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1. 发明申请

US20070269435A1 Artificial proteins with reduced immunogenicity 有权
标题翻译：具有降低免疫原性的人造蛋白
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。

2. 发明授权

US07615217B2 Artificial proteins with reduced immunogenicity 有权
标题翻译：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。

3. 发明授权

US07189830B2 Anti-KSA/IL-2 fusion proteins with reduced immunogenicity 有权
标题翻译：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。

4. 发明申请

US20060062761A1 Modified interferon alpha with reduced immunogenicity 审中-公开
标题翻译：修饰的干扰素α具有降低的免疫原性
公开(公告)号：US20060062761A1
公开(公告)日：2006-03-23
申请号：US10469679
申请日：2002-03-01
申请人： Francis Carr , Graham Carter , Tim Jones , Matthew Baker , John Watkins , Marian Hanlon
发明人： Francis Carr , Graham Carter , Tim Jones , Matthew Baker , John Watkins , Marian Hanlon
IPC分类号： C07K14/56 , C07H21/04 , C12P21/04 , A61K38/21
CPC分类号： C07K7/06 , A61K38/00 , C07K14/56
摘要： The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular to the modification of human interferon alpha and specifically interferon alpha 2(INFα2) to result in proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when use in vivo.
摘要翻译：本发明涉及特别用于人，特别是用于治疗用途的多肽。所述多肽是修饰的多肽，其中所述修饰导致多肽在施用于人受试者时引起免疫应答的倾向降低。本发明特别涉及人干扰素α和特异性干扰素α2（INFalpha2）的修饰，以产生当在体内使用时基本上不具有免疫原性或比任何未修饰的对应物更少免疫原性的蛋白质。

5. 发明申请

US20050054052A1 Modified interferon beta with reduced immunogenicity 有权
标题翻译：修饰的干扰素β具有降低的免疫原性
公开(公告)号：US20050054052A1
公开(公告)日：2005-03-10
申请号：US10471894
申请日：2002-03-15
申请人： Francis Carr , Graham Carter , Tim Jones , John Watkins
发明人： Francis Carr , Graham Carter , Tim Jones , John Watkins
IPC分类号： C12N15/09 , A61K38/21 , A61K39/00 , A61P31/12 , A61P37/02 , C07K7/08 , C07K14/565 , C12N15/22 , C12P21/02 , C07H21/04 , C07K14/765 , C12P21/04
CPC分类号： C07K14/565
摘要： The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of human interferon beta to result in proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.
摘要翻译：本发明涉及特别用于人，特别是用于治疗用途的多肽。所述多肽是修饰的多肽，其中所述修饰导致多肽在施用于人受试者时引起免疫应答的倾向降低。本发明特别涉及人类干扰素β的修饰，以产生当在体内使用时与任何未修饰的对应物基本上不具有免疫原性或较低免疫原性的蛋白质。

6. 发明授权

US07381795B2 Modified interferon beta with reduced immunogenicity 有权
标题翻译：修饰的干扰素β具有降低的免疫原性
公开(公告)号：US07381795B2
公开(公告)日：2008-06-03
申请号：US10471894
申请日：2002-03-15
申请人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
发明人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
IPC分类号： C07K14/00 , C12N15/24
CPC分类号： C07K14/565
摘要： A modified interferon beta (INFβ) is provided, which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered to a human in vivo. The modified INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by a substitution at one or more residues of SEQ ID NO: 1. Preferred substitutions are at residues selected from the group consisting of residue 50, 59, 60, 62, 63, 66, 67, 69, 70, 125, 126, 129, 130, 132, 133, and 138. Examples of suitable substitutions include F50A, L57A, I59A, Y60N, M62A, L63A, I66T, F67H, I69A, F70A, Y125A, Y126A, I129A, L130A, Y132S, L133A, Y138H, and Y138A.
摘要翻译：提供了经修饰的干扰素β（INFbeta），当其在体内施用于人时，其比人INFbeta（SEQ ID NO：1）的免疫原性较低。修饰的INFbeta包含通过在SEQ ID NO：1的一个或多个残基处的取代而与SEQ ID NO：1不同的氨基酸残基序列。优选的取代是选自残基50,59,60，合适的取代的实例包括F50A，L57A，I59A，Y60N，M62A，L63A，I66T，F67H，I69A，SEQ ID NO：6,62,63,66,67,69,70,125,126,129,130,132,133,138。 F70A，Y125A，Y126A，I129A，L130A，Y132S，L133A，Y138H和Y138A。

