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1. 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。

2. 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。

3. 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。

4. 发明申请

US20050222392A1 Anti-idiotype anti-cea antibody molecules and its use as cancer vaccine 审中-公开
标题翻译：抗独特型抗cea抗体分子及其用作癌症疫苗
公开(公告)号：US20050222392A1
公开(公告)日：2005-10-06
申请号：US10510523
申请日：2003-04-07
申请人： Graham Carter , Francis Carr
发明人： Graham Carter , Francis Carr
IPC分类号： C12N15/09 , A61K38/00 , A61K39/00 , A61K39/395 , A61P35/00 , C07K16/08 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/46 , C07K19/00 , C07K16/44
CPC分类号： C07K16/2896 , A61K39/00 , C07K16/3007 , C07K16/4266 , C07K2317/565 , C07K2318/10
摘要： The present invention provides molecules, preferably designed immunoglubulins, suitable for use as an anti-idiotype vaccine to CEA positive tumours. The molecules induce both an MHC class I and MHC class II mediated immune response to the CEA bearing tumour cells for an efficient and sustained host anti-tumour response. The present invention provides modified versions of anti-idiotype anti-CEA antibodies, preferably mouse antibody 708, with improved vaccination properties. The modifications are related to the introduction of sequences tracts deriving from e.g. CEA, CD55 antigen and CEA cancer-specific MHC epitopes into the variable regions of said antibody molecules.
摘要翻译：本发明提供适合用作CEA阳性肿瘤的抗独特型疫苗的分子，优选设计的免疫球蛋白。分子诱导MHC I类和MHC II类介导的对携带肿瘤细胞的CEA的免疫应答，以获得有效和持续的宿主抗肿瘤反应。本发明提供具有改善的疫苗接种性质的抗独特型抗CEA抗体，优选小鼠抗体708的修饰形式。这些修饰涉及引入从例如， CEA，CD55抗原和CEA癌特异性MHC抗原决定基转移到所述抗体分子的可变区中。

5. 发明申请

US20050020494A1 Modified human growth hormone 审中-公开
标题翻译：改良人生长激素
公开(公告)号：US20050020494A1
公开(公告)日：2005-01-27
申请号：US10488662
申请日：2002-08-30
申请人： Francis Carr , Graham Carter
发明人： Francis Carr , Graham Carter
IPC分类号： C12N15/09 , A61K38/27 , A61K39/00 , A61P5/10 , C07K14/61 , C12N15/12 , C12Q1/04
CPC分类号： C07K14/61 , A61K39/00
摘要： The invention relates to the modification of human growth hormone (high) to result in human growth hormone proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in-vivo. The invention relates, furthermore, to T-cell epitome sequences deriving from high, which are immunogenic.
摘要翻译：本发明涉及人体生长激素（高）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少免疫原性的人生长激素蛋白质。此外，本发明还涉及来自高的免疫原性的来自高的T细胞表达序列。

6. 发明申请

US20070014796A1 Method for the production of non-immunogenic proteins 有权
标题翻译：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。

7. 发明申请

US20050240009A1 T-cell epitopes in staphylococcal enterotoxin b 审中-公开
标题翻译：葡萄球菌肠毒素中的T细胞表位b
公开(公告)号：US20050240009A1
公开(公告)日：2005-10-27
申请号：US10525113
申请日：2003-08-18
申请人： Francis Carr , Matthew Baker , Graham Carter
发明人： Francis Carr , Matthew Baker , Graham Carter
IPC分类号： C12N15/09 , A61K38/00 , A61K39/085 , A61K48/00 , A61P35/00 , A61P37/04 , A61P43/00 , C07K2/00 , C07K14/24 , C07K14/31 , C12N15/31 , A61K39/02
CPC分类号： C07K14/31
摘要： The present invention relates to the field of immunology. The invention identifies determinants on staphylococcal enterotoxin B (SEB) able to evoke an immune response. In particular the invention is concerned with the identification of epitopes for T-cells in SEB. The invention relates furthermore to T-cell epitope peptides derived from SEB by means of which it is possible to create modified SEB variants with reduced immunogenicity.
摘要翻译：本发明涉及免疫学领域。本发明鉴定能够诱发免疫应答的葡萄球菌肠毒素B（SEB）的决定因素。特别地，本发明涉及SEB中T细胞表位的鉴定。本发明还涉及从SEB衍生的T细胞表位肽，通过它们可以产生具有降低的免疫原性的修饰的SEB变体。

