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1. 发明申请

WO2005047245A2 FLUORESCENCE ASSAYS WITH IMPROVED SENSITIVITY 审中-公开
标题翻译：具有提高灵敏度的荧光测定
公开(公告)号：WO2005047245A2
公开(公告)日：2005-05-26
申请号：PCT/US2004038183
申请日：2004-11-15
申请人： WISCONSIN ALUMNI RES FOUND , PENN STATE RES FOUND , RAINES RONALD T , CHANDRAN SUNIL S , GLASS TIMOTHY E , LAVIS LUKE D
发明人： RAINES RONALD T , CHANDRAN SUNIL S , GLASS TIMOTHY E , LAVIS LUKE D
IPC分类号： C07D265/34 , C07D311/88 , C07D493/10 , C07D498/02 , C07H21/04 , C12Q1/34 , C12Q1/68 , G01N33/53 , G01N33/58 , C07D
CPC分类号： C12Q1/34 , C07D493/10 , C09B11/24 , C09B19/00 , G01N33/581 , G01N33/582 , G01N2333/916 , G01N2333/924
摘要： Latent fluorescent compounds, comprising a fluorescent molecule with one or more blocking groups attached and optionally one or more urea-containing groups are provided. The urea-containing group can be used to further attach one or more molecules of interest, such as proteins, peptides or nucleic acids. The blocking group(s) is released from the latent fluorescent compound by reaction with a trigger, forming the fluorescent molecule which can be detected. Also provided herein are methods of using latent fluorescent compounds to detect triggers.
摘要翻译：提供了包含具有一个或多个连接基团和任选的一个或多个含脲基团的荧光分子的潜在荧光化合物。含尿素基团可用于进一步连接一种或多种感兴趣的分子，例如蛋白质，肽或核酸。通过与触发剂反应，阻断基团从潜在荧光化合物释放，形成可被检测的荧光分子。本文还提供了使用潜伏荧光化合物来检测触发剂的方法。

2. 发明申请

WO2005020977A1 ALPHA-KETOGLUTARATE POTENTIATORS OF INSULIN SECRETION 审中-公开
标题翻译：胰蛋白酶分泌的ALPHA-葡萄糖酸钙电位
公开(公告)号：WO2005020977A1
公开(公告)日：2005-03-10
申请号：PCT/US2004/027206
申请日：2004-08-20
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , ATTIE, Alan, D. , RABAGLIA, Mary, E. , RAINES, Ronald, T. , GRAY-KELLER, Mark
发明人： ATTIE, Alan, D. , RABAGLIA, Mary, E. , RAINES, Ronald, T. , GRAY-KELLER, Mark
IPC分类号： A61K31/194
CPC分类号： G01N33/507 , A61K31/00 , A61K31/194 , A61K31/225 , A61K31/381 , A61K31/40 , A61K31/401 , A61K31/415 , A61K31/44 , A61K31/4422 , A61K31/455 , G01N33/5008 , G01N33/5038 , G01N2333/62 , Y10S514/866
摘要： The present invention relates to a recognition that an analog of αKG can increase glucose-induced insulin secretion in vitro and in vivo in animals, particularly in mammals, and more particularly in humans and in rodents. By employing the methods of the invention, insulin secretion can be increased.
摘要翻译：本发明涉及αKG的类似物可以在动物，特别是哺乳动物，特别是人和啮齿动物体内和体内增加葡萄糖诱导的胰岛素分泌的认识。通过采用本发明的方法，可以增加胰岛素分泌。

3. 发明申请

WO2005000872A3 COLLAGEN MIMICS 审中-公开
公开(公告)号：WO2005000872A3
公开(公告)日：2005-02-24
申请号：PCT/US2004020046
申请日：2004-06-23
申请人： WISCONSIN ALUMNI RES FOUND , RAINES RONALD T , MITCHELL JULIE C
发明人： RAINES RONALD T , MITCHELL JULIE C
IPC分类号： A61K38/00 , C07K20060101 , C07K5/08 , C07K14/00 , C07K14/78
CPC分类号： C07K5/0827 , A61K38/00 , C07K14/001 , C07K14/78
摘要： A novel collagen mimic comprising a tripeptide unit having the formula (flpYaaGly)n, where flp is 4(S)-fluoro-L-proline, is disclosed. The collagen mimic has increased stability relative to the collagen-related triple helices (ProYaaGly)n, (hypYaaGly)n, and (HypYaaGly)n.
摘要翻译：公开了包含具有式（flpYaaGly）n的三肽单元的新型胶原模拟物，其中flp是4（S） - 氟-L-脯氨酸。胶原模拟物相对于胶原相关的三联螺旋（ProYaaGly）n，（hypYaaGly）n和（HypYaaGly）n具有增加的稳定性。

