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    Immunomodulatory agents and methods of use
    3.
    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
    4.
    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。

    IMMUNOMODULATORY AGENTS AND METHODS OF USE
    6.
    发明申请
    IMMUNOMODULATORY AGENTS AND METHODS OF USE 审中-公开
    免疫组化试剂和使用方法

    公开(公告)号：US20110318382A1

    公开(公告)日：2011-12-29

    申请号：US13166645

    申请日：2011-06-22

    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 ,  A61P31/12 ,  C07H21/04 ,  A61P31/00 ,  A61P31/04 ,  A61K38/14 ,  C07K9/00

    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。

    Antisense compound for inducing immunological tolerance
    7.
    发明授权
    Antisense compound for inducing immunological tolerance 有权
    用于诱导免疫耐受性的反义化合物

    公开(公告)号：US08008469B2

    公开(公告)日：2011-08-30

    申请号：US11941033

    申请日：2007-11-15

    申请人： Dan V. Mourich ,  Hong M. Moulton ,  David J. Hinrichs ,  Patrick L. Iversen

    发明人： Dan V. Mourich ,  Hong M. Moulton ,  David J. Hinrichs ,  Patrick L. Iversen

    IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68 ,  A61K31/70

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

    摘要： A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.

    摘要翻译： 公开了用于选择性杀死抗原活化的T细胞的方法和缀合物。 缀合物由靶向人cFLIP蛋白的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 相对于缀合物对非活化T细胞的摄取，rTAT多肽有效产生缀合物选择性吸收抗原激活的T细胞。 cFLIP反义化合物引起活化的淋巴细胞活化诱导的细胞死亡（AICD）。 该方法可用于治疗移植排斥反应和自身免疫病症。

    Immunosuppression compound and treatment method
    8.
    发明授权
    Immunosuppression compound and treatment method 有权
    免疫抑制化合物和治疗方法

    公开(公告)号：US08501704B2

    公开(公告)日：2013-08-06

    申请号：US12267437

    申请日：2008-11-07

    申请人： Dan V. Mourich ,  Patrick L. Iversen ,  Dwight D. Weller

    发明人： Dan V. Mourich ,  Patrick L. Iversen ,  Dwight D. Weller

    IPC分类号： C12N15/11 ,  A61K48/00 ,  C07H21/02 ,  C07H21/04

    CPC分类号： C12N15/1138 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2310/3513

    摘要： Provided are methods and antisense oligonucleotide analogs for suppressing an immune response in a mammalian subject, for the treatment or prevention of an autoimmune condition or transplantation rejection. The oligonucleotide analogs provided herein comprise a targeting sequence complementary to a preprocessed CTLA-4 mRNA region that spans the splice junction between intron 1 and exon 2 of the preprocessed CTLA-4 mRNA. Also provided are methods of use, in which the oligonucleotides are 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： 提供了用于抑制哺乳动物受试者的免疫应答的方法和反义寡核苷酸类似物，用于治疗或预防自身免疫病症或移植排斥反应。 本文提供的寡核苷酸类似物包含与预处理的CTLA-4 mRNA的内含子1和外显子2之间的剪接连接的预处理的CTLA-4mRNA区域互补的靶向序列。 还提供了使用方法，其中当给受试者施用时，寡核苷酸是有效的，以在宿主细胞内形成异源双链结构（i）由预处理的CTLA-4mRNA和寡核苷酸化合物组成，（ii）其特征在于 解离的Tm至少为45℃，和（iii）增加编码不依赖配体的CTLA-4的加工mRNA与编码全长CTLA-4的加工mRNA的比例增加。

    ANTISENSE COMPOUND FOR INDUCING IMMUNOLOGICAL TOLERANCE
    10.
    发明申请
    ANTISENSE COMPOUND FOR INDUCING IMMUNOLOGICAL TOLERANCE 有权
    用于诱导免疫耐受性的抗体化合物

    公开(公告)号：US20090111977A1

    公开(公告)日：2009-04-30

    申请号：US11941033

    申请日：2007-11-15

    申请人： Dan V. Mourich ,  Hong Mu Moulton ,  David J. Hinrichs ,  Patrick L. Iversen

    发明人： Dan V. Mourich ,  Hong Mu Moulton ,  David J. Hinrichs ,  Patrick L. Iversen

    IPC分类号： C07H21/00

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

    摘要： A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.

    摘要翻译： 公开了用于选择性杀死抗原活化的T细胞的方法和缀合物。 缀合物由靶向人cFLIP蛋白的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 相对于缀合物对非活化T细胞的摄取，rTAT多肽有效产生缀合物选择性吸收抗原激活的T细胞。 cFLIP反义化合物引起活化的淋巴细胞活化诱导的细胞死亡（AICD）。 该方法可用于治疗移植排斥反应和自身免疫病症。