Dalfampridine - USA

On Sep 10, 2018 Federal Circuit upheld Delaware court’s decision that Acorda’s four Ampyra® patents are invalid as obvious.

Acorda Therapeutics, Inc., holds NDA No. 022250, approved by the USFDA under the name “Ampyra®,” for 10 milligram 4-AP (dalfampridine) sustained-release tablets for twice-daily oral administration. Acorda owns U.S. Patent No. 8,007,826; No. 8,663,685; No. 8,354,437; and No. 8,440,703 (Acorda patents) expiring between 2025-2027. Acorda also holds an exclusive license from Elan corporation Inc. to an earlier, broader patent, U.S. Patent No. 5,540,938 (Elan patent) expiring in Jul 2018. The Elan patent, listed in the Orange Book for Ampyra along with the Acorda patents, claims methods of treating patients having certain conditions, including multiple sclerosis, by administering a drug containing a sustained-release formulation of any of certain agents, one of them 4-AP. The later Acorda patents claim species of the Elan patent’s genus claims by adding further, more specific requirements to the Elan patent’s claimed methods. While the Elan patent’s claims broadly cover administering a sustained-release formulation of 4-AP to individuals with multiple sclerosis, the Acorda patents’ claims further specify that such a drug must be administered (1) in a 10 mg dose twice a day (2) at that stable dose for the entire treatment period of at least two weeks (3) to achieve 4-AP serum levels of 15–35 ng/ml and (4) to improve walking.

Roxane, Mylan and Teva submitted ANDA seeking FDA approval to market generic versions of Ampyra. In July 2014, Acorda and Alkermes sued those entities (“defendants”) in the District of Delaware, alleging infringement of several claims in each of the Elan and Acorda patents. The defendants stipulated to infringement but challenged the validity of the asserted claims. The district court held that the asserted claims in the Acorda patents are invalid for obviousness. But the court upheld the asserted claims of the Elan patent against invalidity challenges and enjoined the defendants from activity infringing that patent until it expired on July 30, 2018. Acorda appealed.

Acorda made essentially three arguments on appeal regarding the district court’s ruling that the Acorda patent claims are invalid for obviousness. First, Acorda contends, on a number of grounds, that the district court erred in finding that a person of skill would have had a motivation to combine the prior art to arrive at the Acorda invention and a reasonable expectation of success in doing so. Second, Acorda challenges the court’s determination that the claim limitations relating to pharmacokinetics—i.e., achieving 4-AP serum levels of 15–35 ng/ml—are inherent in the claimed invention and therefore obvious. Third, Acorda argues that the court improperly applied a categorical rule that a blocking patent (the Elan patent) negates any findings in favor of Acorda on the objective indicia of commercial success, failure of others, and long felt but unmet need.

With respect to first point, Acorda argued that prior art, Schwid teaches away from the claimed invention; and that it teaches the administration of sustained-release 4-AP in a titrated dosing regimen rather than a stable-dosing regimen required by claim. However, federal circuit disagreed & said that Schwid supports a motivation to test, with a reasonable expectation of success, a 10 mg twice-daily dose of sustained-release 4-AP to improve walking in multiple sclerosis patients. Schwid itself used a 17.5 mg twice daily dose & found success. Schwid also provides affirmative reason to investigate low doses. Moreover, Acorda has pointed to nothing in Schwid declaring that doses lower than 17.5 mg twice-daily would not be effective in improving walking. And in light of Schwid’s warning that seizures may occur at higher doses, the district court did not clearly err in finding that a person of skill would look to lower doses rather than higher ones. Court also said that the prior art is not limited to titrated dosing (where doses start low and move higher) but rather contains evidence of stable dosing (where the dose starts and stays at the claimed level). Despite certain identified “shortcomings” in the principal references, “the combined message a person of skill in the art would have discerned from Schwid together with the Goodman references was a reasonable expectation of success in treating walking with 4-AP.” Moreover, Expert testimony further supports the district court’s findings. Therefor the district court did not clearly err in finding motivation to combine, and a reasonable expectation of success.

With respect to second point, Acorda did not directly object to the district court’s inherency finding about Hayes, but Acorda suggested that a person of skill would expect that the inherent pharmacokinetic profiles would differ between patients with spinal cord injury (as in Hayes) and patients with multiple sclerosis (as in the Acorda patents). But Acorda cited no support for that assumption, and Acorda appeared to have made the opposite assumption by including the Hayes pharmacokinetic data in its own patents on using 4-AP to treat multiple sclerosis. Acorda’s expert also admitted at trial that Hayes “may certainly show the pharmacokinetic profile that’s analogous to what would be found in MS [multiple sclerosis] patients.

With respect to third point, Acorda focused on the district court’s reliance on the Elan patent as a blocking patent for the Acorda patents’ claimed inventions, in determining that commercial success, failure of others, and long-felt but unmet need did not “support” or “militate in favor of” non-obviousness. Acorda characterizes the district court as having applied a categorical rule that a blocking patent defeats the significance of such objective indicia to the obviousness determination. Federal circuit however, said that district court’s opinion is best read not as invoking a categorical rule, but as drawing conclusions on the limited factual record created in this case bearing on the effect of a blocking patent. Acorda licensed the Elan patent in the late 1990s, before the period of commercial success alleged by Acorda. As to commercial success, the district court found that “no one other than the Elan patentees and their licensees could have practiced the invention of the Acorda patents without facing liability for patent infringement. The risk of such liability would have provided an independent incentive for a patentee not to develop the invention of the Acorda patents, even if those inventions were obvious.” Moreover, when seeking to use 4-AP for multiple sclerosis, Acorda itself sought and obtained a license to the Elan patent. There is no evidence that Elan sought to license the Elan patent to any entity other than Acorda, or that Acorda sought to sublicense the Elan patent, either of which would dilute the power of the blocking patent. And what Elan granted Acorda was an exclusive license, suggesting the significance of the Elan patent’s blocking power. Acorda offered no more persuasive basis for challenging the district court’s findings of the weakness of Acorda’s evidence of the failure of others and long-felt but unmet need as evidence of non-obviousness. Thus, federal circuit saw no error in district court’s finding & upheld the ruling that asserted claims of the Acorda patents are invalid.