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    S99T C-11 Truncated polynucleotides encoding interferon gamma polypeptide variants
    1.
    发明授权
    S99T C-11 Truncated polynucleotides encoding interferon gamma polypeptide variants 失效
    S99T C-11编码干扰素γ多肽变体的截短多核苷酸

    公开(公告)号：US07390638B2

    公开(公告)日：2008-06-24

    申请号：US11115906

    申请日：2005-04-27

    申请人： Bart Van Den Hazel ,  Anne Dam Jensen ,  Frank Bech Nygaard ,  Kim Vilbour Andersen

    发明人： Bart Van Den Hazel ,  Anne Dam Jensen ,  Frank Bech Nygaard ,  Kim Vilbour Andersen

    IPC分类号： C12N15/21 ,  C12N5/00 ,  C12N15/00 ,  C07H21/04

    CPC分类号： C07K14/57 ,  A61K38/00

    摘要： When interferon gamma (IFNG) is produced in mammalian cell lines a heterogenous population of IFNG polypeptides is obtained due to C-terminal processing of the IFNG polypeptide. Clearly, this constitutes a severe problem in that valuable polypeptide material is lost and, further, it is necessary to carry out time-consuming and cumbersome purification in order to obtain a homogenous population of active IFNG polypeptides having the desired length. It has now been found that an IFNG fragment containing 132 amino acid residues (truncated at the nucleotide level by introducing a stop-codon after the codon encoding amino acid residue no. 132) does not undergo C-terminal truncation or, at least, is not significantly C-terminally truncated. Furthermore, as the IFNG fragment containing 132 amino acid residues is active, this opens up the possibility of producing a homogenous active IFNG polypeptide in eukaryotic host cells, such as CHO cells. More particularly, the present invention relates to an IFNG polypeptide variant exhibiting IFNG activity and having the amino acid sequence shown in SEQ ID NO:12. In a highly preferred embodiment of the invention, the variant comprises at least one further modification, such as 1-10 further modifications, relative to the amino acid sequence shown in SEQ ID NO:12. A particular preferred further modification is E38N+S40T.

    摘要翻译： 当在哺乳动物细胞系中产生干扰素γ（IFNG）时，由于IFNG多肽的C末端加工，获得IFNG多肽的异源群体。 显然，这构成了一个严重的问题，即有价值的多肽材料丢失，而且还需要进行耗时且繁琐的纯化，以获得具有所需长度的活性IFNG多肽的均质群体。 现在已经发现，含有132个氨基酸残基的IFNG片段（在编码氨基酸残基132号的密码子后通过引入终止密码子在核苷酸水平被截短）不经历C-末端截短，或至少是 不显着C末端截断。 此外，由于含有132个氨基酸残基的IFNG片段是有活性的，因此可以在真核宿主细胞如CHO细胞中产生均一的活性IFNG多肽。 更具体地，本发明涉及表现出IFNG活性且具有SEQ ID NO：12所示氨基酸序列的IFNG多肽变体。 在本发明的一个非常优选的实施方案中，相对于SEQ ID NO：12所示的氨基酸序列，变体包含至少一个其它修饰，例如1-10个其它修饰。 特别优选的进一步修改是E38N + S40T。

    Interferon gamma polypeptide variants
    2.
    发明授权
    Interferon gamma polypeptide variants 失效
    干扰素γ多肽变体

    公开(公告)号：US06958388B2

    公开(公告)日：2005-10-25

    申请号：US10195707

    申请日：2002-07-15

    申请人： Bart Van Den Hazel ,  Anne Dam Jensen ,  Frank Bech. Nygaard ,  Kim Vilbour Andersen

    发明人： Bart Van Den Hazel ,  Anne Dam Jensen ,  Frank Bech. Nygaard ,  Kim Vilbour Andersen

