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1.发明申请公开(公告)号：US20080234191A1
公开(公告)日：2008-09-25
申请号：US11890900
申请日：2007-08-07
CPC分类号： C07K14/472 , A61K38/00 , C07K14/463 , C07K2319/00
摘要： A modified human complement C3 protein (C3) is disclosed comprising a substitution of a portion of a human C3 protein, with a corresponding portion of a Cobra Venom Factor protein (CVF) which results in a human C3 protein with CVF functions, but with substantially reduced immunogenicity. Advantageously, the C3 protein can be manipulated to contain at least one of the following CVF functions: increased stability of the C3 convertase and increased resistance to the actions of factors H and/or I. A large number of hybrid C3 proteins containing substitutions in the C-terminal portion of the alpha chain of C3 are presented and tested for the above functions. Methods of treatment of diseases such as reperfusion injury, autoimmune diseases, and other diseases of increased complement activation are presented as well as methods of increasing the effectiveness of gene therapeutics and other therapeutics.
摘要翻译： 公开了修饰的人补体C3蛋白（C3），其包含部分人C3蛋白的取代与眼镜蛇毒因子蛋白（CVF）的相应部分，其导致具有CVF功能的人C3蛋白，但基本上 免疫原性降低。 有利地，可以操作C3蛋白以包含以下CVF功能中的至少一种：增加C3转化酶的稳定性和增加对因子H和/或I的作用的抗性。大量含有取代的杂合C3蛋白 呈现C3的α链的C末端部分并进行上述功能的测试。 提出了治疗诸如再灌注损伤，自身免疫疾病和其他增加补体活化的疾病的方法以及增加基因治疗剂和其它治疗剂的有效性的方法。
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公开(公告)号：US5773243A
公开(公告)日：1998-06-30
申请号：US447411
申请日：1995-05-23
摘要： DNA sequences encoding cobra C3, CVF1, and CVF2, as well as plasmids and transformed hosts comprising such DNA sequences, are provided.
摘要翻译： 提供了编码眼镜蛇C3，CVF1和CVF2的DNA序列，以及包含这种DNA序列的质粒和转化宿主。
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3.发明申请公开(公告)号：US20100179092A1
公开(公告)日：2010-07-15
申请号：US12513665
申请日：2007-11-15
IPC分类号： A61K38/16 , C07K14/00 , C07H21/04 , A61P43/00 , C12N15/63 , C12P21/02 , C12N5/10 , C12N1/21 , C12N1/19
CPC分类号： C07K14/472 , A61K38/00
摘要： The invention provides modified human complement C3 proteins, comprising a human C3 protein, wherein amino acid residues in the human C3 protein are substituted with a corresponding portion of a Cobra Venom Factor (CVF) protein, and wherein one or more amino acid residues in the CVF portion of the modified human complement C3 protein are further modified.
摘要翻译： 本发明提供了修饰的人补体C3蛋白，其包含人C3蛋白，其中人C3蛋白中的氨基酸残基被眼镜蛇毒因子（CVF）蛋白的相应部分取代，并且其中一个或多个氨基酸残基 修饰的人补体C3蛋白的CVF部分被进一步修饰。
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公开(公告)号：US20080311132A1
公开(公告)日：2008-12-18
申请号：US11579235
申请日：2005-04-29
IPC分类号： A61K39/44 , C07K19/00 , C07K14/435 , A61P25/28 , C12Q1/00 , C12N5/06 , C07H21/04 , A61P25/16 , A61K38/17
CPC分类号： C07K14/472 , A61K38/00 , C07K14/463 , C07K2319/00
摘要： A modified human complement C3 protein (C3) is disclosed comprising a substitution of a portion of a human C3 protein, with a corresponding portion of a Cobra Venom Factor protein (CVF) which results in a human C3 protein with CVF functions, but with substantially reduced immunogenicity. Advantageously, the C3 protein can be manipulated to contain at least one of the following CVF functions: increased stability of the C3 convertase and increased resistance to the actions of factors H and/or I. A large number of hybrid C3 proteins containing substitutions in the C-terminal portion of the alpha chain of C3 are presented and tested for the above functions. Methods of treatment of diseases such as reperfusion injury, autoimmune diseases, and other diseases of increased complement activation are presented as well as methods of increasing the effectiveness of gene therapeutics and other therapeutics.
