See ISPE Guidelines 10.17.

There is no need for the significant structural element to be novel in absolute terms (i.e. novel per se). Rather, this expression means that in relation to the common property or activity there must be a common part of the chemical structure which distinguishes the claimed compounds from any known compounds having the same property or activity. However, if it can be shown that at least one Markush alternative is not novel, unity of invention should be reconsidered. In particular, if the structure of at least one of the compounds covered by a Markush claim is known together with the property or technical effect under consideration, this is an indication of lack of unity of the remaining compounds (alternatives).