公开(公告)号：US06858709B1

公开(公告)日：2005-02-22

申请号：US09914324

申请日：2000-02-25

申请人： Joan W. Conaway ,  Ronald C. Conaway ,  Takumi Kamura

发明人： Joan W. Conaway ,  Ronald C. Conaway ,  Takumi Kamura

IPC分类号： A61K38/00 ,  C07K14/47 ,  C07K1/10 ,  C07K1/00

CPC分类号： C07K14/4703 ,  A61K38/00 ,  Y10S530/828 ,  Y10S530/835

摘要： Rbx1, an evolutionarily conserved Cullin-interacting RING-H2 finger protein, has been discovered. Mammalian Rbx1 has been identified as a component of the CUL2-containing VHL complex. An Rbx1 homolog from S. cerevisiae has also been identified as a subunit and activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cdk inhibitor Sic1 and for the G1/S cell cycle transition in yeast, providing a link between the multiprotein VHL tumor suppressor complex and cellular ubiquitination. The Rbx1 protein acts as a cellular marker useful (1) in detecting a possible predisposition to certain carcinomas, (2) as a molecular target for treating those carcinomas therapeutically. (3) as a target for inhibition by drugs that manipulate the growth of cells, and (4) as a research tool to better understand the various complex mechanisms of cell ubiquitination, binding of certain activator proteins, fibronectin deposition and other aspects of the cellular division process.

摘要翻译： 已经发现Rbx1是进化上保守的Cullin相互作用的RING-H2指蛋白。 哺乳动物Rbx1已被鉴定为含有CUL2的VHL复合物的组分。 来自酿酒酵母的Rbx1同源物也被鉴定为含有Cdc53的SCF 泛素连接酶的亚基和活化剂，其用于cdk抑制剂Sic1的泛素化和酵母中的G1 / S细胞周期转换所需的，提供了一个链接 在多蛋白VHL肿瘤抑制复合物和细胞泛素化之间。 Rbx1蛋白作为细胞标志物可用于检测某些癌症的可能倾向，（2）作为治疗这些癌症的分子靶标。 （3）作为操纵细胞生长的药物的抑制靶标，以及（4）作为更好地了解细胞泛素化的各种复杂机制，某些激活蛋白的结合，纤连蛋白沉积和细胞的其它方面的研究工具 划分过程。

公开(公告)号：US5965693A

公开(公告)日：1999-10-12

申请号：US858830

申请日：1997-05-19

申请人： Kenneth Jacobs ,  John M. McCoy ,  Edward R. LaVallie ,  Lisa A. Racie ,  David Merberg ,  Maurice Treacy ,  Cheryl Evans

发明人： Kenneth Jacobs ,  John M. McCoy ,  Edward R. LaVallie ,  Lisa A. Racie ,  David Merberg ,  Maurice Treacy ,  Cheryl Evans

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61P1/02 ,  A61P15/08 ,  A61P19/00 ,  A61P25/28 ,  A61P43/00 ,  C07K14/47 ,  C12N5/10 ,  C12N15/12 ,  C12Q1/68 ,  C07K14/435 ,  C12N15/11

CPC分类号： C07K14/47 ,  C07K14/4703 ,  A61K38/00 ,  Y10S530/835

摘要： Novel polynucleotides and the proteins encoded thereby are disclosed.

公开(公告)号：US5610008A

公开(公告)日：1997-03-11

申请号：US461180

申请日：1995-06-05

申请人： Jan E. Schnitzer ,  Bruce S. Jacobson

发明人： Jan E. Schnitzer ,  Bruce S. Jacobson

IPC分类号： G01N33/48 ,  A61K35/12 ,  A61K35/44 ,  C07K14/435 ,  G01N1/04 ,  C12Q1/00

CPC分类号： A61K35/44 ,  Y10S436/813 ,  Y10S530/835 ,  Y10S530/837 ,  Y10S530/839 ,  Y10S530/841 ,  Y10S530/846 ,  Y10S530/849 ,  Y10S530/854 ,  Y10T436/24 ,  Y10T436/25 ,  Y10T436/25375 ,  Y10T436/255

