Molecular Kits and Software for Lymphoid Malignancy Work-ups

用于淋巴恶性肿瘤检查的分子试剂盒和软件

• 批准号: 8647029
• 负责人: David Scott Johnson
• 金额: $ 65.62万
• 依托单位: GIGAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8647029
• 关键词: Aftercare; American; Area; Bioinformatics; Biological Assay; Capillary Electrophoresis; Capital; Cataloging; Catalogs; Cells; Clinical Research; Companions; Computer software; Coupled; Data; Data Set; Diagnostic; Doctor of Philosophy; Equipment; Failure; Feasibility Studies; Future; Genomic DNA; Genotype; Grant; Heavy-Chain Immunoglobulins; Hematologic Neoplasms; Hematopoietic Neoplasms; IGH@ gene cluster; Immune; In Vitro; Laboratories; Licensing; Malignant Neoplasms; Malignant lymphoid neoplasm; Manufacturer Name; Market Research; Marketing; Measurement; Measures; Methods; Metric; Modality; Modeling; Molecular; Monitor; Online Systems; Pathologist; Pathology; Patients; Phase; Plague; Plasmids; Polymerase Chain Reaction; Quality Control; Reagent; Receiver Operator Characteristics; Research; Residual Tumors; Risk; Route; Running; Sampling; Scientist; Sequoia; Severities; Site; Small Business Innovation Research Grant; Specialist; System; T-Cell Receptor gamma-Chain; Testing; Time; Variant; Work; base; beta Chain Antigen T Cell Receptor; college; cost; design; innovation; kappa-Chain Immunoglobulins; leukemia; leukemia/lymphoma; next generation sequencing; peripheral blood; product development; public health relevance; research and development

PROJECT SUMMARY Project Title: Molecular Kits and Software for Lymphoid Malignancy Work-ups Organization: GigaGen Inc. PI: David S. Johnson, Ph.D. The Specific Aim of this Phase II SBIR proposal is to develop four research use only (RUO) multiplexed molecular kits for comprehensive lymphoid malignancy pathology work-ups. Multiplexed amplification coupled with next generation sequencing (NGS) has a large awaiting market for pathology of lymphoid malignancy, significantly decreasing material and labor costs compared with current methods (Drs. Kerschmann, Zehnder, & Negrin LOS). For example, current work-ups for leukemia oligoclonality require laborious customization, cost up to ~$5000 per subject, and have a turnaround time of several weeks. With around 175,000 new lymphoid malignancies per year, and $1000 per work-up, we estimate that the annual market for our kits in the US alone is ~$175 million. The technical innovation resulting from the Phase I SBIR project (Johnson et al., 2012) was a bioinformatics system for "cleaning" the nonrepresentative amplification that plagues multiplexed repertoire amplification (Robins et al., 2012). The market innovation resulting from this proposed Phase II SBIR project would be to provide a faster and cheaper system for lymphoid malignancy work-ups that use immune repertoire analysis ("GigaMune(R) HemeOnc"). In Phase II, we will take the following steps to develop GigaMune(R) HemeOnc: (i) manufacture four original equipment manufacturer (OEM) molecular kits that include amplification master mix, amplification primers, clean-up reagents, and positive control mixes; (ii) implement web-based analysis, QC, and QA software for the four molecular kits; and (iii) use reference samples from the College of American Pathologists (CAP) to quantify the analytical validity of the kits and software. We will be successful in our Phase II project if we achieve the following milestones: (i) across 10 replicate runs at GigaGen, the OEM kits should amplify plasmid positive control mixes such that clonotypes present as low as 0.1% have an average coefficient of variation (CV) of <20% (power=0.8, ¿=0.05) and with an area under the receiver operator characteristic curve (AUC) greater than 0.8 (power=0.8, ¿=0.05); and (ii) across 15 replicate runs at three testing sites, the OEM kits should amplify reference samples such that clonotypes present as low as 0.1% have an average CV of <20% (power=0.8, ¿=0.05) and with an AUC greater than 0.8 (power=0.8, ¿=0.05) and a failure rate <2%. After Phase II is complete, we will market the RUO GigaMune(R) HemeOnc kits and software to pathology labs worldwide. These kits and software will be best in class and facilitate clinical research and development of CLIA laboratory-developed tests (LDTs). In the future, we will explore the advantages of building GigaMune(R) HemeOnc into an FDA-cleared in vitro diagnostic (IVD) kit. For now, the IVD route is not possible, because there are currently no FDA-cleared NGS systems that could be used in conjunction with GigaMune(R) HemeOnc.

项目概要 项目名称：用于淋巴恶性肿瘤检查的分子试剂盒和软件 组织：GigaGen Inc. PI：David S. Johnson，博士 该第二阶段 SBIR 提案的具体目标是开发四种仅供研究使用 (RUO) 的多路复用 用于全面淋巴恶性肿瘤病理学检查的分子试剂盒。 多重扩增与下一代测序（NGS）相结合有一个巨大的等待市场 淋巴恶性肿瘤的病理学，与目前相比显着降低材料和劳动力成本 方法（Kerschmann、Zehnder 博士和 Negrin LOS）。例如，目前针对白血病的检查 寡克隆需要费力的定制，每个受试者的成本高达约 5000 美元，并且周转时间为 几个星期。每年约有 175,000 例新发淋巴恶性肿瘤，每次检查费用为 1000 美元，我们 据估计，仅在美国我们的套件的年市场就约为 1.75 亿美元。由此产生的技术创新 来自第一阶段 SBIR 项目（Johnson 等人，2012）的一个生物信息学系统，用于“清理” 非代表性扩增困扰着多重谱库扩增（Robins et al., 2012）。这 拟议的第二阶段 SBIR 项目带来的市场创新将是提供更快、更便宜的 使用免疫组库分析进行淋巴恶性肿瘤检查的系统（“GigaMune(R) HemeOnc”）。 在第二阶段，我们将采取以下步骤来开发 GigaMune(R) HemeOnc： (i) 制造四个原创产品 设备制造商 (OEM) 分子试剂盒，包括扩增预混液、扩增引物、 净化试剂和阳性对照混合物； (ii) 实施基于网络的分析、QC 和 QA 软件 四个分子试剂盒； (iii) 使用美国病理学家学会 (CAP) 的参考样本 量化套件和软件的分析有效性。如果我们能够在第二阶段项目中取得成功 实现以下里程碑：(i) 在 GigaGen 的 10 次重复运行中，OEM 试剂盒应扩增质粒 阳性对照混合物的克隆型含量低至 0.1%，平均变异系数 (CV) <20%（功效=0.8，¿=0.05）且具有接收者操作特征曲线下面积 (AUC) 大于0.8（功效=0.8，¿=0.05）； (ii) 在三个测试地点进行 15 次重复运行，OEM 套件 应扩增参考样本，使克隆型含量低至 0.1%，平均 CV <20% （power=0.8，¿=0.05）且 AUC 大于 0.8（power=0.8，¿=0.05）且故障率 <2%。 第二阶段完成后，我们将向病理实验室销售 RUO GigaMune(R) HemeOnc 试剂盒和软件 全世界。这些试剂盒和软件将是同类中最好的，并促进临床研究和开发 CLIA 实验室开发的测试 (LDT)。未来，我们将探索构建GigaMune(R)的优势 HemeOnc 被纳入 FDA 批准的体外诊断 (IVD) 试剂盒。目前来说，I​​VD途径是不可能的，因为 目前没有 FDA 批准的 NGS 系统可以与 GigaMune(R) 结合使用 HemeOnc。