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    Methods for regulation of active TNF-.alpha.
    2.
    发明授权
    Methods for regulation of active TNF-.alpha. 失效
    调节活性TNF-α的方法

    公开(公告)号：US5861382A

    公开(公告)日：1999-01-19

    申请号：US436330

    申请日：1995-06-29

    申请人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    发明人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    IPC分类号： A61K31/70 ,  C07H11/00 ,  A01N43/16 ,  C07K14/525 ,  C08B37/10

    CPC分类号： A61K31/7024 ,  A61K31/70 ,  A61K31/7016 ,  C07H11/00 ,  Y10S514/822 ,  Y10S514/825 ,  Y10S514/826 ,  Y10S514/885 ,  Y10S514/886 ,  Y10S530/868

    摘要： Substances comprising disaccharides and substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF-.alpha.) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-.alpha.. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.1 mg/kg human, or at intervals of tip to about 5-8 days, preferably once a week.

    摘要翻译： PCT No.PCT / US93 / 10868 Sec。 371日期：1995年6月29日 102（e）日期1995年6月29日PCT 1993年11月9日PCT公布。 公开号WO94 / 11006 日期1994年5月26日包含二糖的物质和包含基本纯化形式的羧化和/或硫酸化寡糖的物质及其使用方法被公开用于调节宿主中的细胞因子活性。 例如，活性肿瘤坏死因子α（TNF-α）的分泌可以通过给予宿主有效量的本发明的物质而被选择性地抑制或增强。 因此，本发明还涉及药物组合物及其用于预防和/或治疗涉及诱导活性细胞因子分泌的病理过程如TNF-α的用途。 本发明还涉及由宿主引起包括病原体在内的活化剂的存在引起所需的免疫系统相关应答。 本发明的物质和药物组合物可以以非常低的有效剂量（通常低于0.1mg / kg的人），或以尖端间隔至约5-8天，优选每周一次施用。

    Compositions for the regulation of cytokine activity
    3.
    发明授权
    Compositions for the regulation of cytokine activity 失效
    用于调节细胞因子活性的组合物

    公开(公告)号：US07332480B2

    公开(公告)日：2008-02-19

    申请号：US10831288

    申请日：2004-04-26

    申请人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    发明人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    IPC分类号： A61K31/7016 ,  A61K31/727 ,  C08B37/10

    CPC分类号： A61K31/7024 ,  A61K31/70 ,  A61K31/7016 ,  A61K31/727 ,  C07H11/00

    摘要： Substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, including compositions containing same and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of Tumor Necrosis Factor Alpha (TNF-α) can be either inhibited or augmented selectively by administration to the host of effective amounts of substances or their compositions comprising specific oligosaccharides in substantially purified form. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-α. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be daily, at very low effective doses, typically below 0.1 mg/kg human, or at intervals of up to about 5-8 days, preferably once a week.

    摘要翻译： 包括基本上纯化形式的羧化和/或硫酸化寡糖的物质，包括含有它们的组合物和使用它们的方法被公开用于调节宿主中的细胞因子活性。 例如，肿瘤坏死因子α（TNF-α）的分泌可以通过向宿主施用有效量的物质或其包含基本纯化形式的特异性寡糖的组合物来选择性地被抑制或增强。 因此，本发明还涉及药物组合物及其用于预防和/或治疗涉及诱导活性细胞因子分泌的病理过程如TNF-α的用途。 本发明还涉及由宿主引起包括病原体在内的活化剂的存在引起所需的免疫系统相关应答。 本发明的物质和药物组合物可以是非常低的有效剂量，通常低于0.1mg / kg人，或间隔至多约5-8天，优选每周一次。

    Anti-cancer therapeutic compounds
    4.
    发明授权
    Anti-cancer therapeutic compounds 失效
    抗癌治疗化合物

    公开(公告)号：US07285536B2

    公开(公告)日：2007-10-23

    申请号：US10002145

    申请日：2001-12-05

    申请人： Liora Cahalon ,  Irun R. Cohen ,  Ofer Lider ,  Raanan Margalit

    发明人： Liora Cahalon ,  Irun R. Cohen ,  Ofer Lider ,  Raanan Margalit

    IPC分类号： A61K31/70

    CPC分类号： C07H5/06 ,  A61K31/7012 ,  A61K31/7016 ,  A61K31/702 ,  A61K31/7024 ,  A61K31/727 ,  A61K31/737

    摘要： A treatment for cancer, and in particular, of therapeutic compounds which block the ability of cytokines and chemokines to promote metastasis of malignant cells. The therapeutic compound comprises a carboxylated and/or sulfated oligosaccharide, preferably in a substantially purified form, which is a heparin or heparan-sulfate derived saccharide compound. In one embodiment of the present invention, the carbohydrate or oligosaccharide has a molecular weight of no more than about 3000 daltons, preferably lying in the range of about 400 to about 2000 daltons, most preferably between about 400 and about 1100 daltons. Generally, substances of the present invention inhibit tumor cell migration, as determined by biological assays, and comprise molecules of various sugar units of which the basic unit of activity is associated with a disaccharide. However, larger oligosaccharide chains of up to about 10 sugar units, containing the basic disaccharide unit of activity can also function to inhibit such activity.

