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1. 发明专利

IL208391A MUTANTS OF STREPTOKINASE AND THEIR COVALENTLY MODIFIED FORMS 未知
公开(公告)号：IL208391A
公开(公告)日：2013-03-24
申请号：IL20839110
申请日：2010-10-03
申请人： COUNCIL SCIENT IND RES , SHEKHAR KUMAR , NEERAJ MAHESHWARI , GIRISH SAHNI
发明人： SHEKHAR KUMAR , NEERAJ MAHESHWARI , GIRISH SAHNI

2. 发明授权

US09115210B2 Mutants of Streptokinase and their covalently modified forms 有权
标题翻译：链激酶突变体及其共价修饰形式
公开(公告)号：US09115210B2
公开(公告)日：2015-08-25
申请号：US13312770
申请日：2011-12-06
申请人： Shekhar Kumar , Neeraj Maheshwari , Girish Sahni
发明人： Shekhar Kumar , Neeraj Maheshwari , Girish Sahni
IPC分类号： C12N9/96 , C12N9/70 , A61P9/00 , A61K38/48 , C07K14/78 , C07K14/315 , C07K16/40
CPC分类号： C12N9/52 , A61K38/00 , C07K14/3153 , C07K14/78 , C07K16/40 , C07K2319/00 , C12Y304/24029
摘要： The present invention relates to novel mutants of Streptokinase, its functional fragments and covalently modified forms. Methods are provided for the preparation of the bacterial plasminogen activator protein, Streptokinase its muteins, species variants and their covalently modified variants that are characterized by improved therapeutic properties, such as increased proteolytic stability, extended plasma half-lives, reduced immuno-reactivity and enhanced fibrin clot specificity. The method involves either incorporating additional cysteine residues, or substituting cysteine residues for naturally occurring amino acids into non-essential regions of the protein such that the catalytic activity of the resultant protein remains largely unaltered. These cysteine variants were further modified by covalently attaching a cysteine reactive polymer such as polyethylene glycol (PEG) or sulfhydryl-reactive moieties from a group that includes fluorophore, spin labels or other small conjugates. Disclosed herein are site-specific biologically active conjugates of Streptokinases and its covalently modified variants.
摘要翻译：本发明涉及链激酶的新突变体，其功能片段和共价修饰形式。提供了用于制备细菌纤溶酶原激活蛋白，链激酶其突变蛋白，物种变体及其共价修饰变体的方法，其特征在于改善的治疗性质，例如增加的蛋白水解稳定性，延长的血浆半衰期，降低的免疫反应性和增强的纤维蛋白凝块特异性。该方法包括将另外的半胱氨酸残基，或将天然存在的氨基酸的半胱氨酸残基取代到蛋白质的非必需区域中，使得所得蛋白质的催化活性大体上保持不变。通过共价连接半胱氨酸反应性聚合物如聚乙二醇（PEG）或巯基反应性部分从包括荧光团，自旋标记或其它小共轭物的基团进一步修饰这些半胱氨酸变体。本文公开了链激酶及其共价修饰变体的位点特异性生物活性缀合物。

3. 发明申请

US20120213763A1 MUTANTS OF STREPTOKINASE AND THEIR COVALENTLY MODIFIED FORMS 审中-公开
标题翻译： STREPTOKINASE的突变体及其共同修饰的形式
公开(公告)号：US20120213763A1
公开(公告)日：2012-08-23
申请号：US13312770
申请日：2011-12-06
申请人： Shekhar KUMAR , Neeraj MAHESHWARI , Girish SAHNI
发明人： Shekhar KUMAR , Neeraj MAHESHWARI , Girish SAHNI
IPC分类号： A61K38/48 , C12N9/96 , A61P9/00 , C12N9/70
CPC分类号： C12N9/52 , A61K38/00 , C07K14/3153 , C07K14/78 , C07K16/40 , C07K2319/00 , C12Y304/24029
摘要： The present invention relates to novel mutants of Streptokinase, its functional fragments and covalently modified forms. Methods are provided for the preparation of the bacterial plasminogen activator protein, Streptokinase its muteins, species variants and their covalently modified variants that are characterized by improved therapeutic properties, such as increased proteolytic stability, extended plasma half-lives, reduced immuno-reactivity and enhanced fibrin clot specificity. The method involves either incorporating additional cysteine residues, or substituting cysteine residues for naturally occurring amino acids into non-essential regions of the protein such that the catalytic activity of the resultant protein remains largely unaltered. These cysteine variants were further modified by covalently attaching a cysteine reactive polymer such as polyethylene glycol (PEG) or sulfhydryl-reactive moieties from a group that includes fluorophore, spin labels or other small conjugates. Disclosed herein are site-specific biologically active conjugates of Streptokinases and its covalently modified variants.
摘要翻译：本发明涉及链激酶的新突变体，其功能片段和共价修饰形式。提供了用于制备细菌纤溶酶原激活蛋白，链激酶其突变蛋白，物种变体及其共价修饰变体的方法，其特征在于改善的治疗性质，例如增加的蛋白水解稳定性，延长的血浆半衰期，降低的免疫反应性和增强的纤维蛋白凝块特异性。该方法包括将另外的半胱氨酸残基，或将天然存在的氨基酸的半胱氨酸残基取代到蛋白质的非必需区域中，使得所得蛋白质的催化活性大体上保持不变。通过共价连接半胱氨酸反应性聚合物如聚乙二醇（PEG）或巯基反应性部分从包括荧光团，自旋标记或其它小共轭物的基团进一步修饰这些半胱氨酸变体。本文公开了链激酶及其共价修饰变体的位点特异性生物活性缀合物。

