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    Artificial proteins with reduced immunogenicity
    8.
    发明授权
    Artificial proteins with reduced immunogenicity 有权
    具有降低免疫原性的人造蛋白

    公开(公告)号：US07615217B2

    公开(公告)日：2009-11-10

    申请号：US11716878

    申请日：2007-03-12

    申请人： Stephen Gillies ,  Francis J. Carr ,  Jones Tim ,  Graham Carter ,  Anita Hamilton ,  Stephen Williams ,  Marian Hanlon ,  John Watkins ,  Matthew Baker ,  Jeffrey C. Way

    发明人： Stephen Gillies ,  Francis J. Carr ,  Jones Tim ,  Graham Carter ,  Anita Hamilton ,  Stephen Williams ,  Marian Hanlon ,  John Watkins ,  Matthew Baker ,  Jeffrey C. Way

    IPC分类号： A61K39/395

    CPC分类号： C07K16/30 ,  C07K16/28 ,  C07K16/2863 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention relates to artificial modified proteins, preferably fusion proteins, having a reduced immunogenicity compared to the parent non-modified molecule when exposed to a species in vivo. The invention relates, above all, to novel immunoglobulin fusion proteins which essentially consist of an immunoglobulin molecule or a fragment thereof covalently fused via its C-terminus to the N-terminus of a biologically active non-immunoglobulin molecule, preferably a polypeptide or protein or a biologically active fragment thereof. In a specific embodiment, the invention relates to fusion proteins consisting of an Fc portion of an antibody which is fused as mentioned to the non-immunological target molecule which elicits biological or pharmacological efficacy. The molecules of the invention have amino acid sequences which are altered in one or more amino acid residue positions but have in principal the same biological activity as compared with the non-altered molecules. The changes are made in regions of the molecules which are identified as T-cell epitopes, which contribute to an immune reaction in a living host. Thus, the invention also relates to a novel method of making such fusion proteins by identifying said epitopes comprising calculation of T-cell epitope values for MHC Class II molecule binding sites in a peptide by computer-aided methods.

    摘要翻译： 本发明涉及人体修饰蛋白，优选融合蛋白，当与体内物种暴露时，与亲本非修饰分子相比具有降低的免疫原性。 本发明首先涉及新的免疫球蛋白融合蛋白，其基本上由免疫球蛋白分子或其通过C末端与生物活性非免疫球蛋白分子，优选多肽或蛋白质的N末端共价融合的片段组成，或 其生物活性片段。 在一个具体的实施方案中，本发明涉及由抗体的Fc部分组成的融合蛋白，所述Fc部分如提及的非免疫靶标分子融合而引起生物学或药理学功效。 本发明的分子具有氨基酸序列，其在一个或多个氨基酸残基位置被改变，但与未改变的分子相比具有相同的生物学活性。 在被鉴定为T细胞表位的分子的区域中进行改变，其有助于在宿主中的免疫反应。 因此，本发明还涉及通过鉴定所述表位来制备此类融合蛋白的新方法，包括通过计算机辅助方法计算肽中MHC II类分子结合位点的T细胞表位值。

    Method of preparing a modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity
    9.
    发明授权
    Method of preparing a modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity 失效
    制备具有降低免疫原性的改良粒细胞集落刺激因子（G-CSF）的方法

    公开(公告)号：US07392141B2

    公开(公告)日：2008-06-24

    申请号：US10467396

    申请日：2002-02-05

    申请人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  Stephen Williams

    发明人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  Stephen Williams

    IPC分类号： G06F19/00 ,  G06F17/00 ,  G06G7/58 ,  C12P21/06 ,  G01N33/53 ,  G01N33/00 ,  A61K39/00

    CPC分类号： C07K14/535 ,  A61K9/7015 ,  A61K38/00 ,  A61K47/02 ,  A61K47/12 ,  C07K14/54 ,  C07K16/18 ,  C07K16/2866 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/3046 ,  C07K16/464 ,  C07K2319/00 ,  G06F19/16 ,  G06F19/18 ,  Y10S707/99943

    摘要： A method of preparing a modified granulocyte colony stimulating factor (G-CSF) protein having reduced immunogenicity relative to human G-CSF comprises the steps of (i) identifying one or more potential T-cell epitopes within the amino acid sequence of human G-CSF (SEQ ID NO: 1); (ii) designing at least one sequence variant of at least one potential T-cell epitope identified in step (i), wherein the sequence variant eliminates or substantially reduces the MHC class II binding activity of the potential T-cell epitope; (iii) preparing, by recombinant DNA techniques, at least one modified G-CSF protein including a sequence variant designed in step (ii); (iv) evaluating at least one modified G-CSF protein prepared in step (iii) for G-CSF activity and immunogenicity; and (v) selecting a modified G-CSF protein evaluated in step (iv) that has substantially the same therapeutic G-CSF biological activity as, but substantially less immunogenicity than, human G-CSF.

