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41. 发明申请

WO1997045558A1 IDENTIFICATION OF PYRAZINAMIDE-RESISTANT MYCOBACTERIA AND METHODS FOR TREATING MYCOBACTERIAL INFECTIONS 审中-公开
标题翻译：吡虫啉耐药性鉴定及治疗感染性肝炎的方法
公开(公告)号：WO1997045558A1
公开(公告)日：1997-12-04
申请号：PCT/US1997008770
申请日：1997-05-23
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , ZHANG, Ying , SCORPIO, Angelo
IPC分类号： C12Q01/68
CPC分类号： C12Q1/689 , A61K38/00 , C12N9/80 , C12Q2600/156
摘要： Disclosed are methods, probes, primers and kits for identifying pyrazinamide-resistant mycobacteria. These methods can be used to distinguish M. bovis from M. tuberculosis, as well as to identify additional pyrazinamide-resistant mycobacteria. Also disclosed are methods for treating mycobacterial infections by expressing a pncA gene in mycobacteria that infect a mammal, and treating the mammal with pyrazinamide. The invention derives from the discovery of that the molecular basis for pyrazinamide resistance is an alteration in the pncA gene of mycobacteria. The detection of such an alteration is an indicator of PZA-resistant mycobacteria.
摘要翻译：公开了用于鉴定吡嗪酰胺抗性分枝杆菌的方法，探针，引物和试剂盒。这些方法可用于区分牛分枝杆菌与结核分枝杆菌，以及鉴定其他吡嗪酰胺抗性分枝杆菌。还公开了通过在感染哺乳动物的分枝杆菌中表达pncA基因并用吡嗪酰胺处理哺乳动物来治疗分枝杆菌感染的方法。本发明源于发现吡嗪酰胺抗性的分子基础是分枝杆菌pncA基因的改变。这种改变的检测是PZA抗性分枝杆菌的指标。

42. 发明申请

WO1997044814A1 METHOD AND APPARATUS FOR ISOLATING IONS IN AN ION TRAP WITH INCREASED RESOLVING POWER 审中-公开
标题翻译：用于在离子束中分离离子的方法和装置，具有增加的分辨力
公开(公告)号：WO1997044814A1
公开(公告)日：1997-11-27
申请号：PCT/US1997008346
申请日：1997-05-19
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , DOROSHENKO, Vladimir M. , COTTER, Robert, J.
IPC分类号： H01J49/42
CPC分类号： H01J49/424 , H01J49/427
摘要： A method of operation of an ion trap mass spectrometer which isolates a first group of ions having a mass-to-charge ratio range is disclosed. The method includes producing ions from a plurality of atoms or molecules; trapping the ions in the ion trap by applying a trapping voltage to a ring electrode; applying an excitation voltage to a pair of end-cap electrodes; employing as the excitation voltage a broadband excitation waveform having first, second, and third excitation portions, with the first and third excitation portions exciting the ions excluding substantially all of the first group of ions and also excluding substantially all of a second group of ions having a range of mass-to-charge ratios about the at least one mass-to-charge ratio of the first group of ions, and the second excitation portion exciting the second group of ions; applying the first and third excitation portions in order to eject the ions excluding substantially all of the first and second groups of ions; and applying the second excitation portion in order to sequentially eject the ions excluding substantially all of the first group of ions, thereby isolating the first group of ions in the ion trap. Associated apparatus is also disclosed.
摘要翻译：公开了一种离子阱质谱仪的操作方法，其分离具有质荷比范围的第一组离子。该方法包括从多个原子或分子产生离子; 通过向环形电极施加捕获电压来捕获离子阱中的离子; 向一对端帽电极施加激励电压; 使用具有第一，第二和第三激励部分的宽带激励波形作为激励电压，其中所述第一和第三激励部分激励所述离子基本上除了所有第一组离子之外的离子，并且还排除基本上所有第二组离子，关于第一组离子的至少一个质荷比的质量 - 电荷比范围和激发第二组离子的第二激发部分; 施加第一和第三激发部分以排出除了基本上所有第一和第二组离子之外的离子; 以及施加所述第二激发部分以顺序地排出除了基本上所有第一组离子之外的离子，从而隔离离子阱中的第一组离子。还公开了相关装置。

