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81. 发明授权

US07767429B2 Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof 有权
标题翻译：可溶性透明质酸酶糖蛋白（sHASEGP），其制备方法，用途及其组合物
公开(公告)号：US07767429B2
公开(公告)日：2010-08-03
申请号：US10795095
申请日：2004-03-05
申请人： Louis H. Bookbinder , Anirban Kundu , Gregory I. Frost
发明人： Louis H. Bookbinder , Anirban Kundu , Gregory I. Frost
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.
摘要翻译：本发明涉及新型可溶性中性活性透明质酸酶糖蛋白（sHASEGP's）的发现，其制备方法及其用于促进其它分子的施用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。本发明还包含重组sHASEGP的唾液酸化和聚乙二醇化形式，以增强天然存在的屠宰酶的稳定性和血清药代动力学。进一步描述了衍生自真核细胞的基本上纯化的重组sHASEGP糖蛋白的合适制剂，其产生其最佳活性所需的适当糖基化。

82. 发明申请

US20100184845A1 Myeloid Colony Stimulating Factor and Uses Thereof 审中-公开
标题翻译：骨髓集落刺激因子及其用途
公开(公告)号：US20100184845A1
公开(公告)日：2010-07-22
申请号：US12753046
申请日：2010-04-01
申请人： Gregory I. Frost , Per Borgstrom
发明人： Gregory I. Frost , Per Borgstrom
IPC分类号： A61K31/7088 , C12N9/26 , C07H21/04
CPC分类号： C12N9/2408 , A61K38/193 , A61K38/47 , A61K48/00
摘要： The identification of the HYAL1 hyaluronidase enzyme as a human plasma-derived myeloid colony-stimulating factor (CSF), herein designated CSF5-hyaluronidase, its recombinant production and methods of use are described. This protein may be used for the treatment of myelosuppression as may occur after irradiation, chemotherapy or other diseases where an increase in leukocyte levels may be beneficial. For example, CSF5- may be used to enhance the immune response to viral infection or other diseases associated with immune suppression.
摘要翻译：描述了HYAL1透明质酸酶作为人血浆衍生的骨髓集落刺激因子（CSF），本文命名为CSF5-透明质酸酶，其重组生产和使用方法的鉴定。该蛋白质可用于治疗照射，化学疗法或白细胞水平升高可能有益的其它疾病发生的骨髓抑制。例如，CSF5-可用于增强对病毒感染或与免疫抑制相关的其它疾病的免疫应答。

83. 发明授权

US07544499B2 Human chondroitinase glycoprotein (CHASEGP), process for preparing the same, and pharmaceutical compositions comprising thereof 有权
标题翻译：人类软骨素酶糖蛋白（CHASEGP），其制备方法和由其组成的药物组合物
公开(公告)号：US07544499B2
公开(公告)日：2009-06-09
申请号：US10539110
申请日：2003-12-15
申请人： Gregory I. Frost , Anirban Kundu , Louis H. Bookbinder
发明人： Gregory I. Frost , Anirban Kundu , Louis H. Bookbinder
IPC分类号： C12N9/24 , A61K38/47 , C07H21/04
CPC分类号： C12N9/88 , A61K38/47 , C12Y402/02004
摘要： The invention relates to the discovery of a novel Chondroitinase Glycoproteins (CHASEGP's), methods of manufacture, and potential uses in conditions where removal of chondroitin sulfates may be of therapeutic benefit. Chondroitinase Glycoproteins require both a substantial portion of the catalytic domain of the CHASEGP polypeptide and asparagine-linked glycosylation for optimal chondroitinase activity. The invention also includes carboxy-terminal deletion variants of CHASEGP that result in secreted variants of the protein to facilitate manufacture of a recombinant CHASEGP. Further described are suitable formulations of a substantially purified recombinant CHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity. CHASEGP is useful for the degradation of glycosaminoglycans and chondroitin sulfate proteoglycans under clinical conditions where their removal is of therapeutic value.
摘要翻译：本发明涉及新型软骨素酶糖蛋白（CHASEGP）的发现，其制备方法和潜在用途，其中去除硫酸软骨素可具有治疗益处。软骨素酶糖蛋白需要CHASEGP多肽的大部分催化结构域和天冬酰胺连接的糖基化以获得最佳的软骨素酶活性。本发明还包括CHASEGP的羧基末端缺失变体，其导致蛋白质的分泌型变体以促进重组CHASEGP的制备。进一步描述了衍生自真核细胞的基本上纯化的重组CHASEGP糖蛋白的合适制剂，其产生其最佳活性所需的适当糖基化。 CHASEGP可用于在其去除具有治疗价值的临床条件下降解糖胺聚糖和硫酸软骨素蛋白聚糖。

