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21. 发明申请

WO0194383A3 MUTATED FURIN POLYPEPTIDES HAVING IMPROVED CHARACTERISTICS 审中-公开
标题翻译：具有改进特性的突变型蛋白多糖
公开(公告)号：WO0194383A3
公开(公告)日：2002-11-21
申请号：PCT/EP0105991
申请日：2001-05-25
申请人： BAXTER AG
发明人： PLAIMAUER BARBARA , SCHLOKAT UWE
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , C07K14/755 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/64 , C12N15/57 , C12N15/84 , A61K38/48
CPC分类号： C12Y304/21075 , A61K38/00 , A61K48/00 , C07K14/755 , C12N9/6454 , C12N2799/021
摘要： The present invention comprises a furin polypeptide having a modified amino acid sequence between the middle, homo-B-domain and the transmembrane domain compared to wild-type furin which retains proteolytic activity but is secreted at lower levels in cell culture compared to wild-type furin. Additionally, the invention includes nucleic acid molecules encoding such furin polypeptides, vectors and host cells comprising said nucleic acid molecules, compositions comprising said furin polypeptide and methods for producing such compositions.
摘要翻译：本发明包含与野生型弗林蛋白酶相比，在野生型弗林蛋白酶中间具有修饰的氨基酸序列的弗林蛋白酶多肽，该野生型弗林蛋白酶与野生型弗林蛋白酶相比，其保留蛋白水解活性，但在细胞培养物中分泌较低水平弗林。另外，本发明包括编码这种弗林蛋白酶多肽的核酸分子，包含所述核酸分子的载体和宿主细胞，包含所述弗林蛋白多肽的组合物和用于制备这种组合物的方法。

22. 发明申请

WO02002011A1 DNA ENCODING HUMAN SERINE PROTEASE D-G 审中-公开
标题翻译： DNA编码人丝氨酸蛋白酶D-G
公开(公告)号：WO02002011A1
公开(公告)日：2002-01-10
申请号：PCT/US2001/018568
申请日：2001-06-08
IPC分类号： C12N15/09 , A61K31/7088 , A61K38/00 , A61K39/395 , A61K45/00 , A61K48/00 , A61P7/04 , A61P29/00 , A61P35/00 , A61P37/02 , A61P43/00 , C07K16/40 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N9/64 , C12Q1/37 , A61B5/055 , C07H21/04 , C07K16/00 , C12N1/20 , C12N9/00 , C12N9/50 , C12N15/00 , C12P21/06 , C12Q1/00
CPC分类号： C12N9/6454 , A61K38/00 , Y10T436/24
摘要： Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed D-G. The deduced amino acid sequence, and its alignment with other well characterized serine proteases clearly indicates that it is a member of the S1 serine protease family. We have found that the protease D-G mRNA is widely expressed in several tissues throughout the body including epidermis, fibroblasts, keratinocytes, colon, small intestine, stomach, lung, kidney, bone marrow, lymph node, thymus, ovary, prostate, uterus and spinal cord. Interestingly, this protease contains a hydrophobic stretch of amino acids which is a putative transmembrane near the NH2-terminus. Thus, this serine protease is thought to be synthesized as a type II integral protein. We expressed a soluble form of this novel human protease by inserting the portion of the protease D-G cDNA, encoding the catalytic domain, in a zymogen activation construct designed to permit the generic activation of heterologous serine protease catalytic domains. The result is an active preparation of protease D-G that has an activity against a subset of amidolytic substrates. This enzymatically active protease D-G preparation is now amenable to further biochemical analyses for the identification of physiological substrates as well as specific inhibitors.
摘要翻译：这里我们描述了编码我们称为D-G的新型丝氨酸蛋白酶的cDNA的分子鉴定。推导的氨基酸序列及其与其他良好表征的丝氨酸蛋白酶的比对清楚地表明它是S1丝氨酸蛋白酶家族的成员。我们已经发现蛋白酶DG mRNA在全身的几种组织中广泛表达，包括表皮，成纤维细胞，角质形成细胞，结肠，小肠，胃，肺，肾，骨髓，淋巴结，胸腺，卵巢，前列腺，子宫和脊髓线。有趣的是，该蛋白酶含有氨基酸的疏水延伸，氨基酸是NH2末端附近的推定跨膜。因此，认为该丝氨酸蛋白酶被合成为II型整合蛋白。我们通过将编码催化结构域的蛋白酶D-G cDNA的部分插入设计成允许异源丝氨酸蛋白酶催化结构域的通用活化的酶原激活构建体中来表达这种新型人类蛋白酶的可溶形式。其结果是蛋白酶D-G的活性制备，其具有对酰氨基底物亚组的活性。这种酶活性蛋白酶D-G制剂现在适合进一步的生物化学分析用于鉴定生理底物以及特异性抑制剂。

