Brigham & Women's Hosp.,Inc. v. Perrigo Co. United States Court of Appeals of the Federal Circuit,2019 2019 WL 990816 (Nonprecedential decision)

A.

Claim 1 of the ’137 patent is the sole independent claim asserted by Brigham and reads as follows:

1. A method of providing immediate and sustained relief from pain, discomfort and/or symptoms associated with episodic heartburn in a human, said method comprising:

orally administering to a human together or substantially together an antacid in an amount effective to substantially neutralize gastric acid and a histamine H₂-receptor antagonist in an amount effective to substantially inhibit or block gastric acid secretion for providing the human with immediate and sustained relief from pain, discomfort and/or symptoms associated with episodic heartburn, the immediate and sustained relief provided lasting longer in duration than when the human is orally treated with only the antacid and the immediate and sustained relief provided being faster than and lasting at least about as long in duration as when the human is orally treated with only the histamine H₂-receptor antagonist.

The specification defines “immediate and sustained relief,” disclosing:

It should therefore be appreciated that by the term “immediate and sustained relief,” it means herein immediate, temporary and sustained relief which starts within about 5–10 minutes following ingestion of the active ingredients and continues and remains constant for at least about 4–6 hours after ingestion of the active ingredients; the actual ingredients being an antacid and a histamine H₂-receptor antagonist.

B.

The ’137 patent was filed on May 6, 1992, issued in 1993, and expired on May 6, 2012. Brigham exclusively licensed the patent in 1996 to Johnson & Johnson Merck Consumer Pharmaceuticals (“J&J”), also giving J&J the right to pursue any infringement claims. In December 2004, Perrigo sent Brigham a Paragraph IV notice letter informing Brigham that it had submitted an Abbreviated New Drug Application (“ANDA”) to market a combination H₂-blocker/antacid tablet prior to the expiration of the ’137 patent, and Brigham relayed this information to J&J soon thereafter. J&J declined to assert the ’137 patent against Perrigo but did sue on a different patent. Perrigo prevailed and then launched its generic product in 2008. Several years later, in 2013, Brigham brought the present suit accusing Perrigo's generic product of infringing the ’137 patent's independent claim 1 and dependent claims 4, 5, 6, 7, and 12. Perrigo counterclaimed, asserting that the ’137 patent was invalid as anticipated and obvious.

At claim construction, the district court construed the term “immediate and sustained relief” to mean “relief obtained from pain, discomfort and/or symptoms associated with episodic heartburn which starts within about 5–10 minutes following ingestion of the active ingredients and continues for at least about 4–6 hours.”

The parties proceeded to trial. A key dispute was whether Perrigo's generic product provided immediate relief as defined by the ’137 patent. The main evidence regarding this limitation came from clinical data underpinning J&J's branded H₂-blocker/antacid product, Pepcid Complete^®. Brigham argued that the clinical data demonstrated that Pepcid Complete^® provides immediate relief, and since Perrigo's generic product has the same active ingredients and dosages as Pepcid Complete^®, Perrigo's generic product must also provide immediate relief.

The clinical data came from three studies presented in the New Drug Application (“NDA”) for Pepcid Complete^®. The first, Study 98, measured 23 qualifying patients’ esophageal and stomach pH levels after administering Pepcid Complete^® and compared changes in these pH values to controls (an antacid or H₂-blocker alone, or a placebo). Undisputedly, lower (more acidic) esophageal pH may correspond to episodic heartburn, which results from reflux of stomach acid into the esophagus that can cause pain associated with episodic heartburn. In the study, “[a]n episode of acidic reflux was counted as a drop from pH 5 or more to 4 or below . … ” The study was designed to show that Pepcid Complete^® would raise esophageal pH faster than an H₂-blocker alone and comparably fast to an antacid alone.

Although the NDA's description of Study 98 does not directly state whether Pepcid Complete^® provided symptomatic relief from episodic heartburn starting within about 5–10 minutes, as required by claim 1, the NDA does include a figure (Figure 7) of the patients’ mean esophageal pH measured over one minute intervals before and after administration of an antacid, Pepcid Complete^® (“FACT”), an H₂-blocker (“famotidine”), or a placebo.

