Patent Baristas

After a final judgment upholding the validity of the Procter & Gamble Company U.S. Patent 5,583,122, Teva Pharmaceuticals appealed to the US United States Court of Appeals for the Federal Circuit claiming invalidity defenses of obviousness and obviousness-type double patenting.  It fell on deaf ears as the Federal Circuit affirmed the validity. P&G v. Teva Pharma (08-1404-1406).

The ’122 patent claims the compound risedronate, the active ingredient of P&G’s osteoporosis drug Actonel®. In August 2004, P&G sued Teva after Teva planned to market risedronate as a generic equivalent of Actonel®. Teva argued that the ’122 patent was invalid as obvious in light of P&G’s expired U.S. Patent 4,761,406. If that didn’t work, Teva also argued that the ’122 patent is invalid for obviousness-type double patenting.

Risedronate is a member of a group of compounds referred to as bisphosphonates. Bisphosphonates, in general, are active in inhibiting bone resorption. The first two promising bisphosphonates studied for the treatment of metabolic bone diseases, etidronate (EHDP) and clodronate, had clinical problems which prevented their commercialization. P&G conducted a significant amount of experimentation involving hundreds of different bisphosphonate compounds, but could not predict the efficacy or toxicity of the new compounds. Eventually, researchers at P&G identified risedronate as a promising drug candidate.

The district court concluded that the ’406 patent would not have led a person of ordinary skill in the art to identify 2-pyr EHDP as the lead compound. In light of the extremely unpredictable nature of bisphosphonates at the time of the invention, the district court also found that a person of ordinary skill in the art would not have been motivated to make the specific molecular modifications to make risedronate.

The obviousness determination turns on underlying factual inquiries involving: (1) the scope and content of prior art, (2) differences between claims and prior art, (3) the level of ordinary skill in pertinent art, and (4) secondary considerations such as commercial success and satisfaction of a long-felt need.

If a patent challenger makes a prima facie showing of obviousness, the owner may rebut based on “unexpected results” by demonstrating “that the claimed invention exhibits some superior property or advantage that a person of ordinary skill in the relevant art would have found surprising or unexpected.”

Identification of a Lead Compound

An obviousness argument based on structural similarity between claimed and prior art compounds “clearly depends on a preliminary finding that one of ordinary skill in the art would have selected [the prior art compound] as a lead compound.” Even then, the Federal Circuit saw no need to dwell on this point:

We need not reach this question because we conclude that even if 2-pyr EHDP was a lead compound, the evidence does not establish that it would have been obvious to a person of ordinary skill at the time of the invention to modify 2-pyr EHDP to create risedronate.

Obviousness of Risedronate in Light of the Prior Art

To decide whether risedronate was obvious in light of the prior art, a court must determine whether, at the time of invention, a person having ordinary skill in the art would have had “reason to attempt to make the composition” known as risedronate and “a reasonable expectation of success in doing so.”

The district court concluded that, even if 2-pyr EHDP were a lead compound, it would not render the ’122 patent’s claims on risedronate obvious because a person having ordinary skill in the art would not have had reason to make risedronate based on the prior art. The district court concluded that there could have been no reasonable expectation as to risedronate’s success. The Federal Circuit agreed:

The question of obviousness “often turns on the structural similarities and differences between the claimed compound and the prior art compound.”

To successfully argue that a new compound is obvious, the challenger may show “that the prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention.” Thus, in addition to structural similarity between the compounds, a prima facie case of obviousness may be shown by “adequate support in the prior art” for the change in structure.

In light of the Supreme Court’s instruction in KSR, the Federal Circuit has stated that, “[t]o the extent an art is unpredictable, as the chemical arts often are, KSR’s focus on ‘identified, predictable solutions’ may present a difficult hurdle because potential solutions are less likely to be genuinely predictable.” Eisai, 533 F.3d 1353, 1359 (quoting KSR, 127 S. Ct. at 1742). The district court found that Teva failed to clear that hurdle, establishing insufficient motivation for a person of ordinary skill to synthesize and test risedronate. This finding was not clearly erroneous.

Cases following KSR have considered whether a given molecular modification would have been carried out as part of routine testing. See, e.g., Takeda, 492 F.3d at 1360 (discussing the district court’s finding that a modification was not known to be beneficial and was not considered “routine”). When a person of ordinary skill is faced with “a finite number of identified, predictable solutions” to a problem and pursues “the known options within his or her technical grasp,” the resulting discovery “is likely the product not of innovation but of ordinary skill and common sense.”

In this case, there is no credible evidence that the structural modification was routine.