23. 发明申请

WO01071003A1 A NOVEL POLYPEPTIDE, A HUMAN SERINE PROTEASE 8 AND THE POLYNUCLEOTIDE ENCODING THE POLYPEPTIDE 审中-公开
公开(公告)号：WO01071003A1
公开(公告)日：2001-09-27
申请号：PCT/CN2001/000404
申请日：2001-03-23
IPC分类号： A61K38/00 , C12N9/64 , C12N15/57 , A61K38/48 , C07K14/435
CPC分类号： C12N9/6454 , A61K38/00
摘要： The present invention discloses a novel polypeptide, a human serine protease 8, the polynucleotide encoding the polypeptide and the method for producing the polypeptide by DNA recombinant technology. The invention also discloses the uses of the polypeptide in methods for treating various diseases, such as malignant tumour, hemopathy, HIV infection, immunological disease, and various inflammations, etc. The invention also discloses the agonists against the polypeptide and the therapeutic action thereof. The invention also discloses the uses of the polynucleotide encoding the novel human serine protease 8.

24. 发明申请

WO98050560A1 HUMAN PROHORMONE CONVERTASE 4 审中-公开
标题翻译：人民代表大会4
公开(公告)号：WO98050560A1
公开(公告)日：1998-11-12
申请号：PCT/US1998/008871
申请日：1998-05-01
IPC分类号： C12N15/09 , C07K14/435 , C07K16/18 , C07K19/00 , C12N9/50 , C12N9/64 , C12N15/55 , C07K16/40 , C12N5/10 , C12N15/62
CPC分类号： C12N9/6454 , C07K2319/00
摘要： The present invention provides polynucleotide and polypeptide molecules for a novel human prohormone convertase 4. The polynucleotides encoding human prohormone convertase 4, are located on chromosome (19), and may, for example, be used to identify a region of the genome associated with human disease states. The present invention also includes methods for producing the protein and antibodies thereto.
摘要翻译：本发明提供了用于新型人激素转化酶4的多核苷酸和多肽分子。编码人类激素转化酶4的多核苷酸位于染色体（19）上，并且可以例如用于鉴定与人相关的基因组的区域疾病状态。本发明还包括生产蛋白质的方法及其抗体。

