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31.发明授权Methods for treating edema by administering a Soluble Hyaluronidase Glycoprotein (sHASEGP) 有权通过施用可溶性透明质酸糖蛋白（sHASEGP）治疗水肿的方法公开(公告)号：US08765685B2
公开(公告)日：2014-07-01
申请号：US13506783
申请日：2012-05-16
CPC分类号： A61K38/47 , A61K9/0048 , A61K38/00 , A61K39/395 , A61K47/48215 , A61K2039/505 , C12N9/2474 , C12Y302/01035 , Y02A50/475
摘要： Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.
摘要翻译： 提供可溶性中性活性透明质酸酶糖蛋白（sHASEGP），其制备方法及其用于促进其它分子的给药或减轻糖胺聚糖相关病理学的用途。 描述了可溶性中性活性sHASEGP结构域的微活性多肽结构域，其包括功能性中性活性透明质酸酶结构域所需的天冬酰胺连接的糖部分。 包括改进的氨基末端前导肽，其增强sHASEGP的分泌。 还提供了sHASEGP的唾液酸化和聚乙二醇化形式。 还提供了通过施用sHASEGP的治疗方法及其修饰形式。
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32.发明授权公开(公告)号：US07846431B2
公开(公告)日：2010-12-07
申请号：US12660869
申请日：2010-03-04
CPC分类号： A61K38/47 , A61K39/395 , A61K39/3955 , A61K45/06 , A61K2039/505 , C12N9/2408 , C12Y302/01035 , A61K2300/00
摘要： The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated form of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.
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公开(公告)号：US08431380B2
公开(公告)日：2013-04-30
申请号：US12378984
申请日：2009-02-20
IPC分类号： C12N9/26 , A61K38/47 , C12P21/02 , C07K14/435
CPC分类号： A61K38/47 , A61K9/0048 , A61K38/00 , A61K39/395 , A61K47/48215 , A61K2039/505 , C12N9/2474 , C12Y302/01035 , Y02A50/475
摘要： The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.
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公开(公告)号：US20130058893A1
公开(公告)日：2013-03-07
申请号：US13694005
申请日：2012-10-18
IPC分类号： C12N9/26 , A61K38/47 , A61K38/19 , A61K39/395 , A61P29/00 , A61P33/04 , A61P25/16 , A61P33/06 , A61P25/24 , A61P19/02 , A61P31/10 , A61P9/12 , A61P33/00 , A61P31/00 , A61P31/04 , A61P31/12 , C12N9/96
CPC分类号： A61K38/47 , A61K9/0048 , A61K38/00 , A61K39/395 , A61K47/48215 , A61K2039/505 , C12N9/2474 , C12Y302/01035 , Y02A50/475
摘要： Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.
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公开(公告)号：US08450470B2
公开(公告)日：2013-05-28
申请号：US12455657
申请日：2009-06-03
CPC分类号： A61K38/47 , A61K9/0048 , A61K38/00 , A61K39/395 , A61K47/48215 , A61K2039/505 , C12N9/2474 , C12Y302/01035 , Y02A50/475
摘要： Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.
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公开(公告)号：US20090253175A1
公开(公告)日：2009-10-08
申请号：US12455657
申请日：2009-06-03
CPC分类号： A61K38/47 , A61K9/0048 , A61K38/00 , A61K39/395 , A61K47/48215 , A61K2039/505 , C12N9/2474 , C12Y302/01035 , Y02A50/475
摘要： Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.
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37.发明授权公开(公告)号：US09683985B2
公开(公告)日：2017-06-20
申请号：US13200666
申请日：2011-09-27
申请人： Lalitha Kodandapani , Louis H. Bookbinder , Gregory I. Frost , Philip Lee Sheridan , Harold Michael Shepard , Ge Wei , Lei Huang
发明人： Lalitha Kodandapani , Louis H. Bookbinder , Gregory I. Frost , Philip Lee Sheridan , Harold Michael Shepard , Ge Wei , Lei Huang
CPC分类号： G01N33/5011 , C07K16/2863 , C07K16/30 , C07K16/44 , C07K2317/34 , G01N33/5014 , G01N33/5088 , G01N33/53 , G01N2333/71
摘要： Methods for evolving or selecting or producing therapeutic proteins that exhibit reduced adverse side-effects and the resulting proteins are provided. For example, provided herein is an in vitro assay to identify conditionally active therapeutic proteins that exhibit better activity within one in vivo environment compared to another in vivo environment. The methods include the steps of a) testing the activity of a protein under conditions in which normal or increased activity is desired; b) testing the activity of the protein under conditions in which reduced activity compared to normal is desired; and c) comparing the activity in a) with b) and selecting/identifying a protein that has greater activity in a) compared to b). The selected/identified protein is a conditionally active protein.
