In Belcher Pharms, LLC v Hospira, Inc., –F.4e __, 2021 US App. LEXIS 26346 * (Fed. Cir. September 1, 2021) The Federal Circuit upheld a district court ruling by Delaware J. Stark, finding the claims of U.S. Patent No. 9,283,197 (“the 197 patent”) obvious and unenforceable on account of unfair conduct. With respect to the latter, both courts found that Belcher’s scientific director withheld important information from the United States Patent and Trademark Office (“PTO”), the only reasonable inference being a specific intent to deceive.
Belcher’s approved product was a 1 mg / mL formulation of l-epinephrine injection. In submissions to the FDA, Belcher, in an effort to make FDA approval as easy as possible, described the development of its formulation as stemming from a reference product developed by a Swiss company, Sintetica, in 1930s. According to Belcher, Sintetica’s “original formulation” of 1 mg / mL injectable l-epinephrine did not include preservatives or sulfites and had an “old” manufacturing pH range of 2.8 to 3. , 3. In contrast, the NDA described the new composition as having a lower pH range of 2.4-2.6 and explained that “[t]he changes [in pH] was very simple. Belcher, US application 2021. LEXIS 26346 at * 3-4. “In response to the FDA investigation into [the] manufacturing process for the stability validation batches, Belcher stated that the only difference between the Sintetica batches claimed and the formulation proposed by Belcher “relates to the[-]treat the pH ‘and that it’ considers[ed] the in[-]the change in process pH should be a very minor change not requiring additional stability studies. Identifier. at 5. However, when the FDA requested additional information regarding the pH change, Belcher decided to revert to the “old” pH range of the original Sintetica formulation, 2.8-3.3, to avoid a delay. of approval, which Belcher received on July 29, 2015..
Belcher filed for a US patent protecting its product on August 15, 2014. Contrary to what Belcher told the FDA, the patent application described the formulation having a pH between 2.8 and 3.3 as something that “seemed impossible” and “had never been accomplished before. Belcher, US application 2021. LEXIS 26346 at * 5. “The patent likewise indicates that the idea of raising the pH during processing above the 2.2-2.6 range was at odds with what one skilled in the art would have thought prior to the invention. claimed. ” Identifier. Claims 6 and 7 were at issue in the litigation. Claim 6 reads as follows:
6. An injectable liquid pharmaceutical formulation of sterile 1-epinephrine solution; said liquid pharmaceutical formulation having a pH between 2.8 and 3.3; said injectable liquid pharmaceutical formulation mixed in a 1.0 to 1.06 mg / ml aqueous solution of 1-epinephrine, and further comprising a tonicity agent; said liquid pharmaceutical formulation containing no more than about 6% d-epinephrine and no more than about 0.5% adrenalone on release, and no more than about 12% d-epinephrine and no more than about 0.5% adrenalone over a shelf life of at least 12 months.
As can be seen, claim 6 cites a limitation “of a pH between 2.8 and 3.3”.
In response to a rejection of evidence based on a benchmark (the Helenek benchmark) disclosing a preservative and antioxidant free 1 mg / mL formulation of l-epinephrine injection with a pH of 2.2 to 5.0, the Attorney, squarely in the face of what Belcher told the FDA, responded that the claimed range of 2.8 to 3.3 “was found to be unexpectedly critical by the plaintiff to reduce the racemization of l-epinephrine.” . Belcher, US application 2021. LEXIS 26346 at * 8. The claims were granted and the grounds for compensation stated:
The applicant has demonstrated that a pH range between 2.8 and 3.3 is essential to prevent the racemization of L-epinephrine. . . . [T]there is nothing in the prior art which would teach or suggest that the claimed pH range instantaneously between 2.8 and 3.3 would result in the limited racemization and impurities as claimed instantaneously.
Mr. Rubin was the Scientific Director (CSO) of Belcher and participated in the drafting of the patent application and the NDA. He was considered the head of intellectual property at Belcher, although he was not a patent attorney or agent, and served as a liaison between the CEO and the patent attorney.
