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1. 发明申请

WO2011026948A1 STABLE FORMULATIONS OF POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：稳定的多肽制剂及其用途
公开(公告)号：WO2011026948A1
公开(公告)日：2011-03-10
申请号：PCT/EP2010/062975
申请日：2010-09-03
申请人： ABLYNX N.V. , BRIGE, Ann , LABEUR, Christine , DE BRABANDERE, Veronique
发明人： BRIGE, Ann , LABEUR, Christine , DE BRABANDERE, Veronique
IPC分类号： C07K16/24 , C07K16/26 , C07K16/28
CPC分类号： A61K39/39591 , A61K9/0019 , A61K47/02 , A61K47/14 , A61K47/26
摘要： Formulations are provided that contain single variable domains with a good solubility and good stability under different storage, transportation and stress conditions. The formulations are useful as pharmaceutical formulation. The formulation comprises an aqueous carrier with a pH of 5.5 to 8.0, a buffer selected from the group consisting of histidine pH 6.0-6.5, hepes pH 7.0-8.0, MES pH 6.0, succinate pH 6.0-6.5 and acetate pH 5,5-6.0; an excipient; and/or a surfactant selected from Tween 80, Tween 20 and poloxamers. The formulation is further characterized that it has an inorganic salt concentration of 150 mM or lower. The invention further relates to containers and pharmaceutical units comprising such formuSations and to methods for preparing and prophylactic and therapeutic uses of the formulations and pharmaceutical units of the invention.
摘要翻译：提供了在不同储存，运输和应力条件下含有良好溶解度和良好稳定性的单个可变结构域的配方。制剂可用作药物制剂。该制剂包含pH 5.5至8.0的水性载体，选自组氨酸pH 6.0-6.5，pH 7.0-8.0的pH，pH 6.0的MES，琥珀酸盐pH6.0-6.5和乙酸盐的pH5.5的缓冲液， 6.0; 赋形剂和/或选自吐温80，吐温20和泊洛沙姆的表面活性剂。该制剂的特征还在于其具有150mM或更低的无机盐浓度。本发明还涉及包含这种形式的容器和药物单元以及本发明的制剂和药物单元的制备和预防和治疗用途的方法。

2. 发明申请

WO1993025581A1 NEW PEPTIDES AND PROTEINS, PROCESS FOR THEIR PREPARATION AND THEIR USE AS CHOLESTEROL ACCEPTORS 审中-公开
标题翻译：新型肽和蛋白质，其制备方法及其作为胆固醇受体的使用
公开(公告)号：WO1993025581A1
公开(公告)日：1993-12-23
申请号：PCT/EP1993001444
申请日：1993-06-08
申请人： N.V. INNOGENETICS S.A. , ROSSENEU, Maryvonne , BRASSEUR, Robert , DELEYS, Robert , LABEUR, Christine
发明人： N.V. INNOGENETICS S.A.
IPC分类号： C07K15/00
CPC分类号： C07K7/08 , A61K38/00 , C07K14/775
摘要： The invention relates to a protein or a peptide containing or constituted by a peptide derived from peptide 18A and presenting the following characteristics: it is coiled in the form of an alpha helix having 5 turns, each turn bearing 3.6 amino acid residues; the diameter of said helix is from about 13 ANGSTROM to about 16 ANGSTROM ; the distance separating two consecutive turns of said helix being from about 4 ANGSTROM to about 6 ANGSTROM ; the length of the helix being from about 10 ANGSTROM to about 30 ANGSTROM ; it is amphipathic; with said peptide being such that: either the amino acid in position 4 is Glu or Asp, and/or the amino acid in position 6 is Glu or Asp, and/or the amino acid in position 8 is Lys or Arg, and/or the amino acid in position 11 is Glu or Asp. This protein can form complexes with phospholipids, with said complexes being useful for the treatment of cardiovascular diseases.
摘要翻译：本发明涉及含有或由肽18A衍生的肽构成的蛋白质或肽，具有以下特征：其以5匝的α螺旋形式卷曲，每轮转3.6个氨基酸残基; 所述螺旋的直径为约13安培至约16安培; 将所述螺旋的两个连续匝数从约4安瓿分离到约6安瓿的距离; 螺旋线的长度为约10安培至约30安培; 它是两亲性的所述肽使得：位置4中的氨基酸是Glu或Asp，和/或位置6的氨基酸是Glu或Asp，和/或位置8的氨基酸是Lys或Arg，和/或位置11的氨基酸是Glu或Asp。该蛋白质可与磷脂形成复合物，所述复合物可用于治疗心血管疾病。

