公开(公告)号：US06312900B1

公开(公告)日：2001-11-06

申请号：US09364416

申请日：1999-07-30

申请人： Nicholas M. Dean ,  Robert McKay ,  Loren Miraglia ,  Brenda Baker

发明人： Nicholas M. Dean ,  Robert McKay ,  Loren Miraglia ,  Brenda Baker

IPC分类号： C12Q168

CPC分类号： C12N15/1135 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/334 ,  C12N2310/335 ,  C12N2310/3525 ,  C12N2310/3521 ,  C12N2310/3527

摘要： Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of Activating Protein 1 (AP-1) expression are provided. In accordance with various embodiments of the present invention, oligonucleotides are provided which are specifically hybridizable with c-fos or c-jun, the genes encoding c-Fos or c-Jun, respectively. In a preferred embodiment, a method of modulating the metastasis of malignant tumors via modulation of one or more of the AP-1 subunits is provided; this method can be effected using the oligonucleotides of the invention or any other agent which modulates AP-1 or AP-1-mediated transcription.

摘要翻译： 提供了通过调节活化蛋白1（AP-1）表达来治疗和诊断易于治疗的组合物和方法。 根据本发明的各种实施方案，提供了与c-fos或c-jun，分别编码c-Fos或c-Jun的基因特异性杂交的寡核苷酸。 在优选的实施方案中，提供了通过调节一种或多种AP-1亚基来调节恶性肿瘤的转移的方法。 该方法可以使用本发明的寡核苷酸或调节AP-1或AP-1介导的转录的任何其它试剂来实现。

公开(公告)号：US06809193B2

公开(公告)日：2004-10-26

申请号：US09774809

申请日：2001-01-31

申请人： Robert McKay ,  Nicholas M. Dean ,  Brett P. Monia ,  Pamela Nero ,  William A. Gaarde

发明人： Robert McKay ,  Nicholas M. Dean ,  Brett P. Monia ,  Pamela Nero ,  William A. Gaarde

IPC分类号： C12N1585

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C07H21/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/334 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3515 ,  C12Q1/6886 ,  C12Q2600/158 ,  C12N2310/3525

摘要： Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. Methods for inducing apoptosis and for treating diseases or conditions associated with a reduction in apoptosis are also provided.

摘要翻译： 提供了通过调节编码JunN末端激酶（JNK蛋白）的基因的表达进行治疗的疾病或病症的治疗和诊断的组合物和方法。 本文提供了与编码JNK1，JNK2和JNK3的核酸以及其它JNK蛋白及其特异性同种型特异性杂交的寡核苷酸。 还提供了通过用这种寡核苷酸调节一种或多种JNK蛋白质的表达来治疗患有治疗性干预的疾病或障碍的动物的方法。 还提供了用于治疗和诊断与一种或多种JNK蛋白异常表达相关的疾病或病症的方法。 还提供了用于诱导凋亡和用于治疗与凋亡降低相关的疾病或病症的方法。

公开(公告)号：US5985558A

公开(公告)日：1999-11-16

申请号：US837201

申请日：1997-04-14

申请人： Nicholas M. Dean ,  Robert McKay ,  Loren Miraglia ,  Brenda Baker

发明人： Nicholas M. Dean ,  Robert McKay ,  Loren Miraglia ,  Brenda Baker

IPC分类号： A61K38/00 ,  C12N15/113 ,  C12Q1/68 ,  C07H21/04 ,  C12N15/85 ,  C12P19/34

CPC分类号： C12N15/1135 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/334 ,  C12N2310/335

摘要： Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of Activating Protein 1 (AP-1) expression are provided. In accordance with various embodiments of the present invention, oligonucleotides are provided which are specifically hybridizable with c-fos or c-jun, the genes encoding c-Fos or c-Jun, respectively. In a preferred embodiment, a method of modulating the metastasis of malignant tumors via modulation of one or more of the AP-1 subunits is provided; this method can be effected using the oligonucleotides of the invention or any other agent which modulates AP-1 or AP-1-mediated transcription.