At trial, Brigham's fact and expert witness and the inventor of the ’137 patent, Dr. M. Michael Wolfe, testified concerning Figure 7. He opined that “the antacid, whether it was in the combination or by itself, the pH rapidly rose in the esophagus, and it persisted.” With respect to the claimed immediate relief from episodic heartburn, Dr. Wolfe further attested that “the increase in pH is what we're aiming for. It's mopping up of the acid that's present there. If you mop it up, it's going to relieve symptom; it's going to start to relieve symptoms fairly quickly.”

In addition to the data from Figure 7, Study 98 also reported the number and duration of esophageal reflux episodes that occurred in the hour after administration of the drugs. On average, patients experienced between 2 and 5 esophageal reflux episodes over the measurement period.

In addition to the pH study, the NDA included two symptom relief studies, Studies 110 and 127. Study 110 measured “adequate relief for onset of effect within 2 hours, and for duration of effect the number of episodes of heartburn adequately relieved for at least 7 hours.” Adequate relief from heartburn, as determined by a patient's own assessment, was first measured fifteen minutes after administration of one of the drugs listed above. Study 127 was similar to Study 110. It also measured “adequate relief” beginning fifteen minutes after administration.

At trial, Dr. Wolfe testified that the parameter measured in Studies 110 and 127—adequate relief at 15 minutes—would “correlate to immediate relief” within 5–10 minutes, but he admitted that the two parameters were different.

The jury returned a verdict finding that the asserted claims of the ’137 patent were not invalid, that Perrigo's generic product infringed each asserted claim, and that Perrigo's infringement was willful. The jury awarded Brigham damages of about $10 million. The district court entered judgment consistent with the verdict on December 19, 2016, but without specifying damages or resolving Brigham's claim for enhanced damages.

The district court granted JMOL [judgment as a matter of law] of noninfringement because it concluded that Brigham failed to present sufficient evidence of direct infringement. Specifically, the court determined that the clinical evidence did not demonstrate that Pepcid Complete^® provided immediate relief from episodic heartburn.

The district court first assessed Study 98 and Dr. Wolfe's related testimony concerning Figure 7, including his contention that Figure 7 showed immediate relief through its rapid rise in esophageal pH after administering Pepcid Complete^®. However, the court observed that Study 98 defined an episode of acid reflux as requiring esophageal pH to go to 4 or below, but the average pH values in Figure 7 never did so. And, as the study did not otherwise purport to correlate pH recordings to heartburn severity or other symptoms, the court concluded that Figure 7 did not prove that patients in the study were provided with immediate relief.

The district court next considered the symptom relief studies. Because these studies indisputably measured a parameter different from the claimed immediate relief—”adequate relief” at 15 minutes, not the start of relief within 5–10 minutes—the court determined that the symptom relief studies also did not support the infringement verdict.

Given Brigham's proffered evidence of infringement, the district court concluded that “no reasonable jury could have found direct infringement and Perrigo is entitled to judgment as a matter of law” of noninfringement with respect to claim 1. It similarly followed that Brigham could not prove direct infringement of the dependent claims. Consequently, the court vacated the jury's award of damages. The court denied Perrigo's motions for JMOL of invalidity.

Perrigo appealed from the district court's denial of JMOL of invalidity and its denial of Perrigo's evidentiary motion. Brigham cross-appealed from the court's grant of JMOL of noninfringement, its denial of enhanced damages, attorney fees, and pre-judgment interest, and its conclusion with respect to a disputed invention date.

B. Infringement

At trial, Brigham alleged only literal infringement. Literal infringement is a question of fact and requires every limitation in the claim to be found in the accused product. Akzo Nobel Coatings, Inc. v. Dow Chem. Co., 811 F.3d 1334, 1339, 1341 (Fed. Cir. 2016). “If even one limitation is missing or not met as claimed, there is no literal infringement.” Mas-Hamilton Grp. v. LaGard, Inc., 156 F.3d 1206, 1211 (Fed. Cir. 1998). The patentee has the burden of proving literal infringement by a preponderance of the evidence. Enercon GmbH v. Int'l Trade Comm'n, 151 F.3d 1376, 1384 (Fed. Cir. 1998).

Brigham argues that the district court erred in over-turning the jury verdict and granting JMOL of noninfringement. According to Brigham, the court misinterpreted Figure 7 and improperly dismissed the other studies. Based on the totality of the evidence presented, Brigham asserts that a reasonable jury could have found infringement.

Perrigo responds that the district court properly granted JMOL of noninfringement because none of the evidence presented to the jury demonstrated immediate and sustained relief as claimed in the ’137 patent.

