Coastal regions are conceived as innovation gateways. Being open to the world the territories adjacent to marine and ocean coasts absorb latest trends in technologies, techniques, business models, and other advancements. The full spectrum of innovative solutions are transmitted upcountry after being assimilated with respect to regional and national legislation, business culture, available resources, market expectations and other particularities of the territorial community. Exclave position of a region imposes restrictions to the process of knowledge and innovation diffusion, resulting from both its spatial isolation and differences in properties of the regional innovation system from the national innovation system domain. The study focuses on new industrialization of the Kaliningrad region, which by the end of 1991 during perestroika became an isolated part of Russia - the enclave on the Baltic Sea. The paper provides an in-depth case study on regional innovation system dynamics of the Kaliningrad region. The study concludes with policy implications on resetting the innovation gateway role of the region