Example 1:

The claimed invention in Pfizer, Inc. v. Apotex, Inc., was directed to the amlodipine besylate drug product, which was sold in tablet form in the United States under the trademark Norvasc®. Amlodipine and the use of besylate anions were both known at the time of the invention. Amlodipine was known to have the same therapeutic properties as were being claimed for the amlodipine besylate, but Pfizer discovered that the besylate form had better manufacturing properties (e.g., reduced “stickiness”).

Pfizer argued that the results of forming amlodipine besylate would have been unpredictable and therefore nonobvious. The court rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties.

The court found that one of ordinary skill in the art having problems with the machinability of amlodipine would have looked to forming a salt of the compound and would have been able to narrow the group of potential salt-formers to a group of 53 anions known to form pharmaceutically acceptable salts, which would be an acceptable number to form “a reasonable expectation of success.”

Example 2:

The claimed invention in Alza Corp. v. Mylan Labs., Inc., was drawn to sustained-release formulations of the drug oxybutynin in which the drug is released at a specified rate over a 24-hour period. Oxybutynin was known to be highly water-soluble, and the specification had pointed out that development of sustained-release formulations of such drugs presented particular problems.

A prior art patent to Morella had taught sustained-release compositions of highly water-soluble drugs, as exemplified by a sustained-release formulation of morphine. Morella had also identified oxybutynin as belonging to the class of highly water-soluble drugs. The Baichwal prior art patent had taught a sustained-release formulation of oxybutynin that had a different release rate than the claimed invention. Finally, the Wong prior art patent had taught a generally applicable method for delivery of drugs over a 24-hour period. Although Wong mentioned applicability of the disclosed method to several categories of drugs to which oxybutynin belonged, Wong did not specifically mention its applicability to oxybutynin.

The court found that because the absorption properties of oxybutynin would have been reasonably predictable at the time of the invention, there would have been a reasonable expectation of successful development of a sustained-release formulation of oxybutynin as claimed. The prior art, as evidenced by the specification, had recognized the obstacles to be overcome in development of sustained-release formulations of highly water-soluble drugs, and had suggested a finite number of ways to overcome these obstacles. The claims were obvious because it would have been obvious to try the known methods for formulating sustained-release compositions, with a reasonable expectation of success. The court was not swayed by arguments of a lack of absolute predictability.

Example 3:

The Federal Circuit’s decision in In re Kubin, affirmed the Office’s determination in Ex parte Kubin, that the claims in question, directed to an isolated nucleic acid molecule, would have been obvious over the prior art applied. The claim stated that the nucleic acid encoded a particular polypeptide. The encoded polypeptide was identified in the claim by its partially specified sequence, and by its ability to bind to a specified protein.

A prior art patent to Valiante taught the polypeptide encoded by the claimed nucleic acid, but did not disclose either the sequence of the polypeptide, or the claimed isolated nucleic acid molecule. However, Valiante did disclose that by employing conventional methods such as those disclosed by a prior art laboratory manual by Sambrook, the sequence of the polypeptide could be determined, and the nucleic acid molecule could be isolated. In view of Valiante’s disclosure of the polypeptide, and of routine prior art methods for sequencing the polypeptide and isolating the nucleic acid molecule, the Board found that a person of ordinary skill in the art would have had a reasonable expectation that a nucleic acid molecule within the claimed scope could have been successfully obtained.

Relying on In re Deuel, appellant argued that it was improper for the Office to use the polypeptide of the Valiante patent together with the methods described in Sambrook to reject a claim drawn to a specific nucleic acid molecule without providing a reference showing or suggesting a structurally similar nucleic acid molecule. Citing KSR, the Board stated that "when there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." The Board noted that the problem facing those in the art was to isolate a specific nucleic acid, and there were a limited number of methods available to do so. The Board concluded that the skilled artisan would have had reason to try these methods with the reasonable expectation that at least one would be successful. Thus, isolating the specific nucleic acid molecule claimed was “the product not of innovation but of ordinary skill and common sense.”

The Board’s reasoning was substantially adopted by the Federal Circuit. However, it is important to note that in the Kubin decision, the Federal Circuit held that “the Supreme Court in KSR unambiguously discredited” the Federal Circuit’s decision in Deuel, insofar as it “implies the obviousness inquiry cannot consider that the combination of the claim’s constituent elements was ‘obvious to try.’”

Instead, Kubin stated that KSR “resurrects” the Federal Circuit’s own wisdom in O’Farrell, in which “to differentiate between proper and improper applications of ‘obvious to try,’” the Federal Circuit “outlined two classes of situations where ‘obvious to try’ is erroneously equated with obviousness under § 103.”

