In 1966, Graham v. John Deere Co. held that the following must be considered to determine if a patent claim is obvious: determine the scope and content of the prior art; determine the differences between the prior art and the claim at issue; assess the level of ordinary skill in the pertinent art; and evaluate evidence of secondary considerations which are the objective indicia of non-obviousness which include evidence of commercial success, long-felt but unsolved needs, failure of others, and unexpected results. Secondary considerations do not need to be mentioned in the patent disclosures or claims. The ultimate determination of obviousness is a legal conclusion but the underlying Graham inquiries are factual. The scope of the claimed invention is determined by giving the claims the broadest reasonable interpretation consistent with the specification.
2007’s KSR International Co. v. Teleflex Inc. rejected the Federal Circuit’s previously followed rigid teaching, suggestion or motivation (TSM) test for obviousness and held that obviousness analysis must be more flexible to include other factors, like combining prior art elements according to known methods to yield predictable results, simple substitution of one known element for another to obtain predictable results, situations which are obvious to try like choosing from a finite number of identified predictable solutions with a reasonable expectation of success, and other factors.
In pharmaceuticals, lead compound obviousness analysis usually involves analyzing the substitution of a portion of a structurally similar known compound to arrive at the claimed compound. In re Dillon, from the Federal Circuit in 1990, held that a prima facie case of obviousness was established if the prior art suggests or motivates the selection of a structurally similar claimed compound and the prior art had any utility. It was not necessary for the prior art compound to have the same or similar utility as the claimed compound.
The Federal Circuit in 2000, in Yamanouchi Pharm. Co., Ltd. v. Danbury Pharmacal, Inc., provided a lead compound analysis for obviousness which consisted of two steps: first, determining whether a chemist of ordinary skill in the art would select the prior art compounds as lead compounds for modification and next, determining whether the prior art would provide some motivation or reason to a chemist to modify these lead compounds to make the claimed compound. This decision has been misinterpreted in some subsequent cases to suggest that the “lead compound” must be the one that would have been selected by the inventor with the particular goal of making a new commercial drug product. Under KSR and In re Dillon, a lead compound could be any compound that has utility and the motivation to modify it could be simply to make another compound with similar utility.
Some of the Federal Circuit’s decisions of lead compound obviousness analysis appear to be inconsistent post-KSR. Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd. in 2008 held that obviousness based on structural similarity can be proved by “identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound.” Any known compound might possibly serve as a lead compound. In keeping the obviousness inquiry flexible, the requisite motivation can come from any number of sources and need not necessarily be explicit in the art.
By contrast, Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd. from 2007 held that the patent was not obvious because the prior art taught away from the claimed compound. It held that a lead compound means a compound in the prior art that would be most promising to modify in order to improve upon its activity and obtain a compound with better activity. This decision seems inconsistent with both KSR and In re Dillon, because it looks to the motivation of the particular inventor—i.e., to make a better compound. The person of ordinary skill in the art, however, can have any motivation. A compound with a known utility can motivate a person of ordinary skill to make another compound with the same utility, not necessarily a better or even as good a utility as the prior art compound.
Similarly, 2009’s Procter & Gamble Co. v. Teva Pharm. stated that “an obviousness argument based on structural similarity between claimed and prior art compounds clearly depends on a preliminary finding that one or ordinary skill in the art would have selected [the prior art compound] as a lead compound.” Again, the holding is inconsistent with KSR if the court meant that the “lead compound” must be one that would be selected to satisfy the particular inventor’s goal, such as making a commercial product. The same year, Altana Pharma AG v. Teva Pharm.held that there must be some reason for a chemist to select and modify a known compound to establish a prima facie case of obviousness. That statement is true as far as it goes, but it should be understood that any reason to select the compound as a starting point, such as it has some known utility, should suffice to render the claimed compound obvious if the modification is one that is suggested by the art or which would lead a person of ordinary skill to believe that the modification would result in a compound with the same utility as the prior art compound.
In the later Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., the Federal Circuit appeared to be applying a more rigid test for obviousness specifically forbidden by the Supreme Court in KSR and the en banc decision in In re Dillon. Here, the court held that the selection of the lead compound should also take into consideration the compound’s properties. It found that structural similarity between prior art compound and the claimed compound is not enough to render the claimed compound obvious. If the similarity was such that the claimed compound would have been expected to have at least the same utility, and if there was any reason for making the modification, the claimed compound should have been held to be prima facie obvious.
Recently, in this year’s Bristol-Myers Squibb Co. v. Teva Pharm., the court now seems to be setting a higher hurdle for establishing nonobviousness based on unexpected results. Here the court held that a compound is obvious where only small conservative changes are required to the lead compound to make the claimed compound and the prior art teachings would have motivated a chemist to make the claimed compound. Responding to the patent holders contention that a new chemical entity, as a matter of law, cannot be obvious when the claimed invention possesses unexpected properties, the court cited its en banc decision in In re Dillonand explained that an unexpected result or property does not by itself support a finding of nonobviousness. The court added that while a marked superiority in an expected property may be enough in some circumstances to render a compound patentable, a mere difference in degree is insufficient, and differences in degree of a known and expected property are not as persuasive in rebutting obviousness as differences in kind. The Federal Circuit recently denied a petition for rehearing or rehearing en banc by Bristol-Myers Squibb Company, but denied that the decision announced a new standard.
Similarly, in Hoffmann-La Roche Inc. v. Apotex Inc., the court held the patent to be obvious because the prior art had suggested the success of intermittent dosing and also suggested the appropriate dosage size. The court stated that “[t]he evidence of superior efficacy does nothing to undercut the showing that there was a reasonable expectation of success with the 150 mg monthly dose, even if the level of success may have turned out to be somewhat greater than would have been expected.”
The Federal Circuit, after applying a more rigid lead compound obviousness analysis in Otsuka, now appears to be leaning to a more flexible approach in keeping with the dictates of KSR and In re Dillon as evidenced in its recent decisions in Bristol-Myers and Hoffmann-La Roche. However, making the two step lead compound analysis test a necessary part of pharmaceutical obviousness inquiries appears to create an extra hurdle for generics and also appears to be a deviation of the holdings of In re Dillon.