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1. 发明申请

WO1993024834A1 METHOD AND PRODUCT FOR THE SEQUENCE DETERMINATION OF PEPTIDES USING A MASS SPECTROMETER 审中-公开
标题翻译：使用质谱仪序列测定肽的方法和产品
公开(公告)号：WO1993024834A1
公开(公告)日：1993-12-09
申请号：PCT/US1993005070
申请日：1993-05-27
申请人： THE ROCKEFELLER UNIVERSITY , CHAIT, Brian, T. , BEAVIS, Ronald , WANG, Rong , KENT, Stephen, B., H.
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： G01N33/44
CPC分类号： G01N33/6842 , C07K1/107 , C07K1/128 , G01N33/6824 , Y10T436/24 , Y10T436/25 , Y10T436/255
摘要： Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.
摘要翻译：描述了通过形成包含一系列多肽的肽梯级来测序多肽的方法，其中该序列的相邻成员变化一个氨基酸残基，并通过质谱确定多肽中每个氨基酸的同一性和位置。

2. 发明申请

WO1998006752A1 A LEPTIN BINDING PROTEIN AND ITS USE IN METHODS FOR DIAGNOSING AND TREATING ABNORMALITIES OF THE ENDOGENOUS LEPTIN PATHWAY 审中-公开
标题翻译： L蛋白结合蛋白及其在内源性途径途径诊断和治疗异常的方法中的应用
公开(公告)号：WO1998006752A1
公开(公告)日：1998-02-19
申请号：PCT/US1997014597
申请日：1997-08-15
申请人： THE ROCKEFELLER UNIVERSITY , LALLONE, Roger
发明人： THE ROCKEFELLER UNIVERSITY , FRIEDMAN, Jeffrey, M.
IPC分类号： C07K14/775
CPC分类号： C07K14/5759 , A61K38/00 , C07K14/775 , C07K16/18 , C07K16/26 , C07K2317/34 , G01N33/74 , G01N2333/575 , G01N2333/775 , G01N2800/02 , G01N2800/52
摘要： The present invention discloses a leptin binding protein that plays a novel role in the regulation of adiposity and fat content of animals, particularly in mammals. The leptin binding protein binds to leptin in vivo, forming a leptin-leptin binding protein complex that functions to provide a means for regulating body weight and adiposity. The present invention exploits this novel role of the leptin binding protein by providing means for diagnosing, monitoring, treating and curing abnormalities of the endogenous leptin pathway. Apolipoprotein J serves as an example of this new class of leptin binding protein.
摘要翻译：本发明公开了一种瘦素结合蛋白，其在调节动物，特别是哺乳动物的肥胖和脂肪含量方面起新的作用。瘦素结合蛋白在体内与瘦蛋白结合，形成瘦蛋白 - 瘦蛋白结合蛋白复合物，其功能是提供调节体重和肥胖的手段。本发明通过提供用于诊断，监测，治疗和治疗内源性瘦素途径的异常的方法来利用瘦素结合蛋白的这种新颖作用。载脂蛋白J作为这一新型瘦蛋白结合蛋白的一个例子。

3. 发明申请

WO1997041151A2 CHOLINE BINDING PROTEINS FOR ANTI-PNEUMOCOCCAL VACCINES 审中-公开
标题翻译：用于抗肺气肿疫苗的胆固醇蛋白
公开(公告)号：WO1997041151A2
公开(公告)日：1997-11-06
申请号：PCT/US1997007198
申请日：1997-05-01
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , MASURE, H., Robert , ROSENOW, Carsten, I. , TUOMANEN, Elaine , WIZEMAN, Theresa, M.
IPC分类号： C07K14/315
CPC分类号： C07K14/3156 , A61K38/00 , A61K39/00 , A61K48/00 , A61K2039/51
摘要： The invention relates to bacterial choline binding proteins (CBPs) which bind choline. Such proteins are particularly desirable for vaccines against appropriate strains of Gram positive bacteria, particularly streptococcus, and more particularly pneumococcus. Also provided are DNA sequences encoding the bacterial choline binding proteins or fragment thereof, antibodies to the bacterial choline binding proteins, pharmaceutical compositions comprising the bacterial choline binding proteins, antibodies to the bacterial choline binding proteins suitable for use in passive immunization, and small molecule inhibitors of choline binding protein mediated adhesion. Methods for diagnosing the presence of the bacterial choline binding protein, or of the bacteria, are also provided. In a specific embodiment, a streptococcal choline binding protein is an enolase, which demonstrates strong affinity for fibronectin.
摘要翻译：本发明涉及结合胆碱的细菌胆碱结合蛋白（CBP）。对于针对革兰氏阳性菌，特别是链球菌，更特别是肺炎球菌的合适菌株的疫苗，这种蛋白质是特别需要的。还提供了编码细菌胆碱结合蛋白或其片段的DNA序列，细菌胆碱结合蛋白的抗体，包含细菌胆碱结合蛋白的药物组合物，适用于被动免疫的细菌胆碱结合蛋白的抗体和小分子抑制剂的胆碱结合蛋白介导的粘附。还提供了用于诊断细菌胆碱结合蛋白或细菌存在的方法。在具体实施方案中，链球菌胆碱结合蛋白是烯醇化酶，其对纤连蛋白表现出强亲和力。

