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    • 4. 发明申请
    • IDENTIFICATION OF COMPOUNDS THAT TARGET THE RNA-BINDING PROTEIN TIA-1 AN IMPORTANT REGULATOR OF STRESS VULNERABILITY IN BOTH MICE AND HUMANS
    • 靶向RNA结合蛋白TIA-1成为小鼠和人类应激易感性重要调节因子的化合物的鉴定
    • WO2017218697A1
    • 2017-12-21
    • PCT/US2017/037544
    • 2017-06-14
    • THE TRUSTEES COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
    • RAYMAN, Joseph, B.KANDEL, Eric, R.
    • A61K38/17C07K14/435C07K14/47G01N33/68
    • C07K14/47A61K31/375A61K31/5365A61K31/65C07K14/435G01N33/542
    • This invention provides a method of ameliorating the symptoms of, or treating post-traumatic stress disorder in a mammal, the method comprising administering to the mammal an effective amount of a compound that upregulates TIA-1 multimerization. This invention also provides a method of ameliorating the symptoms of, or treating post-traumatic stress disorder in a mammal, the method comprising administering to the mammal an effective amount of a compound that inhibits TIA-1 multimerization. This invention also provides a method for determining whether a predetermined compound upregulates or inhibits TIA-1 multimerization, using fluoresence resonance energy transfer (FRET), the method comprising: expressing recombinant TIA-CFP and TIA-YFP; exposing the recombinant TIA-CFP and TIA-YFP to such predetermined compound; exciting the TIA-CFP with a laser; and measuring the fluorescence of TIA-YFP, wherein an increase in fluorescence relative to TIA-CFP and TIA-YFP not exposed to the predetermined compound indicates that the predetermined compound upregulates TIA-1 multimerization and a decrease in fluorescence relative to TIA-CFP and TIA-YFP not exposed to the predetermined compound indicates that the predetermined compound inhibits TIA-1 multimerization.
    • 本发明提供了改善哺乳动物的症状或治疗创伤后应激障碍的方法,所述方法包括给哺乳动物施用有效量的上调TIA-1多聚化作用的化合物。 本发明还提供了改善哺乳动物的症状或治疗创伤后应激障碍的方法,该方法包括给哺乳动物施用有效量的抑制TIA-1多聚化作用的化合物。 本发明还提供了使用荧光共振能量转移(FRET)确定预定化合物是否上调或抑制TIA-1多聚化的方法,所述方法包括:表达重组TIA-CFP和TIA-YFP; 将重组TIA-CFP和TIA-YFP暴露于这种预定化合物; 用激光激发TIA-CFP; 并测量TIA-YFP的荧光,其中相对于未暴露于预定化合物的TIA-CFP和TIA-YFP的荧光增加表明预定化合物相对于TIA-CFP上调TIA-1多聚化和荧光下降,并且 未暴露于预定化合物的TIA-YFP表明预定化合物抑制TIA-1多聚化。
    • 8. 发明申请
    • SELECT SINGLE NUCLEOTIDE POLYMORPHISMS PREDICTIVE OF RESPONSE TO GLATIRAMER ACETATE
    • 选择单核苷酸多态性对乙酰胆碱反应的预测
    • WO2016172124A1
    • 2016-10-27
    • PCT/US2016/028316
    • 2016-04-19
    • TEVA PHARMACEUTICAL INDUSTRIES LTD.GROSSMAN, IrisHAYDEN, MichaelROSS, Colin, James DouglasLAIFENFELD, DaphnaDAVIS, Matthew
    • GROSSMAN, IrisHAYDEN, MichaelROSS, Colin, James DouglasLAIFENFELD, DaphnaDAVIS, Matthew
    • A61K38/02C12Q1/68
    • C12Q1/6883A61K9/0019A61K38/02A61K45/06C12Q1/6886C12Q2600/106C12Q2600/156
    • The present invention provides a method for treating a human subject afflicted with multiple sclerosis or a single clinical attack consistent, with multiple sclerosis with a pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier, comprising the steps of: (i) determining a genotype of the subject at a location corresponding to the location of one or more single nucleotide polymorphisms (SNPs) selected from the group consisting of: rs1894408, kgp7747883, kgp6599438, rs10162089, rs16886004, kgp8110667, kgp8817856, kgp24415534, kgp6214351 and rs759458, (ii) identifying the subject as a predicted responder to glatiramer acetate if the genotype of the subject contains one or more A alleles at the location of kgp8110667, rs10162089, rs759458 and kgp6214351, or one or more G alleles at the location of kgp24415534, kgp6599438, kgp7747883, kgp8817856, rs16886004 and rs1894408; and iii) administering the pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier to the subject only if the subject is identified as a predicted responder to glatiramer acetate.
    • 本发明提供了一种用多种硬化症或单一临床攻击治疗患有多发性硬化的人类受试者的方法,所述多发性硬化症包括含有醋酸格拉默和药学上可接受的载体的药物组合物,包括以下步骤:(i)确定 对应于选自以下的一个或多个单核苷酸多态性(SNP)的位置的对象:rs1894408,kgp7747883,kgp6599438,rs10162089,rs16886004,kgp8110667,kgp8817856,kgp24415534,kgp6214351和rs759458,(ii)鉴定 该受试者作为乙酸格拉默的预测应答者,如果受试者的基因型在kgp8110667,rs10162089,rs759458和kgp6214351的位置包含一个或多个A等位基因,或位于kgp24415534,kgp6599438,kgp7747883,kgp8817856的一个或多个G等位基因 ,rs16886004和rs1894408; 以及iii)仅当所述受试者被鉴定为乙酸格拉默的预测应答者时,向受试者施用包含乙酸格拉默和药学上可接受的载体的药物组合物。