知搜-全球专利检索

  1. 登录
  2. 注册

搜索结果

32 条记录 (耗时 0.029 秒)

    Artificial proteins with reduced immunogenicity
    1.
    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。

    Anti-KSA/IL-2 fusion proteins with reduced immunogenicity
    3.
    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。

    Enhancing the circulating half-life of antibody-based fusion proteins
    4.
    发明申请
    Enhancing the circulating half-life of antibody-based fusion proteins 审中-公开
    增强基于抗体的融合蛋白的循环半衰期

    公开(公告)号：US20060194952A1

    公开(公告)日：2006-08-31

    申请号：US11430745

    申请日：2006-05-09

    申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

    发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

    IPC分类号： C07H21/04 ,  C07K16/46 ,  C07K14/54

    CPC分类号： C07K16/30 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30

    摘要： Disclosed are methods for the genetic construction and expression of antibody-based fusion proteins with enhanced circulating half-lives. The fusion proteins of the present invention lack the ability to bind to immunoglobulin Fc receptors, either as a consequence of the antibody isotype used for fusion protein construction, or through directed mutagenesis of antibody isotypes that normally bind Fc receptors. The fusion proteins of the present invention may also contain a functional domain capable of binding an immunoglobulin protection receptor.

    摘要翻译： 公开了用于具有增强的循环半衰期的基于抗体的融合蛋白的遗传构建和表达的方法。 作为用于融合蛋白构建的抗体同种型或通过定向诱变通常结合Fc受体的抗体同种型，本发明的融合蛋白缺乏结合免疫球蛋白Fc受体的能力。 本发明的融合蛋白还可以含有能够结合免疫球蛋白保护受体的功能结构域。

    Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation
    6.
    发明申请
    Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation 有权
    异二聚体融合蛋白可用于靶向免疫治疗和一般免疫刺激

    公开(公告)号：US20050137384A1

    公开(公告)日：2005-06-23

    申请号：US10935532

    申请日：2004-09-07

    申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

    发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K47/48 ,  A61P37/04 ,  C07K14/54 ,  C07K16/30 ,  C07K19/00 ,  C12P21/00 ,  C07K16/46

    CPC分类号： C07K14/5434 ,  A61K38/00 ,  A61K2039/57 ,  C07K14/54 ,  C07K16/30 ,  C07K2319/00 ,  C07K2319/30

    摘要： Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.

    摘要翻译： 公开了用异二聚体细胞因子白细胞介素-12产生融合蛋白的方法。 为了确保在融合蛋白中获得融合和非融合亚基的适当比例，使用了基因工程的具体逐步方法。 这包括首先在生产细胞系中表达非融合的p40IL-12亚基，随后或在同一细胞中同时表达第二重组融合蛋白，其由通过肽键连接到p35亚基的p35亚基组成的融合多肽 IL-12。 含有p35融合蛋白的分子不能从转染的哺乳动物细胞中分泌，而与p40亚单位一对一比例没有首先复合，从而确保活性异二聚体融合蛋白的产生。

    ENHANCING THE CIRCULATING HALF-LIFE OF ANTIBODY-BASED FUSION PROTEINS
    7.
    发明申请
    ENHANCING THE CIRCULATING HALF-LIFE OF ANTIBODY-BASED FUSION PROTEINS 审中-公开
    增强基于抗体的融合蛋白的循环寿命

    公开(公告)号：US20090088561A1

    公开(公告)日：2009-04-02

    申请号：US12244520

    申请日：2008-10-02

    申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

    发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

    IPC分类号： C07H21/00

    CPC分类号： C07K16/30 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30

    摘要： Disclosed are methods for the genetic construction and expression of antibody-based fusion proteins with enhanced circulating half-lives. The fusion proteins of the present invention lack the ability to bind to immunoglobulin Fc receptors, either as a consequence of the antibody isotype used for fusion protein construction, or through directed mutagenesis of antibody isotypes that normally bind Fc receptors. The fusion proteins of the present invention may also contain a functional domain capable of binding an immunoglobulin protection receptor.

    摘要翻译： 公开了用于具有增强的循环半衰期的基于抗体的融合蛋白的遗传构建和表达的方法。 作为用于融合蛋白构建的抗体同种型或通过定向诱变通常结合Fc受体的抗体同种型，本发明的融合蛋白缺乏结合免疫球蛋白Fc受体的能力。 本发明的融合蛋白还可以含有能够结合免疫球蛋白保护受体的功能结构域。

    Methods for enhancing the efficacy of IL-2 mediated immune responses
    8.
    发明申请
    Methods for enhancing the efficacy of IL-2 mediated immune responses 审中-公开
    增强IL-2介导免疫反应功效的方法

    公开(公告)号：US20080025947A1

    公开(公告)日：2008-01-31

    申请号：US11825220

    申请日：2007-07-05

    申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

    发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

    IPC分类号： A61K38/20 ,  A61P37/04 ,  C07K14/55

    CPC分类号： C07K16/2866 ,  A61K2039/55533 ,  C07K14/55 ,  C07K16/2812 ,  C07K16/30

    摘要： Methods directed to enhancing the effectiveness of IL-2 in stimulating the immune system is disclosed. According to one method, an antagonist directed against the CD25 subunit of the high-affinity IL-2 receptor complex is administered in conjunction with IL-2. The CD25 antagonist may be an anti-CD25 antibody. According to another method, an anti-IL-2 antibody is administered in conjunction with IL-2. In another method, a mutant IL-2 with diminished ability to bind the CD25 subunit of the high-affinity IL-2 receptor complex is administered. In another method, an CD4 antagonist is administered in conjunction with IL-2 in order to stimulate the immune system.

    摘要翻译： 公开了旨在增强IL-2在刺激免疫系统中的有效性的方法。 根据一种方法，与IL-2结合施用针对高亲和力IL-2受体复合物的CD25亚基的拮抗剂。 CD25拮抗剂可以是抗CD25抗体。 根据另一种方法，抗IL-2抗体与IL-2联合施用。 在另一种方法中，施用了与高亲和力IL-2受体复合物的CD25亚基结合能力降低的突变体IL-2。 在另一种方法中，CD4拮抗剂与IL-2联合施用以刺激免疫系统。