84. 发明申请

US20060247201A1 Myeloid colony stimulating factor and uses thereof 有权
标题翻译：骨髓集落刺激因子及其用途
公开(公告)号：US20060247201A1
公开(公告)日：2006-11-02
申请号：US11431181
申请日：2006-05-09
申请人： Gregory Frost , Per Borgstrom
发明人： Gregory Frost , Per Borgstrom
IPC分类号： A61K48/00 , A61K38/47
CPC分类号： C12N9/2408 , A61K38/193 , A61K38/47 , A61K48/00
摘要： The identification of the HYAL1 hyaluronidase enzyme as a human plasma-derived myeloid colony-stimulating factor (CSF), herein designated CSF5-hyaluronidase, its recombinant production and methods of use are described. This protein may be used for the treatment of myelosuppression as may occur after irradiation, chemotherapy or other diseases where an increase in leukocyte levels may be beneficial. For example, CSF5- may be used to enhance the immune response to viral infection or other diseases associated with immune suppression.
摘要翻译：描述了HYAL1透明质酸酶作为人血浆衍生的骨髓集落刺激因子（CSF），本文命名为CSF5-透明质酸酶，其重组生产和使用方法的鉴定。该蛋白质可用于治疗照射，化学疗法或白细胞水平升高可能有益的其它疾病发生的骨髓抑制。例如，CSF5-可用于增强对病毒感染或与免疫抑制相关的其它疾病的免疫应答。

85. 发明申请

US20060104968A1 Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases 审中-公开
标题翻译：可溶性糖胺聚糖酶及其制备和使用可溶性糖胺聚糖的方法
公开(公告)号：US20060104968A1
公开(公告)日：2006-05-18
申请号：US11238171
申请日：2005-09-27
申请人： Louis Bookbinder , Anirban Kundu , Gregory Frost , Michael Haller , Gilbert Keller , Tyler Dylan
发明人： Louis Bookbinder , Anirban Kundu , Gregory Frost , Michael Haller , Gilbert Keller , Tyler Dylan
IPC分类号： A61K38/47 , C12N9/24
CPC分类号： A61K47/6811 , A61K35/768 , A61K38/465 , A61K38/47 , A61K39/395 , A61K39/3955 , A61K47/60 , A61K2039/505 , C12N7/00 , C12N9/2408 , C12N9/2474 , Y02A50/466 , 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 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.
摘要翻译：本发明涉及新型可溶性中性活性透明质酸酶糖蛋白（sHASEGPs）的发现，其制备方法及其用于促进其它分子的施用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。本发明还包含重组sHASEGP的唾液酸化和聚乙二醇化形式，以增强天然存在的屠宰酶的稳定性和血清药代动力学。进一步描述了衍生自真核细胞的基本上纯化的重组sHASEGP糖蛋白的合适制剂，其产生其最佳活性所需的适当糖基化。

