Patent owners generally look to secondary indicia to bolster their nonobvious defenses when prior art and/or knowledge of a person of ordinary skill in the art (“POSA”) seem to make the obviousness decision a close call. This trend is just as common in Hatch Waxman litigation. Frequently, the active ingredient of a new branded drug exhibits superior, yet unanticipated, benefits over the available therapies at the time of the invention. Alternatively, pharmaceutical companies discover added benefit to the already-approved therapies through Phase III and IV clinical trials and post-hoc analyses of the data collected from these trials. Consequently, patent applicants in the pharmaceutical space tend to argue that their alleged inventions exhibit unexpected results, a secondary indicia of nonobvious, to the Patent Office in the prosecution of their patent applicants or to district court judges in the ensuing litigation. Here, we take a look back at several legal opinions from 2023—a seemingly emblematic year in the world of unexpected results in Hatch Waxman litigation.

To plead unexpected results, and more specifically “[t]o be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014) (citation omitted). A difference of degree is not as persuasive as a difference in kind—i.e., if the range produces “a new property dissimilar to the known property,” rather than producing a predictable result but to an unexpected extent. Id. Furthermore, evidence of superior efficacy does not undercut a reasonable expectation of success. See Hoffmann–La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331, 1333–34 (Fed. Cir. 2014).

In UCB, Inc. v. Actavis Lab'ys UT, Inc., the Federal Circuit was presented with claims directed to a method for stabilizing rotiogine, an active ingredient used to treat Parkinson’s disease. 65 F.4th 679, 694 (Fed. Cir. 2023). Plaintiff UCB argued that rotiogine resistance to crystallize within a claimed weight range provided unexpected improved stability throughout storage of the drug product. Defendant Actavis’s expert testified that the finding is one of degree in that by adding slightly more of an excipient, stability would naturally increase, whereas Plaintiff UCB’s expert testified that there were certain embodiments that did not inhibit crystals, whereas those immediately neighboring the identified claimed range did not, and thus the difference was not one of degree but a difference in kind. The Federal Circuit found that Defendant Actavis’s argument was more persuasive and affirmed the holding of obviousness.

In Taiho Pharm. Co. v. Eugia Pharma Specialities Ltd., the District of Delaware was presented with claims directed to method of treating digestive cancer or breast cancer. 687 F. Supp. 3d 516, 536 (D. Del. 2023). The Patent Office had originally allowed the claims based on the applicant’s argument that twice-daily dosing unexpectantly provided improved efficacy. At trial, the inventor shared that the results “sounded mystical,” but did not expound on why the results were unexpected. This improved efficacy—specifically, antitumor activity—was discovered in Phase 1 rather than Phase 3 trials. The District of Delaware held that the patents were obvious, finding the inventor’s reasoning not credible.

In Amgen Inc. v. Sandoz Inc., the Federal Circuit was presented with claims directed to a composition comprising stereometrically pure apremilast, an active ingredient used to treat psoriasis. 66 F.4th 952, 963-64 (Fed. Cir. 2023). The proffered unexpected result was that the stereometrically pure apremilast resulted in 20-fold higher potency than the racemic mixture. The inventor testified that given the racemate is a 50/50 mixture of enantiomers, a POSA would have expected only a 2-fold higher potency. The Federal Circuit found this reasoning scientifically grounded and persuasive and preserved the validity of the patent in suit.

Looking at Taiho and Amgen, there were three striking differences that likely yielded the difference in the different courts treatment of the patents in suit in question. First, the patent in suit in question in Amgen was a composition patent, while the patent in suit in question in Taiho was a method of treatment patent. Composition patents are generally regarded as providing inherently stronger patent protection. Thus, the unexpected results that buttress the validity of these types of patents seem to be weighed differently by courts as well. Second, the inventor in Amgen testified as more credible than the inventor in Taiho. Amgen’s inventor’s reasoning was scientifically sound, and he communicated that reasoning effectively to the court. Taiho’s inventor’s reasoning was nebulous and vague and did not explain why the invention claimed was novel or nonobvious. Third, the nexus of the unexpected results in Amgen were more clearly argued. This may be because the unexpected results of a compound almost always necessarily have nexus the claims of a compound patent. This may also be because the unexpected results of a method of treatment patent are more appropriately found from Phase III or IV studies, or the data derived from those studies, especially when the unexpected result is clinical efficacy.

The Federal Circuit provided useful feedback in In re Couvaras when presented with an unexpected results argument in the context of claims directed to a method of increasing prostacyclin release in systemic blood vessels to improve vasodilation. 70 F.4th 1374, 1380 (Fed. Cir. 2023). Couvaras argued that the claimed mechanism of action was unexpected, and that the Board erred in finding that it was simply inherent in the claimed method. The Federal Circuit stated that such an argument cannot overcome a prima facie case of obviousness, “even if the nature of that mechanism is unexpected.” “To establish unexpected results, Couvaras would have needed to show that the co-administration of a GABA-a agonist and an ARB provided an unexpected benefit, such as, e.g., better control of hypertension, less toxicity to patients, or the ability to use surprisingly low dosages.”

Even with this guidance from the Federal Circuit in In re Couvaras, the probative value of unexpected results seems to be very fact dependent. Considering the opinions together, there are no bright line rules that can be derived from the Federal Circuit and District Court precedent. Courts seem to weigh evidence largely based on expert testimony. And while the Patent Office’s stamp of approval is helpful, the presumption of validity that courts apply to allowed claims is not always dispositive.