公开(公告)号：US08501703B2

公开(公告)日：2013-08-06

申请号：US12065250

申请日：2006-08-29

申请人： C. Frank Bennett ,  Nicholas M. Dean ,  Ryszard Kole ,  Casey C. Kopczynski

发明人： C. Frank Bennett ,  Nicholas M. Dean ,  Ryszard Kole ,  Casey C. Kopczynski

IPC分类号： A61K48/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2310/3531

摘要： Disclosed herein are compounds, compositions and methods for modulating splicing of a selected target mRNA. Further provided are uses of the disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Methods of enhancing cellular uptake, modulating tissue distribution and enhancing pharmacological activity of RNase H-independent antisense oligonucleotides are also provided.

公开(公告)号：US20110039334A1

公开(公告)日：2011-02-17

申请号：US12065250

申请日：2006-08-29

申请人： C. Frank Bennett ,  Nicholas M. Dean ,  Ryszard M. Kole ,  Casey C. Kopczynski

发明人： C. Frank Bennett ,  Nicholas M. Dean ,  Ryszard M. Kole ,  Casey C. Kopczynski

IPC分类号： C12N5/071 ,  C07H21/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2310/3531

摘要： Disclosed herein are compounds, compositions and methods for modulating splicing of a selected target mRNA. Further provided are uses of the disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Methods of enhancing cellular uptake, modulating tissue distribution and enhancing pharmacological activity of RNase H-independent antisense oligonucleotides are also provided.

摘要翻译： 本文公开了用于调节选定靶mRNA的剪接的化合物，组合物和方法。 还提供了所公开的化合物和组合物在制备用于治疗疾病和病症的药物中的用途。 还提供了增强细胞摄取，调节组织分布和增强RNase H非依赖性反义寡核苷酸的药理活性的方法。

公开(公告)号：US06339066B1

公开(公告)日：2002-01-15

申请号：US08829637

申请日：1997-03-31

申请人： C. Frank Bennett ,  Nicholas M. Dean ,  Phillip Dan Cook ,  Glenn Hoke

发明人： C. Frank Bennett ,  Nicholas M. Dean ,  Phillip Dan Cook ,  Glenn Hoke

IPC分类号： C07H2104

CPC分类号： A61K31/70 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C12N9/0069 ,  C12N9/12 ,  C12N15/10 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/1132 ,  C12N15/1133 ,  C12N15/1135 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12P19/34 ,  C12Q1/68 ,  C12Q1/6813 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q1/701 ,  C12Q2600/158 ,  C12Y113/11012 ,  C12Y207/11013

摘要： Compositions and methods are provided for the treatment and diagnosis of diseases associated with the expression of one or more of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms (isozymes) of protein kinase C (PKC). Oligonucleotides are provided which are targeted to nucleic acids encoding PKC-&bgr;I, PKC-&bgr;II, PKC-&ggr;, PKC-&dgr;, PKC-&egr;, PKC-&zgr; or PKC-&eegr;. Provided herein are oligonucleotides specifically hybridizable with a translation initiation site, 5′-untranslated region, 3′-untranslated region or other targeted region of a &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoform of PKC, wherein at least about 75% of the nucleoside units of a given oligonucleotide are joined together by a stereospecific (i.e., Sp or Rp) phosphorothioate 3′ to 5′ linkages. In preferred embodiments, the oligonucleotides of the disclosure additionally contain one or more chemical modifications. Also disclosed are methods of using the oligonucleotides of the invention for modulating the expression of at least one of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms of PKC and for treating animals suffering from disease amenable to therapeutic intervention by modulating the expression of one or more of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms of PKC.

摘要翻译： 提供组合物和方法用于治疗和诊断与βI，βII，γ，δ，epsi和zgr中的一种或多种的表达相关的疾病。 或蛋白激酶C（PKC）的eta同工型（同工酶）。 提供寡核苷酸，其靶向编码PKC-βI，PKC-βII，PKC-γ，PKC-δ，PKC-epsi，PKC- 或PKC-eta。 本文提供了与翻译起始位点，5'-非翻译区，3'非翻译区或βI，βII，γ，δ，ε1和zgr的其它目标区域特异性杂交的寡核苷酸。 或等位基因型，其中给定寡核苷酸的至少约75％的核苷单位通过立体特异性（即Sp或Rp）硫代磷酸酯3'至5'键连接在一起。 在优选的实施方案中，本公开的寡核苷酸另外含有一种或多种化学修饰。 还公开了使用本发明的寡核苷酸调节βI，βII，γ，δ，epsi和zgr中至少一种的表达的方法。 或eta同种型，并通过调节βI，βII，γ，δ，εi，和zgr中的一种或多种的表达来治疗患有适于治疗性干预的疾病的动物。 或PKC的eta同种型。