43. 发明申请

WO1997018806A1 INHIBITION OF FATTY ACID SYNTHASE AS A MEANS TO REDUCE ADIPOCYTE MASS 审中-公开
标题翻译：脂肪酸合成酶的抑制作为减少ADIPOCYTE质量的手段
公开(公告)号：WO1997018806A1
公开(公告)日：1997-05-29
申请号：PCT/US1996017678
申请日：1996-11-15
申请人： THE JOHNS HOPKINS UNIVERSITY , KUHAJDA, Francis, P. , PASTERNACK, Gary, R. , TOWNSEND, Craig, A. , MANI, Neelakandha, S.
发明人： THE JOHNS HOPKINS UNIVERSITY
IPC分类号： A61K31/365
CPC分类号： A61K31/365
摘要： Weight loss was noted in nude mice treated with cerulenin, a non-competitive inhibitor of FAS. Sustained reduction of adipocyte mass in humans without toxicity would significantly impact disease prevention worldwide. Aside from psychological and self-esteem improvement, weight loss via reduction of adipocyte mass may: (1) ameliorate hyperglycemia associated with non-insulin-dependent diabetes mellitus thereby reducing diabetic complications such as arterial disease, blindness, cataracts, etc., (2) reduce hypertension, (3) reduce risk of coronary artery vascular disease and stroke, and (4) reduce the risk of other complications of massive obesity such as osteoarthritis, surgical complications, etc. There is also potential use in livestock and poultry to reduce the saturated fat content of meat products. Therefore FAS inhibitors are disclosed herein as novel agents for weight reduction. A family of compounds ( gamma -substituted- alpha -methylene- beta -carboxy- gamma -butyrolactones) whose synthesis was based on the cerulenin motif is shown herein to inhibit fatty acid synthesis, inhibit growth in certain susceptible tumor cells, and induce weight loss.
摘要翻译：在使用非竞争性FAS抑制剂的木瓜素处理的裸小鼠中注意到体重减轻。持续减少人体脂肪细胞质量无毒性将严重影响全球疾病预防。除了心理和自尊心的改善之外，通过减少脂肪细胞质量可以减轻体重：（1）改善与非胰岛素依赖性糖尿病相关的高血糖，从而减少糖尿病并发症，如动脉疾病，失明，白内障等（2 ）降低高血压，（3）降低冠状动脉血管疾病和卒中的风险，（4）降低骨质疏松，手术并发症等巨大肥胖的其他并发症的风险。畜禽养殖也有潜在的用途肉制品的饱和脂肪含量。因此，本文公开了FAS抑制剂作为减轻体重的新型药剂。本文显示了其合成基于苏氨酸基序的化合物（γ-取代-α-亚甲基-β-羧基-γ-丁内酯）家族，以抑制脂肪酸合成，抑制某些易感的肿瘤细胞中的生长并诱导体重减轻。

44. 发明申请

WO1996037611A1 EB1 GENE PRODUCT BINDS TO APC 审中-公开
标题翻译： EB1基因产品绑定到APC
公开(公告)号：WO1996037611A1
公开(公告)日：1996-11-28
申请号：PCT/US1996007747
申请日：1996-05-22
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth
IPC分类号： C12N15/12
CPC分类号： C07K14/47 , A61K38/00 , C07K2319/00
摘要： Inactivation of the APC tumor suppressor gene plays an important role in the development of both sporadic and familial forms of colorectal cancers. The majority of these mutations result in the loss of the carboxyl terminus of the APC protein. A cellular protein, EB1, that associates with the carboxyl terminus of APC both in vitro and in vivo has been identified. The EB1 gene is predicted to encode a 268 amino acid protein without significant homology to any protein with known function.
摘要翻译： APC肿瘤抑制基因的失活在结肠直肠癌的散发和家族形式的发展中起重要作用。这些突变中的大多数导致APC蛋白的羧基末端的损失。已经鉴定了在体外和体内与APC的羧基末端缔合的细胞蛋白质EB1。 EB1基因被预测编码268个氨基酸的蛋白质，而与具有已知功能的任何蛋白质没有显着的同源性。

