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公开(公告)号：US06315997B1
公开(公告)日：2001-11-13
申请号：US08976288
申请日：1997-11-21
IPC分类号： A61K39395
CPC分类号： C07K16/465 , A61K38/00 , A61K51/1027 , A61K51/1051 , C07K16/28 , C07K16/3015 , C07K2317/24 , C07K2317/34 , C07K2317/567 , C07K2317/92 , G01N33/574
摘要： An analogue peptide that comprises the variable regions of the light or heavy chains of an antibody of a first species selectively binding to a carcinoma antigen has 1 to 46 amino acids of the framework regions per chain substituted with amino acids such as those present in equivalent positions in antibodies of a species other than the first species, or fragments thereof comprising 1 to 3 variable region CDRs per chain and optionally flanking regions thereof of 1 to 10 or more amino acids, alone or with an N-terminal fragment of 1 to 10 or more amino acids, combinations or mixtures thereof. The polypeptide may also comprise an effector agent and/or be glycosylated, and is presented as a composition with a carrier. The analogue peptides are used in diagnostic kits for carcinomas and methods for in vivo imaging and treating a primary or metastasized carcinoma, and in vitro diagnosing a carcinoma, ex vivo purging neoplastic cells from a biological fluid. RNAs and DNAs encode the analogue peptide, and a hybrid vector carrying the nucleotides and transfected cells express the peptides and a method produces the analogue peptide. An anti-idiotype polypeptide comprises polyclonal antibodies raised against an anti-carcinoma antibody or the analogue peptide of this invention, monoclonal antibodies thereof, Fab, Fab′, (Fab′)2, CDR, variable region, or analogues or fragments thereof, combinations thereof with an oligopeptide comprising a TRP trimer, tandem repeats thereof, or combination or mixtures thereof. An anti-idiotype hybrid polypeptide with an effector agent and the anti-idiotype polypeptide, an anti-carcinoma vaccine, an anti-carcinoma vaccination kit, a method of vaccinating against carcinoma and a method of lowering the serum concentration of a circulating antibody or polypeptide are provided.
摘要翻译： 包含选择性结合癌抗原的第一种物种的抗体的轻链或重链的可变区的类似肽具有每个被每个氨基酸取代的骨架区的1至46个氨基酸，例如存在于等同位置 在除第一种之外的物种的抗体中，或其片段包含1至3个可变区CDR，每个链及其任选侧翼区为1至10个或更多个氨基酸，单独或与1-10个N末端片段或 更多的氨基酸，其组合或混合物。 多肽还可以包含效应剂和/或被糖基化，并且作为具有载体的组合物呈递。 类似物肽用于癌症的诊断试剂盒和体内成像和治疗原发性或转移性癌症的方法，以及体外诊断癌症，从生物流体中离体清除肿瘤细胞。 RNA和DNA编码类似物肽，携带核苷酸和转染细胞的杂交载体表达肽，一种方法产生类似肽。 抗独特型多肽包括针对本发明的抗癌抗体或类似物肽，其单克隆抗体，Fab，Fab'，（Fab'）2，CDR，可变区或其类似物或片段，组合 其具有包含TRP三聚体，其串联重复序列或其组合或混合物的寡肽。 具有效应剂和抗独特型多肽的抗独特型杂合多肽，抗癌疫苗，抗癌疫苗试剂盒，疫苗接种癌的方法和降低循环抗体或多肽的血清浓度的方法 被提供。
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2.发明申请Recombinant Peptides Derived from the Mc3 Anti-BA46 Antibody, Methods of Use Thereof, and Methods of Humanizing Antibody Peptides 审中-公开衍生自Mc3抗BA46抗体的重组肽，其使用方法和人源化抗体肽的方法公开(公告)号：US20090010848A1
公开(公告)日：2009-01-08
申请号：US12143648
申请日：2008-06-20
CPC分类号： A61K51/1093 , A61K38/00 , A61K51/10 , A61K51/1051 , A61K51/1081 , A61K51/1096 , A61K2121/00 , A61K2123/00 , C07K16/3015
摘要： The present invention provides recombinant peptides that specifically and selectively bind to the human milk fat globule (HMFG) antigen, BA46. In particular, the present invention provides recombinant variants of the Mc3 antibody, including humanized versions of Mc3. The variant Mc3 peptides are particularly useful for diagnostic, prognostic, and therapeutic applications in the field of breast cancer.The present invention also provides methods for the humanization of antibodies such as murine monoclonal antibodies. The novel humanization methods are applied to the production of humanized Mc3 antibodies and it is shown that these humanized antibodies retain the ability to engage in high affinity binding to their cognate antigen. Such humanization enables the use of these antibodies for immunodiagnostic and immunotherapeutic applications in humans.
