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1. 发明专利

SK279029B6 TISSUE ACTIVATOR OF PLASMINOGEN T-PA, METHOD FOR PRODUCING THE SAME AND PHARMACEUTICAL COMPOSITION CONTAINING SAME 未知
公开(公告)号：SK279029B6
公开(公告)日：1998-05-06
申请号：SK55890
申请日：1990-02-06
申请人： STERN ANNE , KOHNERT ULRICH , RUDOLPH RAINER , FISCHER STEPHAN , MARTIN ULRICH
发明人： STERN ANNE , KOHNERT ULRICH , RUDOLPH RAINER , FISCHER STEPHAN , MARTIN ULRICH
IPC分类号： C12N15/09 , A61K38/00 , A61K38/46 , A61K38/48 , A61K38/49 , A61P7/02 , C07K1/113 , C07K14/745 , C12N9/64 , C12N9/72 , C12N9/88 , C12N15/58
摘要： This patent describes a tissue activator of plasminogen t-PA which is not glycosylated and it is created by the chain of amino acids and which can be represented by the formula (I). This chain of amino acids is coded by the chain of DNA, the sequence of which can be represented by the formula (III). The above mentioned activator is the main compound of the pharmaceutical composition used for dissolution of blood coagulations.

2. 发明申请

WO1995025168A1 USE OF A RECOMBINANT INHIBITOR FROM ERYTHRINA CAFFRA FOR PURIFYING SERINE PROTEASES 审中-公开
标题翻译：重组缓蚀剂FROM丝氨酸蛋白酶的刺桐caffra清洁利用
公开(公告)号：WO1995025168A1
公开(公告)日：1995-09-21
申请号：PCT/EP1995000926
申请日：1995-03-13
申请人： BOEHRINGER MANNHEIM GMBH , KOHNERT, Ulrich , STERN, Anne , FISCHER, Stephan
发明人： BOEHRINGER MANNHEIM GMBH
IPC分类号： C12N15/15
CPC分类号： C12N9/6459 , C07K14/8114 , C12Y304/21069 , Y10S435/814 , Y10S435/815
摘要： In a process for purifying serine proteases from a protein mixture the serine protease is bonded to an immobilized polypeptide having the activity of a DE-3 inhibitor from Erythrina caffra, the unbonded portions are removed from the protein mixture, the serine protease is separated from the inhibitor, the immobilized inhibitor is separated from the soluble serine protease, and the serine protease is isolated. The process is characterized in that a polypeptide which is the product of a prokaryotic or eukaryotic expression of an exogenic nucleic acid is used as the polypeptide. This inhibitor is noted for its improved specific activity and is suitable in particular for purifying plasminogen activators, such as tissue plasminogen activators (t-PA and derivatives).
摘要翻译：一种用于通过丝氨酸蛋白酶结合到固定化的多肽，其具有从刺桐caffra抑制剂DE-3的活性，从蛋白质混合物中除去未结合的组分，从该抑制剂拆卸丝氨酸蛋白酶，和从可溶丝氨酸蛋白酶中分离固定抑制剂从蛋白质混合物中纯化丝氨酸蛋白酶处理并分离的丝氨酸蛋白酶，其特征在于，多肽被用作是外源核酸的原核或真核表达产物的多肽。这种抑制剂的特征在于增强的比活性和组织纤溶酶原活化剂特别是用于纤溶酶原激活剂的纯化是合适的（t-PA和衍生物）。

3. 发明申请

WO1991002798A2 t-PA MUTANT GK1L 审中-公开
公开(公告)号：WO1991002798A2
公开(公告)日：1991-03-07
申请号：PCT/EP1990001401
申请日：1990-08-22
申请人： BOEHRINGER MANNHEIM GMBH , WEIDLE, Ulrich , STERN, Anne
发明人： BOEHRINGER MANNHEIM GMBH
IPC分类号： C12N15/58
CPC分类号： C12N9/6459 , A61K38/00 , C12Y304/21069
摘要： Recombinant DNA which codes for a protein with the domains G, K1 and L of t-PA, in which the sequences coding for the domains K2 and F of the wild type t-PA gene or the sequences derived therefrom in the context of the genetic code are completely deleted in accordance with the exact exon/intron limits on the t-PA gene. Process for preparing said recombinant DNA. Vectors which contain said recombinant DNA as well as cells which are transformed with said vectors or said recombinant DNA. Protein with fibrinolytic properties by expression of a DNA sequence according to the invention in suitable host cells, which is composed of the amino acid sequences of the domains G, K1 and L of t-PA in this sequence and is possibly glycosylized. Process for preparing it. Fibrinolytic agent containing a protein according to the invention.
摘要翻译：编码具有t-PA结构域G，K1和L的蛋白质的重组DNA，其中编码野生型t-PA基因的结构域K2和F的序列或其在遗传背景下衍生的序列根据t-PA基因的确切外显子/内含子限制，代码完全被删除。制备所述重组DNA的方法。含有所述重组DNA的载体以及用所述载体或所述重组DNA转化的细胞。通过在合适的宿主细胞中表达根据本发明的DNA序列的纤维蛋白溶解性质的蛋白质，其由该序列中t-PA的结构域G，K1和L的结构域G，K1和L的氨基酸序列组成，并且可能被糖基化。准备过程含有本发明蛋白质的纤维蛋白溶解剂。

