Opinion ID: 4445789
Heading Depth: 3
Heading Rank: 1

Heading: 5% and PENNSAID® 2% (as recited in claim 12 of the

Text: ’913 patent) 3 are as follows: J.A. 15915 (table generated by the district court). Each of the ingredients listed above performs a specific function. Diclofenac sodium is the active ingredient. Dimethyl sulfoxide (“DMSO”) is a penetration enhancer, which enhances absorption of the drug into the skin. Ethanol is both a solvent, which dissolves the active ingredient for absorption of the drug into the skin, and a penetration enhancer. Propylene glycol is a solvent. Hydroxypropyl cellulose (“HPC”) is a thickening agent, which increases the viscosity of a formulation. Glycerin is a humectant, which is a nonvolatile substance that holds water onto the skin. And water is a solvent. Actavis contended that the drawbacks to PENNSAID® 1.5%—frequent application and vulnerability to run-off— 3 Claim 12 of the ’913 patent recites a method for applying the formulation that is collectively recited in claims 1, 8, and 9. HZNP MEDICINES LLC v. ACTAVIS LABORATORIES UT, INC. 11 were known, and that a POSITA would have been moti- vated to modify PENNSAID® 1.5% to address these drawbacks by: (a) increasing the absorption to reduce application frequency; (b) thickening the formulation; and (c) reducing the drying time to prevent run-off. Actavis proposed that a POSITA would have had a reasonable expectation that these modifications would address the known drawbacks. Actavis also pointed out that PENNSAID® 1.5% included all of the ingredients required by claim 12 of the ’913 patent except for a thickener (the HPC), in addition to the claimed amounts of DMSO, propylene glycol, and water. As to the remaining limitations in claim 12, Actavis maintained that they were disclosed in the prior art. Actavis argued that all the changes were obvious optimizations of result-effective variables that produced a predictable result in relation to absorption, thickness, and drying times. Horizon, on the other hand, argued that the changes made to PENNSAID® 1.5% were not routine optimiza- tions, and that the results of the various changes could not be predicted by the prior art. According to Horizon, the prior art reflects that the field of topical pharmaceutical formulations is complex and unpredictable. And to arrive at the formulation recited in claim 12 of the ’913 patent, Horizon maintains that a POSITA would have had to: (1) increase the diclofenac concentration from 1.5% to exactly 2%, (2) increase the concentration of ethanol from 11% to exactly the range of 23–29%, (3) add a thickening agent, (4) choose the thickening agent to be HPC, (5) identify the concentration of HPC to be exactly 2.5%, (6) select a viscosity range of between 500 and 5000 cps, and then (7) decide not to change the concentrations of DMSO or pro- pylene glycol, but instead (8) remove or reduce glycerin and/or water to account for the increases in diclofenac, ethanol and thickening agent concentrations and still total 100%, and the [POSITA] 12 HZNP MEDICINES LLC v. ACTAVIS LABORATORIES UT, INC. would also have had to change the method of ad- ministration from 3–4 times per day to twice a day [despite knowing that increasing viscosity makes it harder for drug molecules to penetrate the skin.] J.A. 15921–22. Trial began on March 21, 2017, and continued until March 30, 2017. The parties filed post-trial submissions on April 20, 2017. On May 12, 2017, the district court found that Actavis had not shown, by clear and convincing evidence, that claim 12 of the ’913 patent is invalid for obviousness. On May 22, 2017, the district court entered a final judgment consistent with its holdings and conclusions in the Markman order, the summary-judgment order, and the posttrial findings of fact and conclusions of law. Since claim 12 of the ’913 patent was found to be nonobvious and Actavis had stipulated to infringement of that claim if it was deemed not invalid at trial, the district court ordered that Actavis be enjoined from engaging in the commercial use, offer for sale, or sale of its ANDA product until the expiration of the ’913 patent. Horizon appeals and Actavis cross-appeals the district court’s final judgment. We have jurisdiction under 28 U.S.C. § 1295(a)(1).