25. 发明申请

WO1997005256A2 MAMMALIAN PRO-HORMONE CONVERTASE 审中-公开
公开(公告)号：WO1997005256A2
公开(公告)日：1997-02-13
申请号：PCT/CA1996000520
申请日：1996-08-02
申请人： INSTITUT DE RECHERCHES CLINIQUES DE MONTREAL , SEIDAH, Nabil, G. , DAY, Robert , CHRETIEN, Michel
发明人： INSTITUT DE RECHERCHES CLINIQUES DE MONTREAL
IPC分类号： C12N15/57
CPC分类号： C07K14/005 , A61K48/00 , C12N9/6454 , C12N2740/16122
摘要： This invention relates to a novel and seventh member of the subtilisin-kexin family isolated from rat, which has been named rPC7. The rat spleen cDNA has been totally sequenced. A shorter DNA sequence has been obtained for human, which corresponds to a portion of the catalytic region of a human pro-hormone convertase corresponding to the rat pro-hormone convertase. PC7 clearly distinguishes from the other mammalian members of the subtilisin-kexin family. Its tissue distribution is ubiquitous, but its presence is particularly remarkable in lymphoid tissues. It is present in LoVo cells that are able to cleave the HIV gp160 protein into active gp120/gp41 proteins and that are deficient in other effective pro-hormone convertases known up to date. It is proposed that PC7 is a good candidate as a maturation enzyme responsible for the conversion of HIV gp160 protein in target CD cells. Therefore, silencing the expression of PC7 would lead to the inhibition of the activation of gp160.
摘要翻译：本发明涉及从大鼠中分离的枯草杆菌蛋白酶-Kexin家族的新颖和第七个成员，其被命名为rPC7。大鼠脾脏cDNA已经完全测序。人类已经获得了较短的DNA序列，其对应于对应于大鼠前体激素转化酶的人类前体激素转化酶的一部分催化区域。 PC7明显区别于枯草杆菌蛋白酶-Kexin家族的其他哺乳动物成员。其组织分布普遍存在，但其淋巴组织中的存在特别显着。它存在于能够将HIV gp160蛋白切割成活性gp120 / gp41蛋白质的LoVo细胞中，并且缺乏其他已知的有效的促激素转化酶。建议PC7作为成熟酶的良好候选物，其负责转染靶向CD <+4>细胞中的HIV gp160蛋白质。因此，沉默PC7的表达将导致抑制gp160的活化。

26. 发明申请

WO1996034966A2 ENGINEERING PROTEIN POSTTRANSLATIONAL MODIFICATION IN TRANSGENIC ORGANISMS 审中-公开
标题翻译：转基因生物工程蛋白质后处理改造
公开(公告)号：WO1996034966A2
公开(公告)日：1996-11-07
申请号：PCT/US1996006121
申请日：1996-05-06
申请人： AMERICAN RED CROSS
发明人： AMERICAN RED CROSS , LUBON, Henryk , DROHAN, William, N. , PALEYANDA, Rekha, K.
IPC分类号： C12N15/64
CPC分类号： A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/10 , A01K2227/105 , A01K2267/01 , A61K38/00 , C07K14/75 , C07K2319/00 , C07K2319/02 , C12N9/6454 , C12N9/6464 , C12N15/64 , C12N15/67 , C12N15/8216 , C12N15/8243 , C12N15/85 , C12N15/8509 , C12N2830/008 , C12N2830/85 , C12Y304/21069
摘要： The invention relates to transgenic non-human multicellular organisms that contain polynucleotides for expressing proteins that alter posttranslational modification. In particular, the invention provides multiply-transgenic animals in which a first transgene encodes a first protein, a second transgene encodes a second protein, and expression of the second protein affects the posttranslational modification of the first protein in cells of said organism. Expression in preferred embodiments is in specific cells and the modified protein is secreted into a bodily fluid. The invention provides related methods, proteins and products. An example provides transgenic animals that express human Protein C and the processing protease PACE/furin in mammary glands and secrete both proteins into milk.
摘要翻译：本发明涉及包含用于表达改变翻译后修饰的蛋白质的多核苷酸的转基因非人多细胞生物体。特别地，本发明提供了多转基因动物，其中第一转基因编码第一蛋白质，第二转基因编码第二蛋白质，第二蛋白质的表达影响所述生物细胞中第一蛋白质的翻译后修饰。优选实施方案中的表达在特定细胞中，并且所述修饰的蛋白质被分泌到体液中。本发明提供了相关方法，蛋白质和产物。一个实例提供表达人蛋白C的转基因动物和乳腺中加工蛋白酶PACE /弗林蛋白酶，并将两种蛋白质分泌到牛奶中。

