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  • Writer's pictureYork Faulkner

Acting on Contradictory Motivations before FDA & USPTO Results in Unenforceable Patent

"Not long after these information exchanges with FDA, Belcher filed its patent application before the USPTO—where, acting on motivations to prove novelty over the prior art, Belcher made radically inconsistent statements about the same subject matter. . . ."

In Belcher Pharms., LLC v. Hospira, Inc., No. 2020-1799 (Fed. Cir. Sept. 1, 2021), the U.S. Court of Appeals for the Federal Circuit affirmed the district court’s ruling that U.S. Patent No. 9,283,197 entitled “More Potent and Less Toxic Formulations of Epinephrine and Methods of Medical Use” is unenforceable due to Belcher’s inequitable conduct during prosecution of the patent application. The district court concluded that Belcher withheld material prior art from the USPTO and made factual representations during patent prosecution that contradicted its prior statements to the U.S. Food and Drug Administration.

The context of Belcher’s FDA application explains much about Belcher’s shifting motivations and statements concerning the manufacture of its epinephrine drug product. Belcher’s New Drug Application was a “Section 505(b)(2)” or “paper” NDA, meaning that the application relied, in part, on manufacturing, stability, safety, efficacy, and other data developed by third-party companies for their own epinephrine drug products. In other words, the more closely Belcher’s proposed manufacturing process and product resembled previously approved products, the more likely FDA would approve the paper NDA without requiring additional studies or testing. In the context of a paper NDA therefore, adherence to pre-established rather than novel production methods and product specifications tends to facilitate and expedite FDA approval.

To support FDA approval of its proposed manufacturing process, Belcher’s NDA relied on manufacturing and stability data from four “reference batches” produced by Sintetica SA, a Swiss Company which had registered the first injectable l-epinephrine drug product in Switzerland in 1947. The four Sintetica reference batches disclosed in Belcher’s NDA were a newer, preservative-free version of Sintetica’s l-epinephrine drug product.

According to Belcher’s NDA, “the only difference between the relied-upon Sintetica batches and Belcher’s proposed formulation ‘is related to the in[-]process pH’ and that it ‘consider[ed] the in[-]process pH change to be a very minor change not requiring additional stability studies.’” Belcher Pharms., No. 2020-1799 at 5 (emphasis added). According to the NDA, Belcher reduced the “old” (Sintetica) in-process pH from a range of 2.8 to 3.3 to a “new” range of 2.4 to 2.6. Id. at 4.

FDA responded to Belcher’s change of the in-process pH target by asking Belcher to conduct studies to evaluate the effect of the lower pH on product degradation. Id. at 5. Recognizing that the requested studies would prolong approval, Belcher ultimately told FDA that it would change its production process to conform with the “old” in-process pH range of 2.8 to 3.3 and its known degradation profile. Id. at 6.

Not long after these information exchanges with FDA, Belcher filed its patent application before the USPTO—where, acting on motivations to prove novelty over the prior art, Belcher made radically inconsistent statements about the same subject matter. One of the stated purposes of the claimed invention was reduction of product degradation by controlling, among other things, in-process pH. Regarding the pH range described as “new” but abandoned before FDA due to an unknown degradation profile, Belcher’s patent said 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.’” Id. at 6 (quoting the ’197 patent at Col. 4 lns. 41-47) (emphasis added).

And although described as an “old” Sintetica pH parameter to FDA with a known degradation profile, Belcher’s patent reports that “[i]nadvertently increasing the in-process pH to 2.8-3.3[] unexpectedly reduced” degradation. Id. (quoting the ’197 patent at Col. 4 lns. 48-51). The patent further asserts novelty of the “old” pH range, by declaring that the increased pH “lead 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 was a nonobvious solution to the problem of [degradation]” (the ’197 patent at Col. 4 lns. 55-59).

During the patent’s prosecution, the examiner rejected the claimed pH range of 2.8 to 3.3 as obvious due to a prior art disclosure of pH in the range of 2.2 to 5.0. Belcher responded that the claimed 2.8 to 3.3 pH range “‘was unexpectedly found to be critical by the Applicant to reduce [degradation].’” Belcher Pharms., No. 2020-1799 at 8 (quoting J.A. 1073). The examiner later withdrew the rejection, noting that the “‘there is nothing in the prior art that would teach or suggest the instantly claimed pH range of between 2.8 and 3.3 would result in limited [degradation].'” Id. (quoting J.A. 1088).

The issued ’197 patent was listed in FDA’s Orange Book, and Belcher filed suit against Hospira under the Hatch-Waxman procedures. The district court conducted a bench trial in which Belcher’s chief science officer (“CSO”) testified that he participated in both drafting the company’s NDA and prosecuting the ’197 patent application. Id. at 9-10. According to the CSO’s testimony, “[h]e ‘project-managed everything’ in that role, and ‘it all led to [him].’” Id. at 10 (quoting J.A. 680 (Trial Tr. 150:15-18)).

The district court concluded and the Federal Circuit agreed that Belcher’s characterization of the 2.8 to 3.3 pH range as “old” before FDA was material to patentability and if disclosed to the USPTO, the information would have shown that Belcher’s assertion that its use of the pH range resulted in “unexpected results” was both “false” and “fiction.” Id. at 15. The court emphasized that the CSO “did not merely withhold this information but also used emphatic language to argue that the claimed pH range of 2.8 to 3.3. was a ‘critical’ innovation that ‘unexpectedly’ reduced [degradation].” Id. at 11.

The district court found that the CSO failed to disclose other material information to the USPTO, including the prior art Sintetica product data and information about another prior art product with a pH range of 2.8 to 3.3 made by “JHP” and sold in the United States. The district court rejected the CSO’s asserted belief that the prior art products were irrelevant because the production yields of their manufacturing processes differed from Belcher’s process. Id. at 15. The district court likewise rejected the CSO’s alleged belief that the prior art production processes were merely cumulative because they disclosed pH ranges encompassing the claimed 2.8 to 3.3 range. The court noted that “[t]he examiner allowed the claims only after accepting Belcher’s criticality argument” about the specific narrowly claimed range. Id. at 14.

The Federal Circuit found no clear error in these findings and determined that the single most reasonable inference from the findings was that the CSO and Belcher acted with the specific intent to deceive the USPTO. The Federal Circuit therefore affirmed the district court’s judgement that the ’197 patent is unenforceable due to the CSO’s and Belcher’s inequitable conduct before the USPTO.

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