公开(公告)号：US08524480B2

公开(公告)日：2013-09-03

申请号：US13559063

申请日：2012-07-26

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

IPC分类号： C12N9/16 ,  C07K14/00 ,  C12Q1/44 ,  C12P21/00

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。

公开(公告)号：US20120322137A1

公开(公告)日：2012-12-20

申请号：US13559063

申请日：2012-07-26

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

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。

公开(公告)号：US20110287514A1

公开(公告)日：2011-11-24

申请号：US13180359

申请日：2011-07-11

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

IPC分类号： C12N9/22 ,  C07H21/04 ,  C12N5/09 ,  C12N15/63 ,  C12N1/21

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。

公开(公告)号：US07977079B2

公开(公告)日：2011-07-12

申请号：US12177229

申请日：2008-07-22

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

IPC分类号： C12N15/00 ,  C12N5/10 ,  C12N1/21 ,  C07H21/00 ,  C12N9/16 ,  C12P21/00

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。

公开(公告)号：US20100233809A1

公开(公告)日：2010-09-16

申请号：US12177229

申请日：2008-07-22

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

IPC分类号： C12N15/63 ,  C12N5/00

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。

公开(公告)号：US08247190B2

公开(公告)日：2012-08-21

申请号：US13180359

申请日：2011-07-11

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

IPC分类号： C12Q1/44 ,  A61K38/46 ,  C12N9/16 ,  C07K14/00

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。

公开(公告)号：US07416875B2

公开(公告)日：2008-08-26

申请号：US11454379

申请日：2006-06-16

申请人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

发明人： Ronald T. Raines ,  Julie C. Mitchell ,  Thomas J. Rutkoski

IPC分类号： C12N9/16 ,  C07K14/00 ,  C07H21/00 ,  C12N5/10 ,  C12N1/21 ,  C12N15/00 ,  C12P21/00 ,  C12Q1/44

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。