公开(公告)号：US20070269435A1

公开(公告)日：2007-11-22

申请号：US11716878

申请日：2007-03-12

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

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

IPC分类号： A61K39/395 ,  A61P35/00 ,  C07H21/00 ,  C12P21/08

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，其基本上由通过其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末端共价融合的免疫球蛋白分子或其片段组成，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。

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。

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。