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1.发明授权Mannose-6-phosphate-low density protein reagent effective against hypercholesterolemia 失效甘露糖-6-磷酸低密度蛋白质试剂有效抗高胆固醇血症
公开(公告)号：US4397843A
公开(公告)日：1983-08-09
申请号：US341572
申请日：1982-01-21
IPC分类号： A61K38/00 , A61K47/48 , C07K14/415 , C07K14/775 , A61K37/00
CPC分类号： C07K14/415 , A61K47/4823 , A61K47/48461 , C07K14/775 , A61K38/00
摘要： A new reagent effective in inhibiting cholesterol synthesis 75% in human fibroblasts derived from patients suffering from the disease familial hypercholestrolemia is Man6P-low density lipoprotein and is effective in tissue culture test systems at 100 .mu.g/ml after a ten-hour exposure. The broad purpose of this invention is to modify the receptor specificity of a protein so that it will enter cells which were previously impermeable and exert new effects or reverse a pathological condition. That is, the compound of this invention is a useful reagent in the selective cytotoxic treatment of hypercholesterolemia.
摘要翻译： 人类成纤维细胞中有效抑制胆固醇合成75％的新试剂是源自患有家族性高胆固醇血症的患者，是Man6P-低密度脂蛋白，并且在10小时暴露后以100μg/ ml的组织培养试验系统有效。 本发明的广泛目的是改变蛋白质的受体特异性，使其进入先前不可渗透并发挥新作用或逆转病理状况的细胞。 也就是说，本发明的化合物是高胆固醇血症的选择性细胞毒性治疗中的有用试剂。
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2.发明授权Treatment of graft versus host disease using a mixture of T-lymphocyte specific monoclonal antibody: ricin conjugates 失效使用T淋巴细胞特异性单克隆抗体混合物治疗移植物抗宿主病：蓖麻毒蛋白偶联物
公开(公告)号：US4520226A
公开(公告)日：1985-05-28
申请号：US456401
申请日：1983-01-07
摘要： A reagent and the protocol for the treatment of Graft Versus Host Disease is disclosed. Monoclonal antibodies specific for T-lymphocytes in human donor bone marrow are covalently linked to separate ricin toxin, combined in a mixture to form a treatment reagent, and combined with bone marrow removed from a human donor. The bone marrow-reagent mixture is then infused into an irradiated recipient. This protocol virtually eliminates T-lymphocyte activity, the cause of Graft Versus Host Disease.
摘要翻译： 公开了一种试剂和用于治疗移植物抗宿主病的方案。 在人供体骨髓中特异性T淋巴细胞的单克隆抗体与分离的蓖麻毒素共价连接，混合物混合形成治疗试剂，并与从人供体中移除的骨髓组合。 然后将骨髓 - 试剂混合物输入到照射的受体中。 该协议实际上消除了T淋巴细胞活性，是移植物与宿主病的原因。
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3.发明授权Monoclonal antibody-ricin hybrids as a treatment of murine graft-versus-host disease 失效单克隆抗体 - 蓖麻毒蛋白杂交体作为鼠移植物抗宿主病的治疗
公开(公告)号：US4440747A
公开(公告)日：1984-04-03
申请号：US350223
申请日：1982-02-19
CPC分类号： C07K16/2803 , A61K38/00 , Y10S530/868
摘要： The receptor specificity of toxins can be altered by coupling the intact toxin to monoclonal antibodies directed to the cell surface antigen Thy 1.2. Monoclonal antibody Thy 1.2-ricin (or ricin A chain) is a pretreatment reagent used to eliminate graft-versus-host disease (GVHD) in bone marrow transplants.
摘要翻译： 毒素的受体特异性可以通过将完整毒素与针对细胞表面抗原Thy 1.2的单克隆抗体偶联来改变。 单克隆抗体您的1.2蓖麻毒蛋白（或蓖麻毒素A链）是用于消除骨髓移植中的移植物抗宿主病（GVHD）的预处理试剂。
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4.发明授权Anti Thy 1.2 monoclonal antibody-ricin hybrid utilized as a tumor suppressant 失效抗Thy 1.2单克隆抗体 - 蓖麻毒蛋白混合物用作肿瘤抑制剂
公开(公告)号：US4359457A
公开(公告)日：1982-11-16
申请号：US186735
申请日：1980-09-30
CPC分类号： C07K16/2803 , A61K38/00 , Y10S435/948 , Y10S530/806 , Y10S530/808
摘要： A tumor suppressive composition active against lymphoma consisting of an injection of hybrid protein anti Thy 1.2 monoclonal antibody-ricin and hyperosmotic lactose. The inoculation i.v. of murine tissues in vivo by lymphoma is made at -20 to -25 days and the tumor suppressant composition is used i.v. at Day 1 in an amount of 1-3 .mu.g of anti Thy monoclonal antibody-ricin together with sufficient hyperosmotic lactose to raise the lactose level to 20-30 mM. The broad purpose of this invention is to modify the receptor specificity of a potent toxin such as ricin by coupling it with a monoclonal antibody directed at a specific tumor or differentiation antigen. The object here is to use the reagent to selectively kill tumor cells without affecting normal cells.