    摘要翻译： 癌症治疗，特别是阻断细胞因子和趋化因子促进恶性细胞转移的能力的治疗化合物。 治疗化合物包含羧化和/或硫酸化的寡糖，优选基本上纯化的形式，其是肝素或硫酸乙酰肝素衍生的糖类化合物。 在本发明的一个实施方案中，碳水化合物或寡糖的分子量不超过约3000道尔顿，优选在约400至约2000道尔顿范围内，最优选约400至约1100道尔顿。 通常，本发明的物质通过生物测定法测定，抑制肿瘤细胞迁移，并且包含其基本活性单位与二糖相关的各种糖单元的分子。 然而，含有活性的碱性二糖单位的高达约10个糖单元的较大的寡糖链也可以起到抑制这种活性的作用。

    Compositions for the regulation of cytokine activity
    5.
    发明授权
    Compositions for the regulation of cytokine activity 失效
    用于调节细胞因子活性的组合物

    公开(公告)号：US06750207B1

    公开(公告)日：2004-06-15

    申请号：US09495723

    申请日：2000-02-01

    申请人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    发明人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    IPC分类号： A61K31715

    CPC分类号： A61K31/7024 ,  A61K31/70 ,  A61K31/7016 ,  A61K31/727 ,  C07H11/00

    摘要： A pharmaceutical composition for the regulation of cytokine activity in a subject. The composition features an effective amount of an oligosaccharide to inhibit the cytokine activity, preferably through inhibition of TNF-alpha activity. The oligosaccharide is more preferably up to four saccharide units in length, and optionally and more preferably, is N-sulfated with at least one other sulfur moeity. The compositions are useful for the treatment of various pathological conditions related to, caused by or promoted through, cytokine activity.

    摘要翻译： 用于调节受试者中细胞因子活性的药物组合物。 组合物特征在于有效量的寡糖以抑制细胞因子活性，优选通过抑制TNF-α活性。 寡糖更优选长达四个糖单元，并且任选地并且更优选的是用至少一种其它的硫醇的N-硫酸化。 该组合物可用于治疗与由细胞因子活性引起或促进的各种病理状况。

    Compositions and methods for regulation of active TNF-.alpha.
    6.
    发明授权
    Compositions and methods for regulation of active TNF-.alpha. 失效
    用于调节活性TNF-α的组合物和方法

    公开(公告)号：US6020323A

    公开(公告)日：2000-02-01

    申请号：US486127

    申请日：1995-06-07

    申请人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    发明人： Irun R. Cohen ,  Ofer Lider ,  Liora Cahalon ,  Oded Shoseyov ,  Raanan Margalit

    IPC分类号： A61K31/70 ,  C07H11/00 ,  A01N43/04 ,  A61K39/00 ,  A61K45/05 ,  C07H15/00

    CPC分类号： A61K31/7024 ,  A61K31/70 ,  A61K31/7016 ,  C07H11/00 ,  Y10S514/822 ,  Y10S514/825 ,  Y10S514/826 ,  Y10S514/885 ,  Y10S514/886 ,  Y10S530/868

    摘要： Substances comprising disaccharides and substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF-.alpha.) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-.alpha.. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.1 mg/kg human, or at intervals of up to about 5-8 days, preferably once a week.

    摘要翻译： 公开了包含二糖的物质和包含基本纯化形式的羧化和/或硫酸化寡糖的物质及其使用方法，用于调节宿主中的细胞因子活性。 例如，活性肿瘤坏死因子α（TNF-α）的分泌可以通过给予宿主有效量的本发明的物质而被选择性地抑制或增强。 因此，本发明还涉及药物组合物及其用于预防和/或治疗涉及诱导活性细胞因子分泌的病理过程如TNF-α的用途。 本发明还涉及由宿主引起包括病原体在内的活化剂的存在引起所需的免疫系统相关应答。 本发明的物质和药物组合物可以以非常低的有效剂量（通常低于0.1mg / kg的人）或以至多约5-8天，优选每周一次的间隔施用。

