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公开(公告)号：US20130023447A1
公开(公告)日：2013-01-24
申请号：US13617778
申请日：2012-09-14
Applicant: Jesper KASTRUP , Lars S. Nielsen , Per-Johan Meijer
Inventor： Jesper KASTRUP , Lars S. Nielsen , Per-Johan Meijer
CPC classification number: C12N15/1093 , C07K16/005 , C07K16/1282 , C07K16/2863 , C07K2317/24 , C07K2317/73
Abstract: The invention relates to a procedure for linking cognate pairs of VH and VL encoding sequences from a population of cells enriched in particular surface antigen markers. The linking procedure involves a multiplex molecular amplification procedure capable of linking nucleotide sequences of interest in connection with the amplification, in particular polymerase chain reaction (multiplex PCR). The method is particularly advantageous for the generation of cognate pair libraries as well as combinatorial libraries of variable region encoding sequences from immunoglobulins. The invention also relates to methods for generation of chimeric human/non-human antibodies and expression libraries generated by such methods.
Abstract translation: 本发明涉及从富集特定表面抗原标记的细胞群中连接VH和VL编码序列的同源对的方法。 连接方法涉及能够连接与扩增有关的核苷酸序列的多重分子扩增方法，特别是聚合酶链式反应（多重PCR）。 该方法特别有利于产生同源对文库以及来自免疫球蛋白的可变区编码序列的组合文库。 本发明还涉及用于产生嵌合人/非人抗体的方法和通过这些方法产生的表达文库。
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公开(公告)号：US08283294B2
公开(公告)日：2012-10-09
申请号：US12074066
申请日：2008-02-29
Applicant: Jesper Kastrup , Lars S. Nielsen , Per-Johan Meijer
Inventor： Jesper Kastrup , Lars S. Nielsen , Per-Johan Meijer
CPC classification number: C12N15/1093 , C07K16/005 , C07K16/1282 , C07K16/2863 , C07K2317/24 , C07K2317/73
Abstract: The invention relates to a procedure for linking cognate pairs of VH and VL encoding sequences from a population of cells enriched in particular surface antigen markers. The linking procedure involves a multiplex molecular amplification procedure capable of linking nucleotide sequences of interest in connection with the amplification, in particular polymerase chain reaction (multiplex PCR). The method is particularly advantageous for the generation of cognate pair libraries as well as combinatorial libraries of variable region encoding sequences from immunoglobulins. The invention also relates to methods for generation of chimeric human/non-human antibodies and expression libraries generated by such methods.
Abstract translation: 本发明涉及从富集特定表面抗原标记的细胞群中连接VH和VL编码序列的同源对的方法。 连接方法涉及能够连接与扩增有关的核苷酸序列的多重分子扩增方法，特别是聚合酶链式反应（多重PCR）。 该方法特别有利于产生同源对文库以及来自免疫球蛋白的可变区编码序列的组合文库。 本发明还涉及用于产生嵌合人/非人抗体的方法和通过这些方法产生的表达文库。
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公开(公告)号：US20080227660A1
公开(公告)日：2008-09-18
申请号：US12074066
申请日：2008-02-29
Applicant: Jesper Kastrup , Lars S. Nielsen , Per-Johan Meijer
Inventor： Jesper Kastrup , Lars S. Nielsen , Per-Johan Meijer
CPC classification number: C12N15/1093 , C07K16/005 , C07K16/1282 , C07K16/2863 , C07K2317/24 , C07K2317/73
Abstract: The invention relates to a procedure for linking cognate pairs of VH and VL encoding sequences from a population of cells enriched in particular surface antigen markers. The linking procedure involves a multiplex molecular amplification procedure capable of linking nucleotide sequences of interest in connection with the amplification, in particular polymerase chain reaction (multiplex PCR). The method is particularly advantageous for the generation of cognate pair libraries as well as combinatorial libraries of variable region encoding sequences from immunoglobulins. The invention also relates to methods for generation of chimeric human/non-human antibodies and expression libraries generated by such methods.