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38.发明申请Methods for assessing and identifying or evolving conditionally active therapeutic proteins 有权用于评估和鉴定或发展有条件活性的治疗性蛋白质的方法公开(公告)号：US20120108455A1
公开(公告)日：2012-05-03
申请号：US13200666
申请日：2011-09-27
申请人： Lalitha Kodandapani , Louis H. Bookbinder , Gregory I. Frost , Philip Lee Sheridan , Harold Michael Shepard , Ge Wei , Lei Huang
发明人： Lalitha Kodandapani , Louis H. Bookbinder , Gregory I. Frost , Philip Lee Sheridan , Harold Michael Shepard , Ge Wei , Lei Huang
CPC分类号： G01N33/5011 , C07K16/2863 , C07K16/30 , C07K16/44 , C07K2317/34 , G01N33/5014 , G01N33/5088 , G01N33/53 , G01N2333/71
摘要： Methods for evolving or selecting or producing therapeutic proteins that exhibit reduced adverse side-effects and the resulting proteins are provided. For example, provided herein is an in vitro assay to identify conditionally active therapeutic proteins that exhibit better activity within one in vivo environment compared to another in vivo environment. The methods include the steps of a) testing the activity of a protein under conditions in which normal or increased activity is desired; b) testing the activity of the protein under conditions in which reduced activity compared to normal is desired; and c) comparing the activity in a) with b) and selecting/identifying a protein that has greater activity in a) compared to b). The selected/identified protein is a conditionally active protein.
摘要翻译： 提供了演变或选择或产生表现出减少的副作用减轻的所得蛋白质的方法。 例如，本文提供了一种体外测定法，用于鉴定在体内环境中与另一体内环境相比表现出更好活性的条件活性治疗性蛋白质。 所述方法包括以下步骤：a）在需要正常或增加活性的条件下测试蛋白质的活性; b）在需要降低活性的条件下测试蛋白质的活性; 和c）比较a）中的活性和b）和选择/鉴定在a）中比b）具有更大活性的蛋白质。 所选择/鉴定的蛋白质是有条件活性蛋白质。
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39.发明申请Modified hyaluronidases and uses in treating hyaluronan-associated diseases and conditions 审中-公开修饰的透明质酸酶和用于治疗透明质酸相关疾病和病症的用途公开(公告)号：US20130028856A9
公开(公告)日：2013-01-31
申请号：US13385528
申请日：2012-02-22
申请人： Gregory I. Frost , Ping Jiang , Curtis B. Thompson
发明人： Gregory I. Frost , Ping Jiang , Curtis B. Thompson
IPC分类号： A61K38/46 , G01N33/566 , A61P35/00 , C12Q1/34 , C12Q1/48 , C12Q1/68 , G01N33/573
CPC分类号： A61K38/47 , A61K31/337 , C12N9/2408 , C12N11/08 , A61K2300/00
摘要： Provided are combinations, compositions and kits containing a hyaluronan degrading enzyme, such as a soluble hyaluronidase, for treatment of hyaluronan-associated conditions, diseases and disorders. In one example, the products include an additional agent or treatment. Such products can be used in methods for administering the products to treat the hyaluronan-associated diseases and conditions, for example, hyaluronan-associated cancers, for example, hyaluronan-rich tumors. The methods include administration of the hyaluronan degrading enzyme composition alone or in combination with other treatments. Also provided are methods and compositions for providing sustained treatment effects in hyaluronan-associated diseases and conditions.
摘要翻译： 提供了含有透明质酸降解酶（例如可溶性透明质酸酶）的组合，组合物和试剂盒，用于治疗透明质酸相关病症，疾病和病症。 在一个实例中，产品包括另外的试剂或处理。 这些产品可用于施用产品以治疗透明质酸相关疾病和病症的方法，例如透明质酸相关的癌症，例如富含透明质酸的肿瘤。 所述方法包括单独或与其它治疗组合施用透明质酸降解酶组合物。 还提供了用于在透明质酸相关疾病和病症中提供持续治疗效果的方法和组合物。
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公开(公告)号：US08318154B2
公开(公告)日：2012-11-27
申请号：US12387225
申请日：2009-04-28
申请人： Gregory I. Frost , Igor Bilinsky , Daniel Vaughn , Barry Sugarman
发明人： Gregory I. Frost , Igor Bilinsky , Daniel Vaughn , Barry Sugarman
CPC分类号： A61K38/47 , A61K38/28 , A61K2300/00
摘要： Provided are combinations, compositions and kits containing an fast-acting insulin composition and a hyaluronan degrading enzyme composition formulated for parenteral administration. Such products can be used in methods of treating insulin-treatable diseases or conditions. Also provided are methods for administration of a fast-acting insulin and a hyaluronan degrading enzyme.
摘要翻译： 提供了包含配制用于肠胃外给药的速效胰岛素组合物和透明质酸降解酶组合物的组合，组合物和试剂盒。 这些产品可用于治疗可治疗胰岛素的疾病或病症的方法。 还提供了用于施用速效胰岛素和透明质酸降解酶的方法。
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