首页> 外国专利> isolated fusion protein, homodimer, isolated homodimeric protein, isolated dimer, nucleic acid sequence, isolated polynucleotide, isolated recombinant DNA molecule, pharmaceutical composition, method for producing a protein, and, use of a fusion protein and a dimer

isolated fusion protein, homodimer, isolated homodimeric protein, isolated dimer, nucleic acid sequence, isolated polynucleotide, isolated recombinant DNA molecule, pharmaceutical composition, method for producing a protein, and, use of a fusion protein and a dimer

机译：分离的融合蛋白，同二聚体，分离的同二聚体蛋白，分离的二聚体，核酸序列，分离的多核苷酸，分离的重组DNA分子，药物组合物，蛋白质的制备方法以及融合蛋白和二聚体的用途

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摘要

fusion protein, dimeric protein construction, dimeric protein, pharmaceutical composition, nucleic acid sequence, recombinant DNA molecule, cell line, methods for producing a protein and for stimulating erythrogenesis in a mammal, and, dimer a fusion protein recombinant comprising a portion of human erythropoietin peptide linked to an immunoglobulin peptide portion is described. the fusion protein has a prolonged half-life in vivo compared to naturally occurring or naturally occurring human erythropoietin. in one embodiment of the invention, the protein has an in vivo half-life at least three times that of native human erythropoietin. the fusion protein also demonstrates improved erythropoietic bioactivity compared to native human erythropoietin. in one embodiment, the fusion protein comprises the peptide sequence of an entire human erythropoietin molecule (epo) and the peptide sequence of a human immunoglobulin fc fragment igg 1. the fc fragment in the fusion protein includes the articulation, ch2 and c113 domains of human immunoglobulin iggl. the epo molecule can be linked directly to the fc fragment to avoid foreign peptide linkers and decrease the risk of an immunogenic response when administered in vivo. in one embodiment, the hinge region is a variant of the human fc fragment having a non-cysteine residue in amino acid 6. the invention also relates to the nucleic acid and amino acid sequences encoding the fusion protein and transfected cell lines and methods to produce the fusion protein. the invention further includes pharmaceutical compositions comprising the fusion protein and methods of using the fusion protein and / or the pharmaceutical compositions, for example to stimulate erythropoiesis in individuals in need of therapy.

机译：融合蛋白，二聚体蛋白质结构，二聚体蛋白质，药物组合物，核酸序列，重组DNA分子，细胞系，在哺乳动物中产生蛋白质和刺激红血球生成的方法，以及将包含一部分人类促红细胞生成素的融合蛋白重组体二聚体描述了与免疫球蛋白肽部分连接的肽。与天然存在或天然存在的人类促红细胞生成素相比，该融合蛋白在体内具有延长的半衰期。在本发明的一个实施方案中，该蛋白质的体内半衰期至少是天然人促红细胞生成素的三倍。与天然人促红细胞生成素相比，该融合蛋白还显示出改善的促红细胞生成生物活性。在一个实施方案中，融合蛋白包含整个人促红细胞生成素分子（epo）的肽序列和人免疫球蛋白fc片段igg 1的肽序列。融合蛋白中的fc片段包括人的关节，ch2和c113结构域免疫球蛋白epo分子可直接连接至fc片段，以避免外源肽接头，并降低了体内给药时免疫原性应答的风险。在一个实施方案中，铰链区是在氨基酸6中具有非半胱氨酸残基的人fc片段的变体。本发明还涉及编码融合蛋白和转染的细胞系的核酸和氨基酸序列以及生产方法融合蛋白。本发明进一步包括包含融合蛋白的药物组合物，以及使用融合蛋白和/或药物组合物例如刺激需要治疗的个体的红细胞生成的方法。

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公开/公告号BRPI0706742B8

专利类型
公开/公告日2019-12-24

原文格式PDF
申请/专利权人 NOVAGEN HOLDING CORPORATION;
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申请/专利号BR2007PI06742
发明设计人 HAITAO WANG;JING XU;LONGBIN LIU;RUI ZHANG;YONG DU;
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申请日2007-01-25
分类号A61K9;A61K38;A61K38/18;A61K47/42;A61K47/68;A61P7;C07K14/505;C07K16/18;C07K19;C12N15/13;C12N15/18;C12N15/62;C12P21/02;
国家 BR
入库时间 2022-08-21 11:18:15

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