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108 条记录 (耗时 0.054 秒)

    Targeted site specific antisense oligodeoxynucleotide delivery method
    72.
    发明授权
    Targeted site specific antisense oligodeoxynucleotide delivery method 失效
    靶向位点特异性反义寡脱氧核苷酸递送方法

    公开(公告)号：US06245747B1

    公开(公告)日：2001-06-12

    申请号：US09114399

    申请日：1998-07-13

    申请人： Thomas R. Porter ,  Patrick L. Iversen ,  Gary D. Meyer

    发明人： Thomas R. Porter ,  Patrick L. Iversen ,  Gary D. Meyer

    IPC分类号： A01N4304

    CPC分类号： A61K9/0009 ,  A61K9/0019 ,  A61K9/5015 ,  A61K9/5052 ,  A61K41/0028 ,  A61K47/6925 ,  C12N15/1135 ,  C12N15/87 ,  C12N2310/315

    摘要： The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in utility for agents such as oligonucleotides which are plagued with problems in reaching targeted sites in necessary therapeutic levels. The delivery system includes gas-filled microbubbles formed in a nitrogen-free environment. Microbubbles formed through sonication in a nitrogen-free environment are smaller and more stable than microbubbles sonicated in the presence of room air.

    摘要翻译： 本发明涉及用于递送治疗剂的新的和改进的药物组合物和方法。 本发明的方法和组合物可以与几种治疗剂一起使用，并且可以实现治疗物质的位点特异性递送。 这可以允许较低的剂量和用于改善传统上达到目标部位的药物的功效，并且可以导致药物如寡核苷酸的用途，所述药物如在需要治疗水平达到目标部位时遇到问题的寡核苷酸。递送系统包括形成的充气微泡 在无氮环境中。 在无氮环境中通过超声处理形成的微泡比在室内空气存在下超声处理的微泡更小，更稳定。

    dsRNA MOLECULES COMPRISING OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS
    74.
    发明申请
    dsRNA MOLECULES COMPRISING OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS 有权
    包含具有修饰的互联网连接和/或终端组的寡核苷酸模拟物的dsRNA分子

    公开(公告)号：US20130288369A1

    公开(公告)日：2013-10-31

    申请号：US13819634

    申请日：2011-09-02

    申请人： Patrick L. Iversen

    发明人： Patrick L. Iversen

    IPC分类号： C12N15/113

    CPC分类号： C12N15/113 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2310/344 ,  C12N2310/3513

    摘要： Morpholino oligomers containing modified intersubunit linkages and/or terminal groups are provided for use within dsRNA molecules. The oligomers are oligonucleotide analogs containing predetermined sequences of base-pairing moieties. Also provided are such oligomers conjugated to peptide transporter moieties, where the transporters are preferably composed of arginine subunits, or arginine dimers, alternating with neutral amino acid subunits.

    摘要翻译： 提供含有修饰的亚单位间键和/或末端基团的吗啉代低聚物用于dsRNA分子内。 寡聚体是含有预定序列的碱基配对部分的寡核苷酸类似物。 还提供了与肽转运蛋白部分缀合的这种寡聚体，其中转运蛋白优选由精氨酸亚基或精氨酸二聚体组成，与中性氨基酸亚基交替。

    ANTISENSE ANTIBACTERIAL COMPOUNDS AND METHODS
    75.
    发明申请
    ANTISENSE ANTIBACTERIAL COMPOUNDS AND METHODS 审中-公开
    抗菌抗菌化合物和方法

    公开(公告)号：US20120122769A1

    公开(公告)日：2012-05-17

    申请号：US13294000

    申请日：2011-11-10

    申请人： Patrick L. Iversen

    发明人： Patrick L. Iversen

    IPC分类号： A61K38/14 ,  C07H21/04 ,  C07K17/10 ,  A61K31/7088 ,  A01P1/00 ,  A61K31/7048 ,  A61P31/06 ,  A01N57/16 ,  C12N5/02 ,  C07H21/00 ,  A61K31/7036

    CPC分类号： C12N15/113 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2310/3513

    摘要： Antibacterial antisense compounds and methods of their use in treating a Mycobacterium tuberculosis infection in a mammalian host are disclosed. The compounds include an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotides contain 10-20 nucleotide bases and have a targeting nucleic acid sequence complementary to a target sequence containing or within 20 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 45° to 60° C. The carrier peptide is an arginine-rich peptide containing between 6 and 14 amino acids. Antisense compounds that target host factor genes that facilitate Mycobacterium tuberculosis infection are also provided, as are methods of using these compounds to treat Mycobacterium tuberculosis infections, alone or in combination with other therapies.