3. 发明申请

WO2011098518A2 DELIVERY OF IMMUNOGLOBULIN VARIABLE DOMAINS AND CONSTRUCTS THEREOF 审中-公开
标题翻译：递送免疫球蛋白可变区及其构建体
公开(公告)号：WO2011098518A2
公开(公告)日：2011-08-18
申请号：PCT/EP2011051955
申请日：2011-02-10
申请人： ABLYNX NV , LABEUR CHRISTINE , REVETS HILDE ADI PIERRETTE , HUSSAIN NASIR , POTTER CHARLES
发明人： LABEUR CHRISTINE , REVETS HILDE ADI PIERRETTE , HUSSAIN NASIR , POTTER CHARLES
IPC分类号： A61K47/48 , A61K9/00 , A61K47/38 , C07K16/00
CPC分类号： A61K9/0021 , A61K9/1652 , A61K9/19 , A61K39/39591 , A61K2039/505 , A61K2039/54 , C07K16/36 , C07K2317/22 , C07K2317/569
摘要： The present invention relates to formulations and methods for administering therapeutic molecules comprising immunoglobulin variable domains using needle-free delivery devices.
摘要翻译：本发明涉及使用无针递送装置施用包含免疫球蛋白可变结构域的治疗分子的制剂和方法。

4. 发明申请

WO2009109635A9 NOVEL ANTIGEN BINDING DIMER-COMPLEXES, METHODS OF MAKING AND USES THEREOF 审中-公开
标题翻译：新型抗原结合二聚体复合物，其制备方法及其用途
公开(公告)号：WO2009109635A9
公开(公告)日：2011-08-18
申请号：PCT/EP2009052629
申请日：2009-03-05
申请人： ABLYNX NV , CASTEELS PETER , LAUWEREYS MARC JOZEF , STANSSENS PATRICK , LABEUR CHRISTINE , BOUTTON CARLO , BRIGE ANNE , HOOGENBOOM HENDRICUS RENERUS JACOBUS MATTHEUS , BEIRNAERT ELS ANNA ALICE
发明人： CASTEELS PETER , LAUWEREYS MARC JOZEF , STANSSENS PATRICK , LABEUR CHRISTINE , BOUTTON CARLO , BRIGE ANNE , HOOGENBOOM HENDRICUS RENERUS JACOBUS MATTHEUS , BEIRNAERT ELS ANNA ALICE
IPC分类号： C07K16/00 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/36
CPC分类号： C07K16/00 , C07K16/18 , C07K16/22 , C07K16/2866 , C07K16/36 , C07K2317/22 , C07K2317/569 , C07K2317/626
摘要： In a broad aspect the present invention generally relates to novel dimer-complexes (herein called "non-fused-dimers" or NFDs) comprising single variable domains, methods of making these complexes and uses thereof. These non-covalently bound dimer-complexes consist of two identical monomers that each comprises of one or more single variable domains (homodimers) or of two different monomers that each comprises on or more single variable domains (heterodimers). The subject NFDs have typically altered e.g. improved binding characteristics over their monomeric counterpart. The NFDs of the invention may further be engineered through linkage by a flexible peptide or cysteines in order to improve the stability. This invention also describes conditions under which such NFDs are formed and conditions under which the formation of such dimers can be avoided.
摘要翻译：在广泛的方面，本发明通常涉及包含单可变结构域的新型二聚体复合物（本文称为“非融合二聚体”或NFD），制备这些复合物的方法及其用途。这些非共价结合的二聚体复合物由两个相同的单体组成，每个单体包含一个或多个单个可变结构域（同源二聚体）或两个不同的单体，其各自包含或多个单个可变结构域（异源二聚体）。受试者NFD通常改变例如改善了其单体对应物的结合特性。本发明的NFD可进一步通过柔性肽或半胱氨酸的连接进行工程改造，以提高稳定性。本发明还描述了形成这种NFD的条件和可以避免形成这种二聚体的条件。