4. 发明申请

WO2005100402A1 ANTI-P-SELECTIN ANTIBODIES 审中-公开
标题翻译：抗P-选择素抗体
公开(公告)号：WO2005100402A1
公开(公告)日：2005-10-27
申请号：PCT/EP2005/003581
申请日：2005-04-05
申请人： F.HOFFMANN-LA ROCHE AG , GRAUS, Yvo , HIMBER, Jacques , JANSEN-MOLENAAR, Miranda , KLING, Dorothee , KOPETZKY, Erhard , PARREN, Paul , REBERS, Frank , STEINER, Beat , STERN, Anne , STREIN, Pamela , STUBENRAUCH, Kay-Gunnar , VAN DE WINKEL, Jan , VAN VUGT, Martine
发明人： GRAUS, Yvo , HIMBER, Jacques , JANSEN-MOLENAAR, Miranda , KLING, Dorothee , KOPETZKY, Erhard , PARREN, Paul , REBERS, Frank , STEINER, Beat , STERN, Anne , STREIN, Pamela , STUBENRAUCH, Kay-Gunnar , VAN DE WINKEL, Jan , VAN VUGT, Martine
IPC分类号： C07K16/28
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor Clq. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子Clq的抗P-选择蛋白抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

5. 发明申请

WO1996017928A1 USE OF THE PROTEASE DOMAIN OF HUMAN PLASMINOGEN ACTIVATOR FOR THE TREATMENT OF THROMBOEMBOLIC DISEASES 审中-公开
标题翻译：用于治疗血栓性脑病的人类促胰岛素激活剂的蛋白酶域的应用
公开(公告)号：WO1996017928A1
公开(公告)日：1996-06-13
申请号：PCT/EP1995004717
申请日：1995-11-30
申请人： BOEHRINGER MANNHEIM GMBH , KOHNERT, Ulrich , STERN, Anne , MARTIN, Ulrich , FISCHER, Stephan
发明人： BOEHRINGER MANNHEIM GMBH
IPC分类号： C12N09/72
CPC分类号： C12N9/6459 , A61K38/00 , C12Y304/21069
摘要： The invention relates to the use of thromboembolic proteins. These contain, as their only structural portion effecting thrombolytic activity, the protease domain of human tissue type plasminogen activator. These derivatives show reduced side effects, such as a reduction in bleeding, while demonstrating remarkable in vivo efficacy. The effect is surprising, given their in vitro properties.
摘要翻译：本发明涉及血栓栓塞蛋白的用途。它们作为其影响溶栓活性的唯一结构部分含有人组织型纤溶酶原激活物的蛋白酶结构域。这些衍生物显示降低的副作用，例如出血减少，同时显示出显着的体内功效。鉴于其体外性质，效果令人惊讶。

6. 发明申请

WO1990009437A1 TISSUE PLASMINOGENE ACTIVATOR DERIVATIVE 审中-公开
标题翻译：组织等离子体激活剂衍生物
公开(公告)号：WO1990009437A1
公开(公告)日：1990-08-23
申请号：PCT/EP1990000194
申请日：1990-02-06
申请人： BOEHRINGER MANNHEIM GMBH , STERN, Anne , KOHNERT, Ulrich , RUDOLPH, Rainer , FISCHER, Stephan , MARTIN, Ulrich
发明人： BOEHRINGER MANNHEIM GMBH
IPC分类号： C12N09/64
CPC分类号： C12N9/6459 , A61K38/00 , C07K1/1133 , C12Y304/21069
摘要： A new tissue plasminogene activator (t-PA) derivative is not glycosylized and consists of the amino acid sequence (I). It is coded with the amino acid sequence (II) and possesses outstanding properties when used for dissolving blood clots.