    IPC分类号： A61K38/00 ,  C07K14/57 ,  C07K17/00 ,  A61K38/21 ,  C12P21/04

    CPC分类号： C07K14/57 ,  A61K38/00

    摘要： When interferon gamma (IFNG) is produced in mammalian cell lines a heterogenous population of IFNG polypeptides is obtained due to C-terminal processing of the IFNG polypeptide. Clearly, this constitutes a severe problem in that valuable polypeptide material is lost and, further, it is necessary to carry out time-consuming and cumbersome purification in order to obtain a homogenous population of active IFNG polypeptides having the desired length. It has now been found that an IFNG fragment containing 132 amino acid residues (truncated at the nucleotide level by introducing a stop-codon after the codon encoding amino acid residue no. 132) does not undergo C-terminal truncation or, at least, is not significantly C-terminally truncated. Furthermore, as the IFNG fragment containing 132 amino acid residues is active, this opens up the possibility of producing a homogenous active IFNG polypeptide in eukaryotic host cells, such as CHO cells. More particularly, the present invention relates to an IFNG polypeptide variant exhibiting IFNG activity and having the amino acid sequence shown in SEQ ID NO:12. In a highly preferred embodiment of the invention, the variant comprises at least one further modification, such as 1-10 further modifications, relative to the amino acid sequence shown in SEQ ID NO:12. A particular preferred further modification is E38N+S40T.

    摘要翻译： 当在哺乳动物细胞系中产生干扰素γ（IFNG）时，由于IFNG多肽的C末端加工，获得IFNG多肽的异源群体。 显然，这构成了一个严重的问题，即有价值的多肽材料丢失，而且还需要进行耗时且繁琐的纯化，以获得具有所需长度的活性IFNG多肽的均质群体。 现在已经发现，含有132个氨基酸残基的IFNG片段（在编码氨基酸残基132号的密码子后通过引入终止密码子在核苷酸水平被截短）不经历C-末端截短，或至少是 不显着C末端截断。 此外，由于含有132个氨基酸残基的IFNG片段是有活性的，因此可以在真核宿主细胞如CHO细胞中产生均一的活性IFNG多肽。 更具体地，本发明涉及表现出IFNG活性且具有SEQ ID NO：12所示氨基酸序列的IFNG多肽变体。 在本发明的一个非常优选的实施方案中，相对于SEQ ID NO：12所示的氨基酸序列，变体包含至少一个其它修饰，例如1-10个其它修饰。 特别优选的进一步修改是E38N + S40T。

    Polynucleotides encoding interferon gamma polypeptides
    4.
    发明授权
    Polynucleotides encoding interferon gamma polypeptides 失效
    编码干扰素γ多肽的多核苷酸

    公开(公告)号：US07504237B2

    公开(公告)日：2009-03-17

    申请号：US11377252

    申请日：2006-03-16

    申请人： Anne Dam Jensen ,  Kim Vilbour Andersen ,  Christian Karsten Hansen

    发明人： Anne Dam Jensen ,  Kim Vilbour Andersen ,  Christian Karsten Hansen

    IPC分类号： C12N15/00 ,  C12N15/63 ,  C12N15/85 ,  C07H21/04

    CPC分类号： A61K47/60

    摘要： A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.

    摘要翻译： 一种显示干扰素γ活性并包含与IFG多肽共价连接的至少一个第一非多肽部分的缀合物，所述多肽包含与至少一个引入的和/或至少一个的IFIF多肽的母体IFNG多肽不同的氨基酸序列 去除的氨基酸残基包含非多肽部分的连接基团。 缀合物可用于治疗各种疾病。

    Interferon gamma conjugates
    5.
    发明授权
    Interferon gamma conjugates 失效
    干扰素γ偶联物

    公开(公告)号：US07230081B1

    公开(公告)日：2007-06-12

    申请号：US10130084

    申请日：2000-11-13

    申请人： Anne Dam Jensen ,  Kim Vilbour Andersen ,  Christian Karsten Hansen

    发明人： Anne Dam Jensen ,  Kim Vilbour Andersen ,  Christian Karsten Hansen

    IPC分类号： C07K17/00 ,  A61K38/21 ,  A61K39/00 ,  C12P21/04

    CPC分类号： C07K14/57 ,  A61K38/00

    摘要： A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.

