公开(公告)号：US20070274957A1

公开(公告)日：2007-11-29

申请号：US11715572

申请日：2007-03-07

申请人： Benjamin Neuman ,  David Stein ,  Michael Buchmeier ,  Patrick Iversen

发明人： Benjamin Neuman ,  David Stein ,  Michael Buchmeier ,  Patrick Iversen

IPC分类号： A61K48/00

CPC分类号： C12N15/1131 ,  C12N2310/11 ,  C12N2310/3145 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2760/10011

摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Arenaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Arenavirus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 19 nucleotide region of the 5′-terminal regions of the viral RNA, viral complementary RNA and/or mRNA identified by SEQ ID NO:1.

摘要翻译： 本发明提供了反义抗病毒化合物及其在抑制竞争链球菌科家族病毒生长和用于病毒感染治疗中的用途和生产方法。 这些化合物特别可用于治疗哺乳动物中的雷亚病毒感染。 反义抗病毒化合物是基本上不带电荷的吗啉代寡核苷酸具有12-40个亚基的序列，包括至少12个亚基，其具有与5'末端区域的19个核苷酸区域内的病毒RNA序列相关的区域互补的靶向序列 的病毒RNA，由SEQ ID NO：1鉴定的病毒互补RNA和/或mRNA。

公开(公告)号：US20070265215A1

公开(公告)日：2007-11-15

申请号：US11433308

申请日：2006-05-11

申请人： Patrick Iversen ,  Dwight Weller

发明人： Patrick Iversen ,  Dwight Weller

IPC分类号： A61K48/00

CPC分类号： C12N15/1135 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2310/351 ,  C12N2320/30

摘要： The present invention provides an improved method for reducing the risk or severity of restenosis following cardiac angioplasty. The method includes administering to a target vessel region, a morpholino antisense compound having a phosphorus-containing backbone linkages, and spanning the start codon of a human c-myc mRNA. Also disclosed are novel antisense compounds and compositions, and a method for assaying the effectiveness of antisense delivery and uptake to a target vessel region.

摘要翻译： 本发明提供了用于降低心脏血管成形术后再狭窄风险或严重程度的改进方法。 该方法包括向靶血管区域施用具有含磷骨架键的吗啉代反义化合物，并跨越人c-myc mRNA的起始密码子。 还公开了新的反义化合物和组合物，以及用于测定反义递送和对靶血管区域的摄取的有效性的方法。

公开(公告)号：US20060205693A1

公开(公告)日：2006-09-14

申请号：US11264444

申请日：2005-10-31

申请人： David Stein ,  Patrick Iversen ,  Sina Bavari

发明人： David Stein ,  Patrick Iversen ,  Sina Bavari

IPC分类号： A61K48/00

CPC分类号： C12N15/1131 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/32 ,  C12N2310/3513

摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Filoviridae family, and in the treatment of a viral infection. The compounds and methods relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having: a) a nuclease resistant backbone, b) 15-40 nucleotide bases, and c) a targeting sequence of at least 15 bases in length that hybridizes to a target region selected from the following: i) the AUG start site region of VP35, as exemplified by antisense compounds SEQ ID NO:21-26, ii) the AUG start site region of VP24, as exemplified by antisense compound SEQ ID NO:34, iii) the region 85 to 65 base pairs upstream of the AUG start site of VP24, as exemplified by SEQ ID NO:39, iv) the AUG start site region of polymerase L, as exemplified by antisense compound SEQ ID NO: 17, and v) combinations of (i), (ii), (iii), and/or (iv).

摘要翻译： 本发明提供了反义抗病毒化合物及其在抑制丝状病毒科病毒生长和用于病毒感染治疗中的用途和生产方法。 该化合物和方法涉及哺乳动物中的病毒感染的治疗，包括埃博拉和马尔堡病毒的灵长类动物。 反义抗病毒化合物是基本上不带电荷的吗啉代寡核苷酸，其具有：a）核酸酶抗性主链，b）15-40个核苷酸碱基，和c）长度为至少15个碱基的靶向序列与选自以下的靶区域杂交： i）VP35的AUG起始位点区域，如反义化合物SEQ ID NO：21-26所示，ii）VP24的AUG起始位点区域，如反义化合物SEQ ID NO：34所示，iii）区域85至 VP24的AUG起始位点上游65个碱基对，如SEQ ID NO：39所示，iv）聚合酶L的AUG起始位点区域，如反义化合物SEQ ID NO：17所示，v）（i ），（ii），（iii）和/或（iv）。

