Federal Circuit Affirms Validity of Tarka Patent on Combination Pharmaceutical Product

The Federal Circuit decision in Sanofi-Aventis Deutschland GmbH v. Glenmark Pharmaceuticals Inc., USA, addresses several interesting issues, but is most likely to be cited by other patent holders for its affirmance of the jury verdict that upheld the Tarka patent at issue. The jury found that claims directed to a pharmaceutical composition comprising a combination of active agents were not invalid, even though the compounds per se were known in the art.

The Patent at Issue

The patent at issue was U.S. Patent 5,721,244, which is listed in the Orange Book for the antihypertension drug Tarka®.

Claim 3 was at issue, and depends from claim 1. These claims are presented in the Federal Circuit decision as follows:

1. A pharmaceutical composition comprising:
(a) an angiotensin-converting enzyme inhibitor (ACE inhibitor) . . . , and
(b) a calcium antagonist or a physiologically acceptable salt thereof;
wherein said ACE inhibitor and said calcium antagonist are present in said composition in amounts effective for treating hypertension; . . .

3. A composition according to claim 1, wherein said ACE inhibitor is trandolapril [formula omitted] or a physiologically acceptable salt thereof, or quinapril [formula omitted] or a physiologically acceptable salt thereof.

The District Court Litigation

The district court litigation arose from Glenmark’s filing of an Abbreviated New Drug Application (ANDA) to obtain FDA approval to market a generic version of Tarka®. The 30-month stay of approval of the ANDA expired in 2010, and Glenmark launched its product “at risk” while the litigation was still pending, after the district court denied the plaintiffs’ motion for a preliminary injunction.

The case was tried to a jury, before which Glenmark admitted infringement but asserted invalidity based on obviousness. The jury upheld the validity of the patent, and awarded damages of $15,200,000 for lost profits and $803,514 for price erosion.

The Federal Circuit Decision 

The Federal Circuit decision was authored by Judge Newman and joined by Judge Linn and Judge Wallach.

The Federal Circuit decision summarizes Glenmark’s obviousness arguments as follows:

Glenmark argues that the verdict cannot stand, as a matter of law, on the premise that if a combination of classes of components is already known, all selections within such classes are obvious to try, as a matter of law. Glenmark argues that it is irrelevant that the combination is ultimately found to have unpredicted or superior properties if those properties, though unknown in the prior art, could be attributed to one of the prior art components of the combination.

The Federal Circuit decision identifies the following evidence of non-obviousness that the jury was entitled to rely on:

• The claimed trandolapril ACE inhibitor is a “double-ring” compound, while the prior art had focused on “single-ring” compounds such as enalapril and captopril.
• The previously tested combinations of ACE inhibitors and calcium channel blockers required more than the once daily dosing that was possible with the claimed combination.
• The claimed combination results in improved kidney function and improved blood vessel structure as compared to prior art hypertension treatments.

The Federal Circuit decision provides the following counterpoints to Glenmark’s arguments:

Glenmark argues that because the single-ring inhibitors had been tested in combination with calcium antagonists, it was “obvious to try” every combination of effective ACE inhibitor and calcium channel blocker. Glenmark Br. at 35 (“It is not invention merely to select something from a list of items in the prior art.”).

In KSR International Co. v. Teleflex Inc., … the [Supreme] Court explained that “obvious to try” may apply when “there are a finite number of identified, predictable solutions” to a known problem. … This court has elaborated that the identified path must “present a finite (and small in the context of the art) number of options easily traversed to show obviousness.” ….  As illustrated in In re O’Farrell, …. it would not be “obvious to try” when “the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful.”

Glenmark argues that the inventors’ selection of the double-ring ACE inhibitors for testing in combination with calcium antagonists is of itself evidence that it was obvious to try this combination.

Patentability does not turn on how the invention was made, but on whether it would have been obvious to a person of ordinary skill in the field. In Eisai Co. v. Dr. Reddy’s Laboratories, Ltd., … the court observed that in the medical arts “potential solutions are less likely to be genuinely predictable,” … as compared with other arts such as the mechanical devices in KSR.

Glenmark also argues that later-discovered benefits cannot be considered in an obviousness analysis, here referring to the improved kidney and blood vessel function that were observed after the patent application was filed. 

That is incorrect; patentability may consider all of the characteristics possessed by the claimed invention, whenever those characteristics become manifest.

Does “Obvious to Try” Ever Apply to Pharmaceutical Products?

In addressing Glenmark’s reliance on KSR, Judge Newman emphasizes that the “obvious to try” rationale holds much less sway in the context of  ”the medical arts.” However, she does acknowledge that combination pharmaceutical products can be obvious when the components have been specifically identified in the prior art and the combination does not exhibit any unexpected results. Thus, when supporting patentability of a combination product, it can be important to establish unpredictability and, where possible, unexpected results.