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1. 发明申请

WO2009099672A2 BREAKING IMMUNOLOGICAL TOLERANCE WITH A GENETICALLY ENCODED UNNATURAL AMINO ACID 审中-公开
标题翻译：用遗传编码的非天然氨基酸突破免疫学公差
公开(公告)号：WO2009099672A2
公开(公告)日：2009-08-13
申请号：PCT/US2009/000813
申请日：2009-02-07
申请人： THE SCRIPPS RESEARCH INSTITUTE , GRUNEWALD, Jan , TSAO, Meng-Lin , PERERA, Roshan , LERNER, Richard, A. , SMIDER, Vaughn, V. , SCHULTZ, Peter, G.
发明人： GRUNEWALD, Jan , TSAO, Meng-Lin , PERERA, Roshan , LERNER, Richard, A. , SMIDER, Vaughn, V. , SCHULTZ, Peter, G.
IPC分类号： A61K39/395 , A61K31/19 , A61P37/04 , A61P35/00 , A61P25/28
CPC分类号： C07K16/241 , A61K31/19 , A61K39/0008 , C07K16/44 , Y02A50/491 , Y02A50/492
摘要： The present invention comprises methods and compositions for producing and/or enhancing an immunological response in a subject against a target moiety such as a disease-related moiety by administration of an antigenic version of the target moiety having one or more unnatural amino acid and/or by administration of an antibody against a version of a target moiety having one or more unnatural amino acid which antibody is cross reactive with the natural target moiety.
摘要翻译：本发明包括用于通过施用具有一个靶部分的抗原形式来产生和/或增强受试者针对靶部分如疾病相关部分的免疫应答的方法和组合物或更多非天然氨基酸和/或通过施用针对具有一个或多个非天然氨基酸的形式的靶部分的抗体，所述抗体与天然靶部分交叉反应。

2. 发明公开

EP2890836A2 METHODS AND COMPOSITIONS RELATED TO MODULATORS OF EUKARYOTIC CELLS 有权转让
标题翻译： ZUSAMMENHANG MUS MODERATOREN VON EUKARYOTISCHEN ZELLEN VERFAHREN UND ZUSAMMENSETZUNGEN
公开(公告)号：EP2890836A2
公开(公告)日：2015-07-08
申请号：EP13833286.1
申请日：2013-08-16
申请人： The Scripps Research Institute , Zhang, Hongkai , Wilson, Ian, A. , LERNER, Richard A.
发明人： ZHANG, Hongkai , WILSON, Ian, A. , LERNER, Richard, A.
IPC分类号： C40B50/06 , C12N5/00 , C12P21/06
CPC分类号： C07K16/2863 , C07K14/71 , C07K14/7153 , C07K16/2839 , C07K16/2866 , C07K2317/21 , C07K2317/31 , C07K2317/35 , C07K2317/622 , C07K2317/74 , C07K2317/75 , C07K2317/92 , C07K2319/30 , C40B30/06 , G01N33/6845 , G01N33/6854 , G01N33/746
摘要： The invention provides specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR, or G-CSFR).
摘要翻译：本发明提供了在真核细胞（例如，EpoR，TpoR或G-CSFR的激动剂抗体）中调节表型或影响细胞应答的信号受体或生物分子的特异性激动剂抗体。

3. 发明申请

WO2015095511A3 FUNCTIONAL ANTIBODIES THAT MODULATE CELL DEATH AND RELATED METHODS 审中-公开
公开(公告)号：WO2015095511A3
公开(公告)日：2015-06-25
申请号：PCT/US2014/071136
申请日：2014-12-18
申请人： THE SCRIPPS RESEARCH INSTITUTE , LERNER, Richard, A. , XIE, Jia , ZHANG, Hongkai
发明人： LERNER, Richard, A. , XIE, Jia , ZHANG, Hongkai
IPC分类号： A61K39/00 , C12P21/08 , C12N5/02 , C40B40/02 , G01N33/566 , C07H21/04
摘要： The invention provides methods for identifying antibody modulators of cell death from an intracellularly expressed library of intrabodies or membrane-tethered antibodies. The antibody modulators can promote or inhibit death of various target cells (e.g., tumor cells or neurons). Also provided in the invention are specific functional antibodies which can prevent death of cells caused by viral infections, as well as therapeutic applications of the antibodies. Further provided in the invention are polynucleotide sequences and vectors for expressing the functional antibodies disclosed herein.