5. 发明申请

WO2009109635A2 NOVEL ANTIGEN BINDING DIMER-COMPLEXES, METHODS OF MAKING AND USES THEREOF 审中-公开
标题翻译：新型抗原结合二聚体复合物，其制备方法和用途
公开(公告)号：WO2009109635A2
公开(公告)日：2009-09-11
申请号：PCT/EP2009/052629
申请日：2009-03-05
申请人： ABLYNX NV , CASTEELS, Peter , LAUWEREYS, Marc Jozef , STANSSENS, Patrick , LABEUR, Christine , BOUTTON, Carlo , BRIGÉ, Anne , HOOGENBOOM, Hendricus Renerus Jacobus Mattheus , BEINAERT, Els Anna Alice
发明人： CASTEELS, Peter , LAUWEREYS, Marc Jozef , STANSSENS, Patrick , LABEUR, Christine , BOUTTON, Carlo , BRIGÉ, Anne , HOOGENBOOM, Hendricus Renerus Jacobus Mattheus , BEINAERT, Els Anna Alice
IPC分类号： C07K16/00 , C07K16/22 , C07K16/28 , C07K16/36 , C07K16/18
CPC分类号： C07K16/00 , C07K16/18 , C07K16/22 , C07K16/2866 , C07K16/36 , C07K2317/22 , C07K2317/569 , C07K2317/626
摘要： In a broad aspect the present invention generally relates to novel dimer-complexes (herein called "non-fused-dimers" or NFDs) comprising single variable domains, methods of making these complexes and uses thereof. These non-covalently bound dimer-complexes consist of two identical monomers that each comprises of one or more single variable domains (homodimers) or of two different monomers that each comprises on or more single variable domains (heterodimers). The subject NFDs have typically altered e.g. improved binding characteristics over their monomeric counterpart. The NFDs of the invention may further be engineered through linkage by a flexible peptide or cysteines in order to improve the stability. This invention also describes conditions under which such NFDs are formed and conditions under which the formation of such dimers can be avoided.
摘要翻译：在广义方面，本发明一般涉及包含单个可变结构域的新型二聚体复合物（本文称为“非融合二聚体”或NFD），制备这些复合体的方法及其用途。这些非共价结合的二聚体复合物由两个相同的单体组成，每个单体包含一个或多个单可变结构域（同二聚体）或两个不同的单体，每个单体包含一个或多个单可变结构域（异二聚体）。目标NFD典型地改变了例如改善了与其单体对应物的结合特性。为了提高稳定性，本发明的NFD可以进一步通过一种或多种柔性肽的连接进行工程改造。本发明还描述了形成这种NFD的条件和可以避免形成这种二聚体的条件。

