Example 1:

The claimed invention in was directed to a method for decaffeinating coffee or tea. The prior art (Pagliaro) method produced a decaffeinated vegetable material and trapped the caffeine in a fatty material (such as oil). The caffeine was then removed from the fatty material by an aqueous extraction process. Applicant (Fout) substituted an evaporative distillation step for the aqueous extraction step. The prior art (Waterman) suspended coffee in oil and then directly distilled the caffeine through the oil. The court found that “[b]ecause both Pagliaro and Waterman teach a method for separating caffeine from oil, it would have been prima facie obvious to substitute one method for the other. Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious.”

Example 2:

The claimed invention in In re O’Farrell, was directed to a method for synthesizing a protein in a transformed bacterial host species by substituting a heterologous gene for a gene native to the host species. Generally speaking, protein synthesis in vivo follows a path from DNA to mRNA. Although the prior art Polisky article (authored by two of the three inventors of the application) had explicitly suggested employing the method described for protein synthesis, the inserted heterologous gene exemplified in the article was one that normally did not proceed all the way to the protein production step, but instead terminated with the mRNA. A second reference to Bahl had described a general method of inserting chemically synthesized DNA into a plasmid. Thus, it would have been obvious to one of ordinary skill in the art to replace the prior art gene with another gene known to lead to protein production, because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable.

In response to applicant’s argument that there had been significant unpredictability in the field of molecular biology at the time of the invention, the court stated that the level of skill was quite high and that the teachings of Polisky, even taken alone, contained detailed enabling methodology and included the suggestion that the modification would be successful for synthesis of proteins.

This is not a situation where the rejection is a statement that it would have been “obvious to try” without more. Here there was a reasonable expectation of success. “Obviousness does not require absolute predictability of success.”

Example 3:

The fact pattern in Ruiz v. AB Chance Co., is set forth above in Example 2 in subsection I.A., above.

The prior art showed differing load-bearing members and differing means of attaching the foundation to the member. Therefore, it would have been obvious to one of ordinary skill in the art to substitute the metal bracket taught in Gregory for Fuller’s concrete haunch for the predictable result of transferring the load.

Example 4:

The claimed invention in Ex parte Smith, was a pocket insert for a bound book made by gluing a base sheet and a pocket sheet of paper together to form a continuous two-ply seam defining a closed pocket. The prior art (Wyant) disclosed at least one pocket formed by folding a single sheet and securing the folder portions along the inside margins using any convenient bonding method. The prior art (Wyant) did not disclose bonding the sheets to form a continuous two-ply seam. The prior art (Dick) disclosed a pocket that is made by stitching or otherwise securing two sheets along three of its four edges to define a closed pocket with an opening along its fourth edge.

In considering the teachings of Wyant and Dick, the Board “found that (1) each of the claimed elements is found within the scope and content of the prior art; (2) one of ordinary skill in the art could have combined the elements as claimed by methods known at the time the invention was made; and (3) one of ordinary skill in the art would have recognized at the time the invention was made that the capabilities or functions of the combination were predictable.” Citing KSR, the Board concluded that “[t]he substitution of the continuous, two-ply seam of Dick for the folded seam of Wyant thus is no more than the simple substitution of one known element for another or the mere application of a known technique to a piece of prior art ready for improvement.

Example 5:

The claimed invention in In re ICON Health & Fitness, Inc., was directed to a treadmill with a folding tread base that swivels into an upright storage position, including a gas spring connected between the tread base and the upright structure to assist in stably retaining the tread base in the storage position. On reexamination, the examiner rejected the claims as obvious based on a combination of references including an advertisement (Damark) for a folding treadmill demonstrating all of the claim elements other than the gas spring, and a patent (Teague) with a gas spring. Teague was directed to a bed that folds into a cabinet using a novel dual-action spring that reverses force as the mechanism passes a neutral position, rather than a single-action spring that would provide a force pushing the bed closed at all times. The dual-action spring reduced the force required to open the bed from the closed position, while reducing the force required to lift the bed from the open position.
The Federal Circuit addressed the propriety of making the combination since Teague was in a different field than the application. Teague was found to be reasonably pertinent to the problem addressed in the application because the folding mechanism did not require any particular focus on treadmills, but rather generally addressed problems of supporting the weight of such a mechanism and providing a stable resting position.

