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1. 发明授权

US5525472A Method for production and purification or recombinant Apolipoprotein E from bacteria 失效
标题翻译：来自细菌的生产和纯化方法或重组载脂蛋白E
公开(公告)号：US5525472A
公开(公告)日：1996-06-11
申请号：US333872
申请日：1994-11-03
申请人： Ruth Lifshitz , Meir Fischer , Benjamin Greenman , Daniel Bartfeld
发明人： Ruth Lifshitz , Meir Fischer , Benjamin Greenman , Daniel Bartfeld
IPC分类号： A61K38/00 , A61K47/48 , A61K51/12 , C07K14/775 , C12N1/06 , C12N1/38 , C07K1/30 , C12P21/00
CPC分类号： A61K47/48238 , A61K51/08 , C07K14/775 , C12N1/06 , C12N1/38 , A61K2123/00 , A61K38/00 , Y10S435/803
摘要： Applicants describe methods for purifying human ApoE or analog thereof from recombinant bacterial cells with minimal protein aggregation and degradation during the purification process. The invention involves the addition of neutralized fatty acids to the medium during cell disruption and the use of a non-ionic detergent during the purification process. Additionally applicants describe a method for increasing the production of ApoE or analog thereof in a bacterial host by adding to the culture medium neutralized fatty acids, fatty acid precursors, triglycerides, triglyceride precursors or acetate. Pharmaceutical and diagnostic uses of the ApoE analog are described.
摘要翻译：申请人描述了在纯化过程中从重组细菌细胞纯化人类ApoE或其类似物的方法，其中蛋白质聚集和降解最少。本发明涉及在细胞破碎期间向培养基中加入中和的脂肪酸，以及在纯化过程中使用非离子型洗涤剂。另外，申请人描述了通过向培养基中添加中和的脂肪酸，脂肪酸前体，甘油三酸酯，甘油三酸酯前体或乙酸酯来增加细菌宿主中ApoE或其类似物的产生的方法。描述了ApoE类似物的药物和诊断用途。

2. 发明授权

US6010875A Expressions plasmids containing the deo promoter, and bacterial hosts containing the plasmids 失效
标题翻译：含有deo启动子的表达质粒和含有质粒的细菌宿主
公开(公告)号：US6010875A
公开(公告)日：2000-01-04
申请号：US686465
申请日：1996-07-25
申请人： Meir Fischer
发明人： Meir Fischer
IPC分类号： C07K14/61 , C07K14/775 , C12N9/02 , C12N9/08 , C12N15/70 , C12P21/02
CPC分类号： C12N9/0089 , C07K14/61 , C07K14/775 , C12N15/70 , C12N9/0065 , C07K2319/00 , C07K2319/75
摘要： Plasmids are provided which upon introduction into a suitable Eschericia coli host render the host capable of effecting expression of DNA encoding a desired naturally-occurring polypeptide or polypeptide analog thereof under the control of the deo P1-P2 promoter. Further plasmids are also provided which thermoinducibly direct expression of eucaryotic genes under the control of a .lambda. P.sub.L promoter and a thermolabile repressor protein present on the same plasmid under the control of a deo P1 promoter. These plasmids have been inserted into various hosts, some of which contain DNA encoding the repressor protein.Such plasmids may be used to produce polypeptides such as human copper/zinc superoxide dismutase, hMnSOD-hGPX fusion polypeptides, human manganese superoxide dismutase, human growth hormone, bovine growth, porcine growth, human growth hormone-apolipoprotein E fused polypeptides, apolipoprotein E and various fibronectin domains.
摘要翻译：提供质粒，其在引入合适的大肠杆菌宿主中时，使宿主能够在编号P1-P2启动子的控制下实现编码期望的天然存在的多肽或其多肽类似物的DNA的表达。还提供了进一步的质粒，其在低ΔP启动子控制下，在λPL启动子和存在于相同质粒上的热不稳定阻遏物蛋白质的控制下，导致真核表达的真核基因。这些质粒已经插入到各种宿主中，其中一些含有编码阻抑蛋白的DNA。这样的质粒可用于产生多肽，例如人铜/锌超氧化物歧化酶，hMnSOD-hGPX融合多肽，人锰超氧化物歧化酶，人生长激素，牛生长，猪生长，人生长激素 - 载脂蛋白E融合多肽，载脂蛋白E和各种纤连蛋白结构域。