4. 发明申请

WO2009048909A1 COMPOSITIONS AND METHODS FOR RIBONUCLEASE-BASED THERAPIES 审中-公开
标题翻译：用于基于核糖核酸酶的治疗的组合物和方法
公开(公告)号：WO2009048909A1
公开(公告)日：2009-04-16
申请号：PCT/US2008/079141
申请日：2008-10-08
申请人： QUINTESSENCE BIOSCIENCES, INC. , RAINES, Ronald, T. , RUTKOSKI, Thomas, J. , KINK, John, A. , STRONG, Laura, E.
发明人： RAINES, Ronald, T. , RUTKOSKI, Thomas, J. , KINK, John, A. , STRONG, Laura, E.
IPC分类号： A61K38/46
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005
摘要： The present invention relates generally to conjugates of human ribonucleases and watersoluble polymers, compositions comprising the conjugates and methods of using the same. In particular, the present invention provides conjugates of human ribonucleases and one or more water-soluble polymer compositions (e.g., to increase serum half-life and a pharmacokinetic profile, in vivo biological activity, stability, and/or reduce host immune response to the protein in vivo) as well as methods of using the conjugates in the therapy, treatment, and/or prevention of disease (e.g., cancer).
摘要翻译：本发明一般涉及人核糖核酸酶和水溶性聚合物的缀合物，包含缀合物的组合物及其使用方法。特别地，本发明提供人核糖核酸酶和一种或多种水溶性聚合物组合物的缀合物（例如，以增加血清半衰期和药代动力学特征，体内生物活性，稳定性和/或降低对体内的蛋白质）以及在治疗，治疗和/或预防疾病（例如癌症）中使用缀合物的方法。

5. 发明申请

WO2007139914A2 COLLAGEN MIMICS 审中-公开
公开(公告)号：WO2007139914A2
公开(公告)日：2007-12-06
申请号：PCT/US2007/012451
申请日：2007-05-25
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , RAINES, Ronald, T. , SHOULDERS, Matthew, D. , HODGES, Jonathan, A.
发明人： RAINES, Ronald, T. , SHOULDERS, Matthew, D. , HODGES, Jonathan, A.
IPC分类号： C07K14/78
CPC分类号： C07K14/78 , C07K5/0821 , C07K14/001
摘要： Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-GIy)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.
摘要翻译：公开了具有式（Xaa-Yaa-Gly）n的三肽单元的新型胶原模拟物，其中位置Xaa或Yaa之一是体积大的非吸电子脯氨酸衍生物。通过在天然胶原螺旋中的Xaa或Yaa位置取代脯氨酸衍生物，螺旋的稳定性仅由于相对于现有已知的胶原相关三螺旋的空间效应而增加。还公开了制备新型胶原模拟物的方法。

6. 发明申请

WO2006138558A2 CYTOTOXIC RIBONUCLEASE VARIANTS 审中-公开
标题翻译： CYTOTOXIC RIBONUCLEASE变种
公开(公告)号：WO2006138558A2
公开(公告)日：2006-12-28
申请号：PCT/US2006/023485
申请日：2006-06-16
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , RAINES, Ronald, T. , PHILLIPS, George, N., Jr. , JOHNSON, Jeremy, R. , MCCOY, Jason, G.
发明人： RAINES, Ronald, T. , PHILLIPS, George, N., Jr. , JOHNSON, Jeremy, R. , MCCOY, Jason, G.
IPC分类号： C12N9/22 , A61K38/43
CPC分类号： C12N9/22 , A61K38/00
摘要： This invention relates to cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase 1 hRI complex. Also disclosed is the 3-D structure of the hRI-RNase 1 complex and methods for designing the RNase 1 variants.
摘要翻译：本发明涉及通过分析核糖核酸酶1和核糖核酸酶抑制剂（hRI）之间的相互作用鉴定的人核糖核酸酶1（RNase 1）的细胞毒性变体，如RNase 1 hRI复合物的三维（3-D）原子结构所定义。还公开了hRI-RNase 1复合物的3-D结构和用于设计RNA酶1变体的方法。

7. 发明申请

WO2005000872A2 COLLAGEN MIMICS 审中-公开
公开(公告)号：WO2005000872A2
公开(公告)日：2005-01-06
申请号：PCT/US2004/020046
申请日：2004-06-23
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , RAINES, Ronald, T. , MITCHELL, Julie, C.
发明人： RAINES, Ronald, T. , MITCHELL, Julie, C.
IPC分类号： C07K
CPC分类号： C07K5/0827 , A61K38/00 , C07K14/001 , C07K14/78
摘要： A novel collagen mimic comprising a tripeptide unit having the formula (flpYaaGly) n , where flp is 4(S)-fluoro-L-proline, is disclosed. The collagen mimic has increased stability relative to the collagen-related triple helices (ProYaaGly) n , (hypYaaGly) n , and (HypYaaGly) n .
摘要翻译：公开了包含具有式（flpYaaGly）n的三肽单元的新型胶原模拟物，其中flp是4（S） - 氟-L-脯氨酸。胶原蛋白模拟物相对于胶原相关的三重螺旋（ProYaaGly）n，（hypYaaGly）n和（HypYaaGly）n具有增加的稳定性。

