Inter Partes Review: Patent Killer No More?

Inter Partes review (IPR) can efficiently invalidate drug patents and potentially convey strategic advantages to follow-on drug makers. However, recent changes in the IPR system foretell a tectonic shift in the landscape. Here we summarize these major changes and discuss the implications for the biopharmaceutical community.

Role of PARL-PINK1-Parkin pathway in adipocyte differentiation.

OBJECTIVE: Adipogenesis determines the number of adipocytes which is increased when individuals become obese. Mitochondria undergo remarkable morphological and functional changes during adipogenesis. PTEN-induced kinase 1 (PINK1) is pivotal to maintain mitochondrial homeostasis in neural cells. The present study aimed at investigating effects of PINK1 on adipogenesis and energy metabolism. METHODS: Expression of presenilin associated rhomboid-like protein (PARL), PINK1 and Parkin, as well as the interaction among these proteins was temporally examined during adipogenesis. In addition, the alterations of mitochondrial mass and the energy metabolism were also analyzed. RESULTS: Adipogenic process can be dissected into 3 stages according to the participation of PARL-PINK1-Parkin system. (1) When pre-adipocytes are switched to differentiation, f-PINK1 is subjected to PARL cleavage to generate s-PINK1 at the early stage of differentiation (0-4day). Mitochondrial mass is increased for generating ambient energy to meet the demands for cellular remodeling. (2) At the second stage (5-6day), s-PINK1 persistently accumulates in mitochondria and translocates into cytoplasm to mediate Parkin degradation. Mitochondria are fragmented to reduce their mass. (3) At the late stage (7-8day), only residual autophagy activity is remained when excess mitochondria have been eliminated. This mitochondria clearance maintains energy consumption of mature adipocytes at the minimal levels for storing energy. PARL silencing aborts adipogenesis by inhibiting PPARγ expression and the finely-orchestrated events. CONCLUSIONS: Our findings reveal the sequential adipogenic events directed by PARL-PINK1-Parkin system, add more evidence supporting the convergence of pathogenesis leading to neurodegenerative and metabolic diseases, and provide substantial information for developing novel therapeutic strategies by manipulating adipogenesis.