86. 发明授权

US12123035B2 PH20 polypeptide variants, formulations and uses thereof 有权
公开(公告)号：US12123035B2
公开(公告)日：2024-10-22
申请号：US18068327
申请日：2022-12-19
申请人： Halozyme, Inc.
发明人： Ge Wei , H. Michael Shepard , Qiping Zhao , Robert James Connor
IPC分类号： C12N9/26 , A61K9/00 , A61K38/00 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P3/04 , A61P3/10 , A61P11/00 , A61P27/02 , A61P29/00 , A61P35/00 , A61P43/00 , C07K14/47 , C12Q1/34
CPC分类号： C12N9/2474 , A61K9/0019 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34 , C12Y302/01035 , A61K38/00 , C07K2319/30 , G01N2333/926 , G01N2333/928 , Y02A50/30 , A61K38/28 , A61K2300/00 , A61K38/47 , A61K2300/00
摘要： Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

87. 发明授权

US12110520B2 PH20 polypeptide variants, formulations and uses thereof 有权
公开(公告)号：US12110520B2
公开(公告)日：2024-10-08
申请号：US18068418
申请日：2022-12-19
申请人： HALOZYME, INC.
发明人： Ge Wei , H. Michael Shepard , Qiping Zhao , Robert James Connor
IPC分类号： C12N9/26 , A61K9/00 , A61K38/00 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34
CPC分类号： C12N9/2474 , A61K9/0019 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34 , C12Y302/01035 , A61K38/00 , C07K2319/30 , G01N2333/926 , G01N2333/928 , Y02A50/30 , A61K38/28 , A61K2300/00 , A61K38/47 , A61K2300/00
摘要： Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

88. 发明授权

US12060590B2 PH20 polypeptide variants, formulations and uses thereof 有权
公开(公告)号：US12060590B2
公开(公告)日：2024-08-13
申请号：US18068218
申请日：2022-12-19
申请人： HALOZYME, INC.
发明人： Ge Wei , H. Michael Shepard , Qiping Zhao , Robert James Connor
IPC分类号： C12N9/26 , A61K9/00 , A61K38/00 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P3/04 , A61P3/10 , A61P11/00 , A61P27/02 , A61P29/00 , A61P35/00 , A61P43/00 , C07K14/47 , C12Q1/34
CPC分类号： C12N9/2474 , A61K9/0019 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34 , C12Y302/01035 , A61K38/00 , C07K2319/30 , G01N2333/926 , G01N2333/928 , Y02A50/30 , A61K38/28 , A61K2300/00 , A61K38/47 , A61K2300/00
摘要： Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

89. 发明公开

US20240209337A1 PH20 POLYPEPTIDE VARIANTS, FORMULATIONS AND USES THEREOF 审中-公开
公开(公告)号：US20240209337A1
公开(公告)日：2024-06-27
申请号：US18599428
申请日：2024-03-08
申请人： Halozyme, Inc.
发明人： Ge WEI , H. Michael Shepard , Qiping Zhao , Robert James Connor
IPC分类号： C12N9/26 , A61K9/00 , A61K38/00 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34
CPC分类号： C12N9/2474 , A61K9/0019 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34 , C12Y302/01035 , A61K38/00 , C07K2319/30 , G01N2333/926 , G01N2333/928 , Y02A50/30
摘要： Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

90. 发明授权

US12018298B2 PH20 polypeptide variants, formulations and uses thereof 有权
公开(公告)号：US12018298B2
公开(公告)日：2024-06-25
申请号：US18340482
申请日：2023-06-23
申请人： HALOZYME, INC.
发明人： Ge Wei , H. Michael Shepard , Qiping Zhao , Robert James Connor
IPC分类号： C12N9/26 , A61K9/00 , A61K38/00 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34
CPC分类号： C12N9/2474 , A61K9/0019 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , A61P35/00 , C07K14/47 , C12Q1/34 , C12Y302/01035 , A61K38/00 , C07K2319/30 , G01N2333/926 , G01N2333/928 , Y02A50/30 , A61K38/28 , A61K2300/00 , A61K38/47 , A61K2300/00
摘要： Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

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