Testing the Limits of Therasense: Patent Owner’s Decision Not to Appeal Obviousness Holding Created But-for Materiality and Knowledge of Withheld References Established Intent
In Belcher Pharms, LLC v. Hospira, Inc., --F.4th __, 2021 U.S. App. LEXIS 26346 *(Fed. Cir. Sept. 1, 2021) the Federal Circuit affirmed a district court decision per Judge Stark in Delaware, holding the claims of U.S. Patent No. 9,283,197 (“the ’197 patent”) obvious and unenforceable for inequitable conduct. Regarding the latter, both courts concluded that Belcher’s Chief Science Officer withheld but-for material information from the U.S. Patent and Trademark Office (“PTO”) with the sole reasonable inference being a specific intent to deceive.
Belcher’s approved product was a 1 mg/mL injectable l-epinephrine formulation. In submissions to the FDA, Belcher, in an effort to make FDA approval as easy as possible, described its formulation development as stemming from a reference product developed by a Swiss company, Sintetica, in the 1930s. According to Belcher, Sintetica’s “original formulation” of 1 mg/mL injectable l-epinephrine did not include preservatives and sulfites and had an “old” in-process pH range of 2.8 to 3.3. In contrast, the NDA described the new composition as having a lower pH range of 2.4 to 2.6 and explained that “[t]he switch [in pH] was very simple.” Belcher, 2021 U.S. App. LEXIS 26346 at *3-4. “Responding to the FDA’s inquiry on [the] manufacturing process for the stability validation batches, Belcher stated that 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.’” Id. at *5. When the FDA requested additional information relating to the pH change, however, Belcher decided to switch back to the “old” pH range of Sintetica’s original formulation, 2.8 to 3.3, to avoid a delay in approval, which Belcher received on July 29, 2015.
Belcher filed a U.S. patent application protecting its product on Aug. 15, 2014. In stark contrast to what Belcher told the FDA, the patent application described the formulation having a pH range of 2.8 to 3.3 as something that “seemed impossible” and “had never been accomplished before.” Belcher, 2021 U.S. App. LEXIS 26346 at *5. “The patent similarly states that the idea of raising the in-process pH above the range of 2.2 to 2.6 was contradictory to what one of skill in the art would have thought before the claimed invention.” Id. Claims 6 and 7 were at issue in the litigation. Claim 6 reads:
6. An injectable liquid pharmaceutical formulation of l-epinephrine sterile solution; said liquid pharmaceutical formulation having a pH between 2.8 and 3.3; said injectable liquid pharmaceutical formulation compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine, and further including a tonicity agent; said liquid pharmaceutical formulation including no more than about 6% d-epinephrine and no more than about 0.5% adrenalone at release, and no more than about 12% d-epinephrin and no more than about 0.5% adrenalone over a shelf-life of at least 12 months.
As seen, claim 6 recites a limitation of “a pH between 2.8 and 3.3.”
In response to an obviousness rejection based on a reference (the Helenek reference) disclosing a 1 mg/mL injectable l-epinephrine formulation free of preservatives and antioxidants with a pH of 2.2 to 5.0, the prosecuting attorney, squarely flying in the face of what Belcher told the FDA, responded that the claimed range of 2.8 to 3.3 “was unexpectedly found to be critical by the Applicant to reduce the racemization of l-epinephrine.” Belcher, 2021 U.S. App. LEXIS 26346 at *8. The claims were allowed, and the Reasons for Allowance stated:
Applicant has demonstrated that pH range of between 2.8 and 3.3 is critical to prevent racemization of l-epinephrine . . . . [T]here 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 the limited racemization and impurities as instantly claimed.
Mr. Rubin was Belcher’s Chief Scientific Officer (CSO) and helped draft both the patent application and the NDA. He was considered the head of IP at Belcher, though he is not a patent attorney or agent, and served as the liaison between the CEO and the patent prosecution attorney.