摘要翻译： 提供了通过调节活化蛋白1（AP-1）表达来治疗和诊断易于治疗的组合物和方法。 根据本发明的各种实施方案，提供了与c-fos或c-jun，分别编码c-Fos或c-Jun的基因特异性杂交的寡核苷酸。 在优选的实施方案中，提供了通过调节一种或多种AP-1亚基来调节恶性肿瘤的转移的方法。 该方法可以使用本发明的寡核苷酸或调节AP-1或AP-1介导的转录的任何其它试剂来实现。

公开(公告)号：US5877309A

公开(公告)日：1999-03-02

申请号：US910629

申请日：1997-08-13

申请人： Robert McKay ,  Nicholas M. Dean

发明人： Robert McKay ,  Nicholas M. Dean

IPC分类号： C12N15/09 ,  A61K31/7088 ,  A61K48/00 ,  A61P35/00 ,  C07H21/00 ,  C12N15/113 ,  C12P19/34 ,  C12Q1/68 ,  C07H21/04 ,  C12N15/85

CPC分类号： C12N15/1137 ,  C07H21/00 ,  C12Q1/6886 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/334 ,  C12N2310/3515 ,  C12Q2600/158

摘要： Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. The invention is thus directed to compositions for modulating, diagnostic methods for detecting, and therapeutic methods for inhibiting, the hyperproliferation of cells and formation, development and maintenance of tumors.

摘要翻译： 提供了通过调节编码JunN末端激酶（JNK蛋白）的基因的表达进行治疗的疾病或病症的治疗和诊断的组合物和方法。 本文提供了与编码JNK1，JNK2和JNK3的核酸以及其它JNK蛋白及其特异性同种型特异性杂交的寡核苷酸。 还提供了通过用这种寡核苷酸调节一种或多种JNK蛋白质的表达来治疗患有治疗性干预的疾病或障碍的动物的方法。 还提供了用于治疗和诊断与一种或多种JNK蛋白异常表达相关的疾病或病症的方法。 因此，本发明涉及用于调节，用于检测和用于抑制细胞过度增殖以及形成，发育和维持肿瘤的方法的治疗方法的组合物。

公开(公告)号：US06136603A

公开(公告)日：2000-10-24

申请号：US280799

申请日：1999-03-26

申请人： Nicholas M. Dean ,  James G. Karras ,  Robert McKay

发明人： Nicholas M. Dean ,  James G. Karras ,  Robert McKay

IPC分类号： C12N15/09 ,  A61K31/711 ,  A61K38/00 ,  A61K48/00 ,  A61P11/06 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C12N5/02 ,  C12N15/113 ,  C07H21/04 ,  C12N15/85 ,  C12Q1/68

CPC分类号： C12N15/1136 ,  C12N15/1138 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346

摘要： Compositions and methods are provided for antisense modulation of interleukin-5 signal transduction. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding interleukin-5 and interleukin-5 receptor.alpha. are preferred. Methods of using these compounds for modulation of interleukin-5 signal transduction and for treatment of diseases associated with interleukin-5 signal transduction are also provided.

摘要翻译： 提供组合物和方法用于白细胞介素-5信号转导的反义调节。 针对编码白细胞介素-5和白细胞介素-5受体α的核酸的反义化合物，特别是反义寡核苷酸是优选的。 还提供了使用这些化合物调节白细胞介素-5信号转导和治疗与白细胞介素-5信号转导相关疾病的方法。

公开(公告)号：US06300320B1

公开(公告)日：2001-10-09

申请号：US09225749

申请日：1999-01-05

申请人： Nicholas M. Dean ,  Robert McKay

发明人： Nicholas M. Dean ,  Robert McKay

IPC分类号： A61K3170

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C07H21/00 ,  C07K14/82 ,  C12N9/1205 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Y207/11013 ,  C12N2310/3527 ,  C12N2310/3521 ,  C12N2310/3525

摘要： Methods and compositions are provided for modulating c-jun expression using inhibitors of PKC-&agr;. In preferred embodiments, the specific inhibitors are antisense oligonucleotides hybridizable to PKC-&agr;. In preferred embodiments, the oligonucleotides contain one or more chemical modifications. Methods of modulating c-jun expression and of treating animals suffering from disease amenable to therapeutic intervention by modulating c-jun expression are disclosed

摘要翻译： 提供使用PKC-α抑制剂调节c-jun表达的方法和组合物。 在优选的实施方案中，特异性抑制剂是可与PKC-α杂交的反义寡核苷酸。 在优选的实施方案中，寡核苷酸含有一种或多种化学修饰。 公开了调节c-jun表达和通过调节c-jun表达治疗适于治疗干预的疾病的方法

公开(公告)号：US09071974B2

公开(公告)日：2015-06-30

申请号：US12493214

申请日：2009-06-28

申请人： Robert McKay ,  Sam Emara ,  Steve Hildner ,  Thomas Shanley ,  Wesley Driver ,  Jay Lukin ,  Terry Bahr ,  Tim Berzins ,  Mihaela Mihaylova ,  Nathan Klonoski