公开(公告)号：US20050261249A1

公开(公告)日：2005-11-24

申请号：US11077871

申请日：2005-03-10

申请人： Patrick Iversen ,  Hemant Roy ,  Richard Bestwick

发明人： Patrick Iversen ,  Hemant Roy ,  Richard Bestwick

IPC分类号： A61K48/00 ,  C12N15/113 ,  C12N15/85

CPC分类号： A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C12N15/113 ,  C12N15/8509 ,  C12N2310/11 ,  C12N2310/3145 ,  C12N2310/3233

摘要： A method and composition for of treating cancer, and in particular, for arresting the progression of a solid or primary cancer to a more invasive, metastatic state, are disclosed. The composition includes a substantially uncharged antisense compound (i) having a nuclease-resistant backbone, (ii) capable of uptake by target cancer cells in the subject, (iii) containing between 10-40 nucleotide bases, and (iv) having a base sequence effective to hybridize to a region of processed or preprocessed human SNAIL RNA transcript. The compound, when administered to the subject, is effective to form within target cancer cells in the subject, a base-paired heteroduplex structure composed of human SNAIL RNA transcript and the oligonucleotide compound, where this structure is characterized by a Tm of dissociation of at least 45° C. The compound is administered in an amount sufficient to inhibit SNAIL expression in target cancer cells, thereby to inhibit the progression of the patient's cancer to a more invasive, metastatic state. Also disclosed are methods for preventing the transdifferentiation of peritoneal mesothelial cells and failure of ultrafiltration in a patient undergoing peritoneal dialysis, by including the compound in the patient dialysis fluid.

摘要翻译： 公开了用于治疗癌症的方法和组合物，特别是用于将固体或原发癌的进展阻止到更具侵袭性的转移状态。 组合物包括具有核酸酶抗性骨架的基本上不带电的反义化合物（i），（ii）能够被摄体中靶细胞摄取的能力，（iii）含有10-40个核苷酸碱基和（iv）具有碱基 有效地与经处理或预处理的人SNAIL RNA转录物区域杂交的序列。 该化合物当被施用于受试者时，在受试者的靶癌细胞内形成，由人SNAIL RNA转录物和寡核苷酸化合物组成的碱基配对的异源双链结构是有效的，其中该结构的特征在于解离的Tm 至少45℃。化合物以足以抑制靶癌细胞中SNAIL表达的量施用，从而抑制患者癌症进展到更具侵袭性的转移状态。 还公开了通过将化合物包括在患者透析液中来防止腹膜间皮细胞的转分化和经历腹膜透析的患者中的超滤失败的方法。

公开(公告)号：US20050192237A1

公开(公告)日：2005-09-01

申请号：US09754468

申请日：2001-01-04

申请人： Patrick Iversen

发明人： Patrick Iversen

IPC分类号： A23K1/18 ,  A23K1/16 ,  A23K1/17 ,  A61K31/712 ,  A61K38/00 ,  A61K39/02 ,  A61P31/04 ,  C12N15/09 ,  C12N15/113 ,  A61K48/00 ,  C07F9/6533 ,  C07H21/02

CPC分类号： C12N15/113 ,  A23K20/195 ,  A61K38/00 ,  C12N15/1137 ,  C12N2310/314 ,  C12N2310/3233

摘要： Antisense oligomers directed to bacterial cell division and cell cycle-encoding nucleic acids are capable of selectively modulating the biological activity thereof, and are useful in treatment and prevention of bacterial infection. The antisense oligomers are substantially uncharged, and contain from 8 to 40 nucleotide subunits, including a targeting nucleic acid sequence at least 10 nucleotides in length which is effective to hybridize to (i) a bacterial tRNA or (ii) a target sequence, containing a translational start codon, within a bacterial nucleic acid which encodes a protein associated with cell division or the cell cycle. Such proteins include zipA, sulA, secA, dicA, dicB, diCc, dicF, ftsA, ftsl,ftsN, ftsK, ftsL, ftsQ, ftsw, ftsZ, murC, murD, murE, murF, murg, minC, minD, minE, mraY, mraW, mraZ, seqA, ddlB, carbamate kinase, D-ala D-ala ligase, topoisomerase, alkyl hydroperoxide reductase, thioredoxin reductase, dihydrofolate reductase, and cell wall enzyme.

