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1. 发明申请

WO2007089470A9 ANTIGEN-BINDING PROTEINS TARGETING S. AUREUS ORF0657N 审中-公开
标题翻译：抗原结合蛋白质靶向S. Aureus ORF0657N
公开(公告)号：WO2007089470A9
公开(公告)日：2007-11-01
申请号：PCT/US2007001687
申请日：2007-01-23
申请人： MERCK & CO INC , BROWN MARTHA J , ANDERSON ANNALIESA S , COPE LESLIE D , JANSEN KATHRIN UTE , MCNEELY TESSIE , HARVEY BARRETT , DURR ERBERHARD , ERNST ROBIN
发明人： BROWN MARTHA J , ANDERSON ANNALIESA S , COPE LESLIE D , JANSEN KATHRIN UTE , MCNEELY TESSIE , HARVEY BARRETT , DURR ERBERHARD , ERNST ROBIN
IPC分类号： A61K39/40
CPC分类号： C07K16/1271 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/72 , C07K2317/92
摘要： The present invention features antigen binding protein that bind an ORF0657n target region (SEQ ID NO: 1). ORF0657n is an S. aureus protein. ORF0657n target regions are provided by the mAb 1G3.BD4, mAb 2H2.BE11, mAb 13C7.BC1, and mAb 13G11.BF3 binding sites. In a lethal model challenge, mAb 2H2.BE11 and mAb 13C7.BC1 provided for increased survival against S. aureus infection. There was also protection demonstrated in an ex vivo model with either the IgG1 or the IgG2b form of mAb 2H2; and in a passive immunization murine indwelling catheter model using mAb 2H2.BE11.
摘要翻译：本发明涉及结合ORF0657n靶区（SEQ ID NO：1）的抗原结合蛋白。 ORF0657n是金黄色葡萄球菌蛋白。 ORF0657n靶区由mAb 1G3.BD4，mAb 2H2.BE11，mAb 13C7.BC1和mAb 13G11.BF3结合位点提供。在致死模型挑战中，mAb 2H2.BE11和mAb 13C7.BC1提供了针对金黄色葡萄球菌感染的增加的存活。在具有mAb 2H2的IgG1或IgG2b形式的离体模型中也证实了保护作用; 并在使用mAb 2H2.BE11的被动免疫小鼠留置导管模型中。

2. 发明申请

WO2005095988A3 SELECTION OF BACTERIAL INNER-MEMBRANE ANCHOR POLYPEPTIDES 审中-公开
标题翻译：选择细菌内膜锚固多糖
公开(公告)号：WO2005095988A3
公开(公告)日：2006-03-02
申请号：PCT/US2005009009
申请日：2005-03-18
申请人： UNIV TEXAS , GEORGIOU GEORGE , HARVEY BARRETT R , JEONG KI JUN , IVERSON BRENT L
发明人： GEORGIOU GEORGE , HARVEY BARRETT R , JEONG KI JUN , IVERSON BRENT L
IPC分类号： G01N33/569 , C12N15/10 , C40B40/02 , G01N33/68
CPC分类号： C12N15/1086 , C07K2319/034 , C12N15/1037 , C40B40/02
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FAGS).
摘要翻译：本发明克服了现有技术的缺陷，提供了一种用于分离能够将异源多肽固定在细菌内膜上的多肽的快速方法。在该技术中，候选锚多肽的文库表达为与异源多肽的融合，当与内膜结合时能够被检测。在表达功能性锚定序列的细菌中，异源多肽与内膜的外表面结合。具有功能性锚定序列的细菌可以通过除去外膜以除去非锚定的异源多肽，然后检测锚定的异源多肽来鉴定。可以以多种方式检测这样的细菌，包括使用荧光标记的直接荧光或二级抗体，允许使用有效技术，例如荧光激活细胞分选（FAGS）。

3. 发明申请

WO2005095988A2 SELECTION OF BACTERIAL INNER-MEMBRANE ANCHOR POLYPEPTIDES 审中-公开
标题翻译：选择细菌内膜锚固多糖
公开(公告)号：WO2005095988A2
公开(公告)日：2005-10-13
申请号：PCT/US2005/009009
申请日：2005-03-18
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , GEORGIOU, George , HARVEY, Barrett, R. , JEONG, Ki Jun , IVERSON, Brent, L.
发明人： GEORGIOU, George , HARVEY, Barrett, R. , JEONG, Ki Jun , IVERSON, Brent, L.
IPC分类号： G01N33/68
CPC分类号： C12N15/1086 , C07K2319/034 , C12N15/1037 , C40B40/02
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FAGS).
摘要翻译：本发明克服了现有技术的缺陷，提供了一种用于分离能够将异源多肽固定在细菌内膜上的多肽的快速方法。在该技术中，候选锚多肽的文库表达为与异源多肽的融合，当与内膜结合时能够被检测。在表达功能性锚定序列的细菌中，异源多肽与内膜的外表面结合。具有功能性锚定序列的细菌可以通过除去外膜以除去非锚定的异源多肽，然后检测锚定的异源多肽来鉴定。可以以多种方式检测这样的细菌，包括使用荧光标记的直接荧光或二级抗体，允许使用有效技术，例如荧光激活细胞分选（FAGS）。

