IP Law Daily, PATENT—Fed. Cir.: Patents for re-formulated Neupro held to be invalid on obviousness grounds, (Apr 12, 2023)

By Robert B. Barnett Jr., J.D.

The Federal Circuit agreed with the district court that UCB’s patents for a re-constituted version of Neupro were invalid as obvious from the patents for the original version of Neupro.

In a patent infringement suit involving the Parkinson’s disease patch Neupro in which the Delaware district court invalidated the patents for anticipation and obviousness, the Federal Circuit Court of Appeals has affirmed the decision on obviousness grounds, even as it ruled that the lower court had used the wrong standard to find anticipation. The patent was invalidated because UCB’s new Neupro patents, which addressed the ability to store the drug at room temperature, was an obvious application of the old patents (UCB, Inc. v. Actavis Laboratories UT, Inc., April 12, 2023, Stoll, K.).

Background. UCB developed a patch to treat Parkinson’s disease. The patch administers the drug rotigotine into the bloodstream much more effectively than oral medicine had been able to do. The FDA approved the patch, called Neupro, in 2007. UCB owns several patents covering Neupro. Those patents teach a transdermal theraputic system (TTS) having rotigotine in an amount with polyvinylpyrrolidone (PVP) in the range of 1.5% to 5%. The patents teach a TTS with a ratio of 9% rotigotine to 1.5%-5% PVP by weight. The TTS should have a 9:3 weight ratio of rotigotine to PVP weight.

About three months after Neupro was released, a problem developed when it was determined that Neupro could fail when stored at room temperature. UCB then recalled Neupro in the U.S. Neupro was still sold in Europe under cold-chain conditions and in the U.S. under certain grandfathered conditions.

In 2012, the FDA approved reformulated Neupro, which employs a weight ratio of 9:4 rotigotine to PVP. The new version of Neupro could be stored at room temperature for up to two years.

In 2013, Actavis Laboratories UT, Inc., submitted an Abbreviated New Drug Application (ANDA) to the FDA for permission to produce a generic version of Neupro. In 2014, UCB sued Actavis for infringement of the original Neupro patent. The court granted UCB an injunction to prevent FDA approval of Actavis’s ANDA. The injunction expired in March 2021, when the original Neupro patent expired.

In 2018, while the suit against Actavis was still on appeal, UCB sought a new patent for the new version of Neupro. The new patent discloses a TTS having a range of rotigotine-to-PVP-by-weight of about 9:4 to 9:6.

In 2020, with the injunction still one year away from expiring, UCB sued Actavis again. This second lawsuit was different only in that it asserted infringement of the new patents. The new patents would delay FDA approval of a generic until the new patents expired in December 2030, which was nine more years. Actavis acknowledged that its ANDA would infringe the patents, but it argued that the patents were invalid.

Meanwhile, back in July 2019, UCB sued Mylan Technologies, Inc. in Vermont federal court, because Mylan had sought its own generic version of Neupro, alleging infringement of the new patents. The Vermont federal court agreed to adopt the pending Delaware court’s judgment.

In March 2021, just as the injunction was about to expire, the Delaware district court ruled in Actavis’s favor, finding that the prior patents anticipated all claims made in the new patents. The court reached its decision by applying the “at once envisage” framework set forth in Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2016)). The district court also ruled that the new claims were obvious in view of multiple prior art references, including the earlier patents. UCB appealed those decisions to the Federal Circuit Court of Appeals in Washington, D.C. The pending actions in both Vermont and Delaware were consolidated for purposes of the appeal.

Anticipation. The appellate court agreed with UCB that the Delaware district court erred when it applied Kennametal. The proper framework when a range is claimed, the appellate court ruled, would be to look at whether prior art discloses a point within the claimed range or discloses its own range that overlaps with the claimed range. If the prior art discloses a point with the claimed range, anticipation exists (Ineos USA LLC v. Berry Plastics Corp., 783 F.3d 865, 869 (Fed. Cir. 2015)). If the prior art merely discloses a range that overlaps the claimed range, anticipation exists only if the range describes a claimed range with specificity sufficient to enable a reasonable fact finder to conclude that no reasonable difference exists between them.

In this case, the appellate court said, the new patents disclose a range that overlaps with the claimed range. The district court, however, failed to analyze the two ranges to determine if no reasonable differences exist. Instead, the district court relied on Kennametal’s “immediate envisage” test to identify discrete points in the new patent’s range and then analyze those discrete points. As a result, the appellate court ruled, the district court erred by failing to apply the proper framework for comparing ranges. The appellate court also ruled that the district misapplied Kennametal by extending it beyond its intended application. The district court, therefore, committed legal error on the issue of anticipation, and its decision could not be upheld on that ground.

