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公开(公告)号：US07749956B2
公开(公告)日：2010-07-06
申请号：US11421060
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
CPC分类号： A61K38/2264 , A61K31/155 , A61K38/28 , A61K2300/00
摘要： A method of treating a mammal with an adiponectin mediated disorder comprising administering a therapeutically effective amount of an adiponectin variant with at least a 3-fold increased solubility relative to residues 110-244 of human adiponectin.
摘要翻译： 一种用脂联素介导的病症治疗哺乳动物的方法，包括给予治疗有效量的脂联素变体，相对于人脂连蛋白的残基110-244，其具有至少3倍增加的溶解度。
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公开(公告)号：US07592423B2
公开(公告)日：2009-09-22
申请号：US11421055
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
CPC分类号： C07K14/5759
摘要： An adiponectin variant with one or more amino acid modifications relative to a corresponding parent adiponectin, wherein the adiponectin variant is not glycosylated, the adiponectin variant does not have residues 1-100 relative to human adiponectin, and wherein the solubility of the variant is improved by at least 3-fold relative to residues 110-244 of human adiponectin.
摘要翻译： 具有相对于亲本脂联素的一个或多个氨基酸修饰的脂联素变体，其中所述脂联素变体不被糖基化，所述脂联素变体相对于人脂连蛋白不具有1-100的残基，并且其中变体的溶解度通过 相对于人脂连蛋白的残基110-244至少3倍。
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公开(公告)号：US07709607B2
公开(公告)日：2010-05-04
申请号：US11421059
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
CPC分类号： A61K38/2264
摘要： An adiponectin variant with one or more amino acid modifications relative to a corresponding parent adiponectin, wherein the solubility of the variant is improved by at least 3-fold relative to residues 110-244 of human adiponectin.
摘要翻译： 具有相对于亲本脂联素的一个或多个氨基酸修饰的脂连蛋白变体，其中相对于人脂连蛋白的残基110-244，变体的溶解度提高至少3倍。
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4.发明授权公开(公告)号：US07678886B2
公开(公告)日：2010-03-16
申请号：US11421061
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory L. Moore , Sergei A. Ezhevsky , John R. Desjarlais , Arthur J. Chirino , Darian Cash , Matthew J. Bernett
CPC分类号： A61K38/2264 , A61K47/02
摘要： A composition comprising an adiponectin variant at a concentration of at least 2.0 mg/mL, and a pharmaceutically acceptable carrier, wherein less than 20% of said adiponectin variant would aggregate after storage at 4° C. for one week in 10 mM PO4, 150 mM NaCl buffer.
摘要翻译： 包含浓度为至少2.0mg / mL的脂联素变体的组合物和药学上可接受的载体，其中小于20％的所述脂联素变体在4℃下在10mM PO4,150中保存一周后将聚集 mM NaCl缓冲液。
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5.发明申请公开(公告)号：US20060276395A1
公开(公告)日：2006-12-07
申请号：US11421061
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory Moore , Sergei Ezhevsky , John Desjarlais , Arthur Chirino , Darian Cash , Matthew Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Thi Nguyen , Gregory Moore , Sergei Ezhevsky , John Desjarlais , Arthur Chirino , Darian Cash , Matthew Bernett
IPC分类号： A61K38/17
CPC分类号： A61K38/2264 , A61K47/02
摘要： 1. A composition comprising an adiponectin variant at a concentration of at least 2.0 mg/mL, and a pharmaceutically acceptable carrier, wherein less than 20% of said adiponectin variant would aggregate after storage at 4° C. for one week in 10 mM PO4, 150 mM NaCl buffer.
摘要翻译： 1.包含浓度为至少2.0mg / mL的脂联素变体和药学上可接受的载体的组合物，其中小于20％的所述脂联素变体在4℃下储存一周后在10mM PO中聚集 4mM，150mM NaCl缓冲液。
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公开(公告)号：US07610156B2
公开(公告)日：2009-10-27
申请号：US10956352
申请日：2004-09-30
IPC分类号： G06F19/00
CPC分类号： C07K1/1077 , A61K38/00 , A61K47/60 , C07K14/505 , C07K14/525 , C07K14/535 , C07K14/565 , C07K14/61 , C07K2299/00 , C40B30/02 , G06F19/16
摘要： The present invention relates to the use of simulation technology to rationally optimize the locations and sizes of attached polymeric moieties for modification of therapeutic proteins and the proteins generated from this method.
