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1. 发明申请

WO1997009064A1 USE OF MUTEINS OF WILD-TYPE CYTOKINES AS IMMUNOGENS 审中-公开
标题翻译：使用作为免疫球蛋白的野生型细胞因子
公开(公告)号：WO1997009064A1
公开(公告)日：1997-03-13
申请号：PCT/IT1996000164
申请日：1996-08-22
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CILIBERTO, Gennaro , SAVINO, Rocco , CORTESE, Riccardo
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： A61K39/00
CPC分类号： A61K39/0008 , A61K2039/55505
摘要： These are pharmaceutical compounds used to treat or prevent diseases caused by the over-production of a specific wild-type cytokine, characterised by the fact that they contain as an active principle at least one mutant of that wild-type cytokine. In its widest scope the invention consists in the use of muteins of a specific wild-type cytokine, that are also receptor antagonists of the latter, as immunogens to elicit antibodies directed against this wild-type cytokine and capable of neutralising it in those diesases caused by its excessive production. Figure 4 shows that antibodies developed in NSE/hIL-6 transgenic mice immunised with a human interleukin 6 mutein are capable of recognising wild-type interleukin 6 and of neutralising its biological activity.
摘要翻译：这些是用于治疗或预防由过度产生特异性野生型细胞因子引起的疾病的药物化合物，其特征在于它们作为活性成分包含该野生型细胞因子的至少一种突变体。在其最广泛的范围内，本发明在于使用特异性野生型细胞因子的突变蛋白，其也是后者的受体拮抗剂，作为引发针对该野生型细胞因子的抗体的免疫原，并能够在引起的那些死亡酶中中和由于其过度生产。图4显示用人白细胞介素6突变蛋白免疫的NSE / hIL-6转基因小鼠中产生的抗体能够识别野生型白细胞介素6并中和其生物学活性。

2. 发明申请

WO1996034104A1 ANTAGONISTS OF HUMAN INTERLEUKIN-6 THAT ARE TOTALLY INCAPABLE OF BINDING GP 130, AND THEIR USE IN THE PREPARATION OF PHARMACEUTICAL COMPOUNDS 审中-公开
标题翻译：人类白细胞介素-6的拮抗剂完全不能与GP 130结合，并且它们在制备药物化合物中的应用
公开(公告)号：WO1996034104A1
公开(公告)日：1996-10-31
申请号：PCT/IT1996000084
申请日：1996-04-26
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CILIBERTO, Gennaro , SAVINO, Rocco , PAONESSA, Giacomo
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： C12N15/24
CPC分类号： C07K14/5412 , A61K38/00
摘要： The present invention relates to antagonists of human interleukin-6 that are totally incapable of binding the receptor chain responsible for transduction of the signal associated with this cytokine, that is to say with gp 130. The figure shows the lack of interaction between human interleukin-6 antagonists according to the invention and the protein gp 130.
摘要翻译：本发明涉及完全不能与负责转导与该细胞因子相关的信号的受体链结合的人白细胞介素-6拮抗剂，也就是说与gp 130相似。该图显示了人白细胞介素-6缺乏相互作用， 6拮抗剂和蛋白质gp 130。

3. 发明申请

WO1998013383A1 ADENOVIRAL VECTORS FOR MUTANTS OF HUMAN INTERLEUKIN 6 (HIL-6) WITH HIL-6 ANTAGONIST ACTIVITY, PHARMACEUTICAL COMPOSITIONS THEREWITH AND THEIR USES 审中-公开
标题翻译：具有HIL-6拮抗剂活性的人类白细胞介素6（HIL-6）的突变体载体及其用途的药物组合物
公开(公告)号：WO1998013383A1
公开(公告)日：1998-04-02
申请号：PCT/IT1997000231
申请日：1997-09-24
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , CILIBERTO, Gennaro , SAGGIO, Isabella , SAVINO, Rocco , PERRICAUDET, Michel
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)
IPC分类号： C07K14/54
CPC分类号： A61K38/204 , C07K14/5412 , C12N2799/022
摘要： The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction. The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction.
摘要翻译：本发明的主题是重组缺陷型腺病毒，其包含编码具有人白细胞介素6（hIL-6）拮抗剂或超吸附剂活性的突变蛋白的异源DNA序列。此外，本发明涉及其治疗用途，特别是用于制备用于治疗和/或预防由hIL-6过量产生引起的病理学的药物组合物。本发明的主题是重组缺陷型腺病毒，其包含编码具有人白细胞介素6（hIL-6）拮抗剂或超吸附剂活性的突变蛋白的异源DNA序列。此外，本发明涉及其治疗用途，特别是用于制备用于治疗和/或预防由hIL-6过量产生引起的病理学的药物组合物。