8. 发明申请

US20050181459A1 Method for mapping and eliminating T cell epitopes 审中-公开
标题翻译：映射和消除T细胞表位的方法
公开(公告)号：US20050181459A1
公开(公告)日：2005-08-18
申请号：US11009460
申请日：2004-12-10
申请人： Matthew Baker , Francis Carr , Graham Carter
发明人： Matthew Baker , Francis Carr , Graham Carter
IPC分类号： C12N5/08 , G01N33/48 , G01N33/50 , G01N33/53 , G01N33/567 , G01N33/68 , G06F19/00
CPC分类号： G01N33/6878 , G01N33/5047
摘要： The invention provides methods for the identification of immunogenic regions within the amino acid residue sequence of a polypeptide, such as a therapeutic protein or a fragment thereof. The method comprises the steps of: (i) culturing, in vitro, an aliquot of peripheral blood monocyte cells (PBMC) isolated from a donor in the presence of a peptide for a period of up to about 7 days, the amino acid residue sequence of the peptide being identical to at least a portion of the amino acid residue sequence of the polypeptide of interest, the peptide being selected from a library of peptides, the amino acid residue sequences of the individual peptides of the library collectively encompassing the entire amino acid residue sequence of the polypeptide of interest; culturing the T cell aliquot from step (i) for an additional period of up to about 3 days in the presence of a T cell proliferation-stimulating cytokine to expand the number of T cells therein; (iii) culturing the T cell aliquot from step (ii) for a period of about 4 days in the presence of autologous irradiated PBMC from the same donor and in the presence of an additional amount of the peptide sufficient to re-prime the T cells within the PBMC with the peptide; (iv) determining the level of T cell proliferation of the re-primed T cells relative to an established baseline control level of proliferation; and (v) repeating steps (i) through (iv) with each peptide of the library of peptides to thereby identify at least one immunogenic region within the amino acid residue sequence of the polypeptide of interest.
摘要翻译：本发明提供了鉴定多肽的氨基酸残基序列（例如治疗性蛋白质或其片段）内的免疫原性区域的方法。所述方法包括以下步骤：（i）在体外培养在肽存在下从供体分离至多约7天的外源血液单核细胞（PBMC）的等分试样，所述氨基酸残基序列所述肽与所述多肽的氨基酸残基序列的至少一部分相同，所述肽选自肽文库，所述文库的各个肽的氨基酸残基序列共同包含整个氨基酸所述多肽的残基序列; 在T细胞增殖刺激细胞因子的存在下，将来自步骤（i）的T细胞等分试样培养多达约3天，以扩增其中的T细胞数; （iii）在来自相同供体的自体照射的PBMC的存在下和在足以重新提取T细胞的另外量的肽的存在下，从步骤（ii）培养T细胞等分试样约4天的时间在PBMC内用肽; （iv）相对于已建立的基线对照增殖水平确定重新激活的T细胞的T细胞增殖水平; 和（v）与肽文库的每个肽重复步骤（i）至（iv），从而鉴定感兴趣的多肽的氨基酸残基序列内的至少一个免疫原性区域。

9. 发明申请

US20070148739A1 Fusion proteins of interferon alpha muteins with improved properties 失效
标题翻译：具有改善性质的干扰素α突变蛋白的融合蛋白
公开(公告)号：US20070148739A1
公开(公告)日：2007-06-28
申请号：US10546112
申请日：2004-02-18
申请人： Tim Jones , Matthew Baker , Marian Hanlon , Francis Carr
发明人： Tim Jones , Matthew Baker , Marian Hanlon , Francis Carr
IPC分类号： A61K38/21 , C07H21/04 , C12P21/04 , C07K14/56
CPC分类号： A61K38/212 , C07K14/56 , C07K2319/30
摘要： The invention concerns human interferon alpha and in particular modified forms of interferon alpha 2 with improved properties. The improved proteins contain amino acid substitutions at specific positions that confer increased relative activity in biological assays. The invention provides also modified interferon alpha 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：本发明涉及人类干扰素α，特别涉及具有改进性质的干扰素α2的修饰形式。改进的蛋白质在特定位置含有氨基酸取代，其在生物测定中赋予增加的相对活性。本发明还提供修饰的干扰素α，其具有改善的生物活性，伴随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

US20050256304A1 Modified factor VIII 审中-公开
标题翻译：修改因子VIII
公开(公告)号：US20050256304A1
公开(公告)日：2005-11-17
申请号：US10511559
申请日：2003-04-17
申请人： Tim Jones , Matthew Baker , Francis Carr
发明人： Tim Jones , Matthew Baker , Francis Carr
IPC分类号： C12N15/09 , A61K38/00 , A61K38/10 , A61K38/36 , A61K38/37 , A61K39/00 , A61P7/00 , A61P7/04 , A61P37/06 , C07K7/08 , C07K14/755 , C12N15/12 , C12P21/02
CPC分类号： C07K14/755 , A61K38/37 , A61K39/00
摘要： The invention relates to the modification of human Factor VIII (FVIII) to result in FVIII proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo. The invention relates furthermore to T-cell epitope peptides derived from said non-modified protein by means of which it is possible to create modified FVIII variants with reduced immunogenicity.
摘要翻译：本发明涉及人因子VIII（FVIII）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少免疫原性的FVIII蛋白。本发明进一步涉及衍生自所述非修饰蛋白质的T细胞表位肽，借此可以产生具有降低的免疫原性的修饰的FVIII变体。

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