7. 发明申请

US20090043076A1 Modified interferon beta with reduced immunogenicity 失效
公开(公告)号：US20090043076A1
公开(公告)日：2009-02-12
申请号：US12077120
申请日：2008-03-17
申请人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
发明人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
IPC分类号： C07K14/565
CPC分类号： C07K14/565
摘要： The present invention relates a modified human interferon beta (INFβ) which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered in vivo to a human. The modified human INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.

8. 发明授权

US07615615B2 Modified interferon beta with reduced immunogenicity 失效
标题翻译：修饰的干扰素β具有降低的免疫原性
公开(公告)号：US07615615B2
公开(公告)日：2009-11-10
申请号：US12077120
申请日：2008-03-17
申请人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
发明人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
IPC分类号： C07K14/00 , A61K38/19 , C12N15/24
CPC分类号： C07K14/565
摘要： The present invention relates a modified human interferon beta (INFβ) which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered in vivo to a human. The modified human INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.
摘要翻译：本发明涉及当在体内施用于人时，比人INFbeta（SEQ ID NO：1）具有较少的免疫原性的修饰的人干扰素β（INFbeta）。修饰的人INFbeta包含与SEQ ID NO：1不同的氨基酸残基，其选自L57A，L57C，L57D，L57E，L57G，L57H，L57K，L57N，L57P，L57Q，L57R ，L57S和L57T以及选自H140A，H140C，H140G和H140P的另外的取代基。

9. 发明授权

US07541439B2 Thrombopoietin proteins with improved properties 失效
标题翻译：具有改善性质的血小板生成素蛋白
公开(公告)号：US07541439B2
公开(公告)日：2009-06-02
申请号：US10561097
申请日：2004-06-25
申请人： Matthew Baker , John Watkins
发明人： Matthew Baker , John Watkins
IPC分类号： C07K19/00 , C07K14/52 , A61K38/19 , C12N15/19
CPC分类号： C07K14/524 , A61K38/00 , A61K39/00 , A61K2039/57 , C07K2319/30
摘要： The invention concerns human thrombopoietin and in particular modified forms of thrombopoietin (TPO) with improved properties. The improved proteins contain amino acid substitutions at specific positions within the TPO molecule. The invention provides modified TPO molecules, preferably fusion proteins comprising immunoglobulin constant regions and modified human TPO, with improved biological activity concomitant with reduced immunogenic potential in the protein. The improved proteins are intended for therapeutic use in the treatment of diseases in humans.
摘要翻译：本发明涉及人血小板生成素，特别是具有改进性质的血小板生成素（TPO）的修饰形式。改进的蛋白质在TPO分子内的特定位置含有氨基酸取代。本发明提供修饰的TPO分子，优选包含免疫球蛋白恒定区和修饰的人TPO的融合蛋白，具有改善的生物活性，伴随着蛋白质中的免疫原性潜力降低。改进的蛋白质用于治疗人类疾病的治疗用途。

10. 发明申请

US20060160995A1 Thrombopoietin proteins with improved properties 失效
公开(公告)号：US20060160995A1
公开(公告)日：2006-07-20
申请号：US10561097
申请日：2004-06-25
申请人： Matthew Baker , John Watkins
发明人： Matthew Baker , John Watkins
IPC分类号： C07K16/44
CPC分类号： C07K14/524 , A61K38/00 , A61K39/00 , A61K2039/57 , C07K2319/30
摘要： The invention concerns human thrombopoietin and in particular modified forms of thrombopoietin (TPO) with improved properties. The improved proteins contain amino acid substitutions at specific positions within the TPO molecule. The invention provides modified TPO molecules, preferably fusion proteins comprising immunoglobulin constant regions and modified human TPO, with improved biological activity concomitant with reduced immunogenic potential in the protein. The improved proteins are intended for therapeutic use in the treatment of diseases in humans.

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