By Kevin E. Noonan —

Last week, the Federal Circuit affirmed a finding of inequitable conduct in Apotex v. USB, a relatively rare occurrence in the years after the Federal Circuit's decision in Therasense v. Becton, Dickenson.  In the Therasense case, the Federal Circuit sitting en banc clarified the standards for finding inequitable conduct, in a frank effort to remedy the "plague" on the patent system that the Court believed the inequitable conduct defense had become.  (The historically minded will recall that this isn't the first time that members of the Court identified this particular plague.)  In its decision, the majority decided that the traditional materiality prong of the test for inequitable conduct needed to amount to "but for" materiality, i.e., that the U.S. Patent and Trademark Office would not have granted the patent if the Examiner had been aware of the undisclosed or misrepresented art or information.  For "intent to deceive," the Court held that intent needed to be the "single most reasonable inference" to be drawn from the applicant's behavior, recognizing that finding an express "smoking gun" of intent would be rare.  The most significant change in the law was that the Court prohibited the common practice of using evidence regarding one prong to bolster evidence of the other prong (e.g., if the materiality of the undisclosed art or information was extremely high, courts would accept lesser evidence of intent, with the justification that the applicant would know or should have known that art of such materiality should be disclosed and failure to disclose was evidence of intent).  The Court left open the possibility that, even in the absence of sufficient evidence for either prong there could be evidence of such egregious misconduct that a court, exercising its equitable powers, could find a patent unenforceable for inequitable conduct.

The matter at issue in Apotex was moexipril magnesium, an angiotensin converting enzyme (ACE) inhibitor used to treat hypertension, which was known in the art to be "susceptible to degradation and instability."  The patent-in-suit, U.S. Patent No. 6,767,556, claimed formulation methods, as exemplified in claim 1:

1.    A process of making a solid pharmaceutical composition comprising moexipril magnesium, said process comprising the step of reacting moexipril or an acid addition salt thereof with an alkaline magnesium compound in a controlled manner in the presence of a sufficient amount of solvent for a predetermined amount of time so as to convert greater than 80% of the moexipril or moexipril acid addition salt to moexipril magnesium.

The formulation was prepared by reacting moexipril with (preferably) magnesium hydroxide or magnesium carbonate and formulated by wet granulation.  The accused infringing articles, the drugs Univasc® and Uniretic, were also magnesium-stabilized formulations of moexipril.

During prosecution the Office asserted three references, including U.S. Patent No. 4,743,450, which was listed in the Orange Book and disclosed methods for stabilizing ACE inhibitors using alkaline magnesium compounds; and the Gu scientific journal article, which compared wet granulation and dry powder mixing for formulating moexipril with "alkaline stabilizers and concluding only wet granulation capable of stabilizing moexipril."  These references were disclosed in the specification of the '556 patent, which distinguished the claimed methods and formulations by asserting that "the moexipril hydrochloride and alkaline magnesium compound are capable of an acid-base reaction that is difficult to control and results in uncertainty regarding the final composition of the product."  Moreover, the '556 patent asserted that the Gu article teaches that "only a portion (if any) of the drug may be converted to moexipril magnesium and that stabilization therefore occurs not because of conversion, but because of the presence of the alkaline stabilizing compound in the final product."

During prosecution, the applicant and inventor, Dr. Bernard Charles Sherman (who was also Apotex CEO) addressed three obviousness rejections based on varying combinations of the art by maintaining that there was no evidence that the art-recognized methods taught that moexipril and alkaline magnesium were reacted, instead arguing that these compounds were merely mixed together.

In addition to these arguments, Apotex (at the direction of Dr. Sherman) submitted an expert declaration from Dr. Michael Lipp who testified that the alkaline magnesium stabilizer acts to prevent reactions, and that the stabilizer must remain unreacted to do this, so that a person of ordinary skill would not expect there to be a reaction between moexipril and the magnesium compound:

An additional example particularly relevant to the matter at hand is the UNVASC® [sic] moexipril hydrochloride formulation . . . .  The product monograph for the UNVASC [sic] moexipril hydrochloride formulation lists moexipril hydrochloride as being present in the final formulation in addition to magnesium oxide as an alkaline stabilizer, as per the teachings of the '450 patent which is listed on the FDA Orange Book for this formulation.  As a result, in my opinion, a skilled formulator reading Harris et al. would not expect a reaction to occur between an alkaline or saccharide stabilizer and an ACE inhibitor drug in the formulations disclosed therein.

The claims were granted after Apotex's counsel agreed to include the "greater than 80% conversion" limitation into the claim as allowed, with the reasons for allowance showing (according to the District Court) the materiality of the representations made during prosecution:

The primary reason for allowance is that the prior art does not disclose nor fairly suggest a process of making a pharmaceutical composition comprising moexipril magnesium, comprising the step of reacting moexipril or an acid addition salt thereof with an alkaline magnesium compound so as to convert greater than 80% of the moexipril or moexipril acid addition salt to moexipril magnesium.  Rather, the prior art teaches that only a portion of drug (if any) may be converted to the alkaline salt and that the stable product results entirely or primarily not from conversion to alkaline salts, but from stabilization of the moexipril hydrochloride by the presence of the alkaline stabilizing compound in the final product.

