U.S. Patent Nos. 8,232,250, 8,399,413, and 8,969,302 are directed to higher dose (40mg v. 20mg) and less frequent injection (3 days a week v. daily) of a drug for multiple sclerosis (pages 3-4). Prior art is 20 mg daily based on a clinical trial without an optimal dose finding study, but with a note to try other doses and FDA suggestion to look at less frequent (pages 5-6). Other prior art is 20 mg every other day, shown to be effective, and 40 mg every other day without increase in side effects (pages 6-7). One reference for 40 mg to provide for less frequent dosing was started two years before the priority date but published after (pages 15-16). Use of this non-prior art refence to indicate knowledge and motivation is acceptable if known (pages 16-17). The existence of the study shows a desire to provide less frequent dosing (page 17). The claimed 40 mg 3 times a week is obvious despite allegations of no expectations of success, hindsight, and failure to follow the minimum effective dose principle (pages 21-25).
Hindsight: Be aware of knowledge before the priority date, not just when publication occurred. The knowledge from before the priority date for a reference published after the priority date may indicate motivation try.