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公开(公告)号：US08247190B2
公开(公告)日：2012-08-21
申请号：US13180359
申请日：2011-07-11
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US07416875B2
公开(公告)日：2008-08-26
申请号：US11454379
申请日：2006-06-16
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US08524480B2
公开(公告)日：2013-09-03
申请号：US13559063
申请日：2012-07-26
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US20120322137A1
公开(公告)日：2012-12-20
申请号：US13559063
申请日：2012-07-26
IPC分类号： C12N9/22
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US20110287514A1
公开(公告)日：2011-11-24
申请号：US13180359
申请日：2011-07-11
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US07977079B2
公开(公告)日：2011-07-12
申请号：US12177229
申请日：2008-07-22
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US20100233809A1
公开(公告)日：2010-09-16
申请号：US12177229
申请日：2008-07-22
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005 , Y02A50/473
摘要： This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.
摘要翻译： 本发明涉及RNA酶A超家族成员的改变形式。 核糖核酸酶A可以通过改变其氨基酸序列来修饰为细胞毒性，使得它不会被核糖核酸酶抑制剂容易地结合，同时仍然保留催化性质。 虽然早期的工作已经确定了会导致细胞毒性的RNase A的一些修改，但是使用FADE算法进行分子相互作用分析已经导致了其他几个作为修饰候选的位置。 这些修饰中的一些确实导致具有增加的细胞毒性的RNA酶A变体。
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公开(公告)号：US08697062B2
公开(公告)日：2014-04-15
申请号：US12247438
申请日：2008-10-08
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005
摘要： The present invention relates generally to conjugates of human ribonucleases and water-soluble polymers, compositions comprising the conjugates and methods of using the same. In particular, the present invention provides conjugates of human ribonucleases and one or more water-soluble polymer compositions (e.g., to increase serum half-life and a pharmacokinetic profile, in vivo biological activity, stability, and/or reduce host immune response to the protein in vivo) as well as methods of using the conjugates in the therapy, treatment, and/or prevention of disease (e.g., cancer).
摘要翻译： 本发明一般涉及人核糖核酸酶和水溶性聚合物的缀合物，包含缀合物的组合物及其使用方法。 特别地，本发明提供人核糖核酸酶和一种或多种水溶性聚合物组合物的缀合物（例如，以增加血清半衰期和药代动力学特征，体内生物活性，稳定性和/或降低对 体内的蛋白质）以及在治疗，治疗和/或预防疾病（例如癌症）中使用缀合物的方法。
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公开(公告)号：US20090098101A1
公开(公告)日：2009-04-16
申请号：US12247438
申请日：2008-10-08
CPC分类号： C12N9/22 , A61K38/00 , C12Y301/27005
摘要： The present invention relates generally to conjugates of human ribonucleases and water-soluble polymers, compositions comprising the conjugates and methods of using the same. In particular, the present invention provides conjugates of human ribonucleases and one or more water-soluble polymer compositions (e.g., to increase serum half-life and a pharmacokinetic profile, in vivo biological activity, stability, and/or reduce host immune response to the protein in vivo) as well as methods of using the conjugates in the therapy, treatment, and/or prevention of disease (e.g., cancer).
摘要翻译： 本发明一般涉及人核糖核酸酶和水溶性聚合物的缀合物，包含缀合物的组合物及其使用方法。 特别地，本发明提供人核糖核酸酶和一种或多种水溶性聚合物组合物的缀合物（例如，以增加血清半衰期和药代动力学特征，体内生物活性，稳定性和/或降低对 体内的蛋白质）以及在治疗，治疗和/或预防疾病（例如癌症）中使用缀合物的方法。
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公开(公告)号：US09758569B2
公开(公告)日：2017-09-12
申请号：US11807270
申请日：2007-05-25
CPC分类号： C07K14/78 , C07K5/0821 , C07K14/001
摘要： Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.
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