摘要翻译： 本发明提供了特异性且选择性地结合人乳脂肪球（HMFG）抗原BA46的重组肽。 特别地，本发明提供Mc3抗体的重组变体，包括人源化形式的Mc3。 该变体Mc3肽特别可用于乳腺癌领域的诊断，预后和治疗应用。 本发明还提供了抗体如人单克隆抗体人源化的方法。 新型人源化方法适用于人源化Mc3抗体的产生，并且显示这些人源化抗体保留参与与其同源抗原的高亲和力结合的能力。 这样的人源化使得能够使用这些抗体用于人体免疫诊断和免疫治疗应用。
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公开(公告)号：US06936706B2
公开(公告)日：2005-08-30
申请号：US09947839
申请日：2001-09-06
CPC分类号： C07K16/465 , A61K38/00 , A61K51/1027 , A61K51/1051 , C07K16/28 , C07K16/3015 , C07K2317/24 , C07K2317/34 , C07K2317/567 , C07K2317/92 , G01N33/574
摘要： An analogue peptide that comprises the variable regions of the light or heavy chains of an antibody of a first species selectively binding to a carcinoma antigen has 1 to 46 amino acids of the framework regions per chain substituted with amino acids such as those present in equivalent positions in antibodies of a species other than the first species, or fragments thereof comprising 1 to 3 variable region CDRs per chain and optionally flanking regions thereof of 1 to 10 or more amino acids, alone or with an N-terminal fragment of 1 to 10 or more amino acids, combinations or mixtures thereof. The polypeptide may also comprise an effector agent and/or be glycosylated, and is presented as a composition with a carrier. The analogue peptides are used in diagnostic kits for carcinomas and methods for in vivo imaging and treating a primary or metastasized carcinoma, and in vitro diagnosing a carcinoma, ex vivo purging neoplastic cells from a biological fluid. RNAs and DNAs encode the analogue peptide, and a hybrid vector carrying the nucleotides and transfected cells express the peptides and a method produces the analogue peptide. An anti-idiotype polypeptide comprises polyclonal antibodies raised against an anti-carcinoma antibody or the analogue peptide of this invention, monoclonal antibodies thereof, Fab, Fab′, (Fab′)2, CDR, variable region, or analogues or fragments thereof, combinations thereof with an oligopeptide comprising a TRP trimer, tandem repeats thereof, or combination or mixtures thereof. An anti-idiotype hybrid polypeptide with an effector agent and the anti-idiotype polypeptide, an anti-carcinoma vaccine, an anti-carcinoma vaccination kit, a method of vaccinating against carcinoma and a method of lowering the serum concentration of a circulating antibody or polypeptide are provided.
摘要翻译： 包含选择性结合癌抗原的第一种物种的抗体的轻链或重链的可变区的类似肽具有每个被每个氨基酸取代的骨架区的1至46个氨基酸，例如存在于等同位置 在除第一种之外的物种的抗体中，或其片段包含1至3个可变区CDR，每个链及其任选侧翼区为1至10个或更多个氨基酸，单独或与1-10个N末端片段或 更多的氨基酸，其组合或混合物。 多肽还可以包含效应剂和/或被糖基化，并且作为具有载体的组合物呈递。 类似物肽用于癌症的诊断试剂盒和体内成像和治疗原发性或转移性癌症的方法，以及体外诊断癌症，从生物流体中离体清除肿瘤细胞。 RNA和DNA编码类似物肽，携带核苷酸和转染细胞的杂交载体表达肽，一种方法产生类似肽。 抗独特型多肽包括针对本发明的抗癌抗体或类似物肽产生的多克隆抗体，其单克隆抗体，Fab，Fab'，（Fab'）2，CDR，可变区， 或其类似物或片段，其与包含TRP三聚体，其串联重复序列或其组合或混合物的寡肽的组合。 具有效应剂和抗独特型多肽的抗独特型杂合多肽，抗癌疫苗，抗癌疫苗试剂盒，疫苗接种癌的方法和降低循环抗体或多肽的血清浓度的方法 被提供。
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4.发明授权Polynucleotides encoding modified antibodies with human milk fat globule specificity 失效编码具有人乳脂肪球特异性的修饰抗体的多核苷酸
公开(公告)号：US5792852A
公开(公告)日：1998-08-11
申请号：US977696
申请日：1992-11-16
CPC分类号： C07K16/3015 , A61K38/00 , C07K2317/34
摘要： A polynucleotide encodes a modified antibody, or single chains thereof. The modified antibody has a non-antigen-binding peptide such as the constant regions of an antibody of a first species, peptide hormones, enzymes, and peptide transmitters; and a binding peptide such as the unsubstituted light and heavy chains of the variable region of an antibody of a second species which binds the human milk fat globule (HMFG) antigen. The non-antigen-binding peptide is linked to at least one chain of the binding peptide, the chains may be linked to one another at a site other than the antigenic binding site, and at least one chain of the binding peptide has 1 to 46 amino acids substituted with amino acids selected from specific ones assigned to each site. The polynucleotide and other products are also provided in the form of compositions, with a carrier. The polynucleotides may be RNAs and DNAs, and are also provided as hybrid vectors carrying them, and as transfected cells expressing the modified antibodies or their single chains.
