Obviousness In Drug Combinations ' Unexpected Results Vs. Unexpected Mechanisms Of Action

• Published date: 24 July 2023
• Subject Matter: Intellectual Property, Food, Drugs, Healthcare, Life Sciences, Patent, Food and Drugs Law
• Law Firm: Morrison & Foerster LLP
• Author: Mr Mark D. McBriar, Bu Yin, Ashley E. Sperbeck and Shawn O. Meade

Ascertaining the differences between prior art and claims at issue requires interpreting the claim language and considering both the invention and the prior art references as a whole.¹ The Supreme Court emphasized "the need for caution in granting a patent based on the combination of elements found in the prior art"² and discussed circumstances in which a patent might be determined to be obvious. An objective analysis for determining obviousness includes considering: (1) the scope and content of the prior art, (2) the differences between the prior art and the claims at issue, (3) the level of ordinary skill in the field of art, (4) and any objective indicia of non-obviousness.³ Objective evidence of non-obviousness, or "secondary considerations," includes evidence of commercial success, long-felt but unsolved needs, failure of others, and unexpected results.⁴

Pharmaceutical composition claims and method of treatment claims may often face obviousness rejections and validity challenges involving arguments that a claim feature (e.g., pharmacokinetic parameters or an effect of a therapeutic combination) is inherent. To establish inherency in an obviousness analysis, "the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art."⁵In general, the burden to establish inherency in the obviousness context is high.

A prima facie case of obviousness for methods using a combination of known chemical compounds can be overcome if the combination yields unexpected results, such as a synergistic effect.⁶ The precedential decision of In re Couvaras⁷ contains cautions on the importance of distinguishing between unexpected results obtained with a combination of two known pharmaceuticals as opposed to an unexpected mechanism of action - if a claim merely recites a mechanism of action in a known use of a known compound (or a combination of compounds), the claim limitation is likely inherent and cannot be used to overcome a prima facie case of obviousness, even if the mechanism of action is previously unappreciated or surprising.

Background

Inventor John Couvaras filed a patent application for combatting hypertension, with claims directed to methods of increasing the release of prostacyclin in blood vessels by co-administering two antihypertensive agents: (1) a gamma-aminobutyric acid-a (GABA-a) agonist and (2) an angiotensin II receptor blocker (ARB).⁸ During prosecution of the application...