DC decision finding inequitable conduct based on FDA submissions affirmed

Belcher Pharmaceuticals, LLC v. Hospira, Inc.

Docket No. 2020-1799 (http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/20-1799.OPINION.9-1-2021_1828017.pdf)

REYNA, TARANTO, STOLL

September 1, 2021

Brief Summary:  DC inequitable conduct finding based in part on prior art submitted to the FDA during the approval process affirmed. Summary:  Belcher appealed DC inequitable conduct finding regarding US 9,283,197 directed to injectable epinephrine formulations.  The FC panel opinion explains that the 2014 application leading to the ‘197 patent filed by Belcher’s CEO (Jugal Taneja) “describes the problem of l-epinephrine’s degradation and the resulting need for product overages and sulfite antioxidants, and it claims to provide an answer to this need”, “an answer” that “‘seemed impossible’ and ‘had never been accomplished before’”, and “states that the idea of raising the in-process pH above the range of 2.2 to 2.6 ‘was contradictory to one skilled in the art’ before the claimed invention” and “increasing the in-process pH to 2.8-3.3[] unexpectedly reduced the racemization of l-epinephrine to d-epinephrine at release by approximately two-thirds, from 14% to 5%, respectively.”  This, the patent explained, “led to new methods of manufacturing sulfite-free, l-epinephrine solution with an in-process pH of 2.8 to 3.3, approximately 3.0, which was a nonobvious solution to the problem of racemization” such that “with these new methods, overages could greatly be reduced.”  The disputed claims are directed to a “liquid pharmaceutical formulation having a pH between 2.8 and 3.3” including “1.0 to 1.06 mg/mL l-epinephrine”, and limits to the amounts of certain impurities “over a shelf-life of at least 12 months.”  During prosecution, “Mr. Tajena’s counsel responded” to a prior art (Helenek) rejection by “arguing that Helenek’s 2.2 to 5.0 pH range failed to render obvious the claimed range of 2.8 to 3.3 because the claimed range ‘was unexpectedly found to be critical by the Applicant to reduce the racemization of l-epinephrine’”, citing In re Woodruff (FC 1990 (“the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range”)).  In the reasons for allowance of the claims, “the examiner explained that the cited art failed to render the claims unpatentable ‘in view of Applicant’s demonstration of criticality of a pH range between 2.8 and 3.3.’”  Belcher’s head of intellectual property (Mr. Rubin) testified that he knew of the prior art reference Stepensky “before the ’197 patent was filed” that was “cited…in two separate communications to the FDA during the approval process”.  He also admitted that while the ‘197 patent was being prosecuted “he possessed a label for a 1 mg/mL epinephrine product that a company named JHP had already introduced to the market” that had “a pH in the range of 2.2 to 5.0” (“2.8 to 3.3 (specifically 2.9, 2.9, and 3.1) at 15 months” (“Sintetica’s product”)).  The DC concluded “that clear and convincing evidence demonstrated that Mr. Rubin” (“a key player in the FDA approval process as well as the ’197 patent’s prosecution”) “acted with requisite intent to deceive the PTO” by submitting “data on Sintetica’s and JHP’s products showing a pH within the claimed range” and “not merely withhold[ing] this information but also us[ing] emphatic language to argue that the claimed pH range of 2.8 to 3.3 was a ‘critical’ innovation that ‘unexpectedly’ reduced racemization.”  The FC panel agreed with the DC, finding the withheld information to be “but-for material information” (“the PTO would not have allowed a claim had it been aware” (Therasense, FC 2011; Aventis, FC 2012) and that Belcher clearly and convincingly “knew of the reference, knew that it was material, and made a deliberate decision to withhold it” (Aventis, Therasense; e.g., “Belcher had stated to the FDA that the 2.8 to 3.3 pH range was an ‘old’ range” and “Mr. Rubin performed an about-face” to the PTO.)  The FC panel rejected Mr. Rubin’s arguments that he believed the references “were irrelevant” as “they were different from the asserted claims in certain respects, including their high overages”, comparing this case to its Aventis decision in which it “rejected similar post hoc rationales for withholding material prior art.”  The DC decision was therefore affirmed.