6. 发明申请

WO2011026945A1 STABLE FORMULATIONS OF POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：稳定的多肽制剂及其用途
公开(公告)号：WO2011026945A1
公开(公告)日：2011-03-10
申请号：PCT/EP2010/062972
申请日：2010-09-03
申请人： ABLYNX N.V. , BRIGE, Ann , LABEUR, Christine , LAUWEREYS, Marc Jozef
发明人： BRIGE, Ann , LABEUR, Christine , LAUWEREYS, Marc Jozef
IPC分类号： C07K16/24 , C07K16/26 , C07K16/28
CPC分类号： A61K39/39591 , A61K9/0019 , A61K47/02 , A61K47/14 , A61K47/26
摘要： Stable formulations are provided that contain immunoglobulin single variable domains at a high concentration. The formulations are useful as pharmaceutical formulation and suitable for subcutaneous administration. The formulations can be transported and stored under various stress conditions. The invention further relates to containers and pharmaceutical units comprising such formulations and to methods for preparing and prophylactic and therapeutic uses of the formulations and pharmaceutical units of the invention.
摘要翻译：提供了稳定的制剂，其含有高浓度的免疫球蛋白单可变结构域。该制剂可用作药物制剂并且适于皮下给药。制剂可以在各种压力条件下运输和储存。本发明还涉及包含这些制剂的容器和药物单元以及本发明的制剂和药物单元的制备和预防和治疗用途的方法。

7. 发明申请

WO2009050275A1 A PROTEASE-SENSITIVE SITE IN APOLIPOPROTEIN A1, THERAPEUTIC AND DIAGNOSTIC IMPLICATIONS 审中-公开
标题翻译： APOLIPOPROTEIN A1中的蛋白敏感位点，治疗和诊断意义
公开(公告)号：WO2009050275A1
公开(公告)日：2009-04-23
申请号：PCT/EP2008/064054
申请日：2008-10-17
申请人： PRONOTA N.V. , EYCKERMAN, Sven , KAS, Koen , LABEUR, Christine
发明人： EYCKERMAN, Sven , KAS, Koen , LABEUR, Christine
IPC分类号： C07K14/775 , A61K38/17 , G01N33/50 , G01N33/92
CPC分类号： C07K14/775 , A61K38/00
摘要： The invention relates to the identification of a naturally occurring internal proteolytic cleavage site in the ApoA1 protein, which leads to inactivation of the mature protein. Specific modification of this cleavage site leads to a stabilised ApoA1 protein, which is beneficial for the reverse cholesterol transport. The invention therefore encompasses pharmaceutical compositions comprising a recombinant stabilised variant ApoA1 protein or rHDL particles comprising such a protein, for use in the treatment of patients having reduced HDL or hampered reverse cholesterol transport.
摘要翻译：本发明涉及鉴定ApoA1蛋白质中天然存在的内部蛋白水解切割位点，导致成熟蛋白质失活。该切割位点的特异性修饰导致稳定的ApoA1蛋白，其有利于反向胆固醇转运。因此，本发明包括包含重组稳定变体ApoA1蛋白或包含这种蛋白质的rHDL颗粒的药物组合物，用于治疗具有降低的HDL或阻碍的反向胆固醇转运的患者。

8. 发明申请

WO0250114A3 MODULATION OF ATP-BINDING CASSETTE TRANSPORTER ACTIVITY 审中-公开
标题翻译： ATP结合性转运体活性的调节
公开(公告)号：WO0250114A3
公开(公告)日：2002-08-29
申请号：PCT/EP0115397
申请日：2001-12-21
申请人： UNIV GENT , PEELMAN FRANK , ROSSENEU MARYVONNE , LABEUR CHRISTINE
发明人： PEELMAN FRANK , ROSSENEU MARYVONNE , LABEUR CHRISTINE
IPC分类号： A61K38/00 , C07K14/705 , C12N15/11 , A61K38/17 , G01N33/68
CPC分类号： C07K14/705 , A61K38/00
摘要： The invention relates to the field of ATP-Binding Cassette (ABC) transporter molecules. and to molecules selectively modulating the activity of said ABC transporters. Herein are provided molecules and compounds which selectively modulate the activity of specific ABC transporters. The invention also relates to molecules, compounds and compositions for preventing, treating or alleviating human diseases such as cancer, diseases due to abnormalities of lipid metabolism or lipid absorption or for preventing, treating or alleviating cancer or diseases related to bacterial, fungal or protozoal infections.
摘要翻译：本发明涉及ATP结合盒（ABC）转运蛋白分子领域。并涉及选择性调节所述ABC转运蛋白活性的分子。本文提供了选择性调节特定ABC转运蛋白活性的分子和化合物。本发明还涉及用于预防，治疗或缓解人类疾病如癌症，由于脂质代谢或脂质吸收异常引起的疾病或用于预防，治疗或缓解与细菌，真菌或原生动物感染有关的癌症或疾病的分子，化合物和组合物。