8. 发明申请

WO2006138458A1 CYTOTOXIC RIBONUCLEASE VARIANTS 审中-公开
标题翻译： CYTOTOXIC RIBONUCLEASE变种
公开(公告)号：WO2006138458A1
公开(公告)日：2006-12-28
申请号：PCT/US2006/023298
申请日：2006-06-16
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , RAINES, Ronald, T. , MITCHELL, Julie, C. , RUTKOSKI, Thomas, J.
发明人： RAINES, Ronald, T. , MITCHELL, Julie, C. , RUTKOSKI, Thomas, J.
IPC分类号： C12N15/55 , C12N9/22 , A61K38/00
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译：本发明涉及RNA酶A超家族成员的改变形式。核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。

9. 发明申请

WO2005047245A3 FLUORESCENCE ASSAYS WITH IMPROVED BLOCKING GROUPS 审中-公开
公开(公告)号：WO2005047245A3
公开(公告)日：2005-05-26
申请号：PCT/US2004/038183
申请日：2004-11-15
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , THE PENN STATE RESEARCH FOUNDATION , RAINES, Ronald, T. , CHANDRAN, Sunil, S. , GLASS, Timothy, E. , LAVIS, Luke, D.
发明人： RAINES, Ronald, T. , CHANDRAN, Sunil, S. , GLASS, Timothy, E. , LAVIS, Luke, D.
IPC分类号： C07D311/00
摘要： Latent fluorescent compounds, comprising a fluorescent molecule with one or more blocking groups attached and optionally one or more urea-containing groups are provided. The urea-containing group can be used to further attach one or more molecules of interest, such as proteins, peptides or nucleic acids. The blocking group(s) is released from the latent fluorescent compound by reaction with a trigger, forming the fluorescent molecule which can be detected. Also provided herein are methods of using latent fluorescent compounds to detect triggers.

10. 发明申请

WO2013119690A1 NUCLEIC ACID LIGATION METHOD 审中-公开
标题翻译：核酸配方法
公开(公告)号：WO2013119690A1
公开(公告)日：2013-08-15
申请号：PCT/US2013/024965
申请日：2013-02-06
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , RAINES, Ronald, T. , DESAI, Kevin, K.
发明人： RAINES, Ronald, T. , DESAI, Kevin, K.
IPC分类号： C12P19/34 , C12Q1/68 , C07H21/02 , C07H21/04 , C12N15/10
CPC分类号： C12P19/34 , C12N9/00 , C12N9/93 , C12N15/1093
摘要： Methods and kits for covalently joining a 3' nucleic acid fragment having a 5'-hydroxyl terminus to a 5' nucleic acid fragment having a 3 '-phosphate terminus are disclosed. The methods include the step of contacting the 3'-phosphate terminus of a first nucleic acid molecule and the 5'-hydroxyl terminus of a second nucleic acid molecule with an isolated 2',3'-cyclic phosphate RNA ligase (RtcB) and a purine triphosphate in the presence of manganese (II) ion, whereby the 3 '-phosphate terminus of the first nucleic acid molecule and the 5'-hydroxyl terminus of the second nucleic acid molecule are covalently joined. Although the purine triphosphate used is generally GTP or dGTP, if the method is performed in the presence of an Archease, any purine triphosphate may be used. Accordingly, the disclosed kits include isolated RtcB, along with a purine triphosphate and/or an isolated Archease. Such methods and kits can be used to tag or ligate DNA or RNA on its 3'-phosphate terminus, as long as the terminal residue at the 3'-phosphate terminus is an RNA nucleotide.
摘要翻译：公开了共价连接具有5'-羟基末端的3'核酸片段至具有3'-磷酸末端的5'核酸片段的方法和试剂盒。所述方法包括使第一核酸分子的3'-磷酸末端和第二核酸分子的5'-羟基端与分离的2'，3'-环磷酸酯RNA连接酶（RtcB）和在锰（II）离子存在下的三磷酸嘌呤，由此第一核酸分子的3'-磷酸末端和第二核酸分子的5'-羟基末端共价连接。尽管所用的三磷酸嘌呤通常是GTP或dGTP，但是如果该方法在Archease存在下进行，则可以使用任何嘌呤三磷酸。因此，所公开的试剂盒包括分离的RtcB，以及嘌呤三磷酸酯和/或分离的原料。只要3'-磷酸末端的末端残基是RNA核苷酸，这样的方法和试剂盒可用于标记或连接其3'-磷酸末端上的DNA或RNA。

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