摘要： A process is disclosed which makes possible the isolation of the luminal endothelial cell membrane from associated tissue. It is particularly applicable to vasculature, but broadly is applicable to all tissue cavities which are accessible from adjacent perfusable lumens. The method involves the identification of characteristic molecules (primarily proteins and lipids) associated with the luminal surface of the any endothelial membrane in situ by utilizing a novel membrane-isolation scheme to separate the endothelium from associated tissue. The normal form of that tissue of interest and diseased and/or dysfunctional forms (such as tumors) can then be examined comparatively in order to identify proteins highly enriched and/or unique for normal and abnormal endothelia. This in turn permits the production of antibodies to the proteins of interest in order to develop probes specific for the abnormal tissue, such as vasculature of a tumor. In this method, the endothelial luminal plasmalemma of a given organ is coated with colloidal silica by perfusion, a pellicle is formed, the coated area of tissue is excised and the coated plasmalemma fragments are isolated from the cognate homogenate by centrifugation. The isolated plasmalemma attached to the pellicle can then be subjected to biochemical analysis to identify and catalogue molecules characteristic of the endothelial membrane.

摘要翻译： 公开了一种可以将腔内皮细胞膜与相关组织分离的方法。 它特别适用于脉管系统，但广泛适用于可从相邻可灌注腔内接近的所有组织腔。 该方法涉及通过利用新的膜分离方案来将内皮与相关组织分离，从而鉴定与原位任何内皮膜的腔表面相关联的特征分子（主要是蛋白质和脂质）。 然后可以比较地检查感兴趣的组织的正常形式和患病和/或功能障碍形式（例如肿瘤），以鉴定正常和异常内皮的高度富集和/或独特的蛋白质。 这反过来允许产生针对目的蛋白质的抗体，以便开发特异于异常组织的探针，例如肿瘤脉管系统。 在这种方法中，给予器官的内皮腔内质膜通过灌注涂覆胶体二氧化硅，形成防护薄膜，切下组织的包被区域，并通过离心从同源匀浆中分离包被的浆细胞片段。 然后可以将附着在防护薄膜组件上的分离的等离子体进行生物化学分析，以鉴定和分类内皮膜特征的分子。

公开(公告)号：US5155211A

公开(公告)日：1992-10-13

申请号：US437544

申请日：1989-11-16

申请人： Robert D. Rosenberg

发明人： Robert D. Rosenberg

IPC分类号： A61K38/00 ,  C07K14/475

CPC分类号： C07K14/475 ,  A61K38/00 ,  Y10S530/83 ,  Y10S530/835

摘要： A megakaryocyte stimulatory factor (MSF), purified to homogeneity, is an acidic protein (pI=5.1) with an Mr=15,000 which stimulates PF4-like protein synthesis in rat promegakaryoblast cells by as much as 7-fold, and exhibits half-maximal activity at a concentration of 0.8 pM. MSF exhibits no biologic activity corresponding to other known hemopoietic growth factors, and appears to be specific for the megakaryocyte lineage.In the given examples, MSF was purified to homogeneity (as judged by SDS-PAGE and isoelectric focusing in the presence of 9.2 M urea) from serum-free conditioned medium obtained from cultured human embryonic kidney (HEK) cells, and to near homogeneity from thrombocytopenic plasma. The MSF is isolated by precipitating the MSF with ammonium sulfate at 80% saturation, removing insoluble, non-MSF material and applying the soluble protein to a WGA-Sepharose column, eluting the MSF protein with chitin oligosaccharides, applying the concentrated eluant containing MSF activity to a Biogel P200 column, and chromatographing the eluted MSF fractions on a TSK-G3000 HPLC size exclusion column.

摘要翻译： 纯化到同质性的巨核细胞刺激因子（MSF）是一种酸性蛋白（pI = 5.1），Mr = 15,000，其刺激大鼠原始细胞母细胞中的PF4样蛋白质合成多达7倍，并显示半最大 浓度为0.8 pM的活性。 MSF不表现出与其他已知造血生长因子相对应的生物活性，似乎对巨核细胞谱系具有特异性。 在给定的实施例中，从获自培养的人胚胎肾（HEK）细胞的无血清条件培养基中将MSF纯化至均一性（通过SDS-PAGE和等离子聚焦在9.2M尿素存在下测定），并从几乎均匀 血小板减少性血浆。 MSF通过以80％饱和的硫酸铵沉淀MSF分离，除去不溶性非MSF物质，并将可溶性蛋白质应用于WGA-Sepharose柱，用几丁质寡糖洗脱MSF蛋白，应用含​​有MSF活性的浓缩洗脱液 至Biogel P200柱，并在TSK-G3000 HPLC尺寸排阻柱上色谱分离洗脱的MSF级分。

