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 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 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 erythropoiesis in a mammal, and, dimer a fusion protein A recombinant antibody comprising a human erythropoietin peptide moiety linked to an immunoglobulin peptide moiety is described. The fusion protein has a prolonged in vivo half-life compared to naturally occurring or native-occurring human erythropoietin. In one embodiment of the invention the protein has an in vivo half-life at least three times longer than 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 complete with a human erythropoietin (epo) molecule and the peptide sequence of a human immunoglobulin fc fragment igg 1. The fc fragment in the fusion protein includes the region of human immunoglobulin joint, ch2 and c113 domains. The epo molecule may be linked directly to the fc fragment to prevent foreign peptide linkers and to decrease the risk of an immunogenic response when administered in vivo. In one embodiment, the joint region is a variant of the human fc fragment having an amino acid non-cysteine residue. The invention also relates to 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 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细胞生成的方法，以及将融合蛋白二聚体包含人红细胞生成素的重组抗体描述了与免疫球蛋白肽部分连接的肽部分。与天然存在或天然存在的人促红细胞生成素相比，该融合蛋白具有延长的体内半衰期。在本发明的一个实施方案中，该蛋白质的体内半衰期比天然人促红细胞生成素的体内半衰期至少长三倍。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，融合蛋白包含具有人促红细胞生成素（epo）分子的完整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片段包括人免疫球蛋白接头ch2和ch2的区域。 c113域。 epo分子可以直接连接至fc片段，以防止外源肽接头，并在体内给药时降低免疫原性应答的风险。在一个实施方案中，关节区域是具有氨基酸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的核酸和氨基酸序列以及转染的细胞系和方法。产生融合蛋白。本发明进一步包括包含融合蛋白的药物组合物和使用融合蛋白和/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BRPI0706742B1

专利类型
公开/公告日2019-12-03

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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