    HSP60, HSP60 peptides and T cell vaccines for immunomodulation
    8.
    发明授权
    HSP60, HSP60 peptides and T cell vaccines for immunomodulation 失效
    HSP60，HSP60肽和用于免疫调节的T细胞疫苗

    公开(公告)号：US08691772B2

    公开(公告)日：2014-04-08

    申请号：US11813333

    申请日：2006-01-04

    申请人： Irun R. Cohen ,  Alexandra Zanin-Zhorov ,  Guy Tal ,  Francisco Quintana ,  Meirav Pevsner ,  Osnat Lider ,  Lihi Lider

    发明人： Irun R. Cohen ,  Alexandra Zanin-Zhorov ,  Guy Tal ,  Francisco Quintana ,  Meirav Pevsner ,  Ofer Lider

    IPC分类号： A61K38/00 ,  C07K7/08

    CPC分类号： A61K38/1709 ,  A61K35/17 ,  A61K39/0008 ,  A61K2035/124 ,  A61K2039/5158 ,  A61K2039/53 ,  C12N5/0636 ,  C12N2501/07

    摘要： The present invention provides novel uses for peptide p277—positions 437-460 of human heat shock protein 60 (HSP60)—in modulation of immune responses and inflammatory diseases. The invention further provides novel uses for HSP60 and p277 in the treatment or prevention of hepatic disorders. The invention discloses methods for treating, preventing or ameliorating the symptoms of T cell mediated inflammatory and autoimmune disorders, including hepatic disorders, which comprise administering to a subject in need thereof a composition comprising as an active ingredient an effective quantity of a molecule selected from: HSP60, p277, fragments, analogs, homologs and derivatives thereof, and nucleic acids encoding same. Also disclosed are T cell vaccination methods for treating or preventing T cell mediated disorders.

    摘要翻译： 本发明提供了人类热休克蛋白60（HSP60）的肽p277-位置437-460在调节免疫应答和炎性疾病方面的新用途。 本发明进一步提供HSP60和p277在治疗或预防肝病中的新用途。 本发明公开了治疗，预防或改善T细胞介导的炎症和自身免疫性疾病（包括肝脏疾病）的症状的方法，其包括向有需要的受试者施用包含有效量的选自以下的分子的组合物： HSP60，p277，其片段，类似物，同源物及其衍生物，以及编码其的核酸。 还公开了用于治疗或预防T细胞介导的病症的T细胞疫苗接种方法。

    Methods of using low molecular weight heparins treatment of pathological processes
    9.
    发明授权
    Methods of using low molecular weight heparins treatment of pathological processes 失效
    使用低分子量肝素治疗病理过程的方法

    公开(公告)号：US5474987A

    公开(公告)日：1995-12-12

    申请号：US384203

    申请日：1995-02-03

    申请人： Irun R. Cohen ,  Ofer Lider ,  Rami Hershkoviz

    发明人： Irun R. Cohen ,  Ofer Lider ,  Rami Hershkoviz

    IPC分类号： A61K31/715 ,  A61K20060101 ,  A61K31/727 ,  A61P1/00 ,  A61P1/02 ,  A61P3/08 ,  A61P9/10 ,  A61P29/00 ,  A61P31/12 ,  A61P37/00 ,  A61P37/08 ,  A61K31/725

    CPC分类号： A61K31/715 ,  A61K31/7016 ,  A61K31/7024 ,  A61K31/727 ,  Y10S514/825

    摘要： The present invention relates to methods for the prevention and/or treatment of pathological processes involving the induction of TNF-.alpha. secretion comprising a pharmaceutically acceptable carrier and a low molecular weight heparin (LMWH). In the pharmaceutical compositions of the present invention, the LMWH is present in a low effective dose and is administered at intervals of about 5-8 days. Furthermore, the LMWH is capable of inhibiting in vitro TNF-.alpha. secretion by resting T cells and/or macrophages in response to T cell-specific antigens, mitogens, macrophage activators, disrupted extracellular matrix (dECM), laminin, fibronectin, and the like.

    摘要翻译： 本发明涉及用于预防和/或治疗涉及诱导TNF-α分泌的病理过程的方法，其包含药学上可接受的载体和低分子量肝素（LMWH）。 在本发明的药物组合物中，LMWH以低有效剂量存在，并以约5-8天的间隔施用。 此外，LMWH能够响应于T细胞特异性抗原，有丝分裂原，巨噬细胞激活剂，破坏的细胞外基质（dECM），层粘连蛋白，纤连蛋白等，通过休息T细胞和/或巨噬细胞来抑制体外TNF-α分泌 。