Abstract translation: 本发明涉及从富集特定表面抗原标记的细胞群中连接编码序列的同源对的步骤。 连接方法涉及能够连接与扩增有关的核苷酸序列的多重分子扩增方法，特别是聚合酶链式反应（多重PCR）。 该方法特别有利于产生同源对文库以及来自免疫球蛋白的可变区编码序列的组合文库。 本发明还涉及用于产生嵌合人/非人抗体的方法和通过这些方法产生的表达文库。
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公开(公告)号：US07887805B2
公开(公告)日：2011-02-15
申请号：US12074056
申请日：2008-02-29
Applicant: Mikkel Wandahl Pedersen , Lucilla Steinaa , Allan Jensen , Klaus Koefoed , Per-Johan Meijer , Robert Carlsson , Charles Pyke , Lars S. Nielsen
Inventor： Mikkel Wandahl Pedersen , Lucilla Steinaa , Allan Jensen , Klaus Koefoed , Per-Johan Meijer , Robert Carlsson , Charles Pyke , Lars S. Nielsen
IPC: A61K39/395 , C07K14/71 , C12N15/13
CPC classification number: C07K16/2863 , A61K39/39558 , A61K2039/507 , C07K14/71 , C07K2317/31 , C07K2317/54 , C07K2317/565 , C07K2317/92 , A61K2300/00
Abstract: The invention relates to the field of recombinant antibodies for use in human cancer therapy. More specifically the invention provides compositions or mixtures of antibodies capable of binding human EGFR. Antibody compositions with 3 or more antibodies showed synergy in reduction of proliferation of representative cancer cell lines. Advantageous results have also been obtained with a composition comprising two different chimeric anti-hEGFR antibodies which show a new mechanism of action based on rapid and efficient receptor internalisation, induction of terminal differentiation and subsequent tumour eradication in an animal model. The antibodies of the invention can be manufactured in one bioreactor as a polyclonal antibody.
Abstract translation: 本发明涉及用于人类癌症治疗的重组抗体领域。 更具体地，本发明提供能够结合人EGFR的抗体的组合物或混合物。 具有3种或更多种抗体的抗体组合物在代表性癌细胞系的增殖减少方面表现出协同作用。 使用包含两种不同的嵌合抗hEGFR抗体的组合物也获得了有利的结果，其显示出基于动物模型中快速且有效的受体内化，诱导终末分化和随后的肿瘤根除的新作用机制。 本发明的抗体可以作为多克隆抗体在一个生物反应器中制造。
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公开(公告)号：US06271352B1
公开(公告)日：2001-08-07
申请号：US08466965
申请日：1995-06-06
Applicant: Lars S. Nielsen , Peter Andreasen , Keld Dano , Nils Brunner
Inventor： Lars S. Nielsen , Peter Andreasen , Keld Dano , Nils Brunner
IPC: C07K100
CPC classification number: C07K16/38 , C07K14/8132 , G01N33/577 , G01N33/86 , G01N2333/8132
Abstract: a monoclonal antibody which binds a human endothelial type plasminogen activator inhibitor (PAI-1) produced by dexamethasone-treated human HT-1080 fibrosarcoma cells may be used, inter alia, for determining PAI-1 protein abundance in tumor tissue or a sample of a body fluid. Measurements of this parameter may be useful in predicting the presence or metastasis of a tumor, or of predicting the progression of a known malignant tumor.
Abstract translation: 可以使用结合由地塞米松处理的人HT-1080纤维肉瘤细胞产生的人内皮型纤溶酶原激活物抑制剂（PAI-1）的单克隆抗体，尤其用于测定肿瘤组织中的PAI-1蛋白丰度或 体液。 该参数的测量可用于预测肿瘤的存在或转移，或预测已知恶性肿瘤的进展。
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Patent Agency Ranking
公开(公告)号：US20100310558A1
公开(公告)日：2010-12-09
申请号：US12788202
申请日：2010-05-26
Applicant: Martin B. OLEKSIEWICZ , Lars S. Nielsen , Peter S. Andersen , Margit H. Hansen
Inventor： Martin B. OLEKSIEWICZ , Lars S. Nielsen , Peter S. Andersen , Margit H. Hansen
IPC: A61K39/395 , C40B40/02 , C40B40/10 , C40B50/06 , C07K16/00
CPC classification number: C07K16/00 , C07K16/005 , C07K16/1282 , C07K2317/21 , C07K2317/55 , C12N15/1093 , C12N15/1096 , C40B40/08
Abstract: Multiplex overlap-extension RT-PCR provides an efficient method of linking two or more nucleotide sequences encoding for domains or subunits of a heteromeric protein, in a single reaction. Especially, the linkage of variable region encoding sequences from e.g. immunoglobulins, T cell receptors or B cell receptors is eased with the method of the present invention. This allows for a more efficient way of generating libraries of variable region encoding sequences. The capability to perform the multiplex overlap-extension RT-PCR using template derived from an isolated single cell enables the generation of cognate pair libraries in a high-throughput format.