摘要翻译： 一种抗淋巴瘤活性的肿瘤抑制组合物，其由注射混合蛋白质抗Thy 1.2单克隆抗体 - 蓖麻毒蛋白和高渗乳糖组成。 接种i.v. 通过淋巴瘤在体内的小鼠组织在-20至-25天内进行，并且使用肿瘤抑制剂组合物。 在第1天，将1-3μg抗Thy单克隆抗体 - 蓖麻毒蛋白与足够的高渗乳糖一起将乳糖水平提高至20-30mM。 本发明的广泛目的是通过将其与针对特异性肿瘤或分化抗原的单克隆抗体偶联来改变有效毒素如蓖麻毒蛋白的受体特异性。 这里的目标是使用试剂选择性地杀死肿瘤细胞而不影响正常细胞。
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5.发明授权Chemical modifications of proteins which induce new receptor specificities and therefore elicit new effects in cells 失效诱导新受体特异性的蛋白质的化学修饰，从而在细胞中引起新的作用
公开(公告)号：US4356117A
公开(公告)日：1982-10-26
申请号：US199781
申请日：1980-10-23
IPC分类号： A61K38/00 , A61K47/48 , C07K14/415 , C07K14/775 , C07G7/00
CPC分类号： A61K47/4823 , A61K47/48461 , C07K14/415 , C07K14/775 , A61K38/00 , Y10S435/948 , Y10S530/808 , Y10S530/868
摘要： A new reagent effective in inhibiting cholesterol synthesis 75% in human fibroblasts derived from patients suffering from the disease familial hypercholestrolemia is mannose-6-phosphate-low density lipoprotein and is effective in tissue culture test systems at 100 .mu.g/ml after a ten-hour exposure. The broad purpose of this invention is to modify the receptor specificity of a protein so that it will enter cells which were previously impermeable and exert new effects or reverse a pathological condition. Toxins may also be modified in this manner producing cell type specific and tumor suppressive reagents which are effective in a dose range of 0.3-3 .mu.g. The object here is to use the reagent to selectively kill one cell type which is exerting a pathological effect without affecting normal cells. Among others to which this invention is applicable are Man6P-low density lipoprotein, Man6P-ricin, Man6P-Modeccin, anti Thy 1.2 monoclonal antibody-ricin and anti Thy 1.1 monoclonal antibody-ricin.
摘要翻译： 在家族性高胆固醇血症患者中，有效抑制胆固醇合成75％的新试剂是甘露糖-6-磷酸低密度脂蛋白，在组织培养试验系统中以100μg/ ml有效， 小时曝光。 本发明的广泛目的是改变蛋白质的受体特异性，使其进入先前不可渗透并发挥新作用或逆转病理状况的细胞。 也可以以这种方式修饰毒素，产生在0.3-3μg剂量范围内有效的细胞型特异性和肿瘤抑制试剂。 这里的目的是使用试剂来选择性地杀死一种在不影响正常细胞的情况下发挥病理作用的细胞类型。 本发明适用的其中之一是Man6P-低密度脂蛋白，Man6P-蓖麻毒蛋白，Man6P-Modeccin，抗Thy 1.2单克隆抗体 - 蓖麻毒蛋白和抗Thy1.1单克隆抗体 - 蓖麻毒蛋白。
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6.发明授权Inactivating protein synthesis by incubating anti-Thy 1.1-ricin a chain monoclonal antibody hybrids with target protein cells 失效通过将抗Thy 1.1蓖麻毒蛋白链单克隆抗体杂交体与靶蛋白细胞孵育来灭活蛋白质合成
公开(公告)号：US4520011A
公开(公告)日：1985-05-28
申请号：US350222
申请日：1982-02-19
IPC分类号： A61K47/48 , A61K39/44 , A61K39/395 , A61K45/05
CPC分类号： A61K47/48476
摘要： The rate of protein synthesis inhibition is significantly increased by adding excess ricin B chain to target cells independent of the amount of ricin A chain bound to the cell surface membrane. Ricin is a known toxin from albumin of the castor oil bean and contains an A chain and a B chain for binding to receptors. The present invention is concerned with ricin hybrids such as OX-7-ricin A chain and 19E12-F(ab) ricin A chain which were produced by conjugation of the ricin A chains with anti-Thy 1.1 monoclonal antibodies. The conjugates were utilized in pharmaceutical amounts in mice.