27. 发明申请

WO1995002055A1 NOVEL PROTEIN INHIBITORS OF SERINE PROTEINASES (E.G. FURIN) DERIVED FROM TURKEY OVOMUCOID THIRD DOMAIN 审中-公开
标题翻译：来自土耳其OVOMUCOID第三领域的丝氨酸蛋白酶（E.G.FURIN）的新蛋白抑制剂
公开(公告)号：WO1995002055A1
公开(公告)日：1995-01-19
申请号：PCT/US1994007779
申请日：1994-07-08
申请人： LASKOWSKI, Michael , ANDERSON, Stephen
IPC分类号： C12N15/15
CPC分类号： C12N9/6454 , C07K14/8135 , C07K2319/00
摘要： Novel protein inhibitors of serine proteinases incorporating immediately adjacent to the inhibitor reactive site peptide bond a consensus sequence from substrates of a particular proteinase. The inhibitors include Kazal family inhibitors of subtilisin-like proteinases, and more particularly analogs of turkey ovomucoid third domain protein (6-56) such as A15R-T17K-L18R. The inhibitors inhibit the proteinase activity of enzymes such as human furin. There are further provided polynucleotides comprising one or more sequences of nucleotide bases collectively encoding the amino acid sequence of one of said turkey ovomucoid third domain peptide inhibitors; an expression vector comprising such a polynucleotide; an organism transformed with such an expression vector; and methods of synthesizing such an inhibitor and of inhibiting a serine proteinase.
摘要翻译：结合紧邻抑制剂反应位点肽的丝氨酸蛋白酶的新型蛋白质抑制剂从特定蛋白酶的底物键合共有序列。抑制剂包括枯草杆菌蛋白酶样蛋白酶的Kazal家族抑制剂，更特别是类似物的火鸡卵巢粘蛋白第三结构域蛋白（6-56）如A15R-T17K-L18R。抑制剂抑制酶如人弗林蛋白酶的蛋白酶活性。还提供了包含一个或多个核苷酸碱基序列的多核苷酸，其共同编码所述火鸡卵类粘蛋白第三结构域肽抑制剂之一的氨基酸序列; 包含这种多核苷酸的表达载体; 用这种表达载体转化的生物体; 以及合成这种抑制剂和抑制丝氨酸蛋白酶的方法。

28. 发明申请

WO1993011247A1 PROHORMONE CONVERTASE TRANSFORMED CELLS 审中-公开
标题翻译： PROHORMONE转换转化细胞
公开(公告)号：WO1993011247A1
公开(公告)日：1993-06-10
申请号：PCT/US1992010621
申请日：1992-12-04
申请人： GENENTECH, INC. , GORMAN, Cornelia, M. , GROSKREUTZ, Debyra, J. , MARRIOTT, David
发明人： GENENTECH, INC.
IPC分类号： C12N15/57
CPC分类号： C12N9/6424 , C07K14/475 , C07K14/48 , C07K14/62 , C07K14/64 , C07K2319/00 , C07K2319/02 , C07K2319/75 , C12N9/6454 , C12N15/62 , C12N15/85
摘要： Described is the production of mammalian cells expressing prohormone convertase which facilitates the processing of prohormone precursors to active hormones. Also described are variant prohormone convertases, and prohormones. The transformed cells of the present invention may be used in the synthesis of properly processed polypeptide hormones, and in cell culture to reduce dependence upon added hormones and required serum polypeptide factors.
摘要翻译：描述了表达激素转化酶的哺乳动物细胞的生产，其促进激素原体加工成活性激素。还描述了变体激素转化酶和激素。本发明的转化细胞可用于合成适当加工的多肽激素，以及在细胞培养中以减少对加入的激素和所需血清多肽因子的依赖性。

