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1. 发明授权

US6045793A Recombinant ribonuclease proteins 失效
标题翻译：重组核糖核酸酶蛋白
公开(公告)号：US6045793A
公开(公告)日：2000-04-04
申请号：US875811
申请日：1998-02-19
申请人： Susanna M. Rybak , Dianne L. Newton , Lluis Boque , Alexander Wlodawer
发明人： Susanna M. Rybak , Dianne L. Newton , Lluis Boque , Alexander Wlodawer
IPC分类号： A61K38/46 , A61P35/00 , C07H21/04 , C12N9/22 , C12N15/00
CPC分类号： C12N9/22 , C07K14/55 , C12Y301/27005 , A61K38/00 , C07K2319/00 , C07K2319/74
摘要： The invention relates to ribonucleases derived from a native ribonuclease found in the oocytes of Rana pipiens. Various humanized and recombinant forms of these molecules are described as well as uses for them.
摘要翻译： PCT No.PCT / US97 / 02588 Sec。 371日期1998年2月19日 102（e）1998年2月19日PCT PCT 1997年2月19日PCT公布。公开号WO97 / 31116 日期：1997年8月28日本发明涉及来自蛙属卵母细胞中发现的天然核糖核酸酶的核糖核酸酶。描述了这些分子的各种人源化和重组形式以及它们的用途。

2. 发明授权

US06395276B1 Immunotoxins directed against malignant cells 失效
标题翻译：针对恶性细胞的免疫毒素
公开(公告)号：US06395276B1
公开(公告)日：2002-05-28
申请号：US09071672
申请日：1998-05-01
申请人： Susanna M. Rybak , Dianne L. Newton , David M. Goldenberg
发明人： Susanna M. Rybak , Dianne L. Newton , David M. Goldenberg
IPC分类号： A61K39395
CPC分类号： C07K14/463 , A61K38/00 , A61K47/6817 , A61K47/6849 , C07K16/2803 , C07K16/2833 , C07K16/3061 , C07K2319/00
摘要： The present invention relates to immunotoxins, that effectively kill malignant cells having a given surface marker and nucleic acid constructs encoding them. These reagents comprise a toxic moiety that is derived from a Rana pipiens protein having ribonucleolytic activity linked to an antibody capable of specific binding with a chosen tumor cell.
摘要翻译：本发明涉及免疫毒素，其有效地杀死具有给定表面标志物和编码它们的核酸构建体的恶性细胞。这些试剂包含衍生自具有与能够与所选择的肿瘤细胞特异性结合的抗体连接的核糖核酸分解活性的蛙属蛋白质的毒性部分。

3. 发明授权

US06869604B1 Recombinant anti-tumor RNAse 失效
标题翻译：重组抗肿瘤RNA酶
公开(公告)号：US06869604B1
公开(公告)日：2005-03-22
申请号：US09622613
申请日：1999-03-26
申请人： Susanna M. Rybak , Dianne L. Newton
发明人： Susanna M. Rybak , Dianne L. Newton
IPC分类号： A61K38/00 , A61K47/48 , C12N9/22 , A61K38/47
CPC分类号： C12N9/22 , A61K38/00 , A61K47/6815
摘要： This invention provides for new recombinant ribonuclease proteins which are active when expressed by bacteria. This allows the recombinant ribonucleases of this invention to be fused in-frame with ligand binding moieties to form cytotoxic fusion proteins. Furthermore, these proteins are more active than ribonucleases currently available even though the proteins of this invention lack an N-terminal pyroglutamic acid, which has been found to be necessary for ribonucleolytic activity. Because these proteins are recombinant proteins, mutations which increase cytotoxicity can be engineered.
摘要翻译：本发明提供了当由细菌表达时具有活性的新的重组核糖核酸酶蛋白。这允许本发明的重组核糖核酸酶与配体结合部分框架融合以形成细胞毒性融合蛋白。此外，这些蛋白质比现有的核糖核酸酶更有活性，即使本发明的蛋白质缺乏已经被认为是核糖核酸分解活性所必需的N-末端焦谷氨酸。因为这些蛋白质是重组蛋白，所以可以设计增加细胞毒性的突变。

4. 发明授权

US5840840A Selective RNase cytotoxic reagents 失效
公开(公告)号：US5840840A
公开(公告)日：1998-11-24
申请号：US125462
申请日：1993-09-22
申请人： Susanna M. Rybak , Richard J. Youle , Dianne L. Newton , Peter J. Nicholls
发明人： Susanna M. Rybak , Richard J. Youle , Dianne L. Newton , Peter J. Nicholls
IPC分类号： A61P35/00 , C07K14/79 , C07K16/28 , C07K19/00 , C12N9/22 , C12N15/54 , C12N9/12 , C12P21/04
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.

