Earlier this year the Federal Circuit issued its opinion in Sun Pharmaceutical Industries, Inc. v. Incyte Corporation, a patent case we have been following because it attracted amicus briefs. In this case, the Federal Circuit reviewed a judgment of the Patent Trial and Appeal Board invalidating Sun’s patent claims in an inter partes review proceeding for failure to meet the non-obviousness requirement. In an opinion by Judge Stark, joined by Judges Linn and Hughes, the Federal Circuit affirmed the PTAB’s judgment. In particular, the court held that the Board had “substantial evidence to conclude that a person of ordinary skill would have reasonable expectation” of success in modifying compounds as directed in Sun’s patent claims.
Judge Stark began by highlighting the factual and procedural background of this case.
[The Sun patent (‘149 patent) relates to] novel heteroaryl-substituted pyrrolo[2,3-d]pyrimidines, and pharmaceutically acceptable salts thereof, including the compounds and their use ‘in methods of treating diseases and conditions that are beneficially treated by administering an inhibitor of Janus-associated kinase with selectivity for subtypes 1 and 2 (JAK1/JAK2). . . . Ruxolitinib is a known JAK1/JAK2 inhibitor and is ‘currently approved for the treatment of patients with intermediate or high-risk myelofibrosis.’ . . . The IPR focused primarily on . . . an octo-deuterated ruxolitinib analog, in which every Y2 and Y3 hydrogen is deuterated. In its IPR petition, Incyte presented two obviousness grounds, but the Board only considered one: the combination of Rodgers, Shilling, and the Concert Backgrounder [prior art]. Rodgers is a U.S. patent directed to heteroaryl substituted pyrrolo[2,3,-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrmidines that modulate the activity of Janus kinases. Importantly, Shilling . . . identifies ruxolitinib’s metabolic ‘hotspots’, which are the sites on a compound where oxidative metabolism occurs during in vivo metabolism. . . . The study identifies that the majority of ruxolitinib’s metabolism occurs on its cyclopentyl ring at its four methylene carbons (the Y2 and Y3 positions in . . . the [Sun patent]. . . . The Concert Backgrounder is a marketing publication issued by the original owner of the [Sun patent], Concert. It teaches that deuteration of compounds provides the potential for improved safety, better tolerability, and enhanced efficacy . . . further . . . ‘[d]euteration provides novel agents with the potential for . . . [i]mproved safety[,] . . . [b]etter tolerability[,] . . . [and] [e]nhanced efficacy,’ adding that Concert ‘is deploying its product technology platform to rapidly assemble a pipeline of valuable new deuterated drugs.’
Judge Stark explained how the panel considered the Board’s decision “de novo” and reviewed its “underlying fact-findings for substantial evidence.” He explained how the panel applied the two-step test for determining obviousness for patents involving chemical compounds, which includes first determining “whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds.” Judge Stark then highlighted the second inquiry of the test, “whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead compound to make the claimed compound with a reasonable expectation of success.”
First, Judge Stark concluded that “a person of ordinary skill would have been motivated to deuterate ruxolitinib to modify its pharmacokinetic properties” and cited to “substantial evidence” including expert testimony and combined teachings of the prior art.
Second, Judge Stark concluded that the Board’s findings that “a person of ordinary skill would have been motivated to modify ruxolitinib at its metabolic hotspots on its cyclopentyl ring” were supported by substantial evidence. As support, he cited prior art and expert testimony. Specifically, Judge Stark emphasized expert testimony supporting the position that “there is substantial evidence that an ordinarily skilled artisan would have been motivated to make the specific modifications necessary to modify ruxolitinib to its deuterated analogs.” Furthermore, Judge Stark determined, the Board was correct in concluding that “a person of ordinary skill would have had a reasonable expectation that she could succeed in modifying ruxolitinib to arrive at its tetra- and octo-deuterated analogs, which she would expect to display superior ADME properties.” Again, Judge Stark refered to expert testimony. This testimony indicated “the deuteration strategy” was “predictable” and persons with ordinary skill in the art “would have been able to synthesize the claimed compounds” of Sun’s patent “and would also have expected the resulting compounds to demonstrate metabolic stability.”
While Sun argued that embodiments of it claims “display two unexpected results,” Judge Stark found that there was substantial evidence to “support the Board’s contrary finding” that the differences were “merely a difference in degree and not in kind.” Furthermore, Judge Stark rejected Sun’s argument that there was “evidence of a long-felt but unsolved need.” He explained how the court agreed with the Board that Sun’s patent claims “had not actually satisfied this long-felt need, but only had the ‘potential’ and ‘likelihood’ to do so.” He also concluded that lack of approval by the Food and Drug Administration for compounds described in the patent claims did not provide substantial evidence that that the Sun patent satisfied a long-felt need for alopecia areata treatment.
As a result of its analysis, the Federal Circuit affirmed the judgment of the PTAB, which invalidated Sun’s patent claims.