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1. 发明申请

WO2004009618A3 RECOMBINANT PRODUCTION OF MIXTURES OF ANTIBODIES 审中-公开
标题翻译：重组抗生素混合物的生产
公开(公告)号：WO2004009618A3
公开(公告)日：2004-11-04
申请号：PCT/EP0307690
申请日：2003-07-15
申请人： CRUCELL HOLLAND BV , VAN BERKEL PATRICK HENDRIKUS C , BRUS RONALD HENDRIK PETER , BOUT ABRAHAM , LOGTENBERG TON
发明人： VAN BERKEL PATRICK HENDRIKUS C , BRUS RONALD HENDRIK PETER , BOUT ABRAHAM , LOGTENBERG TON
IPC分类号： A61K39/00 , C07K14/00 , C07K16/00 , C07K16/10 , C07K16/28 , C07K16/30 , C07K16/32 , C12N15/00 , C12P21/02
CPC分类号： C12P21/005 , A61K39/39558 , C07K16/00 , C07K16/10 , C07K16/2803 , C07K16/2833 , C07K16/2851 , C07K16/2896 , C07K16/30 , C07K16/32 , C07K2317/12 , C07K2317/21 , C07K2317/31 , C07K2317/50 , C07K2317/51 , C07K2317/56 , C07K2317/622 , C07K2317/626 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2319/30 , Y02P20/582
摘要： The invention provides methods for producing mixtures of antibodies from a single host cell clone. Thereto a nucleic acid sequence encoding a light chain, and nucleic acid sequences encoding different heavy chains are expressed in a recombinant host cell. The antibodies in the mixtures according to the invention suitably comprise identical light chains paired to different heavy chains capable of pairing to the light chain, thereby forming functional antigen binding domains. Mixtures of antibodies are also provided by the invention. Such mixtures can be used in a variety of fields.
摘要翻译：本发明提供从单个宿主细胞克隆产生抗体混合物的方法。其中编码轻链的核酸序列和编码不同重链的核酸序列在重组宿主细胞中表达。根据本发明的混合物中的抗体合适地包含与能够与轻链配对的不同重链配对的相同的轻链，由此形成功能性抗原结合结构域。抗体的混合物也由本发明提供。这种混合物可用于各种领域。

2. 发明申请

WO0218948A3 DIFFERENTIALLY EXPRESSED EPITOPES AND USES THEREOF 审中-公开
标题翻译：差异显着的外膜及其用途
公开(公告)号：WO0218948A3
公开(公告)日：2003-08-28
申请号：PCT/NL0100636
申请日：2001-08-27
申请人： CRUCELL HOLLAND BV , LOGTENBERG TON , CILENTI LUCIA , BLOEM ANDRIES CHRISTIAAN , ZWIJSSEN RENATE MARIE LOUISE
发明人： LOGTENBERG TON , CILENTI LUCIA , BLOEM ANDRIES CHRISTIAAN , ZWIJSSEN RENATE MARIE LOUISE
IPC分类号： A01K67/027 , A61K39/395 , A61K47/48 , A61P35/00 , C07K14/705 , C07K16/28 , C07K19/00 , C12N5/04 , C12N5/06 , C12N5/08 , C12N5/10 , C12N15/10 , C12N15/13 , C12N15/85 , G01N33/50 , G01N33/577 , G01N33/68
CPC分类号： C07K16/2896 , A01K2217/05 , A61K2039/505 , C07K2317/21 , C07K2317/622
摘要： Provided are among others novel epitopes, methods for finding these epitopes and binding molecules capable of binding to said novel epitopes. In one aspect the invention provides a binding molecule capable of specifically binding to a preferably, post-translationally modified, disease associated molecular marker, associated with diseased cells, whereas said preferably post-translationally modified disease associated molecular marker is not associated with non-diseased cells. In a preferred aspect of the invention, said binding molecule recognizes an epitope present in a subset of CD46 proteins. Said binding molecule is capable of distinguishing between CD46 proteins belonging to the subset and CD46 proteins not belonging to the subset. The binding molecule is preferably an antibody. Medicaments and uses of binding molecules are provided.
摘要翻译：提供了新颖的表位，找到这些表位的方法和能够结合所述新表位的结合分子。在一个方面，本发明提供了能够特异性结合与患病细胞相关的优选，翻译后修饰的疾病相关分子标记的结合分子，而所述优选经翻译后修饰的疾病相关分子标记与非患病相关细胞。在本发明的优选方面，所述结合分子识别存在于CD46蛋白亚组中的表位。所述结合分子能够区分属于该亚型的CD46蛋白和不属于该亚型的CD46蛋白。结合分子优选为抗体。提供了结合分子的药物和用途。

