公开(公告)号：US07211424B1

公开(公告)日：2007-05-01

申请号：US09830837

申请日：1999-11-04

申请人： Nabil G. Seidah ,  Michel Chretien ,  Mieczyslaw Marcinkiewicz

发明人： Nabil G. Seidah ,  Michel Chretien ,  Mieczyslaw Marcinkiewicz

IPC分类号： C12N9/64 ,  C12N15/57 ,  C12N15/79 ,  C07K1/00 ,  C07K16/00

CPC分类号： C12N9/6424

摘要： Using RT-PCR and degenerate oligonucleotides derived from the active site residues of subtilisin-kexin-like serine proteinases, we have identified a highly conserved and phylogenetically ancestral human, rat and mouse type-I membrane-bound proteinase called subtilisin-kexin-isozyme-1 (SKI-1). Computer data bank searches reveals that human SKI-1 was previously cloned but with no identified function. A SKI-1 processed fragment is secreted in culture media in a soluble form. In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of proBDNF. Peptides mimicking SKI-1 cleavages sites are also disclosed. SKI-1 prosegment has an ex vivo inhibitory effect on SKI-1 activity. The prosegment is also processed and secreted in culture media. One of its fragments is found tightly associated with the SKI-1 soluble form. Therapeutic applications for SKI-1 inhibitors are disclosed.

摘要翻译： 使用RT-PCR和衍生自枯草杆菌蛋白酶 - 类克隆丝氨酸蛋白酶的活性位点残基的简并寡核苷酸，我们确定了一种高度保守和系统发育的祖先人类，大鼠和小鼠I型膜结合蛋白酶，称为枯草杆菌蛋白酶 - 1（SKI-1）。 计算机数据库搜索显示人类SKI-1以前被克隆，但没有识别功能。 SKI-1处理的片段以可溶形式分泌在培养基中。 体外研究表明，SKI-1是表现出对于proBDNF的切割具有宽pH最适的Ca 2+ 2 +依赖性丝氨酸蛋白酶。 还公开了模拟SKI-1切割位点的肽。 SKI-1 prosegment具有对SKI-1活性的离体抑制作用。 散文也在文化媒体中被处理和分发。 其中一个片段被发现与SKI-1可溶形式紧密相关。 公开了SKI-1抑制剂的治疗应用。

公开(公告)号：US4632780A

公开(公告)日：1986-12-30

申请号：US281928

申请日：1981-07-10

申请人： Nabil G. Seidah ,  Michel Chretien

发明人： Nabil G. Seidah ,  Michel Chretien

IPC分类号： C07K14/665 ,  C07C103/52

CPC分类号： C07K14/665 ,  Y10S930/26

摘要： There are disclosed the N-terminal fragment of human pro-opiomelanocortin, a glycopeptide composed of 76 amino acid residues, and a process for preparing same from human pituitary glands. The glycopeptide is useful in potentiating the effects of ACTH on steroidogenesis, in stimulating the production of aldosterone, as a diagnostic tool, as well as a reagent for determining its presence in biological fluids and tissues by immunochemical means.

摘要翻译： 公开了人类前乳糖皮质素的N-末端片段，由76个氨基酸残基组成的糖肽，以及由人脑垂体制备其的方法。 糖肽可用于增强ACTH对类固醇生成的作用，刺激醛固酮的产生，作为诊断工具，以及通过免疫化学方法测定其在生物流体和组织中的存在的试剂。

公开(公告)号：US20150190369A1

公开(公告)日：2015-07-09

申请号：US14410774

申请日：2013-06-28

申请人： Majambu Mbikay ,  Francine Sirois ,  Michel Chretien ,  Janice Mayne

发明人： Majambu Mbikay ,  Francine Sirois ,  Michel Chretien ,  Janice Mayne

IPC分类号： A61K31/366 ,  A61K31/7048

CPC分类号： A61K31/366 ,  A61K31/7048 ,  A61K45/06 ,  A61K2300/00

摘要： There is described herein a use of quercetin-3-O-β-D-glucoside (Q3G) for increasing the amount of cell surface low-density lipoprotein receptor (LDLR) on a cell and for reducing the amount of functional proprotein convertase subtilisin/kexin type 9 (PCSK9) secreted by the cell, where the Q3G is formulated for administration to the cell, and where the increase in cell surface LDLR and the decrease in secretion of functional PCSK9 is in comparison to the cell not exposed to Q3G. The use may optionally include the treatment of a statin. There is also described a method of reducing plasma cholesterol levels in a patient in need thereof. The method includes treating the patient with a therapeutically effective amount of Q3G and, optionally, a therapeutically effective amount of a statin.

