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1. 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。

2. 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。

3. 发明申请

WO2010100135A1 NOVEL ANTIGEN BINDING DIMER-COMPLEXES, METHODS OF MAKING/AVOIDING AND USES THEREOF 审中-公开
标题翻译：新型抗原结合二聚物复合物，其制备方法及其用途
公开(公告)号：WO2010100135A1
公开(公告)日：2010-09-10
申请号：PCT/EP2010/052600
申请日：2010-03-02
申请人： ABLYNX N.V. , BRIGE, Ann , LABEUR, Christine , LAUWEREYS, Marc
发明人： BRIGE, Ann , LABEUR, Christine , LAUWEREYS, Marc
IPC分类号： C07K16/00 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/36 , C07K16/24
CPC分类号： C07K16/00 , A61K9/0019 , A61K47/02 , A61K47/14 , A61K47/183 , A61K47/26 , C07K16/18 , C07K16/24 , C07K16/2866 , C07K16/2875 , C07K16/36 , C07K2317/22 , C07K2317/31 , C07K2317/569 , C07K2317/92 , C07K2319/00
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 monomelic 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，其各自包含或多于单个可变结构域（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。

4. 发明申请

WO2011042398A1 IMMUNOGLOBULIN SINGLE VARIABLE DOMAIN DIRECTED AGAINST HUMAN CXCR4 AND OTHER CELL ASSOCIATED PROTEINS AND METHODS TO GENERATE THEM 审中-公开
标题翻译：免疫球蛋白针对人CXCR4和其他细胞相关蛋白的单一变异域及其生成方法
公开(公告)号：WO2011042398A1
公开(公告)日：2011-04-14
申请号：PCT/EP2010/064766
申请日：2010-10-04
申请人： ABLYNX NV , BESTE, Gerald , STAELENS, Stephanie , VANLANDSCHOOT, Peter , PAJUELO, Maria Gonzalez , REVETS, Hilde Adi Pierrette , SCHOTTE, Peter , STALS, Hilde , BRIGE, Ann , DEWILDE, Maarten , STORTELERS, Catelijne
发明人： BESTE, Gerald , STAELENS, Stephanie , VANLANDSCHOOT, Peter , PAJUELO, Maria Gonzalez , REVETS, Hilde Adi Pierrette , SCHOTTE, Peter , STALS, Hilde , BRIGE, Ann , DEWILDE, Maarten , STORTELERS, Catelijne
IPC分类号： C07K16/28 , C07K16/00
CPC分类号： C07K16/2866 , C07K16/00 , C07K2317/22 , C07K2317/31 , C07K2317/565 , C07K2317/567 , C07K2317/569 , C07K2317/76 , C07K2317/92
摘要： The invention relates to immunoglobulin single variable domains directed against specific human CXCR4 epitopes (herein also referred to interchangeably as "compounds of the invention ", "amino acid sequences of the invention ", or "building blocks of the invention ") and polypeptides comprising them (herein also referred to as "polypeptides of the invention ", ''"'compounds of the invention ", or "constructs of the invention "). Furthermore, the present invention relates to nucleic acids encoding the compounds of the invention (also referred to herein as "nucleic acids of the invention" or '"nucleotide sequences of the invention")-, to methods for preparing the compounds of the invention; to host cells expressing or capable of expressing the compounds of the invention; to compositions, and in particular to pharmaceutical compositions, that comprise the compounds of the invention; and to uses of the compounds of the invention and the aforementioned nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes mentioned herein. The invention also relates to methods for generating immunoglobulin single variable domains against a target such as a cell-associated protein and constructs comprising said immunoglobulin single variable domains. The invention also provides immunoglobulin single variable domains obtainable by the methods of the invention. Specifically, the present invention relates to the generation of immunoglobulin single variable domains and constructs thereof by use of epitope walking with multimer libraries. More specifically, the present invention relates to the generation of immunoglobulin single variable domains derived from camelids directed against a particular epitope of a target, in particular against a target with multiple transmembrane spanning domains, including GPCRs and ion channels, by epitope walking with multimer libraries.
摘要翻译：本发明涉及针对特异性CXCR4表位的免疫球蛋白单可变结构域（本文还可以互换地称为“本发明的化合物”，“本发明的氨基酸序列”或“本发明的构建模块”）和包含它们的多肽（本文还称为“本发明的多肽”，“本发明的化合物”或“本发明的构建体”）。此外，本发明涉及编码本发明化合物的核酸（本文中也称为“本发明的核酸”或“本发明的核苷酸序列”） - 制备本发明化合物的方法; 宿主表达或能够表达本发明化合物的细胞; 包括本发明化合物的组合物，特别是药物组合物; 以及本发明化合物和上述核酸，宿主细胞和/或组合物的用途，特别是用于预防，治疗或诊断目的，例如本文提及的预防，治疗或诊断目的。本发明还涉及用于产生针对靶的免疫球蛋白单可变结构域的方法，例如细胞相关蛋白和包含所述免疫球蛋白单可变结构域的构建体。本发明还提供可通过本发明的方法获得的免疫球蛋白单可变结构域。具体而言，本发明涉及通过使用多聚体文库进行表位走路来产生免疫球蛋白单可变结构域及其构建体。更具体地说，本发明涉及通过用多聚体文库进行抗原表位的步骤来产生源自靶的特定表位的骆驼的免疫球蛋白单可变结构域，特别是针对具有多个跨膜跨越结构域（包括GPCR和离子通道）的靶。

