With increasingly complex analysis and dry-lab experiments in post genomic bio-informatics, the importance of computational tools for biologist and scientist has increased. Conventional software engineering practices including agile approaches are not suitable for evolutionary systems application development because of their peculiar characteristics ever evolving nature. In this research work we propose a a Prototype–based Software Development Methodology based on Prototype-based object modeling technique for developing agile software systems/applications. We feel that our proposed methodology is a suitable candidate to model evolutionary systems such as bio-informatics. The research work presents a detailed description of Analysis, Design and Implementation phases. A formal algorithmic representation of the methodology is also provided. Also included is a comparison between class based and prototype based object modeling techniques to highlight the suitability of the later for modeling evolutionary domains. In the end, an Oncology case study explains the working, applicability and suitability of our proposed methodology.