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1. 发明申请

WO1995010538A1 DNA ENCODING THE HUMAN P2U RECEPTOR AND NULL CELLS EXPRESSING P2U RECEPTORS 审中-公开
标题翻译：编码人P2U受体和表达P2U受体的空细胞的DNA
公开(公告)号：WO1995010538A1
公开(公告)日：1995-04-20
申请号：PCT/US1994011260
申请日：1994-10-04
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , THE CURATORS OF THE UNIVERSITY OF MISSOURI , BOUCHER, Richard, C. , WEISMAN, Gary, A. , TURNER, John, T. , HARDEN, Thomas, K. , PARR, Claude, E. , SULLIVAN, Daniel, M. , ERB, Laura, J. , LUSTIG, Kevin, D.
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , THE CURATORS OF THE UNIVERSITY OF MISSOURI
IPC分类号： C07K14/705
CPC分类号： C07K14/705 , A61K38/00
摘要： Isolated DNAs encoding the human P2U receptor are disclosed, along with vectors and host cells containing the same and methods of using the same. Host cells which are essentially free of endogenous P2U receptor expression, and which express a heterologous P2U receptor such as a murine P2U receptor, are also disclosed, along with methods of using the same.
摘要翻译：公开了编码人P2U受体的分离的DNA，以及含有其的载体和宿主细胞以及使用它们的方法。还公开了基本上不含内源性P2U受体表达并且表达异源P2U受体如鼠P2U受体的宿主细胞，以及使用它们的方法。

3. 发明申请

WO1996040059A1 DINUCLEOTIDES USEFUL FOR THE TREATMENT OF LUNG DISEASE 审中-公开
标题翻译：用于治疗肺部疾病的胆管
公开(公告)号：WO1996040059A1
公开(公告)日：1996-12-19
申请号：PCT/US1996009190
申请日：1996-06-06
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , STUTTS, Monroe, J., III , BOUCHER, Richard, C., Jr. , LAZAROWSKI, Eduardo, R. , GEARY, Cara, A.
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： A61K09/12
CPC分类号： C07H21/00 , A61K9/0073 , A61K31/70 , A61K31/7072 , A61K31/7076 , A61K31/7084 , Y10S514/851 , A61K31/495 , A61K2300/00
摘要： A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is disclosed. In a compound of Formula (I): n is from 1 to 6; n is preferably from 2 to 4, and is most preferably 4. X is -OH or -SH, and is preferably -OH. A and B are each independently selected from the group consisting of (a) and (b) wherein R is H or Br. The compounds are useful in the treatment of airway diseases such as cystic fibrosis. Further disclosed are pharmaceutical formulations comprising, in pharmaceutically acceptable carriers (e.g., solid or liquid carriers), a compound of Formula (I) as given above. A method of hydrating mucous secretions in the lungs of a subject in need of such treatment, comprising administering to the lungs of the subject a compound of Formula (I) as given above, is also disclosed. The administering step is preferably carried out by inhalation.
摘要翻译：公开了式（I）化合物或其药学上可接受的盐。在式（I）的化合物中：n为1至6; n优选为2至4，最优选为4.X为-OH或-SH，优选为-OH。 A和B各自独立地选自（a）和（b），其中R是H或Br。该化合物可用于治疗气道疾病如囊性纤维化。进一步公开的是在药学上可接受的载体（例如固体或液体载体）中包含如上所述的式（I）化合物的药物制剂。本发明还公开了一种对需要这种治疗的受试者的肺中的粘液分泌物进行水合的方法，其中还包括对受试者的肺给予如上所述的式（I）的化合物。给药步骤优选通过吸入进行。