4. 发明申请

WO1996018648A1 SUPERAGONISTS AND ANTAGONISTS OF H IL-6, AND 3D MODELLING METHOD FOR THEIR SELECTION 审中-公开
标题翻译： H IL-6的超级和拮抗剂及其选择的3D建模方法
公开(公告)号：WO1996018648A1
公开(公告)日：1996-06-20
申请号：PCT/IT1995000216
申请日：1995-12-13
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CILIBERTO, Gennaro , SAVINO, Rocco , LAHM, Armin , TONIATTI, Carlo
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： C07K14/54
CPC分类号： C07K14/5412 , A61K38/00 , G01N33/6869 , Y10S930/141
摘要： It is known that the ligands of the group of cytokines similar to Interleukin 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurothrophic Factor (CNTF) and Interleukin 11 (IL-11), induce the formation of a receptor complex of which the membrane molecule gp 130 is a part. The present invention refers to a methodology for selecting superagonists, antagonists and superantagonists of human interleukin-6 comprising the following operations: comparing the amino acid sequence of bovine granulocyte colony stimulating factor (bG-CSF) with the sequence of said hormone; and on the basis of the above comparison, formulating a three-dimensional model of said hormone, which allows the identification of residues that form the site of interaction with the specific receptor (Site 1) and those that constitute the site of interaction with gp 130 (Site 2) respectively. The invention allows the identification of these sites in human interleukin-6 and the isolation of variants having, with respect to the wild type hormone, a greater affinity for the specific receptor (superagonists and superantagonists) or affinity for gp 130 reduced or abolished (antagonists and superantagonists). The figure shows a scheme illustrating the methodoly applied to identify site 1 and site 2 in the case of human interleukin-6. The invention also describes the obtaining of specific superagonists and superantagonists of interleukin-6 and the use of superantagonists as low dose inhibitors of the growth of human myeloma cells dependent on wild type interleukin-6.
摘要翻译：众所周知，类似于白细胞介素6（IL-6），即制瘤素M（OSM），白血病抑制因子（LIF），睫状神经营养因子（CNTF）和白介素11（IL-11））的细胞因子组的配体，诱导膜分子gp 130为其一部分的受体复合物的形成。本发明涉及一种用于选择人白细胞介素-6的超级拮抗剂，拮抗剂和超吸收剂的方法，包括以下操作：比较牛粒细胞集落刺激因子（bG-CSF）的氨基酸序列与所述激素的序列; 并且基于上述比较，制定所述激素的三维模型，其允许鉴定形成与特异性受体（位点1）相互作用的位点的残基和构成与gp 130相互作用位点的残基（站点2）。本发明允许在人白细胞介素-6中鉴定这些位点，并且相对于野生型激素的变体的分离对特异性受体（超级拮抗剂和超吸收剂）具有更大的亲合力或对gp 130的亲和力降低或消除（拮抗剂和超级玩家）。该图示出了在人白细胞介素-6的情况下应用于鉴定位点1和位点2的方法的方案。本发明还描述了获得白细胞介素-6的特定的超级拮抗剂和超吸收剂，以及使用超吸收剂作为依赖于野生型白细胞介素-6的人骨髓瘤细胞生长的低剂量抑制剂。

