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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
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。
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公开(公告)号：US06958388B2
公开(公告)日：2005-10-25
申请号：US10195707
申请日：2002-07-15
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。
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公开(公告)号：US07524931B2
公开(公告)日：2009-04-28
申请号：US10521008
申请日：2003-06-23
CPC分类号： C07K14/57 , A61K38/00 , A61K48/00 , C07K14/4723
摘要： The present invention relates to novel full-length interferon gamma (IFNG) polypeptide variants having interferon gamma activity. The full-length interferon gamma polypeptide variants of the invention are obtained by performing selected modifications in the C-terminal part of the molecule. The full-length interferon gamma polypeptide variants of the invention are useful in therapy, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis.
摘要翻译： 本发明涉及具有干扰素γ活性的新型全长干扰素γ（IFNG）多肽变体。 通过在分子的C末端部分进行选择的修饰来获得本发明的全长干扰素γ多肽变体。 本发明的全长干扰素γ多肽变体可用于治疗，特别是用于治疗间质性肺部疾病，例如特发性肺纤维化。
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公开(公告)号：US07232562B2
公开(公告)日：2007-06-19
申请号：US10369495
申请日：2003-02-19
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。
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公开(公告)号：US07504237B2
公开(公告)日：2009-03-17
申请号：US11377252
申请日：2006-03-16
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。
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公开(公告)号：US07230081B1
公开(公告)日：2007-06-12
申请号：US10130084
申请日：2000-11-13
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。
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7.发明授权Polynucleotides encoding S99T interferon gamma polypeptide variants and means of expression 失效编码S99T干扰素γ多肽变体的多核苷酸和表达手段公开(公告)号：US07419805B2
公开(公告)日：2008-09-02
申请号：US11158848
申请日：2005-06-22
申请人： Anne Dam Jensen
发明人： Anne Dam Jensen
摘要： The present invention relates to novel interferon gamma polypeptide variants having interferon gamma (IFNG) activity, methods for their preparation, pharmaceutical compositions comprising the polypeptide variants and their use in the treatment of diseases, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis.These novel polypeptide variants all comprise the substitution S99T as compared to the amino acid sequence of huIFNG or fragments thereof. By performing this mutation the naturally occurring N-glycosylation site present at position 97 is significantly better utilized.Preferably, the variants comprise further modifications, e.g. in order to increase the AUC of such variants when administered subcutaneously.
摘要翻译： 本发明涉及具有干扰素γ（IFNG）活性的新型干扰素γ多肽变体，其制备方法，包含多肽变体的药物组合物及其在治疗疾病中的用途，特别是用于治疗间质性肺疾病，例如 特发性肺纤维化。 与huIFNG或其片段的氨基酸序列相比，这些新型多肽变体全部包含取代S99T。 通过进行该突变，存在于位置97处的天然存在的N-糖基化位点被显着地更好地利用。 优选地，变体包括进一步的修饰，例如。 以便在皮下施用时增加这些变体的AUC。
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公开(公告)号：US07038015B2
公开(公告)日：2006-05-02
申请号：US10116273
申请日：2002-04-04
申请人： Anne Dam Jensen
发明人： Anne Dam Jensen
摘要： The present invention relates to novel interferon gamma polypeptide variants having interferon gamma (IFNG) activity, methods for their preparation, pharmaceutical compositions comprising the polypeptide variants and their use in the treatment of diseases, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis.These novel polypeptide variants all comprise the substitution S99T as compared to the amino acid sequence of huIFNG or fragments thereof. By performing this mutation the naturally occurring N-glycosylation site present at position 97 is significantly better utilized.Preferably, the variants comprise further modifications, e.g. in order to increase the AUC of such variants when administered subcutaneously.
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