3. 发明授权

US09534013B2 Purification of proteins with cationic surfactant 有权
标题翻译：用阳离子表面活性剂纯化蛋白质
公开(公告)号：US09534013B2
公开(公告)日：2017-01-03
申请号：US11918292
申请日：2006-04-12
申请人： Meir Fischer , Eliyahu Harosh
发明人： Meir Fischer , Eliyahu Harosh
IPC分类号： C07K1/30
CPC分类号： C12N9/0048 , C07K1/30 , C07K14/565 , C07K16/00 , C07K16/36 , C07K2317/622 , C07K2317/76 , C12P21/02 , C12Y107/03003
摘要： The subject invention provides a method for purifying a target protein from a mixture comprising the target protein and contaminating protein, comprising the steps of exposing the mixture to an effective amount of a cationic surfactant such that the contaminating protein is preferentially precipitated and recovering the target protein. Proteins purified according to the method of the invention are also provided.
摘要翻译：本发明提供了从包含目标蛋白质和污染蛋白质的混合物中纯化靶蛋白的方法，包括以下步骤：将混合物暴露于有效量的阳离子表面活性剂，使得污染蛋白质被优先沉淀并回收靶蛋白。还提供了根据本发明的方法纯化的蛋白质。

4. 发明授权

US5795776A Expression plasmids regulated by an OSMB promoter 失效
标题翻译：由OSMB启动子调节的表达质粒
公开(公告)号：US5795776A
公开(公告)日：1998-08-18
申请号：US216851
申请日：1994-03-22
申请人： Meir Fischer
发明人： Meir Fischer
IPC分类号： C12N15/09 , C07K14/02 , C07K14/61 , C12N1/21 , C12N9/02 , C12N9/08 , C12N9/16 , C12N15/55 , C12N15/70 , C12P21/00 , C12R1/19 , C07H21/04 , C12N15/63 , C12P21/02
CPC分类号： C07K14/005 , C07K14/61 , C12N15/70 , C12N9/0089 , C12N9/16 , C12N2730/10122
摘要： Plasmids are provided which upon introduction into a suitable host render the host capable of effecting expression of DNA encoding a desired polypeptide under the control of an osmB promoter. Such plasmids may be used to produce polypeptides such as superoxide dismutases, acetylcholinesterase, growth hormones and hepatitis antigen.
摘要翻译：提供质粒，其在引入合适的宿主中时，使宿主能够在osmB启动子的控制下进行编码所需多肽的DNA的表达。这样的质粒可用于产生多肽，例如超氧化物歧化酶，乙酰胆碱酯酶，生长激素和肝炎抗原。

5. 发明申请

US20090317889A1 Purification of Proteins With Cationic Surfactant 有权
标题翻译：用阳离子表面活性剂纯化蛋白质
公开(公告)号：US20090317889A1
公开(公告)日：2009-12-24
申请号：US11918292
申请日：2006-04-12
申请人： Meir Fischer , Eliyahu Harosh
发明人： Meir Fischer , Eliyahu Harosh
IPC分类号： C12N9/06 , C07K1/30
CPC分类号： C12N9/0048 , C07K1/30 , C07K14/565 , C07K16/00 , C07K16/36 , C07K2317/622 , C07K2317/76 , C12P21/02 , C12Y107/03003
摘要： The subject invention provides a method for purifying a target protein from a mixture comprising the target protein and contaminating protein, comprising the steps of exposing the mixture to an effective amount of a cationic surfactant such that the contaminating protein is preferentially precipitated and recovering the target protein. Proteins purified according to the method of the invention are also provided.
摘要翻译：本发明提供了从包含目标蛋白质和污染蛋白质的混合物中纯化靶蛋白的方法，包括以下步骤：将混合物暴露于有效量的阳离子表面活性剂，使得污染蛋白质被优先沉淀并回收靶蛋白。还提供了根据本发明方法纯化的蛋白质。

