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    • 11. 发明申请
    • METHOD OF PREVENTING THE INJURY OR DEATH OF RETINAL CELLS AND TREATING OCULAR DISEASES
    • 预防视网膜细胞损伤或死亡并治疗眼部疾病的方法
    • WO0109327A3
    • 2001-08-02
    • PCT/US0020710
    • 2000-07-28
    • GENENTECH INCASHKENAZI AVI JBAKER KEVIN PGODDARD AUDREYGODOWSKI PAUL JGURNEY AUSTIN LKLJAVIN IVAR JLAFLEUR MONIQUEMARK MELANIE RMARSTERS SCOT APITTI ROBERT MWATANABE COLIN KWOOD WILLIAM I
    • ASHKENAZI AVI JBAKER KEVIN PGODDARD AUDREYGODOWSKI PAUL JGURNEY AUSTIN LKLJAVIN IVAR JLAFLEUR MONIQUEMARK MELANIE RMARSTERS SCOT APITTI ROBERT MWATANABE COLIN KWOOD WILLIAM I
    • A61K38/00A61K38/17C07K14/47C07K14/705C07K16/18C12N15/12C12N15/62
    • C07K14/4703A61K38/00C07K14/70578G01N2800/164
    • The present invention relates to the use of PRO polypeptides to delay, prevent or rescue retinal neurons, including photoreceptors, other retinal cells or supportive cells (e.g. Müller cells or RPE cells) from injury and/or death. Conditions comprehended by treatment of the present PRO polypeptides (including variants), antibodies, compositions and articles of manufacture include: retinal detachment, age-related and other maculopathies, photic retinopathies, surgery-induced retinopathies (either mechanically or light-induced), toxic retinopathies including those resulting from foreign bodies in the eye, diabetic retinopathies, retinopathy of prematurity, viral retinopathies such as CMV or HIV retinopathy related to AIDS, uveitis, ischemic retinopathies due to venous or arterial occlusion or other vascular disorder, retinopathies due to trauma or penetrating lesions of the eye, peripheral vitreoretinopathy, and inherited retinal degenerations. Exemplary retinal degenerations include e.g., hereditary spastic paraplegia with retinal degeneration (Kjellin and Barnard-Scholz syndromes), retinitis pigmentosa, Stargardt disease, Usher syndrome (retinitis pigmentosa with congenital hearing loss), and Refsum syndrome (retinitis pigmentosa, hereditary hearing loss, and polyneuropathy). Additional disorders which result in death of retinal neurons include, retinal tears, detachment of the retina and pigment epithelium, degenerative myopia, acute retinal necrosis syndrome (ARN), traumatic chorioretinopathies or contusion (Purtscher's Retinopathy) and edema.
    • 本发明涉及PRO多肽用于延迟,预防或挽救视网膜神经元(包括光感受器,其他视网膜细胞或支持细胞(例如Müller细胞或RPE细胞)免受损伤和/或死亡)。 通过治疗本发明的PRO多肽(包括变体),抗体,组合物和制造品而理解的病症包括:视网膜脱离,年龄相关性和其他黄斑病,光视网膜病,手术诱导的视网膜病(机械或光诱导),毒性 视网膜病变,包括由眼内异物引起的视网膜病,糖尿病性视网膜病,早产儿视网膜病,病毒视网膜病如与AIDS有关的CMV或HIV视网膜病,葡萄膜炎,由于静脉或动脉闭塞或其他血管病导致的缺血性视网膜病,由创伤引起的视网膜病, 穿透性眼部病变,外周玻璃体视网膜病变和遗传性视网膜变性。 示例性视网膜变性包括例如具有视网膜变性(Kjellin和Barnard-Scholz综合征)的遗传性痉挛性截瘫,色素性视网膜炎,Stargardt病,Usher综合征(具有先天性听力丧失的视网膜色素变性)和Refsum综合征(视网膜色素变性,遗传性听力丧失和 多发性神经病)。 导致视网膜神经细胞死亡的其它疾病包括视网膜撕裂,视网膜和色素上皮脱离,退行性近视,急性视网膜坏死综合征(ARN),创伤性脉络膜视网膜病变或挫伤(Purtscher视网膜病变)和水肿。
    • 19. 发明申请
    • RECEPTOR ACTIVATION BY GAS6
    • 受体激活由GAS6
    • WO1996028548A1
    • 1996-09-19
    • PCT/US1996003031
    • 1996-03-05
    • GENENTECH, INC.CHEN, JianHAMMONDS, R., GlennGODOWSKI, Paul, J.MARK, Melanie, R.MATHER, Jennie, P.LI, Ronghao
    • GENENTECH, INC.
