By Chris Holman
Sun Pharmaceutical v. Incyte, 2023 WL 5370639, Not Reported in Fed. Rptr. (Fed. Cir. Aug. 22, 2023)
Bald Girls Do Lunch (“BDGL”) is a nonprofit organization dedicated to improving the quality of life for females living with alopecia areata (“AA”). AA has been described as “an autoimmune skin disease resulting in partial to complete hair loss on all hair-bearing areas of the body, including, for example, on the face, resulting in loss of eyebrows and eyelashes.” According to BDGL, “AA is not a simple cosmetic problem—it is a chronic, often devastating condition that has substantial and wideranging implications, affecting patient’s physical, mental, and emotional health. Indeed, in severe cases, AA can lead to chronic depression.”
On August 22, the Federal Circuit issued a nonprecedential opinion in the case of Sun Pharmaceutical v. Incyte affirming an IPR decision that struck down as obvious all the claims in a patent directed towards a promising new treatment option for AA. The patent is directed towards certain deuterated derivatives of ruxolitinib. Ruxolitinib is a JAK1/JAK2 inhibitor “currently approved for the treatment of patients with intermediate or high-risk myelofibrosis.” Deuteration involves replacing one or more hydrogen atoms of a drug with deuterium, an isotope of hydrogen, to slow the CYP-mediated metabolism of a drug or to reduce the formation of undesirable metabolites, which can result in improved safety, tolerability, or efficacy. The claims encompass an octo-deuterated ruxolitinib analog identified as “CTP-543,” a potential treatment for AA that has been granted “Fast Track” and “Breakthrough Therapy” designations, which means that FDA will expedite its review as a new drug.
BDGL filed an amicus curiae brief in support of the patent owner, Sun Pharmaceutical, which focuses on one specific aspect of the Patent Trial and Appeal Board’s decision, i.e., the Board’s evaluation of one of the objective indicia of nonobviousness, “long-felt but unsolved need.” The Board found that while CTP-543 has the “potential” and “likelihood” of satisfying the need for an effective treatment for AA, as of now it has not actually satisfied the need for an FDA-approved treatment for AA, because it has yet to receive FDA marketing approval.
In its brief, BDGL argues that in 2012, at the time of the patent’s effective filing date, there was a long-felt, unmet need for a new treatment option for AA. No FDA-approved AA treatment existed, and off-label treatments were ineffective or not tolerable long-term, or both, and many caused unwanted side effects, ranging from unpleasant or undesirable to potentially serious. BDGL argues in its brief that the proper time for assessing the presence of a long-felt, unmet need is at the time of patent filing, and that the determination of whether that need has been satisfied should be based on the treatment as claimed in the as-filed patent application, not upon a marketed product embodying the patented invention. The organization points to the FDA’s decision to grant CTP-543 expedited review status as evidence of the long-felt, unmet need for treatment for AA patients, as well as positive results in completed Phase 3 clinical trials.
BDGL’s brief concludes by warning that the Board’s approach “threatens to upend the well-established obviousness analysis – solely with respect to patents on technology that requires premarket regulatory approval such as pharmaceutical patents – and threatens to impede the development of innovative pharmaceutical treatment necessary to care for patients, particularly for patients suffering from conditions for which no treatment otherwise exists.”
A unanimous panel of the Federal Circuit was not persuaded, however, upholding the Board’s determination with respect to objective indicia as well as its ultimate conclusion that all of the claims were obvious. The Federal Circuit explained:
Assuming, without deciding, that the need for an effective and safe alopecia areata treatment existed, the Board had substantial evidence for its finding that CTP-543 had not actually satisfied this long-felt need, but only had the “potential” and “likelihood” to do so. While we agree with Sun (and amicus Bald Girls Do Lunch) that FDA approval is not a prerequisite to showing that a long-felt need has been met, and FDA’s designation of CTP-543 for “Breakthrough Therapy” and “Fast-Track” approval are probative of nonobviousness, here Sun expressly framed its objective indicia argument as “CTP-543 satisfies the long-felt need for an FDA-approved, evidence-based alopecia areata treatment,” (emphasis added), and the Board reasonably found that CTP-543 had not met this need because it lacked FDA approval. Thus, substantial evidence supports the Board’s conclusion that Sun did not prove that CTP-543 has satisfied this long-felt need.
Note the emphasis that the Federal Circuit places on Sun Pharmaceutical’s decision to frame the issue on appeal as whether CTP-543 had satisfied the need for an “FDA-approved” AA treatment, seeming to suggest that the outcome might have been different if Sun Pharmaceutical had simply argued that the drug had satisfied the need for a new treatment option for AA, without any explicit mention of FDA approval. In a footnote, the court specifically notes that “evidence provided by the amicus, Bald Girls Do Lunch, but not otherwise in the record cannot be considered on appeal.”
Sun Pharmaceutical v. Incyte raises the question of whether deuterated analogs of prior art compounds will generally be found obvious. I suspect that the answer is no, and as is the case with claims directed towards enantiomers, the determination will be fact-dependent and made on a case-by-case basis. In this particular case, the Board found that the prior art references of record (which included a marketing publication issued by Concert Pharmaceuticals, the original owner of the patent) disclosed (1) that ruxolitinib is a promising drug candidate; (2) that deuteration of compounds provides the potential for improved safety, better tolerability, and enhanced efficacy; and (3) the specific locations of certain metabolic “hotspots” on ruxolitinib, which are the sites on a compound were oxidative metabolism occurs during in vivo metabolism. These “hotspots” correspond to the locations where the compounds claimed in the patent are deuterated.
I can imagine scenarios in which a deuterated analog of a prior art compound might be deemed nonobvious. For example, if the prior art did not provide sufficient motivation to deuterate the particular compound at issue, or did not identify specific metabolic “hotspots” as likely locations for deuteration. Or in some cases a court might find that there was not a reasonable likelihood of success in creating or using a particular deuterated compound.
Fortunately, this was a nonprecedential decision. Given the length of time that generally elapses between the filing and issuance of a patent and FDA approval of the corresponding patented compound, a determination of obviousness will often occur prior to FDA marketing approval. Would the outcome in this case have been different if FDA had approved CTP-543 during the intervening time between the Board decision and the Federal Circuit’s decision? If the FDA does eventually approve CTP-543, will Sun Pharmaceuticals have any avenue to revisit the issue in the courts or the PTO?