>>Published online before print June 2, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.1131899100
Applied Biological Sciences
Crystalline monoclonal antibodies for subcutaneous delivery
Mark X. Yang, Bhami Shenoy, Matthew Disttler, Reena Patel, Margaret McGrath, Sergey Pechenov, and Alexey L. Margolin *
Altus Biologics, Inc., 625 Putnam Avenue, Cambridge, MA 02139
Communicated by Alexander M. Klibanov, Massachusetts Institute of Technology, Cambridge, MA, April 1, 2003 (received for review January 23, 2003)
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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