7. 发明申请

WO2009046978A1 PROTEIN EXPRESSION FROM MULTIPLE NUCLEIC ACIDS 审中-公开
标题翻译：来自多种核酸的蛋白质表达
公开(公告)号：WO2009046978A1
公开(公告)日：2009-04-16
申请号：PCT/EP2008/008523
申请日：2008-10-09
申请人： F. HOFFMANN-LA ROCHE AG , GOEPFERT, Ulrich , KNOETGEN, Hendrik , KOPETZKI, Erhard , STERN, Anne
发明人： GOEPFERT, Ulrich , KNOETGEN, Hendrik , KOPETZKI, Erhard , STERN, Anne
IPC分类号： C12N15/69 , C12N15/85 , C07K16/00
CPC分类号： C12N15/85 , C07K16/18 , C07K16/28 , C07K16/2812 , C07K16/2854 , C07K16/2866 , C07K16/2896 , C07K2317/14 , C07K2317/21 , C07K2317/51 , C07K2317/515 , C12P21/00
摘要： The current invention reports a method for the recombinant production of a secreted heterologous immunoglobulin in a CHO cell comprising the following steps: i) providing a CHO cell, which is adapted to growth in suspension culture, adapted to growth in serum-free medium, mycoplasma free, and virus free, ii) providing a vector comprising a prokaryotic origin of replication, a first nucleic acid conferring resistance to a prokaryotic selection agent, a second nucleic acid encoding the heavy chain of said heterologous immunoglobulin, a third nucleic acid encoding the light chain of said heterologous immunoglobulin, a fourth nucleic acid conferring resistance to a eukaryotic selection agent, iii) transfecting said CHO cell, wherein said transfecting comprises a) transfecting said CHO cell with said vector comprising a fourth nucleic acid conferring resistance to a first eukaryotic selection agent, b) selecting a CHO cell by growth in cultivation medium containing said first eukaryotic selection agent, c) transfecting said selected CHO cell with said vector comprising a fourth nucleic acid conferring resistance to a second eukaryotic selection agent different to said first eukaryotic selection agent, d) selecting a CHO cell by selected growth in cultivation medium containing said first and said second eukaryotic selection agent, iv) cultivating said transfected CHO cell in a medium in the presence of said first and second eukaryotic selection agent, under conditions suitable for the expression of said second, and third nucleic acid, and v) recovering said secreted heterologous immunoglobulin from the cultivation medium.
摘要翻译：本发明报告了在CHO细胞中重组产生分泌的异源免疫球蛋白的方法，其包括以下步骤：i）提供适于在悬浮培养物中生长的CHO细胞，适于在无血清培养基中生长，支原体免费和无病毒，ii）提供包含原核复制起点的载体，赋予原核选择剂抗性的第一核酸，编码所述异源免疫球蛋白的重链的第二核酸，编码光的第三核酸所述异源免疫球蛋白链，赋予对真核选择剂的抗性的第四核酸，iii）转染所述CHO细胞，其中所述转染包括a）用包含第四核酸的所述载体转染所述CHO细胞，赋予对第一真核选择性的抗性试剂，b）通过在含有所述第一种真核生物的培养基中生长来选择CHO细胞 c）用所述载体转染所述选择的CHO细胞，所述载体包含赋予与所述第一真核选择试剂不同的第二真核选择剂的抗性的第四核酸，d）通过在含有所述第一和第二真核选择试剂的培养基中选择生长来选择CHO细胞，所述第二真核选择剂，iv）在所述第一和第二真核选择剂的存在下，在适于表达所述第二和第三核酸的条件下，在培养基中培养所述转染的CHO细胞，和v）回收所述分泌的异源免疫球蛋白。

8. 发明申请

WO9905264A3 PRODUCTION OF HUMAN MUTANT PROTEINS IN HUMAN CELLS BY HOMOLOGOUS RECOMBINATION 审中-公开
标题翻译：通过同源重组MAKING在人类细胞中的人突变蛋白
公开(公告)号：WO9905264A3
公开(公告)日：1999-04-22
申请号：PCT/EP9804583
申请日：1998-07-22
申请人： ROCHE DIAGNOSTICS GMBH , STERN ANNE , HONOLD KONRAD
发明人： STERN ANNE , HONOLD KONRAD
IPC分类号： C12N15/09 , A61K38/00 , A61K38/49 , C12N5/10 , C12N9/04 , C12N9/72 , C12N15/10 , C12N15/90
CPC分类号： C12N15/102 , A61K38/00 , C12N15/902
摘要： A process is disclosed for producing mutant proteins of eukaryotic polypeptides in eukaryotic cells by homologous recombination. Also disclosed is a process for producing human cells suitable for producing human mutant proteins. Finally, the invention concerns the human cells produced by this process and the mutant human proteins obtained therefrom, as well as pharmaceutical compositions containing these mutant proteins.
摘要翻译：本发明涉及一种用于通过同源重组生产在真核细胞真核多肽，突变蛋白的方法。此外，本发明涉及一种用于生产适合于生产人类突变蛋白人细胞的方法。最后，本发明涉及通过所述方法和由其获得突变的人蛋白质，以及含有这些突变蛋白的药物制剂生产的人细胞。