摘要翻译： 多核苷酸编码修饰的抗体或其单链。 修饰的抗体具有非抗原结合肽，例如第一种的抗体的恒定区，肽激素，酶和肽发射体; 和结合肽，例如结合人乳脂肪球（HMFG）抗原的第二种抗体的可变区的未取代的轻链和重链。 非抗原结合肽与结合肽的至少一个链连接，链可以在除抗原结合位点之外的位置彼此连接，并且结合肽的至少一个链具有1至46个 用分配到每个位点的特定氨基酸取代的氨基酸。 多核苷酸和其它产品也以组合物的形式提供载体。 多核苷酸可以是RNA和DNA，并且也作为携带它们的杂交载体以及表达修饰抗体或其单链的转染细胞提供。
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公开(公告)号：US5532135A
公开(公告)日：1996-07-02
申请号：US46103
申请日：1993-04-08
IPC分类号： G01N33/535 , G01N33/543 , G01N33/574 , G01N33/537 , G01N33/544
CPC分类号： G01N33/535 , G01N33/54306 , G01N33/57415 , G01N33/57484 , G01N2333/705 , G01N2333/924 , G01N2333/938 , Y10S435/81
摘要： An in vitro solid-phase, competitive assay for detecting the presence of a peptide analyte in a biological sample comprises contacting a fusion protein, of first and second peptides, with a solid supported first antibody or fragment thereof, which binds the first peptide, adding a biological sample containing the peptide analyte and a second antibody or fragment thereof which binds the peptide analyte and the second peptide. The second antibody is allowed to bind any free analyte present in the sample, and to form solid supported complexes of fusion protein and antibody. The amount of solid supported second antibody detected is then compared to a control. When the amount of peptide analyte in the sample increases the amount of second antibody bound to the solid support decreases. An optional final addition of an antibody-binding molecule helps detect the solid supported complexes of the fusion protein and the second antibody or fragment. The assay may be utilized for detecting neoplastic antigens from tumors or their metastases by using a second peptide that binds specifically to an antibody specific to an antigen, such as an epithelial mammary cell antigen. A kit for detecting the presence of neoplastic tissue comprises the fusion protein, a first antibody or fragment thereof specifically binding the first peptide, and a second antibody or fragment thereof specifically binding the second peptide, and optionally a device for detecting the second antibody or fragment thereof, such as a labeled antibody-binding molecule.
