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May 26, 2022by Beau Burton

Conclusions of obviousness require a reasonable expectation of successfully making and using an applicant’s claimed invention. Ex parte Micka (Appeal 2021-003755) is a recent decision from the Patent Trial and Appeal Board (“Board”) that shows whether there is a reasonable expectation of success can depend on the number of selections required to arrive at a claimed invention and how those selections would have been expected to affect the resulting combination of elements/ingredients.

The claims in Micka were directed to a process of preparing a solid dosage form by blending an active pharmaceutical ingredient (API) with a natural gum and a particular combination of  hydrophilic gelling polymers, “wherein the solid dosage form deters abuse and provides immediate release of the at least one API.”

The Examiner relied on a prior art reference for the specific ingredients and alleged that it would have been obvious to combine them in the manner claimed because the reference describes blending the ingredients and the dosage form as providing immediate release and being abuse resistant. This, however, was not the complete picture.

First, the appellant pointed out that the prior art described hundreds of polymers, diluents, binders, lubricants, disintegrants, gelling agents, plasticizers, and release modifiers at any concentration from 0-95% w/w in the abuse deterrent compositions. According to the appellant’s estimate, which the Examiner did not contest, the prior art disclosed ~17 trillion possible combinations of polymers, diluents, binders, lubricants, disintegrants, gelling agents, plasticizers, and release modifiers before even considering the concentrations.

Second, the appellant pointed out that the prior art’s focus was on controlled release compositions. The appellant’s argument here was not as strong because the prior art reference did use the phrase “immediate release,” but only once in the abstract. The Examiner grabbed onto this single mention of “immediate release” to argue there would have been a motivation and a reasonable expectation of success. The Board did not agree.

The Examiner’s error here resided in the fact that the prior art reference did not differentiate between excipients that would result in controlled release and immediate release. In the Examiner’s view, this was irrelevant because the same ingredients were suitable for making both. Not only did the Board disagree with this finding, but the Board also found that the prior art taught the choice of ingredients affects the release such that “it cannot be the case that any and all of these possible combinations will provide immediate release dosage forms.” Having no guide for what ingredient(s) could provide an immediate release composition, the Board found there was no reasonable expectation of success and reversed the rejection.

Takeaway: The factual scenarios under which the lack of a reasonable expectation of success can be successfully argued are less common than motivation to combine. A key in Micka was the claimed composition providing the immediate release of the API. And the facts in Micka were particularly strong because of the litany of selections required to arrive at the claimed composition and the complete lack of guidance as to which selections would have resulted in the immediate release property. Without claiming the immediate release property, the obviousness determination would have devolved into whether it would have been obvious to select the combination of ingredients – a more difficult position to rebut.

Judges: J. Morgan, J. Schneider, M. Valek


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May 20, 2022by Yanhong Hu

In Ex parte Stone (Appeal 2021-004177), the Patent Trial and Appeal Board (“Board”) reversed the Examiner’s obviousness rejection citing Lucas, Kaersgaard, and Wu because the Examiner did not meet his initial burden of presenting a prima facie case of obviousness.

Appellant’s claimed invention in Stone was directed to a method of “selectively removing a proteinaceous impurity from a sample comprising at least an immunoglobulin and the proteinaceous impurity.” It included steps of “adjusting the solution pH of the sample, such that the pH is within 2.0 pH units of the isoelectric point of the proteinaceous impurity to be selectively removed,” then “contacting the sample with activated carbon, [which] selectively binds the proteinaceous impurity,” and “removing the activated carbon from the sample.”

Lucas described the presence of contaminants in monoclonal antibodies and also taught that the contaminants should be removed to produce monoclonal antibodies of the highest purity. However, Lucas did not disclose how to remove the contaminants. The Examiner acknowledged this deficiency. The Examiner found that Kaersgaard described removing PEG from immunoglobulins using activated carbon and Wu described removing proteinaceous material from corn syrup using activated carbon. The Examiner also found that Wu disclosed that the maximum adsorption of the proteinaceous material by the activated carbon occurred at the protein’s isoelectric point. The Examiner thus determined that it would have been obvious to a skilled artisan “to remove the impurities of Lucas” by Wu’s method “motivated by the desire for highest purity, described by Lucas;” and reasoned that because Kaersgaard “teach[es] using very similar methods for purifying immunoglobulins, and explicitly discuss[es] using the methods to remove other impurities, an artisan in this field would attempt this process with a reasonable expectation of success.”

Appellant argued that the combination of cited references did not suggest the claimed method or provide the motivation to combine Wu with Lucas and Kaersgaard. Specifically, Appellant argued that none of the cited references described the selective removal of a protein impurity from other proteins, noting that Kaersgaard disclosed removing PEG rather than a protein impurity from immunoglobulins and Wu disclosed removing proteins from corn syrup, but did not teach selectively removing a proteinaceous impurity from other proteins based on the isoelectric point of the impurity as required by Appellant’s claimed method.

