Each milliliter of the injectable solution contains 100 IU of biosynthetic insulin, 0.058 mg zinc chloride, 6 mg trometamol, 20 mg glycerol, 0.01 mg poly(oxyethylene, oxypropylene)glycol, 2.7 mg phenol (a preservative), 3.7 mg hydrochloric acid, and up to 1 ml water.
c. Analysis Turning first to reason to combine, we disagree with Patent Owner that, to meet its burden as a matter of law, Petitioner must provide prior art evidence that insulin glargine had a tendency to aggregate.
To the contrary, as noted above, the ’652 patent describes the hydrophobic surfaces of glass storage vials, stopper materials of sealing caps, the air-water interface, and siliconized daily use syringes as promoting aggregation.
As to pH, the background of the ’652 patent states that “[e]specially at acidic pH, insulins ... show a decreased stability and an increased proneness to aggregation on thermal and physicomechanical stress, which can make itself felt in the form of turbidity and precipitation (particle formation) (Brange et al., J. Ph.
As noted previously, Patent Owner also argues that Petitioner fails to account for the potential negative consequences of adding a nonionic surfactant to the Lantus Label and Owens insulin glargine formulations.