公开(公告)号：US07563778B2

公开(公告)日：2009-07-21

申请号：US10984919

申请日：2004-11-10

申请人： Karl-Hermann Schlingensiepen ,  Wolfgang Brysch

发明人： Karl-Hermann Schlingensiepen ,  Wolfgang Brysch

IPC分类号： A01N43/04 ,  C11Q1/68 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/1136 ,  A61K38/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  C12N15/1135 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/3125 ,  C12N2310/3145 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/351

摘要： A method for the preparation of an antisense oligonucleotide or derivative thereof comprising the steps of: selecting a target nucleic acid, if necessary elucidating its sequence; generating the antisense oligonucleotide with the proviso that: the oligonucleotide comprises at least 8 residues; the oligonucleotide comprises at maximum twelve elements, which are capable of forming three hydrogen bonds each to cytosine bases; the oligonucleotide does not contain four or more consecutive elements, capable of forming three hydrogen bonds each with four consecutive cytosine bases (CCCC) within the target molecule or alternatively four or more consecutive elements of GGGG; the oligonucleotide does also not contain 2 or more series of three consecutive elements, capable of forming three hydrogen bonds each with three consecutive cytosine bases (CCC) within the target molecule, or alternatively 2 or more series of three consecutive elements of GGG; and the ratio between residues forming two hydrogen bonds per residue (2H-bond-R) with the target molecule and those residues forming three hydrogen bonds per residue (3H-bond-R) with the target molecule, is ruled by the following specifications: 3H-bond-R/3H-bond-R+2H-bond-R≧0.29; and synthesizing the oligonucleotide thus generated in a per se known manner.

摘要翻译： 一种制备反义寡核苷酸或其衍生物的方法，包括以下步骤：如果需要，选择靶核酸阐明其序列; 产生反义寡核苷酸，条件是：寡核苷酸包含至少8个残基; 该寡核苷酸包含最多12个元件，其能够形成各自与胞嘧啶碱基的三个氢键; 寡核苷酸不含有四个或更多个连续的元件，能够在目标分子内形成三个氢键，每个具有四个连续的胞嘧啶碱基（CCCC），或者四个或更多个连续的GGGG元件; 寡核苷酸还不含有两个或更多个三个连续元件的系列，能够在目标分子内形成三个连接的胞嘧啶碱基（CCC）的三个氢键，或者另外两个或更多个三个连续的GGG元件系列; 并且与目标分子形成每个残基（2H-键-R）的两个氢键与每个残基形成三个氢键（3H-键-R）的残基与靶分子之间的比例由下列规格表示： 3H键-R / 3H键-R + 2H-键-R = 0.29; 并以本身已知的方式合成由此产生的寡核苷酸。

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。

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：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：US20040266720A1

公开(公告)日：2004-12-30

申请号：US10893086

申请日：2004-07-16

申请人： AVI BioPharma, Inc.

发明人： Patrick L. Iversen ,  Robert Hudziak

IPC分类号： A61K048/00 ,  C07H021/02

CPC分类号： C12N15/113 ,  A61K38/00 ,  C07F9/65583 ,  C12N15/1132 ,  C12N15/1135 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/3145 ,  C12N2310/3233 ,  C12N2320/33

摘要： Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5null end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.

公开(公告)号：US20030171335A1

公开(公告)日：2003-09-11

申请号：US10272865

申请日：2002-10-16

发明人： David A. Stein ,  Douglas E. Skilling ,  Patrick L. Iversen ,  Alvin W. Smith

IPC分类号： A61K031/675 ,  C07F009/6533 ,  A61K048/00

CPC分类号： A61K31/712 ,  A61K31/7125 ,  A61K38/00 ,  C12N15/1131 ,  C12N2310/3145 ,  C12N2310/3233 ,  Y02A50/463

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 are substantially uncharged oligomers having a targeting base sequence that is substantially complementary to a viral target sequence which spans the AUG start site of the first open reading frame of the viral genome.

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。 反义抗病毒化合物是具有与病毒基因组的第一开放阅读框的AUG起始位点跨越的病毒靶序列基本上互补的靶向碱基序列的基本上不带电荷的寡聚体。