公开(公告)号：US20090081218A1

公开(公告)日：2009-03-26

申请号：US12180455

申请日：2008-07-25

申请人： Haitao WANG ,  Yong DU ,  Rui ZHANG ,  Jing XU ,  Longbin LIU

发明人： Haitao WANG ,  Yong DU ,  Rui ZHANG ,  Jing XU ,  Longbin LIU

IPC分类号： A61K39/395 ,  C07K16/18 ,  C12N9/50 ,  C07H21/04 ,  C12P21/04 ,  C12N5/06

CPC分类号： C12N15/62 ,  A61K47/6811 ,  A61K47/6835 ,  C07K2317/53 ,  C07K2319/30

摘要： A fusion protein having a non-immunoglobulin polypeptide having a cysteine residue proximal to the C terminal thereof, and an immunoglobulin component with a mutated hinge region is provided. The mutation comprises a point mutated site corresponding in position to the position in a native hinge region of the cysteine residue located nearest the cysteine residue of the non-Ig component. The distance from the cysteine residue of the non-immunoglobulin polypeptide and any remaining cysteine residues of the mutated hinge region is sufficient to prevent the formation of a disulphide bond therebetween.

摘要翻译： 提供了具有非免疫球蛋白多肽的融合蛋白，其具有接近其C末端的半胱氨酸残基和具有突变的铰链区的免疫球蛋白组分。 该突变包括位于位于最接近非Ig组分的半胱氨酸残基的半胱氨酸残基的天然铰链区的位置的点突变位点。 与非免疫球蛋白多肽的半胱氨酸残基和突变的铰链区的任何剩余半胱氨酸残基的距离足以防止其间形成二硫键。

公开(公告)号：US20230265143A1

公开(公告)日：2023-08-24

申请号：US17700251

申请日：2022-03-21

申请人： Novagen Holding Corporation

发明人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

IPC分类号： C07K14/505 ,  A61K9/00 ,  A61K47/68 ,  A61K38/00

CPC分类号： C07K14/505 ,  A61K9/0019 ,  A61K47/6811 ,  A61K38/00 ,  C07K2317/53 ,  C07K2319/30

摘要： A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin. In one embodiment of the invention, the protein has a half-life in vivo at least three fold higher than native human erythropoietin. The fusion protein also exhibits enhanced erythropoietic bioactivity in comparison to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human immunoglobulin IgG1. The Fc fragment in the fusion protein includes the hinge region, CH2 and CH3 domains of human immunoglobulin IgG1. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen the risk of an immunogenic response when administered in vivo. In one embodiment the hinge region is a human Fc fragment variant having a non-cysteine residue at amino acid 6. The invention also relates to nucleic acid and amino acid sequences encoding the fusion protein and transfected cell lines and methods for producing 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 subjects in need of therapy.

公开(公告)号：US11279742B2

公开(公告)日：2022-03-22

申请号：US15992068

申请日：2018-05-29

申请人： Novagen Holding Corporation

发明人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

IPC分类号： A61K38/18 ,  C07K14/505 ,  C07K16/00 ,  A61K9/00 ,  A61K47/68 ,  A61K38/00

摘要： A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin. In one embodiment of the invention, the protein has a half-life in vivo at least three fold higher than native human erythropoietin. The fusion protein also exhibits enhanced erythropoietic bioactivity in comparison to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human immunoglobulin IgG1. The Fc fragment in the fusion protein includes the hinge region, CH2 and CH3 domains of human immunoglobulin IgG1. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen the risk of an immunogenic response when administered in vivo. In one embodiment the hinge region is a human Fc fragment variant having a non-cysteine residue at amino acid 6. The invention also relates to nucleic acid and amino acid sequences encoding the fusion protein and transfected cell lines and methods for producing 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 subjects in need of therapy.

公开(公告)号：US10117949B2

公开(公告)日：2018-11-06

申请号：US12162320

申请日：2007-01-25

申请人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

发明人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

IPC分类号： C07K14/505 ,  A61K38/18 ,  A61K39/00 ,  A61K47/48 ,  A61K38/00

摘要： A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin. In one embodiment of the invention the protein has a half-life in vivo at least three fold higher than native human erythropoietin. The fusion protein also exhibits enhanced erythropoietic bioactivity in comparison to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human immunoglobulin IgG1. The Fc fragment in the fusion protein includes the hinge region, CH2 and CH3 domains of human immunoglobulin IgG1. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen the risk of an immunogenic response when administered in vivo. In one embodiment the hinge region is a human Fc fragment variant having a non-cysteine residue at amino acid 6. The invention also relates to nucleic acid and amino acid sequences encoding the fusion protein and transfected cell lines and methods for producing 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 subjects in need of therapy.

公开(公告)号：US20120100099A1

公开(公告)日：2012-04-26

申请号：US13275205

申请日：2011-10-17

申请人： Haitao WANG ,  Longbin LIU ,  Rui ZHANG ,  Jing XU ,  Yong DU

发明人： Haitao WANG ,  Longbin LIU ,  Rui ZHANG ,  Jing XU ,  Yong DU

IPC分类号： A61K38/19 ,  C12N9/48 ,  A61P43/00 ,  C12N5/10 ,  C12N15/62 ,  C07K19/00 ,  C12P21/00

CPC分类号： C12N15/62 ,  A61K47/6811 ,  A61K47/6835 ,  C07K2317/53 ,  C07K2319/30

摘要： A fusion protein having a non-immunoglobulin polypeptide having a cysteine residue proximal to the C terminal thereof, and an immunoglobulin component with a mutated hinge region is provided. The mutation comprises a point mutated site corresponding in position to the position in a native hinge region of the cysteine residue located nearest the cysteine residue of the non-Ig component. The distance from the cysteine residue of the non-immunoglobulin polypeptide and any remaining cysteine residues of the mutated hinge region is sufficient to prevent the formation of a disulphide bond therebetween.

