This case is an appellate review of the district court’s findings regarding patent obviousness and priority date.

Background

Amgen produces and markets apremilast, a medication for the treatment of certain types of psoriasis and psoriatic arthritis, under the brand name Otezla. Amgen also owns three patents — the ’638, ’101, and ’541 patents — covering Otezla. Sandoz submitted an Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of apremilast. Celgene, the prior owner of the asserted patents, then sued Sandoz for infringing them, and Amgen was substituted as plaintiff when Celgene transferred Amgen these three patents. The district court (District of New Jersey) held that the asserted claims of the ’638 and ’101 patents were not invalid as obvious and that the asserted claims of the ’541 patent were invalid as obvious. 

Both Amgen and Sandoz appealed. Regarding the ’638 patent, Sandoz argued that the district court erred in failing to find a motivation to isolate apremilast from a known racemic mixture and also for failing to find a reasonable expectation of success in separating the mixture. Regarding the ’101 patent, Sandoz argued that the district court erred in holding that the ’515 provisional application inherently disclosed the crystalline Form B of apremilast and thus that it did not provide the necessary written description support to entitle the patent to a March 2002 priority date. Regarding the ’541 patent, Amgen argued that the district court erred in holding that the claimed dose-titration schedule would have been obvious.

Issues

1. Is the ’638 patent invalid as obvious given objective indicia of non-obviousness?
2. Did the ’515 provisional application provide necessary written description support to entitle the ’101 patent to a March 2002 priority date?
3. Would the claimed dose-titration schedule in the ’541 patent have been obvious?

Holding(s)

1. No. The ’638 patent is not invalid as obvious given objective indicia of non-obviousness.
2. Yes. The ’515 provisional application provides the necessary written description support to entitle the ’101 patent to a March 2002 priority date.
3. Yes. The claimed dose-titration schedule in the ’541 patent would have been obvious.

Reasoning

(1) The Federal Circuit found no clear error in the district court’s holding that Sandoz did not meet its burden of establishing that the prior art gave a skilled artisan reason or motivation to isolate apremilast from a known racemic mixture, i.e., to resolve the racemic mixture into its enantiomers. The Federal Circuit held that the district court properly credited both parties’ experts and found Amgen’s expert to be more persuasive. Amgen’s expert had provided information establishing that resolving a racemic mixture is a difficult process based on trial-and-error experimentation with many possible options for the solvent system at the time. 

As for the objective indicia, the Federal Circuit affirmed that the trial record established the presence of unexpected results, including testimony from a researcher listed as an inventor on the ’638 patent, stating that they did not expect a 20-fold difference in potency between apremilast alone and the apremilast containing racemic mixture. The Federal Circuit also credited other objective indicia, each supported by expert testimony, such as long-felt need, failure of others in the field, and industry and regulatory skepticism.

(2) The Federal Circuit found that crystalline Form B of apremilast is actually disclosed in the ’515 provisional application, which provided support for relevant claims in the ’101 patent to be entitled to a March 2002 priority date. The Court noted that Amgen provided over a dozen of experiment results to show the procedure in Example 2 of the ’515 provisional application resulted in crystalline Form B of apremilast and that Sandoz provided no evidence to show that the procedure “may have been capable of producing a crystalline Form other than Form B.” The Court further held that it did not need to reach the issue of inherent disclosure because inherency is not required given the experiment results and expert testimony.

(3) The Federal Circuit affirmed the district court ruling that credited Sandoz’s expert testimony that titrating doses to treat a patient with psoriasis is well within a skilled artisan’s ability. The Court agreed that modifying the dosing schedule (dose titration) taught in a prior art reference would have been obvious to a skilled artisan. The Court found that when prescribing drugs with known dose-dependent adverse events in the early weeks of treatment, a skilled artisan would have been motivated to use the prior art schedule “as a starting point and extend it to titrate the dosing up in smaller amounts.” Thus, citing Genentech, Inc. v. Sandoz Inc., 55 F.4th 1368, 1376–77 (Fed. Cir. 2022), the Federal Circuit held that varying a dose in response to the occurrence of side effects is well-known and obvious to the skilled artisan.