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1. 发明公开

EP0862583A1 SPRAY-DRYING HAEMOGLOBIN 失效
标题翻译：血红蛋白喷雾干燥
公开(公告)号：EP0862583A1
公开(公告)日：1998-09-09
申请号：EP96932079.0
申请日：1996-09-10
申请人： STAAT DER NEDERLANDEN, DE MINISTER VAN DEFENSIE, voor deze: HET HOOFD VAN DE AFDELING MILITAIR GENEESKUNDIG BELEID , Bleeker, Willem Karel
发明人： TAHEY, Jeroen, Joost, Valentijn , HENS, Henri, Joseph, Hubert , BAKKER, Joachim, Cornelis , BIESSELS, Petrus, Theodurus, Maria , BLEEKER, Willem, Karel
IPC分类号： C07K14
CPC分类号： C07K14/805
摘要： The present invention relates to a method to obtain a dried haemoglobin product, that is stable during extended storage (over years) at ambient temperature (4-30 °C) and dissolves quickly (within 10 minutes, preferably within 5 minutes, more preferably within 1 minute), easily (without the use of special facilities) and completely (in a clear, dark red solution with minimal particulate contamination). The solution reconstituted from the dried haemoglobin has sufficient low levels of methaemoglobin to effectively function as an oxygen carring solution after reconstitution and upon parenteral administration to a patient. Besides the reconstituted product has a physiologically acceptable formulation (osmolarity: typically 250-350 mosm/1) and has colloid-osmotic activity. The drying process is applicable for haemoglobin, modified haemoglobin, recombinant haemoglobin and/or encapsulated haemoglobin preparations. The process to obtain the dried haemoglobin product is based on spray-granulation with addition of one or more protective additives. Besides, a carrier substance might be used to reduce particulate contamination. To prevent oxidation of haemoglobin, the process and storage can be performed under oxygen free conditions by the use of nitrogen or any other inert gas.

2. 发明申请

WO2008145140A2 TRANSGENIC ANIMALS PRODUCING MONOVALENT HUMAN ANTIBODIES AND ANTIBODIES OBTAINABLE FROM THESE ANIMALS 审中-公开
标题翻译：生产从这些动物获得的单一人类抗体和抗体的转基因动物
公开(公告)号：WO2008145140A2
公开(公告)日：2008-12-04
申请号：PCT/DK2008050127
申请日：2008-05-30
申请人： GENMAB AS , SCHUURMAN JANINE , VINK TOM , VAN DE WINKEL JAN , LABRIJN ARAN FRANK , PARREN PAUL , BLEEKER WILLEM KAREL , BEURSKENS FRANK , VAN BERKEL PATRICK
发明人： SCHUURMAN JANINE , VINK TOM , VAN DE WINKEL JAN , LABRIJN ARAN FRANK , PARREN PAUL , BLEEKER WILLEM KAREL , BEURSKENS FRANK , VAN BERKEL PATRICK
IPC分类号： C12N15/85 , C07K16/28
CPC分类号： C07K16/2887 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/283 , C07K16/2863 , C07K2317/21 , C07K2317/55 , C07K2317/732 , C07K2317/77 , C07K2317/90 , C12N15/8509 , C12N2740/16011
摘要： The invention relates to novel non-human transgenic animals, which upon antigenic stimulation are capable of producing monovalent antibodies binding to a selected antigen, modified heavy chain transgenes, methods for producing the non-human transgenic animals, methods for immunizing the non-human transgenic animals for as well as monovalent antibodies obtainable by such immunization methods.
摘要翻译：本发明涉及新型非人转基因动物，其在抗原刺激时能够产生结合选定抗原的单价抗体，修饰的重链转基因，用于产生非人转基因动物的方法，用于免疫非人转基因动物的方法动物以及通过这种免疫方法可获得的单价抗体。