The court also considered whether one skilled in the art would have been led to combine the teachings of Damark and Teague. Appellant argued that Teague teaches away from the invention because it directs one skilled in the art not to use single-action springs and does not satisfy the claim limitations as the dual-action springs would render the invention inoperable. The Federal Circuit considered these arguments and found that, while Teague at most teaches away from using single-action springs to decrease the opening force, it actually instructed that single-action springs provide the result desired by the inventors, which was to increase the opening force provided by gravity. As to inoperability, the claims were not limited to single-action springs and were so broad as to encompass anything that assists in stably retaining the tread base, which is the function that Teague accomplished. Additionally, the fact that the counterweight mechanism from Teague used a large spring, which appellant argued would overpower the treadmill mechanism, ignores the modifications that one skilled in the art would make to a device borrowed from the prior art. One skilled in the art would size the components from Teague appropriately for the application.
ICON is another useful example for understanding the scope of analogous art. The art applied concerned retaining mechanisms for folding beds, not treadmills. When determining whether a reference may properly be applied to an invention in a different field of endeavor, it is necessary to consider the problem to be solved. It is certainly possible that a reference may be drawn in such a way that its usefulness as a teaching is narrowly restricted. However, in ICON, the problem to be solved was not limited to the teaching of the “treadmill” concept. The Teague reference was analogous art because “Teague and the current application both address the need to stably retain a folding mechanism,” and because “nothing about ICON’s folding mechanism requires any particular focus on treadmills."

ICON is also informative as to the relationship between the problem to be solved and existence of a reason to combine. “Indeed, while perhaps not dispositive of the issue, the finding that Teague, by addressing a similar problem, provides analogous art to ICON’s application goes a long way towards demonstrating a reason to combine the two references. Because ICON’s broad claims read on embodiments addressing that problem as described by Teague, the prior art here indicates a reason to incorporate its teachings.”

The Federal Circuit’s discussion in ICON also makes clear that if the reference does not teach that a combination is undesirable, then it cannot be said to teach away. An assessment of whether a combination would render the device inoperable must not “ignore the modifications that one skilled in the art would make to a device borrowed from the prior art.”

Example 6:

Agrizap, Inc. v. Woodstream Corp., involved a stationary pest control device for electrocution of pests such as rats and gophers, in which the device is set in an area where the pest is likely to encounter it. The only difference between the claimed device and the prior art stationary pest control device was that the claimed device employed a resistive electrical switch, while the prior art device used a mechanical pressure switch. A resistive electrical switch was taught in two prior art patents, in the contexts of a hand-held pest control device and a cattle prod.

In determining that the claimed invention was obvious, the Federal Circuit noted that “[t]he asserted claims simply substitute a resistive electrical switch for the mechanical pressure switch” employed in the prior art device.

In this case, the prior art concerning the hand-held devices revealed that the function of the substituted resistive electrical switch was well known and predictable, and that it could be used in a pest control device. According to the Federal Circuit, the references that taught the hand-held devices showed that “the use of an animal body as a resistive switch to complete a circuit for the generation of an electric charge was already well known in the prior art.”

Finally, the Federal Circuit noted that the problem solved by using the resistive electrical switch in the prior art hand-held devices – malfunction of mechanical switches due to dirt and dampness – also pertained to the prior art stationary pest control device.

The Federal Circuit recognized Agrizap as “a textbook case of when the asserted claims involve a combination of familiar elements according to known methods that does no more than yield predictable results.” Agrizap exemplifies a strong case of obviousness based on simple substitution that was not overcome by the objective evidence of nonobviousness offered. It also demonstrates that analogous art is not limited to the field of applicant’s endeavor, in that one of the references that used an animal body as a resistive switch to complete a circuit for the generation of an electric charge was not in the field of pest control.

Example 7:

The invention at issue in Muniauction, Inc. v. Thomson Corp., was a method for auctioning municipal bonds over the Internet. A municipality could offer a package of bond instruments of varying principal amounts and maturity dates, and an interested buyer would then submit a bid comprising a price and interest rate for each maturity date. It was also possible for the interested buyer to bid on a portion of the offering. The claimed invention considered all of the noted parameters to determine the best bid. It operated on conventional Web browsers and allowed participants to monitor the course of the auction.

