Patent Trial And Appeal Board Denies Inter Partes Review Of Patent Claiming The Deuterated Form Of A Known Compound

In Neptune Generics, LLC v. Auspex Pharmaceuticals, Inc., IPR2015-01313, Paper No. 25 (PTAB Dec. 9, 2015) ("Neptune"), the Patent Trial and Appeal Board ("the Board") issued an opinion denying institution of inter partes review of U.S. Patent No. 7,456,317 B2 ("the '317 patent"). The '317 patent claims an analog of venlafaxine (Effexor®) in which nine carbon-hydrogen (C-H) bonds are replaced with carbon-deuterium (C-D) bonds. ('317 patent, col. 5:61-67) Claim 1 is representative:

Venlafaxine's mechanism of action and metabolism have been studied extensively (id. at col. 4:6-19), and both venlafaxine and its active metabolite have half-lives that are much shorter than that "regarded as ideal for this class of compounds by most clinicians." (Id. at col. 4:41-50) Venlafaxine is a serotonin and norepinephrine reuptake inhibitor approved for the treatment of depression, generalized anxiety disorder, panic disorder, and social anxiety disorder. As the '317 patent acknowledges, "[d]euteration of pharmaceuticals to improve pharmacokinetics (PK), pharmacodynamics (PD), and toxicity profiles has been demonstrated previously with some classes of drugs." (Id. at col. 3:47-49)1

The '317 patent describes nearly 100 deuterated venlafaxine analogs, including the claimed one (id. at col. 10:51-col. 26:45), and states that enriching for deuterium alters the ratio of active venlafaxine metabolites, reduces unwanted metabolites, and increases the half-life of the parent drug and its metabolites. (Id. at col. 6:27-33)

The Petitioner challenged claim 1 of the '317 patent as being obvious over Fogelman2 in view of Miwa.3,4 The Petitioner primarily relied on Fogelman's disclosure that the major metabolites of venlafaxine are O-desmethylvenlafaxine ("ODV"), N-desmethylvenlafaxine ("NDV"), and N,O-didesmethylvenlafaxine ("N,O-DV"), depicted below.

(Neptune, Paper 25 at 9.) Fogelman states that "ODV has a receptor affinity profile similar to its parent compound [venlafaxine], while the latter two metabolites have little if any affinity for the . . . receptor sites." (Id. at 6) Fogelman further states that "approximately 90% of total intrinsic clearance was accounted for by the O-demethylation pathway," in which the venlafaxine methoxy group is converted to a hydroxy. (Id. at 7, 11)

The Petitioner relied on Miwa for the "teaching that for some drugs, isotope substitution (i.e., from hydrogen to deuterium) may reduce the rate of drug metabolism, and, therefore, may...