Sound patent protection is a necessity to justify the time and expense of developing new pharmaceutical products. To be patentable, an invention must be completely novel and be the result of inventive activity, that is, it would not have been obvious to a skilled person at the time it was made. But when is this the case?

In spring 2007, the Supreme Court ruled on KSR International v. Teleflex, commenting for the first time in decades on the meaning of "obviousness" under patent law. Although KSR did not involve a pharmaceutical patent, there has been concern that the ruling would make it harder to defend existing patents. Moreover, some infringers argued that principles of chemical patent law should be jettisoned to the detriment of pharmaceutical patentees. Fortunately, as the dust clears, the KSR case and subsequent decisions are providing a clearer map for navigating this uncertain legal landscape.

In KSR, the Supreme Court struck down as obvious a patent for an adjustable automotive pedal assembly, declaring that the pedal assembly merely combined previously known parts (such as an electric sensor and an adjustable pedal) to yield "predictable" results. According to the Court, when a patent simply combines previously known elements to produce a result that was no more than expected, the combination would be obvious. On the other hand, inventions involving known elements that work together in an unpredictable manner would not be obvious.

Thus, an important principle reaffirmed in KSR is that a patent is more likely to be upheld if an invention is unpredictable in view of what was already known. This is good news for pharmaceutical innovators, because drug development is notoriously unpredictable.

Unpredictable Benefits

The Supreme Court in KSR provided guidance on predictability: if there is market pressure to solve a particular problem, few possible solutions, and predictable results, then a skilled person has good reason to pursue the invention, and one's ultimate success might be viewed as obvious. However, if the field prior to the invention is littered with cautionary tales that "taught away" from the invention—such as failures or concerns about the feasibility, safety, or efficacy of the invention—then the inventor's ultimate success would not be deemed obvious.

This emphasis on unpredictability was illustrated in recent litigation concerning Eisai's antiulcer drug AcipHex (rabeprazole), which garners over $1-billion in annual worldwide sales.  The infringer alleged that the patented compound was obvious because a skilled person would have known to prune a particular chemical side chain from a structurally similar known compound to yield the patented drug. The court, however, determined that this modification was not a "predictable solution," because that side group was credited in a prior publication with bestowing certain desirable traits. Consequently, the advantages of pruning the side chain were not predictable and the patent not obvious.

Litigation involving Takeda's Actos (pioglitazone), a $2-billion diabetes drug, demonstrates the importance of "teaching away" to assessing patent obviousness. The infringer alleged that the patented compound was obvious over a known "compound b." However, compound b had negative effects, including increased body weight. Because of these effects, the court determined that modifying compound b was not a "predictable" solution for diabetes.

What does all this mean for pharmaceutical patent owners? While it is relatively common to document surprising or unexpectedly positive results, it may be similarly helpful to catalog the blind alleys and failures that predated ultimate success. We recommend close coordination between research and legal functions to identify and maintain helpful documents and to interview key individuals. Even if it is not possible to follow such an approach with every patent filing, if you are (or anticipate) defending a patent's validity, it is never too early to begin compiling evidence of unpredictability and teaching away. Commercial pharmaceuticals are typically the lucky result of extensive screening and testing from laboratory assays to clinical trials. Documenting and telling the story of how a particular compound beat the odds can be the difference between success and failure in patent litigation.

The KSR decision weakened predictable mechanical combination patents by making them easier to invalidate. But the unpredictability of drug development suggests that KSR will have less effect in pharmaceutical patent litigation. Innovator companies can inoculate themselves against patent challenges by clearly establishing actual facts that taught away from their inventions.