This study presents an exploration on extending the action of therapeutic proteins by crystallization strategy without new molecular entities generation. Recombinant human interferon α-2b (rhIFN), a model protein drug in this case, was crystallized using a hanging drop vapor diffusion method. A novel chelating technique with metal ions was employed to promote crystals formation. The physico-chemical characterization of the protein crystals, including morphology, particle size, X-ray diffraction, circular dichroism and biological potency evaluations were performed. In addition, the in vitro release behavior of rhIFN from crystal lattice suggested an exciting possibility of protein crystals as a long-acting formulation. The work described here demonstrates the possibility of spherical crystals of biomacromolecules for controllable delivery application of therapeutic proteins.