3. 发明申请

WO0148485A9 SELECTING LIBRARY MEMBERS CAPABLE OF BINDING TO EPITOPES 审中-公开
标题翻译：选择能够与EPITOPES绑定的库成员
公开(公告)号：WO0148485A9
公开(公告)日：2002-09-06
申请号：PCT/NL0000941
申请日：2000-12-21
申请人： CRUCELL HOLLAND BV , LOGTENBERG TON
发明人： LOGTENBERG TON
IPC分类号： G01N33/53 , A61K38/00 , A61K39/395 , A61P35/00 , C07K1/14 , C07K16/00 , C07K16/28 , C07K16/30 , C12N15/09 , C12P21/08 , C12Q1/02 , G01N33/68
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/00 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/732 , C07K2317/734 , G01N33/6854 , G01N33/6857
摘要： The invention provides a method for selecting at least one member from a library of proteinaceous molecules comprising providing at least one cell and/or a functional equivalent thererof, with at least part of said library under conditions that allow binding of any such member to an epitope in and/or on said cells and/or said functional equivalent thereof, removing unbound proteinaceous molecules and selecting said at least one member, wherein said library comprises at least one mutant of a proteinaceous molecule capable of binding to said epitope.
摘要翻译：本发明提供了从蛋白质分子文库中选择至少一个成员的方法，包括提供至少一种细胞和/或其功能等价物，其中至少部分所述文库在允许任何这样的成员与表位结合的条件下在所述细胞和/或其所述功能等同物中和/或之上，去除未结合的蛋白质分子并选择所述至少一个成员，其中所述文库包含至少一个能够结合所述表位的蛋白质分子的突变体。

4. 发明申请

WO0148485A2 USE OF A NATIVE EPITOPE FOR SELECTING EVOLVED BINDING MEMBERS FROM A LIBRARY OF MUTANTS OF A PROTEIN CAPABLE OF BINDING TO SAID EPITOPE 审中-公开
标题翻译：用于选择具有结合蛋白质的蛋白质的图像的革兰氏结肠成员的本征抗原决定簇用于结合抗原决定簇
公开(公告)号：WO0148485A2
公开(公告)日：2001-07-05
申请号：PCT/NL0000941
申请日：2000-12-21
申请人： CRUCELL HOLLAND BV , LOGTENBERG TON
发明人： LOGTENBERG TON
IPC分类号： G01N33/53 , A61K38/00 , A61K39/395 , A61P35/00 , C07K1/14 , C07K16/00 , C07K16/28 , C07K16/30 , C12N15/09 , C12P21/08 , C12Q1/02 , G01N33/68
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/00 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/732 , C07K2317/734 , G01N33/6854 , G01N33/6857
摘要： The invention provides a method for selecting at least one member from a library of proteinaceous molecules comprising providing at least one cell and/or a functional equivalent thererof, with at least part of said library under conditions that allow binding of any such member to an epitope in and/or on said cells and/or said functional equivalent thereof, removing unbound proteinaceous molecules and selecting said at least one member, wherein said library comprises at least one mutant of a proteinaceous molecule capable of binding to said epitope.
摘要翻译：本发明提供了一种从蛋白质分子文库中选择至少一个成员的方法，包括提供至少一个细胞和/或其功能等同物，至少部分所述文库在允许任何这样的成员与表位结合的条件下在和/或所述细胞和/或其功能等同物上，去除未结合的蛋白质分子并选择所述至少一种成员，其中所述文库包含能够结合所述表位的蛋白质分子的至少一个突变体。