5. 发明授权

US07189393B2 Recombinant anti-tumor RNAse 失效
标题翻译：重组抗肿瘤RNA酶
公开(公告)号：US07189393B2
公开(公告)日：2007-03-13
申请号：US09948391
申请日：2001-09-06
申请人： Susanna M. Rybak , Dianne L. Newton
发明人： Susanna M. Rybak , Dianne L. Newton
IPC分类号： A61K38/43
CPC分类号： C12N9/22 , A61K38/00 , A61K47/6815
摘要： This invention provides for new recombinant ribonuclease proteins which are active when expressed by bacteria. This allows the recombinant ribonucleases of this invention to be fused in-frame with ligand binding moieties to form cytotoxic fusion proteins. Furthermore, these proteins are more active than ribonucleases currently available even though the proteins of this invention lack an N-terminal pyroglutamic acid, which has been found to be necessary for ribonucleolytic activity. Because these proteins are recombinant proteins, mutations which increase cytotoxicity can be engineered.
摘要翻译：本发明提供了当由细菌表达时具有活性的新的重组核糖核酸酶蛋白。这允许本发明的重组核糖核酸酶与配体结合部分框架融合以形成细胞毒性融合蛋白。此外，这些蛋白质比现有的核糖核酸酶更有活性，即使本发明的蛋白质缺乏已经被认为是核糖核酸分解活性所必需的N-末端焦谷氨酸。因为这些蛋白质是重组蛋白，所以可以设计增加细胞毒性的突变。

6. 发明授权

US07029899B1 Selective toxicity of amino-terminal modified rnase a superfamily polypeptides 失效
标题翻译：氨基末端修饰的rnase一个超家族多肽的选择性毒性
公开(公告)号：US07029899B1
公开(公告)日：2006-04-18
申请号：US09807556
申请日：1999-11-01
申请人： Susanna M. Rybak , Dianne L. Newton
发明人： Susanna M. Rybak , Dianne L. Newton
IPC分类号： A61K38/46 , C12N15/54 , C12N15/62 , C12N15/00 , C07H21/04
CPC分类号： C12Y301/27005 , A61K38/00 , C12N9/22
摘要： This invention provides RNase A superfamily polypeptides with modified amino terminal which can be used to selectively kill target Kaposi's sarcoma cells, neoplastic endothelial cells, and non-neoplastic endothelial cells. In certain embodiments of the invention, the amino terminal modification consists of an addition of 4 amino acid sequence consisting of the SLHV sequence at position −4 to −1 to the eosinophil derived neurotoxin protein. The amino terminal addition is capable of directing the claimed RNase A superfamily polypeptides to proliferating endothelial cells, such as Kaposi's sarcoma cells, and selectively killing these cells.
摘要翻译：本发明提供具有修饰氨基末端的RNase A超家族多肽，其可用于选择性地杀死目标卡波西肉瘤细胞，肿瘤内皮细胞和非肿瘤内皮细胞。在本发明的某些实施方案中，氨基末端修饰包括由嗜酸性粒细胞衍生的神经毒素蛋白质在-4至-1位置的SLHV序列的4个氨基酸序列的添加。氨基末端加成能够将所要求保护的RNase A超家族多肽引导至增殖性内皮细胞，例如卡波西氏肉瘤细胞，并选择性地杀死这些细胞。

7. 发明授权

US5955073A Selective RNase cytotoxic reagents 失效
标题翻译：选择性RNase细胞毒素试剂
公开(公告)号：US5955073A
公开(公告)日：1999-09-21
申请号：US891848
申请日：1997-07-09
申请人： Susanna M. Rybak , Richard J. Youle , Dianne L. Newton , Peter J. Nicholls
发明人： Susanna M. Rybak , Richard J. Youle , Dianne L. Newton , Peter J. Nicholls
IPC分类号： A61P35/00 , C07K14/79 , C07K16/28 , C07K19/00 , C12N9/22 , C12N15/54 , A61K38/46 , C12N15/62
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.
摘要翻译：本发明涉及选择性细胞毒性RNase试剂。试剂包含毒性部分，其是与识别部分连接的核糖核酸酶，其结合特异性细胞表面标记物。识别部分与细胞上的表面标记的结合允许有毒部分选择性地杀死细胞。为了降低免疫原性，优选毒性部分和缀合物的识别部分对于试剂用于其中的物质是内源的。旨在用于人的细胞毒性试剂优选具有人核糖核酸酶（例如血管生成素）的毒性部分和作为人源化嵌合抗体的识别部分。人核糖核酸酶和嵌合抗体优选形成融合蛋白。本发明还涉及包含细胞毒性试剂的药物组合物以及涉及使用细胞毒性试剂的治疗方法。

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