The only difference between the prior art bidding system and the claimed invention was the use of a conventional Web browser. At trial, the district court had determined that Muniauction’s claims were not obvious. Thomson argued that the claimed invention amounted to incorporating a Web browser into a prior art auction system, and was therefore obvious in light of KSR. Muniauction rebutted the argument by offering evidence of skepticism by experts, copying, praise, and commercial success. Although the district court found the evidence to be persuasive of nonobviousness, the Federal Circuit disagreed. It noted that a nexus between the claimed invention and the proffered evidence was lacking because the evidence was not coextensive with the claims at issue. For this reason, the Federal Circuit determined that Muniauction’s evidence of secondary considerations was not entitled to substantial weight.

The Federal Circuit analogized this case to Leapfrog Enters., Inc. v. Fisher-Price, Inc. The Leapfrog case involved a determination of obviousness based on application of modern electronics to a prior art mechanical children’s learning device. In Leapfrog, the court noted that market pressures would have prompted a person of ordinary skill to use modern electronics in the prior art device. Similarly in Muniauction, market pressures would have prompted a person of ordinary skill to use a conventional Web browser in a method of auctioning municipal bonds.

Example 8:

In Aventis Pharma Deutschland v. Lupin, the claims were drawn to the 5(S) stereoisomer of the blood pressure drug ramipril in stereochemically pure form, and to compositions and methods requiring 5(S) ramipril. The 5(S) stereoisomer is one in which all five stereocenters in the ramipril molecule are in the S rather than the R configuration. A mixture of various stereoisomers including 5(S) ramipril had been taught by the prior art. The question before the court was whether the purified single stereoisomer would have been obvious over the known mixture of stereoisomers.

The record showed that the presence of multiple S stereocenters in drugs similar to ramipril was known to be associated with enhanced therapeutic efficacy. For example, when all of the stereocenters were in the S form in the related drug enalapril (SSS enalapril) as compared with only two stereocenters in the S form (SSR enalapril), the therapeutic potency was 700 times as great.

There was also evidence to indicate that conventional methods could be used to separate the various stereoisomers of ramipril.

The district court saw the issue as a close case, because, in its view, there was no clear motivation in the prior art to isolate 5(S) ramipril. However, the Federal Circuit disagreed, and found that the claims would have been obvious. The Federal Circuit cautioned that requiring such a clearly stated motivation in the prior art to isolate 5(S) ramipril ran counter to the Supreme Court’s decision in KSR, and the court stated:

Requiring an explicit teaching to purify the 5(S) stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR.

The Aventis court also relied on the settled principle that in chemical cases, structural similarity can provide the necessary reason to modify prior art teachings. The Federal Circuit also addressed the kind of teaching that would be sufficient in the absence of an explicitly stated prior art-based motivation, explaining that an expectation of similar properties in light of the prior art can be sufficient, even without an explicit teaching that the compound will have a particular utility.
In the chemical arts, the cases involving so-called “lead compounds” form an important subgroup of the obviousness cases that are based on substitution. The Federal Circuit has had a number of opportunities since the KSR decision to discuss the circumstances under which it would have been obvious to modify a known compound to arrive at a claimed compound. The following cases explore the selection of a lead compound, the need to provide a reason for any proposed modification, and the predictability of the result.

Example 9:

Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., concerns the pharmaceutical compound rabeprazole. Rabeprazole is a proton pump inhibitor for treating stomach ulcers and related disorders. The Federal Circuit affirmed the district court’s summary judgment of nonobviousness, stating that no reason had been advanced to modify the prior art compound in a way that would destroy an advantageous property.

Co-defendant Teva based its obviousness argument on the structural similarity between rabeprazole and lansoprazole. The compounds were recognized as sharing a common core, and the Federal Circuit characterized lansoprazole as a “lead compound.” The prior art compound lansoprazole was useful for the same indications as rabeprazole, and differed from rabeprazole only in that lansoprazole has a trifluoroethoxy substituent at the 4-position of the pyridine ring, while rabeprazole has a methoxypropoxy substituent. The trifluoro substituent of lansoprazole was known to be a beneficial feature because it conferred lipophilicity to the compound. The ability of a person of ordinary skill to carry out the modification to introduce the methoxypropoxy substituent, and the predictability of the result were not addressed.

