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    • 1. 发明授权
    • CA125 gene and its use for diagnostic and therapeutic interventions
    • CA125基因及其在诊断和治疗干预中的应用
    • US08124728B2
    • 2012-02-28
    • US10475117
    • 2003-10-17
    • Timothy O'BrienJohn BeardLowell Underwood
    • Timothy O'BrienJohn BeardLowell Underwood
    • C07K14/00C07K14/435
    • C07K14/47A61K38/00C12Q1/6886C12Q2600/158
    • The CA125 gene has been cloned. The CA125 molecule comprises three major domains: an extracellular amino terminal domain; a large multiple repeat domain; and a carboxy terminal domain which includes a transmembrane anchor with a short cytoplasmic domain. Additionally, an amino terminal extension is present. The molecular structure is dominated by a repeat domain comprising more than sixty 156-amino-acid repeat units The repeat units encompass an interactive disulfide bridged C-enclosure and the site of OC125 and M11 binding. The CA125 molecule is anchored at its carboxy terminal through a transmembrane domain and a short cytoplasmic tail. The structure has potential for use as a new gold standard for detecting the CA125 antigen, and can provide a basis for the development of a vaccine useful for the treatment of ovarian cancer and other carcinomas where CA125 is elevated.
    • 已经克隆了CA125基因。 CA125分子包含三个主要的结构域:细胞外氨基末端结构域; 一个大的多重重复域; 和包含具有短细胞质结构域的跨膜锚的羧基末端结构域。 此外,存在氨基末端延伸。 分子结构由包含多于六十六个156个氨基酸重复单元的重复结构域所支配。重复单元包含交互式二硫键桥接的C-封闭物和OC125和M11结合位点。 CA125分子在其羧基末端通过跨膜结构域和短的胞质尾部锚定。 该结构有可能用作检测CA125抗原的新金标准,可为开发可用于治疗CA125升高的卵巢癌和其他癌症的疫苗提供依据。
    • 2. 发明申请
    • CA125 gene and its use for diagnostic and therapeutic interventions
    • CA125基因及其在诊断和治疗干预中的应用
    • US20100331536A1
    • 2010-12-30
    • US12455366
    • 2009-06-01
    • Timothy O'BrienJohn BeardLowell Underwood
    • Timothy O'BrienJohn BeardLowell Underwood
    • C07H21/04
    • C07K14/47A61K38/00C12Q1/6886C12Q2600/156C12Q2600/158
    • The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. An amino terminal extension is presented, which comprises four genomic exons. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. More specifically, this invention is directed to a CA125 cDNA sequence which can be introduced into animal or human cells to achieve transcription or expression of the cDNA.
    • 已经克隆了CA125基因,并且已经鉴定了多个重复序列以及羧基末端。 CA125分子包含三个主要的结构域:细胞外氨基末端结构域(Domain 1); 一个大的多重重复域(域2); 和包含具有短细胞质结构域的跨膜锚的羧基末端结构域(结构域3)。 氨基末端结构域以其O-糖基化的能力为主,其结果是丝氨酸和苏氨酸残基的丰富度。 提供氨基末端延伸,其包含四个基因组外显子。 分子结构由包含156个氨基酸重复单元的重复结构域所支配,其包含表位结合位点。 已经确定,排序和连续地排列在CA125领域结构中的60多个重复单位。 更具体地,本发明涉及可以引入动物或人类细胞以实现cDNA转录或表达的CA125 cDNA序列。
    • 4. 发明授权
    • CA125 gene and its use for diagnostic and therapeutic interventions
    • CA125基因及其在诊断和治疗干预中的应用
    • US08895703B2
    • 2014-11-25
    • US11975668
    • 2007-10-19
    • Timothy O'BrienJohn BeardLowell Underwood
    • Timothy O'BrienJohn BeardLowell Underwood
    • C07K16/00C12P21/08C07K14/705C07K16/30
    • C07K14/705C07K16/3092
    • The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. An amino terminal extension is present. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. The repeat units encompass an interactive disulfide bridged C-enclosure and the site of OC125 and M11 binding. The repeat sequences demonstrated 70-85% homology to each other. Expression of the repeats was demonstrated in E. coli. The CA125 molecule is anchored at its carboxy terminal through a transmembrane domain and a short cytoplasmic tail.