    • C12N15/12
    • C07K14/745A61K38/00
    • An activator of the Rse and Mer receptor protein tyrosine kinases has been identified. The activator is encoded by growth arrest-specific gene 6 (gas6). Accordingly, the invention provides a method of activating the Rse or Mer receptor using gas6 polypeptide. Furthermore, the invention provides a method of enhancing survival, proliferation or differentiation of cells having the Rse or Mer receptor incorporated in their cell membranes which involves those cells to gas6 polypeptide. The types of cells which can be treated according to the method include glial cells such as Schwann cells and mononuclear cells. Kits and articles of manufacture which include gas6 polypeptide are further provided. The invention also relates to gas6 variants.
    • 已经鉴定了Rse和Mer受体蛋白酪氨酸激酶的激活剂。 活化剂由生长停滞特异性基因6(gas6)编码。 因此,本发明提供了使用gas6多肽来激活Rse或Mer受体的方法。 此外,本发明提供了一种增强细胞的存活,增殖或分化的方法,所述细胞具有并入其细胞膜中的Rse或Mer受体,其将这些细胞涉及至气体多肽。 根据该方法可以治疗的细胞类型包括神经胶质细胞如雪旺氏细胞和单核细胞。 进一步提供包含gas6多肽的试剂盒和制品。 本发明还涉及gas6变体。
    • 20. 发明申请
    • KINASE RECEPTOR ACTIVATION ASSAY
    • 激素受体激活测定
    • WO1995014930A1
    • 1995-06-01
    • PCT/US1994013329
    • 1994-11-18
    • GENENTECH, INC.GODOWSKI, Paul, J.MARK, Melanie, R.SADICK, Michael, DanielWONG, Wai, Lee, Tan
    • GENENTECH, INC.
    • G01N33/573
    • C12N9/12A61K38/00C07K14/705C07K14/71C07K14/715C07K16/28C12Q1/485G01N33/54306G01N33/566G01N33/573G01N2333/705G01N2333/912G01N2333/9121G01N2500/00
    • An assay for measuring activation (i.e., autophosphorylation) of a tyrosine kinase receptor of interest is disclosed. a) A first solid phase is coated with a substantially homogeneous population of cells so that the cells adhere to the first solid phase. The cells have either an endogenous tyrosine kinase receptor or have been transformed with DNA encoding a receptor or "receptor construct" and the DNA has been expressed so that the receptor or receptor construct is presented in the cell membranes of the cells. b) A ligand is then added to the solid phase having the adhering cells, such that the tyrosine kinase receptor is exposed to the ligand. c) Following exposure to the ligand, the adherent cells are solubilized, thereby releasing cell lysate. d) A second solid phase is coated with a capture agent which binds specifically to the tyrosine kinase receptor, or, in the case of a receptor construc, to the flag polypeptide. e) The cell lysate obtained in step c) is added to the wells containing the adhering capture agent so as to capture the receptor or receptor construct to the wells. f) A washing step is then carried out, so as to remove unbound cell lysate, leaving the captured receptor or receptor construct. g) The captured receptor or receptor construct is exposed to a labelled anti-phosphotyrosine antibody which identifies phosphorylated residues in the tyrosine kinase receptor. h) Binding of the anti-phosphotyrosine antibody to the captured receptor or receptor construct is measured.
    • 公开了用于测量感兴趣的酪氨酸激酶受体的活化(即自身磷酸化)的测定法。 a)第一固相涂覆有基本上均匀的细胞群,使得细胞粘附到第一固相。 细胞具有内源性酪氨酸激酶受体或已经用编码受体或“受体构建体”的DNA转化,并且已经表达了DNA,使得受体或受体构建体存在于细胞的细胞膜中。 b)然后将配体加入到具有粘附细胞的固相中,使得酪氨酸激酶受体暴露于配体。 c)暴露于配体后,粘附细胞溶解,从而释放细胞裂解物。 d)第二固相包被与酪氨酸激酶受体特异性结合的捕获剂,或者在受体构建的情况下,与标记多肽结合。 e)将步骤c)中获得的细胞裂解物加入到含有粘附捕获剂的孔中,以将孔或受体构建体捕获到孔中。 f)然后进行洗涤步骤,以除去未结合的细胞裂解物,留下捕获的受体或受体构建体。 g)将捕获的受体或受体构建体暴露于标记的抗磷酸酪氨酸抗体,其鉴定酪氨酸激酶受体中的磷酸化残基。 h)测量抗磷酸酪氨酸抗体与捕获的受体或受体构建体的结合。