9. 发明申请

WO2010125187A3 METHOD FOR THE PRODUCTION OF DOMAIN ANTIBODIES 审中-公开
标题翻译：产生抗体的方法
公开(公告)号：WO2010125187A3
公开(公告)日：2011-01-20
申请号：PCT/EP2010055916
申请日：2010-04-30
申请人： ABLYNX NV , SCHOTTE PETER , STANSSENS PATRICK , LABEUR CHRISTINE , JONNIAUX JEAN-LUC , LAUWEREYS MARC JOZEF
发明人： SCHOTTE PETER , STANSSENS PATRICK , LABEUR CHRISTINE , JONNIAUX JEAN-LUC
IPC分类号： C07K16/00 , C07K16/18 , C07K16/28 , C12N15/81 , C12P1/02
CPC分类号： C12P21/005 , C07K16/00 , C07K16/18 , C07K16/2875 , C07K2317/14 , C07K2317/24 , C07K2317/35 , C07K2317/56 , C07K2317/569 , C07K2317/624 , C07K2317/626
摘要： The present disclosure relates to a method for producing a domain antibody in a host other than E. coli, preferably yeast, comprising a) applying conditions that promote the formation of disulfide bridges in domain antibodies, or b) removing domain antibodies lacking at least one disulfide bridge, or c) a combination of (a) and (b). More specifically, the present disclosure relates to a method, wherein said conditions that promote the formation of disulfide brides are selected from one or more of the following: a) addition of oxidizing agents, preferably oxidizing metal ions, preferably one or more selected from Cu2+, Fe2+, Fe3+ and Zn2+; b) co-expression of the domain antibody with a thiol lsomerase,- c) adapting the culturing conditions by one or more selected from the following: lowering culturing temperature and/or optimizing the culturing medium, including but not limited to reduction of methanol feed for hosts requiring a methanol feed, lowering conductivity of the culture medium, addition of yeast extract and/or peptone, or any combination thereof; d) refolding the domain antibody in the presence of denaturant and redox-buffer e) treating the domain antibody by oxygenation, increasing temperature, increasing pH, high pressure or any combination thereof, and f ) combinations of any of a) through e), or wherein conditions that remove domain antibodies lacking at least one disulfide bridge are selected from a) binding domain antibodies comprising free thiol groups to suitable reactive groups, including but not limited to immobilized thiol groups, optionally under denaturing conditions; b) reverse phase high performance chromatography.
摘要翻译：本公开内容涉及在除大肠杆菌以外，优选酵母中的宿主中产生结构域抗体的方法，其包括a）施加促进结构域抗体中二硫键形成的条件，或b）除去缺少至少一个二硫键，或c）（a）和（b）的组合。更具体地，本公开涉及一种方法，其中促进形成二硫化物新娘的所述条件选自以下一种或多种：a）加入氧化剂，优选氧化金属离子，优选选自Cu 2+的一种或多种，，Fe2 +，Fe3 +和Zn2 +; b）结构域抗体与硫醇异构酶共表达，c）使培养条件适应一种或多种选自以下的培养条件：降低培养温度和/或优化培养基，包括但不限于还原甲醇进料对于需要甲醇进料的主体，降低培养基的导电性，添加酵母提取物和/或蛋白胨或其任何组合; d）在变性剂和氧化还原缓冲剂存在下重折叠结构域抗体e）通过氧合，升高温度，增加pH，高压或其任何组合来处理结构域抗体，以及f）a）至e），或者其中除去缺少至少一个二硫键的结构域抗体的条件选自a）包含游离硫醇基团的结合域抗体适合于适当的反应性基团，包括但不限于固定硫醇基团，任选地在变性条件下; b）反相高效液相色谱法。

