The use of the tag for academic users was unrestricted; however, commercial users had to pay royalties to Roche. The original patent expired on 11 Feb 2003, and is now public property; current claims to royalties are based on a much narrower set of more recent patents. Suitable tag sequences are available free for commercial use; for example, MK(HQ)6 may be used for enhanced expression in "E. coli" and tag removal. The total number of histidine residues may vary in the tag from as low as two, to as high as 10 or more His residues. N- or C-terminal his-tags may also be followed or preceded, respectively, by a suitable amino acid sequence that facilitates removal of the polyhistidine-tag using endopeptidases. This extra sequence is not necessary if exopeptidases are used to remove N-terminal His-tags (e.g., Qiagen TAGZyme). Furthermore, exopeptidase cleavage may solve the unspecific cleavage observed when using endoprotease-based tag removal. Polyhistidine-tags are often used for affinity purification of genetically modified proteins.