    摘要翻译： 一种显示干扰素γ活性并包含与IFG多肽共价连接的至少一个第一非多肽部分的缀合物，所述多肽包含与至少一个引入的和/或至少一个的IFIF多肽的母体IFNG多肽不同的氨基酸序列 去除的氨基酸残基包含非多肽部分的连接基团。 缀合物可用于治疗各种疾病。

    E38N interferon gamma polypeptide variants
    6.
    发明授权
    E38N interferon gamma polypeptide variants 失效
    E38N干扰素γ多肽变体

    公开(公告)号：US07232562B2

    公开(公告)日：2007-06-19

    申请号：US10369495

    申请日：2003-02-19

    申请人： Anne Dam Jensen ,  Kim Vilbour Andersen ,  Christian Karsten Hansen

    发明人： Anne Dam Jensen ,  Kim Vilbour Andersen ,  Christian Karsten Hansen

    IPC分类号： A61K38/21 ,  A61K39/00 ,  C07K17/00 ,  C12P21/04

    CPC分类号： A61K47/60

    摘要： A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.

    摘要翻译： 一种显示干扰素γ活性并包含与IFG多肽共价连接的至少一个第一非多肽部分的缀合物，所述多肽包含与至少一个引入的和/或至少一个的IFIF多肽的母体IFNG多肽不同的氨基酸序列 去除的氨基酸残基包含非多肽部分的连接基团。 缀合物可用于治疗各种疾病。

    METHOD FOR PREPARING MODIFIED POLYPEPTIDES
    7.
    发明申请
    METHOD FOR PREPARING MODIFIED POLYPEPTIDES 审中-公开
    制备改性多糖的方法

    公开(公告)号：US20120107852A1

    公开(公告)日：2012-05-03

    申请号：US13272681

    申请日：2011-10-13

    申请人： Torben Halkier ,  Anders Hjelholt Pedersen ,  Jens Sigurd Okkels ,  Kim Vilbour Andersen

    发明人： Torben Halkier ,  Anders Hjelholt Pedersen ,  Jens Sigurd Okkels ,  Kim Vilbour Andersen

    IPC分类号： C12Q1/48

    CPC分类号： C12N15/1058 ,  C07K1/107 ,  C07K14/31 ,  C07K19/00 ,  C12N15/1034

    摘要： Methods for producing polypeptide with altered immunogenicity or improved stability properties are disclosed. The methods involve a) expressing a diversified population of nucleotide sequences encoding a polypeptide of interest, b) screening the polypeptides expressed in step a) for function, immunogenicity and/or stability, c) selecting functional polypeptides having altered immunogenicity and/or increased stability, e.g. functional in vivo half-life as compared to the polypeptide of interest, and d) optionally subjecting the nucleotide sequence encoding the polypeptide selected in step c) to one or more repeated cycles of steps a)-c). In a further step the expressed polypeptides of step a) or c) can be conjugated to at least one non-polypeptide moiety.

    摘要翻译： 公开了产生具有改变的免疫原性或改善的稳定性的多肽的方法。 所述方法包括：a）表达编码感兴趣多肽的核苷酸序列的多样化群体，b）筛选功能，免疫原性和/或稳定性在步骤a）中表达的多肽，c）选择具有改变的免疫原性和/或增加稳定性的功能性多肽 ，例如 与目的多肽相比具有功能的体内半衰期，和d）任选地将编码步骤c）中选择的多肽的核苷酸序列经历步骤a）-c）的一个或多个重复循环。 在另一步骤中，步骤a）或c）的表达多肽可以与至少一个非多肽部分缀合。