公开(公告)号：US6117847A

公开(公告)日：2000-09-12

申请号：US94714

申请日：1998-06-15

申请人： C. Frank Bennett ,  Nicholas M. Dean

发明人： C. Frank Bennett ,  Nicholas M. Dean

IPC分类号： A61K38/00 ,  C12N9/12 ,  C12N15/113 ,  C12Q1/68 ,  A61K31/70 ,  C07H21/00

CPC分类号： C12N15/1137 ,  C12N9/12 ,  C12Q1/6876 ,  C12Q1/6883 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Q2600/158

摘要： Compositions and methods are provided for modulating the expression of protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. The oligonucleotides are from 5 to 50 nucleotides in length and in one referred embodiment are from 12 to 18 nucleotides in length. The oligonucleotides may be chimeric oligonucleotides and in a preferred embodiment comprise at least one 2'-O-methoxyethyl modification. Pharmaceutical compositions comprising the oligonucleotides of the invention are also provided. Methods of inhibiting protein kinase C expression and methods of treating conditions associated with expression of protein kinase C using oligonucleotides of the invention are disclosed.

摘要翻译： 提供组合物和方法用于调节蛋白激酶C的表达。提供靶向编码PKC的核酸的寡核苷酸。 寡核苷酸长度为5至50个核苷酸，并且在一个所提及的实施方案中，长度为12至18个核苷酸。 寡核苷酸可以是嵌合寡核苷酸，并且在优选的实施方案中包含至少一个2'-O-甲氧基乙基修饰。 还提供了包含本发明的寡核苷酸的药物组合物。 公开了使用本发明的寡核苷酸抑制蛋白激酶C表达的方法和与蛋白激酶C的表达相关的病症的治疗方法。

公开(公告)号：US6015892A

公开(公告)日：2000-01-18

申请号：US578615

申请日：1996-01-11

申请人： C. Frank Bennett ,  Russell T. Boggs ,  Nicholas M. Dean

发明人： C. Frank Bennett ,  Russell T. Boggs ,  Nicholas M. Dean

IPC分类号： C12N15/09 ,  A61K31/7088 ,  A61K31/711 ,  A61K31/712 ,  A61K31/7125 ,  A61K38/00 ,  A61K48/00 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07H21/00 ,  C07H21/04 ,  C07K14/705 ,  C12N5/10 ,  C12N9/12 ,  C12N15/113 ,  C12Q1/48 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/50 ,  G01N33/53 ,  G01N33/566 ,  G01N33/573 ,  G01N33/68 ,  C07H21/02 ,  C12N15/85

CPC分类号： C12N15/1137 ,  A61K48/00 ,  C07H21/00 ,  C07K14/70564 ,  C12N9/12 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Y207/11013 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3521 ,  C12N2310/3527 ,  C12N2310/3533 ,  C12Q2600/158

摘要： Compositions and methods are provided for the treatment and diagnosis of diseases associated with protein kinase C. Oligonucleotides are provided which are specifically hybridizable with a PKC gene or mRNA. Oligonucleotides specifically hybridizable with a particular PKC isozyme, set of isozymes or mRNA transcript are provided. Methods of treating conditions amenable to therapeutic intervention by modulating protein kinase C expression with an oligonucleotide specifically hybridizable with a PKC gene or mRNA are disclosed. Compositions and methods are provided for the treatment, detection and diagnosis of diseases associated with protein kinase C alpha and specific transcripts thereof. New nucleic acid sequences are provided which encode 3' untranslated regions of human protein kinase C alpha polynucleotide probes for PKC alpha are also disclosed.

摘要翻译： PCT No.PCT / US94 / 07770 Sec。 371日期1996年1月11日 102（e）日期1996年1月11日PCT提交1994年7月8日PCT公布。 出版物WO95 / 02069 日期1995年1月19日提供了用于治疗和诊断与蛋白激酶C相关的疾病的组合物和方法。提供与PKC基因或mRNA特异性杂交的寡核苷酸。 提供了与特定的PKC同功酶特异性杂交的寡核苷酸，一组同功酶或mRNA转录物。 公开了通过用与PKC基因或mRNA特异性杂交的寡核苷酸调节蛋白激酶C表达来治疗适于治疗干预的病症的方法。 提供组合物和方法用于治疗，检测和诊断与蛋白激酶Cα相关的疾病及其特异性转录物。 提供了新的核酸序列，其编码编码PKCα的人蛋白激酶C 3多核苷酸探针的3'非翻译区。