公开(公告)号：US4377513A

公开(公告)日：1983-03-22

申请号：US291848

申请日：1981-08-10

申请人： Kaname Sugimoto ,  Yasushi Hayashibara

发明人： Kaname Sugimoto ,  Yasushi Hayashibara

IPC分类号： A61K38/16 ,  A61K35/12 ,  A61K38/00 ,  A61K38/22 ,  C07K14/505 ,  C12N15/00 ,  A61K37/24 ,  C07G7/00

CPC分类号： C07K14/505 ,  A61K38/00 ,  Y10S435/848 ,  Y10S530/808 ,  Y10S530/809 ,  Y10S530/826 ,  Y10S530/828 ,  Y10S530/835 ,  Y10S530/837

摘要： The present invention relates to a process for the production of human erythropoietin.More precisely, the invention relates to a process for the mass production of human erythropoietin, comprising in vivo multiplication of human lymphoblastoid cells capable of producing human erythropoietin, and human erythropoietin production by the multiplied human lymphoblastoid cells.The human erythropoietin production according to the present invention is much higher, in terms of human erythropoietin production per cell, than that attained by conventional processes using in vitro tissue culture; thus, human erythropoietin can be used in a sufficient amount for the prevention and treatment of human diseases.

摘要翻译： 本发明涉及一种生产人促红细胞生成素的方法。 更确切地说，本发明涉及大规模生产人促红细胞生成素的方法，包括能够产生人促红细胞生成素的人类淋巴母细胞样细胞的体内增殖和由繁殖的人类淋巴母细胞细胞产生的促红细胞生成素。 根据本发明的人促红细胞生成素的生产比使用体外组织培养的常规方法获得的要高得多，就人细胞促红细胞生成素的产生而言， 因此，人类促红细胞生成素可以以足够的量用于预防和治疗人类疾病。

公开(公告)号：US07326537B2

公开(公告)日：2008-02-05

申请号：US11076158

申请日：2005-03-10

申请人： Henrik S. Olsen ,  Mark D. Adams

发明人： Henrik S. Olsen ,  Mark D. Adams

IPC分类号： G01N33/53 ,  G07N33/68

CPC分类号： C07H21/04 ,  A61K38/00 ,  C07K14/575 ,  C07K16/26 ,  C07K2317/24 ,  C07K2317/55 ,  Y10S530/835

摘要： The present invention relates to human Corpuscles of Stannius polypeptides and DNA (RNA) encoding such polypeptides. Also provided is a procedure for producing such polypeptides by recombinant techniques and antagonists against such polypeptides. Human Corpuscles of Stannius protein inhibits calcium uptake and reduces renal excretion of phosphate. Also provided is a diagnostic assay to detect mutations in the nucleic acid sequence encoding the polypeptide and for altered concentrations of the polypeptide in a sample derived from a host.

摘要翻译： 本发明涉及人类Stannius多肽多糖和编码这种多肽的DNA（RNA）。 还提供了通过重组技术和针对这种多肽的拮抗剂生产此类多肽的方法。 人类斯坦尼斯蛋白质蛋白质抑制钙摄取并减少磷酸盐的肾排泄。 还提供了用于检测编码多肽的核酸序列中的突变和来自宿主的样品中多肽的变化浓度的诊断测定法。

公开(公告)号：US20020146791A1

公开(公告)日：2002-10-10

申请号：US10116051

申请日：2002-04-05

申请人： Human Genome Sciences, Inc.