These two classes of situations are: (1) when what would have been “obvious to try” would have been to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful; and (2) when what was “obvious to try” was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it.

Example 4:

Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., is an example of a chemical case in which the Federal Circuit found that the claimed invention was not obvious. The claimed compound was pioglitazone, a member of a class of drugs known as thiazolidinediones (TZDs) marketed by Takeda as a treatment for Type 2 diabetes. The Takeda case brings together the concept of a “lead compound” and the obvious-to-try argument.

Alphapharm had filed an Abbreviated New Drug Application with the Food and Drug Administration, which was a technical act of infringement of Takeda’s patent. When Takeda brought suit, Alphapharm’s defense was that Takeda’s patent was invalid due to obviousness. Alphapharm argued that a two-step modification – involving homologation and ring-walking – of a known compound identified as “compound b” would have produced pioglitazone, and that it was therefore obvious.

The district court found that there would have been no reason to select compound b as a lead compound. There were a large number of similar prior art TZD compounds; fifty-four were specifically identified in Takeda’s prior patent, and the district court observed that “hundreds of millions” were more generally disclosed. Although the parties agreed that compound b represented the closest prior art, one reference taught certain disadvantageous properties associated with compound b, which according to the district court would have taught the skilled artisan not to select that compound as a lead compound. The district court found no prima facie case of obviousness, and stated that even if a prima facie case had been established, it would have been overcome in this case in view of the unexpected lack of toxicity of pioglitazone.

The Federal Circuit affirmed the decision of the district court, citing the need for a reason to modify a prior art compound. The Federal Circuit quoted KSR, stating:

The KSR Court recognized that “[w]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.”

In such circumstances, “the fact that a combination was obvious to try might show that it was obvious under § 103.”

That is not the case here. Rather than identify predictable solutions for antidiabetic treatment, the prior art disclosed a broad selection of compounds any one of which could have been selected as a lead compound for further investigation. Significantly, the closest prior art compound (compound b, the 6-methyl) exhibited negative properties that would have directed one of ordinary skill in the art away from that compound. Thus, this case fails to present the type of situation contemplated by the Court when it stated that an invention may be deemed obvious if it was “obvious to try.” The evidence showed that it was not obvious to try.

Accordingly, Office personnel should recognize that the obvious to try rationale does not apply when the appropriate factual findings cannot be made. In Takeda, there was a recognized need for treatment of diabetes. However, there was no finite number of identified, predictable solutions to the recognized need, and no reasonable expectation of success. There were numerous known TZD compounds, and although one clearly represented the closest prior art, its known disadvantages rendered it unsuitable as a starting point for further research, and taught the skilled artisan away from its use. Furthermore, even if there had been reason to select compound b, there had been no reasonable expectation of success associated with the particular modifications necessary to transform compound b into the claimed compound pioglitazone. Thus, an obviousness rejection based on an obvious to try rationale was not appropriate in this situation.

Example 5:

The case of Ortho-McNeil Pharm., Inc. v. Mylan Labs, Inc., provides another example in which a chemical compound was determined not to be obvious. The claimed subject matter was topiramate, which is used as an anti-convulsant.

In the course of working toward a new anti-diabetic drug, Ortho-McNeil’s scientist had unexpectedly discovered that a reaction intermediate had anti-convulsant properties. Mylan’s defense of invalidity due to obviousness rested on an obvious to try argument. However, Mylan did not explain why it would have been obvious to begin with an anti-diabetic drug precursor, especially the specific one that led to topiramate, if one had been seeking an anti-convulsant drug. The district court ruled on summary judgment that Ortho-McNeil’s patent was not invalid for obviousness.

The Federal Circuit affirmed. The Federal Circuit pointed out that there was no apparent reason a person of ordinary skill would have chosen the particular starting compound or the particular synthetic pathway that led to topiramate as an intermediate. Furthermore, there would have been no reason to test that intermediate for anticonvulsant properties if treating diabetes had been the goal.

The Federal Circuit recognized an element of serendipity in this case, which runs counter to the requirement for predictability. Summarizing their conclusion with regard to Mylan’s obvious to try argument, the Federal Circuit stated:

[T]his invention, contrary to Mylan’s characterization, does not present a finite (and small in the context of the art) number of options easily traversed to show obviousness. . . . KSR posits a situation with a finite, and in the context of the art, small or easily traversed, number of options that would convince an ordinarily skilled artisan of obviousness. . . . [T]his clearly is not the easily traversed, small and finite number of alternatives that KSR suggested might support an inference of obviousness.