摘要翻译： 用于检测生物样品中肽分析物的存在的体外固相竞争性测定包括将第一和第二肽的融合蛋白与固定的第一抗体或其片段接触，其结合第一肽，加入 包含肽分析物的生物样品和结合肽分析物和第二肽的第二抗体或其片段。 允许第二抗体结合存在于样品中的任何游离分析物，并形成固体支持的融合蛋白和抗体的复合物。 然后将检测到的固体支持的第二抗体的量与对照相比较。 当样品中肽分析物的量增加时，与固体支持物结合的第二抗体的量减少。 抗体结合分子的任选最终添加有助于检测融合蛋白和第二抗体或片段的固体支持的复合物。 该测定法可用于通过使用特异性结合抗原特异性抗体（例如上皮乳腺细胞抗原）的第二种肽来检测肿瘤或其转移瘤的肿瘤抗原。 用于检测肿瘤组织存在的试剂盒包含融合蛋白，特异性结合第一肽的第一抗体或其片段，以及特异性结合第二肽的第二抗体或其片段，以及任选的用于检测第二抗体或片段的装置 例如标记的抗体结合分子。
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公开(公告)号：US4584268A
公开(公告)日：1986-04-22
申请号：US583456
申请日：1984-02-24
IPC分类号： G01N33/574 , B65D71/00
CPC分类号： G01N33/57415 , Y10S435/96 , Y10S435/975 , Y10S436/80 , Y10S436/804 , Y10S436/808 , Y10S436/813 , Y10S530/806
摘要： Methods and compositions are provided for detecting the presence of carcinomas in a mammalian host by measuring the level of normal surface antigens specific for a differentiated cell in the serum of the host as compared to the normal level of such antigen. The method finds particular use in detecting residual carcinomas after therapy or in detecting the recurrence of neoplastic tissue, and assigning a tissue of origin to the neoplastic tissue.
摘要翻译： 提供了用于通过测量与该抗原正常水平相比，在宿主血清中分化细胞特异的正常表面抗原水平，来检测哺乳动物宿主中癌的存在的方法和组合物。 该方法特别用于检测治疗后的残留癌症或检测肿瘤组织的复发，并将肿瘤组织的原始组织分配。
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公开(公告)号：US06190885B1
公开(公告)日：2001-02-20
申请号：US08134198
申请日：1993-10-08
IPC分类号： C12P2104
CPC分类号： G01N33/54306 , G01N33/535 , G01N33/57415 , G01N33/57484 , G01N2333/705 , G01N2333/924 , G01N2333/938
摘要： A fusion protein comprises a sequence of amino acids which binds antibodies specific to the human milk fat globule (HMFG) differentiation antigens. Specific amino acid sequences are provided, and a fusion protein may be used as an immunogen and for diagnostic purposes.
摘要翻译： 融合蛋白包含结合对人乳脂肪球（HMFG）分化抗原特异性的抗体的氨基酸序列。 提供了具体的氨基酸序列，并且融合蛋白可以用作免疫原并用于诊断目的。
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8.发明授权Highly sensitive and specific solid-phase competitive assay utilizing a fusion protein 失效使用融合蛋白的高度灵敏和特异性的固相竞争性测定
公开(公告)号：US5514558A
公开(公告)日：1996-05-07
申请号：US129540
申请日：1993-09-30
IPC分类号： G01N33/535 , G01N33/543 , G01N33/574 , G01N33/544 , G01N33/563
CPC分类号： G01N33/535 , G01N33/54306 , G01N33/57415 , G01N33/57484 , G01N2333/705 , G01N2333/924 , G01N2333/938 , Y10S435/81
摘要： An in vitro solid-phase, competitive assay for detecting the presence of a peptide analyte in a biological sample, comprising contacting a fusion protein made of a first peptide and a second peptide to a solid supported first antibody which specifically binds to the first peptide, adding thereto a biological sample containing a peptide analyte, adding a second antibody specifically binding to the analyte and the second peptide, and allowing the second antibody to bind any free analyte present in the sample and the solid supported fusion protein to form analyte-second antibody and solid supported fusion protein-second antibody complexes, and determining the amount of solid supported second antibody present and comparing it to a control. When the amount of peptide analyte in the sample increases the amount of a second antibody bound to the solid support decreases. An optional final addition of an antibody-binding molecule helps detect the antibody-fusion protein complex bound to the solid support. The assay may be utilized for detecting neoplastic antigens from tumors or their metastases by utilizing a fusion protein containing an antigen of an epithelial mammary cell. A kit for detecting the presence of a neoplastic tissue comprises the fusion protein along with a first antibody specifically binding to the first peptide, and a second antibody specifically binding to the second peptide, and optionally a means for detecting the second antibody or fragment thereof, such as an antibody-binding molecule.
