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1. 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。

2. 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。

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

WO2013115425A1 METHODS FOR SCREENING AN ANTIBODY BY ONE-CYCLE PANNING 审中-公开
标题翻译：通过单循环筛选筛选抗体的方法
公开(公告)号：WO2013115425A1
公开(公告)日：2013-08-08
申请号：PCT/KR2012/000934
申请日：2012-02-08
申请人： SCRIPPS KOREA ANTIBODY INSTITUTE , THE SCRIPPS RESEARCH INSTITUTE , ZHANG, Hongkai , LERNER, Richard A.
发明人： ZHANG, Hongkai , LERNER, Richard A.
IPC分类号： G01N33/53 , G01N33/543 , C12Q1/68
CPC分类号： C07K16/005 , C07K16/1063 , C07K16/248 , C07K16/2866 , C07K2317/21 , C07K2317/565 , C07K2317/569 , C07K2317/622
摘要： The present invention relates to a method for screening an antibody specifically binding to a target antigen and a method for producing a polypeptide specifically binding to a target polypeptide. This method could be applied to select an antibody or polypeptide from a large collection of homologous or heterogeneous molecules that are contained in combinatorial libraries.
摘要翻译：本发明涉及用于筛选特异性结合靶抗原的抗体的方法和用于产生与靶多肽特异性结合的多肽的方法。该方法可用于从组合文库中包含的大量同源或异质分子中选择抗体或多肽。

5. 发明申请

WO2016161244A2 METHODS AND COMPOSITIONS RELATED TO GPCR AGONIST POLYPEPTIDES 审中-公开
标题翻译：与GPCR激动剂聚合物相关的方法和组合物
公开(公告)号：WO2016161244A2
公开(公告)日：2016-10-06
申请号：PCT/US2016/025490
申请日：2016-04-01
申请人： THE SCRIPPS RESEARCH INSTITUTE
发明人： LERNER, Richard, A. , ZHANG, Hongkai , MC DONALD, Patricia , XIE, Jia , STURCHLER, Emmanuel
IPC分类号： A61K38/17 , C12N15/867
CPC分类号： C07K14/605 , A61K38/00 , C07K2319/00 , C07K2319/30
摘要： The invention provides combinatorial peptide or polypeptide libraries that can become membrane tethered once expressed in cells. The invention additionally provides methods for selecting peptide modulators (e.g., agonists) of GPCRs from the combinatorial libraries of the invention. The invention also provides novel GPCR polypeptide modulators, e.g., biased polypeptide agonists of the glucagon-like peptide 1 receptor (GLP-1R). The invention further provides methods of promoting insulin sensitivity, lowering blood glucose, and reducing body weight as well as methods for treating various diseases such as diabetes and obesity.
摘要翻译：本发明提供组合肽或多肽文库，其可以在细胞中表达后变成膜结合。本发明另外提供了用于从本发明的组合文库中选择GPCRs的肽调节剂（例如激动剂）的方法。本发明还提供新的GPCR多肽调节剂，例如胰高血糖素样肽1受体（GLP-1R）的偏向多肽激动剂。本发明还提供了促进胰岛素敏感性，降低血糖和减轻体重的方法以及用于治疗各种疾病如糖尿病和肥胖症的方法。

6. 发明申请

WO2017197081A2 KV1.3-BLOCKING VENOM PEPTIDE VARIANTS AND RELATED USES 审中-公开
标题翻译： KV1.3阻断性的VENOM肽变体及相关用途
公开(公告)号：WO2017197081A2
公开(公告)日：2017-11-16
申请号：PCT/US2017/032102
申请日：2017-05-11
申请人： THE SCRIPPS RESEARCH INSTITUTE
发明人： LERNER, Richard, A. , ZHANG, Hongkai
IPC分类号： C12Q1/68

