公开(公告)号：US06548651B1

公开(公告)日：2003-04-15

申请号：US09689155

申请日：2000-10-12

申请人： Peter E. Nielsen ,  Liam Good ,  Henrik Frydenlund Hansen ,  Frederik Beck ,  Leila Malik ,  Carsten Schou ,  Margit Wissenbach ,  Birgit Kjaeldgaard Giwercman

发明人： Peter E. Nielsen ,  Liam Good ,  Henrik Frydenlund Hansen ,  Frederik Beck ,  Leila Malik ,  Carsten Schou ,  Margit Wissenbach ,  Birgit Kjaeldgaard Giwercman

IPC分类号： C07H2104

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K47/62 ,  A61L2/0082 ,  C12N2310/152 ,  C12N2310/3181 ,  C12N2310/323 ,  C12N2310/3233 ,  C12N2310/33 ,  C12N2310/3513

摘要： The present invention relates to novel drugs which may be used in combating infectious micro-organisms, particularly bacteria. More specifically, the invention relates to peptide nucleic acid (PNA) sequences that are modified by conjugating cationic peptides to the PNA moiety in order to obtain novel PNA molecules that exhibit enhanced anti-infective properties.

摘要翻译： 本发明涉及可用于对抗感染性微生物，特别是细菌的新型药物。 更具体地，本发明涉及通过将阳离子肽与PNA部分缀合而修饰的肽核酸（PNA）序列，以获得表现出增强的抗感染性质的新型PNA分子。

公开(公告)号：US08026355B2

公开(公告)日：2011-09-27

申请号：US12765673

申请日：2010-04-22

申请人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： C07H21/04

CPC分类号： C07H21/04

摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

摘要翻译： 提供针对存活蛋白基因的寡核苷酸用于调节存活蛋白的表达。 组合物包含针对编码存活蛋白的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节存活蛋白表达和治疗与存活素过表达，突变存活蛋白或两者表达相关的疾病的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。

公开(公告)号：US20100292311A1

公开(公告)日：2010-11-18

申请号：US12765673

申请日：2010-04-22

申请人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K31/713 ,  A61P35/00

CPC分类号： C07H21/04

摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

摘要翻译： 提供针对存活蛋白基因的寡核苷酸用于调节存活蛋白的表达。 组合物包含针对编码存活蛋白的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节存活蛋白表达和治疗与存活素过表达，突变存活蛋白或两者表达相关的疾病的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。

公开(公告)号：US07741309B2

公开(公告)日：2010-06-22

申请号：US12493625

申请日：2009-06-29

申请人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K48/00

CPC分类号： C07H21/04

摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

摘要翻译： 提供针对存活蛋白基因的寡核苷酸用于调节存活蛋白的表达。 组合物包含针对编码存活蛋白的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节存活蛋白表达和治疗与存活素过表达，突变存活蛋白或两者表达相关的疾病的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。

公开(公告)号：US08173428B2

公开(公告)日：2012-05-08

申请号：US12249676

申请日：2008-10-10

申请人： Christoph Rosenbohm ,  Lene Sonderbye Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens Bo Hansen ,  Marlene Asklund

发明人： Christoph Rosenbohm ,  Lene Sonderbye Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens Bo Hansen ,  Marlene Asklund

IPC分类号： C12N15/00 ,  C12N5/00 ,  C07H21/04

CPC分类号： C12N15/1135 ,  A61K38/00 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/319 ,  C12N2310/3341

摘要： The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5′-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx(Gx)(c)-3′, and preferably of the general formula 5′-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3′, wherein capital letters designate an LNA nucleotide analogue selected from β-D-oxy-LNA, β-D-thio-LNA, β-D-amino-LNA and α-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumor development in vivo. The LNA oligonucleotides are superior to other LNA oligonucleotides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.

摘要翻译： 本公开涉及具有通式5' - （MeC x）（Tx）MeC x As A stscscsastsgsgsMeC x A x（G x）（c）-3'的（亚）序列的LNA寡核苷酸，优选通式为5'-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3' 其中大写字母表示选自以下的LNA核苷酸类似物：-D-oxy-LNA，＆bgr; -D-thio-LNA，＆bgr; -D-氨基-LNA和α-L-氧-LNA，小字母表示脱氧核苷酸 ，下划线表示如上定义的LNA核苷酸类似物或脱氧核苷酸。 这样的LNA寡核苷酸在通过反义机制抑制存活蛋白的表现方面表现出惊人的良好性质，从而导致体内肿瘤发展的减少或抑制。 LNA寡核苷酸优于靶向通过功能读数如凋亡诱导和增殖抑制测定的存活mRNA的其他LNA寡核苷酸，并且在转染的癌细胞系中下调存活蛋白mRNA和蛋白质的有效性，并且与紫杉醇优良结合诱导凋亡 与其他LNA寡核苷酸相比。