3. 发明申请

WO2008145141A1 METHOD FOR EXTENDING THE HALF-LIFE OF EXOGENOUS OR ENDOGENOUS SOLUBLE MOLECULES 审中-公开
标题翻译：扩增异源或内源可溶性分子半衰期的方法
公开(公告)号：WO2008145141A1
公开(公告)日：2008-12-04
申请号：PCT/DK2008/050128
申请日：2008-05-30
申请人： GENMAB A/S , SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BEURSKENS, Frank , BLEEKER, Willem Karel , VAN BERKEL, Patrick
发明人： SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BEURSKENS, Frank , BLEEKER, Willem Karel , VAN BERKEL, Patrick
IPC分类号： C07K16/28
CPC分类号： C07K16/283 , C07K16/2812 , C07K16/2863 , C07K16/2887 , C07K2317/732
摘要： The present invention relates to methods for extending the in vivo half-life of an exogenous soluble therapeutic molecule administered to a subject, by administering to said subject the exogenous soluble molecule and a monovalent antibody that binds to the exogenous soluble molecule, as well as method for treating a disease or disorder associated with an insufficient level of an endogenous soluble molecule in a subject, by administering to said subject a monovalent antibody that binds to the endogenous soluble molecule.
摘要翻译：本发明涉及通过向所述受试者施用外源可溶性分子和结合外源可溶性分子的单价抗体以及方法，用于延长给予受试者的外源可溶性治疗分子的体内半衰期的方法，以及方法用于治疗与受试者内源性可溶性分子水平不足相关的疾病或病症，通过向所述受试者施用结合内源性可溶性分子的单价抗体。

4. 发明申请

WO2008145140A3 TRANSGENIC ANIMALS PRODUCING MONOVALENT HUMAN ANTIBODIES AND ANTIBODIES OBTAINABLE FROM THESE ANIMALS 审中-公开
公开(公告)号：WO2008145140A3
公开(公告)日：2008-12-04
申请号：PCT/DK2008/050127
申请日：2008-05-30
申请人： GENMAB A/S , SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BLEEKER, Willem Karel , BEURSKENS, Frank , VAN BERKEL, Patrick
发明人： SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BLEEKER, Willem Karel , BEURSKENS, Frank , VAN BERKEL, Patrick
IPC分类号： C12N15/85 , C07K16/28
摘要： The invention relates to novel non-human transgenic animals, which upon antigenic stimulation are capable of producing monovalent antibodies binding to a selected antigen, modified heavy chain transgenes, methods for producing the non-human transgenic animals, methods for immunizing the non-human transgenic animals for as well as monovalent antibodies obtainable by such immunization methods.

5. 发明申请

WO2008145139A1 FUSION OR LINKED PROTEINS WITH EXTENDED HALF LIFE 审中-公开
标题翻译：融合或连接的蛋白质与扩展的半衰期
公开(公告)号：WO2008145139A1
公开(公告)日：2008-12-04
申请号：PCT/DK2008/050126
申请日：2008-05-30
申请人： GENMAB A/S , SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BLEEKER, Willem Karel , BEURSKENS, Frank , VAN BERKEL, Patrick
发明人： SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BLEEKER, Willem Karel , BEURSKENS, Frank , VAN BERKEL, Patrick
IPC分类号： C07K16/28 , A61K47/48
CPC分类号： C07K16/28 , A61K47/6813 , A61K47/6849 , C07K16/283 , C07K16/2863 , C07K16/2887 , C07K2317/53 , C07K2317/732 , C07K2317/77 , C07K2319/33
摘要： The present invention provides fusion proteins comprising a first molecule, and a second molecule which is a monovalent immunoglobulin or a fragment of a monovalent immunoglobulin with a long half-life when administered in vivo, methods of making such fusion proteins, pharmaceutical compositions comprising such fusion proteins, and uses thereof.
摘要翻译：本发明提供包含第一分子和第二分子的融合蛋白，其是当体内施用时具有长半衰期的单价免疫球蛋白或单价免疫球蛋白的片段的第二分子，制备此类融合蛋白的方法，包含这种融合的药物组合物蛋白质及其用途。

6. 发明申请

WO2008145137A2 NON-GLYCOSYLATED MONOVALENT ANTIBODIES 审中-公开
标题翻译：非糖化单一抗体
公开(公告)号：WO2008145137A2
公开(公告)日：2008-12-04
申请号：PCT/DK2008/050124
申请日：2008-05-30
申请人： GENMAB A/S , SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BLEEKER, Willem Karel , VAN BERKEL, Patrick , BEURSKENS, Frank
发明人： SCHUURMAN, Janine , VINK, Tom , VAN DE WINKEL, Jan , LABRIJN, Aran Frank , PARREN, Paul , BLEEKER, Willem Karel , VAN BERKEL, Patrick , BEURSKENS, Frank
IPC分类号： C07K16/00
CPC分类号： C07K16/00 , C07K16/2812 , C07K16/283 , C07K16/2863 , C07K2317/21 , C07K2317/53 , C07K2317/55 , C07K2317/71 , C07K2317/732 , C07K2317/76 , C07K2317/77
摘要： The present invention provides non-glycosylated monovalent antibodies with a long half-life when administered in vivo, methods of making such monovalent antibodies, pharmaceutical compositions comprising such antibodies, and uses of the monovalent antibodies.
摘要翻译：本发明提供了在体内施用时具有长半衰期的非糖基化单价抗体，制备这种单价抗体的方法，包含此类抗体的药物组合物和单价抗体的用途。