4. 发明申请

WO1997005195A1 METHOD OF DETECTING LUNG DISEASE 审中-公开
标题翻译：检测肺疾病的方法
公开(公告)号：WO1997005195A1
公开(公告)日：1997-02-13
申请号：PCT/US1996012377
申请日：1996-07-24
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , BOUCHER, Richard, C., Jr.
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： C08K05/15
CPC分类号： A61K9/0078 , A61K31/66 , A61K33/14 , A61K45/06 , A61K31/70 , A61K31/495 , A61K31/7004 , A61K31/165 , A61K31/14 , A61K2300/00
摘要： A method of facilitating the obtaining of a mucus sample from at least one lung of a subject comprises administering to at least one lung of the subject, in an amount effective to hydrate lung mucus secretions and/or stimulate cilia beat frequency therein, uridine 5'-triphosphate, an active analog thereof, or a pharmaceutically acceptable salt of either thereof, and, optionally, concurrently administering to said at least one lung a physiologically acceptable salt in an amount effective to hydrate lung mucus secretions therein. A sputum or mucus sample is then collected from said at least one lung, which sample can then be analyzed for lung disease. Pharmaceutical compositions useful for carrying out the method comprise UTP or a salt thereof, alone or in combination with a physiologically acceptable salt, or a pharmaceutically acceptable salt of either thereof. The composition may be a liquid/liquid suspension composition or a dry powder composition.
摘要翻译：促进从受试者的至少一个肺获得粘液样品的方法包括以有效水合肺粘液分泌物和/或刺激其中的纤毛节拍频率的剂量给予受试者的至少一个肺，尿苷5' 三磷酸盐，其活性类似物或其药学上可接受的盐，并且任选地，以有效水合物中的肺粘液分泌物的量向所述至少一个肺施用生理上可接受的盐。然后从所述至少一个肺采集痰液或粘液样品，然后可以分析该样品的肺部疾病。可用于实施该方法的药物组合物包含UTP或其盐单独或与其生理学上可接受的盐或其药学上可接受的盐组合。组合物可以是液体/液体悬浮液组合物或干粉组合物。

5. 发明申请

WO1996018385A1 METHODS OF TREATING LUNG DISEASE 审中-公开
标题翻译：治疗肺疾病的方法
公开(公告)号：WO1996018385A1
公开(公告)日：1996-06-20
申请号：PCT/US1995016066
申请日：1995-12-11
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , BOUCHER, Richard, C. , STUTTS, Monroe, Jackson
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： A61K09/12
CPC分类号： A61K31/7076 , A61K9/0073 , A61K31/4965 , A61K31/675 , Y10S514/851 , A61K2300/00
摘要： Methods of hydrating lung mucous secretions in the lungs of a subject are disclosed. The methods involve administering benzamil or phenamil (figures 1 and 2) to the lungs of the subject in an amount effective to hydrate lung mucous secretions. The administratiion step is carried out via aerosol and the method is useful for the treatment of cystic fibrosis and chronic bronchitis.
摘要翻译：公开了在受试者的肺中保湿肺粘液分泌物的方法。所述方法包括以有效水合肺粘膜分泌物的量将受试者的苯甲酰胺或苯胺（图1和2）施用于受试者的肺。施用步骤通过气雾剂进行，该方法可用于治疗囊性纤维化和慢性支气管炎。