4. 发明申请

WO2014035693A2 METHODS AND COMPOSITIONS RELATED TO MODULATORS OF EUKARYOTIC CELLS 审中-公开
标题翻译：与真核细胞调节剂相关的方法和组合物
公开(公告)号：WO2014035693A2
公开(公告)日：2014-03-06
申请号：PCT/US2013/055362
申请日：2013-08-16
申请人： THE SCRIPPS RESEARCH INSTITUTE , ZHANG, Hongkai , WILSON, Ian, A. , LERNER, Richard, A.
发明人： ZHANG, Hongkai , WILSON, Ian, A. , LERNER, Richard, A.
IPC分类号： C40B30/06
CPC分类号： C07K16/2863 , C07K14/71 , C07K14/7153 , C07K16/2839 , C07K16/2866 , C07K2317/21 , C07K2317/31 , C07K2317/35 , C07K2317/622 , C07K2317/74 , C07K2317/75 , C07K2317/92 , C07K2319/30 , C40B30/06 , G01N33/6845 , G01N33/6854 , G01N33/746
摘要： The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist, of a target molecule (e.g.,. a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.
摘要翻译：本发明提供鉴定真核细胞的蛋白质调节剂（例如抗体激动剂）的方法。方法通常涉及在真核细胞类型（例如，哺乳动物细胞）内表达组合试剂文库（例如通过慢病毒载体），然后直接选择靶分子的激动剂（例如，抗体）（例如，一种信号受体），其调节细胞中的表型或引起细胞反应。一些相关方法涉及共培养表达组合试剂文库和第二细胞的细胞，然后选择调节第二细胞中表型或引起细胞应答的试剂。优选地，所述试剂是抗体，并且在每个单个细胞表达不超过3个抗体文库的不同成员的条件下被引入并在起始细胞中表达。此外，本发明提供了鉴定能够重新编程或反向分化靶细胞的蛋白质激动剂的方法。本发明还提供了调节表型或在真核细胞（例如EpoR，TpoR或G-CSFR的激动剂抗体）中调节细胞应答的信号传导受体或生物分子的特异性激动剂抗体。本发明还提供了从组合抗体文库中选择可以调节细胞表型的双特异性抗体的方法。

5. 发明申请

WO2002081647A2 BIOLUMINESCENT PLANTS AND METHODS OF MAKING SAME 审中-公开
标题翻译：生物发光植物及其制备方法
公开(公告)号：WO2002081647A2
公开(公告)日：2002-10-17
申请号：PCT/US2002/011116
申请日：2002-04-08
申请人： THE SCRIPPS RESEARCH INSTITUTE , KAY, Steve, A. , KUHLMANN, Tina , LERNER, Richard, A.
发明人： KAY, Steve, A. , KUHLMANN, Tina , LERNER, Richard, A.
IPC分类号： C12N
CPC分类号： C12N15/8241
摘要： A genetically modified plant cell containing a heterologous nucleotide sequence encoding a bioluminescent polypeptide, which is expressed in amount sufficient to produce at least about 750,000 photons of visible light/mm 2 /second, is provided, as is a visibly bioluminescent transgenic plant, which contains such a genetically modified plant cell. Also provided is a recombinant nucleic acid molecule, which contains a plant translational enhancer operatively linked to a nucleotide sequence encoding a bioluminescent polypeptide. In addition, methods of producing a genetically modified plant cell that is visibly bioluminescent introducing a transgene encoding a bioluminescent polypeptide into a plant cell, whereby the bioluminescent polypeptide is expressed at a level that produces at least about 750,000 photons of visible light/mm 2 /second are provided, as are kits containing such visibly bioluminescent compositions.
摘要翻译：提供了含有编码生物发光多肽的异源核苷酸序列的遗传修饰的植物细胞，其以足以产生至少约750000个可见光/ mm 2 /秒的光子的量表达，如可见生物发光转基因植物，其含有这样的遗传修饰的植物细胞。还提供了重组核酸分子，其包含与编码生物发光多肽的核苷酸序列可操作地连接的植物翻译增强子。另外，生产显性生物发光的转基因植物细胞的方法是将编码生物发光多肽的转基因导入植物细胞，由此生物发光多肽以至少约75万光束的可见光/ mm 2表达 > /秒，以及含有这种可视生物发光组合物的试剂盒。