45. 发明申请

WO1995023875A1 IN VITRO TRANSPOSITION OF ARTIFICIAL TRANSPOSONS 审中-公开
标题翻译：人体运输的人体运输
公开(公告)号：WO1995023875A1
公开(公告)日：1995-09-08
申请号：PCT/US1995002520
申请日：1995-03-02
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , DEVINE, Scott, E. , BOEKE, Jef, D. , BRAITERMAN, Lelita, T.
IPC分类号： C12Q01/68
CPC分类号： C12N15/90 , C12Q1/6869 , C12Q1/6895
摘要： We have developed efficient methods of creating artificial transposons and inserting these transposons into DNA targets in vitro, primarily for the purpose of mapping and sequencing DNA. A target DNA has been engineered to convert virtually any DNA sequence, or combination of sequences, into an artificial transposon; hence, custom transposons containing any desired feature can be easily designed and constructed. Such transposons are then efficiently inserted into DNA targets, in vitro, using the integrase activity present in yeast Ty1 virus-like particles. Primers complementary to the transposon termini can be used to sequence DNA flanking any transposon insertion.
摘要翻译：我们已经开发了有效的方法来创建人工转座子，并将这些转座子在体外插入到DNA靶标中，主要是为了测序和测序DNA的目的。目标DNA已被设计成将几乎任何DNA序列或序列的组合转化成人工转座子; 因此，可以容易地设计和构造含有任何期望特征的定制转座子。然后使用存在于酵母Ty1病毒样颗粒中的整合酶活性，将该转座子在体外有效地插入DNA靶标中。与转座子末端互补的引物可用于对任何转座子插入侧翼的DNA进行序列比对。

46. 发明申请

WO1995020952A1 INHIBITORS OF POLY(ADP-RIBOSE) SYNTHETASE AND USE THEREOF TO PREVENT NMDA NEUROTOXICITY 审中-公开
标题翻译：聚（ADP-RIBOSE）合成酶的抑制剂及其用于预防NMDA神经毒性
公开(公告)号：WO1995020952A1
公开(公告)日：1995-08-10
申请号：PCT/US1995001189
申请日：1995-02-02
申请人： THE JOHNS HOPKINS UNIVERSITY , THE UNITED STATES OF AMERICA, NATIONAL INSTITUTE ON DRUG ABUSE, ADDICTION RESEARCH CENTER
发明人： THE JOHNS HOPKINS UNIVERSITY , THE UNITED STATES OF AMERICA, NATIONAL INSTITUTE ON DRUG ABUSE, ADDICTION RESEARCH CENTER , ZHANG, Jie , DAWSON, Valina, L. , DAWSON, Ted, M. , SNYDER, Solomon, H.
IPC分类号： A61K31/165
CPC分类号： A61K31/47 , A61K31/165
摘要： Inhibitors of poly(ADP-ribose) synthetase can be used to prevent neurotoxicity mediated through N-methyl-D-aspartate (NMDA) receptors. Poly(ADP-ribose) synthetase inhibitors can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.
摘要翻译：聚（ADP-核糖）合成酶的抑制剂可用于预防由N-甲基-D-天冬氨酸（NMDA）受体介导的神经毒性。聚（ADP-核糖）合成酶抑制剂可用于治疗血管性中风和神经变性疾病如阿尔茨海默氏病，帕金森病和亨廷顿舞蹈病。