6. 发明申请

WO1994028726A2 METHOD OF TREATING RETAINED PULMONARY SECRETIONS 审中-公开
标题翻译：治疗保留的脉搏分泌的方法
公开(公告)号：WO1994028726A2
公开(公告)日：1994-12-22
申请号：PCT/US1994006486
申请日：1994-06-08
申请人： THE WELLCOME FOUNDATION LIMITED , THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , MOLINA y VEDIA, Luis, M. , STUTTS, Monroe, Jackson , BOUCHER, Richard, C., Jr. , HENKE, David, C.
发明人： THE WELLCOME FOUNDATION LIMITED , THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： A16K37/02
CPC分类号： A61K38/164 , A61K38/04 , A61K38/12 , Y10S514/826 , Y10S514/851 , Y10S514/924 , A61K2300/00
摘要： A method of facilitating the clearance of retained pulmonary secretions in a subject using lantibiotics is disclosed. The method comprises administering to the lungs of the subject an effective amount of a lantibiotic. The lantibiotic is preferably administered by topically applying it to the respiratory epithelia, such as by generating an aerosol thereof which is then inhaled by the subject. A preferred lantibiotic for carrying out the present invention is duramycin. The method may be used in treating disorders such as cystic fibrosis, chronic bronchitis, and asthma. Also disclosed is a method of combatting tuberculosis comprising administering a lantibiotic to a subject in need of such treatment.
摘要翻译：公开了一种利用羊毛硫抗生素促进受试者残留肺分泌物清除的方法。该方法包括向受试者的肺部施用有效量的蓝霉素。羊毛硫抗生素优选通过将其局部施用于呼吸上皮，例如通过产生其随后被受试者吸入的气雾剂来施用。用于实施本发明的优选的羊毛硫抗生素是耐久霉素。该方法可用于治疗诸如囊性纤维化，慢性支气管炎和哮喘等疾病。还公开了一种抗结核病的方法，其包括对需要这种治疗的受试者施用蓝霉素。

7. 发明申请

WO1998058050A1 IMMORTALIZED HUMAN HEPATIC CELL LINE AND METHOD OF MAKING THE SAME 审中-公开
标题翻译：完整的人体细胞系及其制备方法
公开(公告)号：WO1998058050A1
公开(公告)日：1998-12-23
申请号：PCT/US1997019764
申请日：1997-08-21
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , BLASSER, Judith, F., H. , CHIAO, Chia , KAUFMANN, William, K. , KAUFMAN, David, G.
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： C12N01/20
CPC分类号： C12N5/067 , C12N2500/25 , C12N2500/84 , C12N2500/90 , C12N2510/04
摘要： An immortalized human hepatic cell line is disclosed. The cell line is created by lipofection of primary cultures of normal human fetal hepatic cells with a plasmid containing the second and third exons of the human c-myc gene driven by an SV-40 promoter. Cytochemical, morphological and phenotypical analyses indicated that the resulting cell line has hepatocyte characteristics. When these cells were analyzed after 90 passages they continued to express selected hepatocyte markers, including albumin and gamma-fibrinogen. Transmission electron microscopy reveals that the cells exhibit epithelial features, including desmosomal junctions and numerous surface microvilli, and form structures that resemble bile canaliculi. Methods of making the disclosed immortal hepatic cell line are also disclosed.
摘要翻译：公开了永生化的人肝细胞系。细胞系通过用包含由SV-40启动子驱动的人c-myc基因的第二和第三外显子的质粒通过正常人胎儿肝细胞的原代培养物的脂质转染来产生。细胞化学，形态学和表型分析表明所得细胞系具有肝细胞特征。当这些细胞在90代后被分析时，它们继续表达选定的肝细胞标志物，包括白蛋白和γ-纤维蛋白原。透射电子显微镜显示细胞表现出上皮特征，包括细胞外结合和许多表面微绒毛，并形成类似于胆小管的结构。还公开了公开的永生性肝细胞系的方法。

8. 发明申请

WO1998020042A1 HUMAN BLUE-LIGHT PHOTORECEPTOR hCRY2 审中-公开
标题翻译：人类蓝光光电子hCRY2
公开(公告)号：WO1998020042A1
公开(公告)日：1998-05-14
申请号：PCT/US1997020920
申请日：1997-11-04
申请人： HUMAN GENOME SCIENCES, INC. , THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , WEI, Ying-Fei , RUBEN, Steven, M. , SANCAR, Aziz , HSU, Shiao-Wen, D. , KAZANTSEV, Aleksey, G.
发明人： HUMAN GENOME SCIENCES, INC. , THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： C07K14/705
CPC分类号： C07K14/705 , C07K2319/00 , C12N2799/026
摘要： The present invention relates to a novel member of the blue-light photoreceptor family of receptors. In particular, isolated nucleic acid molecules are provided encoding the human hCRY2 receptor. hCRY2 polypeptides are also provided as are vectors, host cells, antibodies, and recombinant methods for producing the same.
摘要翻译：本发明涉及蓝光感光体受体家族的新成员。特别地，提供编码人hCRY2受体的分离的核酸分子。还提供hCRY2多肽，载体，宿主细胞，抗体和用于制备它们的重组方法。