We agree with Perrigo that the district court's JMOL of noninfringement was proper. The parties’ dispute centers on whether the evidence at trial was sufficient to show that Pepcid Complete^®, and by implication Perrigo's generic product, provides “immediate … relief from pain, discomfort and/or symptoms associated with episodic heartburn.” The district court's construction of this term is undisputed: immediate relief means “relief obtained from pain, discomfort and/or symptoms associated with episodic heartburn which starts within about 5–10 minutes following ingestion of the active ingredients.” As we discuss, Brigham's evidence was insufficient to show immediate relief as claimed, and no reasonable jury could have found otherwise.

Brigham's infringement case relied primarily on the clinical studies 98, 110, and 127 reported in the NDA for Pepcid Complete^®. Like the district court, we begin with Figure 7 of Study 98, reproduced earlier. Figure 7 depicts mean esophageal pH before and after Pepcid Complete^® or a control drug is administered to a set of patients. The sole heartburn symptom related to esophageal pH measured in the study was acidic reflux, and “[a]n episode of acidic reflux was counted as a drop from pH 5 or more to 4 or below.” None of the curves at any point in Figure 7 depict a mean pH below 4. Nor does the study disclose individual esophageal pH data.

Because Study 98 defined an episode of acidic reflux as requiring a drop in pH to below 4, but the pH curves in Figure 7 never drop below 4, the district court concluded that Figure 7 could not prove that the patients in Study 98 taking Pepcid Complete^® were provided with immediate relief from episodic heartburn within 5–10 minutes. We agree. While Figure 7 does show a rapid rise in esophageal pH after administering Pepcid Complete^®, that rise is untethered to any symptomatic relief. It cannot support the jury verdict that Pepcid Complete^® provides immediate relief from episodic heartburn within 5–10 minutes. At most, the study suggests that Pepcid Complete^® might provide immediate and sustained relief; such speculative data, however, cannot sustain Brigham's burden of proof.

We next consider Studies 110 and 127, which did report symptomatic relief from heartburn. However, the district court concluded that these studies could not support the infringement verdict because they each measured “adequate relief” beginning at 15 minutes, not immediate relief starting within 5–10 minutes as claimed. There is no dispute that adequate relief first measured at 15 minutes after administration is a parameter different from relief starting 5–10 minutes after administration. As Studies 110 and 127 did not measure the result that Brigham claimed in the ’137 patent, we agree with the district court that they do not support the jury verdict.

On appeal, Brigham argues that the evidence of adequate relief at 15 minutes necessarily showed onset of relief within 5–10 minutes. But at most, Dr. Wolfe's testimony only indicated that the measured parameter would “correlate to” the claimed result. Data merely correlating to the claimed limitation does not suffice to prove literal infringement. As Dr. Wolfe testified regarding the data on adequate relief at 30 minutes, “[w]e have no idea” how many patients in Studies 110 and 127 were provided relief starting within 5–10 minutes because that result was not measured or even estimated in either study. Although a jury is entitled to draw reasonable inferences from circumstantial evidence, reasonable inferences themselves must be more than speculation and conjecture. Because only speculation supports Brigham's contention that data showing adequate relief at 15 minutes implies that relief started within 5–10 minutes, it cannot sustain the jury verdict.

Brigham also points to other evidence purportedly showing that Pepcid Complete^® provided the claimed immediate relief—that antacids were conventionally known to act quickly, and that the NDA stated that Pepcid Complete^® worked as quickly as an antacid. However, none of this evidence indicates that Pepcid Complete^® provides immediate relief within 5–10 minutes as claimed. It therefore cannot support the infringement verdict.

Last, we consider the bare assertion by Dr. Wolfe, the inventor of the ’137 patent, that he ingested Perrigo's product after litigation began, and that it provided immediate relief as claimed. Considering the absence of any clinical data demonstrating the claimed immediate relief, we conclude that this uncorroborated, conclusory, and interested testimony is insufficient to carry Brigham's burden of proof and to sustain the jury verdict.

Having considered the totality of the evidence, we agree with the district court that Brigham failed as a matter of law to prove that Perrigo's product meets the claimed limitation of providing immediate relief from episodic heartburn within 5–10 minutes. Because each asserted claim contains this limitation, the court did not err in concluding that the infringement verdict and damages award could not stand.