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    Artificial proteins with reduced immunogenicity
    3.
    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
    4.
    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。

    Modified antibodies to prostate-specific membrane antigen and uses thereof
    5.
    发明授权
    Modified antibodies to prostate-specific membrane antigen and uses thereof 有权
    前列腺特异性膜抗原的修饰抗体及其用途

    公开(公告)号：US07045605B2

    公开(公告)日：2006-05-16

    申请号：US10160505

    申请日：2002-05-30

    申请人： Neil Bander ,  Francis J. Carr ,  Anita Hamilton

    发明人： Neil Bander ,  Francis J. Carr ,  Anita Hamilton

    IPC分类号： C07K16/00 ,  A61K39/395 ,  C12P21/00 ,  C12N15/02

    CPC分类号： C07K16/3069 ,  A61K47/6869 ,  A61K51/1072 ,  A61K2039/505 ,  C07K2317/56

    摘要： Modified antibodies, or antigen-binding fragments thereof, to the extracellular domain of human prostate specific membrane antigen (PSMA) are provided. The modified anti-PSMA antibodies, or antigen-binding fragments thereof, have been rendered less immunogenic compared to their unmodified counterparts to a given species, e.g., a human. Pharmaceutical compositions including the aforesaid antibodies, nucleic acids, recombinant expression vectors and host cells for making such antibodies and fragments are also disclosed. Methods of using the antibodies of the invention to detect human PSMA, or to ablate or kill a PSMA-expressing cell, e.g., a PSMA-expressing cancer or prostatic cell, either in vitro or in vivo, are also provided.

    摘要翻译： 提供了修饰抗体或其抗原结合片段到人前列腺特异性膜抗原（PSMA）的细胞外结构域。 修饰的抗PSMA抗体或其抗原结合片段与其给定物种（例如人）的未修饰对应物相比，具有较少的免疫原性。 还公开了包含上述抗体，核酸，重组表达载体和用于制备此类抗体和片段的宿主细胞的药物组合物。 还提供了使用本发明的抗体来检测人类PSMA或在体外或体内烧伤或杀死表达PSMA的细胞例如表达PSMA的癌症或前列腺细胞的方法。

    Method for the production of non-immunogenic proteins
    7.
    发明申请
    Method for the production of non-immunogenic proteins 有权
    生产非免疫原性蛋白的方法

    公开(公告)号：US20070014796A1

    公开(公告)日：2007-01-18

    申请号：US11516295

    申请日：2006-09-06

    申请人： Francis Carr ,  Fiona Adair ,  Anita Hamilton ,  Graham Carter

    发明人： Francis Carr ,  Fiona Adair ,  Anita Hamilton ,  Graham Carter

    IPC分类号： A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C07K16/30 ,  C07K14/74

    CPC分类号： G01N33/6878 ,  A61K38/00 ,  C07K14/3153 ,  C07K16/461 ,  C07K2319/00 ,  G06F19/00

    摘要： A target protein is rendered less immunogenic to a given species by (a) determining at least part of the amino acid sequence of the target protein; (b) identifying in the amino acid sequence one or more potential epitopes for T-cells (“T-cell epitopes”) of the given species; and (c) modifying the amino acid sequence to eliminate at least one of the T-cell epitopes identified in step (b) to reduce the immunogenicity of the protein when exposed to the immune system of the given species.

    摘要翻译： 通过（a）确定靶蛋白的至少一部分氨基酸序列，靶蛋白对给定物种的免疫原性降低; （b）在氨基酸序列中鉴定给定物种的T细胞（“T细胞表位”）的一个或多个潜在表位; 和（c）修饰氨基酸序列以消除步骤（b）中鉴定的至少一种T细胞表位，以降低当暴露于给定物种的免疫系统时蛋白质的免疫原性。

    Immunogenicity-reduced anti-cr1 antibody and compositions and methods of treatment based thereon
    9.
    发明申请
    Immunogenicity-reduced anti-cr1 antibody and compositions and methods of treatment based thereon 审中-公开
    免疫原性降低的抗cr1抗体及其组合物和治疗方法

    公开(公告)号：US20070224196A1

    公开(公告)日：2007-09-27

    申请号：US10551525

    申请日：2004-03-29

    申请人： Jeff Himawan ,  Anita Hamilton ,  Francis Carr

    发明人： Jeff Himawan ,  Anita Hamilton ,  Francis Carr

    IPC分类号： A61K48/00 ,  A61K31/70 ,  A61K39/395 ,  C12N5/06 ,  C07K16/28

    CPC分类号： C07K16/28 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/31

    摘要： The invention provides immunogenicity-reduced antibodies or antibody fragments that bind a human CR1 receptor. The immunogenicity-reduced anti-CR1 antibody of the invention comprises one or more non-human sequences modified to comprise one or more amino acid substitutions so that the immunogenicity-reduced antibody id non-immunogenic or less immunogenic to a human. The invention also provides bispecific molecules comprising such an immunogenicity-reduced anti-CR1 antibody and an antigen-recognition portion that binds a pathogen. The invention further provides methods and compositions for the treatment of diseases or disorders caused by a blood-borne immunogenic pathogen using the bispecific molecule the invention of the invention.

    摘要翻译： 本发明提供结合人CR1受体的免疫原性降低的抗体或抗体片段。 本发明的免疫原性降低的抗CR1抗体包含一个或多个修饰为包含一个或多个氨基酸取代的非人序列，使得免疫原性降低的抗体id对人免疫原性较小或免疫原性较小。 本发明还提供了包含这种免疫原性降低的抗CR1抗体和结合病原体的抗原识别部分的双特异性分子。 本发明还提供了用于治疗由使用本发明的本发明的双特异性分子的由血源性免疫原性病原体引起的疾病或病症的方法和组合物。