Solid-phase competitive assay utilizing a fusion protein
    1.
    发明授权
    Solid-phase competitive assay utilizing a fusion protein 失效
    使用融合蛋白的固相竞争性测定

    公开(公告)号:US5532135A

    公开(公告)日:1996-07-02

    申请号:US46103

    申请日:1993-04-08

    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。

    Method and compositions for carcinoma diagnosis
    2.
    发明授权
    Method and compositions for carcinoma diagnosis 失效
    癌症诊断方法和组成

    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

    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。

    Anti-KC4 humanized monoclonal antibody and cells that express the antibody
    3.
    再颁专利
    Anti-KC4 humanized monoclonal antibody and cells that express the antibody 失效
    抗KC4人源化单克隆抗体和表达抗体的细胞

    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。

    Modified antibodies with human milk fat globule specificity and uses
    4.
    发明授权
    Modified antibodies with human milk fat globule specificity and uses 失效
    改良抗体与人乳脂肪球特异性及用途

    公开(公告)号:US06936706B2

    公开(公告)日:2005-08-30

    申请号:US09947839

    申请日:2001-09-06

    IPC分类号: A61K38/00 C07K16/30 C07H21/02

    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。

    Use of modified antibodies with human milk fat globule specificity
    5.
    发明授权
    Use of modified antibodies with human milk fat globule specificity 失效
    使用具有人乳脂肪球特异性的修饰抗体

    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

    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。

    Recombinant peptides derived from the Mc3 anti-BA46 antibody, methods of use thereof, and methods of humanizing antibody peptides
    6.
    发明授权
    Recombinant peptides derived from the Mc3 anti-BA46 antibody, methods of use thereof, and methods of humanizing antibody peptides 失效
    衍生自Mc3抗BA46抗体的重组肽,其使用方法和抗体肽人源化方法

    公开(公告)号:US06309636B1

    公开(公告)日:2001-10-30

    申请号:US08525539

    申请日:1995-09-14

    IPC分类号: A61K33395

    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。 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。

    Modified antibodies with human milk fat globule specificity
    8.
    发明授权
    Modified antibodies with human milk fat globule specificity 失效
    具有人乳脂肪球特异性的修饰抗体

    公开(公告)号:US5804187A

    公开(公告)日:1998-09-08

    申请号:US129930

    申请日:1993-09-30

    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').sub.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。

    Polynucleotides encoding modified antibodies with human milk fat globule
specificity
    9.
    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

    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。

    Method of treating human breast cancer by administration of radiolabeled
antibody and unsaturated fatty acids
    10.
    发明授权
    Method of treating human breast cancer by administration of radiolabeled antibody and unsaturated fatty acids 失效
    通过给予放射性标记抗体和不饱和脂肪酸治疗人乳腺癌的方法

    公开(公告)号:US5766571A

    公开(公告)日:1998-06-16

    申请号:US496339

    申请日:1995-06-29

    摘要: An improved in vivo method of inhibiting or retarding the growth of malignant tumor cells in a subject comprises administering the subject antitumor therapy, the improvement comprising administering to the subject at least one product comprising an agent selected from the group consisting of polyunsaturated fatty acids, prostaglandins, prostacyclins, thromboxanes, leukotrienes, malone-aldehyde, triene epoxides, analogs thereof, salts thereof and mixtures thereof, the antitumor therapy and the product being administered in amounts and for a period of time effective to attain the desired effect. An in vivo method of inhibiting or retarding the growth of malignant tumor cells comprises administering to a subject in need of such treatment at least one anti-cell antigen specific radiolabeled antibody and at least one product comprising an agent such as polyunsaturated fatty acids, prostaglandins, prostacyclins, thromboxanes, leukotrienes, malonealdehyde, triene epoxides, salts thereof and mixtures thereof, the antibody and the product being administered in amount and for a period of time effective to attain the desired effect. A kit for use in antitumor therapy comprises in separate containers an antitumor agent such as a chemotherapeutic agent, an antitumor hormonal agent, an anti-target cell antibody, external and an internal irradiation agents, or biological response modifiers, and an agent such as polyunsaturated fatty acids, prostaglandins, prostacyclins, thromboxanes, leukotrienes, malonealdehyde, triene epoxides, salts thereof or mixtures thereof.

    摘要翻译: 抑制或延缓受试者恶性肿瘤细胞生长的改进的体内方法包括施用本发明的抗肿瘤疗法,其改进包括向受试者施用至少一种产品,其包含选自多不饱和脂肪酸,前列腺素 ,前列环素,血栓素,白三烯,丙二醛,三烯环氧化物,其类似物,其盐及其混合物,抗肿瘤治疗和产品以有效达到期望效果的量和一段时间来施用。 抑制或延缓恶性肿瘤细胞生长的体内方法包括向需要这种治疗的受试者施用至少一种抗细胞抗原特异性放射性标记的抗体和至少一种包含诸如多不饱和脂肪酸,前列腺素, 前列环素,血栓素,白三烯,糠醛,三烯环氧化物,其盐和其混合物,所述抗体和产物以有效达到所需效果的量和一段时间来施用。 用于抗肿瘤治疗的试剂盒包括在单独的容器中,抗肿瘤剂如化学治疗剂,抗肿瘤激素剂,抗靶细胞抗体,外部和内部照射剂或生物反应调节剂,以及诸如多不饱和剂 脂肪酸,前列腺素,前列环素,血栓素,白三烯,麝香醛,三烯环氧化物,其盐或其混合物。