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    • 5. 发明授权
    • Atherosclerotic plaque specific antigens, antibodies thereto, and uses
thereof
    • 动脉粥样硬化斑块特异性抗原,抗体及其用途
    • US6025477A
    • 2000-02-15
    • US386221
    • 1995-02-09
    • Emanuel Calenoff
    • Emanuel Calenoff
    • A61K38/00A61K41/00A61K47/48C07K14/47C07K14/78C07K16/18C07K16/46C12N5/18G01N33/533G01N33/543G01N33/544G01N33/564G01N33/68G01N33/92C07K17/00
    • A61K47/48538A61K47/4843A61K47/48676C07K14/47C07K14/78C07K16/18C07K16/468G01N33/533G01N33/543G01N33/544G01N33/564G01N33/686G01N33/92A61K38/00G01N2800/323
    • This invention provides purified antigens which are indicative of the presence of atherosclerotic plaque. Different concentrations of these antigens have been found to coincide with the progression of atherosclerosis. The subject invention also provides different hybridoma cell lines which produce monoclonal antibodies directed to antigens associated with atherosclerosis and a hybridoma cell line which produces monoclonal antibodies directed to antigen associated with normal artery and not with plaque. The atherosclerotic plaque antigen, and monoclonal antibodies made thereto, are used in various methods for detecting in a biological sample an antigen present in, and indicative of the presence of, atherosclerotic plaque. The monoclonal antibodies are also used in methods of imaging atherosclerotic plaque, and treating atherosclerosis. The methods of treating atherosclerosis include a method of digesting atherosclerotic plaque with enzymes, and a method of ablating atherosclerotic plaque using radiation. The subject invention also provides a method of treating atherosclerotic plaque by directly delivering a drug to the plaque. The subject invention further provides a method for treating atherosclerosis by blocking the synthesis of atherosclerotic plaque or by blocking binding of antibodies to the antigen.
    • 本发明提供了指示存在动脉粥样硬化斑块的纯化抗原。 已经发现不同浓度的这些抗原与动脉粥样硬化的进展相一致。 本发明还提供了不同的杂交瘤细胞系,其产生针对与动脉粥样硬化相关的抗原的单克隆抗体和产生针对与正常动脉相关的抗原而不与斑块相关的抗原的单克隆抗体的杂交瘤细胞系。 动物动脉粥样硬化斑块抗原及其制备的单克隆抗体用于各种方法用于在生物样品中检测存在于动脉粥样硬化斑块中并存在动脉粥样硬化斑块的抗原。 单克隆抗体也用于成像动脉粥样硬化斑块和治疗动脉粥样硬化的方法。 治疗动脉粥样硬化的方法包括用酶消化动脉粥样硬化斑块的方法,以及使用辐射消融动脉粥样硬化斑块的方法。 本发明还提供了通过将药物直接递送至斑块来治疗动脉粥样硬化斑块的方法。 本发明还提供了通过阻断动脉粥样硬化斑块的合成或通过阻断抗体与抗原的结合来治疗动脉粥样硬化的方法。
    • 8. 发明申请
    • Myelin specific IgE unencumbered by corresponding blocking antibodies as a causative factor in multiple sclerosis
    • 髓鞘特异性IgE不受相应的阻断抗体作为多发性硬化症的致病因子的阻碍
    • US20080267988A1
    • 2008-10-30
    • US12082515
    • 2008-04-11
    • Emanuel Calenoff
    • Emanuel Calenoff
    • A61K39/00G01N33/53G01N33/567C07K16/42
    • G01N33/564A61K38/00C07K7/06G01N2800/285
    • Optimization and validation of a serum test confirms symptomatic autoimmune diseases e.g. multiple sclerosis (MS) or rheumatoid arthritis, and identifies early, silent diseases. The methods involve testing of subject sera for the presence of epitope-specific serum IgE and also non-IgE antibodies. The tests are immunoassays wherein serum autoantibodies complex with peptides structurally mimicking humoral, autoimmune epitopes on, for example, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP) for MS. Each peptide: (1) is 5-6 amino acids long; (2) structurally and functionally mimics the surface region of its parent protein; and (3) offers a correct fit for the antigen binding site of a single specific autoantibody. Relapse prediction tests and therapies employ the peptides.
