Pepcid complete® – USA

On Feb 28, 2019 Federal Circuit affirmed district court that Brigham failed as a matter of law to prove that Perrigo’s generic product meets the claimed limitation.

Perrigo appealed from the order of the U.S. District Court for the District of Massachusetts denying judgment of invalidity as a matter of law of U.S. Patent 5,229,137 (expired on May 6, 2012) on the basis of anticipation and obviousness. Brigham and Women’s Hospital, Inc. cross-appealed from the same order granting judgment of noninfringement as a matter of law. Brigham’s ’137 patent is directed to a method for treating episodic heartburn by co-administering two known types of heartburn medications, H2-receptor antagonists (known as H2-blockers) and antacids. Antacids were known to provide fast but momentary relief from heartburn; in contrast, H2-blockers were known to provide slower but longer-lasting relief. Critically, the method of treatment as claimed requires that co-administering an antacid and H2-blocker achieves a certain clinical result: “immediate and sustained relief from pain, discomfort and/or symptoms associated with episodic heartburn.” The dispositive issue on appeal is whether Perrigo’s product meets the “immediate and sustained relief” limitation.

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.

Background:

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 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. Perrigo then moved for JMOL of noninfringement and invalidity on the date of the revised deadline. Brigham also then moved for enhanced damages. Additionally, in Brigham’s opposition to Perrigo’s JMOL motions, Brigham contended that Perrigo’s motions were untimely under Rule 50(b). Soon afterwards, in February 2017, Perrigo noticed an appeal from the district court’s December 19 judgment. Perrigo again moved for JMOL and noticed a second appeal on May 19 and May 11, 2017, respectively, this time from the district court’s April decision. The district court then considered the pending motions and granted JMOL 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. 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.

Appeal:

During appeal Brigham argued that the district court erred in overturning 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 asserted that a reasonable jury could have found infringement. Perrigo responded 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. Federal circuit agreed 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 discussed, Brigham’s evidence was insufficient to show immediate relief as claimed, and no reasonable jury could have found otherwise.

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. 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. Court next considered Studies 110 and 127, which did report symptomatic relief from heartburn. 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.

Having considered the totality of the evidence, Federal Circuit agreed 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.