发明人： Henrik S. Olsen ,  Mark D. Adams

IPC分类号： C12N009/99 ,  C07H021/04 ,  C12P021/02 ,  C12N005/06

CPC分类号： C07H21/04 ,  A61K38/00 ,  C07K14/575 ,  C07K16/26 ,  C07K2317/24 ,  C07K2317/55 ,  Y10S530/835

摘要： The present invention relates to human Corpuscles of Stannius polypeptides and DNA (RNA) encoding such polypeptides. Also provided is a procedure for producing such polypeptides by recombinant techniques and antagonists against such polypeptides. Human Corpuscles of Stannius protein inhibits calcium uptake and reduces renal excretion of phosphate. Also provided is a diagnostic assay to detect mutations in the nucleic acid sequence encoding the polypeptide and for altered concentrations of the polypeptide in a sample derived from a host.

摘要翻译： 本发明涉及人类Stannius多肽多糖和编码这种多肽的DNA（RNA）。 还提供了通过重组技术和针对这种多肽的拮抗剂生产此类多肽的方法。 人类斯坦尼斯蛋白质蛋白质抑制钙摄取并减少磷酸盐的肾排泄。 还提供了用于检测编码多肽的核酸序列中的突变和来自宿主的样品中多肽的变化浓度的诊断测定法。

公开(公告)号：US6043216A

公开(公告)日：2000-03-28

申请号：US837226

申请日：1997-04-10

申请人： F. Gary Toback ,  John C. Lieske

发明人： F. Gary Toback ,  John C. Lieske

IPC分类号： A61K38/00 ,  C07K14/47 ,  C07K16/18 ,  G01N33/50 ,  G01N33/60 ,  A61K38/17 ,  C07K1/14

CPC分类号： G01N33/5044 ,  C07K14/4703 ,  C07K16/18 ,  G01N33/5008 ,  G01N33/5029 ,  G01N33/5091 ,  G01N33/60 ,  A61K38/00 ,  C07K2317/77 ,  Y10S530/835

摘要： An autocrine crystal adhesion inhibitor called CAI is an anionic, sialic acid-containing glycoprotein secreted by kidney epithelial cells that blocks adhesion of calcium oxalate monohydrate (COM) crystals to the cell surface. Novel amino acid sequences are shown for the amino-acid terminus and 6 interval fragments. Persons may be classified according to risk of developing kidney stones, by measuring the amount of CAI in a biological sample. Treatment efficacy is also monitored by this method. CAI is administered in vivo to prevent nephrolithiasis. A rapid, simple assay to detect agents that inhibit adhesion of COM crystals to the surface of kidney epithelial cells is characterized.

摘要翻译： 称为CAI的自分泌结晶粘附抑制剂是由肾上皮细胞分泌的阴离子，含唾液酸的糖蛋白，其阻断草酸钙一水合物（COM）晶体与细胞表面的粘附。 显示氨基酸末端和6个间隔片段的新氨基酸序列。 可以通过测量生物样品中的CAI的量，根据发展肾结石的风险对患者进行分类。 也通过该方法监测治疗效果。 CAI在体内施用以预防肾结石。 表征快速，简单的检测抑制COM晶体粘附到肾上皮细胞表面的试剂。

公开(公告)号：US5955422A

公开(公告)日：1999-09-21

申请号：US100197

申请日：1993-08-02

申请人： Fu-Kuen Lin

发明人： Fu-Kuen Lin

IPC分类号： A61K38/00 ,  A61K38/16 ,  C07K14/505 ,  C07K16/22 ,  C12N15/70 ,  C12N15/81 ,  C12N15/85

CPC分类号： C07K14/505 ,  C07K16/22 ,  C12N15/70 ,  C12N15/81 ,  C12N15/85 ,  A61K38/00 ,  C12N2800/108 ,  Y10S530/835

摘要： Disclosed are novel polypeptides possessing part or all of the primary structural conformation and one or more of the biological properties of mammalian erythropoietin ("EPO") which are characterized in preferred forms by being the product of procaryotic or eucaryotic host expression of an exogenous DNA sequence. Illustratively, genomic DNA, cDNA and manufactured DNA sequences coding for part or all of the sequence of amino acid residues of EPO or for analogs thereof are incorporated into autonomously replicating plasmid or viral vectors employed to transform or transfect suitable procaryotic or eucaryotic host cells such as bacteria, yeast or vertebrate cells in culture. Upon isolation from culture media or cellular lysates or fragments, products of expression of the DNA sequences display, e.g., the immunological properties and in vitro and in vivo biological activities of EPO of human or monkey species origins. Disclosed also are chemically synthesized polypeptides sharing the biochemical and immunological properties of EPO. Also disclosed are improved methods for the detection of specific single stranded polynucleotides in a heterologous cellular or viral sample prepared from, e.g., DNA present in a plasmid or viral-borne cDNA or genomic DNA "library".

