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：US20070049542A1

公开(公告)日：2007-03-01

申请号：US11432216

申请日：2006-05-10

申请人： Bruce Geller ,  Jesse Deere ,  Patrick Iversen ,  Dwight Weller

发明人： Bruce Geller ,  Jesse Deere ,  Patrick Iversen ,  Dwight Weller

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

CPC分类号： C12N15/1137 ,  C07F9/65583 ,  C07F9/65613 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/3145 ,  C12N2310/3233

摘要： A method and antisense compound for inhibiting the growth of pathogenic bacterial cells are disclosed. The compound contains no more than 12 nucleotide bases and has a targeting nucleic acid sequence of no fewer than 10 bases in length that is 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. The compound binds to a target mRNA with a Tm of between 50° to 60° C. The relatively short antisense compounds are substantially more active than conventional antisense compounds having a targeting base sequence of 15 or more bases.

公开(公告)号：US20070037764A1

公开(公告)日：2007-02-15

申请号：US11433257

申请日：2006-05-11

申请人： Dan Mourich ,  Patrick Iversen ,  Richard Bestwick ,  Dwight Weller

发明人： Dan Mourich ,  Patrick Iversen ,  Richard Bestwick ,  Dwight Weller

IPC分类号： A61K48/00 ,  C07F9/6533

CPC分类号： A61K31/675 ,  C07K2319/10 ,  C12N15/1132 ,  C12N2310/11 ,  C12N2810/6054

摘要： The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of human immunodeficiency virus-1 (HOV-1), as in treatment of a viral infection. The antisense antiviral compounds have morpholino subunits linked by uncharged phosphorodiamidate linkages interspersed with cationic phosphorodiamidate linkages. An exemplary embodiment of the invention provides an antisense compound directed to the HIV Vif gene, causing the production of defective HIV- 1 virions in an infected individual.

摘要翻译： 本发明提供了用于抑制人免疫缺陷病毒-1（HOV-1）生长的反义抗病毒化合物及其用于治疗病毒感染的方法。 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。 本发明的一个示例性实施方案提供了针对HIV Vif基因的反义化合物，导致在感染个体中产生有缺陷的HIV-1病毒粒子。

公开(公告)号：US20060276425A1

公开(公告)日：2006-12-07

申请号：US11433033

申请日：2006-05-11

申请人： Dan Mourich ,  Patrick Iversen ,  Dwight Weller

发明人： Dan Mourich ,  Patrick Iversen ,  Dwight Weller

IPC分类号： A61K48/00

CPC分类号： A61K31/675 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/3233 ,  C12N2310/3513

摘要： A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound, including partially positively charged, containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:33, to form a duplex structure between said compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in said cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.

摘要翻译： 公开了一种用于将人树突状细胞诱导到T细胞的抗原特异性激活能力降低的条件下，并且在成熟树突状细胞中细胞外IL-10的产生增加的方法和组合物。 暴露于基本上不带电荷的反义化合物，包括部分带正电荷的含有12-40个亚基的碱基序列，以及与其经处理的预处理或加工的人CD86转录物的表达敏感区域有效杂交的碱基序列 形成SEQ ID NO：33，以形成所述化合物和具有至少45℃的Tm的转录物之间的双链体结构。双链体阻断所述细胞中全长CD86的表达，这反过来导致减少 抗原特异性激活T细胞的能力，以及在成熟树突状细胞中细胞外IL-10的产生增加。

公开(公告)号：US20070122821A1

公开(公告)日：2007-05-31

申请号：US11433724

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 ,  C12Q1/68 ,  C07F9/6533

CPC分类号： C12N15/1136 ,  A61K31/675 ,  A61K47/645 ,  C07H21/00 ,  C07K7/08 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/3145 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2320/30 ,  C12Q1/6876 ,  C12Q2600/158 ,  Y10T436/143333

摘要： A method and compound for treating skeletal muscle mass deficiency in a human subject are disclosed. The composition is an oligomer of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, contains between 10-40 nucleotide bases, has a base sequence effective to hybridize to an expression-sensitive region of processed or preprocessed human myostatin RNA transcript, identified, in its processed form, by SEQ ID NO:6, and is capable of uptake by target muscle cells in the subject. In practicing the method, the compound is administered in an amount and at a dosage schedule to produce an overall reduction in the level of serum myostatin measured in the patient, and preferably to bring the myostatin level within the a range determined for normal, healthy individuals.

摘要翻译： 公开了一种用于治疗人类受试者骨骼肌质量不足的方法和化合物。 该组合物是吗啉代亚基的低聚物和将一个亚基的吗啉代氮连接到相邻亚单位的5'环外碳的含磷亚基间键，含有10-40个核苷酸碱基之间，具有有效地与表达杂交的碱基序列 经处理或预处理的人肌生成抑制素RNA转录物的敏感区域，以其加工形式由SEQ ID NO：6鉴定，并且能够被摄体中的靶肌细胞摄取。 在实施该方法中，化合物以量和剂量方案施用以产生在患者体内测量的血清肌生成抑制素水平的总体降低，优选使肌生成抑制素水平在正常健康个体确定的范围内 。

