4.4. Cynomolgus monkeys

All cynomolgus monkeys used to test the various IL-2 fusion proteins had never received a human protein (Charles River Laboratories, Edinburgh, Scotland and Hoffmann-La Roche, Nutley, NJ). All procedures were performed with adherence to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Roche Institutional Animal Care and Use Committee and the Roche Ethics Committee for Animal Welfare. Individual subcutaneous doses were based on body weight and were formulated in 25 mM Citrate, 300 mM Arginine, pH6.7 with 0.5% normal cynomolgus serum. Arginine is included in the buffer to reduce the likelihood of aggregation [54]. The safety, efficacy and biologic responses to treatments were monitored in all blood samples taken during the studies using clinical hematology and chemistry analyses. Lymphocyte and eosinophil numbers were obtained from the clinical hematology complete blood count and, in conjunction with flow cytometry data, were used to calculate absolute numbers (cells/mm³ or cells/ml) of specific cell subsets.