The determination of obviousness is a legal conclusion based on underlying facts. Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1290-91 (Fed. Cir. 2013). After a bench trial, we review the district court's factual findings for clear error and its conclusions of law de novo.

“[T]he problem motivating the patentee may be only one of many addressed by the patent's subject matter.” Id. at 420; see Janssen Pharm., Inc. v. Teva Pharm. USA, Inc., 97 F.4th 915, 929 (Fed. Cir. 2024) (“A motivation ‘may be found in many different places and forms.'” (quoting Allergan, Inc. v. Sandoz, Inc., 726 F.3d 1286, 1292 (Fed. Cir. 2013)). “What matters is the objective reach of the claim.” KSR, 550 U.S. at 419.

Because a thrice-weekly 40mg injection would result in a total weekly dose very close to that in the already-approved daily 20mg injection—120mg/week versus 140mg/week—the district court found a POSITA would have had a reasonable expectation of success in pursuing the thrice-weekly dose frequency in terms of effectiveness, patient adherence, and FDA approval. Id. at *19 (quoting Allergan, Inc. v. Sandoz Inc ., 726 F.3d 1286, 1291 (Fed. Cir. 2013) ("The potential for FDA approval also may properly be considered, as it was here, in determining whether one of ordinary skill would be motivated to develop a drug product and whether there was skepticism regarding the efficacy of such a product.") ). The district court gave appropriate weight to the testimony of Dr. Green regarding patient compliance with thrice-weekly administrations and the Rebif® regimen, noting that "[e]ven though Rebif® is a different MS drug with a different mechanism of action, ... those in the art would still be motivated to try dosing GA three times a week based on the higher rates of patient adherence to the Rebif® therapy."

There is a distinction between limiting the obviousness inquiry to pre-invention evidence and finding post-invention evidence unpersuasive, however. See Allergan Inc. v. Sandoz Inc., 726 F.3d 1286, 1293 (Fed.Cir.2013) (“We agree with the court's finding that this result was unexpected. However, we do not find that these unexpected results are sufficient to outweigh the other evidence of obviousness.”).

We have held an invention to be obvious despite findings of unexpected results. See, e.g., Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1293 (Fed.Cir.2013); Alcon Research, Ltd. v. Apotex, Inc., 687 F.3d 1362, 1365, 1369–70 (Fed.Cir.2012); Pfizer, 480 F.3d at 1372. B.

“Obviousness ... is a legal conclusion based on underlying facts.” Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, at 1290, 2013 WL 1810852, at *4 (Fed.Cir. May 1, 2013). “The underlying factual considerations in an obviousness analysis include the scope and content of the prior art, the differences between the prior art and the claimed invention, the level of ordinary skill in the art, and any relevant secondary considerations,” which include “commercial success, long-left but unsolved needs, failure of others, and unexpected results.”

A POSA's “[m]otivation to combine may be found in many different places and forms.” Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1197 (Fed. Cir. 2014) (quoting Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1292 (Fed. Cir. 2013)). “[C]ase law does not require that a particular combination must be the preferred, or the most desirable, combination described

Chemists also expressed concern that the five-chlorothiophene moiety would produce toxic metabolites.”); Allergan, Inc. v. Sandoz, 726 F.3d 1286, 1291-92 (Fed. Cir. 2013) (holding that “FDA approval may be relevant to the obviousness inquiry” and “[t]he potential for FDA approval also may properly be considered ... in determining whether. . . there was skepticism regarding the efficacy of such a product”).

To prove obviousness, a party must show that a skilled artisan would have been motivated to combine the prior art teachings to create the claimed treatment method with a reasonable expectation of success. SeeAllergan, Inc. v. Sandoz Inc. , 726 F.3d 1286, 1291 (Fed. Cir. 2013). The improvement over prior art must be "more than the predictable use of prior art elements according to their established functions."

The factual determinations underlying the obviousness analysis include consideration of the scope and content of the prior art; the differences between the prior art and the claimed subject matter as a whole; the level of skill in the art; and any relevant secondary factors, also known as objective evidence of non-obviousness. Allergan, Inc. v. Sandoz Inc. , 726 F.3d 1286, 1290–91 (Fed.Cir.2013). Secondary considerations include surprising or unexpected results, prior art teaching away from the claimed invention, and unpredictability in the art.