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    • 3. 发明申请
    • MATERIALS AND METHODS FOR IDENTIFYING PATIENTS SUSCEPTIBLE TO DEVELOPING TAXANE INDUCED NEUROPTHY
    • 用于鉴定不利于发展TAXANE诱发神经病的患者的材料和方法
    • WO2012103522A3
    • 2013-04-04
    • PCT/US2012023032
    • 2012-01-27
    • UNIV INDIANA RES & TECH CORPRADOVICH MILANSCHNEIDER BRYAN P
    • RADOVICH MILANSCHNEIDER BRYAN P
    • C12Q1/68C12N15/11
    • C12Q1/6883C12Q2600/156C12Q2600/172
    • A randomized phase III study with a planned accmal (n=4950); GWAS performed ors 2204 patients to compare genotypes with efficacy and toxicities. The phenotype for this study is time to first grade 2-4 neuropathy. GVVAS is conducted using the Xnfmium HumanOmnil platform from Illumma which assessed 1.2 million SNPs per patient. Comparisons are made using Cox regression analysis with correction for multiple comparisons (Bonferroni) and established clinical trial co-variates (race, age, tumor size, LN status). Toxicity data indicates that 576 patients experienced grade 2-4 neuropathy and 1633 did not. Clinical predictors for neuropathy include age (12.9% increase with each decade; p=0.004) and African American race (HR=2.1; p=4.5 x 10-11). Six SNPs with MAF>5% demonstrate associations with neuropathy (rho
    • 一项随机III期研究,计划生育(n = 4950); GWAS执行或2204例患者比较基因型与功效和毒性。 本研究的表型是2-4级神经病变的时间。 GVVAS使用Illumma的Xnfmium HumanOmnil平台进行,每个患者评估了120万个SNP。 使用Cox回归分析进行比较,校正多次比较(Bonferroni)和建立的临床试验共变量(种族,年龄,肿瘤大小,LN状态)。 毒性数据表明576例患者出现2-4级神经病变,1633例未发现。 神经病的临床预测因素包括年龄(每十年增加12.9%,p = 0.004)和非裔美国人(HR = 2.1; p = 4.5 x 10-11)。 六个具有MAF> 5%的SNP表现出与神经病变的关联(rho <5chi 10-7)。 这些SNP位于两个基因:RWDD3和TECTA。 RWDD3中的错义SNP在15个月随访期间显示出%的神经病变:纯合野生型为27%,杂合子为40%,纯合变体为60%(等位基因剂量效应:HR = 1.5; p = 8)。 MAF <5%的多个其他SNP也与神经病有关(p <5×10-7)。
    • 4. 发明申请
    • MATERIALS AND METHODS FOR IDENTIFYING PATIENTS SUSCEPTIBLE TO DEVELOPING TAXANE INDUCED NEUROPTHY
    • 用于鉴定不利于发展TAXANE诱发神经病的患者的材料和方法
    • WO2012103522A2
    • 2012-08-02
    • PCT/US2012/023032
    • 2012-01-27
    • INDIANA UNIVERSITY RESEARCH & TECHNOLOGY CORPORATIONRADOVICH, MilanSCHNEIDER, Bryan, P.
    • RADOVICH, MilanSCHNEIDER, Bryan, P.
    • C12Q1/6883C12Q2600/156C12Q2600/172
    • A randomized phase III study with a planned accmal (n=4950); GWAS performed ors 2204 patients to compare genotypes with efficacy and toxicities. The phenotype for this study is time to first grade 2-4 neuropathy. GVVAS is conducted using the Xnfmium HumanOmnil platform from Illumma which assessed 1.2 million SNPs per patient. Comparisons are made using Cox regression analysis with correction for multiple comparisons (Bonferroni) and established clinical trial co-variates (race, age, tumor size, LN status). Toxicity data indicates that 576 patients experienced grade 2-4 neuropathy and 1633 did not. Clinical predictors for neuropathy include age (12.9% increase with each decade; p=0.004) and African American race (HR=2.1; p=4.5 x 10 -11 ). Six SNPs with MAF>5% demonstrate associations with neuropathy (ρ -7 ). These SNPs reside in two genes: RWDD3 and TECTA. A missense SNP in RWDD3 demonstrates % neuropathy at 15 months follow-up: 27% for homozygous wild-type, 40% for heterozygotes, and 60% for homozygous variant (allele dose-effect: HR=1.5; p=8.5 χ 10 -8 ). Multiple other SNPs with MAF -7 ).
    • 一项随机III期研究,计划生育(n = 4950); GWAS执行或2204例患者比较基因型与功效和毒性。 本研究的表型是2-4级神经病变的时间。 GVVAS使用Illumma的Xnfmium HumanOmnil平台进行,每个患者评估了120万个SNP。 使用Cox回归分析进行比较,校正多次比较(Bonferroni)和建立的临床试验共变量(种族,年龄,肿瘤大小,LN状态)。 毒性数据表明576例患者出现2-4级神经病变,1633例未发现。 神经病的临床预测因素包括年龄(每十年增加12.9%,p = 0.004)和非裔美国人(HR = 2.1; p = 4.5 x 10-11)。 六个具有MAF> 5%的SNP表现出与神经病变(→-7)的关联。 这些SNP位于两个基因:RWDD3和TECTA。 RWDD3中的错义SNP显示15个月随访期间的%神经病变:纯合野生型27%,杂合子40%,纯合变体60%(等位基因剂量效应:HR = 1.5; p = 8.5〜 8)。 多个其他SNP与MAF-7)。