5. 发明申请

WO0228903A3 HEAVY CHAIN LIBRARIES 审中-公开
标题翻译：重型图书馆
公开(公告)号：WO0228903A3
公开(公告)日：2003-01-23
申请号：PCT/NL0100670
申请日：2001-09-12
申请人： CRUCELL HOLLAND BV , LOGTENBERG TON , HOUTZAGER ERWIN
发明人： LOGTENBERG TON , HOUTZAGER ERWIN
IPC分类号： C07K16/00 , C12N15/10 , C40B40/02
CPC分类号： C40B40/02 , C07K16/00 , C07K2317/21 , C07K2317/56 , C12N15/1037
摘要： The invention provides libraries which comprise binding molecules that are adapted to expression in an expression organism, but which are also transferable to a human context without undergoing a change in conformation and/or build up. The invention therefore provides a method for producing a human monoclonal antibody, said method comprising: providing a library of binding molecules, the binding domain of which consists essentially of human heavy chain variable fragments in a functional format, selecting from said library at least one heavy chain variable fragment having a desired binding affinity, and inserting a nucleic acid encoding said heavy chain variable fragment into a nucleic acid encoding the complementary part of at least a heavy chain of said human monoclonal antibody, allowing for expression of the resulting heavy chain and for assembly of said heavy chain with a desired light chain, and producing a human monoclonal antibody. The conformation of said heavy chain variable fragment is such that it retains its binding affinity whether it is in phage display or in its normal heavy chain environment. A method for making a library for use in said method is also herewith provided, as well as methods of keeping heavy chain variable fragments in said conformation. The present invention allows for producing larger libraries than the known ones. Besides, loss of specificities and affinities because of expression problems are reduced.
摘要翻译：本发明提供了包含适于在表达生物体中表达但可转移至人类上下文而不经历构象变化和/或增殖的结合分子的文库。因此，本发明提供了一种生产人单克隆抗体的方法，所述方法包括：提供结合分子文库，其结合域基本上由功能性格式的人重链可变片段组成，从所述文库中选择至少一种重具有期望的结合亲和力的链可变片段，以及将编码所述重链可变片段的核酸插入编码所述人单克隆抗体的至少重链的互补部分的核酸中，允许所得重链的表达，用所需的轻链组装所述重链，并产生人单克隆抗体。所述重链可变片段的构象使得其保持其结合亲和力，无论是在噬菌体展示还是在其正常的重链环境中。还提供了用于制备用于所述方法的文库的方法，以及在所述构象中保持重链可变片段的方法。本发明允许生产比已知的更大的库。此外，由于表达问题而导致的特殊性和亲和力的丧失也减少了。