10. 发明申请

WO2010125187A2 METHOD FOR THE PRODUCTION OF DOMAIN ANTIBODIES 审中-公开
标题翻译：产生抗体的方法
公开(公告)号：WO2010125187A2
公开(公告)日：2010-11-04
申请号：PCT/EP2010/055916
申请日：2010-04-30
申请人： ABLYNX NV , SCHOTTE, Peter , STANSSENS, Patrick , LABEUR, Christine , JONNIAUX, Jean-Luc , LAUWEREYS, Marc Jozef
发明人： SCHOTTE, Peter , STANSSENS, Patrick , LABEUR, Christine , JONNIAUX, Jean-Luc
IPC分类号： C07K16/00 , C12N15/81 , C12P1/02 , C07K16/28 , C07K16/18
CPC分类号： C12P21/005 , C07K16/00 , C07K16/18 , C07K16/2875 , C07K2317/14 , C07K2317/24 , C07K2317/35 , C07K2317/56 , C07K2317/569 , C07K2317/624 , C07K2317/626
摘要： The present invention relates to a method for producing a domain antibody in a host other than E. coli, preferably yeast, comprising a) applying conditions that promote the formation of disulfide bridges in domain antibodies, or b) removing domain antibodies lacking at least one disulfide bridge, or c) a combination of (a) and (b). More specifically, the present invention relates to a method, wherein said conditions that promote the formation of disulfide brides are selected from one or more of the following: a) addition of oxidizing agents, preferably oxidizing metal ions, preferably one or more selected from Cu2+, Fe2+, Fe3+ and Zn2+; b) co-expression of the domain antibody with a thiol isomerase; c) adapting the culturing conditions by one or more selected from the following: lowering culturing temperature and/or optimizing the culturing medium, including but not limited to reduction of methanol feed for hosts requiring a methanol feed, lowering conductivity of the culture medium, addition of yeast extract and/or peptone, or any combination thereof; d) refolding the domain antibody in the presence of denaturant and redox-buffer e) treating the domain antibody by oxygenation, increasing temperature, increasing pH, high pressure or any combination thereof, and f ) combinations of any of a) through e), or wherein conditions that remove domain antibodies lacking at least one disulfide bridge are selected from a) binding domain antibodies comprising free thiol groups to suitable reactive groups, including but not limited to immobilized thiol groups, optionally under denaturing conditions; b) reverse phase high performance chromatography.
摘要翻译：本发明涉及在除大肠杆菌以外，优选酵母中的宿主中产生结构域抗体的方法，该方法包括：a）施加促进结构域抗体中二硫键形成的条件，或b）去除缺少至少一个二硫键，或c）（a）和（b）的组合。更具体地说，本发明涉及一种方法，其中促进形成二硫化物新鲜的所述条件选自以下一种或多种：a）加入氧化剂，优选氧化金属离子，优选选自Cu2 + ，Fe2 +，Fe3 +和Zn2 +; b）结构域抗体与硫醇异构酶的共表达; c）使培养条件适应以下选自以下的一种或多种：降低培养温度和/或优化培养基，包括但不限于还原需要甲醇进料的宿主的甲醇进料，降低培养基的导电性，加入的酵母提取物和/或蛋白胨，或其任何组合; d）在变性剂和氧化还原缓冲剂存在下重折叠结构域抗体e）通过氧合，升高温度，增加pH，高压或其任何组合来处理结构域抗体，以及f）a）至e），或者其中除去缺少至少一个二硫键的结构域抗体的条件选自a）包含游离硫醇基团的结合域抗体适合于适当的反应性基团，包括但不限于固定硫醇基团，任选地在变性条件下; b）反相高效液相色谱法。

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