9. 发明申请

WO1998008935A1 IMMORTALIZED HUMAN HEPATIC CELL LINE 审中-公开
标题翻译：完全免疫的人体细胞系
公开(公告)号：WO1998008935A1
公开(公告)日：1998-03-05
申请号：PCT/US1997014745
申请日：1997-08-21
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , BLASSER, Judith, F., H. , CHIAO, Chia
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
IPC分类号： C12N05/08
CPC分类号： C12N5/067 , C12N2500/25 , C12N2500/84 , C12N2500/90 , C12N2510/04
摘要： An immortalized human hepatic cell line is disclosed. The cell line is created by lipofection of primary cultures of normal human fetal hepatic cells with a plasmid containing the second and third exons of the human c-myc gene driven by an SV-40 promoter. Cytochemical, morphological and phenotypical analyses indicate that the resulting cell line has hepatocyte characteristics. When these cells were analyzed after 90 passages they continued to express selected hepatocyte markers, including albumin and gamma-fibrinogen. Transmission electron microscopy reveals that the cells exhibit epithelial features, including desmosomal junctions and numerous surface microvilli, and form structures that resemble bile canaliculi. Methods of making the disclosed immortal hepatic cell line are also disclosed.
摘要翻译：公开了永生化的人肝细胞系。通过用包含由SV-40启动子驱动的人c-myc基因的第二和第三外显子的质粒对正常人胎儿肝细胞的原代培养物进行脂质转染来产生细胞系。细胞化学，形态学和表型分析表明所得细胞系具有肝细胞特征。当这些细胞在90代后被分析时，它们继续表达选定的肝细胞标志物，包括白蛋白和γ-纤维蛋白原。透射电子显微镜显示细胞表现出上皮特征，包括细胞外结合和许多表面微绒毛，并形成类似于胆小管的结构。还公开了公开的永生性肝细胞系的方法。

10. 发明申请

WO1997030074A1 ISOLATION AND USE OF SH3 BINDING PEPTIDES 审中-公开
标题翻译：分离和使用SH3结合肽
公开(公告)号：WO1997030074A1
公开(公告)日：1997-08-21
申请号：PCT/US1997002298
申请日：1997-02-14
申请人： CYTOGEN CORPORATION , THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
发明人： CYTOGEN CORPORATION , THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , SPARKS, Andrew, B. , KAY, Brian, K. , THORN, Judith, M. , QUILLIAM, Lawrence, A. , DER, Channing, J. , FOWLKES, Dana, M. , RIDER, James, E.
IPC分类号： C07K05/04
CPC分类号： C07K7/06 , A61K38/00 , A61K47/62 , C07K7/08 , C07K14/001 , C07K14/435 , C07K2319/00 , C40B30/04 , G01N33/5008 , G01N33/5011 , G01N33/5041 , G01N33/573 , G01N33/68 , G01N33/6845
摘要： Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins comprising SH3 and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.
摘要翻译：在本发明中公开了对蛋白质的Src同源性区域3（SH3）结构域具有一般和特异性结合亲和力的肽。特别地，SH3结合肽已经从已经筛选分离物的噬菌体展示的随机肽文库中分离，所述分离物结合包含SH3和谷胱甘肽S-转移酶（GST）的细菌融合蛋白。公开了优选的肽，其包含核心序列的侧翼核心7-聚体序列（优选共有基序）和两个或多个，优选至少六个额外的氨基酸残基，总长度为9，优选至少13，氨基酸残基和不超过约45个氨基酸残基。这些肽表现出对某些SH3结构域的优先结合亲和力。优选的肽显示出对Src家族蛋白质的特异性结合亲和力。提出了体外和体内结果，证明了这些肽的生化活性。

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