    • 血清测试的优化和验证证实了症状性自身免疫疾病,例如 多发性硬化症(MS)或类风湿性关节炎,并确定早期,沉默性疾病。 该方法涉及测试受试血清中存在表位特异性血清IgE和非IgE抗体。 测试是免疫测定,其中血清自身抗体与肽结合模拟例如髓磷脂碱性蛋白(MBP),髓磷脂少突胶质细胞糖蛋白(MOG)和蛋白脂质蛋白(PLP))的体液,自身免疫表位。 每个肽:(1)长5-6个氨基酸; (2)在结构上和功能上模拟其亲本蛋白质的表面区域; 和(3)提供了单一特异性自身抗体的抗原结合位点的正确拟合。 复发预测测试和疗法使用肽。
    • 10. 发明授权
    • Atherosclerotic plaque specific antigens, antibodies thereto, and uses
thereof
    • 动脉粥样硬化斑块特异性抗原,抗体及其用途
    • US5811248A
    • 1998-09-22
    • US480434
    • 1995-06-07
    • Charles C. DitlowFrancis W. ChenEmanuel Calenoff
    • Charles C. DitlowFrancis W. ChenEmanuel Calenoff
    • G01N33/533G01N33/92G01N33/574C07K16/18G01N33/53
    • G01N33/92G01N33/533C07K2317/24G01N2800/323
    • An antigen comprising 5,7 cholestadien-3.beta.-ol (7-dehydrocholesterol) or a compound having a structure similar to 5,7 cholestadien-3.beta.-ol and a quaternary ammonium salt is provided. Also provided is a method of generating an antibody using the aforementioned antigen, as well as antibodies produced thereby and fragments of such antibodies. The invention also provides a rat myeloma cell line Z2D3 73/30 1D10 and a murine-human chimeric monoclonal antibody produced thereby. A CDR-grafted antibody comprising a CDR region amino acid sequence from hybridoma Z2D3 or hybridoma Z2D3/3E5 and framework and constant region amino acid sequences from a human immunoglobulin is further provided. Also provided are methods for imaging atherosclerotic plaque, ablating atherosclerotic plaque, detecting and quantitatively determining in a sample an antigen indicative of the presence of atherosclerotic plaque, reducing the amount of atherosclerotic plaque in a blood vessel, and treating atherosclerosis in a subject. The invention also provides peptides having amino acid sequences which are the same or substantially the same as those of the aforementioned murine-human chimeric monoclonal antibody, as well as isolated nucleic acid sequences encoding therefore.
    • 提供了包含5,7胆固醇-3β-醇(7-脱氢胆固醇)或具有类似于5,7胆固醇-3β-醇和季铵盐结构的化合物的抗原。 还提供了使用上述抗原产生抗体的方法,以及由此产生的抗体和这种抗体的片段。 本发明还提供了大鼠骨髓瘤细胞系Z2D3 73/30 1D10和由此产生的鼠 - 人嵌合单克隆抗体。 还提供了包含来自杂交瘤Z2D3或杂交瘤Z2D3 / 3E5的CDR区氨基酸序列和来自人免疫球蛋白的框架和恒定区氨基酸序列的CDR-移植抗体。 还提供了用于成像动脉粥样硬化斑块,消融动脉粥样硬化斑块的方法,在样品中检测和定量测定表明动脉粥样硬化斑块存在的抗原,减少血管中的动脉粥样硬化斑块的量,以及治疗受试者的动脉粥样硬化。 本发明还提供了具有与上述鼠 - 人嵌合单克隆抗体相同或基本相同的氨基酸序列的肽以及由此编码的分离的核酸序列。