6. 发明申请

WO2008006102A3 USE OF RETRO-ALDOL REACTION TO GENERATE REACTIVE VINYL KETONE FOR ATTACHMENT TO ANITIBODY MOLECULES BY MICHAEL ADDITION REACTION FOR USE IN IMMUNOSTAINING AND IMMUNOTARGETING 审中-公开
公开(公告)号：WO2008006102A3
公开(公告)日：2008-01-10
申请号：PCT/US2007/073046
申请日：2007-07-09
申请人： THE SCRIPPS RESEARCH INSTITUTE , SINHA, Subhash, C. , BARBAS, Carlos, F., III , LERNER, Richard, A.
发明人： SINHA, Subhash, C. , BARBAS, Carlos, F., III , LERNER, Richard, A.
IPC分类号： C12P7/26 , C07K16/00 , C12N9/02
摘要： The present invention is directed to methods for formation of a chemically programmed antibody comprising the steps of: (1) reacting a conjugate comprising a signal module covalently linked to a proadapter with a catalytic moiety selected from the group consisting of a catalytic antibody and a Fab fragment of a catalytic antibody, wherein the proadapter includes therein a precursor to a reactive moiety activated to a reactive moiety by a reaction catalyzed by the catalytic moiety; and (2) crosslinking the reactive moiety to a side chain of an amino acid residue in the active site of the catalytic moiety to produce the chemically programmed antibody. The invention also encompasses chemically programmed antibodies formed by these methods, methods for their use, and pharmaceutical compositions, as well as proadaptors and conjugates including them. Chemically programmed antibodies are useful for the treatment of cancer, particularly in metastasis.

7. 发明申请

WO2005023831A1 DETECTION OF CHOLESTEROL OZONATION PRODUCTS 审中-公开
标题翻译：检测胆固醇消毒产品
公开(公告)号：WO2005023831A1
公开(公告)日：2005-03-17
申请号：PCT/US2004/029063
申请日：2004-09-03
申请人： THE SCRIPPS RESEARCH INSTITUTE , WENTWORTH, Paul , LERNER, Richard, A.
发明人： WENTWORTH, Paul , LERNER, Richard, A.
IPC分类号： C07J9/00
CPC分类号： C07K16/44 , C07C35/44 , C07C49/523 , C07C49/757 , C07C251/76 , C07C251/82 , C07C251/84 , C07C311/49 , C07C2601/14 , C07C2601/16 , C07C2602/08 , C07C2602/24 , C07C2603/40 , C07D313/04 , C07J9/00 , C07J41/0005 , C07J61/00 , C07K16/18 , G01N33/92 , G01N2800/044
摘要： The invention relates to detection of cholesterol ozonation products that are generated by atherosclerotic plaque material, and to methods of detecting vascular conditions that relate to the accumulation and oxidation of cholesterol.
摘要翻译：本发明涉及由动脉粥样硬化斑块材料产生的胆固醇臭氧化产物的检测，以及检测与胆固醇积聚和氧化有关的血管病症的方法。

8. 发明申请

WO2005023830A2 THERAPEUTIC PROCEDURES 审中-公开
标题翻译：治疗程序
公开(公告)号：WO2005023830A2
公开(公告)日：2005-03-17
申请号：PCT/US2004/028685
申请日：2004-09-03
申请人： THE SCRIPPS RESEARCH INSTITUTE , WENTWORTH, Paul , LERNER, Richard, A.
发明人： WENTWORTH, Paul , LERNER, Richard, A.
IPC分类号： C07J
CPC分类号： C07J61/00 , C07C49/523 , C07C49/757 , C07C59/353 , C07D313/04 , C07J9/00 , C07J9/005
摘要： As illustrated herein, cholesterol is oxidized when it is present in atherosclerotic plaques. This reaction generates cytotoxic cholesterol oxidation or ozonation products. The present application is directed to the products of cholesterol ozonation, binding entities directed against such products, and methods of using such binding entities and cytotoxins to treat a variety of diseases.
摘要翻译：如本文所示，当胆固醇存在于动脉粥样硬化斑块中时，胆固醇被氧化。该反应产生细胞毒性胆固醇氧化或臭氧化产物。本申请涉及胆固醇臭氧化产物，针对这些产品的结合实体，以及使用这些结合实体和细胞毒素治疗各种疾病的方法。

