公开(公告)号：US08946176B2

公开(公告)日：2015-02-03

申请号：US13275377

申请日：2011-10-18

申请人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

发明人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

IPC分类号： C12N15/113 ,  C12N9/02

CPC分类号： C12N15/1137 ,  A01K67/00 ,  A61K48/00 ,  C12N9/0093 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/33 ,  C12N2310/335 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/50 ,  C12N2310/53 ,  C12Y117/04001

摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.

摘要翻译： 本发明涉及用于抑制RRM2基因表达的双链核糖核酸（dsRNA）。 本发明还涉及包含dsRNA或核酸分子的药物组合物或其编码与其药学上可接受的载体的载体; 使用所述药物组合物治疗由RRM2基因表达引起的疾病的方法; 以及抑制细胞中RRM2表达的方法。

公开(公告)号：US09938531B2

公开(公告)日：2018-04-10

申请号：US15415415

申请日：2017-01-25

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

IPC分类号： C12N15/113

CPC分类号： C12N15/1137 ,  A01K67/00 ,  A61K48/00 ,  C12N9/0093 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/33 ,  C12N2310/335 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/50 ,  C12N2310/53 ,  C12Y117/04001

摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.

公开(公告)号：US5834279A

公开(公告)日：1998-11-10

申请号：US813940

申请日：1997-03-03

申请人： Harvey Rubin ,  Fude Yang ,  David Avarbock ,  Sean Curran

发明人： Harvey Rubin ,  Fude Yang ,  David Avarbock ,  Sean Curran

IPC分类号： C12N1/21 ,  C12N9/02 ,  C12N9/90 ,  C12N15/31 ,  C12N9/03

CPC分类号： C12N9/0093 ,  C12N9/90 ,  C12Y117/04001 ,  C12Y599/01002 ,  A01K2217/05

摘要： Nucleic acid molecules that encode R2 subunit protein and topoisomerase I protein, fragments thereof, recombinant expression vectors and host cells are disclosed. Oligonucleotide molecules with nucleotide sequences complimentary to a nucleotide sequence encode R2 subunit protein and topoisomerase I protein are disclosed.

摘要翻译： 公开了编码R2亚基蛋白和拓扑异构酶I蛋白的核酸分子，其片段，重组表达载体和宿主细胞。 公开了具有与编码R2亚单位蛋白质和拓扑异构酶I蛋白质的核苷酸序列互补的核苷酸序列的寡核苷酸分子。

公开(公告)号：US20170137827A1

公开(公告)日：2017-05-18

申请号：US15415415

申请日：2017-01-25

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

IPC分类号： C12N15/113

CPC分类号： C12N15/1137 ,  A01K67/00 ,  A61K48/00 ,  C12N9/0093 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/33 ,  C12N2310/335 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/50 ,  C12N2310/53 ,  C12Y117/04001

摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.

公开(公告)号：US20150113670A1

公开(公告)日：2015-04-23

申请号：US14578716

申请日：2014-12-22

申请人： ARROWHEAD RESEARCH CORPORATION

发明人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

IPC分类号： C12N15/113 ,  A01K67/00

CPC分类号： C12N15/1137 ,  A01K67/00 ,  A61K48/00 ,  C12N9/0093 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/33 ,  C12N2310/335 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/50 ,  C12N2310/53 ,  C12Y117/04001 ,  C12N2310/3521

摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.

摘要翻译： 本发明涉及用于抑制RRM2基因表达的双链核糖核酸（dsRNA）。 本发明还涉及包含dsRNA或核酸分子的药物组合物或其编码与其药学上可接受的载体的载体; 使用所述药物组合物治疗由RRM2基因表达引起的疾病的方法; 以及抑制细胞中RRM2表达的方法。

公开(公告)号：US06602499B1

公开(公告)日：2003-08-05

申请号：US09302952

申请日：1999-04-30

申请人： E. Antonio Chiocca ,  Xandra O. Breakefield

发明人： E. Antonio Chiocca ,  Xandra O. Breakefield

IPC分类号： A61K3500

CPC分类号： B82Y5/00 ,  A61K31/675 ,  A61K35/763 ,  A61K38/415 ,  A61K38/44 ,  A61K45/06 ,  A61K47/6891 ,  A61K48/00 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/16332 ,  C12N2710/16632 ,  C12N2710/16643 ,  C12Y114/14 ,  C12Y117/04001 ,  A61K2300/00

摘要： The present invention relates to viral mutants and methods of using these viral mutants for selectively killing neoplastic cells. The viral mutants of the invention are capable of selectively killing neoplastic cells by a combination of viral mediated oncolysis and anti-cancer (“suicide”) gene therapy.