29. 发明申请

WO9106314A3 PHARMACEUTICAL COMPOSITION HAVING AN ENDOPROTEOLYTIC ACTIVITY; A PROCESS FOR ENDOPROTEOLYTICALLY PROCESSING (PRECURSOR) PROTEINS AND FOR THE (MICRO)BIOLOGICAL PRODUCTION OF PROTEINS 审中-公开
标题翻译：具有内分泌活性的药物组合物; 用于内切酶加工（前体）蛋白质和（微生物）生物学蛋白质的方法
公开(公告)号：WO9106314A3
公开(公告)日：1991-09-05
申请号：PCT/NL9000151
申请日：1990-10-12
申请人： HOLLAND BIOTECHNOLOGY
发明人： VAN DE VEN WILLEM JAN MARIE , VAN DEN OUWELAND ANNA MARIA WI , VAN DUIJNHOVEN JOHANNES LAMBER , ROEBROEK ANTONIUS JOHANNES MAR , KONING PIET NICO MARIA
IPC分类号： A01K67/027 , A61K38/00 , A61K38/46 , A61K38/48 , A61P35/00 , A61P43/00 , C07K14/755 , C07K14/82 , C07K16/32 , C07K16/40 , C12N5/10 , C12N9/48 , C12N9/62 , C12N9/64 , C12N15/09 , C12N15/62 , C12P7/64 , C12P21/02 , C12P21/06 , A61K37/547
CPC分类号： C12N9/6454 , A61K38/482 , C07K14/755 , C07K14/82 , C07K16/32 , C07K16/40 , C07K2319/00 , C07K2319/02 , C07K2319/23 , C07K2319/32 , C07K2319/50 , C07K2319/60 , C12N9/48 , C12N9/62 , C12N15/62 , C12P21/06
摘要： The invention is based on the finding that furin belongs to a family of endoproteolytically active enzymes and relates to a process for the in vitro cleavage of a protein by treating the protein in the presence of Ca2+ ions with furin or a furin-like enzyme, or an endoproteolytically active fragment, derivative or fusion protein of furin or furin-like enzyme. The invention can be used for the (micro)biological production of a protein by culturing genetically engineered cells expressing a proform of the protein as well as furin or a furin-like enzyme and isolating the protein formed. The invention also relates to a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers, diluents or adjuvants, as well as an endoproteolytically active amount of furin or a furin-like enzyme, or a fragment or derivative of furin or furin-like enzyme having an endoproteolytic activity.

30. 发明申请

WO2017007796A1 MULTISPECIFIC ANTIGEN-BINDING MOLECULES AND USES THEREOF 审中-公开
标题翻译：多重抗原结合分子及其用途
公开(公告)号：WO2017007796A1
公开(公告)日：2017-01-12
申请号：PCT/US2016/041055
申请日：2016-07-06
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： ANDREEV, Julian , THAMBI, Nithya , DELFINO, Frank , MARTIN, Joel , THURSTON, Gavin , CYGNAR, Katherine , PAPADOPOULOS, Nicholas
IPC分类号： C07K16/28 , C07K16/46 , C07K16/22 , C07K16/12 , C07K16/32 , C07K16/18 , C07K14/435 , A61K47/48
CPC分类号： A61K47/48569 , A61K47/6803 , A61K47/6849 , A61K47/6851 , A61K47/6855 , A61K47/6879 , A61K2039/507 , C07K14/4702 , C07K16/1203 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/2833 , C07K16/2866 , C07K16/2869 , C07K16/2896 , C07K16/30 , C07K16/32 , C07K2317/21 , C07K2317/31 , C07K2317/35 , C07K2317/76 , C07K2317/77 , C07K2319/00 , C07K2319/30 , C12N9/6454
摘要： The present disclosure provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present disclosure can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the disclosure, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present disclosure results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the disclosure, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present disclosure causes or facilitates the targeted killing of tumor cells.
摘要翻译：本公开提供多特异性抗原结合分子及其用途。多特异性抗原结合分子包含特异性结合靶分子的第一抗原结合结构域和特异性结合内在效应蛋白的第二抗原结合结构域。在一些实施方案中，本公开的多特异性抗原结合分子可以是能够结合靶分子和内化效应蛋白的双特异性抗体。在本公开的某些实施方案中，通过本公开的多特异性抗原结合分子同时结合靶分子和内化效应蛋白导致目标分子的活性比所述靶分子的结合更大程度地减弱靶分子单独。在本公开的其它实施方案中，靶分子是肿瘤相关抗原，并且本公开的多特异性抗原结合分子同时结合肿瘤相关抗原和内化效应蛋白导致或促进靶向杀伤肿瘤细胞。

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