    摘要翻译： 公开了抗细菌反义化合物及其用于治疗哺乳动物宿主中结核分枝杆菌感染的方法。 所述化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，并且具有与包含编码细菌复制必需的细菌蛋白质的细菌mRNA的翻译起始密码子在下游方向的20个碱基内的靶序列互补的靶向核酸序列 其中化合物以45℃至60℃的Tm结合靶mRNA。载体肽是含有6至14个氨基酸的富含精氨酸的肽。 还提供靶向促进结核分枝杆菌感染的宿主因子基因的反义化合物，以及使用这些化合物单独或与其它疗法组合治疗结核分枝杆菌感染的方法。

    Immunomodulatory agents and methods of use
    76.
    发明授权
    Immunomodulatory agents and methods of use 有权
    免疫调节剂及使用方法

    公开(公告)号：US07989608B2

    公开(公告)日：2011-08-02

    申请号：US12344143

    申请日：2008-12-24

    申请人： Dan V. Mourich ,  Patrick L. Iversen

    发明人： Dan V. Mourich ,  Patrick L. Iversen

    IPC分类号： C07H21/04 ,  C12N15/11

    CPC分类号： C12N15/1136 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3233

    摘要： An antisense oligonucleotide compound, composition, vaccine and methods for treating a variety of conditions characterized by up-regulation of IL-10 in a mammalian subject are disclosed. The compound (i) is composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, (ii) is capable of uptake by monocytes, lymphocytes, and dendritic cells in a mammalian subject, (iii) contains between 10-40 nucleotide bases, and (iv) has a base sequence effective to hybridize to at least 12 contiguous bases of a target sequence contained in an exon-2 or exon-4 slice site region of human IL-10 pre-mRNA.

    摘要翻译： 公开了一种反义寡核苷酸化合物，组合物，疫苗和用于治疗特征在哺乳动物受试者中上调IL-10的各种病症的方法。 化合物（i）由吗啉基亚单位和含有一个亚基的吗啉代氮与相邻亚单位的5'环外碳键合的含磷亚基间键组成，（ii）能够被单核细胞，淋巴细胞和树突状细胞吸收 哺乳动物受试者，（iii）含有10-40个核苷酸碱基，和（iv）具有有效杂交到包含在外显子2或外显子-4切片位点区域中的靶序列的至少12个连续碱基的碱基序列 人IL-10前mRNA。

    IMMUNOMODULATORY AGENTS AND METHODS OF USE
    77.
    发明申请
    IMMUNOMODULATORY AGENTS AND METHODS OF USE 有权
    免疫组化试剂和使用方法

    公开(公告)号：US20090246221A1

    公开(公告)日：2009-10-01

    申请号：US12344143

    申请日：2008-12-24

    申请人： Dan V. Mourich ,  Patrick L. Iversen

    发明人： Dan V. Mourich ,  Patrick L. Iversen

    IPC分类号： A61K39/385 ,  A61K31/7088 ,  C07H21/00 ,  A61P37/04

    CPC分类号： C12N15/1136 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3233

    摘要： An antisense oligonucleotide compound, composition, vaccine and methods for treating a variety of conditions characterized by up-regulation of IL-10 in a mammalian subject are disclosed. The compound (i) is composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, (ii) is capable of uptake by monocytes, lymphocytes, and dendritic cells in a mammalian subject, (iii) contains between 10-40 nucleotide bases, and (iv) has a base sequence effective to hybridize to at least 12 contiguous bases of a target sequence contained in an exon-2 or exon-4 slice site region of human IL-10 pre-mRNA.

    摘要翻译： 公开了一种反义寡核苷酸化合物，组合物，疫苗和用于治疗特征在哺乳动物受试者中上调IL-10的各种病症的方法。 化合物（i）由吗啉基亚单位和含有一个亚基的吗啉代氮与相邻亚单位的5'环外碳键合的含磷亚基间键组成，（ii）能够被单核细胞，淋巴细胞和树突状细胞吸收 哺乳动物受试者，（iii）含有10-40个核苷酸碱基，和（iv）具有有效杂交到包含在外显子2或外显子-4切片位点区域中的靶序列的至少12个连续碱基的碱基序列 人IL-10前mRNA。

    Tissue specific peptide conjugates and methods
    78.
    发明申请
    Tissue specific peptide conjugates and methods 审中-公开
    组织特异性肽缀合物和方法

    公开(公告)号：US20090099066A1

    公开(公告)日：2009-04-16

    申请号：US12217040

    申请日：2008-06-30

    申请人： Hong M. Moulton ,  Patrick L. Iversen

    发明人： Hong M. Moulton ,  Patrick L. Iversen

    IPC分类号： A61K38/14 ,  A61K38/10

    CPC分类号： C12N15/87 ,  C07K2319/33 ,  C12N2810/40

    摘要： Cell-penetrating peptides useful for targeting a therapeutic compound to a selected mammalian tissue, methods for their identification, methods of forming conjugate compounds containing such peptides, and conjugates formed thereby are disclosed. The cell-penetrating peptides are 8 to 30 amino acid residues in length and consist of subsequences selected from the group consisting of RXR, RX, RB, and RBR; where R is arginine, B is β-alanine, and each X is independently —C(O)—(CHR1)n—NH—, where n is 4-6 and each R1 is independently H or methyl, such that at most two R1's are methyl. In one embodiment, X is a 6-aminohexanoic acid residue.

    摘要翻译： 可用于将治疗化合物靶向选定的哺乳动物组织的细胞穿透肽，其鉴定方法，形成含有此类肽的缀合物的方法和由此形成的缀合物。 细胞穿透肽的长度为8至30个氨基酸残基并由选自RXR，RX，RB和RBR的子序列组成; 其中R是精氨酸，B是β-丙氨酸，每个X独立地是-C（O） - （CHR 1）n -NH-，其中n是4-6，并且每个R 1独立地是H或甲基，使得至多两个 R1是甲基。 在一个实施方案中，X是6-氨基己酸残基。