Abstract translation: 多重重叠延伸RT-PCR提供了在单个反应中连接编码异聚蛋白的结构域或亚单位的两个或多个核苷酸序列的有效方法。 特别地，可变区编码序列的连接。 免疫球蛋白，T细胞受体或B细胞受体通过本发明的方法得以缓解。 这允许生成可变区编码序列库的更有效的方式。 使用衍生自孤立的单个细胞的模板进行多重重叠延伸RT-PCR的能力使得能够以高通量格式生成同源对文库。
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公开(公告)号：US20090137003A1
公开(公告)日：2009-05-28
申请号：US12230885
申请日：2008-09-05
Applicant: Anne B. Tolstrup , Johan Lantto , Finn C. Wiberg , Lars S. Nielsen
Inventor： Anne B. Tolstrup , Johan Lantto , Finn C. Wiberg , Lars S. Nielsen
CPC classification number: C07K16/1027 , A61K2039/505 , A61K2039/507 , C07K2317/21 , C07K2317/34 , C07K2317/76
Abstract: The invention relates to a method for manufacturing recombinant anti-RSV antibodies and antibody compositions. The method comprises obtaining a collection of cells transfected with a collection of variant nucleic acid sequences, wherein each cell in the collection is transfected with and capable of expressing one distinct anti-RSV antibody. The cells are cultured under suitable conditions for expression of the anti-RSV antibody/antibodies. The nucleic acid sequence is introduced into the cells by transfection with expression vectors, which avoid site-specific integration. The present method is suitable for manufacturing recombinant mono- and polyclonal anti-RSV antibodies for therapeutic uses.
Abstract translation: 本发明涉及一种制备重组抗RSV抗体和抗体组合物的方法。 该方法包括获得用变体核酸序列的集合转染的细胞的集合，其中集合中的每个细胞被转染并能够表达一种不同的抗RSV抗体。 在合适的条件下培养细胞以表达抗RSV抗体/抗体。 通过用表达载体转染将核酸序列引入细胞，这避免了位点特异性整合。 本发明的方法适用于制备用于治疗用途的重组单克隆抗体和多克隆抗RSV抗体。
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8.发明授权Plasminogen activator inhibitor monoclonal antibodies, hybridomas, monoclonal antibody production and use of the antibodies for assay of the inhibitors 失效纤溶酶原激活物抑制剂单克隆抗体，杂交瘤，单克隆抗体的产生和抗体用于测定抑制剂
公开(公告)号：US5422245A
公开(公告)日：1995-06-06
申请号：US900364
申请日：1992-06-18
Applicant: Lars S. Nielsen , Peter A. Andreasen , Keld Dano
Inventor： Lars S. Nielsen , Peter A. Andreasen , Keld Dano
IPC: C07K14/81 , C07K16/38 , G01N33/577 , G01N33/86 , G01N33/573
CPC classification number: C07K16/38 , C07K14/8132 , G01N33/577 , G01N33/86 , G01N2333/8132 , Y10S435/96
Abstract: In a method of producing monoclonal antibodies against endothelial type plasminogen activator inhibitor and immunologically similar inhibitors myeloma cells are fused with antibody-producing cells obtained from mammals which have been immunized with said plasminogen activator inhibitor or with antibody-producing cells, which in vitro have been immunized with said plasminogen activator inhibitor and the hybridomas producing antibodies against the above mentioned inhibitor are selected. The antibody-producing cells are preferably spleen cells or lymph node cells, most preferably spleen cells, obtained from mice immunized with the above mentioned inhibitor. The monoclonal antibodies against endothelial type plasminogen activator inhibitor can be used for purification of plasminogen activator inhibitor, for removal of plasminogen activator inhibitor, from body fluids and other biological materials, for neutralization of the inhibitory activity of the plasminogen activator inhibitor and for detection, identification, immunostaining and quantification, e.g. by the ELISA technique, of plasminogen activator inhibitor in body fluids, normal or malignant cells and tissues, and other biological materials. Furthermore, as some of the monoclonal antibodies obtained bound complexes of urikinase type plasminogen activator with endothelial type inhibitor while others did not, the monoclonal antibodies obtained can be used for the quantification of free versus complex-bound inhibitor.
