LONG-TERM CULTURE OF HUMAN ADULT CARDIAC MYOCYTES

Myogen提出开发和优化成人心肌细胞的长期培养系统。 失败的移植和非失败的器官供体人心脏将用于分离心肌细胞进行培养。将对培养的细胞进行表征以验证其表型。开发的培养系统最终将用于建立高通量筛选程序，用于鉴定心肌衰竭和重塑中的重要分子事件，并寻找用于治疗心力衰竭的化合物。这样的系统目前不可用，并且应该显著影响心力衰竭的新治疗的搜索，心力衰竭目前在美国每年涉及260，000例死亡。在第I阶段，Myogen将分离人成年心肌细胞，并将应用新的培养技术以实现细胞在培养物中存活至少一个月。 将对培养细胞的形态和基因表达模式进行表征。在第二阶段，Myogen将使用开发的培养系统来展示用于靶点鉴定和验证的高通量生物筛选以及用于药物研究和开发的高通量化合物筛选。在第三阶段，Myogen将通过化合物开发，合作研究和许可将开发的技术商业化。拟议的商业应用：本项目的目标是开发心力衰竭的靶点识别和靶点验证。心力衰竭治疗和诊断鉴定的高通量筛选程序的开发。据估计，对于每个经过验证的目标，大约3000万至4000万美元的商业前付款将来自许可费，研发资金，里程碑付款和股权。这一数字不包括未来商业化产生的特许权使用费，这将产生额外的收入。

Myogen proposes to develop and optimize a long-term culture system for adult human cardiac myocytes. Failing explanted and non-failing organ donor human hearts will be used to isolate cardiac myocytes for culture. The cultured cells will be characterized to validate their phenotype. The developed culture systems will ultimately be used to establish high throughput screening programs for identification of important molecular events in myocardial failure and remodeling and to search for compounds for the treatment of heart failure. Such a system is not currently available, and should significantly impact the search for novel treatment of heart failure, which is currently implicated in 260,000 deaths per year in the U.S. In Phase I Myogen will isolate human adult cardiac myocytes and will apply novel culture techniques to achieve survival of cells in culture for at least one month. Cultured cells will be characterized with respect to their morphology and gene expression patterns. In Phase II Myogen will use the developed culture system to demonstrate high throughput biological screens for target identification and validation and high throughput compound screens for drug research and development. In Phase III Myogen will commercialize the developed technology through compound development, collaborative research, and licensing. PROPOSED COMMERCIAL APPLICATIONS: Development of target identification and target validation for heart failure is the goal of this project. Development of high throughput screening programs for therapeutic and diagnostic identification in heart failure. It is estimated that for each validated target, approximately $30- 40 million in precommercial payments will be generated from licensing fees, R&D funding, milestone payments, and equity. This figure does not include future royalties from commercialization which will generate additional revenue.