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1. 发明授权

US10328130B2 Modified hyaluronidases and uses in treating hyaluronan-associated diseases and conditions 有权
公开(公告)号：US10328130B2
公开(公告)日：2019-06-25
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： C12N9/26 , A61K38/47 , C12N11/08 , A61K31/337
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.

2. 发明授权

US09034323B2 Method for control of post-prandial glucose 有权
标题翻译：餐后葡萄糖的控制方法
公开(公告)号：US09034323B2
公开(公告)日：2015-05-19
申请号：US13998040
申请日：2013-09-24
申请人： Gregory I. Frost , Igor Bilinsky , Daniel Vaughn , Barry Sugarman
发明人： Gregory I. Frost , Igor Bilinsky , Daniel Vaughn , Barry Sugarman
IPC分类号： A61K38/46 , A61K38/28 , C07K14/62 , A61K38/47
CPC分类号： A61K38/47 , A61K38/28 , A61K2300/00
摘要： Provided are methods for control of post-prandial glucose in diabetic subjects by administering a fast-acting insulin analog and a hyaluronidase degrading enzyme. The fast-acting insulin analog and a hyaluronidase are administered between 15 minutes before the meal and 30 minutes after commencing the meal.
摘要翻译：提供了通过施用快速作用的胰岛素类似物和透明质酸酶降解酶来控制糖尿病受试者的餐后葡萄糖的方法。快餐胰岛素类似物和透明质酸酶在餐前15分钟和开始餐后30分钟之间施用。

3. 发明授权

US08431380B2 Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof 有权
公开(公告)号：US08431380B2
公开(公告)日：2013-04-30
申请号：US12378984
申请日：2009-02-20
申请人： Louis Bookbinder , Anirban Kundu , Gregory I. Frost
发明人： Louis 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.

4. 发明授权

US08431124B2 Methods for treating a disease characterized by an excess of hyaluronan by administering a soluble hyaluronidase glycoprotein (sHASEGP) 有权
标题翻译：通过施用可溶性透明质酸糖蛋白（sHASEGP）治疗特征在于透明质酸过量的疾病的方法，
公开(公告)号：US08431124B2
公开(公告)日：2013-04-30
申请号：US12386473
申请日：2009-04-16
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： A61K38/47 , A61K38/43 , A61K38/17 , C12N9/26 , C12P21/02
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。

5. 发明申请

US20130058893A1 Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof 有权
公开(公告)号：US20130058893A1
公开(公告)日：2013-03-07
申请号：US13694005
申请日：2012-10-18
申请人： Louis Bookbinder , Anirban Kundu , Gregory I. Frost
发明人： Louis Bookbinder , Anirban Kundu , Gregory I. Frost
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.

6. 发明申请

US20120294830A1 Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases 有权
公开(公告)号：US20120294830A1
公开(公告)日：2012-11-22
申请号：US13507540
申请日：2012-07-06
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： A61K38/46 , A61K39/13 , A61K35/76 , A61K39/29 , A61K39/145 , A61K38/21 , A61K39/165 , A61K39/20 , A61K39/02 , A61K39/385 , A61K38/20 , A61P29/00 , A61P9/10 , A61P35/00 , A61P25/00 , A61K39/395
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.

7. 发明授权

US08202517B2 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：US08202517B2
公开(公告)日：2012-06-19
申请号：US12378969
申请日：2009-02-20
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： A61K38/47 , C12N9/26 , 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。

8. 发明申请

US20120093770A1 Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases 有权
公开(公告)号：US20120093770A1
公开(公告)日：2012-04-19
申请号：US13374248
申请日：2011-12-15
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： A61K38/47 , A61K39/05 , A61K39/29 , A61K38/21 , A61K39/165 , A61K33/24 , A61K38/20 , A61P31/00 , A61P27/12 , A61P3/10 , A61P35/00 , A61P3/00 , A61P31/12 , A61P7/02 , A61P33/04 , A61P33/02 , A61P31/06 , A61P31/08 , A61P29/00 , A61K39/395
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.

9. 发明申请

US20110152359A1 Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising threreof 有权
标题翻译：可溶性透明质酸酶糖蛋白（sHASEGP），其制备方法，用途和包含三价
公开(公告)号：US20110152359A1
公开(公告)日：2011-06-23
申请号：US12928890
申请日：2010-12-21
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： A61K48/00 , C12N15/63 , C12N5/10
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。

10. 发明申请

US20110008309A1 Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases 有权
标题翻译：可溶性糖胺聚糖酶和制备和使用可溶性糖胺聚糖酶的方法
公开(公告)号：US20110008309A1
公开(公告)日：2011-01-13
申请号：US12802864
申请日：2010-06-15
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： A61K38/47 , A61P29/00
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.
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。

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