9. 发明申请

WO1996001312A1 NON-GLYCOSYLATED PLASMINOGEN ACTIVATOR DERIVATIVES AND THEIR USE IN CONDITIONS INVOLVING A HIGH RISK OF BLEEDING 审中-公开
标题翻译：非糖基化蛋白溶酶原衍生物及其出血风险增加
公开(公告)号：WO1996001312A1
公开(公告)日：1996-01-18
申请号：PCT/EP1995002391
申请日：1995-06-20
申请人： BOEHRINGER MANNHEIM GMBH , KOHNERT, Ulrich , STERN, Anne , MARTIN, Ulrich , FISCHER, Stephan
发明人： BOEHRINGER MANNHEIM GMBH
IPC分类号： C12N09/64
CPC分类号： C12N9/6459 , A61K38/00 , C12Y304/21069
摘要： The invention concerns a non-glycosylated tissue plasminogen activator derivative which contains the essential parts of at least one Kringle domain and a B-chain with serine protease activity of the tissue plasminogen activator and which is characterized in that each of the amino-acids 296 to 299 (Lys-His-Arg-Arg) is replaced by alanine. Owing to the low risk of bleeding associated with its use, this derivative is particularly suitable for use in the treatment of subchronic thromboembolic disorders.
摘要翻译：其含有至少一个三环域和所述主要部分与组织纤溶酶原激活的丝氨酸蛋白酶活性的B链和非糖基化的组织纤溶酶原激活衍生物的特征在于，在针对每一种情况下的氨基酸296-299（赖氨酸组氨酸 - 精氨酸 - 精氨酸）丙氨酸被替换，由于出血的风险低是特别适用于亚慢性血栓栓塞性病症的治疗。

10. 发明申请

WO1996031606A1 MUTANT OF THE ERYTHRINA CAFFRA TYPE INHIBITOR AND THE USE OF THE SAID MUTANT FOR PURIFYING SERIN PROTEASES 审中-公开
标题翻译：刺桐caffra型抑制剂的突变体及其使用丝氨酸蛋白酶的清洁
公开(公告)号：WO1996031606A1
公开(公告)日：1996-10-10
申请号：PCT/EP1996001388
申请日：1996-03-29
申请人： BOEHRINGER MANNHEIM GMBH , KOHNERT, Ulrich , STERN, Anne , WOZNY, Manfred , FISCHER, Stephan
发明人： BOEHRINGER MANNHEIM GMBH
IPC分类号： C12N15/15
CPC分类号： C12N9/6459 , C07K14/8114 , C12Y304/21069
摘要： The invention concerns a polypeptide which has the activity of an inhibitor DE-3 from Erythrina caffra and reversibly and selectively binds serin proteases from a protein mixture, obtained by culturing prokaryotic or eukaryotic host cells transformed or transfected with a nucleic acid which codes for the polypeptide in question in such a way that the host cells, under favourable nutrient conditions, can express the polypeptide. The invention also concerns the isolation of the polypeptide. The polypeptide is characterised by having an amino acid sequence which is functionally analogous to SEQ ID NO:2, is in one region over 85 % homologous with the region of amino acids 39-139 of that sequence, has two disulphide bridges and begins N-terminally with SEQ ID NO:4 or with a SEQ ID NO:4 extended N terminally by methionin, has a binding capacity for tissue plasminogen activators of 1.25 MU/ml or more. The polypeptide in question is especially suitable for use in purifying plasminogen activators such as tissue plasminogen activators (t-PA and derivatives).
摘要翻译：其具有从刺桐caffra抑制剂DE-3的活性和可逆地和选择性的丝氨酸蛋白酶的多肽从蛋白质混合物通过对所述的方式多肽培养用一种核酸转化的编码原核或真核宿主细胞结合，或被转染，其允许宿主细胞以表达合适的营养条件下，所述多肽和分离所述多肽，其特征在于，所述多肽具有的氨基酸序列，其是功能上类似于SEQ ID NO：2，在超过的部分区域 85％的同源性的氨基酸这个序列的39-139的区域中，具有两个二硫键和N端与SEQ ID NO：4或具有甲硫氨酸N-末端延伸SEQ ID NO：4点的开始和1.25 MU的组织型纤溶酶原激活剂的结合能力 / ml和具有更多的，特别是用于清洁v 合适的纤溶酶原活化剂，如组织纤维蛋白溶酶原活化剂（t-PA和衍生物）。

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