6. 发明授权

US5248604A Enzymatically active recombinant human acetylcholinesterase and hosts and vectors for expression thereof 失效
标题翻译：酶活的重组人乙酰胆碱酯酶和宿主和载体用于表达
公开(公告)号：US5248604A
公开(公告)日：1993-09-28
申请号：US732962
申请日：1991-07-22
申请人： Meir Fischer
发明人： Meir Fischer
IPC分类号： A61K38/00 , C12N9/18 , C12N15/70 , C12Q1/46 , C12Q1/68 , G01N33/58
CPC分类号： C12N15/70 , C12N9/18 , C12Q1/46 , C12Q1/6886 , G01N33/581 , A61K38/00
摘要： The subject invention provides an enzymatically active nonglycosylated, recombinant, human acetylcholinesterase comprising at least one polypeptide characterized by an amino acid sequence which is substantially identical to the amino acid sequence of naturally-occurring human acetylcholinesterase. The subject invention additionally provides an enzymatically active recombinant human acetylcholinesterase comprising at least one polypeptide characterized by an amino acid sequence in which serine is substituted for cys 611 in the sequence of naturally-occurring, human acetylcholinesterase and an enzymatically active recombinant human acetylcholinesterase comprising at least one polypeptide characterized by the presence of a methionine of the N-terminus of the amino acid sequence of naturally-occurring human acetylcholinesterase.
摘要翻译：本发明提供了一种酶促活性非糖基化的重组人乙酰胆碱酯酶，其包含至少一个特征在于与天然存在的人乙酰胆碱酯酶的氨基酸序列基本相同的氨基酸序列的多肽。本发明另外提供了一种酶促活化的重组人乙酰胆碱酯酶，其包含至少一个多肽，其特征在于氨基酸序列，其中丝氨酸被取代天然存在的人乙酰胆碱酯酶序列中的cys 611和至少包含酶促活化的重组人乙酰胆碱酯酶一种多肽，其特征在于存在天然存在的人乙酰胆碱酯酶的氨基酸序列的N-末端的甲硫氨酸。

7. 发明授权

US5945304A Expression plasmids regulated by an osmB promoter 失效
标题翻译：由osmB启动子调节的表达质粒
公开(公告)号：US5945304A
公开(公告)日：1999-08-31
申请号：US897043
申请日：1997-07-18
申请人： Meir Fischer
发明人： Meir Fischer
IPC分类号： C12N15/09 , C07K14/02 , C07K14/61 , C12N1/21 , C12N9/02 , C12N9/08 , C12N9/16 , C12N15/55 , C12N15/70 , C12P21/00 , C12R1/19 , C12P21/02 , C07H21/04
CPC分类号： C07K14/005 , C07K14/61 , C12N15/70 , C12N9/0089 , C12N9/16 , C12N2730/10122
摘要： Plasmids are provided which upon introduction into a suitable host render the host capable of effecting expression of DNA encoding a desired polypeptide under the control of an osmB promoter. Such plasmids may be used to produce polypeptides such as superoxide dismutases, acetylcholinesterase, growth hormones and hepatitis antigen.
摘要翻译：提供质粒，其在引入合适的宿主中时，使宿主能够在osmB启动子的控制下进行编码所需多肽的DNA的表达。这样的质粒可用于产生多肽，例如超氧化物歧化酶，乙酰胆碱酯酶，生长激素和肝炎抗原。

8. 发明授权

US5801017A Production of recombinant factor Xa inhibitor of leech Hirudo medicinalis 失效
标题翻译：水蛭药材重组因子Xa抑制剂的生产
公开(公告)号：US5801017A
公开(公告)日：1998-09-01
申请号：US226264
申请日：1994-04-08
申请人： Moshe M. Werber , Elisha P. Zeelon , Avigdor Levanon , Rachel Guy , Arie Goldlust , Meir Rigbi , Amos Panet , Meir Fischer
发明人： Moshe M. Werber , Elisha P. Zeelon , Avigdor Levanon , Rachel Guy , Arie Goldlust , Meir Rigbi , Amos Panet , Meir Fischer
IPC分类号： C12N15/09 , A61K38/00 , A61K38/45 , A61K38/46 , A61P7/02 , A61P31/12 , A61P43/00 , C07K1/16 , C07K14/815 , C07K16/38 , C12N1/21 , C12N9/99 , C12N15/15 , C12P21/02 , C12P21/08 , C12R1/19 , C12N15/63
CPC分类号： C07K14/815 , C07K16/38 , A61K38/00
摘要： The present invention provides a recombinant polypeptide having the amino acid sequence X-tyr.sup.26 -gly.sup.110 where tyr.sup.26 -gly.sup.110 is identical to the sequence shown in FIG. 10, and wherein X is methionine or absent and wherein asn.sup.72 may be substituted by pro. The invention further provides a method of producing the polypeptide which comprises transforming a host cell with an expression plasmid encoding the polypeptide, culturing the transformed host cell so that the cell produces the polypeptide encoded by the plasmid, and a method of recovering the polypeptide so produced.
摘要翻译：本发明提供具有氨基酸序列X-tyr26-gly110的重组多肽，其中tyr26-gly110与图1所示的序列相同。 10，并且其中X是甲硫氨酸或不存在，并且其中asn72可以被亲代替。本发明还提供了一种生产多肽的方法，其包括用编码多肽的表达质粒转化宿主细胞，培养转化的宿主细胞，使得细胞产生由质粒编码的多肽，以及回收如此产生的多肽的方法。

