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This paper presents a Branch and Price approach for a real-life Bus Driver Scheduling problem with a complex set of break constraints. The column generation uses a set partitioning model as master problem and a resource constrained shortest path problem as subproblem. Due to the complex constraints, the branch and price algorithm adopts several novel ideas to improve the column generation in the presence of a high-dimensional subproblem, including exponential arc throttling and a dedicated two-stage dominance algorithm. Evaluation on a publicly available set of benchmark instances shows that the approach provides the first provably optimal solutions for small instances, improving best-known solutions or proving them optimal for 48 out of 50 instances, and yielding an optimality gap of less than 1% for more than half the instances.