This is not a trivial problem, as you can see by googling mixed integer least squares (MILS). Much will depend on the nature of the parameters, the number of variables you are using in the fit, and how exact the solution needs to be. One approach would be to start by rounding the coefficients that must be integer and improve the solution using annealing or genetic algorithms to jig the integer coefficients while fitting the remainder in the usual least square way, but that wouldn't have the elegance of some of the specific methods used for this sort of problem. However, I don't know of a package in scipy that implements those more sophisticated algorithms, perhaps someone else on this list who knows more about these things than I can point you in the right direction.

Chuck