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    • 9. 发明授权
    • erbB-3 nucleic acids
    • erbB-3核酸
    • US06639060B1
    • 2003-10-28
    • US09170699
    • 1998-10-13
    • Matthias H. KrausStuart A. Aaronson
    • Matthias H. KrausStuart A. Aaronson
    • C12N1511
    • C07K16/32A61K38/00A61K47/6843C07K14/82C07K2317/34G01N33/5748G01N33/57484G01N2500/02G01N2500/04
    • A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGFR and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180erbB-3.
    • 通过v-erbB与正常基因组人DNA的严格杂交进行检测,检测出与表皮生长因子受体(EGFR)和erbB-2基因不同的DNA片段。 克隆的DNA片段的表征将v-erbB同源性的区域分别与EGFR和erbB-2蛋白的酪氨酸激酶结构域内的连续区域分别具有64%和67%最近同源性的3个外显子。 cDNA克隆揭示了具有结构特征的预测的148kd跨膜多肽,其将其识别为erbB家族的成员,促使将新基因命名为erbB-3。 它被映射到人染色体12q11-13,并且显示在上皮起源的多种正常组织中表达为6.2kb转录物。 在某些人类乳腺肿瘤细胞系中证明了显着升高的erbB-3 mRNA水平。 这些发现表明,如EGFR和erbB-2的情况,erbB-3表达的增加在一些人类恶性肿瘤中起作用。 使用erbB-3特异性抗体(多克隆或单克隆),将erbB-3蛋白鉴定为180kDa糖蛋白gp180
    • 10. 发明授权
    • Fusion proteins that include antibody and nonantibody portions
    • 包含抗体和非抗体部分的融合蛋白
    • US06403769B1
    • 2002-06-11
    • US08613743
    • 1996-02-22
    • William J. LarochelleStuart A. AaronsonOlaf Dirsch
    • William J. LarochelleStuart A. AaronsonOlaf Dirsch
    • C12P2108
    • C07K14/71A61K38/00C07K16/00C07K2319/02
    • The high affinity which is characteristic of homodimers of IgG heavy chains is achieved, along with favorable secretion and flexibility/adaptability properties, in a fusion protein that has a nonantibody portion, comprised of an effector domain, joined to the aminoterminal end of an IgG-derived sequence consisting of a hinge:CH2:CH3 segment which lacks a CH1 domain, with a heterologous signal peptide preferably provided upstream of the nonantibody portion. Chimeric molecules of this structure can be secreted readily in stable form by mammalian cells transfected with DNA encoding the molecule, and are amenable to rapid, efficient purification to homogeneity, for example, using protein A. These molecules are effective substitutes for monoclonal antibodies in contexts such as flow cytometry, immunohistochemistry, immunoprecipitation and ELISAs. A fusion protein as described also can be used in screening for agonists and antagonists to the cognate binding partner of the nonantibody portion of the fusion protein. Moreover, chimeric molecules in which the nonantibody portion contains a growth factor domain are internalized, essentially like the natural growth factor, in contrast to the situation that generally pertains with respect to antibodies which are directed to external receptor domains.
    • 在具有非抗体部分的融合蛋白中实现了IgG重链的同源二聚体特征的高亲和力,以及有利的分泌和柔性/适应性特性,该融合蛋白包括与IgG-氨基末端的氨基末端结合的效应结构域, 衍生的序列由铰链:缺少CH1结构域的CH2:CH3区段组成,异源信号肽优选设置在非抗体部分的上游。 这种结构的嵌合分子可以通过用编码该分子的DNA转染的哺乳动物细胞以稳定的形式分泌,并且可以快速,有效地纯化成均匀性,例如使用蛋白质A.这些分子是上下文中单克隆抗体的有效替代物 如流式细胞术,免疫组织化学,免疫沉淀和ELISA。 还描述了融合蛋白,用于筛选融合蛋白非抗体部分的同源结合配偶体的激动剂和拮抗剂。 此外,与通常涉及针对外部受体结构域的抗体的情况相反,非抗体部分含有生长因子结构域的嵌合分子基本上与天然生长因子内在化。