This Federal Circuit opinion analyzes the presumption of obviousness and the obviousness challenge based on prior art that describes a wider range of doses than what is claimed.
Background
Janssen Pharmaceuticals, Inc. and Janssen Pharmaceutica NV (collectively, “Janssen”) market and sell Invega Sustenna, an extended-release intramuscular injectable formulation of paliperidone palmitate used to treat schizophrenia. Janssen sued Teva Pharmaceuticals USA, Inc. (“Teva”) under the Hatch-Waxman Act, 35 U.S.C. § 271(e)(2) in the United States District Court for the District of New Jersey alleging patent infringement relating to U.S. Patent No. 9,439,906 (the ’906 Patent), after Teva filed an Abbreviated New Drug Application (“ANDA”) seeking FDA approval to market a generic version of Invega Sustenna. The ’906 Patent covers specific dosing regimens for Invega Sustenna.
Following two bench trials and a prior Federal Circuit review, the only remaining issue was Teva’s obviousness challenge to the ’906 Patent.
The parties agreed that claims 2, 10, 13, 20, and 21 are representative. Claim 2 recites a regimen involving a first dose of about 150 mg-eq and, about a week later, a second dose of about 100 mg-eq—collectively, “loading doses”—followed by monthly maintenance doses of 25–150 mg-eq. The loading doses are injected into the deltoid muscle, while the maintenance doses may be injected into either the deltoid or gluteal muscle. Claims 10 and 13 address reduced dosages for patients with renal impairment. Claims 20 and 21 cover a range of particle sizes for the injectable formulations.
Teva’s obviousness challenge primarily relied on three prior art references, all generated by Janssen:
- NCT00210548 (‘548 protocol), a clinical protocol evaluating three doses of paliperidone palmitate (50, 100, or 150 mg-eq, administered at specific intervals in schizophrenia patients);
- U.S. Patent No. 6,555,544 (“’544 patent”), which describes depot intramuscular or subcutaneous formulations containing a “therapeutically effective amount” of paliperidone palmitate; and
- International Publication No. WO 2006/114384 (WO ’384), which describes preparing aseptic crystalline paliperidone palmitate and injecting it in doses from 0.25 ml to 1.50 ml.
Teva argued that, because the prior art references describe dosing ranges that encompass those in the representative claims, there should be a presumption of obviousness.
Both parties also presented expert testimony and additional references regarding whether the use of loading doses to speed absorption was obvious, whether the claimed method was expected to be safe and effective, and whether it was likely that a skilled artisan would arrive at the claimed methods for treating patients with mild renal impairment.
The district court found that Teva had not proven any asserted claim of the ’906 Patent invalid for obviousness. The court also rejected Teva’s presumption of obviousness argument, finding three distinctions between the claims and the prior art: dosage amounts, dosing sequence, and deltoid injection. Teva challenged the district court’s findings on appeal.
Issue(s)
- Should the district court have applied a presumption of obviousness?
- Did the district court err in weighing the evidence supporting its finding that the patent is not invalid based on obviousness?
Holding(s)
- No, the district court did not err by declining to apply a presumption of obviousness.
- No, the district court did not err in weighing the evidence.
Reasoning
Presumption of Obviousness
The Federal Circuit rejected Teva’s argument that a presumption of obviousness arises simply because the dose ranges in the ’548 protocol overlap with the claimed loading and maintenance doses. The court explained that whether a presumption applies depends on the inventive context, the breadth of the prior art ranges, motivations to optimize, and standard expectations from routine experimentation.
The panel relied on several key differences, including the timing and sequencing of injections and the use of decreasing loading doses, to find that the presumption should not apply. The court emphasized that the loading dose regimen and its sequencing involve more than simply selecting a value from within a prior art range. The requirement of deltoid muscle administration was also cited as a factor weighing against application of the presumption.
Obviousness
The Federal Circuit affirmed the district court’s finding that Teva failed to show sufficient motivation to combine the prior art to arrive at the claimed invention or a reasonable expectation of success.
The Federal Circuit determined that the prior art did not disclose the specific claimed loading-dose regimen, and that Teva failed to demonstrate motivation for a skilled artisan to use a large initial loading dose followed by a reduced second loading dose. Although both sides presented expert testimony, the court deferred to the district court’s crediting of Janssen’s expert that a skilled artisan would not use long-acting injectables for “loading” or to speed absorption, but would instead rely on reducing particle size. There was adequate evidentiary support for rejecting Teva’s theory on motivation to combine the prior art references.
On reasonable expectation of success, the Federal Circuit found no clear error in the district court’s reliance on expert testimony that a multi-dose regimen introduces unpredictability and complexities absent from a single-dose regimen, thus undermining a reasonable expectation of success. The court also found no error in the district court’s conclusion that the lack of relevant safety and efficacy data in the cited Janssen references supported no reasonable expectation of success.
Finally, the Federal Circuit found that Teva failed to establish motivation for specific dosing regimens for patients with renal impairment. The district court appropriately relied on expert testimony that patients with moderate to severe renal impairment should not receive Invega Sustenna, and that the prior art did not address dosages for mild renal impairment. The Federal Circuit found no error in the district court’s evaluation of expert testimony in rejecting Teva’s motivation argument.