摘要翻译： 公开了具有部分或全部主要结构构象和哺乳动物促红细胞生成素（“EPO”）的一种或多种生物学特性的新型多肽，其特征在于优选形式，其为外源DNA序列的原核或真核宿主表达的产物 。 说明性地，编码EPO或其类似物的氨基酸残基序列的部分或全部的基因组DNA，cDNA和制备的DNA序列被掺入用于转化或转染合适的原核或真核宿主细胞的自主复制质粒或病毒载体，例如 细菌，酵母或脊椎动物细胞。 当从培养基或细胞裂解物或片段分离时，DNA序列的表达产物显示例如人或猴物种来源的EPO的免疫学特性和体外和体内生物学活性。 还公开了共享EPO的生物化学和免疫学性质的化学合成的多肽。 还公开了用于检测由例如存在于质粒或病毒携带的cDNA或基因组DNA“文库”中的DNA制备的异源细胞或病毒样品中特异性单链多核苷酸的改进方法。

公开(公告)号：US4507229A

公开(公告)日：1985-03-26

申请号：US603346

申请日：1984-04-24

申请人： Hans Bohn

发明人： Hans Bohn

IPC分类号： G01N33/53 ,  C07K1/22 ,  C07K14/00 ,  C07K14/435 ,  C07K14/47 ,  C07K16/18 ,  G01N33/531 ,  C07G7/00 ,  A61K35/42 ,  A61K35/50 ,  A61K39/395

CPC分类号： C07K14/4721 ,  C07K16/18 ,  Y10S530/806 ,  Y10S530/834 ,  Y10S530/835 ,  Y10S530/838 ,  Y10S530/842 ,  Y10S530/844 ,  Y10S530/851

摘要： The protein PP.sub.4 which has(a) an electrophoretic mobility in the range between that of .alpha..sub.1 and .alpha..sub.2 globulins;(b) an isoelectric point of 4.85.+-.0.15;(c) a sedimentation coefficient s.sub.20,w.sup.0 of 3.3.+-.0.2S;(d) a molecular weight determined in polyacrylamide gel containing sodium dodecylsulfate (DSD) of 35,000.+-.5,000;(e) an extinction coefficient E.sub.1 cm.sup.1% (280 nm) of 5.9.+-.0.6;(f) a carbohydrate content of 2.4.+-.0.94% (g/100 g) (mannose 0.3.+-.0.2%, galactose 0.4.+-.0.2%, xylose 0.1.+-.0.4%, glucose 0.2.+-.0.1%, glucosamine 1.0.+-.0.2% and neuraminic acid 0.4.+-.0.2%) and(g) a specified aminoacid composition, and a process for its preparation are described. PP.sub.4 can be used to prepare antisera which can be employed to detect and determine PP.sub.4 in body fluids in order to diagnose diseases of particular organs, as a "marker" to monitor the progress of a disease or to check therapy.

摘要翻译： 蛋白质PP4，其具有（a）在α1和α2球蛋白之间的范围内的电泳迁移率; （b）等电点4.85 +/- 0.15; （c）沉降系数s20，w0为3.3±0.2S; （d）在含有35,000 +/- 5,000的十二烷基硫酸钠（DSD）的聚丙烯酰胺凝胶中测定的分子量; （e）消光系数E1cm1％（280nm）为5.9 +/- 0.6; （f）碳水化合物含量为2.4±0.94％（g / 100g）（甘露糖0.3±0.2％，半乳糖0.4±0.2％，木糖0.1±0.4％，葡萄糖0.2±0.1 ％，葡糖胺1.0 +/- 0.2％，神经氨酸0.4±0.2％）和（g）指定的氨基酸组合物及其制备方法。 PP4可用于制备抗血清，可用于检测和测定体液中的PP4，以诊断特定器官的疾病，作为监测疾病进展或检查治疗的“标志物”。