7. 发明申请

WO2016064673A1 PROXIMITY BASED METHODS FOR SELECTION OF BINDING PARTNERS 审中-公开
标题翻译：用于选择合作伙伴的基于近似的方法
公开(公告)号：WO2016064673A1
公开(公告)日：2016-04-28
申请号：PCT/US2015/055941
申请日：2015-10-16
申请人： THE SCRIPPS RESEARCH INSTITUTE
发明人： LERNER, Richard, A. , ZHANG, Hongkai , XIE, Jia
IPC分类号： C04B40/02
CPC分类号： C12N15/1037 , C12N15/1055 , C12N15/1086 , G01N33/542 , G01N33/566 , G01N2333/726
摘要： The invention provides methods for identifying binding partners (e.g., peptide ligands) that binds to a target protein (e.g., a cellular receptor). The methods entail co-localized expression of the target protein and candidate binding partners, and selection of binding partners based on their proximity in the plasma membrane.
摘要翻译：本发明提供用于鉴定结合靶蛋白（例如，细胞受体）的结合配偶体（例如肽配体）的方法。该方法需要靶蛋白和候选结合配偶体的共定位表达，以及基于其在质膜中的接近度的结合配偶体的选择。

8. 发明申请

WO2016205784A1 METHODS AND COMPOSITIONS FOR PRODUCING ACTIVATED NATURAL KILLER CELLS AND RELATED USES 审中-公开
标题翻译：用于生产活化的自然杀伤细胞的方法和组合物及相关用途
公开(公告)号：WO2016205784A1
公开(公告)日：2016-12-22
申请号：PCT/US2016/038338
申请日：2016-06-20
申请人： THE SCRIPPS RESEARCH INSTITUTE
发明人： LERNER, Richard, A. , YEA, Kyungmoo , ZHANG, Hongkai , XIE, Jia
IPC分类号： A61K39/395 , C40B30/06
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/622 , C07K2317/75 , C07K2317/92 , C12N5/00
摘要： The invention provides methods for generating activated natural killer (NK) cells from acute myeloid leukemia (AML) cells. The methods involve contacting the AML cells with a TpoR agonist antibody, and culturing the cell mixture under conditions to allow conversion of the AML cells into NK cells. Also provided in the invention are therapeutic methods of using a pharmaceutical composition containing a TpoR agonist antibody or NK cells described herein for treating various diseases or disorders, e.g., tumors or pathogenic infections. The invention further provides TpoR agonist antibodies that can be employed in these methods.
摘要翻译：本发明提供从急性骨髓性白血病（AML）细胞产生活化的天然杀伤（NK）细胞的方法。所述方法包括使AML细胞与TpoR激动剂抗体接触，并在允许AML细胞转化为NK细胞的条件下培养细胞混合物。本发明还提供了使用含有本文所述的TpoR激动剂抗体或NK细胞的药物组合物治疗各种疾病或病症例如肿瘤或致病性感染的治疗方法。本发明还提供可用于这些方法的TpoR激动剂抗体。

9. 发明公开

EP3277302A2 METHODS AND COMPOSITIONS RELATED TO GPCR AGONIST POLYPEPTIDES 审中-公开
标题翻译：与GPCR激动剂多肽相关的方法和组合物
公开(公告)号：EP3277302A2
公开(公告)日：2018-02-07
申请号：EP16774283.2
申请日：2016-04-01
申请人： The Scripps Research Institute
发明人： LERNER, Richard, A. , ZHANG, Hongkai , MC DONALD, Patricia , XIE, Jia , STURCHLER, Emmanuel
IPC分类号： A61K38/00 , A61P3/10 , A61P3/04 , C07K14/605
CPC分类号： C07K14/605 , A61K38/00 , C07K2319/00 , C07K2319/30
摘要： The invention provides combinatorial peptide or polypeptide libraries that can become membrane tethered once expressed in cells. The invention additionally provides methods for selecting peptide modulators (e.g., agonists) of GPCRs from the combinatorial libraries of the invention. The invention also provides novel GPCR polypeptide modulators, e.g., biased polypeptide agonists of the glucagon-like peptide 1 receptor (GLP-1R). The invention further provides methods of promoting insulin sensitivity, lowering blood glucose, and reducing body weight as well as methods for treating various diseases such as diabetes and obesity.

10. 发明授权

EP2890836B1 METHODS RELATED TO MODULATORS OF EUKARYOTIC CELLS 有权转让
公开(公告)号：EP2890836B1
公开(公告)日：2019-07-17
申请号：EP13833286.1
申请日：2013-08-16
申请人： The Scripps Research Institute
发明人： ZHANG, Hongkai , WILSON, Ian, A. , LERNER, Richard, A.
IPC分类号： G01N33/50 , G01N33/74 , C07K16/28

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