47. 发明申请

WO1995015400A1 GENOTYPING BY SIMULTANEOUS ANALYSIS OF MULTIPLE MICROSATELLITE LOCI 审中-公开
标题翻译：通过同时分析多个微阵列位置进行基因分析
公开(公告)号：WO1995015400A1
公开(公告)日：1995-06-08
申请号：PCT/US1994013945
申请日：1994-12-05
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , LEVITT, Roy, C.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6858 , C12Q2563/143 , C12Q2537/143
摘要： Despite the introduction of molecular methods, such as the polymerase chain reaction, and the discovery of highly polymorphic microsatellite markers, genotyping remains a rate limiting factor in our ability to localize disease genes by linkage. This invention provides a method for genotyping multiple loci by semi-automated fluorescence-based techniques that is both highly accurate and efficient as compared to conventional techniques. The semi-automated techniques developed will be useful in high resolution genomic analyses including: linkage studies, cancer genetics, forensics, and cytogenetics including studies of uniparental disomy or other patterns of chromosomal inheritance.
摘要翻译：尽管引入了分子方法，如聚合酶链反应和高度多态性微卫星标记的发现，但是基因分型仍然是我们通过连锁定位疾病基因的能力的速率限制因素。本发明提供了一种通过基于半自动荧光的技术对多个基因座进行基因分型的方法，其与常规技术相比是高度准确和高效的。开发的半自动化技术将在高分辨率基因组分析中有用，包括：连锁研究，癌症遗传学，取证和细胞遗传学，包括对单亲二倍体或其他染色体遗传模式的研究。

48. 发明申请

WO1994025625A1 MEANS FOR DETECTING FAMILIAL COLON CANCER (FCC) 审中-公开
标题翻译：检测家族性癌症（FCC）的手段
公开(公告)号：WO1994025625A1
公开(公告)日：1994-11-10
申请号：PCT/US1994004785
申请日：1994-05-02
申请人： THE JOHNS HOPKINS UNIVERSITY , DE LA CHAPELLE, Albert
发明人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/683 , A61K38/00 , C07K14/82 , C12Q1/6886 , C12Q2600/112 , C12Q2600/156 , C12Q2600/172
摘要： Markers of chromosome 2 are associated with cancer predisposition, as shown by linkage analysis, in a significant fraction of families with a history of colon and other cancers. Tumors from these patients progressed through the same series of accumulated mutations in oncogenes and tumor suppressor genes found in non-familial cases, but showed no losses of heterozygosity for the linked chromosome 2 markers. DNA from the tumors (but not normal tissues) in most familial cases revealed a consistent and distinct abnormality: rearrangemnets in short repeated sequences throughout their genomes. This abnormality suggests that a large number of replication errors had occurred during tumor development. Methods are presented for detecting the presence of the gene which predisposes people to have a colon and other tumors and for utilizing this information for diagnostic, prognostic, and preventive purposes. DNA markers useful for such methods are also described.
摘要翻译：染色体2的标记与癌症倾向相关，如通过连锁分析所显示的，具有结肠和其他癌症病史的家族的很大一部分。来自这些患者的肿瘤通过在非家族性病例中发现的致癌基因和肿瘤抑制基因的相同序列的累积突变进行，但是对于连锁的2号染色体标记物，没有显示出杂合性的损失。在大多数家族性病例中，肿瘤（但不是正常组织）的DNA显示出一致和明显的异常：在整个基因组中以短的重复序列重新排列。这种异常表明在肿瘤发展过程中发生了大量的复制错误。提出了用于检测易患人群具有结肠和其他肿瘤的基因的存在并用于诊断，预后和预防目的的方法。还描述了对这些方法有用的DNA标记。