4. 发明申请

WO2007089470A3 ANTIGEN-BINDING PROTEINS TARGETING S. AUREUS ORF0657N 审中-公开
标题翻译：抗原结合蛋白质定位S. AUREUS ORF0657N
公开(公告)号：WO2007089470A3
公开(公告)日：2008-01-24
申请号：PCT/US2007001687
申请日：2007-01-23
申请人： MERCK & CO INC , BROWN MARTHA J , ANDERSON ANNALIESA S , COPE LESLIE D , JANSEN KATHRIN UTE , MCNEELY TESSIE , HARVEY BARRETT , DURR ERBERHARD , ERNST ROBIN
发明人： BROWN MARTHA J , ANDERSON ANNALIESA S , COPE LESLIE D , JANSEN KATHRIN UTE , MCNEELY TESSIE , HARVEY BARRETT , DURR ERBERHARD , ERNST ROBIN
IPC分类号： G01N33/53 , C12N5/06 , C12N5/16
CPC分类号： C07K16/1271 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/72 , C07K2317/92
摘要： The present invention features antigen binding protein that bind an ORF0657n target region (SEQ ID NO: 1). ORF0657n is an S. aureus protein. ORF0657n target regions are provided by the mAb 1G3.BD4, mAb 2H2.BE11, mAb 13C7.BC1, and mAb 13G11.BF3 binding sites. In a lethal model challenge, mAb 2H2.BE11 and mAb 13C7.BC1 provided for increased survival against S. aureus infection. There was also protection demonstrated in an ex vivo model with either the IgG1 or the IgG2b form of mAb 2H2; and in a passive immunization murine indwelling catheter model using mAb 2H2.BE11.
摘要翻译：本发明涉及结合ORF0657n靶区（SEQ ID NO：1）的抗原结合蛋白。 ORF0657n是金黄色葡萄球菌蛋白。 ORF0657n靶区域由mAb 1G3.BD4，mAb 2H2.BE11，mAb 13C7.BC1和mAb 13G11.BF3结合位点提供。在致死模型挑战中，mAb 2H2.BE11和mAb 13C7.BC1提供了对金黄色葡萄球菌感染的增加的存活。在具有mAb 2H2的IgG1或IgG2b形式的离体模型中也证实了保护作用; 并在使用mAb 2H2 .BE11的被动免疫小鼠留置导管模型中。

5. 发明申请

WO2007089470A2 ANTIGEN-BINDING PROTEINS TARGETING S. AUREUS ORF0657N 审中-公开
标题翻译：靶向S. AUREUS ORF0657N的抗原结合蛋白
公开(公告)号：WO2007089470A2
公开(公告)日：2007-08-09
申请号：PCT/US2007/001687
申请日：2007-01-23
申请人： MERCK & CO., INC. , BROWN, Martha, J. , ANDERSON, Annaliesa, S. , COPE, Leslie, D. , JANSEN, Kathrin, Ute , MCNEELY, Tessie , HARVEY, Barrett , DURR, Erberhard , ERNST, Robin
发明人： BROWN, Martha, J. , ANDERSON, Annaliesa, S. , COPE, Leslie, D. , JANSEN, Kathrin, Ute , MCNEELY, Tessie , HARVEY, Barrett , DURR, Erberhard , ERNST, Robin
IPC分类号： A61K39/40
CPC分类号： C07K16/1271 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/72 , C07K2317/92
摘要： The present invention features antigen binding protein that bind an ORF0657n target region (SEQ ID NO: 1). ORF0657n is an S. aureus protein. ORF0657n target regions are provided by the mAb 1G3.BD4, mAb 2H2.BE11, mAb 13C7.BC1, and mAb 13G11.BF3 binding sites. In a lethal model challenge, mAb 2H2.BE11 and mAb 13C7.BC1 provided for increased survival against S. aureus infection. There was also protection demonstrated in an ex vivo model with either the IgG1 or the IgG2b form of mAb 2H2; and in a passive immunization murine indwelling catheter model using mAb 2H2.BE11.
摘要翻译：本发明的特征在于结合ORF0657n靶区域（SEQ ID NO：1）的抗原结合蛋白。 ORF0657n是一个S。金黄色蛋白。 ORF0657n靶区由mAb 1G3.BD4，mAb 2H2.BE11，mAb 13C7.BC1和mAb 13G11.BF3结合位点提供。在致命的模型挑战中，mAb 2H2.BE11和mAb 13C7.BC1提供了针对S的存活增加。金黄色葡萄球菌感染。在体外模型中还显示出具有mAb 2H2的IgG1或IgG2b形式的保护作用; 以及使用mAb 2H2.BE11的被动免疫鼠科留置导管模型。