The district court found that Mr. Rubin owed a duty of candor and good faith to the PTO under 37 C.F.R. §1.56. Belcher Pharms., LLC v. Hospira, Inc., 450 F. Supp. 3d 512, 548 (D.Del. Mar. 31, 2020). The district court made a finding of fact that “Rubin was aware of, but did not disclose to Belcher’s prosecuting attorney or the Patent Office, multiple prior art disclosures of epinephrine products with pHs in the claimed range of 2.8 to 3.3, including the Stepensky reference, the JHP Adrenalin Product [with a pH in the range of 2.8 to 3.3], and Sintetica’s epinephrine products[.]” Id. at 535. “[T]he specification failed to disclose prior art that had pHs above 2.6, despite their indisputable existence and Rubin’s knowledge of them.” Id. at 548. Mr. Rubin also knew of some of the references because they were disclosed to the FDA. “The district court found implausible Mr. Rubin’s testimony at trial that he withheld JHP’s product, Sintetica’s product and Stepensky because he believed that they were irrelevant [due to differences in the quantity of epinephrine in these products].” Belcher, 2021 U.S. App. LEXIS 26346 at *16.
The court found that each of the three withheld prior art disclosures was but-for material to patentability “because they disclosed two aspects of the asserted claims: the pH range and the impurity levels.” Id. at *15. Furthermore, the district court found that “Mr. Rubin acted with the requisite intent to deceive.” Id. The court concluded: “Mr. Rubin made ‘misleadingly incomplete, if not plainly inaccurate’ statements combined with active omission of relevant information.” Belcher, 450 F.Supp.3d at 551. “This was an inequitable breach of his duty of candor and good faith that warrants an equitable solution.” Id. The court found no direct evidence of intent to deceive by Mr. Rubin, but all the facts taken together persuaded the court, clearly and convincingly, that the only reasonable inference was deceptive intent. Id. at 550.
The Federal Circuit began its analysis by noting that since Belcher did not appeal the obviousness finding based, inter alia, on JHP’s epinephrine product, that prior art product is “necessarily material.” Belcher, 2021 U.S. App. LEXIS 26346 at *18. Further, the Federal Circuit rejected Belcher’s arguments that the withheld art was immaterial as cumulative to the Helenek reference addressed during prosecution because Belcher argued during the prosecution that the claimed range was “critical” and not specifically disclosed in Helenek. Id.
With respect to intent, Belcher again argued that Mr. Rubin withheld the references because he believed they were irrelevant. Id. at *21. The Federal Circuit rejected this argument and upheld the district court’s finding of specific intent to deceive:
The district court found Mr. Rubin’s reasons for withholding the JHP product to be implausible and not credible. … But the district court also relied on other record evidence to support its intent finding, including Mr. Rubin’s prior knowledge of the JHP product, his central role in both FDA approval and patent prosecution, and his arguments to the examiner about the “criticality” of the 2.8 to 3.3 pH range despite knowing that Sintetica’s batches used the same range.
Id. at *22-23.
Therefore, the Federal Circuit affirmed the district court’s decision that the ’197 patent is unenforceable for inequitable conduct. Id. at *23.
There may be many times when an inventor or company needs to make submissions to various regulatory bodies as well as the PTO. Certain differences in these submissions may be justified and even expected depending on the purposes of the submission. However, this can create a vulnerability if the inventor or company makes inconsistent arguments to the different regulatory bodies. Regular coordination and communication between patent counsel and regulatory counsel can help minimize this potential issue.
There is also the advice of the MPEP, which is to err on the side of disclosure:
When in doubt, it is desirable and safest to submit information. Even though the attorney, agent, or applicant doesn’t consider it necessarily material, someone else may see it differently and embarrassing questions can be avoided. The court in U.S. Industries v. Norton Co., 210 USPQ 94, 107 (N.D. N.Y. 1980) stated ”[i]n short, the question of relevancy in close cases, should be left to the examiner and not the applicant.” See also LaBounty Mfg., Inc. v. U.S. Int’l Trade Comm’n, 958 F.2d 1066, 22 USPQ2d 1025 (Fed. Cir. 1992).
MPEP § 2004.
Thus, it might be prudent for prosecution attorneys to ask applicants for relevant statements made to other regulatory agencies to ensure consistency in statements made to the PTO.