Oscorp Colonels are the highest rank of all Oscorp guards. They come with full-body Oscorp Guard armor and a giant Oscorp-style Gatling gun ready to destroy anything in their path. Their main purpose is to be Oscorp's most feared Guard group, but, formerly, during the cross-species virus incident, they were the Guards in charge of destroying cross-species.
It is extremely difficult to take out these Guards. One's best chance would be to do it by stealth; Colonels are invulnerable. They'll shoot down any opponent in the front, but they can't turn around fast enough with the gun they have to defeat anything behind them. Thus, they are also equipped with an area-of-effect grenade that is mainly designed to control cross-species before their capture, but if it is set right, it can harm full humans as well. Spider-Man can make quick work of them by tying them up in a web-like cocoon and dangle them from the ceilings, as he does in most of his encounters with these brutes.