5. 发明申请

WO1995000852A2 A METHODOLOGY FOR SELECTING SUPERAGONISTS, ANTAGONISTS AND SUPERANTAGONISTS OF HORMONES WHOSE RECEPTOR COMPLEX INCLUDES GP 130 审中-公开
标题翻译：选择受体复合物的雄激素的拮抗剂，拮抗剂和超抗体的方法包括GP 130
公开(公告)号：WO1995000852A2
公开(公告)日：1995-01-05
申请号：PCT/IT1994000095
申请日：1994-06-23
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , SAVINO, Rocco , LAHM, Armin , CILIBERTO, Gennaro
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： G01N33/68
CPC分类号： C07K14/475 , C07K14/52 , G01N33/6863 , G01N33/6869 , G01N33/74 , G01N2500/00
摘要： It has been found that the ligands of the group of cytokins similar to Interleukin 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) and Interleukin 11 (IL-11), induce formation of a receptor complex of which the membrane molecule gp 130 is a part. It is thus possible to formulate the hypothesis that two different surfaces of the protein (in this class of hormones), known as site 1 and site 2, bind to two different molecules: site 1 to the specific receptor and site 2 to gp 130. The invention allows the identification of these sites and the isolation of variants having, with respect to the wild hormone, a greater affinity for the specific receptor (superagonists and superantagonists) or affinity for gp 130 reduced or abolished (antagonists and superantagonists). The figure shows the construct pHen DELTA hIL-6 and the production of phasmidic particles that can be used to select agonists of Interleukin 6.
摘要翻译：已经发现，与白细胞介素6（IL-6）相似的细胞分裂素组，即制瘤素M（OSM），白血病抑制因子（LIF），睫状神经营养因子（CNTF）和白介素11（IL-11）），诱导膜分子gp 130是其一部分的受体复合物的形成。因此，可以制定假设，称为位点1和位点2的蛋白质（在该类激素中）的两个不同表面结合两个不同的分子：位点1到特异性受体和位点2至gp 130。本发明允许鉴定这些位点和相对于野生型激素具有对特定受体（超级拮抗剂和超吸收剂）的较大亲和力或对gp 130的亲和力降低或消除（拮抗剂和超吸收剂）的变体的分离。该图显示了可以用于选择白细胞介素6激动剂的pHen DELTA hIL-6的构建体和产生粒子的粒子。

6. 发明申请

WO1998022128A1 USE OF CNTF (CILIARY NEUROTROPHIC FACTOR) RECEPTOR ACTIVATORS FOR THE TREATMENT OF OBESITY 审中-公开
标题翻译： CNTF（CILIARY NEUROTROPHIC FACTOR）受体激活剂用于治疗肥胖症的使用
公开(公告)号：WO1998022128A1
公开(公告)日：1998-05-28
申请号：PCT/IT1997000283
申请日：1997-11-18
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CILIBERTO, Gennaro , COSTA, Patrizia , PAONESSA, Giacomo , LAZZARO, Domenico , GLOAGUEN, Isabelle , DI MARCO, Annalise , DE MARTIS, Anna , LAUFER, Ralph , CORTESE, Riccardo
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： A61K38/18
CPC分类号： A61K38/185 , A61K38/2264 , A61K48/00 , A61K2300/00
摘要： The present invention refers to the use of hCNTF (human ciliary neurotrophic factor), mutants thereof or other molecules that activate the CNTF receptor, for the preparation of drugs for the treatment of obesity and associated diseases, for example hyperglycemia. Figure 1 shows the anti-obesity effect of hCNTF and leptin on body weight (left panels) and on food intake (right panels) in genetically obese mice and in mice with diet-induced obesity (DIO).
摘要翻译：本发明涉及hCNTF（人纤维神经营养因子），其突变体或活化CNTF受体的其它分子用于制备用于治疗肥胖症和相关疾病例如高血糖症的药物。图1显示了在遗传肥胖小鼠和饮食诱导的肥胖（DIO）的小鼠中，hCNTF和瘦素对体重（左图）和食物摄取（右图）的抗肥胖作用。

7. 发明申请

WO1996017869A2 INTERLEUKIN-6 (IL-6) ANTAGONISTS 审中-公开
标题翻译：白细胞介素-6（IL-6）拮抗剂
公开(公告)号：WO1996017869A2
公开(公告)日：1996-06-13
申请号：PCT/IT1995000208
申请日：1995-12-05
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , CILIBERTO, Gennaro , TONIATTI, Carlo
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： C07K14/715
CPC分类号： C07K14/7155 , A61K38/00
摘要： These are antagonists of interleukin-6, characterised in that they consist of soluble forms of the receptor alpha of human IL-6 (shIL-6R alpha ) containing one or more mutation in the gp130 binding interface. In a preferred embodiment, the mutations are present in a position chosen from the group comprising Ala 228, Asn 230, His 280 and Asp 281. These antagonists can be used as agents capable of preventing and treating diseases caused by abnormal IL-6 activity. The figure shows the antagonist activity of the mutant Ala228Asp/Asn 230Asp/His280Ser/Asp281Val in comparison with the agonist properties of wild type shIL-6R alpha . This antagonist can be used for preparation of drugs for the prevention, control and treatment of diseases caused by abnormal IL-6 bioactivity.
摘要翻译：这些是白介素-6的拮抗剂，其特征在于它们由在gp130结合界面中含有一个或多个突变的人IL-6（shIL-6Rα）的受体α的可溶形式组成。在优选的实施方案中，突变存在于选自Ala 228，Asn 230，His 280和Asp 281的位置。这些拮抗剂可用作能够预防和治疗由异常IL-6活性引起的疾病的药剂。该图显示与野生型shIL-6Rα的激动剂性质相比，突变体Ala228Asp / Asn 230Asp / His280Ser / Asp281Val的拮抗剂活性。该拮抗剂可用于制备用于预防，控制和治疗由异常IL-6生物活性引起的疾病的药物。