4. 发明申请

WO1997003660A2 MODULATION OF PROTEIN PHOSPHATASE ACTIVITY AND USES RELATING TO FERTILITY AND CONTRACEPTION 审中-公开
标题翻译：蛋白磷酸酶活性的调节和与肥胖相关的使用
公开(公告)号：WO1997003660A2
公开(公告)日：1997-02-06
申请号：PCT/US1996011805
申请日：1996-07-17
申请人： THE ROCKEFELLER UNIVERSITY , OREGON REGIONAL PRIMATE RESEARCH CENTER, INC.
发明人： THE ROCKEFELLER UNIVERSITY , OREGON REGIONAL PRIMATE RESEARCH CENTER, INC. , FIGUEIREDO DA CRUZ E SILVA, Edgar , GREENGARD, Paul , VIJAYARAGHAVAN, Srinivasan , SMITH, Gary, Daniel
IPC分类号： A61K31/00
CPC分类号： A61K31/675 , A61K31/00 , A61K31/35
摘要： Mammalian sperm motility can be regulated by modulation of a protein phosphatase-1 (PP-1). Such modulation can be used to increase the fertility of individuals whose sperm are either immotile or submotile by treatment with a phosphatase inhibitor either in vitro or in vivo (during sperm maturation in the epididymis). Conversely, activators of GSK-3 activity which increase the phosphatase activity of motile sperm, can be utilized to decrease sperm motility and reduce the chances for reproductive success.
摘要翻译：哺乳动物精子活力可通过调节蛋白磷酸酶-1（PP-1）来调节。这种调节可用于通过在体外或体内（在附睾精子成熟期间）用磷酸酶抑制剂处理来增加精子是不动的或潜伏的个体的生育力。相反，增加活动精子的磷酸酶活性的GSK-3活性激活剂可用于降低精子活力并降低生殖成功的机会。

5. 发明申请

WO1996040943A1 USE OF GRAM-POSITIVE BACTERIA TO EXPRESS RECOMBINANT PROTEINS 审中-公开
标题翻译：使用GRAM阳性细菌来表达重组蛋白
公开(公告)号：WO1996040943A1
公开(公告)日：1996-12-19
申请号：PCT/US1996009965
申请日：1996-06-06
申请人： THE ROCKEFELLER UNIVERSITY , DARZINS, Aldis , WHITEHEAD, Stephen , HRUBY, Dennis
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： C12N15/62
CPC分类号： C07K14/31 , A61K38/00 , A61K39/00 , C07K14/315 , C07K2319/00 , C07K2319/02 , C07K2319/035 , C07K2319/23 , C07K2319/50 , C07K2319/705 , C07K2319/735 , C12N15/62 , C12N15/74
摘要： A novel system for cloning and expression of genes in gram-positive bacteria. The expression system is based on the finding that many gram-positive bacteria sort proteins to their cell surface through cis-acting N-terminal signal sequences and C-terminal anchor regions. In particular, the cell sorting signals of the streptococcal M6 protein, a well-known surface molecule, are used to construct a gram-positive expression system, designated SPEX (Streptococcal Protein Expression). Expression is achieved by cloning the gene of interest into an appropriate SPEX cassette which is then stably introduced into a bacterial host, such as the human commensal Streptococcus gordonii. Depending on the SPEX vector used, recombinant proteins can be anchored to the cell wall prior to release by specific endoproteolytic cleavage or secreted into the culture medium during bacterial growth. The use of host bacteria lacking extracellular proteases should protect secreted proteins from proteolytic degradation. Several expression vectors in this system also produce specifically-tagged recombinant proteins which allows for a one-step purification of the resulting product.
摘要翻译：用于克隆和表达革兰氏阳性菌中基因的新系统。表达系统基于许多革兰氏阳性细菌通过顺式作用的N末端信号序列和C末端锚定区域将蛋白质分解到其细胞表面的发现。特别地，使用众所周知的表面分子的链球菌M6蛋白的细胞分选信号来构建称为SPEX（链球菌蛋白表达）的革兰氏阳性表达系统。通过将感兴趣的基因克隆到适当的SPEX盒中，然后将其稳定地导入细菌宿主例如人共生型链球菌（Streptococcus gordonii）中来实现表达。根据所使用的SPEX载体，重组蛋白质可以在通过特异性内切蛋白酶切割释放之前锚定到细胞壁上，或在细菌生长过程中分泌到培养基中。缺乏细胞外蛋白酶的宿主细菌的使用应保护分泌的蛋白质免于蛋白水解降解。该系统中的几种表达载体也产生特异性标记的重组蛋白，其允许对所得产物进行一步纯化。