摘要翻译： 本文描述了槲皮素-3-O-和bgr-D-葡萄糖苷（Q3G）用于增加细胞上的细胞表面低密度脂蛋白受体（LDLR）的量并减少功能性前体蛋白转化酶枯草杆菌蛋白酶的量 由细胞分泌的kKin 9型（PCSK9），其中Q3G配制用于给细胞，并且其中细胞表面LDLR的增加和功能性PCSK9的分泌减少与未暴露于Q3G的细胞相比。 使用可以任选地包括他汀类药物的治疗。 还描述了在有需要的患者中降低血浆胆固醇水平的方法。 该方法包括用治疗有效量的Q3G和任选的治疗有效量的他汀类药物治疗患者。

公开(公告)号：US5789564A

公开(公告)日：1998-08-04

申请号：US712241

申请日：1996-09-12

申请人： Nabil G. Seidah ,  Michel Chretien

发明人： Nabil G. Seidah ,  Michel Chretien

IPC分类号： A61K39/395 ,  B01D15/08 ,  C07H21/00 ,  C07K17/10 ,  C12N9/64 ,  C12N15/57 ,  C12N15/86 ,  C12Q1/68 ,  G01N33/573 ,  C07H21/04

CPC分类号： C12N9/6454 ,  C07K2319/00

摘要： The present invention relates to pro-hormone convertases and polypeptidic fragments thereof, nucleic acids encoding them, recombinant viruses expressing these convertases, polyclonal antibodies directed against the convertases, diagnostic kits for the detection and measurement of the convertase content in cell or tissue lysates, culture media or biological fluids by RIA. Diagnostic kits were also developped for detection or measurement of nucleic acids, preferably mRNAs, in cell or tissue lysates by hybridization. The invention also concerns oligonucleotides useful as probes or as primers for DNA synthesis. These oligonucleotides were included in the diagnostic kits as well as used for the obtention of specific fragments of the convertases which have served, together with native convertases, as antigens for the obtention of antibodies. The convertases were produced by mammalian cell lines transfected with the recombinant viruses and purified on affinity columns which are also an object of the invention. Processes for producing the native convertases, fragments thereof and antibodies are also described and claimed.

摘要翻译： 本发明涉及前激素转化酶及其多肽片段，编码它们的核酸，表达这些转化酶的重组病毒，针对转化酶的多克隆抗体，用于检测和测量细胞或组织裂解物中转化酶含量的诊断试剂盒，培养物 培养基或生物液体。 还开发了诊断试剂盒，用于通过杂交检测或测量细胞或组织裂解物中的核酸，优选mRNA。 本发明还涉及可用作探针或用作DNA合成的引物的寡核苷酸。 这些寡核苷酸被包括在诊断试剂盒中，并且用于获得已经与天然转化酶一起服用作为获得抗体的抗原的转化酶的特异性片段。 转化酶由用重组病毒转染的哺乳动物细胞系产生，并且在亲和柱上纯化也是本发明的目的。 还描述和要求保护天然转化酶，其片段和抗体的方法。

公开(公告)号：US07900964B2

公开(公告)日：2011-03-08

申请号：US11993102

申请日：2006-06-06

申请人： Jean-Michel Chretien ,  Arnaud Cocu ,  Jean-Louis Colmont ,  Thierry Derchu

发明人： Jean-Michel Chretien ,  Arnaud Cocu ,  Jean-Louis Colmont ,  Thierry Derchu

IPC分类号： B62D21/00

CPC分类号： B62D21/155 ,  B60R19/12 ,  B60R19/34 ,  B62D21/152

摘要： A section of a motor vehicle front low area includes a first extendable elongated part, whose rear end is placed in front of a vehicle structural element embodied in a form of a cradle, whereas the front end thereof is connected to a bar-type structural element of the vehicle by a first connection device. The rear end of the first elongated part is movably mounted in front of the cradle-shaped vehicle structural element. The first connection device includes a connection in a form of a slide bar enabling a substantially longitudinal movement to be carried out and a removable stop member for normally hindering movement up to the removal.