9. 发明授权

US5593860A Expression plasmids containing the deo promoter, and bacterial hosts containing the plasmids 失效
标题翻译：含有deo启动子的表达质粒和含有质粒的细菌宿主
公开(公告)号：US5593860A
公开(公告)日：1997-01-14
申请号：US261750
申请日：1994-06-17
申请人： Meir Fischer
发明人： Meir Fischer
IPC分类号： C07K14/61 , C07K14/775 , C12N9/02 , C12N9/08 , C12N15/70 , C12P21/00 , C12N15/00
CPC分类号： C12N9/0089 , C07K14/61 , C07K14/775 , C12N15/70 , C12N9/0065 , C07K2319/00 , C07K2319/75
摘要： Plasmids are provided which upon introduction into a suitable Escherichia coli host render the host capable of effecting expression of DNA encoding a desired naturally-occurring polypeptide or polypeptide analog thereof under the control of the deo P1-P2 promoter. Further plasmids are also provided which thermoinducibly direct expression of eucaryotic genes under the control of a .lambda. P.sub.L promoter and a thermolabile repressor protein present on the same plasmid under the control of a deo P1 promoter. These plasmids have been inserted into various hosts, some of which contain DNA encoding the repressor protein.Such plasmids may be used to produce polypeptides such as human copper/zinc superoxide dismutase, hMnSOD-hGPX fusion polypeptides, human manganese superoxide dismutase, human growth hormone, bovine growth, porcine growth, human growth hormone-apolipoprotein E fused polypeptides, apolipoprotein E and various fibronectin domains.
摘要翻译：提供质粒，其在引入合适的大肠杆菌宿主中时，使宿主能够在编码P1-P2启动子的控制下实现编码期望的天然存在的多肽或其多肽类似物的DNA的表达。还提供了进一步的质粒，其在低ΔP启动子控制下，在λPL启动子和存在于相同质粒上的热不稳定阻遏物蛋白质的控制下，导致真核表达的真核基因。这些质粒已经插入到各种宿主中，其中一些含有编码阻抑蛋白的DNA。这样的质粒可用于产生多肽，例如人铜/锌超氧化物歧化酶，hMnSOD-hGPX融合多肽，人锰超氧化物歧化酶，人生长激素，牛生长，猪生长，人生长激素 - 载脂蛋白E融合多肽，载脂蛋白E和各种纤连蛋白结构域。

10. 发明授权

US5548068A Somatotropins with alterations in the alpha-helix 1 region, and combinations with other mutations 失效
标题翻译：具有α螺旋1区域改变的生长激素，以及与其他突变的组合
公开(公告)号：US5548068A
公开(公告)日：1996-08-20
申请号：US363982
申请日：1994-12-23
申请人： Meir Fischer , Michael R. Lebens , Deborah T. Chaleff
发明人： Meir Fischer , Michael R. Lebens , Deborah T. Chaleff
IPC分类号： A61K38/27 , A61P43/00 , C07K1/113 , C07K14/00 , C07K14/415 , C07K14/575 , C07K14/61 , C12N15/09 , C12N15/18
CPC分类号： C07K1/1133 , C07K14/61
摘要： The present invention relates to somatotropin analogues with amino acid changes in the alpha-helix 1 regions of said somatotropins, alone or in combination with mutations in the alpha-helix 3 and/or alpha-helix 2 regions, plus combinations with other changes to the native amino acid sequence of somatotropins. The resulting analogues are stable for formulation in sustained release formulations, while maintaining biological activity. Further, methods for conducting site-directed mutagenesis on DNA encoding proteins and/or polypeptide also are provided.
摘要翻译：本发明涉及在所述生长激素的α-螺旋1区域中具有氨基酸变化的生长激素类似物，单独或与α-螺旋3和/或α-螺旋2区域中的突变组合，以及与生长激素的天然氨基酸序列。所得类似物在持续释放制剂中的制剂是稳定的，同时保持生物活性。此外，还提供了对编码蛋白质和/或多肽的DNA进行定点诱变的方法。

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