September 2013
The Prior Art’s Failure to Appreciate a Problem Solved by the Claimed Invention Indicates an Absence of a Reason to Attempt to Improve upon the Prior Art
| Judges: Rader (author), O’Malley, Reyna |
| [Appealed from Board] |
In Leo Pharmaceutical Products, Ltd. v. Rea, No. 12-1520 (Fed. Cir. Aug. 12, 2013), the Federal Circuit reversed the Board’s claim construction and obviousness determination, concluding that the Board incorrectly found the invention obvious over the prior art and incorrectly weighed the objective indicia of nonobviousness.
U.S. Patent No. 6,753,013 (“the ’013 patent”) is a National Stage entry of PCT/DK2000/00033 filed on January 27, 2000, and is owned by Leo Pharmaceutical Products, Ltd. (“Leo”). The ’013 patent is directed to pharmaceutical compositions for the treatment of psoriasis comprising a combination of at least one vitamin D analog, at least one corticosteroid, and at least one solvent selected from a particular group of solvents. The ’013 patent teaches that, prior to its filing date, a storage stable combination of a vitamin D analog and a corticosteroid in a single formulation did not exist. Because of the storage stability problem, the two drugs had to be administered separately, and this generated patient compliance issues.
The ’013 patent teaches that previous combination formulations were not storage stable because of the divergent pH requirements of vitamin D analogs, which require a basic environment, and corticosteroids, which require an acidic environment. After recognizing the storage stability problem, Leo discovered that use of a particular group of solvents, including polyoxypropylene 15 stearyl ester (“POP-15-SE”), solved the instability problem by allowing the vitamin D analog and corticosteroid to coexist in a single formulation.
In 2006, Galderma R&D requested reexamination of the ’013 patent. On reexamination, the examiner rejected the claims as obvious in view of three prior art references: U.S. Patent No. 4,083,974 to Turi (“Turi”) filed in 1977; U.S. Patent No. 4,610,978 to Dikstein (“Dikstein”) filed in 1984; and International Patent Application Publication No. WO 94/13353 to Serup (“Serup”) filed in 1993.
Turi discloses an anti-inflammatory pharmaceutical composition comprising a steroid and
POP-15-SE, and teaches that the compositions do not contain water, gels, or alcohol. Turi does not teach the use of vitamin D, the stability issues when a corticosteroid and vitamin D are combined, or the use of POP-15-SE or a corticosteroid for the treatment of psoriasis.
Dikstein discloses dermatological compositions comprising a vitamin D analog and a corticosteroid, and teaches that vitamin D can treat psoriasis. Dikstein teaches that corticosteroids have side effects, but is silent on whether vitamin D can treat the side effects. Each of Dikstein’s examples contain almond oil or propylene glycol, and some of them also contain water. Dikstein shows no appreciation of the storage stability issues and does not teach the use of POP-15-SE or any other solvent that would overcome the stability problem.
Serup discloses formulations comprising a vitamin D analog, a steroid, and water with examples that further comprise either almond oil, propylene glycol, or alcohol. Serup teaches that vitamin D treats the side effects of the steroid, but is silent regarding instability of the combined aqueous formulation or any other solvent that would overcome the stability problem.
During reexamination, Leo (1) amended claim 1 to recite, inter alia, that “the pharmaceutical composition is storage stable and non-aqueous”; (2) presented prior art medical reports discouraging the combination of vitamin D and a corticosteroid; and (3) provided experimental data showing that the presence of water, almond oil, propylene glycol, and alcohol was detrimental to the combined formulation. The PTO, however, maintained that the claims were obvious. Leo appealed to the Board, which affirmed the PTO’s determination and adopted the reasoning of the examiner.
Leo appealed the Board’s decision to the Federal Circuit, which reversed based on its finding of several flaws in the Board’s analysis. First, the Court held that the Board’s claim construction of the term “storage stable” was impermissibly narrow. Finding that the specification does not specifically define “storage stable,” the Board relied on the specific stability test disclosed in one of the ’013 patent’s examples. The Court held that the Board erred by defining the claim term far short of its broadest reasonable meaning because the example was just one disclosure of a stability test. The Court did not adopt a specific alternative meaning for the term, noting that such a finding was unnecessary for addressing the remainder of the appeal.
“[A]n invention can often be the recognition of a problem itself.” Slip op. at 11.