6. 发明申请

WO02057290A8 NOVEL FIBRONECTIN EPITOPES AND PROTEINACEOUS MOLECULES CAPABLE OF BINDING SAID EPITOPES 审中-公开
标题翻译：新型纤维蛋白抗原蛋白和蛋白质分子可以结合结合物
公开(公告)号：WO02057290A8
公开(公告)日：2003-11-13
申请号：PCT/NL0200042
申请日：2002-01-18
申请人： CRUCELL HOLLAND BV , DE KRUIF CORNELIS ADRIAAN , LOGTENBERG TON , PENNINGS MARINUS THEODORUS THO , DE BOER HENRIETTE CHRISTINE
发明人： DE KRUIF CORNELIS ADRIAAN , LOGTENBERG TON , PENNINGS MARINUS THEODORUS THO , DE BOER HENRIETTE CHRISTINE
IPC分类号： A01H5/00 , A01K67/027 , A61K38/00 , A61K39/395 , A61K51/10 , A61P35/00 , C07K14/78 , C07K14/82 , C07K16/18 , C07K16/30 , C07K16/32 , C12N5/06 , C12N5/10 , C12N15/09 , C07K16/28 , C12N15/13 , G01N33/53
CPC分类号： C07K16/30 , A61K51/1045 , A61K51/1093 , A61K2039/505 , C07K14/78 , C07K16/18 , C07K2317/21 , C07K2317/565 , C07K2317/622
摘要： Means and method for at least partial inhibition of tumor growth are provided. Methods makes use of binding molecules capable of specifically binding to an epitope present on a subset of fibronectin proteins. By providing an individual with a binding molecule of the invention it is possible to interfere with sites of angiogenesis or sites that seen active angiogenesis in the recent past. Through this interference blood flow is at least in part inhibited. Through this inhibition it is possible to at least in part inhibit processes dependent on active angiogenesis in said individual, such as tumor growth.
摘要翻译：提供了至少部分抑制肿瘤生长的方法和方法。方法利用能够特异性结合存在于纤连蛋白亚群子上的表位的结合分子。通过为个体提供本发明的结合分子，可以干扰近来血管生成的位点或看到活性血管生成的部位。通过这种干扰血流至少部分被抑制。通过这种抑制，有可能至少部分抑制依赖于所述个体的活性血管发生的过程，例如肿瘤生长。

7. 发明申请

WO02057290A3 NOVEL FIBRONECTIN EPITOPES AND PROTEINACEOUS MOLECULES CAPABLE OF BINDING SAID EPITOPES 审中-公开
标题翻译：新型纤维结合蛋白表位和蛋白质分子能够结合所表达的表位
公开(公告)号：WO02057290A3
公开(公告)日：2002-11-21
申请号：PCT/NL0200042
申请日：2002-01-18
申请人： CRUCELL HOLLAND BV , DE KRUIF CORNELIS ADRIAAN , LOGTENBERG TON , PENNINGS MARINUS THEODORUS THO , DE BOER HENRIETTE CHRISTINE
发明人： DE KRUIF CORNELIS ADRIAAN , LOGTENBERG TON , PENNINGS MARINUS THEODORUS THO , DE BOER HENRIETTE CHRISTINE
IPC分类号： A01H5/00 , A01K67/027 , A61K38/00 , A61K39/395 , A61K51/10 , A61P35/00 , C07K14/78 , C07K14/82 , C07K16/18 , C07K16/30 , C07K16/32 , C12N5/06 , C12N5/10 , C12N15/09 , C07K16/28 , C12N15/13 , G01N33/53
CPC分类号： C07K16/30 , A61K51/1045 , A61K51/1093 , A61K2039/505 , C07K14/78 , C07K16/18 , C07K2317/21 , C07K2317/565 , C07K2317/622
摘要： Means and method for at least partial inhibition of tumor growth are provided. Methods makes use of binding molecules capable of specifically binding to an epitope present on a subset of fibronectin proteins. By providing an individual with a binding molecule of the invention it is possible to interfere with sites of angiogenesis or sites that seen active angiogenesis in the recent past. Through this interference blood flow is at least in part inhibited. Through this inhibition it is possible to at least in part inhibit processes dependent on active angiogenesis in said individual, such as tumor growth.
摘要翻译：提供了用于至少部分抑制肿瘤生长的手段和方法。方法利用能够特异性结合存在于纤连蛋白蛋白质子集上的表位的结合分子。通过向个体提供本发明的结合分子，有可能干扰最近过去见到活性血管生成的血管生成部位或部位。通过这种干扰，血流至少部分受到抑制。通过该抑制，可以至少部分抑制依赖于所述个体中的活性血管生成的过程，例如肿瘤生长。

