Dear expert scientists whom I respect

I really need your suggestion to get through to the repetitive failure in the double digest RE cloning into the company-made TOP10F E.coli, which results in empty vector clones

My PCR insert and vector size are 1kb and 4 kb, respectively. Both of them are double digested using two incompatible restriction enzymes (at concentration of 500 ng insert and 500 ng vector). Ligation of digested products were performed each at 1:3 and 1:5 vector to insert ratio at 4C overnight and 5 uL of Ligated mixtures was transformed into the 50 uL host cell. I have tried the double digestion separately (1.5 hours each) and simultaneously(overnight) and gel purify for digested products. The number of grown clones for separate digestion were not as much as overnight simultaneous digestion but no recombinant insert found after conducting PCR of isolated plasmid. For control, I always included background control (digested vector and insert without ligase to observe whether or not an uncut plasmid is still present) and proceeded to transformation for these two digestion optimization, however this control also showed many background colonies. Does it mean that one of the REs is not optimally digested ?

Any help would be highly appreciated

Thank you