Thus, Ortho-McNeil helps to clarify the Supreme Court’s requirement in KSR for “a finite number” of predictable solutions when an obvious to try rationale is applied: under the Federal Circuit’s case law “finite” means “small or easily traversed” in the context of the art in question. As taught in Abbott, discussed above, it is essential that the inquiry be placed in the context of the subject matter at issue, and each case must be decided on its own facts.

Example 6:

In Bayer Schering Pharma A.G. v. Barr Labs., Inc., the claimed invention was an oral contraceptive containing micronized drospirenone marketed as Yasmin®. The prior art compound drospirenone was known to be a poorly water-soluble, acid-sensitive compound with contraceptive effects. It was also known in the art that micronization improves the solubility of poorly water soluble drugs.

Based on the known acid sensitivity, Bayer had studied how effectively an enteric-coated drospirenone tablet delivered a formulation as compared to an intravenous injection of the same formulation to measure the “absolute bioavailability” of the drug. Bayer added an unprotected (normal) drospirenone tablet and compared its bioavailability to that of the enteric-coated formulation and the intravenous delivery. Bayer expected to find that the enteric-coated tablet would produce a lower bioavailability than an intravenous injection, while the normal pill would produce an even lower bioavailability than the enteric-coated tablet. However, they found that despite observations that drospirenone would quickly isomerize in a highly acidic environment (supporting the belief that an enteric coating would be necessary to preserve bioavailability), the normal pill and the enteric-coated pill resulted in the same bioavailability. Following this study, Bayer developed micronized drospirenone in a normal pill, the basis for the disputed patent.

The district court found that a person having ordinary skill in the art would have considered the prior art result that a structurally related compound, spirorenone, though acid-sensitive, would nevertheless absorb in vivo, would have suggested the same result for drospirenone. It also found that while another reference taught that drospirenone isomerizes in vitro when exposed to acid simulating the human stomach, a person of ordinary skill would have been aware of the study’s shortcomings, and would have verified the findings as suggested by a treatise on the science of dosage form design, which would have then showed that no enteric coating was necessary.

The Federal Circuit held that the patent was invalid because the claimed formulation was obvious. The Federal Circuit reasoned that the prior art would have funneled the formulator toward two options. Thus, the formulator would not have been required to try all possibilities in a field unreduced by the prior art. The prior art was not vague in pointing toward a general approach or area of exploration, but rather guided the formulator precisely to the use of either a normal pill or an enteric-coated pill.

It is important for Office personnel to recognize that the mere existence of a large number of options does not in and of itself lead to a conclusion of nonobviousness. Where the prior art teachings lead one of ordinary skill in the art to a narrower set of options, then that reduced set is the appropriate one to consider when determining obviousness using an obvious to try rationale.

Example 7:

The case of Sanofi-Synthelabo v. Apotex, Inc., also sheds light on the obvious to try line of reasoning. The claimed compound was clopidogrel, which is the dextrorotatory isomer of methyl alpha- 5(4,5,6,7-tetrahydro(3,2-c)thienopyridyl)(2-chlorophenyl)-acetate. Clopidogrel is an anti-thrombotic compound used to treat or prevent heart attack or stroke. The racemate, or mixture of dextrorotatory and levorotatory (D- and L-) isomers of the compound, was known in the prior art. The two forms had not previously been separated, and although the mixture was known to have anti-thrombotic properties, the extent to which each of the individual isomers contributed to the observed properties of the racemate was not known and was not predictable.

The district court assumed that in the absence of any additional information, the D-isomer would have been prima facie obvious over the known racemate. However, in view of the evidence of unpredicted therapeutic advantages of the D-isomer presented in the case, the district court found that any prima facie case of obviousness had been overcome. At trial, the experts for both parties testified that persons of ordinary skill in the art could not have predicted the degree to which the isomers would have exhibited different levels of therapeutic activity and toxicity. Both parties’ experts also agreed that the isomer with greater therapeutic activity would most likely have had greater toxicity. Sanofi witnesses testified that Sanofi’s own researchers had believed that the separation of the isomers was unlikely to have been productive, and experts for both parties agreed that it was difficult to separate isomers at the time of the invention. Nevertheless, when Sanofi ultimately undertook the task of separating the isomers, it found that they had the “rare characteristic of ‘absolute stereoselectivity,’” whereby the D-isomer provided all of the favorable therapeutic activity but no significant toxicity, while the L-isomer produced no therapeutic activity but virtually all of the toxicity. Based on this record, the district court concluded that Apotex had not met its burden of proving by clear and convincing evidence that Sanofi’s patent was invalid for obviousness. The Federal Circuit affirmed the district court’s conclusion.