Obviousness. Turning to obviousness, the district court had ruled that obviousness existed for two reasons: (1) the overlap in the claimed range in the two patents failed to rebut obviousness and (2) the prior art’s 9:2 and 9:3 TTS examples as modified by the original patents’ teachings of a range of 1.5% to 5% PVP rendered the claims obvious. The appellate court ruled that it would not address the second reason because the first reason sufficiently established obviousness.

The appellate court noted that a presumption of obviousness exists when a claimed range overlaps with a range disclosed in prior art (Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299, 1311 (Fed Cir. 2006)). This presumption can be overcome only by a showing that (1) the prior art teaches away from the claimed range, (2) the claimed range produces new and unexpected results, or (3) other evidence demonstrates non-obviousness. UCB argued that all three conditions existed. The “other evidence” in this case, according to UCB, was significant sales of re-formulated Neupro. Thus, obviousness would be deemed to exist, unless UCB could establish one of the three exceptions.

Teaching away. The appellate court ruled that the lower court did not err when it rejected UCB’s argument that re-formulated Neupro changed the state of the art, thus rendering all prior patents irrelevant. In both patent groups, crystallization occurred due to hydrogen bonding between two rotigotine molecules. Although the re-formulated version might have been more stable and less soluble than the original version, only small changes were necessary to achieve the stabilization.

The appellate court went on to note that no error was found in the lower court’s conclusion that the new patents were not teaching away from the claimed range. “Teaching away” occurs when a person of ordinary skill would be discouraged from following the path set out in the original patents. In this case, the district court had found, the new patent “merely expresses a general preference for an alternative invention but does not ‘criticize, discredit or otherwise discourage’ investigation into the invention claimed” (In re: Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)). Thus, the appellate court ruled, the lower court’s finding that the prior art does not teach away from the range of 9:4 to 9:6 weight ratio of rotigotine to PVP was not clearly erroneous.

Unexpected results. UCB argued that the lack of crystallization in patches having a rotigotine-to-PVP-weight ratio within the 9:4 to 9:6 weight range was unexpected because original Neupro did crystallize. “A difference of degree is not as persuasive as a difference in kind,” the appellate court said. Expert testimony had established that adding slightly more PVP to increase stability was a change of degree that involved no new properties. Additional evidence established that a person of ordinary skill would expect the ratio range in the earlier version and the ratio range in the re-constituted version to provide stability similarly. Expert testimony, for example, established that “PVP was the most effective crystallization inhibitor tested.” Furthermore, a person of ordinary skill would expect that increasing the concentration of PVP in a TTS would increase the stability of the drug. And, finally, a person of ordinary skill would have known that only minor changes to the amount of PVP were necessary to address crystallization of original Neupro because of the success with cold-chain storage.

Other suggestions by UCB to justify its argument that the new patents produced unexpected results were also rejected. Any reported changes were “similar in kind” to the prior examples. Thus, the appellate court agreed with the lower court that no new and unexpected results were produced.

Other evidence. The appellate court then turned to UCB’s claim that the commercial success of new Neupro justified a reversal of the lower court’s ruling. “We have repeatedly held,” the appellate court said, “there must be a legally and factually sufficient connection between the evidence and the patent claims.” Commercial success is not enough because any number of reasons could explain the success. What was needed was evidence that the commercial success resulted from the changes in the new patent.

The district court had ruled that evidence of commercial success due to the new patents was weak because the patents acted as blocking patents intended to dissuade competitors from developing a rotigotine TTS. The appellate court agreed with that assessment, and it agreed with the lower court that UCB had failed to satisfy the “other evidence” exception.

The Federal Circuit, therefore, affirmed the lower court’s ruling that the claims were invalid as obvious.

The Case is No. 21-1924.

Attorneys: Richard L. Rainey (Covington & Burling LLP) and Jack B. Blumenfeld (Morris, Nichols, Arsht & Tunnell LLP) for UCB, Inc., UCB Pharma GmbH, LTS Lohmann Therapie-Systeme AG and LTS Lohmann Therapie-Systeme AG. John C. O'Quinn (Kirkland & Ellis LLP) for Actavis Laboratories UT, Inc. Deepro Mukerjee (Katten Muchin Rosenman LLP) for Mylan Technologies Inc.

Companies: UCB, Inc.; UCB Pharma GmbH; LTS Lohmann Therapie-Systeme AG; LTS Lohmann Therapie-Systeme AG; Actavis Laboratories UT, Inc.; Mylan Technologies Inc.

Cases: Patent FedCirNews GCNNews