摘要翻译： 不依赖于与细胞表面膜结合的蓖麻毒蛋白A链的量，通过向目标细胞加入过量的蓖麻毒素B链，蛋白质合成抑制率显着增加。 蓖麻毒素是来自蓖麻油豆白蛋白的已知毒素，含有与受体结合的A链和B链。 本发明涉及通过将蓖麻毒素A链与抗Thy1.1单克隆抗体缀合而产生的蓖麻毒蛋白杂合物，例如OX-7-蓖麻毒蛋白A链和19E12-F（ab）蓖麻毒蛋白A链。 在小鼠中以药物量使用缀合物。
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7.发明授权
公开(公告)号：US4500637A
公开(公告)日：1985-02-19
申请号：US399257
申请日：1982-07-19
CPC分类号： C07K16/28 , A61K38/00 , Y10S436/824 , Y10S530/806 , Y10S530/809 , Y10S530/868
摘要： A monoclonal antibody known as TA-1 directed against human T-cells is covalently linked to the toxin ricin and used to treat human donor bone marrow before the marrow is infused into a human recipient.
摘要翻译： 称为TA-1的针对人类T细胞的单克隆抗体与毒素蓖麻毒素共价连接，并用于治疗人类供体骨髓，然后将骨髓输注入人类受体。
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公开(公告)号：US5840840A
公开(公告)日：1998-11-24
申请号：US125462
申请日：1993-09-22
CPC分类号： C07K14/79 , C07K16/2881 , C07K19/00 , C12N9/22 , C07K2317/24 , C07K2317/622 , C07K2319/00
摘要： The present invention relates to a selective cytotoxic RNase reagent. The reagent comprises a toxic moiety that is an RNase linked to a recognition moiety that binds a specific cell surface marker. Binding of the recognition moiety to a surface marker on a cell allows the toxic moiety to selectively kill the cell. To reduce immunogenicity, preferably the toxic moiety and the recognition moiety of the conjugate are endogenous to the species in which the reagent is intended for use. Cytotoxic reagents intended for use in humans preferably have as the toxic moiety a human ribonuclease, such as angiogenin, and as the recognition moiety as humanized chimeric antibody. The human ribonuclease and chimeric antibody preferably form a fused protein. The present invention also relates to pharmaceutical compositions including the cytotoxic reagent as well as treatment methods involving the use of the cytotoxic reagent.
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9.发明授权Immunotoxins for treatment of intracranial lesions and as adjunct to chemotherapy 失效用于治疗颅内损伤和辅助化疗的免疫毒素
公开(公告)号：US5352447A
公开(公告)日：1994-10-04
申请号：US925417
申请日：1992-08-10
申请人： Virginia Johnson , Richard J. Youle
发明人： Virginia Johnson , Richard J. Youle
CPC分类号： A61K47/48592 , A61K47/483 , A61K47/48484 , A61K47/48623 , C07K14/34 , A61K38/00 , Y10S424/832
摘要： A potent and specific immunotoxin is prepared by coupling a binding-site inactivated diphtheria toxin (CRM 107) to a new binding moiety consisting of transferrin or a monoclonal antibody against the human transferrin receptor. These immunotoxins are tumor specific and lack the nonspecific toxicity produced by the binding activity of the native toxin. The immunotoxin is useful in treating primary brain tumors, metastatic tumors to the brain, CSF-borne tumors, leptomeningeal leukemia and leptomeningeal carcinomatosis.
摘要翻译： 通过将结合位点灭活的白喉毒素（CRM 107）与由转铁蛋白或针对人转铁蛋白受体的单克隆抗体组成的新结合部分偶联来制备有效和特异性的免疫毒素。 这些免疫毒素是肿瘤特异性的，并且缺乏由天然毒素的结合活性产生的非特异性毒性。 免疫毒素可用于治疗原发性脑肿瘤，转移性脑肿瘤，脑脊液肿瘤，脑膜性白血病和脑膜炎等。
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公开(公告)号：US5728383A
公开(公告)日：1998-03-17
申请号：US258712
申请日：1994-06-13
申请人： Virginia Johnson , Richard J. Youle
发明人： Virginia Johnson , Richard J. Youle
IPC分类号： A61K38/00 , A61K47/48 , C07K14/34 , A61K39/395
CPC分类号： C07K14/34 , A61K47/48592 , A61K47/48623 , A61K38/00 , Y10S424/832
摘要： Potent and specific immunotoxins are prepared by conjugation of moieties binding to receptors on the surface of tumor cells to a mutant diphtheria toxin having A-chain translocation activity, but lacking membrane-binding activity. The immunotoxins are used to treat primary tumors of neurologic origin, metastatic tumors of small cell lung carcinoma or breast carcinoma origin, leptomeningeal leukemia and leptomeningeal carcinomatosis. The preferred route of administration of the immunotoxin is to a compartment of the body containing cerebrospinal fluid.
摘要翻译： 通过将与肿瘤细胞表面上的受体结合的部分与具有A链易位活性但缺乏膜结合活性的突变白喉毒素结合来制备有效的和特异性的免疫毒素。 免疫毒素用于治疗神经源性原发性肿瘤，小细胞肺癌或乳腺癌起源的转移性肿瘤，脑膜性白血病和脑膜性肺炎。 免疫毒素的优选给药途径是包含脑脊液的身体的隔室。
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