摘要翻译： 本发明涉及病毒突变体和使用这些病毒突变体选择性杀死肿瘤细胞的方法。 本发明的病毒突变体能够通过病毒介导的溶瘤和抗癌（“自杀”）基因治疗的组合选择性地杀死肿瘤细胞。

公开(公告)号：US20020004488A1

公开(公告)日：2002-01-10

申请号：US09155246

申请日：1998-09-24

发明人： JIM A. WRIGHT ,  AIPING H. YOUNG

IPC分类号： A61K048/00 ,  C07H021/02 ,  C07H021/04

CPC分类号： A61K38/44 ,  A61K48/00 ,  C12Y117/04001 ,  Y02A50/471

摘要： The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.

摘要翻译： 本发明提供了通过使肿瘤细胞与生长调节量的哺乳动物的核糖核苷酸还原酶R1的可表达核酸序列接触来调节人或其他哺乳动物细胞恶性的方法。 本发明还提供并使用生长调节量的核糖核苷酸还原酶R1蛋白或生物活性肽来调节人或其他哺乳动物细胞的恶性。 该方法提供哺乳动物核糖核苷酸还原酶的R1组分的一般升高的表达。 可表达的核酸序列可以是用于基因治疗的载体的形式。

公开(公告)号：US20160186139A1

公开(公告)日：2016-06-30

申请号：US14122226

申请日：2012-05-29

申请人： University of Washington

发明人： Michael Regnier ,  Michael Laflamme ,  Charles Murry ,  F. Steven Korte ,  Scott Lundy ,  Stephen Denison Hauschka ,  Jeffrey S. Chamberlain

IPC分类号： C12N5/077 ,  C12N9/02 ,  A61K48/00 ,  A61K35/34 ,  A61K9/00 ,  C12N15/86 ,  C12N7/00

CPC分类号： C12N5/0657 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/0375 ,  A61K9/0019 ,  A61K35/34 ,  A61K48/005 ,  C07K14/4716 ,  C12N7/00 ,  C12N9/0093 ,  C12N15/8509 ,  C12N15/86 ,  C12N2750/14132 ,  C12N2750/14143 ,  C12N2799/022 ,  C12N2799/025 ,  C12Y117/04001 ,  C12Y117/04002

摘要： Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.

摘要翻译： 提供了用于改善哺乳动物心脏功能，心肌收缩力和放松的组合物和方法。 用包含核糖核苷酸还原酶亚基R1编码核酸序列的一个或多个表达载体转染的心肌细胞和可操作地连接到启动子的核糖核苷酸还原酶亚基R2-编码核酸序列的哺乳动物心肌接种。 还提供了通过移植过量表达R1和R2的供体细胞将dATP递送至心肌的组合物和方法。 因此，原位产生dATP并通过在供体细胞和宿主心肌细胞之间建立的间隙连接递送。 或者，具有R1和R2编码构建体的病毒载体直接给予哺乳动物。 通过施用包含编码L48Q，61Q或L57Q cTnC变体的核酸序列的载体也可以改善心脏功能。

公开(公告)号：US20120159657A1

公开(公告)日：2012-06-21

申请号：US13275377

申请日：2011-10-18

申请人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

发明人： John Frederick Boylan ,  Birgit Bramlage ,  Markus Hossbach ,  John Reidhaar-Olson

IPC分类号： A01K67/00 ,  C12N5/00 ,  A61P35/00 ,  C12N15/63 ,  C12N15/113 ,  A61K31/713

CPC分类号： C12N15/1137 ,  A01K67/00 ,  A61K48/00 ,  C12N9/0093 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/33 ,  C12N2310/335 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/50 ,  C12N2310/53 ,  C12Y117/04001

摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.

摘要翻译： 本发明涉及用于抑制RRM2基因表达的双链核糖核酸（dsRNA）。 本发明还涉及包含dsRNA或核酸分子的药物组合物或其编码与其药学上可接受的载体的载体; 使用所述药物组合物治疗由RRM2基因表达引起的疾病的方法; 以及抑制细胞中RRM2表达的方法。

公开(公告)号：US20030087866A1

公开(公告)日：2003-05-08

申请号：US10223655

申请日：2002-08-20

申请人： GENESENSE TECHNOLOGIES INC.

发明人： Jim A. Wright ,  Aiping H. Young

IPC分类号： A61K048/00 ,  C12N015/85

CPC分类号： A61K38/44 ,  A61K48/00 ,  C12Y117/04001 ,  Y02A50/471

摘要： The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.