On Apr. 12, 2023, Federal Circuit affirmed district court’s decision that asserted claims of US 10,130,589 are invalid.

 

Background:

The US’589 patent is listed in Orange Book for Neupro® (Rotigotine) film/patch, which is used to treat Parkinson’s disease. The technology at issue relates to transdermal therapeutic systems (TTSs), which deliver drugs through the patient’s skin and thus avoid complications with oral treatments. These patches contain drugs in an “amorphous,” form as crystalline form cannot cross the skin barrier. Consequently, crystallization in patches can reduce the amount of drug leaving the patch and hence reduce a patient’s dose. Original Neupro® contains a dispersion of amorphous rotigotine and polyvinylpyrrolidone (PVP). In August 2007, some three months after the original Neupro® U.S. launch, it was discovered that a new crystalline form of rotigotine—“Form II”—occurred when rotigotine was stored at room temperature. In 2012, the FDA approved a new version of Neupro® (reformulated Neupro®), which employs a weight ratio of 9:4 rotigotine to PVP. The reformulated Neupro® exhibits long-term stability at room temperature with a two-year shelf-life. In 2013, Actavis submitted ANDA to the FDA for approval of a generic version of a transdermal rotigotine patch. UCB filed suit and in its decision, district court upheld the validity of 6,884,434 patent and found 8,232,414 patent invalid.

 

In 2018—while UCB I was on appeal—UCB filed the patent application that matured into the patent-in-suit, the ’589 patent. The ’589 patent claims priority from a provisional application filed in December 2009. The ’589 patent discloses and claims a TTS having a range of rotigotine to PVP ratios by weight of about 9:4 to about 9:6. The patent explains that no crystals were observed at room temperature for up to 24 months. In March 2019, UCB again filed a lawsuit against Actavis, accusing Actavis’s same ANDA of infringement for US’589 patent. Actavis conceded that, if the ’589 patent is valid, then its ANDA would infringe. In March 2021, the district court ruled on Actavis’s invalidity defenses. Applying the “at once envisage” framework for anticipation articulated in Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2015), the district court found that the Muller patents anticipate all asserted claims. Separately, the district court held that the asserted claims would have been obvious in view of multiple prior art references, including the Muller patents. UCB appealed.

 

Appeal:

UCB argued that the district court committed legal error by applying the wrong law—Kennametal and the “immediately envisage” line of cases—in its anticipation analysis. Federal circuit agreed and said that here, it is undisputed that the Muller patents disclose a range that overlaps with the claimed range. In finding that the Muller patents anticipate the asserted claims of the ’589 patent, however, the district court did not apply the traditional framework for analyzing overlapping ranges. The district court relied on testimony from an Actavis expert, Dr. Robin Rogers, that a person of ordinary skill in the art would read Muller’s range to teach “a few examples” of TTSs with specific weight ratios. Based on this testimony, the district court found that “[a] POSA would envisage examples at whole and half integer percentages of PVP and would not look in more granular detail. Here, the district court’s use of Kennametal—supporting its finding that Muller’s range recites a specific example and thus that the specific example anticipates the entire range recited in the ’589 patent claims—goes beyond Kennametal’s intended application. Therefore, it is a legal error.

 

With respect to obviousness, Federal Circuit said that since the range claimed in the ’589 patent overlaps with the ranges taught by the Muller patents, Actavis has established a prima facie case of obviousness. District court correctly found based on expert testimony and prior art, crystallization in both Form I and Form II occurs due to hydrogen bonding between two rotigotine molecules. And while Form II is considered more stable and less soluble than Form I, other evidence, including expert testimony, indicated that small, rather than systemic, changes to TTSs were needed to achieve stabilization. Further, the court found that a person of ordinary skill would expect that increasing the concentration of PVP in a TTS would increase the stability of the amorphous drug. Only minor changes to the amount of PVP were needed to address crystallization of original Neupro. Also, the district court’s finding that Tang does not teach away is not clearly erroneous. Tang does not criticize, discredit, or otherwise dissuade a skilled artisan from investigating the claimed range of ratios. Tang expresses a preference for a higher PVP percentage (a 9:18 rotigotine to PVP weight ratio), but it does not teach away from the claimed range. Moreover, the claimed range did not produce new and unexpected results. The court determined that results obtained in the alleged invention and those in prior art, like the ’747 Muller patent, are “similar in kind . . . [and] with similar levels of stability (i.e., lack of crystallization).” With respect to commercial success, court found that UCB’s Muller patents (blocking patent) weakened its evidence of commercial success. Therefore, the asserted claims are invalid as obvious.