摘要翻译： 提供了具有非免疫球蛋白多肽的融合蛋白，其具有接近其C末端的半胱氨酸残基和具有突变的铰链区的免疫球蛋白组分。 该突变包括位于位于最接近非Ig组分的半胱氨酸残基的半胱氨酸残基的天然铰链区的位置的点突变位点。 与非免疫球蛋白多肽的半胱氨酸残基和突变的铰链区的任何剩余半胱氨酸残基的距离足以防止其间形成二硫键。

公开(公告)号：US08067548B2

公开(公告)日：2011-11-29

申请号：US12180455

申请日：2008-07-25

申请人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

发明人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

IPC分类号： C12P21/08 ,  A61K39/00

CPC分类号： C12N15/62 ,  A61K47/6811 ,  A61K47/6835 ,  C07K2317/53 ,  C07K2319/30

摘要： A fusion protein having a non-immunoglobulin polypeptide having a cysteine residue proximal to the C terminal thereof, and an immunoglobulin component with a mutated hinge region is provided. The mutation comprises a point mutated site corresponding in position to the position in a native hinge region of the cysteine residue located nearest the cysteine residue of the non-Ig component. The distance from the cysteine residue of the non-immunoglobulin polypeptide and any remaining cysteine residues of the mutated hinge region is sufficient to prevent the formation of a disulphide bond therebetween.

摘要翻译： 提供了具有非免疫球蛋白多肽的融合蛋白，其具有接近其C末端的半胱氨酸残基和具有突变的铰链区的免疫球蛋白组分。 该突变包括位于位于最接近非Ig组分的半胱氨酸残基的半胱氨酸残基的天然铰链区的位置的点突变位点。 与非免疫球蛋白多肽的半胱氨酸残基和突变的铰链区的任何剩余半胱氨酸残基的距离足以防止其间形成二硫键。

公开(公告)号：US20100303759A1

公开(公告)日：2010-12-02

申请号：US12665682

申请日：2007-06-22

申请人： Haitao Wang ,  Chunsheng Mao ,  Jizhi Li ,  Ling Wang ,  Yong Du ,  Longbin Liu ,  Jing Xu ,  Rui Zhang

发明人： Haitao Wang ,  Chunsheng Mao ,  Jizhi Li ,  Ling Wang ,  Yong Du ,  Longbin Liu ,  Jing Xu ,  Rui Zhang

IPC分类号： A61K38/21 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10 ,  C07K14/555 ,  A61P35/04 ,  A61P31/12

CPC分类号： C07K14/56 ,  A61K38/00 ,  C07K14/555

摘要： This application relates to recombinant human interferon-like proteins. In one embodiment a recombinant protein created by gene shuffling technology is described having enhanced anti-viral and anti-proliferative activities in comparison to naturally occurring human interferon alpha 2b (HuIFN-α2b). The invention encompasses a polynucleotide encoding the protein and recombinant vectors and host cells comprising the polynucleotide. Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID No: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon therapy, such as viral diseases and cancer.

公开(公告)号：US20090297522A1

公开(公告)日：2009-12-03

申请号：US12162320

申请日：2007-01-27

申请人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

发明人： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

IPC分类号： A61K39/395 ,  C07K16/18 ,  C12N15/11 ,  C12N15/00 ,  C12N5/06 ,  C12P21/02

CPC分类号： C07K14/505 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/6811 ,  C07K2317/53 ,  C07K2319/30

摘要： A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin. In one embodiment of the invention the protein has a half-life in vivo at least three fold higher than native human erythropoietin. The fusion protein also exhibits enhanced erythropoietic bioactivity in comparison to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human immunoglobulin IgG1. The Fc fragment in the fusion protein includes the hinge region, CH2 and CH3 domains of human immunoglobulin IgG1. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen the risk of an immunogenic response when administered in vivo. In one embodiment the hinge region is a human Fc fragment variant having a non-cysteine residue at amino acid 6. The invention also relates to nucleic acid and amino acid sequences encoding the fusion protein and transfected cell lines and methods for producing 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 subjects in need of therapy.

摘要翻译： 描述了包含与免疫球蛋白肽部分连接的人促红细胞生成素肽部分的重组融合蛋白。 与天然存在的或重组的天然人促红细胞生成素相比，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，蛋白质的体内半衰期比天然人促红细胞生成素高至少三倍。 与天然人促红细胞生成素相比，融合蛋白也表现出增强的红细胞生物活性。 在一个实施方案中，融合蛋白包含人促红细胞生成素（EPO）分子的完整肽序列和人免疫球蛋白IgG1的Fc片段的肽序列。 融合蛋白中的Fc片段包括人免疫球蛋白IgG1的铰链区，CH2和CH3结构域。 EPO分子可以直接连接到Fc片段，以避免外来的肽接头并且当在体内施用时减轻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具有非半胱氨酸残基的人Fc片段变体。本发明还涉及编码融合蛋白和转染细胞系的核酸和氨基酸序列以及用于产生融合蛋白的方法。 本发明还包括包含融合蛋白的药物组合物和使用融合蛋白和/或药物组合物的方法，例如刺激需要治疗的受试者的红细胞生成。