To be patentable, an invention must not have been obvious at the time the invention was made. But how do courts actually determine this?
The fundamental difficulty is that courts are being asked to make a hypothetical judgment—whether or not an invention would have been obvious—long after the fact. The patent law is clear that the judgment should be made based only on what was known at the time the invention was made, and that the way in which the inventor developed the invention—whether by flash of genius or trial and error—should not be relevant. Unfortunately, even though legally it should not, hindsight and the inventor's own work can color this determination, since inventions often seem obvious after the fact.
One of the best counters to the use of hindsight is objective evidence (sometimes called "secondary considerations"), because this type of evidence provides concrete guideposts that are less susceptible to the distortions of time. There are a number of widely-accepted forms of objective evidence.
- Failure of others: Did others try but fail?
- Commercial success: Has the invention been well-received in the market as demonstrated through sales and market share?
- Industry acceptance: Have others licensed the patent?
- Long-felt need: Did the invention solve a long-known problem?
- Unexpected results: Were the results unexpected in view of teachings in the relevant field?
- Skepticism of others: Did others express disbelief about the safety or efficacy of the invention?
- Copying of others: Once the invention became known, did others try to copy it?
Although not formally required to overcome an obviousness challenge, the importance of this type of evidence should not be overlooked. Notably, the Supreme Court reaffirmed its relevance in 2007, categorizing objective evidence in KSR International v. Teleflex as a core part of the obviousness determination. Indeed, the Court in KSR cited the lack of favorable objective evidence as one factor in invalidating the patent in that case.
A pair of facially-similar cases involving patents for drug stereoisomers illustrates how differences in objective evidence can lead to very different outcomes.
In the first case, the patent covering Forest Pharmaceutical's antidepressant Lexapro (escitalopram oxalate), a selective serotonin reuptake inhibitor, was upheld as non-obvious. The patent related to a substantially pure "stereoisomer" of escitalopram. The infringer contended that the claimed invention would have been obvious in view of known mixtures of stereoisomers, known techniques to separate stereoisomers, and a general expectation that one stereoisomer would be more potent than the other.
But this analysis was not found persuasive. First, both the inventors and others had previously failed in efforts to resolve the stereoisomer. Second, the pure stereoisomer was unexpectedly found to have twice the potency of the known mixture. Third, the drug was shown to be a commercial success. In view of this favorable objective evidence, all of which suggested that the invention would not have been obvious, the court upheld the patent covering Lexapro, thereby maintaining patent exclusivity for the innovator company.
Six days later, the same court reached a dramatically different outcome in a case involving the patent covering the angiotensin-converting enzyme inhibitor (ACE inhibitor) Altace (ramipril) from King Pharmaceuticals. In that case, the patent recited compounds, hypotensive compositions, and methods for reducing blood pressure involving a particular stereoisomer of ramipril in which all five stereo centers in the compound adopt a spatial arrangement called an "S" configuration.
The infringer argued that the claimed invention would have been obvious over prior art references disclosing the structure of ramipril, a method of making ramipril that yielded a mixture of stereoisomers, and the knowledge that other ACE inhibitors were known to be more potent in the "all-S" configuration. Unlike in the case of Lexapro, there was no evidence of failure of others, and the court was not convinced that the "all-S" stereoisomer displayed unexpected benefits. Accordingly, the court concluded that the invention would have been obvious, invalidating the patent. Of particular relevance, the court expressly contrasted its holding with that of in the Lexapro case, where objective evidence supported the determination of non-obviousness.
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While the above illustrations involve pharmaceutical stereoisomers, favorable objective evidence can be critical for any patent litigation in which obviousness is in dispute. For example, favorable objective evidence was instrumental in fending off an obviousness challenge to a biotechnology patent claiming human recombinant erythropoietin (EPO).
The challenger argued that the patent would have been obvious over prior art disclosures of methods of creating EPO-producing cells. But the court was not persuaded, finding as highly probative evidence of a long-felt need for the mass production of EPO that had existed prior to the invention. The court also commented that many skilled artisans had tried but failed to produce recombinant EPO, and that the invention opened the floodgates to a lucrative market that was previously unavailable. In view of this favorable objective evidence, the court dismissed the challenger's obviousness arguments and upheld the validity of the patent.
What does all this mean for pharmaceutical patent owners? In litigation, particularly when facing an obviousness challenge to a patent, it is critical to present a compelling story of how the invention came about, including the blind alleys and failures as well as the ultimate success. We recommend compiling documents and recollections concerning important inventions before they are lost to the passage of time. While it is not feasible to take such steps with every patent filing, successful new pharmaceutical products face inevitable patent challenges from would be generic competitors. It is never too early to begin collecting evidence of unpredictability, teaching away, failure of others, and other objective evidence. In the end, such evidence can be the difference between success and failure in patent litigation.