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Stock award plan - Share-based Compensation (Details) - USD ($)
$ in Thousands
12 Months Ended
Dec. 31, 2017
Dec. 31, 2016
Dec. 31, 2015
Share-based compensation expense recorded in the statement of operations      
Share-based compensation expense $ 30,559 $ 35,009 $ 33,979
Research and development      
Share-based compensation expense recorded in the statement of operations      
Share-based compensation expense 15,456 16,812 16,138
Selling, general and administrative      
Share-based compensation expense recorded in the statement of operations      
Share-based compensation expense $ 15,103 $ 18,197 $ 17,841