The most common substantive rejection of a USPTO trademark application is due to a “likelihood of confusion” under Trademark Act Section 2(d).
A response to a 2(d) refusal is often complex. Of course, each situation is unique and depends upon the marks at issue, their relative strength or weakness and/or dilution, the goods and/or services at issue, and much more.
Below is a recent Office Action Response filed by our firm. As you can see, it includes not only a substantial substantive argument, but a lot of tangible evidence attached.