Despite the significant similarity between the structures, the Federal Circuit did not find any reason to modify the lead compound. According to the Federal Circuit:

Obviousness based on structural similarity thus 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. . . . In keeping with the flexible nature of the obviousness inquiry, the requisite motivation can come from any number of sources and need not necessarily be explicit in the art. Rather “it is sufficient to show that the claimed and prior art compounds possess a ‘sufficiently close relationship . . . to create an expectation,’ in light of the totality of the prior art, that the new compound will have ‘similar properties’ to the old.”

The prior art taught that introducing a fluorinated substituent was known to increase lipophilicity, so a skilled artisan would have expected that replacing the trifluoroethoxy substituent with a methoxypropoxy substituent would have reduced the lipophilicity of the compound. Thus, the prior art created the expectation that rabeprazole would be less useful than lansoprazole as a drug for treating stomach ulcers and related disorders because the proposed modification would have destroyed an advantageous property of the prior art compound. The compound was not obvious as argued by Teva because, upon consideration of all of the facts of the case, a person of ordinary skill in the art at the time of the invention would not have had a reason to modify lansoprazole so as to form rabeprazole.

Office personnel are cautioned that the term “lead compound” in a particular opinion can have a contextual meaning that may vary from the way a pharmaceutical chemist might use the term. In the field of pharmaceutical chemistry, the term “lead compound” has been defined variously as “a chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters;” “[a] compound that exhibits pharmacological properties which suggest its development;” and “a potential drug being tested for safety and efficacy.”

The Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound: “Obviousness based on structural similarity thus 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.”

Thus, Office personnel should recognize that a proper obviousness rejection of a claimed compound that is useful as a drug might be made beginning with an inactive compound, if, for example, the reasons for modifying a prior art compound to arrive at the claimed compound have nothing to do with pharmaceutical activity. The inactive compound would not be considered to be a lead compound by pharmaceutical chemists, but could potentially be used as such when considering obviousness. Office personnel might also base an obviousness rejection on a known compound that pharmaceutical chemists would not select as a lead compound due to expense, handling issues, or other business considerations. However, there must be some reason for starting with that lead compound other than the mere fact that the “lead compound” merely exists.

Example 10:

The claimed chemical compound was also found to be nonobvious in Procter & Gamble Co. v. Teva Pharm. USA, Inc. The compound at issue was risedronate – the active ingredient of Procter & Gamble’s osteoporosis drug Actonel®. Risedronate is an example of a bisphosphonate, which is a class of compounds known to inhibit bone resorption.

When Procter & Gamble sued Teva for infringement, Teva defended by arguing invalidity for obviousness over one of Procter & Gamble’s earlier patents. The prior art patent did not teach risedronate, but instead taught thirty-six other similar compounds including 2-pyr EHDP that were potentially useful with regard to osteoporosis. Teva argued obviousness on the basis of structural similarity to 2-pyr EHDP, which is a positional isomer of risedronate.

The district court found no reason to select 2-pyr EHDP as a lead compound in light of the unpredictable nature of the art, and no reason to modify it so as to obtain risedronate. In addition, there were unexpected results as to potency and toxicity. Therefore the district court found that Teva had not made a prima facie case, and even if it had, it was rebutted by evidence of unexpected results.

The Federal Circuit affirmed the district court’s decision. The Federal Circuit did not deem it necessary in this case to consider the question of whether 2-pyr EHDP had been appropriately selected as a lead compound. Rather, the Federal Circuit reasoned that, if 2-pyr EHDP is presumed to be an appropriate lead compound, there must be both a reason to modify it so as to make risedronate and a reasonable expectation of success. Here, there was no evidence that the necessary modifications would have been routine, so there would have been no reasonable expectation of success.

Procter & Gamble is also informative in its discussion of the treatment of secondary considerations of non-obviousness. Although the court found that no prima facie case of obviousness had been presented, it proceeded to analyze Procter & Gamble’s proffered evidence countering the alleged prima facie case in some detail, thus shedding light on the proper treatment of such evidence.