8. 发明申请

WO1994026886A2 PROCESS FOR THE PREPARATION OF IMMUNOGENS OR DIAGNOSTIC REAGENTS, AND IMMUNOGENS OR DIAGNOSTIC REAGENTS THEREBY OBTAINABLE 审中-公开
标题翻译：制备免疫原或诊断试剂的方法，以及可获得的免疫原或诊断试剂
公开(公告)号：WO1994026886A2
公开(公告)日：1994-11-24
申请号：PCT/IT1994000054
申请日：1994-05-05
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , FELICI, Franco , LUZZAGO, Alessandra , NICOSIA, Alfredo , MONACI, Paolo , CORTESE, Riccardo
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： C12N15/10
CPC分类号： C40B40/02 , A61K39/00 , C07K14/005 , C07K14/4713 , C07K16/32 , C07K2319/40 , C07K2319/735 , C12N15/1037 , C12N2730/10122 , C12N2770/24222 , Y10S436/811
摘要： A process for the preparation of immunogens or diagnostic reagents that mimic an antigen or a pathogenic organism specific to a disease, essentially characterized by the following operations: identification of at least one antibody that reacts with the antigen or pathogenic organism specific to the disease; construction of phage libraries which display on the surface of the capsid oligopeptides, expressed from random sequence oligonucleotidic inserts introduced into a gene coding for a phage capsid protein using genetic manipulation techniques (for example using a plasmid engineered for the purposes of the invention, the genetic map of which is shown in the figure); selection of the phages that display on the surfaces of the capsid antigenic oligopeptides recognized by said antibody; optional use of the selected phages and/or fragments thereof and/or their derivatives for the formulation of diagnostic kits for the specific pathogenic agent, or in general for the diseases, including immunological disorders typical of so-called autoimmune diseases, with known or unknown etiology and/or pathogenesis; optional use of the selected phages and/or fragments thereof and/or their derivatives for the formulation of an antagonist of the antigen-antibody reactions for treatment of the disease induced by said antigen; optional use of the selected phages and/or fragments thereof and/or their derivatives to induce a tolerance of the phenomena of hypersensitivity and/or allergy to compounds and/or natural or synthetic preparations; optional immunization of an organism by means of the selected phages and/or fragments thereof and/or their derivatives; and optional verification of the presence, in the serum of the immunized organism, of antibodies that recognize the above antigen or organism specific to the disease.
摘要翻译：一种制备模拟抗原或疾病特异性的致病生物的免疫原或诊断试剂的方法，其基本特征在于以下操作：鉴定与该疾病特异性的抗原或致病生物反应的至少一种抗体; 构建在衣壳寡肽的表面上显示的噬菌体文库，其由使用遗传操作技术引入到编码噬菌体衣壳蛋白的基因中的随机序列寡核苷酸插入物表达（例如使用为本发明目的而设计的质粒，遗传地图如图所示）; 选择在所述抗体识别的衣壳抗原寡肽的表面上显示的噬菌体; 任选使用所选择的噬菌体和/或其片段和/或其衍生物用于制备用于特定病原体的诊断试剂盒，或一般用于包括已知或未知的所谓自身免疫性疾病典型的免疫学疾病的疾病病因和/或发病机制; 任选使用所选择的噬菌体和/或其片段和/或其衍生物用于制备用于治疗由所述抗原诱导的疾病的抗原 - 抗体反应的拮抗剂; 任选使用所选择的噬菌体和/或其片段和/或其衍生物以诱导对化合物和/或天然或合成制剂的过敏和/或过敏现象的耐受性; 通过所选择的噬菌体和/或其片段和/或其衍生物任选地免疫生物体; 并且可选地验证在免疫生物体的血清中存在识别上述对该疾病特异性的抗原或生物体的抗体。