Abstract translation: 在产生针对内皮型纤溶酶原激活物抑制剂和免疫相似抑制剂的单克隆抗体的方法中，骨髓瘤细胞与已经用所述纤溶酶原激活物抑制剂或抗体产生细胞免疫的哺乳动物获得的抗体产生细胞融合，所述细胞体外已被 选择用所述纤溶酶原激活物抑制剂免疫并产生针对上述抑制剂的抗体的杂交瘤。 抗体产生细胞优选是从用上述抑制剂免疫的小鼠获得的脾细胞或淋巴结细胞，最优选脾细胞。 针对内皮型纤溶酶原激活物抑制剂的单克隆抗体可用于从体液和其他生物材料中纯化用于去除纤溶酶原激活物抑制剂的纤溶酶原激活物抑制剂，用于中和纤溶酶原激活物抑制剂的抑制活性和检测，鉴定 ，免疫染色和定量，例如 通过ELISA技术，体液，正常或恶性细胞和组织中的纤溶酶原激活物抑制剂等生物材料。 此外，由于一些单克隆抗体获得了结合尿激酶型纤溶酶原激活物与内皮型抑制剂的复合物，而其他单克隆抗体则没有获得单克隆抗体，可用于定量游离与复合结合的抑制剂。
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公开(公告)号：US20120009623A1
公开(公告)日：2012-01-12
申请号：US13243768
申请日：2011-09-23
Applicant: Anne B. Tolstrup , Johan Lantto , Finn C. Wiberg , Lars S. Nielsen
Inventor： Anne B. Tolstrup , Johan Lantto , Finn C. Wiberg , Lars S. Nielsen
CPC classification number: C07K16/1027 , A61K2039/505 , A61K2039/507 , C07K2317/21 , C07K2317/34 , C07K2317/76
Abstract: The invention relates to a method for manufacturing recombinant anti-RSV antibodies and antibody compositions. The method comprises obtaining a collection of cells transfected with a collection of variant nucleic acid sequences, wherein each cell in the collection is transfected with and capable of expressing one distinct anti-RSV antibody. The cells are cultured under suitable conditions for expression of the anti-RSV antibody/antibodies. The nucleic acid sequence is introduced into the cells by transfection with expression vectors, which avoid site-specific integration. The present method is suitable for manufacturing recombinant mono- and polyclonal anti-RSV antibodies for therapeutic uses.
Abstract translation: 本发明涉及一种制备重组抗RSV抗体和抗体组合物的方法。 该方法包括获得用变体核酸序列的集合转染的细胞的集合，其中集合中的每个细胞被转染并能够表达一种不同的抗RSV抗体。 在合适的条件下培养细胞以表达抗RSV抗体/抗体。 通过用表达载体转染将核酸序列引入细胞，这避免了位点特异性整合。 本发明的方法适用于制备用于治疗用途的重组单克隆抗体和多克隆抗RSV抗体。
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公开(公告)号：US07749697B2
公开(公告)日：2010-07-06
申请号：US10572431
申请日：2004-09-17
Applicant: Martin B. Oleksiewicz , Lars S. Nielsen , Peter S. Andersen , Margit H. Hansen
Inventor： Martin B. Oleksiewicz , Lars S. Nielsen , Peter S. Andersen , Margit H. Hansen
CPC classification number: C07K16/00 , C07K16/005 , C07K16/1282 , C07K2317/21 , C07K2317/55 , C12N15/1093 , C12N15/1096 , C40B40/08
Abstract: Multiplex overlap-extension RT-PCR provides an efficient method of linking two or more nucleotide sequences encoding for domains or subunits of a heteromeric protein, in a single reaction. Especially, the linkage of variable region encoding sequences from e.g. immunoglobulins, T cell receptors or B cell receptors is eased with the method of the present invention. This allows for a more efficient way of generating libraries of variable region encoding sequences. The capability to perform the multiplex overlap-extension RT-PCR using template derived from an isolated single cell enables the generation of cognate pair libraries in a high-throughput format.
Abstract translation: 多重重叠延伸RT-PCR提供了在单个反应中连接编码异聚蛋白的结构域或亚单位的两个或多个核苷酸序列的有效方法。 特别地，可变区编码序列的连接。 免疫球蛋白，T细胞受体或B细胞受体通过本发明的方法得以缓解。 这允许生成可变区编码序列库的更有效的方式。 使用衍生自孤立的单个细胞的模板进行多重重叠延伸RT-PCR的能力使得能够以高通量格式生成同源对文库。
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