The Federal Circuit noted in dicta that even if a prima facie case of obviousness had been established, sufficient evidence of unexpected results was introduced to rebut such a showing. At trial, the witnesses consistently testified that the properties of risedronate were not expected, offering evidence that researchers did not predict either the potency or the low dose at which the compound was effective. Tests comparing risedronate to a compound in the prior art reference showed that risedronate outperformed the other compound by a substantial margin, could be administered in a greater amount without an observable toxic effect, and was not lethal at the same levels as the other compound. The weight of the evidence and the credibility of the witnesses were sufficient to show unexpected results that would have rebutted an obviousness determination. Thus, nonobviousness can be shown when a claimed invention is shown to have unexpectedly superior properties when compared to the prior art.

The court then addressed the evidence of commercial success of risedronate and the evidence that risedronate met a long felt need. The court pointed out that little weight was to be afforded to the commercial success because the competing product was also assigned to Procter & Gamble. However, the Federal Circuit affirmed the district court’s conclusion that risedronate met a long-felt, but unsatisfied need. The court rejected Teva’s contention that because the competing drug was available before Actonel7, there was no unmet need that the invention satisfied. The court emphasized that whether there was a long-felt but unsatisfied need is to be evaluated based on the circumstances as of the filing date of the challenged invention – not as of the date that the invention is brought to market.

It should be noted that the lead compound cases do not stand for the proposition that identification of a single lead compound is necessary in every obviousness rejection of a chemical compound. For example, one might envision a suggestion in the prior art to formulate a compound having certain structurally defined moieties, or moieties with certain properties. If a person of ordinary skill would have known how to synthesize such a compound, and the structural and/or functional result could reasonably have been predicted, then a prima facie case of obviousness of the claimed chemical compound might exist even without identification a particular lead compound. As a second example, it could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. Thus, Office personnel should recognize that in certain situations, it may be proper to reject a claimed chemical compound as obvious even without identifying a single lead compound.

Example 11:

The decision reached by the Federal Circuit in Altana Pharma AG v. Teva Pharm. USA, Inc, as discussed below, involved a motion for preliminary injunction and did not include a final determination of obviousness. However, the case is instructive as to the issue of selecting a lead compound.

The technology involved in Altana was the compound pantoprazole, which is the active ingredient in Altana’s antiulcer drug Protonix®. Pantoprazole belongs to a class of compounds known as proton pump inhibitors that are used to treat gastric acid disorders in the stomach.

Altana accused Teva of infringement. The district court denied Altana’s motion for preliminary injunction for failure to establish a likelihood of success on the merits, determining that Teva had demonstrated a substantial question of invalidity for obviousness in light of one of Altana’s prior patents. Altana’s patent discussed a compound referred to as compound 12, which was one of eighteen compounds disclosed. The claimed compound pantoprazole was structurally similar to compound 12. The district court found that one of ordinary skill in the art would have selected compound 12 as a lead compound for modification, and the Federal Circuit affirmed.

Obviousness of a chemical compound in view of its structural similarity to a prior art compound may be shown by identifying some line of reasoning that would have led one of ordinary skill in the art to select and modify the prior art compound in a particular way to produce the claimed compound. The necessary line of reasoning can be drawn from any number of sources and need not necessarily be explicitly found in the prior art of record. The Federal Circuit determined that ample evidence supported the district court’s finding that compound 12 was a natural choice for further development.

For example, Altana’s prior art patent claimed that its compounds, including compound 12, were improvements over the prior art; compound 12 was disclosed as one of the more potent of the eighteen compounds disclosed; the patent examiner had considered the compounds of Altana’s prior art patent to be relevant during the prosecution of the patent in suit; and experts had opined that one of ordinary skill in the art would have selected the eighteen compounds to pursue further investigation into their potential as proton pump inhibitors.

In response to Altana’s argument that the prior art must point to only a single lead compound for further development, the Federal Circuit stated that a “restrictive view of the lead compound test would present a rigid test similar to the teaching-suggestion-motivation test that the Supreme Court explicitly rejected in KSR . . . . The district court in this case employed a flexible approach – one that was admittedly preliminary – and found that the defendants had raised a substantial question that one of skill in the art would have used the more potent compounds of [Altana’s prior art] patent, including compound 12, as a starting point from which to pursue further development efforts. That finding was not clearly erroneous.”