4. 发明申请

US20100034804A1 MUTANTS OF STREPTOKINASE AND THEIR COVALENTLY MODIFIED FORMS 有权
标题翻译： STREPTOKINASE的突变体及其共同修饰的形式
公开(公告)号：US20100034804A1
公开(公告)日：2010-02-11
申请号：US12415142
申请日：2009-03-31
申请人： Shekhar Kumar , Neeraj Maheshwari , Girish Sahni
发明人： Shekhar Kumar , Neeraj Maheshwari , Girish Sahni
IPC分类号： A61K38/48 , C12N9/70 , C12N9/96 , A61P9/00 , A61P9/10
CPC分类号： C12N9/52 , A61K38/00 , C07K14/3153 , C07K14/78 , C07K16/40 , C07K2319/00 , C12Y304/24029
摘要： The present invention relates to novel mutants of Streptokinase, its functional fragments and covalently modified forms. Methods are provided for the preparation of the bacterial plasminogen activator protein, Streptokinase its muteins, species variants and their covalently modified variants that are characterized by improved therapeutic properties, such as increased proteolytic stability, extended plasma half-lives, reduced immuno-reactivity and enhanced fibrin clot specificity. The method involves either incorporating additional cysteine residues, or substituting cysteine residues for naturally occurring amino acids into non-essential regions of the protein such that the catalytic activity of the resultant protein remains largely unaltered. These cysteine variants were further modified by covalently attaching a cysteine reactive polymer such as polyethylene glycol (PEG) or sulfhydryl-reactive moieties from a group that includes fluorophore, spin labels or other small conjugates. Disclosed herein are site-specific biologically active conjugates of Streptokinases and its covalently modified variants.
摘要翻译：本发明涉及链激酶的新突变体，其功能片段和共价修饰形式。提供了用于制备细菌纤溶酶原激活蛋白，链激酶其突变蛋白，物种变体及其共价修饰变体的方法，其特征在于改善的治疗性质，例如增加的蛋白水解稳定性，延长的血浆半衰期，降低的免疫反应性和增强的纤维蛋白凝块特异性。该方法包括将另外的半胱氨酸残基，或将天然存在的氨基酸的半胱氨酸残基取代到蛋白质的非必需区域中，使得所得蛋白质的催化活性大体上保持不变。通过共价连接半胱氨酸反应性聚合物如聚乙二醇（PEG）或巯基反应性部分从包括荧光团，自旋标记或其它小共轭物的基团进一步修饰这些半胱氨酸变体。本文公开了链激酶及其共价修饰变体的位点特异性生物活性缀合物。

5. 发明授权

US08093032B2 Mutants of streptokinase and their covalently modified forms 有权
标题翻译：链激酶突变体及其共价修饰形式
公开(公告)号：US08093032B2
公开(公告)日：2012-01-10
申请号：US12415142
申请日：2009-03-31
申请人： Shekhar Kumar , Neeraj Maheshwari , Girish Sahni
发明人： Shekhar Kumar , Neeraj Maheshwari , Girish Sahni
IPC分类号： C12N9/00 , C12N9/70 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N9/52 , A61K38/00 , C07K14/3153 , C07K14/78 , C07K16/40 , C07K2319/00 , C12Y304/24029
摘要： The present invention relates to novel mutants of Streptokinase, its functional fragments and covalently modified forms. Methods are provided for the preparation of the bacterial plasminogen activator protein, Streptokinase its muteins, species variants and their covalently modified variants that are characterized by improved therapeutic properties, such as increased proteolytic stability, extended plasma half-lives, reduced immuno-reactivity and enhanced fibrin clot specificity. The method involves either incorporating additional cysteine residues, or substituting cysteine residues for naturally occurring amino acids into non-essential regions of the protein such that the catalytic activity of the resultant protein remains largely unaltered. These cysteine variants were further modified by covalently attaching a cysteine reactive polymer such as polyethylene glycol (PEG) or sulfhydryl-reactive moieties from a group that includes fluorophore, spin labels or other small conjugates. Disclosed herein are site-specific biologically active conjugates of Streptokinases and its covalently modified variants.
摘要翻译：本发明涉及链激酶的新突变体，其功能片段和共价修饰形式。提供了用于制备细菌纤溶酶原激活蛋白，链激酶其突变蛋白，物种变体及其共价修饰变体的方法，其特征在于改善的治疗性质，例如增加的蛋白水解稳定性，延长的血浆半衰期，降低的免疫反应性和增强的纤维蛋白凝块特异性。该方法包括将另外的半胱氨酸残基，或将天然存在的氨基酸的半胱氨酸残基取代到蛋白质的非必需区域中，使得所得蛋白质的催化活性大体上保持不变。通过共价连接半胱氨酸反应性聚合物如聚乙二醇（PEG）或巯基反应性部分从包括荧光团，自旋标记或其它小共轭物的基团进一步修饰这些半胱氨酸变体。本文公开了链激酶及其共价修饰变体的位点特异性生物活性缀合物。

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