摘要翻译： 公开了修饰的人补体C3蛋白（C3），其包含部分人C3蛋白的取代与眼镜蛇毒因子蛋白（CVF）的相应部分，其导致具有CVF功能的人C3蛋白，但基本上 免疫原性降低。 有利地，可以操作C3蛋白以包含以下CVF功能中的至少一种：增加C3转化酶的稳定性和增加对因子H和/或I的作用的抗性。大量含有取代的杂合C3蛋白 呈现C3的α链的C末端部分并进行上述功能的测试。 提出了治疗诸如再灌注损伤，自身免疫疾病和其他增加补体活化的疾病的方法以及增加基因治疗剂和其它治疗剂的有效性的方法。
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公开(公告)号：US08632780B2
公开(公告)日：2014-01-21
申请号：US11579235
申请日：2005-04-29
CPC分类号： C07K14/472 , A61K38/00 , C07K14/463 , C07K2319/00
摘要： A modified human complement C3 protein (C3) is disclosed comprising a substitution of a portion of a human C3 protein, with a corresponding portion of a Cobra Venom Factor protein (CVF) which results in a human C3 protein with CVF functions, but with substantially reduced immunogenicity. Advantageously, the C3 protein can be manipulated to contain at least one of the following CVF functions: increased stability of the C3 convertase and increased resistance to the actions of factors H and/or I. A large number of hybrid C3 proteins containing substitutions in the C-terminal portion of the alpha chain of C3 are presented and tested for the above functions. Methods of treatment of diseases such as reperfusion injury, autoimmune diseases, and other diseases of increased complement activation are presented as well as methods of increasing the effectiveness of gene therapeutics and other therapeutics.
摘要翻译： 公开了修饰的人补体C3蛋白（C3），其包含部分人C3蛋白的取代与眼镜蛇毒因子蛋白（CVF）的相应部分，其导致具有CVF功能的人C3蛋白，但基本上 免疫原性降低。 有利地，可以操作C3蛋白以包含以下CVF功能中的至少一种：增加C3转化酶的稳定性和增加对因子H和/或I的作用的抗性。大量含有取代的杂合C3蛋白 呈现C3的α链的C末端部分并进行上述功能的测试。 提出了治疗诸如再灌注损伤，自身免疫疾病和其他增加补体活化的疾病的方法以及增加基因治疗剂和其它治疗剂的有效性的方法。
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公开(公告)号：US11903996B2
公开(公告)日：2024-02-20
申请号：US15288830
申请日：2016-10-07
IPC分类号： A61K38/17 , C07K14/47 , A61P37/04 , A61K47/10 , C12N15/62 , C12N15/79 , C12N9/64 , A61K38/00 , C07K14/015
CPC分类号： A61K38/1725 , A61K47/10 , A61P37/04 , C07K14/015 , C07K14/47 , C07K14/472 , C12N15/62 , C12N15/79 , A61K38/00 , C12N9/64 , Y02A50/30
摘要： The invention relates generally to a modified human C3 protein containing a number of single amino acid changes in the α and β-chain of human C3 protein, designed to increase the affinity of the modified protein to factor B or Bb, to decrease the affinity of the modified protein to factor H, and to reduce the immunogenicity of the modified protein as compared to the native human C3 protein, a nucleotide sequence encoding the modified C3 protein, a plasmid or viral vector containing the nucleotide sequence for expression the modified C3 protein, and a host cell containing the plasmid or viral vector. We also present a polyethylene glycol covalently bound to the modified C3 protein for reducing immunogenicity and increasing plasma half-life of the modified C3 protein; a method for depleting complement in a patient by administering the modified C3 protein to the patient in an amount effective to deplete complement; a method of ameliorating effects caused by or disease or a method of ameliorating reperfusion injury in a patient by delivering the modified C3 protein.
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公开(公告)号：US20190016766A1
公开(公告)日：2019-01-17
申请号：US16058867
申请日：2018-08-08
摘要： The invention relates generally to derivatives of human C3 protein containing a number of single amino acid changes in the α- and β-chains of C3, designed to increase the affinity of the modified protein to factor B, to lessen the affinity of the modified protein for factor H, and to reduce the immunogenicity of the modified protein as compared to unmodified protein. The invention also presents methods of using these modified proteins for the treatment of certain cancers.
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公开(公告)号：US20180369328A1
公开(公告)日：2018-12-27
申请号：US15288830
申请日：2016-10-07
摘要： The invention relates generally to a modified human C3 protein containing a number of single amino acid changes in the α and β-chain of human C3 protein, designed to increase the affinity of the modified protein to factor B or Bb, to decrease the affinity of the modified protein to factor H, and to reduce the immunogenicity of the modified protein as compared to the native human C3 protein, a nucleotide sequence encoding the modified C3 protein, a plasmid or viral vector containing the nucleotide sequence for expression the modified C3 protein, and a host cell containing the plasmid or viral vector. We also present a polyethylene glycol covalently bound to the modified C3 protein for reducing immunogenicity and increasing plasma half-life of the modified C3 protein; a method for depleting complement in a patient by administering the modified C3 protein to the patient in an amount effective to deplete complement; a method of ameliorating effects caused by or disease or a method of ameliorating reperfusion injury in a patient by delivering the modified C3 protein.
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