6. 发明申请

WO2005019409A3 COMBINATORIAL PROTEIN LIBRARY SCREENING BY PERIPLASMIC EXPRESSION 审中-公开
标题翻译：通过外周表达组合蛋白图书馆筛选
公开(公告)号：WO2005019409A3
公开(公告)日：2007-07-12
申请号：PCT/US0321928
申请日：2003-07-15
申请人： UNIV TEXAS , HARVEY BARRETT R , GEORGIOU GEORGE , IVERSON BRENT I
发明人： HARVEY BARRETT R , GEORGIOU GEORGE , IVERSON BRENT I
IPC分类号： A61K38/00 , A61K39/00 , A61K39/07 , A61K39/395 , A61K39/40 , C07H21/04 , C07K7/00 , C07K16/00 , C07K16/12 , C12N20060101 , C12N1/21 , C12N15/10 , C12N15/13 , C12N15/70 , C12Q1/02 , C12Q1/04 , C12Q3/00 , G01N33/53 , G01N33/554 , G01N33/569 , G01N33/68
CPC分类号： C07K16/005 , C07K2317/622 , C07K2317/92 , C12N15/1034 , C12Q1/025 , G01N33/6845
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in the periplasm of gram negative bacteria and mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the outer surface-expression of ligand fusion proteins employed with phage display. The inventors have also provided improved antobodies that were initially prepared using the sceening methods developed.
摘要翻译：本发明通过提供用于分离能够结合小分子和肽的结合蛋白的快速方法来克服现有技术的缺陷。在该技术中，候选结合蛋白（例如抗体序列）的文库在革兰氏阴性细菌的周质中表达并与标记的配体混合。在表达具有对配体具有亲和性的重组多肽的克隆中，与结合蛋白结合的标记配体的浓度增加，允许细胞与文库的其余部分分离。当使用靶配体的荧光标记时，可以通过荧光激活细胞分选（FACS）分离细胞。该方法比现有技术的方法更快速，并且避免了与噬菌体展示使用的配体融合蛋白的外表面表达相关的问题。本发明人还提供了改进的本体，其最初使用所开发的方法制备。

7. 发明申请

WO2005019409A2 COMBINATORIAL PROTEIN LIBRARY SCREENING BY PERIPLASMIC EXPRESSION 审中-公开
标题翻译：通过周边表达组合蛋白图书馆筛选
公开(公告)号：WO2005019409A2
公开(公告)日：2005-03-03
申请号：PCT/US2003/021928
申请日：2003-07-15
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , HARVEY, Barrett, R. , GEORGIOU, George , IVERSON, Brent, I.
发明人： HARVEY, Barrett, R. , GEORGIOU, George , IVERSON, Brent, I.
IPC分类号： C12N
CPC分类号： C07K16/005 , C07K2317/622 , C07K2317/92 , C12N15/1034 , C12Q1/025 , G01N33/6845
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in the periplasm of gram negative bacteria and mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the outer surface-expression of ligand fusion proteins employed with phage display. The inventors have also provided improved antobodies that were initially prepared using the sceening methods developed.
摘要翻译：本发明通过提供用于分离能够结合小分子和肽的结合蛋白的快速方法来克服现有技术的缺陷。在该技术中，候选结合蛋白（例如抗体序列）的文库在革兰氏阴性细菌的周质中表达并与标记的配体混合。在表达对配体具有亲和性的重组多肽的克隆中，与结合蛋白结合的标记配体的浓度增加，并允许细胞与文库的其余部分分离。当使用靶配体的荧光标记时，可以通过荧光激活细胞分选（FACS）分离细胞。该方法比现有技术方法更快速，并且避免了与噬菌体展示一起使用的配体融合蛋白的外表面表达相关的问题。本发明人还提供了改进的本体，其最初使用所开发的方法制备。

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