公开(公告)号：US20070111962A1

公开(公告)日：2007-05-17

申请号：US11595161

申请日：2006-11-08

申请人： Dan Mourich ,  Patrick Iversen ,  Dwight Weller

发明人： Dan Mourich ,  Patrick Iversen ,  Dwight Weller

IPC分类号： A61K48/00 ,  C07F9/6533

CPC分类号： C12N15/1138 ,  C12N2310/11 ,  C12N2310/3233 ,  C12N2310/3513

摘要： A method and compound for suppressing an immune response in a mammalian subject, for the treatment or prevention of an autoimmune condition or transplantation rejection are disclosed. The compound is an antisense oligonucleotide analog compound having a targeting sequence complementary to a preprocessed CTLA-4 mRNA region identified by SEQ ID NO: 1, spanning the splice junction between intron 1 and exon 2 of the preprocessed mRNA of the subject. The compound is effective, when administered to a subject, to form within host cells, a heteroduplex structure (i) composed of the preprocessed CTLA-4 mRNA and the oligonucleotide compound, (ii) characterized by a Tm of dissociation of at least 45° C., and (iii) resulting in an increased ratio of processed mRNA encoding ligand-independent CTLA-4 to processed mRNA encoding full-length CTLA-4.

摘要翻译： 公开了用于抑制哺乳动物受试者的免疫应答的方法和化合物，用于治疗或预防自身免疫病症或移植排斥反应。 化合物是具有与SEQ ID NO：1鉴定的预处理的CTLA-4mRNA区域互补的靶向序列的反义寡核苷酸类似物化合物，跨越受试者的预处理mRNA的内含子1和外显子2之间的剪接连接。 该化合物在给受试者施用时在宿主细胞内形成，由预处理的CTLA-4mRNA和寡核苷酸化合物组成的异源双链体结构（i），（ii）特征在于解离的Tm至少为45° （iii）导致编码与配体无关的CTLA-4的加工的mRNA与编码全长CTLA-4的加工的mRNA的比例增加。

公开(公告)号：US20060269587A1

公开(公告)日：2006-11-30

申请号：US11497482

申请日：2006-07-31

申请人： Patrick Iversen ,  Dwight Weller

发明人： Patrick Iversen ,  Dwight Weller

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

CPC分类号： A61K31/07

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 uncharged 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.

公开(公告)号：US20050288246A1

公开(公告)日：2005-12-29

申请号：US11136245

申请日：2005-05-23

申请人： Patrick Iversen ,  Dwight Weller ,  Jed Hassinger

发明人： Patrick Iversen ,  Dwight Weller ,  Jed Hassinger

IPC分类号： A61K48/00 ,  C12N15/11 ,  C12N15/113 ,  C12N15/85

CPC分类号： C12N15/113 ,  A61K48/0008 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/11 ,  C12N2310/3145 ,  C12N2310/3233 ,  C12N2310/331 ,  C12N2310/3513 ,  C12N2320/32

摘要： A therapeutic oligomer-peptide conjugate, and methods of using the conjugate are disclosed. The conjugate includes (a) a substantially uncharged oligonucleotide analog compound having a base sequence that includes a string of bases that are complementary to four or more contiguous cytosine bases in a target nucleic acid region to which the compound is intended to bind, and (b) conjugated to the compound, an arginine-rich peptide effective to enhance the uptake of the compound into target cells. The string of bases in the compound includes at least one inosine base positioned in the string so as to limit the number of contiguous guanine bases in said string to three or fewer. The conjugate has greater cellular uptake than the compound alone, by virtue of the arginine-rich peptide, and substantially greater antisense activity greater activity than the conjugate in the absence of inosine-for guanine substitutions.

摘要翻译： 公开了治疗性低聚物 - 肽缀合物和使用该缀合物的方法。 缀合物包括（a）具有碱基序列的基本上不带电的寡核苷酸类似物化合物，其碱基序列包括与化合物所要结合的靶核酸区域中的四个或更多个连续胞嘧啶碱基互补的碱基序列，和（b ），富含精氨酸的肽有效地增强化合物进入靶细胞的摄取。 所述化合物中的碱基串包括位于所述串中的至少一个肌苷碱基，以将所述串中的连续鸟嘌呤碱基的数目限制为三个或更少。 通过富含精氨酸的肽，缀合物比单独的化合物具有更大的细胞摄取，并且在不存在肌苷 - 用于鸟嘌呤取代的情况下，具有比缀合物更大的反义活性。

公开(公告)号：US20060063150A1

公开(公告)日：2006-03-23

申请号：US11226995

申请日：2005-09-14

申请人： Patrick Iversen ,  David Stein

发明人： Patrick Iversen ,  David Stein

IPC分类号： C12Q1/70 ,  G06F19/00 ,  C12P19/34 ,  A61K48/00

CPC分类号： C12N15/1131 ,  C07K19/00 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2310/531 ,  C12N2320/11 ,  C12N2770/00011 ,  C12N2770/10011 ,  C12N2770/12011 ,  C12N2770/16011 ,  C12N2770/20011 ,  C12N2770/24011 ,  C12N2770/28011 ,  C12N2770/32011 ,  C12N2770/36011

摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picornoviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.

摘要翻译： 本发明提供反义抗病毒化合物及其在抑制黄病毒科，细小病毒科，杯状病毒科，披膜病毒科，动脉病毒科，科罗亚病毒科，蛔虫科和乙肝病毒科的病毒生长中的用途和生产方法。 反义抗病毒化合物是具有12-40个亚基序列的基本上不带电荷的吗啉代寡核苷酸，包括至少12个亚基，其具有与在5'-末端40个碱基内的茎环二级结构相关的区域互补的靶向序列 病毒的正义RNA链。

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。