9. 发明申请

WO2009009045A2 ESCAPE LIBRARIES OF TARGET POLYPEPTIDES 审中-公开
标题翻译： ESCAPE目标聚合物图书馆
公开(公告)号：WO2009009045A2
公开(公告)日：2009-01-15
申请号：PCT/US2008/008367
申请日：2008-07-08
申请人： THE SCRIPPS RESEARCH INSTITUTE , LERNER, Richard, A. , BRENNER, Sydney , DICKERSON, Tobin, J. , JANDA, Kim, D.
发明人： LERNER, Richard, A. , BRENNER, Sydney , DICKERSON, Tobin, J. , JANDA, Kim, D.
IPC分类号： C40B30/06
CPC分类号： G01N33/6845 , C12N15/1037 , G01N2500/02
摘要： The present invention provides methods for identifying escape variants of a target polypeptide. The methods typically involve generating a library of variant polypeptides of the target polypeptide on a replicable display platform (e.g., phage display), identifying variant polypeptides which maintain the ability to bind to a known binding partner of the target polypeptide, and examining the identified variant polypeptides to identify escape variants whose binding to the binding partner is not antagonized by a library of known compounds which disrupt binding between the target polypeptide and the binding partner. The methods can further entail screening a library of candidate antagonist agents to identify a cognate antagonist agent which antagonizes binding between the escape variant and the binding partner. Additional escape variants can be identified by creating a library of further variant polypeptides of the identified escape variant, and subject the further variant polypeptides to the screening process. In each subsequent round of screening, the identified antagonist agent is combined with the library of known compounds employed in the previous round of screening. The invention also provides related methods for identifying novel antagonist agents of a target polypeptide. Further provided are vectors and kits for displaying a functional multimeric target protein on the surface of a phage.
摘要翻译：本发明提供了鉴定靶多肽逃避变体的方法。所述方法通常涉及在可复制的显示平台（例如，噬菌体展示）上产生靶多肽的变体多肽文库，鉴定维持结合目标多肽的已知结合配偶体的能力的变体多肽，并检查鉴定的变体用于鉴定与结合配偶体结合的逃避变体的多肽不被破坏靶多肽和结合配偶体之间的结合的已知化合物文库拮抗。所述方法可进一步包括筛选候选拮抗剂试剂盒，以鉴定拮抗逃生变体与结合配偶体之间结合的同源拮抗剂。可以通过产生所鉴定的逃避变体的另外的变体多肽的文库来鉴定另外的逃避变体，并将进一步的变体多肽进行筛选过程。在随后的每一轮筛选中，将所鉴定的拮抗剂与前一轮筛选中使用的已知化合物的文库组合。本发明还提供了鉴定目标多肽的新型拮抗剂的相关方法。还提供了用于在噬菌体表面上显示功能性多聚体靶蛋白的载体和试剂盒。

10. 发明申请

WO2004044191A1 ANTIMICROBIAL ACTIVITY OF ANTIBODIES PRODUCING REACTIVE OXYGEN SPECIES 审中-公开
标题翻译：生产反应性氧化物种的抗体的抗微生物活性
公开(公告)号：WO2004044191A1
公开(公告)日：2004-05-27
申请号：PCT/EP2003/012709
申请日：2003-11-13
申请人： NOVARTIS AG , NOVARTIS PHARMA GMBH , THE SCRIPPS RESEARCH INSTITUTE , WENTWORTH, Paul , LERNER, Richard, A.
发明人： WENTWORTH, Paul , LERNER, Richard, A.
IPC分类号： C12N9/00
CPC分类号： A61K33/40 , A61K39/40 , A61K39/42 , A61K2039/505 , C07K16/00 , C07K16/1232 , C07K16/1235 , C07K2317/55 , Y02A50/397 , Y02A50/474 , Y02A50/482 , Y02A50/484
摘要： The invention provides compositions having antibodies that can generate reactive oxygen species when exposed to singlet oxygen, as well as methods of using the compositions, for example, to treat microbial infections.
摘要翻译：本发明提供具有当暴露于单线态氧时可产生活性氧物种的抗体的组合物，以及使用该组合物例如治疗微生物感染的方法。

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