Office personnel should recognize that even when only a small number of possible choices exist, the obvious to try line of reasoning is not appropriate when, upon consideration of all of the evidence, the outcome would not have been reasonably predictable and the inventor would not have had a reasonable expectation of success. In Bayer, there were art-based reasons to expect that both the normal pill and the enteric-coated pill would be therapeutically suitable, even though not all prior art studies were in complete agreement. Thus, the result obtained was not unexpected. In Sanofi, on the other hand, there was strong evidence that persons of ordinary skill in the art, prior to the separation of the isomers, would have had no reason to expect that the D-isomer would have such strong therapeutic advantages as compared with the L-isomer. In other words, the result in Sanofi was unexpected.

Example 8:

In Rolls-Royce, PLC v. United Tech. Corp., the Federal Circuit addressed the obvious to try rationale in the context of a fan blade for jet engines. The case had arisen out of an interference proceeding. Finding that the district court had correctly determined that there was no interference-in-fact because Rolls-Royce’s claims would not have been obvious in light of United’s application, the Federal Circuit affirmed.

The Federal Circuit described the fan blade of the count as follows:

Each fan blade has three regions – an inner, an intermediate, and an outer region. The area closest to the axis of rotation at the hub is the inner region. The area farthest from the center of the engine and closest to the casing surrounding the engine is the outer region. The intermediate region falls in between. The count defines a fan blade with a swept-forward inner region, a swept-rearward intermediate region, and forward-leaning outer region.

United had argued that it would have been obvious for a person of ordinary skill in the art to try a fan blade design in which the sweep angle in the outer region was reversed as compared with prior art fan blades from rearward to forward sweep, in order to reduce endwall shock. The Federal Circuit disagreed with United’s assessment that the claimed fan blade would have been obvious based on an obvious to try rationale. The Federal Circuit pointed out that in a proper obvious to try approach to obviousness, the possible options for solving a problem must have been “known and finite.”
In this case, nothing in the prior art would have suggested that changing the sweep angle as Rolls-Royce had done would have addressed the issue of endwall shock. Thus, the Federal Circuit concluded that changing the sweep angle “would not have presented itself as an option at all, let alone an option that would have been obvious to try.”

The decision in Rolls-Royce is a reminder to Office personnel that the obvious to try rationale can properly be used to support a conclusion of obviousness only when the claimed solution would have been selected from a finite number of potential solutions known to persons of ordinary skill in the art.

Example 9:

The case of Perfect Web Tech., Inc. v. InfoUSA, Inc., provides an example in which the Federal Circuit held that a claimed method for managing bulk e-mail distribution was obvious on the basis of an obvious to try argument. In Perfect Web, the method required selecting the intended recipients, transmitting the e-mails, determining how many of the e-mails had been successfully received, and repeating the first three steps if a pre-determined minimum number of intended recipients had not received the e-mail.

The Federal Circuit affirmed the district court’s determination on summary judgment that the claimed invention would have been obvious. Failure to meet a desired quota of e-mail recipients was a recognized problem in the field of e-mail marketing. The prior art had also recognized three potential solutions: increasing the size of the initial recipient list; resending e-mails to recipients who did not receive them on the first attempt; and selecting a new recipient list and sending e-mails to them. The last option corresponded to the fourth step of the invention as claimed.

The Federal Circuit noted that based on “simple logic,” selecting a new list of recipients was more likely to result in the desired outcome than resending to those who had not received the e-mail on the first attempt. There had been no evidence of any unexpected result associated with selecting a new recipient list, and no evidence that the method would not have had a reasonable likelihood of success. Thus, the Federal Circuit concluded that, as required by KSR, there were a “finite number of identified, predictable solutions,” and that the obvious to try inquiry properly led to the legal conclusion of obviousness.

The Federal Circuit in Perfect Web also discussed the role of common sense in the determination of obviousness. The district court had cited KSR for the proposition that “[a] person of ordinary skill is also a person of ordinary creativity, not an automaton,” and found that “the final step [of the claimed invention] is merely the logical result of common sense application of the maxim ‘try, try again.’” In affirming the district court, the Federal Circuit undertook an extended discussion of common sense as it has been applied to the obviousness inquiry, both before and since the KSR decision.

The Federal Circuit pointed out that application of common sense is not really an innovation in the law of obviousness when it stated, “Common sense has long been recognized to inform the analysis of obviousness if explained with sufficient reasoning.”