Application Notes

6 APPLICATION NOTE ©2017 NanoTemper Technologies, Inc. South San Francisco, CA, USA. All Rights Reserved. storage at 25°C 0 4 8 12 16 20 -40 -30 -20 -10 0 0 4 8 12 16 20 0 4 8 12 16 0 4 8 12 16 20 0 4 8 12 16 20 F01 F02 F03 F04 F05 DDG (kJ/mol) DDG (kJ/mol) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) 20 95.0 95.5 96.0 96.5 97.0 97.5 98.0 98.5 99.0 99.5 100.0 month 12 9 Monomer / % initial value 6 95.0 95.5 96.0 96.5 97.0 97.5 98.0 98.5 99.0 99.5 100.0 17 month 12 9 Monomer / % storage at 5 °C initial value 6 F01 F02 F03 F04 F05 0 2 4 6 10 14 17 12 9 month Turbidity / FNU wavelength 400-600 nm initial value 6 8 12 0 2 4 6 8 10 12 14 16 month 12 9 initial value 6 Turbidity / FNU wavelength 400-600 nm A B C storage at 25°C storage at 5 °C 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 Figure 3: Comparison of aggregation prediction by chemical denaturation and long-term stability measurements. (A) Chemical denaturation data of mAb1 in formulations 1-5. Shown are the changes in ∆G° (∆∆G° values) relative to the ∆G° of the lowest mAb concentration. (B) Determination of monomer contents of mAb1 in formulations 1-5 by HPSEC at 5 °C and 25 °C over a time period of 17 and 12 months, respectively. (C) Turbidity measurements of mAb1 in formulations 1-5 by nephelometry at 5 °C and 25 °C over a time period of 17 and 12 months, respectively. storage at 25°C 0 4 8 12 16 20 -40 -30 -20 -10 0 0 4 8 12 16 20 0 4 8 12 16 0 4 8 12 16 20 0 4 8 12 16 20 F01 F02 F03 F04 F05 DDG (kJ/mol) DDG (kJ/mol) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) 20 95.0 95.5 96.0 96.5 97.0 97.5 98.0 98.5 99.0 99.5 100.0 month 12 9 Monomer / % initial value 6 95.0 95.5 96.0 96.5 97.0 97.5 98.0 98.5 99.0 99.5 100.0 17 month 12 9 Monomer / % storage at 5 °C initial value 6 F01 F02 F03 F04 F05 0 2 4 6 10 14 17 12 9 month Turbidity / FNU wavelength 400-600 nm initial value 6 8 12 0 2 4 6 8 10 12 14 16 month 12 9 initial value 6 Turbidity / FNU wavelength 400-600 nm A B C storage at 25°C storage at 5 °C 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 storage at 25°C 0 4 8 12 16 20 -40 -30 -20 -10 0 0 4 8 12 16 20 0 4 8 12 16 0 4 8 12 16 20 0 4 8 12 16 20 F01 F02 F03 F04 F05 DDG (kJ/mol) DDG (kJ/mol) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) mAb (mg/ml) 20 95.0 95.5 96.0 96.5 97.0 97.5 98.0 98.5 99.0 99.5 100.0 month 12 9 Monomer / % initial value 6 95.0 95.5 96.0 96.5 97.0 97.5 98.0 98.5 99.0 99.5 100.0 17 month 12 9 Monomer / % storage at 5 °C initial value 6 F01 F02 F03 F04 F05 0 2 4 6 10 14 17 12 9 month Turbidity / FNU wavelength 400-600 nm initial value 6 8 12 0 2 4 6 8 10 12 14 16 month 12 9 initial value 6 Turbidity / FNU wavelength 400-600 nm A B C storage at 25°C storage at 5 °C 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 -40 -30 -20 -10 0 10 20 mAb (mg/mL) mAb (mg/mL) mAb (mg/mL) mAb (mg/mL) mAb (mg/mL)

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