8. 发明申请

WO2009157771A3 ANTIBODY PRODUCING NON-HUMAN MAMMALS 审中-公开
标题翻译：抗生素生产非人类哺乳动物
公开(公告)号：WO2009157771A3
公开(公告)日：2010-02-18
申请号：PCT/NL2009050381
申请日：2009-06-29
申请人： MERUS B V , HOUTZAGER ERWIN , PINTO RUI DANIEL , LOGTENBERG TON , THROSBY MARK , KRAMER ROBERT ARJEN , DE KRUIF CORNELIS ADRIAAN
发明人： HOUTZAGER ERWIN , PINTO RUI DANIEL , LOGTENBERG TON , THROSBY MARK , KRAMER ROBERT ARJEN , DE KRUIF CORNELIS ADRIAAN
IPC分类号： A01K67/027 , C07K16/00 , C12N5/10 , C12N15/85
CPC分类号： A01K67/0276 , A01K67/0275 , A01K2217/052 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K2317/21 , C07K2317/24 , C12N15/8509 , C12N2800/30
摘要： The invention provides transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. The invention further provides methods for producing an immunoglobulin from the transgenic, non-human animal.
摘要翻译：本发明提供了包含编码免疫球蛋白轻链的核酸的转基因非人动物，其中免疫球蛋白轻链是人类，人类样或人源化的。为核酸提供了使其对DNA重排和/或体细胞超突变有抗性的手段。在一个实施方案中，所述核酸包含用于在发育成熟B细胞的细胞的某一发育阶段期间在细胞中表达所需分子的表达盒。本发明还提供从转基因非人动物中产生免疫球蛋白的方法。

9. 发明申请

WO2005068622A3 MIXTURES OF BINDING PROTEINS 审中-公开
标题翻译：结合蛋白的混合物
公开(公告)号：WO2005068622A3
公开(公告)日：2006-03-02
申请号：PCT/NL2005000036
申请日：2005-01-19
申请人： MERUS B V , LOGTENBERG TON , HOOGENBOOM HENDRICUS RENERUS J
发明人： LOGTENBERG TON , HOOGENBOOM HENDRICUS RENERUS J
IPC分类号： C12P21/08 , C07K16/00 , C12N5/10 , C12P21/02
CPC分类号： C12N15/1086 , C07K16/10 , C07K16/20 , C07K16/40 , C07K2317/22 , C07K2317/569 , C07K2318/20 , C12N15/1082
摘要： The invention provides methods for the production of libraries of cells expressing at least two separate single polypeptide chain binding proteins, in which the binding proteins have different target epitopes. Such libraries are made by integration of the nucleic acid sequences encoding the polypeptide chains into the genome of the host cell, and selecting for cells that have successfully integrated these nucleic acids. The selected cells are preferably subjected to a cloning step. Mixtures of binding proteins are produced without having to individually produce each of the components of the mixture. A library of cells wherein essentially each cell encodes at least two single polypeptide chain binding proteins having different target epitopes is also herewith provided, as well as methods for producing a composition comprising at least two separate single polypeptide chain binding proteins having different target epitopes.
摘要翻译：本发明提供了产生表达至少两种分开的单个多肽链结合蛋白的细胞文库的方法，其中结合蛋白具有不同的靶表位。通过将编码多肽链的核酸序列整合到宿主细胞的基因组中并选择成功整合这些核酸的细胞来制备此类文库。所选择的细胞优选进行克隆步骤。产生结合蛋白的混合物，而不必单独产生混合物的每种组分。还提供了其中基本上每个细胞编码至少两种具有不同靶表位的单个多肽链结合蛋白的细胞库，以及用于产生包含至少两种具有不同靶表位的单独多肽链结合蛋白的组合物的方法。

10. 发明专利

DE60038132T2 未知
公开(公告)号：DE60038132T2
公开(公告)日：2009-04-02
申请号：DE60038132
申请日：2000-12-21
申请人： CRUCELL HOLLAND BV
发明人： LOGTENBERG TON
IPC分类号： C07K16/00 , G01N33/53 , A61K38/00 , A61K39/395 , A61P35/00 , C07K1/14 , C07K16/28 , C07K16/30 , C12N15/09 , C12N15/10 , C12P21/08 , C12Q1/02 , G01N33/68

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