The District Court found that the '556 patent had been obtained through inequitable conduct, based on the following evidence of materiality and intent to deceive.  The District Court found that Dr. Sherman, the named inventor, Apotex CEO and person in charge of prosecution and litigation knew that the prior art accused product was made using the claimed process and thus the process was known in the prior art, but concealed this information from the Office and misrepresented the facts through his counsel and expert witness.  The following evidence supported these findings regarding materiality:

1.    Dr. Sherman conceded during trial that, before filing the '556 patent application, he had a "strong suspicion" and a "belief" that Univasc® was made according to his claimed process.

2.    "[O]n the same day the application was filed, Dr. Sherman conducted tests comparing Univasc to an Apotex moexipril product with no alkaline stabilizer.  In his handwritten notes, Dr. Sherman concluded that the Apotex product was 'much less stable than the magnesium salt,' implying at least a suspicion that Univasc consisted of moexipril magnesium."

3.    "About a month [thereafter], Dr. Sherman's suspicion was confirmed by two Apotex scientists who produced a detailed mass spectrometry report on Univasc and concluded that moexipril in Univasc is 'mainly present' as moexipril magnesium."

As explained in the Federal Circuit's opinion:

The district court also found that Dr. Sherman made several misrepresentations to the PTO regarding the prior art.  In particular, Dr. Sherman misrepresented the nature of Univasc and the '450 patent by asserting that the moexipril hydrochloride in Univasc was not reacted but merely combined with an alkaline magnesium compound.  The district court also found that Dr. Sherman, in the specification and through Dr. Lipp's declaration, mischaracterized the Gu article by asserting that only a minor portion of the drug, if any, is converted to moexipril magnesium.  Lastly, the district court found that Dr. Sherman lied in the '556 patent application by including certain examples of experiments that were never conducted.  The court noted that each example is written in the past tense as if it had occurred, but Dr. Sherman admitted at trial that the experiments were made up in his head.

The court found that Dr. Sherman failed to inform Dr. Lipp of the true facts about Univasc and shielded him from the truth, which resulted in a declaration that Dr. Sherman knowingly submitted to the PTO to perpetuate his mischaracterizations of the prior art.  Dr. Lipp testified that he was specifically asked to limit his discussions to only the documents provided by Apotex, which did not include any information regarding the tests conducted on Univasc or Dr. Sherman's knowledge of the product.

These misrepresentations satisfied the Therasense "but for" materiality standard, according to the District Court, because "the Examiner adopted Dr. Sherman's repeated misrepresentations verbatim and would not have allowed the claims had he been aware that Univasc contained moexipril magnesium."

The District Court also found that, even if the evidence did not satisfy the "but for" test for materiality, Dr. Sherman's conduct during prosecution amounted to "egregious misconduct" under the Therasense standard.  The District Court further "observed that Dr. Sherman abused the patent system by targeting a competitor's existing and widely available product and seeking to obtain a patent on it through lies and deception for the purpose of suing that competitor."

With regard to intent to deceive, the District Court found that the "single most reasonable inference" to be drawn from the evidence, including Dr. Sherman's "overall pattern of misconduct and his poor credibility at trial" and "demeanor and evasive testimony at trial" established by clear and convincing evidence the intent to deceive required under Therasense.

The Federal Circuit affirmed, finding that the District Court's determination on materiality and intent to deceive not clearly erroneous and its ultimate decision not an abuse of discretion.  In an opinion by Judge Reyna, joined by Judges Wallach and Hughes, the Court agreed that the evidence from the Examiner's "Reasons for Allowance" established that there were "affirmative misrepresentations of material facts" because Dr. Sherman knew the statements made during prosecution were not true.  The opinion did draw an important distinction, however:

To be clear, we agree with Apotex that Dr. Sherman had no duty to disclose his own suspicions or beliefs regarding the prior art.  There is nothing wrong with advocating, in good faith, a reasonable interpretation of the teachings of the prior art.  The misconduct at issue, however, goes beyond failing to disclose a personal belief or alternative interpretations of the prior art; here, Dr. Sherman affirmatively and knowingly misrepresented material facts regarding the prior art.

As to intent, the Federal Circuit stated that "[Dr. Sherman] knew enough to recognize that he was crossing the line from legitimate advocacy to genuine misrepresentation of material facts."

Finally, the Federal Circuit did not reach the "egregious misconduct" determination because the evidence of materiality and intent were sufficient and thus the District Court's inequitable conduct determination was not an abuse of discretion.  However, the opinion did note that Dr. Sherman's actions "come close" to that standard, stating that "[w]e find particularly significant and inexcusable the fact that Dr. Sherman arranged for the preparation and submission of an expert declaration containing false statements instrumental to issuance of the patent."

Apotex Inc. v. UCB, Inc. (Fed. Cir. 2014)
Panel: Circuit Judges Reyna, Wallach, and Hughes
Opinion by Circuit Judge Reyna