9. 发明申请

WO1997001634A2 POLYPEPTIDE FOR REPAIRING GENETIC INFORMATION, NUCLEOTIDIC SEQUENCE WHICH CODES FOR IT AND PROCESS FOR THE PREPARATION THEREOF (GUANINE THYMINE BINDING PROTEIN - GTBP) 审中-公开
标题翻译：用于修复遗传信息的多肽，其编码的核苷酸序列及其制备方法（GUANINE THYMIN BINDING PROTEIN-GTBP）
公开(公告)号：WO1997001634A2
公开(公告)日：1997-01-16
申请号：PCT/IT1996000131
申请日：1996-06-27
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , JIRICNY, Josef , PALOMBO, Fabio , GALLINARI, Paola
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： C12N15/12
CPC分类号： C07K14/47 , A01K2217/05 , A61K38/00 , A61K48/00 , C07K14/82 , C07K16/18 , C12Q1/6886 , C12Q2600/136
摘要： The present invention relates to a new protein, GTBP (Guanine Thymine Binding Protein), that binds to G/T DNA mismatches to mediate repair of genetic information, to methods for detection of this protein, to the nucleotidic sequence encoding this protein and to processes for obtaining the above-mentioned protein using genetic engineering techniques. Furthermore, the present invention has as its object the detection in tumor tissues of the mutant GTBP gene in order to prevent and provide rapid diagnosis of human colorectal tumor forms. The figure shows the absence of GTBP-specific activity in cells obtained from human colorectal tumors.
摘要翻译：本发明涉及结合G / T DNA错配以介导遗传信息修复的新型蛋白质GTBP（鸟嘌呤胸腺嘧啶结合蛋白），该蛋白质检测方法，编码该蛋白质的核苷酸序列和方法用于使用遗传工程技术获得上述蛋白质。此外，本发明的目的是在突变型GTBP基因的肿瘤组织中检测以预防和提供人结肠直肠肿瘤形式的快速诊断。该图显示在从人结肠直肠肿瘤获得的细胞中不存在GTBP特异性活性。

10. 发明申请

WO1996037619A1 METHOD FOR REPRODUCING IN VITRO THE RNA-DEPENDENT RNA POLYMERASE AND TERMINAL NUCLEOTIDYL TRANSFERASE ACTIVITIES ENCODED BY HEPATITIS C VIRUS (HCV) 审中-公开
标题翻译：用于复制HCV依赖性RNA聚合酶和由乙型肝炎病毒（HCV）编码的终末核转移活性的方法
公开(公告)号：WO1996037619A1
公开(公告)日：1996-11-28
申请号：PCT/IT1996000106
申请日：1996-05-24
申请人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. , DE FRANCESCO, Raffaele , TOMEI, Licia , BEHRENS, Sven-Erik
发明人： ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.
IPC分类号： C12N15/54
CPC分类号： C12N9/1241 , C12N9/127 , C12N2799/026
摘要： This is a method for reproducing in vitro the RNA-dependent RNA polymerase activity associated with hepatitis C virus. The method is characterized in that sequences contained in NS5B are used in the reaction mixture. The terminal nucleotidyl transferase activity, a further property of the NS5B protein, can also be reproduced using this method. The method takes advantage of the fact that the NS5B protein, either purified to apparent homogeneity or present in extracts of overproducing organisms, can catalyse the addition of ribonucleotides to the 3'-termini of exogenous or endogenous RNA molecules. The invention also relates to a composition of matter that comprises sequences contained in NS5B, and to the use of these compositions for the set up of an enzymatic test capable of selecting, for therapeutic purposes, compounds that inhibit the enzymatic activity associated with NS5B. The figure shows plasmids used in the method to produce hepatitis C virus RNA-dependent RNA polymerase and terminal nucleotidyl transferase in cultivated eukaryotic and prokaryotic cells.
摘要翻译：这是一种在体外再生与丙型肝炎病毒相关的RNA依赖性RNA聚合酶活性的方法。该方法的特征在于在反应混合物中使用包含在NS5B中的序列。末端核苷酸转移酶活性，NS5B蛋白质的另一个性质也可以使用这种方法再现。该方法利用了纯化至表观均一性或存在于产生过量生物体的提取物中的NS5B蛋白可以催化向外源或内源RNA分子的3'末端加入核糖核苷酸的事实。本发明还涉及包含NS5B中包含的序列的物质组合物，以及这些组合物用于建立能够为治疗目的选择抑制与NS5B相关的酶活性的化合物的酶学试验的用途。该图显示了用于在培养的真核和原核细胞中产生丙型肝炎病毒RNA依赖性RNA聚合酶和末端核苷酸转移酶的方法中使用的质粒。

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