摘要翻译： 针对细菌细胞分裂和细胞周期编码核酸的反义寡聚体能够选择性调节其生物活性，并且可用于治疗和预防细菌感染。 反义寡聚体基本上不带电，并且含有8至40个核苷酸亚基，包括长度为至少10个核苷酸的靶向核酸序列，其有效地与（i）细菌tRNA杂交或（ii）靶序列杂交，其含有 在编码与细胞分裂或细胞周期相关的蛋白质的细菌核酸内的翻译起始密码子。 这些蛋白质包括zipA，sulA，secA，dicA，dicB，diCc，dicF，ftsA，fts1，ftsN，ftsK，ftsL，ftsQ，ftsw，ftsZ，murC，murD，murE，murF，murg，minC，minD，minE， ，mraW，mraZ，seqA，ddlB，氨基甲酸酯激酶，D-ala D-ala连接酶，拓扑异构酶，烷基氢过氧化物还原酶，硫氧还蛋白还原酶，二氢叶酸还原酶和细胞壁酶。

公开(公告)号：US20050171044A1

公开(公告)日：2005-08-04

申请号：US11022358

申请日：2004-12-22

申请人： David Stein ,  Richard Bestwick ,  Patrick Iversen ,  Benjamin Neuman ,  Michael Buchmeier

发明人： David Stein ,  Richard Bestwick ,  Patrick Iversen ,  Benjamin Neuman ,  Michael Buchmeier

IPC分类号： A61K48/00 ,  C07F9/6533 ,  C07H21/02 ,  C07K14/165 ,  C12N15/113

CPC分类号： C07H21/02 ,  C07K14/005 ,  C12N15/1131 ,  C12N2310/11 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2770/20022

摘要： A method and oligonucleotide compound for inhibiting replication of a nidovirus in virus-infected animal cells are disclosed. The compound (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the infected cells, (iii) contains between 8-25 nucleotide bases, and (iv) has a sequence capable of disrupting base pairing between the transcriptional regulatory sequences in the 5′ leader region of the positive-strand viral genome and negative-strand 3′ subgenomic region. In practicing the method, infected cells are exposed to the compound in an amount effective to inhibit viral replication.

摘要翻译： 公开了用于抑制病毒感染的动物细胞中的Nidovirus复制的方法和寡核苷酸化合物。 化合物（i）具有核酸酶抗性主链，（ii）能够被感染细胞摄取，（iii）含有8-25个核苷酸碱基之间，和（iv）具有能够破坏转录之间碱基配对的序列 正链病毒基因组和负链3'亚基因组区域的5'前导区域中的调节序列。 在实施该方法中，感染的细胞以有效抑制病毒复制的量暴露于化合物。

公开(公告)号：US20050113328A1

公开(公告)日：2005-05-26

申请号：US10981989

申请日：2004-11-04

申请人： Gayathri Devi ,  Patrick Iversen

发明人： Gayathri Devi ,  Patrick Iversen

IPC分类号： A61K31/675 ,  A61K48/00 ,  C07F9/6533 ,  C12N20060101

CPC分类号： A61K31/675 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2320/31

摘要： A method and compound for enhancing the lethality of an anti-cancer therapy, such as radiation, chemotherapy, or TRAIL protein, are disclosed. The compound is composed of morpholino subunits joined by phosphorodiamidate linkages, and has a targeting sequence that is complementary to an AUG start, IRES, or splice-donor region of the transcript for human X-linked inhibitor of apoptosis protein (XIAP). The method includes exposing cancer cells to the compound.