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公开(公告)号：US20080113410A1
公开(公告)日：2008-05-15
申请号：US11930051
申请日：2007-10-30
IPC分类号： C12P21/02 , G06F19/00 , C07H21/04 , C07K14/535 , C07K14/565
CPC分类号： C07K1/1077 , A61K38/00 , A61K47/60 , C07K14/505 , C07K14/525 , C07K14/535 , C07K14/565 , C07K14/61 , C07K2299/00 , G16B15/00 , G16B35/00 , G16C20/60
摘要： The present invention relates to the use of simulation technology to rationally optimize the locations and sizes of attached polymeric moieties for modification of therapeutic proteins and the proteins generated from this method.
摘要翻译： 本发明涉及使用模拟技术来合理优化连接的聚合物部分的位置和大小，用于修饰治疗性蛋白质和由该方法产生的蛋白质。
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公开(公告)号：US20070054359A1
公开(公告)日：2007-03-08
申请号：US11421062
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Nguyen , Gregory Moore , Sergei Ezhevsky , John Desjarlais , Arthur Chirino , Darian Cash , Matthew Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Nguyen , Gregory Moore , Sergei Ezhevsky , John Desjarlais , Arthur Chirino , Darian Cash , Matthew Bernett
IPC分类号： C07K14/475 , C07K14/52 , C12P21/06
CPC分类号： C07K14/5759
摘要： An adiponectin variant with at least a 3-fold increased solubility relative to residues 110-244 of human adiponectin, wherein the adiponectin variant has at least one covalently attached non-peptide moiety at at least one position selected from the group consisting of: A108, Y109, S146, D179, E220, R221, and L224, relative to human adiponectin
摘要翻译： 脂联素变体与人脂联素的残基110-244相比具有至少3倍增加的溶解度，其中所述脂连蛋白变体在选自以下的至少一个位置具有至少一个共价连接的非肽部分：A108， Y109，S146，D179，E220，R221和L224相对于人脂连蛋白
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公开(公告)号：US20060270598A1
公开(公告)日：2006-11-30
申请号：US11421060
申请日：2006-05-30
申请人： Jonathan Zalevsky , Duc-Hanh Nguyen , Gregory Moore , Sergei Ezhevsky , John Desjarlais , Arthur Chirino , Darian Cash , Matthew Bernett
发明人： Jonathan Zalevsky , Duc-Hanh Nguyen , Gregory Moore , Sergei Ezhevsky , John Desjarlais , Arthur Chirino , Darian Cash , Matthew Bernett
IPC分类号： A61K38/17
CPC分类号： A61K38/2264 , A61K31/155 , A61K38/28 , A61K2300/00
摘要： A method of treating a mammal with an adiponectin mediated disorder comprising administering a therapeutically effective amount of an adiponectin variant with at least a 3-fold increased solubility relative to residues 110-244 of human adiponectin
摘要翻译： 一种用脂联素介导的病症治疗哺乳动物的方法，其包括给予治疗有效量的脂联素变体，其相对于人脂连蛋白的残基110-244具有至少3倍增加的溶解度
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公开(公告)号：US20070015909A1
公开(公告)日：2007-01-18
申请号：US11328901
申请日：2006-01-09
申请人： Darian Cash , Arthur Chirino , John Desjarlais , Sergei Ezhevsky , Gregory Moore , Duc-Hahn Nguyen , Jonathan Zalevsky
发明人： Darian Cash , Arthur Chirino , John Desjarlais , Sergei Ezhevsky , Gregory Moore , Duc-Hahn Nguyen , Jonathan Zalevsky
IPC分类号： C07K14/715 , A61K38/17 , C07H21/04
CPC分类号： C07K14/52 , A61K38/00 , C07K14/5759
摘要： Adiponectin variants comprising one or more amino acid modifications to corresponding wild-type adiponectins at positions having predetermined hydrophobicity, predetermined polarity, predetermined electrostatic potential, Met, aromatic amino acid, Cys corresponding to position 152 of SEQ ID NO:1, amino acid affecting isoelectric point of the wild-type or variant adiponectin, amino acid affecting beta sheet formation, helix capping, or dipole interactions, or a combination thereof, wherein the adiponectin variants exhibit improved stability, solubility or soluble expression, expression yield, the ability to induce phosphorylation of AMPK, or a combination thereof, as compared to the corresponding wild-type adiponectins.
摘要翻译： 在具有预定疏水性，预定极性，预定静电位，Met，芳香族氨基酸，对应于SEQ ID NO：1的位置152的Cys，影响等电点的氨基酸的位置，包含与相应的野生型脂连蛋白的一个或多个氨基酸修饰的脂连蛋白变体 野生型或变体脂联素的点，影响β片形成的氨基酸，螺旋封端或偶极相互作用或其组合，其中脂联素变体表现出改善的稳定性，溶解性或可溶性表达，表达产量，诱导磷酸化的能力 的AMPK，或其组合，与相应的野生型脂连蛋白相比。
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