Innovation ecosystems tied to academic medical centers (AMCs) are inextricably linked to policy, practices, and infrastructure resulting from the Bayh–Dole Act in 1980. Bayh–Dole smoothed the way to patenting and licensing new drugs and, to some degree, medical devices and diagnostic reagents. Property rights under Bayh–Dole provided significant incentive for industry investments in clinical trials, clinical validation, and industrial scale-up of products that advanced health care. Bayh–Dole amplified private investment in biotechnology drug development and, from the authors’ perspective, did not significantly interfere with the ability of AMCs to produce excellent peer-reviewed science. In today’s policy environment, it is increasingly difficult to patent and license products based on the laws of nature—as the scope of patentability has been narrowed by case law and development of a suitable clinical and business case for the technology is increasingly a gating consideration for licensees. Consequently, fewer academic patents are commercially valuable. The role of technology transfer organizations in engaging industry partners has thus become increasingly complex. The partnering toolbox and organizational mandate for commercialization must evolve toward novel collaborative models that exploit opportunities for future patent creation (early drug discovery), data exchange (precision medicine using big data), cohort assembly (clinical trials), and decision rule validation (clinical trials). These inputs contribute to intellectual property rights, and their clinical exploitation manifests the commercialization of translational science. New collaboration models between AMCs and industry must be established to leverage the assets within AMCs that industry partners deem valuable.