By using two model proteins, glucose oxidase and lipase, we demonstrate that dry crystalline formulations are significantly more stable than their amorphous counterparts. The results of Fourier-transform infrared spectroscopy indicate that crystalline proteins better maintain their native conformation in accelerated stability studies. The lower tendency of crystalline proteins to aggregate is confirmed by size-exclusion chromatography. The data suggest that protein crystallization may significantly improve some aspects of protein handling, and change the way biopharmaceuticals are produced, formulated, and delivered.

Therapeutic applications for mAbs have increased dramatically in recent years, but the large quantities required for clinical efficacy have limited the options that might be used for administration and thus have placed certain limitations on the use of these agents. We present an approach that allows for s.c. delivery of a small volume of a highly concentrated form of mAbs. Batch crystallization of three Ab-based therapeutics, rituximab, trastuzumab, and infliximab, provided products in high yield, with no detectable alteration to these proteins and with full retention of their biological activity in vitro. Administration s.c. of a crystalline preparation resulted in a remarkably long pharmacokinetic serum profile and a dose-dependent inhibition of tumor growth in nude mice bearing BT-474 xenografts (human breast cancer cells) in vivo. Overall, this approach of generating high-concentration, low-viscosity crystalline preparations of therapeutic Abs should lead to improved ease of administration and patient compliance, thus providing new opportunities for the biotechnology industry.

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