公开(公告)号：US07713738B2

公开(公告)日：2010-05-11

申请号：US10776934

申请日：2004-02-10

申请人： Bo Hansen ,  Charlotte Albæk Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albæk Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： C12N5/00

CPC分类号： C07H21/04

摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

公开(公告)号：US20090318362A1

公开(公告)日：2009-12-24

申请号：US12493625

申请日：2009-06-29

申请人： Jens Bo rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Jens Bo rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K38/10 ,  A61P35/00

CPC分类号： C07H21/04

摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

摘要翻译： 提供针对存活蛋白基因的寡核苷酸用于调节存活蛋白的表达。 组合物包含针对编码存活蛋白的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节存活蛋白表达和治疗与存活素过表达，突变存活蛋白或两者表达相关的疾病的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。

公开(公告)号：US20080188432A1

公开(公告)日：2008-08-07

申请号：US11640123

申请日：2006-12-15

申请人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K31/7052 ,  C07H21/04

CPC分类号： C12N15/1135 ,  A61K38/00 ,  C07H21/04 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/33 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346

摘要： Oligonucleotides directed against the Ha-ras gene are provided for modulating the expression of Ha-ras. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Ha-ras. Methods of using these compounds for modulation of Ha-ras expression and for the treatment of diseases associated with either overexpression of Ha-ras, expression of mutated Ha-ras or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

摘要翻译： 提供针对Ha-ras基因的寡核苷酸用于调节Ha-ras的表达。 组合物包含针对编码Ha-ras的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节Ha-ras表达和治疗与Ha-ras的过表达有关的疾病，突变型Ha-ras或两者的表达的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。

公开(公告)号：US20120322848A1

公开(公告)日：2012-12-20

申请号：US13443557

申请日：2012-04-10

申请人： Christoph Rosenbohm ,  Lene S. Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens B. Hansen ,  Marlene Asklund

发明人： Christoph Rosenbohm ,  Lene S. Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens B. Hansen ,  Marlene Asklund

IPC分类号： A61K31/712 ,  A61P35/02 ,  A61P35/00

CPC分类号： C12N15/1135 ,  A61K38/00 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/319 ,  C12N2310/3341

摘要： The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5′-(MeCx)(Tx)MeCxAsAstsCsCsastsgsgsMeCxAx(Gx)(c)-3′, and preferably of the general formula 5′-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3′, wherein capital letters designate an LNA nucleotide analogue selected from β-D-oxy-LNA, β-D-thio-LNA, β-D-amino-LNA and α-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumour development in vivo. The LNA oligonucleotides are superior to other LNA oligonucletides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.

摘要翻译： 本公开内容涉及具有通式5'（（MeCx）（Tx）MeCxAsAstsCsCsastsgsgsMeCxAx（Gx）（c）-3'，优选通式为5'-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3'的（亚）序列的LNA寡核苷酸， 其中大写字母表示选自以下的LNA核苷酸类似物：-D-oxy-LNA，＆bgr; -D-thio-LNA，＆bgr; -D-氨基-LNA和α-L-氧-LNA，小字母表示脱氧核苷酸 ，下划线表示如上定义的LNA核苷酸类似物或脱氧核苷酸。 这样的LNA寡核苷酸在通过反义机制抑制存活蛋白的表现方面表现出惊人的良好性质，从而导致体内肿瘤发展的减少或抑制。 LNA寡核苷酸优于靶向通过功能读数（如凋亡诱导和增殖抑制）测量的存活mRNA的其他LNA寡核苷酸，并且在转染的癌细胞系中下调Survivin mRNA和蛋白质，并且与Taxol优异结合诱导凋亡有效 与其他LNA寡核苷酸相比。

公开(公告)号：US20120088907A1

公开(公告)日：2012-04-12

申请号：US13183365

申请日：2011-07-14

申请人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： C07H21/04

CPC分类号： C07H21/04

摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

摘要翻译： 提供针对存活蛋白基因的寡核苷酸用于调节存活蛋白的表达。 组合物包含针对编码存活蛋白的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节存活蛋白表达和治疗与存活素过表达，突变存活蛋白或两者表达相关的疾病的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。