6. 发明申请

WO1996029406A3 NUCLEAR LOCALIZATION FACTOR ASSOCIATED WITH CIRCADIAN RHYTHMS 审中-公开
公开(公告)号：WO1996029406A3
公开(公告)日：1996-09-26
申请号：PCT/US1996003830
申请日：1996-03-20
申请人： THE ROCKEFELLER UNIVERSITY , UNIVERSITY OF PENNSYLVANIA
发明人： THE ROCKEFELLER UNIVERSITY , UNIVERSITY OF PENNSYLVANIA , YOUNG, Michael, W. , SEHGAL, Amita , VOSSHALL, Leslie, B. , PRICE, Jeffrey, L. , MYERS, Michael, P.
IPC分类号： C12N15/12

7. 发明申请

WO1996021011A3 PEPTIDES SPECIFIC FOR THE FIRST Crk-SH3 DOMAIN 审中-公开
公开(公告)号：WO1996021011A3
公开(公告)日：1996-07-11
申请号：PCT/US1995016979
申请日：1995-12-28
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , HANAFUSA, Hidesaburo , KNUDSEN, Beatrice, S. , FELLER, Stephan, M. , KURIYAN, John , WU, Xiaodong , ZHENG, Jie , COWBURN, David
IPC分类号： C12N15/11

8. 发明申请

WO1996017061A1 AN SH3 KINASE DOMAIN ASSOCIATED PROTEIN, A SIGNALLING DOMAIN THEREIN, NUCLEIC ACIDS ENCODING THE PROTEIN AND THE DOMAIN, AND DIAGNOSTIC AND THERAPEUTIC USES THEREOF 审中-公开
标题翻译： AN SH3激酶相关蛋白，信号域，编码蛋白和域的核酸及其诊断和治疗用途
公开(公告)号：WO1996017061A1
公开(公告)日：1996-06-06
申请号：PCT/US1995015512
申请日：1995-11-30
申请人： THE ROCKEFELLER UNIVERSITY , THE MAX DELBRVECK CENTER FOR MOLECULAR MEDICINE
发明人： THE ROCKEFELLER UNIVERSITY , THE MAX DELBRVECK CENTER FOR MOLECULAR MEDICINE , SUDOL, Marius , CHEN, Henry , BORK, Peer
IPC分类号： C12N15/12
CPC分类号： C07K14/47 , A61K38/00 , C07K14/46 , C07K2319/00
摘要： The present invention relates to regulation and control of cellular processes by SH3-domain binding proteins, by putative signalling domains of such proteins, ligands of the signalling domain, and diagnosis and therapy based on the activity of such proteins, signalling domains, and ligands.
摘要翻译：本发明涉及通过SH3结构域结合蛋白调节和控制细胞过程，通过这些蛋白质的推定的信号转导域，信号结构域的配体，以及基于这些蛋白质，信号结构域和配体的活性的诊断和治疗。