The Board agreed with the Appellant. The Board noted that Lucas identified the need to remove protein contaminants but did not teach how to do so. The Board also noted that neither Kaersgaard nor Wu described selective removal of a protein. In particular, Wu described removal of all protein contaminants, despite teaching that the maximum adsorption of a protein could be achieved using the pH of the protein’s isoelectric point. The Board noted that the Examiner did not provide adequate reasoning to modify Wu to selectively remove impurities. Specifically, regarding the Examiner’s contention that Appellant’s arguments “assume that a person of skill in the art cannot make the leap from the explicit experiments and motivations of the reference to other, closely related applications and goals,” the Board pointed out that the Examiner did not provide a reason for making the “leap” from adsorbing all proteins from a solution to adsorbing only certain proteins based on their isoelectric point.

The Board emphasized that it was the Examiner who had the initial burden of presenting a prima facie case of obviousness and that ordinary creativity and/or common sense “cannot be used as a wholesale substitute for reasoned analysis and evidentiary support, especially when dealing with a limitation missing from the prior art references specified.” The Board cautioned that although the Supreme Court emphasized “an expansive and flexible approach” to the obviousness approach, it also reaffirmed the importance of determining “whether there was an apparent reason to combine the known elements in the fashion claimed by the patent at issue.”

Because the Examiner failed to provide sufficient reason to selectively remove proteinaceous impurity as claimed, the Board reversed the Examiner’s obviousness rejection.

Takeaway:  Obviousness can be established by combining or modifying the teachings of prior art references to produce a claimed invention where there is some teaching, suggestion, or motivation to do so and there is a reasonable expectation of success. The Examiner in Stone did not establish obviousness because, although Wu disclosed adsorption of a protein was related to the pH of the protein’s isoelectric point, the Examiner failed to present sufficient reasoning to modify Wu’s teachings to achieve the claimed selective removal of a proteinaceous impurity. As the Board pointed out, an examiner’s assertion of ordinary creativity and/or common sense cannot substitute for reasoned analysis and evidentiary support.

Judges:  E. B. Grimes, R. M. Lebovitz, and G. C. Best


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February 17, 2022by Richard Treanor

Even a casual, unscientific survey of recent PTAB decisions shows a clear and unmistakable trend: shorter decisions, with little or no discussion of issues not specifically raised by Appellant. While those seeking review of an Examiner’s decision could, at one time, expect both an independent review of the underlying rejection as well as consideration of their arguments, the PTAB is now more likely to focus solely on, and respond only to, those issues raised in Appellant’s brief. Indeed, 20% of recent decisions in Tech Centers 1600 and 1700 included the following language:

We review the appealed rejections for error based upon the issues Appellant identifies, and in light of the arguments and evidence produced thereon. Ex parte Frye, 94 USPQ2d 1072, 1075 (BPAI 2010) (precedential), cited with approval in In re Jung, 637 F.3d 1356, 1365 (Fed. Cir. 2011) (“[I]t has long been the Board’s practice to require an applicant to identify the alleged error in the examiner’s rejections.”).

Whether this trend is due to an increased workload at the PTAB, represents an attempt to reduce pendency, or is caused by something else altogether doesn’t really matter. What matters is that Appellants recognize this new reality and respond to it.

Unfortunately, this means that Appeal Briefs may need to include secondary arguments that, at one time, might have been left out as being distracting. More importantly, however, it is imperative to include, wherever possible, those arguments that appear to be “in favor” at the PTAB (i.e., those arguments that appear regularly in cases where the Examiner is reversed), and to present them prominently.

Right now, the “in favor” argument for Appellants unquestionably is whether the prior art provides a reasonable expectation of success. We have written extensively about this in our blog (link, link, link, link, link), saw it at the end of last year at the Federal Circuit in Teva Pharm. U.S. v. Corcept Therapeutics, Inc., 2021-1360 (Fed. Cir. Dec. 7, 2021) (invalidating the claim requires proof of “a reasonable expectation of success in achieving the specific invention claimed”), and may soon see it addressed at the Supreme Court in Apotex Inc. v. Cephalon, Inc., where infringer Apotex, in their Writ of Certiorari, neatly summed up the doctrine’s current pro-applicant, pro-patentee, pro-validity understanding that an obvious-to-try approach is only sufficient to invalidate where there is a reasonable expectation of success:

[T]he Federal Circuit seems to believe that if there is any uncertainty about whether an obvious-to-try approach will succeed, that potentially compromises the motivation to try an obvious solution to a pressing problem, and therefore produces patent monopolies for what is obvious to try. Indeed, so ingrained has the motive-to-try-what-is-likely-to-succeed test now become in the Federal Circuit’s obviousness psyche, that the Federal Circuit now sometimes includes motivation as a fifth Graham factor.

Because a “no reasonable expectation of success” argument cuts against the establishment of a prima facie case, success on this issue does away with any need for a showing of unexpected results, which can sometimes be difficult to provide. Thus, until there is something to the contrary diminishing this doctrine’s current status, understanding, and application, best practice issue advocacy dictates that whenever a “no reasonable expectation of success” argument can be made, it should be made. Supporting such a position during prosecution with a Declaration makes ignoring it, and refuting it, very difficult for both the Examiner and the PTAB.