    • 已经克隆了CA125基因,并且已经鉴定了多个重复序列以及羧基末端。 CA125分子包含三个主要的结构域:细胞外氨基末端结构域(Domain 1); 一个大的多重重复域(域2); 和包含具有短细胞质结构域的跨膜锚的羧基末端结构域(结构域3)。 存在氨基末端延伸。 分子结构由包含156个氨基酸重复单元的重复结构域所支配。 已经确定,排序和连续地排列在CA125领域结构中的60多个重复单位。 重复单元包括交互式二硫键桥接的C-封闭物和OC125和M11结合位点。 重复序列显示了70-85%的同源性。 在大肠杆菌中证实了重复的表达。 CA125分子在其羧基末端通过跨膜结构域和短的胞质尾部锚定。
    • 6. 发明授权
    • CA125 gene and its use for diagnostic and therapeutic interventions
    • CA125基因及其在诊断和治疗干预中的应用
    • US09556245B2
    • 2017-01-31
    • US12455366
    • 2009-06-01
    • Timothy O'BrienJohn BeardLowell Underwood
    • Timothy O'BrienJohn BeardLowell Underwood
    • C12Q1/68C07K14/47C07H21/00A61K38/00
    • C07K14/47A61K38/00C12Q1/6886C12Q2600/156C12Q2600/158
    • The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. An amino terminal extension is presented, which comprises four genomic exons. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. More specifically, this invention is directed to a CA125 cDNA sequence which can be introduced into animal or human cells to achieve transcription or expression of the cDNA.
    • 已经克隆了CA125基因,并且已经鉴定了多个重复序列以及羧基末端。 CA125分子包含三个主要的结构域:细胞外氨基末端结构域(Domain 1); 一个大的多重重复域(域2); 和包含具有短细胞质结构域的跨膜锚的羧基末端结构域(结构域3)。 氨基末端结构域以其O-糖基化的能力为主,其结果是丝氨酸和苏氨酸残基的丰富度。 提供氨基末端延伸,其包含四个基因组外显子。 分子结构由包含156个氨基酸重复单元的重复结构域所支配,其包含表位结合位点。 已经确定,排序和连续地排列在CA125领域结构中的60多个重复单位。 更具体地,本发明涉及可以引入动物或人类细胞以实现cDNA转录或表达的CA125 cDNA序列。
    • 7. 发明申请
    • CA125 gene and its use for diagnostic and therapeutic interventions
    • US20090035819A1
    • 2009-02-05
    • US11975668
    • 2007-10-19
    • Timothy O'BrienJohn BeardLowell Underwood
    • Timothy O'BrienJohn BeardLowell Underwood
    • C12P21/06C07H21/00C07K16/18C12N5/00
    • C07K14/705C07K16/3092
    • The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is assembled by combining five genomic exons, four very short amino terminal sequences and one extraordinarily large exon. This domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. Additionally, an amino terminal extension is present, which comprises four genomic exons. The amino acid composition of the amino terminal extension was found to be consistent with the amino acid composition of the amino terminal domain. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. The repeat units encompass an interactive disulfide bridged C-enclosure and the site of OC125 and M11 binding. The repeat sequences demonstrated 70-85% homology to each other. Expression of the repeats was demonstrated in E. coli. The CA125 molecule is anchored at its carboxy terminal through a transmembrane domain and a short cytoplasmic tail. The carboxy terminal also contains a proteolytic cleavage site approximately 50 amino acids upstream from the transmembrane domain, which allows for proteolytic cleavage and release of the CA125 molecule. Any one of the repeat domains has the potential for use as a new gold standard for detecting and monitoring the presence of the CA125 antigen. Further, the repeat domains or other domains, especially the c-terminal to the repeat domain also provide a basis for the development of a vaccine, which would be useful for the treatment of ovarian cancer and other carcinomas where CA125 is elevated.
    • 8. 发明申请
    • Repeat sequences of the ca125 gene and their use for diagnostic and therapeutic interventions
    • US20070015907A1
    • 2007-01-18
    • US10475117
    • 2002-04-12
    • Timothy O'BrienJohn BeardLowell Underwood
    • Timothy O'BrienJohn BeardLowell Underwood
    • C07K14/705C07H21/04
    • C07K14/47A61K38/00C12Q1/6886C12Q2600/158
    • The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is assembled by combining five genomic exons, four very short amino terminal sequences and one extraordinarily large exon. This domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. Additionally, an amino terminal extension is present, which comprises four genomic exons. The amino acid composition of the amino terminal extension was found to be consistent with the amino acid composition of the amino terminal domain. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. The repeat units encompass an interactive disulfide bridged C-enclosure and the site of OC125 and M11 binding. The repeat sequences demonstrated 70-85% homology to each other. Expression of the repeats was demonstrated in E. coli. The CA125 molecule is anchored at its carboxy terminal through a transmembrane domain and a short cytoplasmic tail. The carboxy terminal also contains a proteolytic cleavage site approximately 50 amino acids upstream from the transmembrane domain, which allows for proteolytic cleavage and release of the CA125 molecule. Any one of the repeat domains has the potential for use as a new gold standard for detecting and monitoring the presence of the CA125 antigen. Further, the repeat domains or other domains, especially the c-terminal to the repeat domain also provide a basis for the development of a vaccine, which would be useful for the treatment of ovarian cancer and other carcinomas where CA125 is elevated.