5. 发明申请

WO2012056000A1 METHOD FOR THE PRODUCTION OF IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS 审中-公开
标题翻译：生产免疫球蛋白单变量域的方法
公开(公告)号：WO2012056000A1
公开(公告)日：2012-05-03
申请号：PCT/EP2011/068982
申请日：2011-10-28
申请人： ABLYNX NV , BRIGE, Ann , WALCARIUS, Bart , MEYVIS, Yves , SERGI, Mauro
发明人： BRIGE, Ann , WALCARIUS, Bart , MEYVIS, Yves , SERGI, Mauro
IPC分类号： C07K16/00 , C07K16/18
CPC分类号： C07K16/18 , C07K16/00 , C07K16/28 , C07K2317/14 , C07K2317/24 , C07K2317/31 , C07K2317/40 , C07K2317/569
摘要： The present disclosure relates to an improved method for the manufacture of immunoglobulin single variable domains. More specifically, the present disclosure relates to a method of producing immunoglobulin single variable domains in which the proportion of carbamylated variants is strongly reduced or absent and to improved immunoglobulin single variable domains obtainable by methods of the present disclosure.
摘要翻译：本公开涉及用于制造免疫球蛋白单可变结构域的改进方法。更具体地说，本公开内容涉及产生免疫球蛋白单可变结构域的方法，其中氨基甲酰化变体的比例强烈降低或不存在，以及通过本公开的方法可获得的改进的免疫球蛋白单可变结构域。

6. 发明申请

WO2011161266A1 IMPROVED IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS AND CONSTRUCTS THEREOF DIRECTED AGAINST CXCR4 审中-公开
标题翻译：改进的免疫球蛋白单克隆抗体的变异域及其构建方法
公开(公告)号：WO2011161266A1
公开(公告)日：2011-12-29
申请号：PCT/EP2011/060738
申请日：2011-06-27
申请人： ABLYNX NV , SCHOTTE, Peter , BRIGE, Ann , DEWILDE, Maarten , STALS, Hilde , STRUBBE, Beatrijs
发明人： SCHOTTE, Peter , BRIGE, Ann , DEWILDE, Maarten , STALS, Hilde , STRUBBE, Beatrijs
IPC分类号： C07K16/28 , C07K16/00 , A61P37/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/22 , C07K2317/35 , C07K2317/569 , C07K2317/62 , C07K2317/76 , C07K2319/00 , Y02A50/394
摘要： The present invention relates to amino acid sequences that are directed against CXCR4; as well as protein, constructs and compounds comprising the same; and also nucleic acids encoding the same.
摘要翻译：本发明涉及针对CXCR4的氨基酸序列; 以及蛋白质，构建体和包含其的化合物; 以及编码其的核酸。

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