by Dennis Crouch
The Federal Circuit recently sided with the accused infringers Teva and Apotex, affirming the invalidation claims from four Vanda patents covering methods of using tasimelteon to treat circadian rhythm disorders. However, the patent owner has petitioned the court for en banc rehearing, arguing the panel improperly disregarded evidence of nonobviousness. Responsive briefing from the generics are due on August 1.
This case provides an interesting look at the application of the obviousness standard to pharmaceutical treatment methods.
Background: Vanda Pharmaceuticals owns patents covering use of the drug tasimelteon to treat Non-24-Hour Sleep-Wake Disorder (Non-24), a condition caused by lack of synchronization between a person’s circadian rhythm and the 24-hour day. Tasimelteon is sold under the brand name Hetlioz and has over $100m in annual sales. Several generic drug makers, including Teva and Apotex, filed Abbreviated New Drug Applications (ANDAs) with the FDA seeking to market generic versions of tasimelteon and with allegations. Vanda sued, alleging infringement of four patents that were listed in the Orange Book. RE46604 (Claim 3); US10149829 (Claim 14); US9730910 (Claim 4); US10376487 (Claim 5). The district court found all asserted claims obvious based on prior art teachings about tasimelteon and related drugs. Vanda appealed.
In a May 2023 decision, the Federal Circuit affirmed the invalidity ruling. The panel found no error in the district court’s determination that the prior art would have provided a reasonable expectation of success for the claimed inventions.
Key Aspects of the Federal Circuit’s Obviousness Analysis
The inventions here involved fairly narrow differences, and the Federal Circuit concluded that a PHOSITA would have seen a reasonable expectation of success:
- Administering without food: There was a motivation to try and a reasonable expectation of success here since FDA guidance recommended food studies, and there are just two potential options (with or without food). There result here is close to a per-se obviousness ruling.
- 20 mg dose to “entrain patients”: The prior art disclosed 20 mg dose and suggested entrainment. Still obvious even though the prior study results (Rajaratnam) were not statistically significant. In a different patent application, Vanda had characterized Rajaratnam as showing that an oral dose of 20 mg was effective. The court also noted that an ongoing clinical trial at the time was testing 20 mg — further contributed to the expectation of success.
- Avoiding Co-administration with CYP enzyme inhibitors: A similar drug (ramelton) had shown problems with co-administration with these CYP enzyme inhibitors, creating a reasonable expectation that tasimelteon would also show similar results. On this point, the testimony was that PHOSITA would not have “ruled out an interaction.”
The key with all of these is reliance on KSR‘s flexible approach and expanded use of the reasonable expectation of success standard. Although Vanda argued objective indicia, it was given very little consideration by the appellate panel.
Vanda’s Petition for Rehearing En Banc
Vanda’s en banc brief asks three questions:
- With or Without Food: Whether method-of-treatment patents directed to the effect of food on a particular drug are per se obvious because of FDA Guidance acknowledging that food may affect the bioavailability of drugs and should be studied.
- Clinical Trial as Evidence of Reasonable Expectation of Success: Whether a disclosure showing existence of an ongoing clinical trial is evidence of a reasonable expectation of success as to the result of the trial. See OSI Pharms v. Apotex (Fed. Cir. 2019) (clinical trial provides only hope, not expectation of success).
- Results from Similar Drug: Whether a drug-drug interaction patent is obvious when a POSA could not “rule out” the interaction because another compound in the same general category has shown such an interaction.
The petition urges the full Federal Circuit court to take the case en banc to maintain uniformity of obviousness precedents. I’m sure that companies in the life sciences sector will be closely watching this case as it continues to unfold.