By Chris Holman
In re Couvaras, 2023 WL 3984753 (Fed. Cir. June 14, 2023)
A prima facie obvious combination of prior art chemical compounds can sometimes be deemed nonobvious if the result of the combination is sufficiently surprising, such as when a combination of pharmaceutical active ingredients results in an unexpected synergy. See, e.g., Sanofi-Aventis Deutschland GmbH v. Glenmark Pharms. Inc., USA, 748 F.3d 1354 (Fed. Cir. 2014). In a recent Federal Circuit decision, In re Couvaras, Judge Lourie (writing for a unanimous panel) explains the important distinction between unexpected results in a pharmaceutical combination product as opposed to the mere recitation of an unexpected mechanism of action.
The case is an appeal of a Patent Trial and Appeal Board decision affirming an Examiner’s rejection of the claims at issue as obvious. A representative claim recites:
11. A method of increasing prostacyclin release in systemic blood vessels of a human individual with essential hypertension to improve vasodilation, the method comprising the steps of:
providing a human individual expressing GABA-a receptors in systemic blood vessels due to essential hypertension;
providing a composition of a dosage of a GABA-a agonist and a dosage of an ARB combined into a deliverable form, the ARB being an Angiotensin II, type 1 receptor antagonist;
delivering the composition to the human individual’s circulatory system by co-administering the dosage of a GABA-a agonist and the dosage of the ARB to the human individual orally or via IV;
synergistically promoting increased release of prostacyclin by blockading angiotensin II in the human individual through the action of the dosage of the ARB to reduce GABA-a receptor inhibition due to angiotensin II presence during a period of time, and
activating the uninhibited GABA-a receptors through the action of the GABA-a agonist during the period of time; and
relaxing smooth muscle of the systemic blood vessels as a result of increased prostacyclin release.
Judge Lourie leads off the decision by observing that, while the claims at issue “literally recite methods of increasing prostacyclin release … by co-administering two well-known types of antihypertensive agents[, i]n reality, the claims relate to combatting hypertension with known antihypertensive agents and claiming their previously unappreciated mechanism of action.”
He then affirms the Board’s conclusion that it “is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” It was undisputed that the two types of active agents recited in the claims, GABA-a agonists and ARBs, were both known to be useful for alleviating hypertension.
The appellant, citing Honeywell International Inc. v. Mexichem Amanco Holdings S.A., 865 F.3d 1348, 1355 (Fed. Cir. 2017), argued that the mechanism of action recited in the claims, i.e., the increased release of prostacyclin, was unexpected, and that the Board had erred in dismissing the limitation as having no patentable weight due to inherency. But the Federal Circuit rejected this argument, noting that “Honeywell held that ‘unexpected properties may cause what may appear to be an obvious composition to be nonobvious,’ not that unexpected mechanisms of action must be found to make the known use of known compounds nonobvious.” The court agreed with the Board that the recitation of various mechanistic steps in the claims was insufficient to overcome the prima facie obviousness of the claimed methods, observing that:
While mechanisms of action may not always meet the most rigid standards for inherency, they are still simply results that naturally flow from the administration of a given compound or mixture of compounds. Reciting the mechanism for known compounds to yield a known result cannot overcome a prima facie case of obviousness, even if the nature of that mechanism is unexpected.
. . .
To establish unexpected results, Couvaras would have needed to show that the co-administration of a GABA-a agonist and an ARB provided an unexpected benefit, such as, e.g., better control of hypertension, less toxicity to patients, or the ability to use surprisingly low dosages. We agree with the Board that no such benefits have been shown, and therefore no evidence of unexpected results exist.