7. 发明申请

WO1997010268A1 SPRAY-DRYING HAEMOGLOBIN 审中-公开
标题翻译：喷雾干燥HEMOGLOBIN
公开(公告)号：WO1997010268A1
公开(公告)日：1997-03-20
申请号：PCT/NL1996000355
申请日：1996-09-10
申请人： STICHTING CENTRAAL LABORATORIUM VAN DE BLOEDTRANSFUSIEDIENST VAN HET NEDERLANDSE RODE KRUIS , TAHEY, Jeroen, Joost, Valentijn , HENS, Henri, Joseph, Hubert , BAKKER, Joachim, Cornelis , BIESSELS, Petrus, Theodurus, Maria , BLEEKER, Willem, Karel
发明人： STICHTING CENTRAAL LABORATORIUM VAN DE BLOEDTRANSFUSIEDIENST VAN HET NEDERLANDSE RODE KRUIS
IPC分类号： C07K14/805
CPC分类号： C07K14/805
摘要： The present invention relates to a method to obtain a dried haemoglobin product, that is stable during extended storage (over years) at ambient temperature (4-30 DEG C) and dissolves quickly (within 10 minutes, preferably within 5 minutes, more preferably within 1 minute), easily (without the use of special facilities) and completely (in a clear, dark red solution with minimal particulate contamination). The solution reconstituted from the dried haemoglobin has sufficient low levels of methaemoglobin to effectively function as an oxygen carring solution after reconstitution and upon parenteral administration to a patient. Besides the reconstituted product has a physiologically acceptable formulation (osmolarity: typically 250-350 mosm/1) and has colloid-osmotic activity. The drying process is applicable for haemoglobin, modified haemoglobin, recombinant haemoglobin and/or encapsulated haemoglobin preparations. The process to obtain the dried haemoglobin product is based on spray-granulation with addition of one or more protective additives. Besides, a carrier substance might be used to reduce particulate contamination. To prevent oxidation of haemoglobin, the process and storage can be performed under oxygen free conditions by the use of nitrogen or any other inert gas.
摘要翻译：本发明涉及一种获得干燥血红蛋白产品的方法，其在环境温度（4-30℃）的延长储存（多年）内是稳定的，并快速溶解（在10分钟内，优选在5分钟内，更优选在 1分钟），容易（不使用特殊设施）和完全（在清洁，深红色溶液中，微粒污染最小）。从干燥的血红蛋白重建的溶液具有足够低水平的高铁血红蛋白，以便在重建后和向患者肠胃外给药时有效地起氧护甲溶液的作用。此外，重构产品具有生理可接受的制剂（渗透压：通常为250-350 mosm / l），并且具有胶体渗透活性。干燥过程适用于血红蛋白，修饰血红蛋白，重组血红蛋白和/或包封的血红蛋白制剂。获得干燥的血红蛋白产物的方法是基于喷雾造粒，加入一种或多种保护性添加剂。此外，可以使用载体物质来减少颗粒污染。为了防止血红蛋白的氧化，可以通过使用氮气或任何其它惰性气体在无氧条件下进行该过程和储存。