49. 发明申请

WO1994021814A1 ANTIBODIES AND ASSAYS FOR DETERMINING MUTATIONS IN THE APC GENE 审中-公开
标题翻译：用于确定APC基因中突变的抗体和测定
公开(公告)号：WO1994021814A1
公开(公告)日：1994-09-29
申请号：PCT/US1994002987
申请日：1994-03-21
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , HILL, David, E. , JOHNSON, Karen, A. , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12P21/08
CPC分类号： C07K16/18 , C07K14/47 , C07K16/22 , C07K2319/00
摘要： Antibodies and assays employing them are taught which are useful for detecting the bulk of mutations which occur in the APC gene in familial adenomatous polyposis. The antibodies are specific for epitopes in the amino terminal or carboxy terminal portion of the protein. A variety of immunoassay formats are described which are all based on the observation that the bulk of the APC mutations which occur in familial adenomatous polyposis and sporadic colorectal carcinomas result in truncated APC proteins. Generally, either the size of APC proteins is determined or the relative binding of amino terminal-binding antibodies to carboxy terminal-binding antibodies is determined.
摘要翻译：教导了使用它们的抗体和测定法，其可用于检测家族性腺瘤性息肉病中APC基因中发生的大量突变。抗体对蛋白质的氨基末端或羧基末端部分中的表位是特异性的。描述了各种免疫测定方法，这些形式都是基于观察到发生在家族性腺瘤性息肉病和散发性结肠直肠癌中的大部分APC突变导致截短的APC蛋白。通常，确定APC蛋白的大小或确定氨基末端结合抗体与羧基末端结合抗体的相对结合。

50. 发明申请

WO1994017192A2 LYSOSOMAL TARGETING OF IMMUNOGENS 审中-公开
标题翻译：免疫球蛋白的体外靶向
公开(公告)号：WO1994017192A2
公开(公告)日：1994-08-04
申请号：PCT/US1994000588
申请日：1994-01-21
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , AUGUST, J., Thomas , PARDOLL, Drew, M. , GUARNIERI, Frank, G.
IPC分类号： C12N15/62
CPC分类号： C07K14/70539 , A61K39/00 , C07K14/705 , C07K2319/06 , C07K2319/40 , Y02A50/412 , Y10S530/806
摘要： The inventors have discovered a targeting signal that will direct proteins to the endosomal/lysosomal compartment, and they have demonstrated that chimeric proteins containing a luminal antigenic domain and a cytoplasmic endosomal/lysosomal targeting signal will effectively target antigens to that compartment, where the antigenic domain is processed and peptides from it are presented on the cell surface in association with major histocompatibility (MHC) class II molecules. Chimeric DNA encoding the antigen of interst, linked to an endosomal/lysosomal targeting sequence, inserted in an immunization vector, can introduce the chimeric genes into cells, where the recombinant antigens are expressed and targeted to the endosomal/lysosomal compartment. As a result, the antigens associate more efficiently with MHC class II molecules, providing enhanced in vivo stimulation of CD4 T cells specific for the the recombinant antigen. Delivering antigens to an endosomal/lysosomal compartment by means of chimeric constructs containing such lysosomal targeting signals will be of value in any vaccination or immunization strategy that seeks to stimulate CD4 MHC class II restricted immune responses.
摘要翻译：本发明人已经发现了将蛋白质引导到内体/溶酶体区室的靶向信号，并且他们已经证明含有腔内抗原结构域和细胞质内体/溶酶体靶向信号的嵌合蛋白将有效地将抗原靶向该区室，其中抗原结构域被处理，并且来自它的肽与主要组织相容性（MHC）II类分子相关联地呈现在细胞表面上。插入到免疫载体中的编码与体内/溶酶体靶向序列连接的interst抗原的嵌合DNA可将嵌合基因导入细胞，其中重组抗原被表达并靶向内体/溶酶体区室。结果，抗原更有效地与MHC II类分子相关联，提供对重组抗原特异性的CD4 + T细胞的增强的体内刺激。通过含有这样的溶酶体靶向信号的嵌合构建体将抗原递送到内体/溶酶体区域将在任何试图刺激CD4 + MHC II类受限免疫应答的疫苗接种或免疫策略中是有价值的。

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