摘要翻译： 机动车辆前部小区域的一部分包括第一可延伸的细长部分，其后端被放置在以托架的形式体现的车辆结构元件的前面，而其前端连接到杆形结构元件 的第一连接装置。 第一细长部件的后端可移动地安装在摇篮式车辆结构件的前面。 第一连接装置包括能够执行基本上纵向移动的滑动条形式的连接和用于通常阻碍直到移除的移动的可移除止动构件。

公开(公告)号：US20100201159A1

公开(公告)日：2010-08-12

申请号：US11993102

申请日：2006-06-06

申请人： Jean-Michel Chretien ,  Arnaud Cocu ,  Jean-Louis Colmont ,  Thierry Derchu

发明人： Jean-Michel Chretien ,  Arnaud Cocu ,  Jean-Louis Colmont ,  Thierry Derchu

IPC分类号： B62D25/20

CPC分类号： B62D21/155 ,  B60R19/12 ,  B60R19/34 ,  B62D21/152

摘要： A section of a motor vehicle front low area includes a first extendable elongated part, whose rear end is placed in front of a vehicle structural element embodied in a form of a cradle, whereas the front end thereof is connected to a bar-type structural element of the vehicle by a first connection device. The rear end of the first elongated part is movably mounted in front of the cradle-shaped vehicle structural element. The first connection device includes a connection in a form of a slide bar enabling a substantially longitudinal movement to be carried out and a removable stop member for normally hindering movement up to the removal.

摘要翻译： 机动车辆前部小区域的一部分包括第一可延伸的细长部分，其后端被放置在以托架的形式体现的车辆结构元件的前面，而其前端连接到杆形结构元件 的第一连接装置。 第一细长部件的后端可移动地安装在摇篮式车辆结构件的前面。 第一连接装置包括能够执行基本上纵向移动的滑动条形式的连接和用于通常阻碍直到移除的移动的可移除止动构件。

公开(公告)号：US4607023A

公开(公告)日：1986-08-19

申请号：US644672

申请日：1984-08-27

申请人： Gaetan Thibault ,  Raul Garcia ,  Marc Cantin ,  Nabil Seidah ,  Claude Lazure ,  Michel Chretien

发明人： Gaetan Thibault ,  Raul Garcia ,  Marc Cantin ,  Nabil Seidah ,  Claude Lazure ,  Michel Chretien

IPC分类号： A61K38/00 ,  C07K14/58 ,  A61K37/24 ,  C07K7/08 ,  C07K7/10

CPC分类号： C07K14/58 ,  A61K38/00

摘要： Novel peptides in substantially pure form and selected from the group of peptides having the amino acid sequence:X-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Y-ZwhereinY is selected from the group consisting of -Asn, -Asn-Ser, -Asn-Ser-Phe, -Asn-Ser-Phe-Arg, and -Asn-Ser-Phe-Arg-Tyr;Z is OH or NH.sub.2 ; andX is selected from the group consisting of H, Ser-, Ser-Ser-, Arg-Ser-Ser-, Arg-Arg-Ser-Ser-, Leu-Arg-Arg-Ser-Ser, Ser-Leu-Arg-Arg-Ser-Ser-, Arg-Ser-Leu-Arg-Arg-Ser-Ser-, Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-, Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser, Ala-Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-, Leu-Ala-Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser, and Glu-Val-Pro-Trp-Thr-Gly-Glu-Val-Asn-Pro-Ser-Gln-Arg-Asp-Gly-Gly-Ala-Leu-Gly-Arg-Gly-Pro-Trp-Asp-Pro-Ser-Asp-Arg-Ser-Ala-Leu-Lys-Ser-Lys-Leu-Arg-Ala-Leu-Leu-Ala-Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-,are disclosed as having diuretic, natriuretic, vasorelaxant, hypotensive or anti-hypertensive properties.