摘要翻译： 公开了用于增强抗癌疗法的致死率的方法和化合物，例如辐射，化疗或TRAIL蛋白。 该化合物由通过磷酰二胺键连接的吗啉亚基组成，并且具有与人X连锁凋亡蛋白抑制剂（XIAP）的转录物的AUG起始，IRES或剪接供体区互补的靶向序列。 该方法包括将癌细胞暴露于化合物。

公开(公告)号：US20070265214A1

公开(公告)日：2007-11-15

申请号：US11431968

申请日：2006-05-10

申请人： David Stein ,  Douglas Skilling ,  Patrick Iversen ,  Alvin Smith ,  Dwight Weller

发明人： David Stein ,  Douglas Skilling ,  Patrick Iversen ,  Alvin Smith ,  Dwight Weller

IPC分类号： A61K31/675

CPC分类号： A61K31/675

摘要： The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds have morpholino subunits linked by uncharged phosphorodiamidate linkages interspersed with cationic phosphorodiamidate linkages.

摘要翻译： 本发明提供反义抗病毒化合物及其用于抑制微小核糖核酸病毒，杯状病毒，披膜病毒和黄病毒家族病毒生长的方法，如治疗病毒感染。 反义抗病毒化合物具有通过分散有阳离子磷酰二胺键的不带电的磷酰二胺键连接的吗啉亚基。

公开(公告)号：US20070135333A1

公开(公告)日：2007-06-14

申请号：US11487009

申请日：2006-07-13

申请人： Bruce Geller ,  Patrick Iversen ,  Lucas Tilley

发明人： Bruce Geller ,  Patrick Iversen ,  Lucas Tilley

IPC分类号： A61K48/00

CPC分类号： A61K48/00 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2320/50

摘要： An antibacterial antisense conjugate and method of using the same for treating a bacterial infection in a mammalian host are disclosed. The conjugate includes an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotide contains 10-20 nucleotide bases and has a targeting nucleic acid sequence complementary to a target sequence containing or within 10 bases, in a downstream direction, of the translational start codon of a bacterial mRNA that encodes a bacterial protein essential for bacterial replication, where the compound binds to a target mRNA with a Tm of between 50° to 60° C. The carrier peptide is an arginine-rich peptide containing between 6 and 12 amino acids.

摘要翻译： 公开了一种抗菌反义结合物及其用于治疗哺乳动物宿主细菌感染的方法。 缀合物包括与载体肽缀合的反义寡核苷酸，其显着增强寡核苷酸的抗菌活性。 反义寡核苷酸含有10-20个核苷酸碱基，并且具有与含有或在其下游方向的10个碱基的靶序列互补的靶向核酸序列，其编码细菌复制物必需的细菌蛋白质的细菌mRNA的翻译起始密码子 其中化合物与50℃至60℃之间的T mRNA结合靶mRNA。载体肽是含有6至12个氨基酸的富含精氨酸的肽。

公开(公告)号：US20070129323A1

公开(公告)日：2007-06-07

申请号：US11518058

申请日：2006-09-08

申请人： David Stein ,  Cornelis Rijnbrand ,  Patrick Iversen ,  Dwight Weller

发明人： David Stein ,  Cornelis Rijnbrand ,  Patrick Iversen ,  Dwight Weller

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07F9/6533

CPC分类号： C12N15/1131 ,  C12N2310/11 ,  C12N2310/3145 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2770/32311 ,  C12N2770/32711

摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Picornaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Enterovirus and/or Rhinovirus infection in a mammal. The antisense antiviral compounds are substantially uncharged, including partially positively charged, morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 32 nucleotide region of the viral 5′ untranslated region identified by SEQ ID NO:4.

摘要翻译： 本发明提供反义抗病毒化合物及其在抑制小核糖核酸病毒科家族病毒生长和用于病毒感染治疗中的用途和生产方法。 所述化合物特别可用于治疗哺乳动物中的肠病毒和/或鼻病毒感染。 反义抗病毒化合物是基本上不带电的，包括部分带正电荷的吗啉代寡核苷酸具有12-40个亚基的序列，包括至少12个亚基，其具有与与32个核苷酸区域内的病毒RNA序列相关的区域互补的靶向序列 由SEQ ID NO：4鉴定的病毒5'非翻译区。