Last week the Patent Trial and Appeal Board invalidated Concert Pharmaceuticals’ patent covering modified ruxolitinib compounds in a final inter partes review decision, despite having initially denied institution of the underlying petition. The Board found all claims of U.S. Patent No. 9,249,149 obvious over the prior art. Ruxolitinib is the active ingredient in Concert’s Jakafi® product, indicated for treatment of myelofibrosis. The ’149 patent claims deuterated ruxolitinib compounds and suggests these compounds may have other potential clinical applications beyond myelofibrosis treatment.
Concert’s patent explains that many drugs have poor ADME properties (adsorption, distribution, metabolism, and excretion) which decreases their efficacy in treating disease. Deuterium modification—replacing hydrogen atoms of a drug with deuterium atoms—can improve a drug’s metabolic properties. However, the patent states that the impact of deuterium modification on a drug’s metabolic properties is unpredictable, such that trial and error is the only path forward.
The Board initially denied Incyte Corporation’s IPR petition in October 2017, finding that Incyte provided neither a reason why a person of ordinary skill in the art (“POSA”) would have chosen ruxolitinib as a lead compound, nor a motivation to deuterate the compound. The Board reasoned that Incyte did not show that a POSA would have had reason to choose ruxolitinib “as opposed to any other compound with known clinical efficacy” and even if they had, a POSA would not have understood that ruxolitinib was in need of the potential clinical benefits of deuterium modification.
The Board reversed course in April 2018, granting Incyte’s request for rehearing because it was “persuaded that [it] applied an overly restrictive standard for the lead compound analysis.” In the institution decision, the Board reasoned that the prior art taught “useful properties” of ruxolitinib that would have led a POSA to choose it as a lead compound.
In the final written decision, the Board applied the standard lead compound analysis where obviousness is based on the determination of whether: (1) a POSA would have selected the prior art compound as a lead compound for further development efforts, and (2) there was reason to modify that compound to make the claimed compound with a reasonable expectation of success.
Under step one, the Board found that the prior art taught ruxolitinib and demonstrated useful properties of ruxolitinib that would have led a chemist to select it as a lead compound (which Concert did not dispute).
Under step two, the Board found that the prior art would have motivated a POSA to make deuterated ruxolitinib compounds based upon the structural similarity of the claimed compounds and the prior art compounds, and deuteration’s potential to improve ADME properties. (Incidentally, there was no discussion of any prior art identifying ruxolitinib as having ADME limitations.)
As to reasonable expectation of success, the Board rejected Concert’s efforts to challenge whether a POSA would have reasonably expected deuteration of ruxolitinib to achieve “metabolic change.” The Board also disagreed with Concert’s argument that a POSA would not have predicted the effect that deuteration would have on the chemical profile of the drug. The Board clarified that the proper inquiry is whether a POSA “would have had a reasonable expectation of successfully making the claimed invention in light of the prior art” (emphasis in original). Thus, the Board was satisfied that the prior art provided a reasonable expectation of successfully deuterating ruxolitinib compounds and that the deuterated compounds “may display superior ADME properties” (emphasis added).
While it remains to be seen whether this decision will stand on appeal, the Board’s decision would indicate that a petitioner need not prove a POSA would have known that modifying a lead compound would yield a superior—or even effective—drug; the inquiry is instead whether a POSA would have reasonably expected that a claimed compound “may” display superior properties. We will monitor this case to see how appellate review impacts the Board’s holding.