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公开(公告)号：US5762927A
公开(公告)日：1998-06-09
申请号：US827772
申请日：1997-04-11
CPC分类号： C07K16/2809 , A61K38/164 , A61K39/39541 , A61K47/48238 , A61K47/48484 , A61K47/48561 , C07K14/34 , C07K2319/00
摘要： Disclosed is a method of inhibiting a rejection response by a primate to a transplanted organ. One exposes the primate to a mutant diphtheria toxin linked to anti-CD3 antibody so as to largely eliminate the host's peripheral blood T cell lymphocyte population. At the same time as, or after, the exposure step one administers to the primate's thymus gland donor lymphocytes. Transplantation of the organ follows. The primate is tolerized to the transplanted organ.
摘要翻译： 公开了一种抑制灵长类动物对移植器官的排斥反应的方法。 将灵长类动物暴露于与抗CD3抗体连接的突变白喉毒素，从而大大消除宿主的外周血T细胞淋巴细胞群体。 在同一时间或之后，暴露步骤一个施用于灵长类动物的胸腺供体淋巴细胞。 随机移植器官。 灵长类动物容忍移植器官。
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2.发明授权公开(公告)号：US07517527B2
公开(公告)日：2009-04-14
申请号：US09389565
申请日：1999-09-03
CPC分类号： C07K16/2809 , A61K47/6829 , A61K47/6849 , A61K2039/505 , C07K2317/77
摘要： Provided is a method of treating an autoimmune disease in an animal comprising administering to the animal an antibody-DT mutant immunotoxin which routes by the anti-CD3 pathway, or derivatives thereof, under conditions such that the autoimmune disease is treated. In a further embodiment, the invention provides a method of treating T cell leukemias or lymphomas in an animal comprising administering to the animal an antibody-DT mutant immunotoxin which routes by the anti-CD3 pathway, or derivatives thereof, under conditions such that the T cell leukemias or lymphomas are treated.
摘要翻译： 本发明提供一种治疗动物自身免疫性疾病的方法，其特征在于，在对自身免疫性疾病进行治疗的条件下，对该动物施用抗CD3通路途径的抗体-DD突变型免疫毒素或其衍生物。 在另一个实施方案中，本发明提供了一种治疗动物中的T细胞白血病或淋巴瘤的方法，其包括对所述动物施用抗CD3通路途径的抗体-DD突变体免疫毒素或其衍生物， 治疗细胞白血病或淋巴瘤。
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3.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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4.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：US20110086416A1
公开(公告)日：2011-04-14
申请号：US12718673
申请日：2010-03-05
申请人： David M. Neville, Jr. , Jerry Todd Thompson , Huaizhong Hu , Jung-Hee Woo , Shenglin Ma , Jonathan Mark Hexham , Mary Ellen Digan
发明人： David M. Neville, Jr. , Jerry Todd Thompson , Huaizhong Hu , Jung-Hee Woo , Shenglin Ma , Jonathan Mark Hexham , Mary Ellen Digan
CPC分类号： C07K19/00 , A61K47/6829 , A61K47/6849 , C07K5/1008 , C07K7/06 , C07K7/08 , C07K14/34 , C07K16/2809 , C07K2317/24 , C07K2317/622 , C07K2319/00
摘要： The present invention described and shown in the specification and drawings provides novel recombinant DT-based immunotoxins, and, more specifically anti-T cell immunotoxin fusion proteins. Also provided are immunotoxins that can be expressed in bacterial, yeast, or mammalian cells. The invention also provides means for expression of the immunotoxin fusion protein. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.
摘要翻译： 在说明书和附图中描述和示出的本发明提供了新的重组DT-基免疫毒素，更具体地，提供了抗T细胞免疫毒素融合蛋白。 还提供了可以在细菌，酵母或哺乳动物细胞中表达的免疫毒素。 本发明还提供了表达免疫毒素融合蛋白的方法。 要强调的是，该摘要被提供以符合要求抽象的规则，允许搜索者或其他读者快速确定技术公开内容的主题。 提交它的理解是，它不会用于解释或限制权利要求的范围或含义。
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公开(公告)号：US5167956A
公开(公告)日：1992-12-01
申请号：US653164
申请日：1991-02-11
IPC分类号： A61K38/00 , A61K47/48 , C07K14/705 , C07K16/00
CPC分类号： A61K47/48561 , A61K47/48438 , C07K14/705 , C07K16/00 , A61K38/00 , C07K2319/00 , C07K2319/33 , C07K2319/55
摘要： The present invention relates to an immunotoxin. The invention further relates to a method of treating T cell leukemias and lymphomas, graft-versus-host diseases, and autoimmune diseases by administering an immunotoxin.
摘要翻译： 本发明涉及免疫毒素。 本发明还涉及通过施用免疫毒素来治疗T细胞白血病和淋巴瘤，移植物抗宿主病和自身免疫性疾病的方法。
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7.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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公开(公告)号：US08921097B2
公开(公告)日：2014-12-30
申请号：US12957165
申请日：2010-11-30
申请人： David M. Neville, Jr. , Jung-Hee Woo , Yuan-Yi Liu
发明人： David M. Neville, Jr. , Jung-Hee Woo , Yuan-Yi Liu
CPC分类号： C07K1/18 , A61K47/6829 , A61K47/6849 , C07K16/2809 , C07K2317/622 , C07K2319/00 , C12N1/16
摘要： The present invention relates to a method of expressing an immunotoxin in Pichia pastoris strain mutated to toxin resistance comprising a) growing the Pichia pastoris in a growth medium comprising an enzymatic digest of protein and yeast extract and maintaining a dissolved oxygen concentration at 40% and above; and b) performing methanol induction with a limited methanol feed of 0.5-0.75 ml/min/IO L of initial volume during induction along with a continuous infusion of yeast extract at a temperature below 17.5° C., antifoaming agent supplied up to 0.07%, agitation reduced to 400 RPM, and the induction phase extended out to 163 h.
摘要翻译： 本发明涉及一种在对抗毒素抗性进行突变的巴斯德毕赤酵母菌株中表达免疫毒素的方法，包括：a）在含有蛋白质和酵母提取物的酶促消化物的生长培养基中培养巴斯德毕赤酵母，并将溶解氧浓度保持在40％以上 ; 和b）在诱导期间以0.5-0.75ml / min / IOL的初始体积的有限甲醇进料进行甲醇诱导，同时在低于17.5℃的温度下连续输注酵母提取物，消泡剂提供高达0.07％ ，搅拌降至400RPM，诱导期延长至163小时。
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9.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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10.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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