Turning to the Board’s obviousness determination, the Court held that the Board erred in finding that it would have been obvious to combine vitamin D and a corticosteroid in a single formulation based on the prior art references. The Court noted that the claimed invention was not simply a combination of elements found in the prior art. Noting that “an invention can often be the recognition of a problem itself,” the Court found that Leo’s invention recognized and solved a problem with storage stability that was unrecognized and unsolved by the prior art. Slip op. at 11. For example, though Dikstein and Serup disclose the combination of vitamin D and a corticosteroid, neither appreciates the stability problems of a single formulation thereof. Absent such recognition, the Court reasoned there was no reason for one of skill in the art to improve upon, for example, the formulation of Dikstein or Serup using Turi. Moreover, the Court found that the medical research reports provided by Leo during reexamination taught away from the combination.
Next, the Court held that the Board erred in finding a motivation to combine the corticosteroid POP-15-SE composition of Turi with vitamin D according to Dikstein or Serup. Noting that no one in fact did make such a composition until Leo did a decade later, the Court reasoned that the combination of Turi and vitamin D is only straightforward in hindsight.
Third, the Court held that the Board erred in finding that the prior art provided a strong reason for preparing a nonaqueous vitamin D and corticosteroid formulation with POP-15-SE. Specifically, the Board found that the skilled artisan would have added a vitamin D analog of Serup or Dikstein to Turi’s POP-15-SE composition of a corticosteroid. According to the Court, however, substantial evidence did not support the Board’s theory that the skilled artisan would deviate from the aqueous Serup and/or Dikstein compositions. The Court also disagreed with the Board’s finding that Turi excludes the solvents of Serup and Dikstein, finding, to the contrary, that such statements either taught away from or at least provided no motivation to combine.
Fourth, the Court held that the Board erred in finding that POP-15-SE would have been the obvious choice as a solvent for formulating vitamin D and a corticosteroid. Specifically building on the Board’s conclusion that Turi excludes the solvents used by Serup and Dikstein, POP-15-SE would have been the logical nonaqueous choice to use for improving Serup and Dikstein. Dikstein and Serup, however, reported that the combination of vitamin D and a corticosteroid in their respective compositions led to the surprising relief of side effects associated with steroidal application and more complete healing. Based on these surprising results, the Court found no reason to further improve upon the compositions of Serup and Dikstein as proposed by the Board.
The Court then held that the Board erred in finding that the claimed invention would have been obvious to try. Specifically, the Board found that the skilled artisan would have been capable of selecting the correct formulation from the more than eight different classes of additives in the prior art including diluents, buffers, thickeners, and lubricants, and more than ten different composition categories including liniments, lotions, applicants, creams, ointments, pastes, or gels. To the contrary, the Court found that “the breadth of these choices and the numerous combinations indicate that these disclosures would not have rendered the claimed invention obvious to try.” Id. at 16 (citing Rolls-Royce PLC v. United Techs. Corp., 603 F.3d 1325, 1339 (Fed. Cir. 2010)). Moreover, the Court again noted that more than ten years had elapsed since the critical date of the nearest-in-time prior art reference without emergence of a storage stable formulation as further evidence that the claimed invention was not obvious to try. Thus, the Court concluded that, rather than a finite number of identifiable, predictable solutions, the prior art provided no direction as to which of the many solutions were likely to be successful and, in fact, taught away from the combination of the claims.
Finally, the Court held that the Board erred in finding that the case of obviousness outweighed Leo’s asserted objective indicia of nonobviousness. Specifically, the Board found that Leo’s experimental data showing storage stability of the claimed composition was not surprising or unexpected. Noting that “[o]bjective indicia ‘can be the most probative evidence of nonobviousness in the record, and enables the court to avert the trap of hindsight,’” the Court found extensive evidence of unexpected results that, together with the entire obviousness analysis, presented a compelling case of nonobviousness. Id. at 20 (quoting Crocs, Inc. v. Int’l Trade Comm’n, 598 F.3d 1294, 1310 (Fed. Cir. 2010)). In addition to the experimental data showing the storage stability of the claimed invention, Leo presented comparative data showing significant degradation of the compositions of the Serup and Dikstein compositions, as well as degradation of a composition of Serup that had been improved with the POP-15-SE solvent of Turi. The Court reasoned that the comparative data provided strong evidence that the ’013 patent’s combination of known elements yielded more than just predictable results.
The Court further noted evidence of long-felt but unresolved need and commercial success in the record. Specifically, more than twenty-two years had passed since Turi published and fourteen years since Dikstein published, yet Leo was the first to provide a single formulation comprising a vitamin D analog and a corticosteroid. Additionally, Leo’s product Talconex®, embodying the elements of the ’013 patent, was the first FDA-approved single formulation product and enjoyed commercial success. The Court reversed the Board’s decision, holding that the invention of the ’013 patent would not have been obvious.