9. 发明申请

WO1995035112A2 MODULATORS OF PNEUMOCOCCAL ADHESION TO CELLULAR TARGETS INVOLVING THE PLATELET ACTIVATING FACTOR RECEPTOR, AND USES THEREOF 审中-公开
标题翻译：涉及平板激活因子受体的细胞粘附的肺炎粘附调节剂及其用途
公开(公告)号：WO1995035112A2
公开(公告)日：1995-12-28
申请号：PCT/US1995007687
申请日：1995-06-19
申请人： THE ROCKEFELLER UNIVERSITY , BETH ISRAEL HOSPITAL ASSOCIATION
发明人： THE ROCKEFELLER UNIVERSITY , BETH ISRAEL HOSPITAL ASSOCIATION , TUOMANEN, Elaine, I. , CUNDELL, Diana, R. , GERARD, Norma, P.
IPC分类号： A61K31/70
CPC分类号： A61K31/7008 , A61K31/00 , A61K31/341 , A61K31/343 , A61K31/551 , A61K38/1793 , A61K39/3955 , A61K31/7016 , A61K2300/00
摘要： The present invention relates to compositions and methods for preventing pneumococcal infection. In particular, the invention relates to identification of the major reception for Streptococcus pneumoniae on activated human cells, and diagnostic and therapeutic conpositions and methods based thereon. In particular, the invention relates to the discovery that platelet activating factor (PAF) receptor is an adhesive ligand for pneumococcal adherence to activated lung epithelial and venous endothelial (i.e., host) cells. Accordingly, the present invention is directed to a method for preventing or treating an infection with Streptococcus pneumoniae by administering an antogonist of platelet activating factor receptor. The invention further relates to recognition that adherence to activated cells also involves a carbohydrate ligand found on such activated cells. Thus, a method for inhibiting pneumococcal adherence may further comprise administering an amount of carbohydrate containing an N-acetyl-D-glucosamine motif. It has been found that resting lung epithelial and venous endothelial cells bear two classes of receptors containing different carbohydrate motifs. Thus, the invention further provides for administering an amount of a second carbohydrate selected from the group consisting of a carbohydrate containing a disaccharide N-acetyl-D-galactosamine beta 1-4Gal motif, a disaccharide N-acetyl-D-galactosamine beta 1-3Gal motif, and a mixture thereof. In addition, the invention provides pharmaceutical compositions comprising such agents that inhibit binding of pneumococci to human cells. In a specific example, platelet activating factor receptor antagonists and disaccharides are shown to inhibit binding of pneumococci to activated lung epithelial cells and venous endothelial cells, as well as cells transfected with the platelet activating factor receptor, in vitro.
摘要翻译：本发明涉及预防肺炎球菌感染的组合物和方法。特别地，本发明涉及鉴定活化的人细胞上的肺炎链球菌的主要接收，以及基于此的诊断和治疗结合及方法。特别地，本发明涉及血小板活化因子（PAF）受体是用于肺炎球菌粘附于活化的肺上皮和静脉内皮（即宿主）细胞的粘合剂配体的发现。因此，本发明涉及一种预防或治疗肺炎链球菌感染的方法，该方法是通过施用血小板激活因子受体的脱发子。本发明还涉及认识到对活化细胞的依附性还涉及在这种活化细胞上发现的碳水化合物配体。因此，抑制肺炎球菌粘附的方法还可以包括给予一定量的含有N-乙酰基-D-葡糖胺基序的碳水化合物。已经发现，休息的肺上皮和静脉内皮细胞具有包含不同碳水化合物基序的两类受体。因此，本发明进一步提供一定量的第二种碳水化合物，其选自含有二糖N-乙酰基-D-半乳糖胺β1-4Gal基序的碳水化合物，二糖N-乙酰基-D-半乳糖胺β1- 3Gal图案及其混合物。此外，本发明提供了包含抑制肺炎球菌与人细胞结合的药剂的药物组合物。在具体实例中，血小板激活因子受体拮抗剂和二糖在体外显示出抑制肺炎球菌与活化的肺上皮细胞和静脉内皮细胞以及转染血小板活化因子受体的细胞的结合。

10. 发明申请

WO1995021381A1 METHODS AND AGENTS FOR MEASURING AND CONTROLLING MULTIDRUG RESISTANCE 审中-公开
标题翻译：测量和控制多电阻电阻的方法和试剂
公开(公告)号：WO1995021381A1
公开(公告)日：1995-08-10
申请号：PCT/US1995001247
申请日：1995-01-31
申请人： THE ROCKEFELLER UNIVERSITY , BOARD OF TRUSTEES OPERATING MICHIGAN STATE UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , BOARD OF TRUSTEES OPERATING MICHIGAN STATE UNIVERSITY , SIMON, Sanford, M. , SCHINDLER, Melvin, M., S.
IPC分类号： G01N33/84
CPC分类号： G01N33/5011
摘要： The predominent effect of pH change on multidrug resistance (MDR) independent of active drug efflux has been demonstrated in tumor cells throught studies of the drugs doxorubicin and daunomycin. Specifically, the distribution of both drugs was monitored in fibrobalsts and myeloma cells to examine the role of pH in drug partitioning . The invention comprises in one aspect the treatment of MDR by administering a therapeutically effective amount of a pH modulator. Diagnostic utilities are contemplated and extend to drug discovery assays and methods for measuring monitoring the status of the onset or development of pH-related conditions such as MDR, as well as the measurement of intracellular drug accumulation. Therapeutic compositions include a composition comprising a pH modulator alone or in combination with the dose-limited therapeutic agent(s), and a pharmaceutically acceptable excipient, are also contemplated.
摘要翻译：在药物多柔比星和道诺霉素的肿瘤细胞中已经证明了pH变化对多药耐药性（MDR）的主要影响，与药物流出有关。具体来说，在纤维板和骨髓瘤细胞中监测两种药物的分布，以检查pH在药物分配中的作用。本发明在一个方面包括通过施用治疗有效量的pH调节剂治疗MDR。诊断实用程序被考虑并且扩展到药物发现测定和用于测量监测pH相关条件如MDR的发作或发展的状态以及细胞内药物积累的测量的方法。治疗组合物还包括包含单独或与剂量受限治疗剂组合的pH调节剂和药学上可接受的赋形剂的组合物。

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