A real defense is a justification for a maker or drawer not to honor a negotiable instrument even if it has been transferred to a holder in due course (or "HDC") because it makes the instrument “void” according to Uniform Commercial Code §3-305 comment 1, thus it can’t be "cut off" by the transfer to an HDC. Contrast this with personal defenses (such as failure of consideration), which cannot protect the maker against the claims by an HDC.
Read more about Real Defense: Ten Types of Real Defenses Depending Upon State Law
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