8. 发明申请

WO2009030239A1 NOVEL METHODS AND ANTIBODIES FOR TREATING CANCER 审中-公开
标题翻译：用于治疗癌症的新方法和抗体
公开(公告)号：WO2009030239A1
公开(公告)日：2009-03-12
申请号：PCT/DK2008/050220
申请日：2008-09-05
申请人： GENMAB A/S , VAN DE WINKEL, Jan , PARREN, Paul , BLEEKER, Willem, Karel , EDVARDSEN, Klaus , LAMMERTS VAN BUEREN, Jeroen , VALERIUS, Thomas , DECHANT, Michael , WEISNER, Wencke , BERGER, Sven
发明人： VAN DE WINKEL, Jan , PARREN, Paul , BLEEKER, Willem, Karel , EDVARDSEN, Klaus , LAMMERTS VAN BUEREN, Jeroen , VALERIUS, Thomas , DECHANT, Michael , WEISNER, Wencke , BERGER, Sven
IPC分类号： C07K16/28 , C07K16/32 , A61K39/395 , C07K16/46
CPC分类号： C07K16/40 , A61K2039/505 , A61K2039/507 , C07K16/2863 , C07K16/44 , C07K16/468 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/54 , C07K2317/565 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/92 , G01N33/573
摘要： The invention relates to novel methods for the treatment of tumors, comprising administration of a bispecific antibody or a combination of two or more non-cross-blocking antibodies that recognize the same target antigen or antigenic complex. In particular, the invention relates to a method for inducing complement-mediated cell killing in the treatment of a tumor, said method comprising combined administration, to a human being in need thereof, of a first antibody and a second antibody, wherein - said first antibody binds EGFR, - said second antibody binds EGFR, - said first and second antibody are non-cross-blocking, and - the dosage regimen is such that CDC is obtained at the tumor site.
摘要翻译：本发明涉及用于治疗肿瘤的新方法，包括施用双特异性抗体或两种或多种识别相同靶抗原或抗原复合物的非交叉阻断抗体的组合。特别地，本发明涉及一种诱导补体介导的细胞杀伤治疗肿瘤的方法，所述方法包括向有需要的人共同施用第一抗体和第二抗体，其中 - 所述第一抗体结合EGFR，所述第二抗体结合EGFR，所述第一抗体和第二抗体是非交叉阻断的，并且所述给药方案使得在肿瘤部位获得CDC。

9. 发明申请

WO2004056847A3 HUMAN MONOCLONAL ANTIBODIES TO EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) 审中-公开
标题翻译：人类生殖因子受体（EGFR）的单克隆抗体
公开(公告)号：WO2004056847A3
公开(公告)日：2005-06-16
申请号：PCT/US0340463
申请日：2003-12-16
申请人： GENMAB AS , VAN DE WINKEL JAN G J , VAN DIJK MARCUS ANTONIUS , HALK EDWARD , GERRITSEN ARNOUT F , PETERSEN JOERGEN , BAADSGAARD OLE , BLEEKER WILLEM KAREL , PARREN PAUL
发明人： VAN DE WINKEL JAN G J , VAN DIJK MARCUS ANTONIUS , HALK EDWARD , GERRITSEN ARNOUT F , PETERSEN JOERGEN , BAADSGAARD OLE , BLEEKER WILLEM KAREL , PARREN PAUL
IPC分类号： C07K16/28 , A61K39/395
CPC分类号： C07K16/2863 , A01K2217/05 , A01K2217/075 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2317/21 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , G01N33/56966
摘要： Isolated human monoclonal antibodies which specifically bind to human EGFR, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.
摘要翻译：公开了与人EGFR特异性结合的分离的人单克隆抗体以及相关的基于抗体的组合物和分子。人抗体可以通过经历V-D-J重组和同种型转换能够产生人单克隆抗体多重同种型的转染瘤或非人转基因动物例如转基因小鼠产生。还公开了包含人抗体，非人转基因动物和产生人抗体的杂交瘤的药物组合物，以及使用人抗体的治疗和诊断方法。

10. 发明申请

WO2004056847A2 HUMAN MONOCLONAL ANTIBODIES TO EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) 审中-公开
标题翻译：人类生殖因子受体（EGFR）的单克隆抗体
公开(公告)号：WO2004056847A2
公开(公告)日：2004-07-08
申请号：PCT/US2003/040463
申请日：2003-12-16
申请人： GENMAB A/S , MEDAREX, INC. , VAN DE WINKEL, Jan, G., J. , VAN DIJK, Marcus, Antonius , HALK, Edward , GERRITSEN, Arnout, F. , PETERSEN, Jørgen , BAADSGAARD, Ole , BLEEKER, Willem, Karel , PARREN, Paul
发明人： VAN DE WINKEL, Jan, G., J. , VAN DIJK, Marcus, Antonius , HALK, Edward , GERRITSEN, Arnout, F. , PETERSEN, Jørgen , BAADSGAARD, Ole , BLEEKER, Willem, Karel , PARREN, Paul
IPC分类号： C07K
CPC分类号： C07K16/2863 , A01K2217/05 , A01K2217/075 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2317/21 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , G01N33/56966
摘要： Isolated human monoclonal antibodies which specifically bind to human EGFR, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.
摘要翻译：公开了与人EGFR特异性结合的分离的人单克隆抗体以及相关的基于抗体的组合物和分子。人抗体可以通过经历V-D-J重组和同种型转换能够产生人单克隆抗体多重同种型的转染瘤或非人转基因动物例如转基因小鼠产生。还公开了包含人抗体，非人转基因动物和产生人抗体的杂交瘤的药物组合物，以及使用人抗体的治疗和诊断方法。

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