发明人： Robert McKay ,  Sam Emara ,  Steve Hildner ,  Thomas Shanley ,  Wesley Driver ,  Jay Lukin ,  Terry Bahr ,  Tim Berzins ,  Mihaela Mihaylova ,  Nathan Klonoski

IPC分类号： H04W4/00 ,  H04W12/12 ,  H04L29/06 ,  H04M1/663 ,  H04M1/725 ,  H04W4/14

CPC分类号： H04L63/02 ,  H04L63/0236 ,  H04L63/0853 ,  H04L63/14 ,  H04M1/663 ,  H04M1/72552 ,  H04W4/14 ,  H04W12/10 ,  H04W12/12

摘要： Methods, systems, and software for mediating SMS messages, and especially type 0 SMS messages, in a wireless mobile communications device configured to send and receive data using a GSM protocol and including a subscriber identity module (“SIM”) including electronic hardware and computer software executed by the hardware such that the SIM is configured to send, receive, and process messages using a Short Message System (“SMS”) between the wireless mobile communications device and a communications network. One aspect includes a method for mediating SMS messages comprising: configuring electronic hardware on the wireless mobile communications device to implement a firewall on the wireless mobile communications device, the firewall configured to identify and optionally mediate infrastructure SMS messages.

摘要翻译： 在用于使用GSM协议发送和接收数据的无线移动通信设备中的SMS消息，特别是0类SMS消息的中介方法，系统和软件，并且包括包括电子硬件和计算机的用户识别模块（“SIM”） 由硬件执行的软件，使得SIM被配置为使用无线移动通信设备和通信网络之间的短消息系统（“SMS”）发送，接收和处理消息。 一个方面包括一种用于中介SMS消息的方法，包括：在无线移动通信设备上配置电子硬件以在无线移动通信设备上实现防火墙，防火墙被配置为识别和可选地调解基础设施SMS消息。

公开(公告)号：US09045754B2

公开(公告)日：2015-06-02

申请号：US11745429

申请日：2007-05-07

申请人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/3515 ,  C12Y203/0102 ,  C12N2310/3521

摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.

摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。

公开(公告)号：US20090325615A1

公开(公告)日：2009-12-31

申请号：US12493214

申请日：2009-06-28

申请人： Robert McKay ,  Sam Emara ,  Steven Hildner ,  Thomas Shanley ,  Wesley Driver ,  Jay Lukin ,  Terry Bahr ,  Tim Berzins ,  Mihaela Mihaylova ,  Nathan Klonoski

发明人： Robert McKay ,  Sam Emara ,  Steven Hildner ,  Thomas Shanley ,  Wesley Driver ,  Jay Lukin ,  Terry Bahr ,  Tim Berzins ,  Mihaela Mihaylova ,  Nathan Klonoski

IPC分类号： H04W4/00 ,  H04M1/00

CPC分类号： H04L63/02 ,  H04L63/0236 ,  H04L63/0853 ,  H04L63/14 ,  H04M1/663 ,  H04M1/72552 ,  H04W4/14 ,  H04W12/10 ,  H04W12/12

摘要： Methods, systems, and software for mediating SMS messages, and especially type 0 SMS messages, in a wireless mobile communications device configured to send and receive data using a GSM protocol and including a subscriber identity module (“SIM”) including electronic hardware and computer software executed by the hardware such that the SIM is configured to send, receive, and process messages using a Short Message System (“SMS”) between the wireless mobile communications device and a communications network. One aspect includes a method for mediating SMS messages comprising: configuring electronic hardware on the wireless mobile communications device to implement a firewall on the wireless mobile communications device, the firewall configured to identify and optionally mediate infrastructure SMS messages.

摘要翻译： 在用于使用GSM协议发送和接收数据的无线移动通信设备中的SMS消息，特别是0类SMS消息的中介方法，系统和软件，并且包括包括电子硬件和计算机的用户识别模块（“SIM”） 由硬件执行的软件，使得SIM被配置为使用无线移动通信设备和通信网络之间的短消息系统（“SMS”）发送，接收和处理消息。 一个方面包括一种用于中介SMS消息的方法，包括：在无线移动通信设备上配置电子硬件以在无线移动通信设备上实现防火墙，防火墙被配置为识别和可选地调解基础设施SMS消息。

公开(公告)号：US20090306179A1

公开(公告)日：2009-12-10

申请号：US12299609

申请日：2007-05-07

申请人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： A61K31/7052 ,  C07H21/00 ,  C12N5/00 ,  A61P3/00

CPC分类号： C12N15/113 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/3515 ,  C12Y203/0102 ,  C12N2310/3521

摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.

摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。