Inequitable conduct is an affirmative defense to patent infringement, but the bar for proving it is a high one. A defendant must prove by clear and convincing evidence that the patentee intentionally deceived the Patent Office on a matter that, by a preponderance of the evidence, was material to prosecution. Hospira, Inc. successfully met the high bar of inequitable conduct when Belcher Pharmaceuticals sued it for infringing its patent claiming a not-so-inventive epinephrine formulation (the ‘197 patent). The Federal Circuit recently affirmed a Delaware district court, finding that Belcher’s Chief Science Officer (CSO), Mr. Darren Rubin, intentionally mislead the USPTO in prosecuting the ‘197 patent.

In 2012 Belcher submitted a New Drug Application (NDA) to the FDA for approval of a known sulfite-free epinephrine formulation with a slight twist. The NDA described a new in-process pH range of 2.4 to 2.6. According to Belcher’s NDA this was the only new aspect of the formulation. Otherwise, the NDA was purely literature-based, taken almost entirely from a formulation by Sintetica SA teaching a pH range of 2.8 to 3.3. In response to the NDA, the FDA requested data concerning the effect of the lower in-process pH range on racemization of the drug. Rather than delay FDA approval, Belcher decided to revert to Sintetica’s 2.8-3.3 pH range since it already had literature support and its effect on racemization was known. Consequently, Belcher conducted racemization studies in the 2.8-3.3 pH range and provided the data to the FDA. The FDA approved Belcher’s NDA on July 29, 2015.
In 2014, after reverting to Sintetica’s 2.8-3.3 pH range, Belcher filed a patent application claiming to have discovered that a pH range of 2.8 to 3.3 provided a new method of producing sulfite-free epinephrine. Considering that this is exactly the same range taught by the prior art Sintetica reference the prosecution went surprisingly well. The government’s examiner issued only one Office action rejecting the claims as obvious over a published Canadian application by Helenek which taught a sulfite-free epinephrine formulation with a pH range between 2.2 and 5.0. Ordinarily, when a prior art reference teaches a range that encompasses a claimed range, the claimed range is not considered inventive. That is, unless Belcher could show that its claimed range produced an unexpected effect over the prior art. Contradicting its statements to the FDA, Belcher argued to the USPTO 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.’” As a direct result of Belcher’s argument, the examiner withdrew his rejections and allowed the ‘197 patent, which issued March 15, 2016.

At trial Belcher’s CSO, Mr. Rubin, testified that he participated in drafting Belcher’s NDA for its sulfite-free epinephrine product, and in drafting and prosecuting the ‘197 patent. Mr. Rubin further testified that he was aware of Sintetica’s epinephrine formulation with a 2.8 to 3.3 pH range, that Belcher’s NDA described this range as old in the art, and that he was aware of two other references that directly bear on the claimed formulation including the relationship between the claimed pH range and racemization. According to Mr. Rubin, he withheld the information from the USPTO because he believed that it was irrelevant. The district court found his explanation implausible. While acknowledging a lack of direct evidence of intent, the court indicated that the available evidence was clear and convincing, and that the only reasonable inference that could be drawn was that Mr. Rubin intentionally misled the USPTO. Accordingly, the district court found the ‘197 patent unenforceable for inequitable conduct, and invalid for obviousness over the withheld information.

On appeal, the standard of review for intent to deceive and materiality of the information withheld is clear error, and the standard of review for the ultimate finding of inequitable conduct is abuse of discretion. Affirming the district court, the Federal Circuit noted that withheld information can be material even if it does not meet the clear and convincing standard required to invalidate an issued patent. It is enough that the withheld information would have prevented an examiner from issuing the patent. Here, the withheld information not only would have blocked issuance, the issued patent was actually found invalid for obviousness over the same information under the higher clear and convincing standard. Therefore, the Federal Circuit concluded that the information Mr. Rubin withheld from the USPTO was necessarily material.

With respect to intent, the Federal Circuit found that Mr. Rubin’s prior knowledge of all the information withheld from the patent examiner, and his central role in both the FDA approval process and prosecution of the ‘197 patent was controlling. Mr. Rubin made contradictory arguments to the FDA and USPTO, on issues concerning the very same evidence, which were dispositive of both matters. Consequently, the Federal Circuit found no clear error in the district court’s finding of intent to deceive the USPTO, and no abuse of discretion in its finding of inequitable conduct.

Mr. Rubin’s statements to the FDA and USPTO were more than contradictory. His statements to the FDA clearly and convincingly demonstrated that he knew his factual representations to the USPTO were false. He evidently believed he could make false statements with impunity. The FDA and USPTO are two different bureaucracies with no systematic coordination; who would know. Mr. Rubin underestimated the power of litigation discovery and a well-planned deposition. He was boxed into admitting knowledge of material facts, and his integral role in statements made to the FDA and USPTO. At that point he found himself in the indefensible position of denying the materiality of obviously material facts.

The Belcher case has captured the attention U.S. Senators Tom Tillis and Patrick Leahy, who recently sent a letter to interim USPTO Director Hirshfeld urging the agency “to take action to require applicants to disclose relevant statements they have made to other agencies relating to inventions discussed in their patent applications”. The senators suggested “creation of a smooth, predictable, and regular channel of information from other federal agencies to the Patent Office”.

[1] Belcher Pharmaceuticals, LLC v. Hospira, Inc., 2021 WL 3889810 at 6-7, 2020-1799 (Fed. Circ. 2021).
[2] More Potent and Less Toxic Formulations of Epinephrine and Methods of Medical Use, U.S. Patent No. 9,283,197 (issued Mar. 15, 2016).
[3] Belcher, at 2.
[4] Belcher, at 2.
[5] Belcher, at 2(“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.’”).
[6] Belcher, at 1.
[7] Belcher, at 2.
[8] Belcher, at 2.
[9] Belcher, at 3.
[10] Belcher, at 4.
[11] Belcher, at 4.
[12] Belcher, at 5.
[13] Belcher, at 5.
[14] Microsoft Corp. v. I4I Ltd. Partnership, 564 U.S. 91 (2011)(holding that § 282 requires invalidity defenses to be proven by clear and convincing evidence).
[15] Belcher, at 6.
[16] Letter to Mr. Andrew Hirshfeld, https://www.leahy.senate.gov/imo/media/doc/20210909%20Letter%20to%20PTO%20on%20FDA%20submissions.pdf (last accessed September 17, 2021).
[17] Id.