Case Name: Braintree Labs., Inc. v. Novel Labs., Inc., Case No. 3:11-cv-01341-PGS-LHG, 2015 U.S. Dist. LEXIS 70993 (D.N.J. June 2, 2015) (Sheridan, J.) 

Drug Product and Patent(s)-in-Suit: Suprep^® Bowel Prep Kit (sodium sulfate / potassium sulfate / magnesium sulfate); U.S. Pat. No. 6,964,149 ("the '149 patent")

Nature of the Case and Issue(s) Presented: The matter was before the court on remand from the Federal Circuit. The Federal Circuit reversed the district court's decision granting summary judgment in favor of Braintree and findings that Novel infringed the asserted claims of the '149 patent. That reversal was based on the Federal Circuit's finding that two claim terms—"clinically significant electrolyte shifts" and "patient"—were improperly construed by the district court. Having given those terms their proper claim construction, the Federal Circuit directed the district court on remand to determine whether Suprep avoids producing "clinically significant electrolyte shifts" in a "patient" based on the clinical-trial date in the trial record. The court found that Suprep did not produce clinically significant electrolyte shifts and was, thus, a covered product. Therefore, the court further found that Novel’s proposed ANDA product, which is equivalent to Suprep, would infringe the asserted claims.

Why Braintree Prevailed: It was uncontroverted that there were four Suprep clinical trials conducted by Braintree at the direction of the FDA and that each study constituted of patients within the patient population. Both parties’ experts used those trials to support their findings. The ultimate issue that the court considered was the way in which to interpret the data from each of the clinical trials. Braintree argued that the best approach to answer the Federal Circuit’s query regarding whether the patient population had alteration of electrolytes outside the normal range was to utilize a means analysis, the standard or fundamental approach to address patient population inquiries and the most basic concept Dr. Heitjan, Braintree’s expert, teaches to his students. Novel argued that the Federal Circuit required a percentage approach to determine if there are clinically significant electrolyte shifts: determination of the percentage of the patient population that is not within the normal range of electrolyte levels.

The court adopted Braintree’s approach, finding that a percentage analysis omits factors that a mean analysis considers. For instance, the percentage approach does not measure variability of the patient population, but the means approach does. Variability can occur "between-subject" and "within-subject." "Between-subject" variability refers to differences in measurements between different people. "Within-subject" variability refers to differences in measurements taken from one individual over time. Moreover, intrinsic factors that can affect electrolyte levels from patient-to-patient include age, gender, exercise, ethnicity, and whether the patient is using other drugs. Likewise, extrinsic factors that can affect electrolyte levels from patient-to-patient include fasting, dehydration, time of blood draw, stress and hyperventilation. These factors are present in the context of colonoscopy preps, and a mean approach considers such variability. The explanation of variability, coupled with the court’s finding that Novel’s expert’s testimony was "less than credible," resulted in the finding that the mean approach was the best methodology to utilize.

Braintree's expert witness calculated the means and 95% confidence intervals for the sample population who took Suprep for relevant electrolytes. He made these calculations at baseline, at the colonoscopy time point a few hours after administration of SUPREP and at the follow-up time point 30 days later. The means barely changed at all between these three time points for each electrolyte, and did not approach the outer limits of the normal range. He repeated this same analysis, or an analogous one depending on blood draws, for the other clinical trials, and achieved the same results: the means barely changed at all between the three time points for each electrolyte, and did not approach the outer limits of the normal range. Thus, the court found that the results of Braintree's means analysis showed that Suprep did not produce any clinically significant electrolyte shifts in the patient population under the Federal Circuit’s claim constructions, and that Novel’s ANDA product, equivalent to SUPREP, would infringe the asserted claims.