公开(公告)号：US5801154A

公开(公告)日：1998-09-01

申请号：US835770

申请日：1997-04-08

申请人： Edgardo Baracchini ,  C. Frank Bennett ,  Nicholas M. Dean

发明人： Edgardo Baracchini ,  C. Frank Bennett ,  Nicholas M. Dean

IPC分类号： A61K38/00 ,  C07H21/00 ,  C12N15/113 ,  C12N15/85 ,  A61K48/00 ,  C07H21/04 ,  C12Q1/68

CPC分类号： C12N15/1138 ,  C07H21/00 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3517

摘要： Compositions and methods are provided for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of the synthesis or metabolism of multidrug resistance-associated protein (MRP). In accordance with referred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding MRP. In a preferred embodiment, the oligonucleotide has at least one 2'-methoxyethoxy modification. Methods of preventing the development of multidrug resistance and of improving the efficacy of chemotherapy are also disclosed.

摘要翻译： 提供组合物和方法用于治疗和诊断适于通过调节多药耐药相关蛋白（MRP）的合成或代谢来治疗的疾病或病症。 根据所提及的实施方案，提供了与编码MRP的核酸特异性杂交的寡核苷酸。 在优选的实施方案中，寡核苷酸具有至少一个2'-甲氧基乙氧基修饰。 还公开了预防多药耐药性发展和提高化学疗效的方法。

公开(公告)号：US06537973B1

公开(公告)日：2003-03-25

申请号：US10025139

申请日：2001-12-18

申请人： C. Frank Bennett ,  Nicholas M. Dean ,  Jon T. Holmlund ,  F. Andrew Dorr

发明人： C. Frank Bennett ,  Nicholas M. Dean ,  Jon T. Holmlund ,  F. Andrew Dorr

IPC分类号： C07H2104

CPC分类号： C12Q1/6883 ,  A61K38/00 ,  C07H21/00 ,  C12N9/12 ,  C12N15/1137 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3521 ,  C12N2310/3527 ,  C12N2310/3533 ,  C12Q1/6876 ,  C12Q2600/158 ,  C12Y207/11013

摘要： Compositions and methods are provided for the treatment and diagnosis of diseases associated with protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. In preferred embodiments, the oligonucleotides contain one or more chemical modifications. Methods of modulating PKC expression and of treating animals suffering from disease amenable to therapeutic intervention by modulating protein kinase C expression using oligonucleotides targeted to PKC are disclosed.

公开(公告)号：US20130190380A1

公开(公告)日：2013-07-25

申请号：US13532254

申请日：2012-06-25

申请人： Nicholas M. Dean ,  J. Gordon Foulkes ,  Niall O'Donnell ,  C. Frank Bennett ,  Susan M. Frier

发明人： Nicholas M. Dean ,  J. Gordon Foulkes ,  Niall O'Donnell ,  C. Frank Bennett ,  Susan M. Frier

IPC分类号： C12N15/113

CPC分类号： C12N15/1136 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/30 ,  C12N2310/3521

摘要： This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds.

公开(公告)号：US20110213011A1

公开(公告)日：2011-09-01

申请号：US13035772

申请日：2011-02-25

申请人： Nicholas M. Dean ,  J. Gordon Foulkes ,  Susan M. Freier ,  C. Frank Bennett ,  William A. Gaarde

发明人： Nicholas M. Dean ,  J. Gordon Foulkes ,  Susan M. Freier ,  C. Frank Bennett ,  William A. Gaarde

IPC分类号： A61K31/7088 ,  C07H21/00 ,  A61P17/02 ,  A61P43/00

CPC分类号： A61K31/7088

摘要： Provided are compounds capable of inhibiting SMAD3 and compositions containing same as well as methods using such compounds for treating fibrosis and scarring.

摘要翻译： 提供能够抑制SMAD3的化合物和含有它们的组合物以及使用这些化合物治疗纤维化和瘢痕形成的方法。

公开(公告)号：US20100056607A1

公开(公告)日：2010-03-04

申请号：US12374635

申请日：2007-07-18

申请人： Kenneth W. Dobie ,  Nicholas M. Dean ,  C. Frank Bennett

发明人： Kenneth W. Dobie ,  Nicholas M. Dean ,  C. Frank Bennett

IPC分类号： A61K31/7088 ,  C07H21/04 ,  C12N5/02

CPC分类号： C12N15/1135 ,  C12N2310/11

摘要： Disclosed herein are compounds, compositions and methods for modulating the expression of HBXIP in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

摘要翻译： 本文公开了用于调节细胞，组织或动物中HBXIP表达的化合物，组合物和方法。 还提供了目标验证的方法。 还提供了所公开的化合物和组合物在制备用于治疗疾病和病症的药物中的用途。