hydrogen, alkyl, alkenyl, optionally substituted benzyl, hydroxyl, alkoxy. alkenyloxy or optionally substituted benzyloxy; R 4 is hydrogen, alkyl, alkenyl, optionally substituted benzyl or hydroxyl; and R 5 and R 6 are each independently hydrogen, alkyl, alkenyl or optionally substituted benzyl).
The polyhydroxyphenol derivatives and quinone analogues exhibit a potent inhibitory activity against bone resorption and are useful as preventive and therapeutic agents for bone and cartilage deseases.

摘要翻译： 作为骨和软骨疾病预防和治疗剂是有用的化合物; 和药物组合物含有相同。 该化合物的通式（I）和醌类似物从衍生物存在的多羟基酚衍生物（worin R 1是烷基，任选地substituiertem苄基，或任选地substituiertem芳基;氢R 2是烷基，烯基或任选substituiertem苄基;氢R 3是， 烷基，烯基，任选取代的苄基，羟基，烷氧基链烯基氧基或任选substituiertem苄氧基;. R4是氢，烷基，链烯基，任选取代的苄基或羟基;且R5和R6各自独立地是氢，烷基，链烯基或任选取代的苄基）。 多羟基酚衍生物和醌类似物表现出对骨吸收的有效抑制活性，作为骨和软骨deseases预防和治疗药物是有用的。

公开(公告)号：EP0919617A4

公开(公告)日：2001-04-11

申请号：EP97918417

申请日：1997-05-13

申请人： HOECHST MARION ROUSSEL LTD

发明人： KITAGAWA HIROSHI ,  JITSUKAWA TOMOFUMI ,  NAKAGAWA HIRAKU ,  YANAGISAWA SACHIKO

IPC分类号： G01N33/53 ,  A61K39/395 ,  A61P43/00 ,  C07H21/04 ,  C07K14/51 ,  C07K16/22 ,  C12N5/00 ,  C12N5/10 ,  C12N15/02 ,  C12N15/08 ,  C12P21/00 ,  C12P21/04 ,  C12P21/08 ,  C12R1/91 ,  G01N33/577 ,  C12N15/12

CPC分类号： C07K16/22 ,  C07K14/51

摘要： A mouse anti-human MP52 monoclonal antibody which binds to dimeric human MP52 but not to monomeric human MP52. This mouse monoclonal antibody comprising IgG and having a high specificity can be obtained by sensitizing mice with human MP52 (CHO-MP52) produced in CHO cells and human MP52 (rhMP52) produced in escherichia coli. This antibody is useful in, for example, purifying or assaying human MP52 produced by genetic engineering techniques.

公开(公告)号：EP1078054A1

公开(公告)日：2001-02-28

申请号：EP99917029.3

申请日：1999-05-14

申请人： Hoechst Marion Roussel, Ltd.

发明人： KAWAI, Shinji ,  KIMURA, Michio ,  MURAKI, Yoshifumi,Hoechst Marion Roussel Ltd. ,  KATSUURA, Mieko

IPC分类号： C12N15/12 ,  C07K14/51 ,  C12P21/02 ,  A61K38/18

CPC分类号： C07K14/51 ,  A61K38/00

摘要： The purpose is to provide a monomer protein effective for prevention and therapeutic treatment of bone and/or cartilage diseases. Said purpose is achieved by a monomer protein having an amino acid sequence of which cysteine contributing to dimer formation of a protein belonging to TGF-β superfamily has been replaced with another amino acid. In comparison with the corresponding dimer protein, the monomer protein has a two-fold higher activity in an osteoblast cell line to induce differentiation. Other amino acids are exemplified by serine, threonine, alanine, and valine, and preferably alanine. Said protein is prepared by using Escherichia coli, yeast, insect cells, and mammal cells that have been transformed by a plasmid having a DNA sequence capable of expression of said monomer protein.

公开(公告)号：EP0994093A4

公开(公告)日：2000-05-17

申请号：EP97922050

申请日：1997-05-14

申请人： HOECHST MARION ROUSSEL LTD

发明人： SAKAI KUNIKAZU ,  SATOH YUSUKE ,  DOI KAZUYUKI ,  KITAMURA KAZUYUKI

IPC分类号： A61K31/12 ,  A61P3/00 ,  A61P19/10 ,  A61P43/00 ,  C07C45/00 ,  C07C45/46 ,  C07C45/51 ,  C07C45/62 ,  C07C45/68 ,  C07C45/71 ,  C07C49/713 ,  C07C49/743 ,  C07C49/747 ,  C07C49/825 ,  C07C49/83 ,  C07C49/835 ,  C07C49/84

CPC分类号： C07C49/84 ,  C07C45/00 ,  C07C45/46 ,  C07C45/512 ,  C07C45/62 ,  C07C45/68 ,  C07C45/71 ,  C07C49/713 ,  C07C49/743 ,  C07C49/747 ,  C07C49/825 ,  C07C49/83 ,  C07C49/835

摘要： Compounds useful as preventive and therapeutic agents for bone and cartilage diseases; and drug compositions containing the same. The compounds are polyhydroxyphenol derivatives of general formula (I) and quinone analogues derived therefrom (wherein R1 is alkyl, optionally substituted benzyl or optionally substituted aryl; R2 is hydrogen, alkyl, alkenyl or optionally substituted benzyl; R3 is hydrogen, alkyl, alkenyl, optionally substituted benzyl, hydroxyl, alkoxy, alkenyloxy or optionally substituted benzyloxy; R4 is hydrogen, alkyl, alkenyl, optionally substituted benzyl or hydroxyl; and R5 and R6 are each independently hydrogen, alkyl, alkenyl or optionally substituted benzyl). The polyhydroxyphenol derivatives and the quinone analogues exhibit a potent inhibitory activity against bone resorption and are useful as preventive and therapeutic agents for bone and cartilage diseases.

摘要翻译： 用作骨和软骨疾病预防和治疗剂的化合物; 和含有它们的药物组合物。 所述化合物是通式（I）的多羟基酚衍生物和由其衍生的醌类似物（其中R1是烷基，任选取代的苄基或任选取代的芳基; R2是氢，烷基，烯基或任选取代的苄基; R3是氢，烷基， 任选取代的苄基，羟基，烷氧基，烯氧基或任选取代的苄氧基; R 4为氢，烷基，烯基，任选取代的苄基或羟基;并且R 5和R 6各自独立地为氢，烷基，烯基或任选取代的苄基。 多羟基酚衍生物和醌类似物表现出对骨吸收的有效抑制活性，并且可用作骨和软骨疾病的预防和治疗剂。