To rebut a prima facie case of obviousness, evidence of unexpected functions and results of the invention may be presented. In Knoll Pharmaceutical Company, Inc. v. Teva Pharmaceuticals USA, Inc., No. 03-1300 (Fed. Cir. May 19, 2004), to demonstrate the non-obviousness of its patented combination of hydrocodone and ibuprofen, Knoll submitted evidence of the combination’s unexpected results. The evidence included results of studies conducted after Knoll’s patent had issued. In considering the evidence, the Federal Circuit ruled that “[e]vidence developed after the patent grant is not excluded from consideration . . . There is no requirement that an invention’s properties and advantages were fully known before the patent application was filed . . . Nor is it improper to conduct additional experiments and provide later-obtained data in support of patent validity.”
Although obviousness of an invention is determined according to the state of the art at the time of the invention, the Federal Circuit’s ruling to allow evidence developed after patent grant to show unexpected results is consistent with prior court decisions. In In re Chu, 66 F.3d 292 (Fed. Cir. 1995), the Federal Circuit held that even when an applicant’s specification does not discuss the invention’s unexpected results, evidence of the unexpected results must be considered. The Federal Circuit in In re Chu stated that to require an applicant to include such evidence and arguments in the specification, “would be to require patent applicants to divine the rejections the PTO will proffer when patent applications are filed.”
In Weather Engineering Corp. of America v. United States, 614 F.2d 281, 284 n.4 (Ct. Cl. 1980), the court discusses an analysis and a harmonization of two lines of cases that compete with respect to whether “a patentee may invoke in support of his invention advantages of which he was not aware.” The court in Weather, quoting D.S. Chisum, ‘Afterthoughts’ and Undisclosed Advantages as Evidence of Patentability: From Salt Dredges to Polystyrenes, 57 J. Pat. Off. Soc’y 437 (1975), indicates that whether post-grant evidence of an unexpected result may be considered depends upon whether the discovered result can be characterized as an afterthought. Thus, according to the court, if an unexpected result inherently flows from a method disclosed in a patent, or if it is significantly tied to the intended use of a product as disclosed in an applicant’s specification, evidence of the result should be considered since the unexpected result is not merely an afterthought.
In Knoll, the Federal Circuit noted that Knoll’s specification acknowledges that Knoll’s combination provides a surprising analgesic effect. The Federal Circuit further noted that three of the later studies concerned the combination’s synergistic interaction when administered for pain relief, and that the fourth study concerned “an aspect not unrelated to pain relief.” The Federal Circuit thereby expressly noted that the evidence regarding the combination’s unexpected results relates to the surprising results discussed in Knoll’s specification.
Thus, one can infer from the Federal Circuit in Knoll that to respond to litigation attacks on validity, it is not improper to conduct post grant experiments to obtain data tending to show an unexpected result of the patented invention, at least where the unexpected result is not a mere afterthought.
 Compare Diamond Rubber Co. v. Consolidated Rubber Tire Co., 220 U.S. 428 (1911), with Lincoln Engineering Co. v. Stewart-Warner Corp., 303 U.S. 545 (1938).
 Simplex Piston Ring Co. v. Horton-Gallo-Creamer Co., 61 F.2d 748, 750 (2d Cir. 1932).
 See In re Zenitz, 333 F.2d 924, 927 (CCPA 1964) (“It is true he made no mention of the separation of hypotensive and tranquilizing activity, but . . . the advantage of minimized hypotensive activity would inherently flow from the indicated use of the compounds as tranquilizers.”).