摘要翻译： 选自具有以下氨基酸序列的肽基本上纯的形式的新型肽：X-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu -Gly-Cys-YZ，其中Y选自-Asn，-Asn-Ser，-Asn-Ser-Phe，-Asn-Ser-Phe-Arg和-Asn-Ser-Phe-Arg-Tyr ; Z是OH或NH 2; 并且X选自H，Ser-，Ser-Ser-，Arg-Ser-Ser-，Arg-Arg-Ser-Ser-，Leu-Arg-Arg-Ser-Ser，Ser-Leu-Arg -Arg-Ser-Ser-，Arg-Ser-Leu-Arg-Arg-Ser-Ser-，Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-，Gly-Pro-Arg-Ser-Leu- Arg-Arg-Ser-Ser，Ala-Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-，Leu-Ala-Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser ，Glu-Val-Pro-Trp-Thr-Gly-Glu-Val-Asn-Pro-Ser-Gln-Arg-Asp-Gly-Gly-Ala-Leu-Gly-Arg-Gly-Pro-Trp-Asp -Pro-Ser-Asp-Arg-Ser-Ala-Leu-Lys-Ser-Lys-Leu- Arg-Ala-Leu-Leu-Ala-Gly-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser - 被披露为具有利尿，利钠，血管舒张，降压或抗高血压的性质。

公开(公告)号：US20090275504A1

公开(公告)日：2009-11-05

申请号：US12115382

申请日：2008-05-05

申请人： Janice Mayne ,  Michel Chretien ,  Majambu Mbikay

发明人： Janice Mayne ,  Michel Chretien ,  Majambu Mbikay

IPC分类号： A61K38/08 ,  C07K7/06 ,  C07K14/00 ,  A61K31/7105 ,  C07K7/08 ,  C07K16/00 ,  C12N15/63 ,  A61K38/16 ,  C07H21/04

CPC分类号： C07K16/40 ,  A61K38/00 ,  A61K2039/53 ,  C12N9/6408

摘要： The present invention provide PCSK9 polypeptides, fragments thereof and methods of modulating PCSK9 phosphorylation and low density lipoprotein degradation.

摘要翻译： 本发明提供PCSK9多肽，其片段和调节PCSK9磷酸化和低密度脂蛋白降解的方法。

公开(公告)号：US5840529A

公开(公告)日：1998-11-24

申请号：US545562

申请日：1995-10-19

申请人： Nabil G. Seidah ,  Robert Day ,  Michel Chretien

发明人： Nabil G. Seidah ,  Robert Day ,  Michel Chretien

IPC分类号： G01N33/50 ,  A61K48/00 ,  C07K14/16 ,  C07K16/40 ,  C12N5/00 ,  C12N5/10 ,  C12N9/64 ,  C12N15/09 ,  C12N15/57 ,  C12P21/00 ,  C12Q1/68 ,  C12R1/91 ,  G01N33/53 ,  C07H21/04 ,  C07K14/00 ,  C12N15/63

CPC分类号： C07K14/005 ,  C12N9/6454 ,  A61K48/00 ,  C12N2740/16122

摘要： This invention relates to a novel and seventh member of the subtilisin-kexin family isolated from rat, which has been named rPC7. The rat spleen cDNA has been totally sequenced. A shorter DNA sequence has been obtained for human, which corresponds to a portion of the catalytic region of a human pro-hormone convertase corresponding to the rat pro-hormone convertase. PC7 clearly distinguishes from the other mammalian members of the subtilisin-kexin family. Its tissue distribution is ubiquitous, but its presence is particularly remarkable in lymphoid tissues. It is present in LoVo cells that are able to cleave the HIV gp160 protein into active gp120/gp41 proteins and that are deficient in other effective pro-hormone convertases known up to date. Therefore, it is proposed that PC7 is a good candidate as a maturation enzyme responsible for the conversion of HIV gp160 protein in target CD.sup.+4 cells.

摘要翻译： 本发明涉及从大鼠中分离的枯草杆菌蛋白酶-Kexin家族的新颖和第七个成员，其被命名为rPC7。 大鼠脾脏cDNA已经完全测序。 人类已经获得了较短的DNA序列，其对应于对应于大鼠前体激素转化酶的人类前体激素转化酶的一部分催化区域。 PC7明显区别于枯草杆菌蛋白酶-Kexin家族的其他哺乳动物成员。 其组织分布普遍存在，但其淋巴组织中的存在特别显着。 它存在于能够将HIV gp160蛋白切割成活性gp120 / gp41蛋白质的LoVo细胞中，并且缺乏其他已知的有效的促激素转化酶。 因此，建议PC7作为负责在目标CD + 4细胞中转染HIV gp160蛋白质的成熟酶的良好候选物。