摘要翻译： 用于检测生物样品中肽分析物的存在的体外固相竞争性测定法，包括将由第一肽和第二肽制成的融合蛋白与固体支持的第一抗体接触，所述第一抗体特异性结合第一肽， 向其中加入含有肽分析物的生物样品，添加与分析物和第二肽特异性结合的第二抗体，并允许第二抗体结合存在于样品中的任何游离分析物和固体支持的融合蛋白以形成分析物 - 第二抗体 和固体支持的融合蛋白 - 第二抗体复合物，并确定存在的固体支持的第二抗体的量并将其与对照进行比较。 当样品中肽分析物的量增加时，与固体支持物结合的第二抗体的量减少。 抗体结合分子的可选最终添加有助于检测与固体支持物结合的抗体 - 融合蛋白复合物。 该测定法可用于通过利用含有上皮乳腺细胞抗原的融合蛋白来检测肿瘤或其转移瘤的肿瘤抗原。 用于检测肿瘤组织存在的试剂盒包括融合蛋白以及与第一肽特异性结合的第一抗体，以及特异性结合第二肽的第二抗体，以及任选的用于检测第二抗体或其片段的方法， 例如抗体结合分子。
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9.发明授权Monoclonal antibody specific to a novel glycoprotein antigen on human carcinoma cells 失效单克隆抗体对人类癌细胞的新型糖蛋白抗原特异性
公开(公告)号：US5077220A
公开(公告)日：1991-12-31
申请号：US237218
申请日：1988-08-26
CPC分类号： C07K16/30 , C07K16/3015 , A61K38/00
摘要： A hybridoma cell line is provided which is capable of producing monoclonal antibodies which bind to a unique determinant site on the surface and/or in the cytoplasm of human breast carcinoma cells and carcinoma cells of other adenocarcinomas and on the surface of normal human breast epithelial cells. The cell line of the invention was developed by immunizing mice with a select group of immunogens and a conventional myeloma cell line for fusion with the murine splenocytes harvested.The monoclonal antibody is identified as the BrE2 monoclonal antibody. The antigen is characterized as a high molecular weight glycoprotein complex having a molecular exceeding 400,000 daltons. This monoclonal antibody is especially useful for diagnostic, prognostic and therapeutic applications in human breast cell carcinoma.
摘要翻译： 提供了能够产生单克隆抗体的单克隆抗体，其结合人乳腺癌细胞的表面和/或细胞质和其他腺癌的癌细胞和正常人乳腺上皮细胞表面上的独特决定簇位点 。 通过用选择的免疫原组和常规骨髓瘤细胞系免疫小鼠来开发本发明的细胞系，以与收获的小鼠脾细胞融合。 单克隆抗体被鉴定为BrE2单克隆抗体。 该抗原的特征在于分子量超过400,000道尔顿的高分子量糖蛋白复合物。 该单克隆抗体特别可用于人乳腺癌细胞的诊断，预后和治疗应用。
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10.再颁专利公开(公告)号：USRE40535E1
公开(公告)日：2008-10-07
申请号：US10144047
申请日：2002-05-14
CPC分类号： C07K16/3015 , A61K38/00
摘要： An anti-KC-4 humanized monoclonal antibody that comprises the variable regions of the light and heavy chains of the anti-KC-4 murine antibody, wherein the light chain has 7 amino acids and the heavy chain has 12 amino acids of the framework regions substituted with amino acid present in equivalent positions in antibodies of a species other than munne, and the constant regions of a human antibody. The antibody may be labeled and/or glycosylated, and is presented as a composition with a carrier. The anti-KC-4 monoclonal antibody is used in diagnostic kits for cancer and in in vivo methods of imaging and treating a primary or metastasized cancer, and in vitro diagnosis and ex vivo purging neoplastic cells from a biological fluid. RNAs and DNAs encode the monoclonal antibody, and a hybrid vector carrying the nucleotides and transfected cells express the peptides.
摘要翻译： 抗KC-4人源化单克隆抗体，其包含抗KC-4鼠抗体的轻链和重链的可变区，其中轻链具有7个氨基酸，重链具有12个氨基酸的构架区 被替换为存在于除munne以外的物种的抗体中的等同位置的氨基酸和人抗体的恒定区。 抗体可以被标记和/或糖基化，并且作为具有载体的组合物存在。 抗KC-4单克隆抗体用于癌症的诊断试剂盒和用于成像和治疗原发性或转移性癌症的体内方法，以及来自生物流体的体外诊断和离体清除肿瘤细胞。 RNA和DNA编码单克隆抗体，携带核苷酸和转染细胞的杂交载体表达肽。
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