    摘要翻译： 制备相对于人G-CSF具有降低的免疫原性的修饰的粒细胞集落刺激因子（G-CSF）蛋白质的方法包括以下步骤：（i）鉴定人G-蛋白的氨基酸序列内的一个或多个潜在T细胞表位， CSF（SEQ ID NO：1）; （ii）设计步骤（i）中鉴定的至少一个潜在T细胞表位的至少一个序列变体，其中所述序列变体消除或显着降低潜在T细胞表位的MHC II类结合活性; （iii）通过重组DNA技术制备至少一种修饰的G-CSF蛋白，包括在步骤（ii）中设计的序列变体; （iv）评估在步骤（iii）中制备的至少一种修饰的G-CSF蛋白质的G-CSF活性和免疫原性; 和（v）选择在步骤（iv）中评估的与人G-CSF具有基本上相同的治疗性G-CSF生物学活性但显着更低的免疫原性的修饰的G-CSF蛋白质。

    Anti-KSA/IL-2 fusion proteins with reduced immunogenicity
    10.
    发明授权
    Anti-KSA/IL-2 fusion proteins with reduced immunogenicity 有权
    抗KSA / IL-2融合蛋白具有降低的免疫原性

    公开(公告)号：US07189830B2

    公开(公告)日：2007-03-13

    申请号：US10468370

    申请日：2002-02-18

    申请人： Stephen Gillies ,  Francis J. Carr ,  Jones Tim ,  Graham Carter ,  Anita Hamilton ,  Stephen Williams ,  Marian Hanlon ,  John Watkins ,  Matthew Baker ,  Jeffrey C. Way

    发明人： Stephen Gillies ,  Francis J. Carr ,  Jones Tim ,  Graham Carter ,  Anita Hamilton ,  Stephen Williams ,  Marian Hanlon ,  John Watkins ,  Matthew Baker ,  Jeffrey C. Way

    IPC分类号： C07K14/55 ,  C12N15/62

    CPC分类号： C07K16/30 ,  C07K16/28 ,  C07K16/2863 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention relates to artificial modified proteins, preferably fusion proteins, having a reduced immunogenicity compared to the parent non-modified molecule when exposed to a species in vivo. The invention relates, above all, to novel immunoglobulin fusion proteins which essentially consist of an immunoglobulin molecule or a fragment thereof covalently fused via its C-terminus to the N-terminus of a biologically active non-immunoglobulin molecule, preferably a polypeptide or protein or a biologically active fragment thereof. In a specific embodiment, the invention relates to fusion proteins consisting of an Fc portion of an antibody which is fused as mentioned to the non-immunological target molecule which elicits biological or pharmacological efficacy. The molecules of the invention have amino acid sequences which are altered in one or more amino acid residue positions but have in principal the same biological activity as compared with the non-altered molecules. The changes are made in regions of the molecules which are identified as T-cell epitopes, which contribute to an immune reaction in a living host. Thus, the invention also relates to a novel method of making such fusion proteins by identifying said epitopes comprising calculation of T-cell epitope values for MHC Class II molecule binding sites in a peptide by computer-aided methods.

    摘要翻译： 本发明涉及人体修饰蛋白，优选融合蛋白，当与体内物种暴露时，与亲本非修饰分子相比具有降低的免疫原性。 本发明首先涉及新的免疫球蛋白融合蛋白，其基本上由免疫球蛋白分子或其通过C末端与生物活性非免疫球蛋白分子，优选多肽或蛋白质的N末端共价融合的片段组成，或 其生物活性片段。 在一个具体的实施方案中，本发明涉及由抗体的Fc部分组成的融合蛋白，所述Fc部分如提及的非免疫靶标分子融合而引起生物学或药理学功效。 本发明的分子具有氨基酸序列，其在一个或多个氨基酸残基位置被改变，但与未改变的分子相比具有相同的生物学活性。 在被鉴定为T细胞表位的分子的区域中进行改变，其有助于在宿主中的免疫反应。 因此，本发明还涉及通过鉴定所述表位来制备此类融合蛋白的新方法，包括通过计算机辅助方法计算肽中MHC II类分子结合位点的T细胞表位值。