The district court held that Mr. Rubin owed a duty of candor and good faith to the PTO under 37 CFR §1.56. Belcher Pharms., LLC v Hospira, Inc., 450 F. Supp. 3d 512, 548 (Del. 31 March 2020). The district court found that “Rubin was aware of, but did not disclose to Belcher’s attorney or the Patent Office, multiple disclosures of prior art of epinephrine products with pHs in the range. claimed from 2.8 to 3.3, including the Stepensky reference, the adrenaline product JHP [with a pH in the range of 2.8 to 3.3], and Sintetica’s epinephrine products[.]” Identifier. to 535. “[T]The specification did not disclose the prior art which had pHs above 2.6, despite their unmistakable existence and Rubin’s knowledge. User ID. at 548. Mr. Rubin was also familiar with some of the references because they were disclosed to the FDA. “The District Court found Mr. Rubin’s testimony at trial implausible that he withheld JHP’s product, Sintetica and Stepensky’s product because he thought they were irrelevant. [due to differences in the quantity of epinephrine in these products]. ” Belcher, US application 2021. LEXIS 26346 at * 16.
The court concluded that each of the three prior art disclosures retained was only an important element for patentability “because they disclosed two aspects of the claimed claims: the pH range and the levels of impurities”. User ID. at 15. In addition, the district court found that “Mr. Rubin acted with the requisite intent to deceive. Identifier. The court concluded: “Mr. Rubin made ‘deceptively incomplete, if not downright inaccurate’ statements combined with an active omission of relevant information. Belcher, 450 F.Supp.3d at 551. “This was an unfair breach of his duty of frankness and good faith which justifies an equitable solution.” Identifier. The court found no direct evidence of an intent to deceive on Mr. Rubin’s part, but all the facts taken together convinced the court, clearly and convincingly, that the only reasonable inference was misleading intent. . User ID. to 550.
The Federal Circuit began its analysis by noting that since Belcher did not appeal the finding of evidence based, inter alia, on JHP’s epinephrine product, that the prior art product is “necessarily important. “. Belcher, US application 2021. LEXIS 26346 at * 18. Further, the Federal Circuit rejected Belcher’s arguments that the chosen art was unimportant as a cumulative to the Helenek reference discussed during the chase because Belcher argued during the chase that the claimed range was “critical.” and was not specifically disclosed in Helenek. Identifier.
With respect to intent, Belcher again argued that Mr. Rubin withheld the references because he believed they were irrelevant. Identifier. to * 21. The Federal Circuit rejected this argument and upheld the district court’s conclusion regarding the specific intent to deceive:
The district court ruled that Mr. Rubin’s reasons for withholding the JHP product were implausible and not credible. … But the district court also relied on other recorded evidence to support its finding of intent, including Mr. Rubin’s prior knowledge of the JHP product, his central role in the FDA approval and the patent lawsuit, and its arguments to the Examiner about the “criticality” of the pH range 2.8-3.3 despite the fact that the Sintetica lots used the same range.
User ID. at * 22-23.
Therefore, the Federal Circuit upheld the district court’s ruling that the ‘197 patent is inapplicable for unfair conduct. User ID. to * 23.
To take away
There may be times when an inventor or a company must make submissions to various regulatory bodies as well as to the PTO. Some differences in these submissions may be justified and even expected depending on the objectives of the submission. However, this can create a vulnerability if the inventor or the company presents inconsistent arguments to different regulators. Regular coordination and communication between patent attorneys and regulatory advisers can help minimize this potential problem.
There is also the advice of the MPEP, which is to err on the side of disclosure:
When in doubt, it is desirable and safer to submit information. While the lawyer, agent, or plaintiff may not necessarily view it as important, someone else may view it differently and embarrassing questions can be avoided. The court in US Industries v. Norton Co., 210 USPQ 94, 107 (NDNY 1980) stated ”[i]In short, the question of relevance in close cases should be left to the examiner and not to the applicant. See also LaBounty Mfg., Inc. v. US Int’l Trade Comm’n, 958 F.2d 1066, 22 USPQ2d 1025 (Fed. Cir. 1992).
MPEP § 2004.
Thus, it might be prudent for prosecutors to ask applicants for relevant statements made to other regulators in order to ensure consistency in statements made to the PTO.
© 2021 Finnegan, Henderson, Farabow, Garrett & Dunner, LLPRevue nationale de droit, volume XI, number 263