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December 3, 2021by Richard Treanor

In attempting to overcome obviousness rejections, our initial focus often centers on the differences between the cited references and the claimed invention. We do this in the hope of finding reasons that, even when the references are combined, the claimed invention would not be taught (no prima facie case). When such reasons are not present, we then generally look for a lack of motivation to combine the references which, unfortunately, has lately become more and more difficult to establish. However, in August the Federal Circuit issued a decision in Eli Lilly & Co. v. Teva Pharm. Int’l GmbH, 2020-1876 (Fed. Cir. Aug. 16, 2021) reminding us that, even where there is motivation to combine references, and even when all the claim limitations are provided by the combination, there is a third, separate requirement that must be met in order to establish a prima facie case of obviousness – a reasonable expectation of success in accomplishing what is required by the claims must also be present.

The Eli Lilly decision was one of three decisions issued on the same day in related inter partes review proceedings between Eli Lilly and Teva concerning patents related to monoclonal antibodies useful for the treatment of headaches. Importantly, in Eli Lilly the court found the claims’ preamble statements of “intentional purpose” (i.e., treating headaches) to be limiting. Then, citing Novartis Pharm. Corp. v. W.-Ward Pharm. Int’l Ltd., 923 F.3d 1051 (Fed. Cir. 2019) and summarizing the holding in that case as finding that “it was not enough for the [defendant] to have shown that a skilled artisan would have pursued the claimed method as a treatment option, but the [defendant] also had to show that the skilled artisan would have reasonably expected to achieve success in the treatment,” the Federal Circuit affirmed the PTAB’s finding that Lilly had failed to establish a reasonable expectation of success in pursuing the claimed method due to the uncertain and unpredictable nature of the underlying technology, even though the applied references taught all the limitations of the contested claims, and even though there was motivation to combine the references.

The Eli Lilly case is thus a good reminder for patent practitioners that, even in the face of what appears to be a very good prima facie case, there may be a pathway to patentability through the “no reasonable expectation of success” route, especially in unpredictable/newly developing arts.

Judges: Lourie, Bryson, O’Malley


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April 6, 2021by Richard Treanor

In February, the Federal Circuit issued a decision in Takeda Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd. concerning the obviousness of a chemical compound. Perhaps the most interesting aspect of the court’s decision was the framework that they used in making their decision.

The case arose in ANDA litigation, with Takeda alleging that Torrent would infringe Takeda’s Orange Book-listed patent claiming certain alogliptin benzoates. Torrent defended by alleging obviousness – both statutory obviousness (35 U.S.C. 103) and non-statutory obviousness-type double patenting – and in all cases relied on the obvious modification of a “lead compound” to produce Takeda’s claimed compounds.

In Takeda, central to the court’s ultimate decision-making process was determining whether there was a “reasonable expectation of success” in making Torrent’s suggested modifications. But in essentially answering this question before it was asked, the court prefaced its discussion with the following statement:

Relevant to ‘the assessment of [reasonable] expectation of success’ in all three of [Torrent’s] invalidity theories … is the undisputed factual finding that ‘in the relevant art of pharmaceutical development, very small changes in molecular structure can have dramatic effects on the properties of the molecule,’ …. Indeed, ‘the more distantly related two chemical structures are, the less probable it will be that they have the same biological effect.’ … Against this backdrop, we turn to the details of Appellants’ invalidity theories.

As one might guess just from reading this opening decisional framework, the court found in favor of Takeda, holding that a skilled artisan would not have been motivated to modify Torrent’s lead compound with a reasonable expectation of success.

Takeaway: Does the Takeda case provide us with a roadmap to nonobviousness? Perhaps. In Takeda patentee used expert testimony, buttressed by a publication, to establish the unpredictability of chemical structural changes vis-à-vis functionality in the relevant pharmaceutical art. In the absence of evidence to the contrary, the Federal Circuit found it very easy to affirm the validity of Takeda’s claims and deny Torrent’s allegations of obviousness. Using this strategy during prosecution should yield the same results, with the advantage of an “adversary” (i.e., the Examiner) who lacks the resources of a pharmaceutical litigant.

Judges: Dyk, Mayer, Chen


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March 31, 2021by Beau Burton

A conclusion of obviousness requires that a skilled artisan would have had a reason to combine the teachings of the prior art references to achieve the claimed invention, and that the skilled artisan would have had a reasonable expectation of success from doing so.

The reasonable expectation of success requirement can be difficult to challenge during prosecution because the reply is consistently that “only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness.” In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985). This seemingly insurmountable conclusion is compounded by a lack of bright-line rules defining when a reasonable expectation of success exists. However, Ex parte Saerens provides a nice example of facts resulting in a conclusion that a skilled artisan would not have had a reasonable expectation of success. Appeal No. 2020-005386 (PTAB Feb. 25, 2021) (non-precedential).

The claims in Saerens were drawn to a method for fermenting cocoa beans with at least one Pichia kluyveri yeast strain, where the fermented cocoa beans exhibited particular ratios of isobutyl acetate/isobutanol and isoamyl acetate/isoamyl alcohol.

The Examiner relied on a primary reference for its disclosure of adding pectinolytic yeast during cocoa bean fermentation and cited a secondary reference for evidence that certain strains of Pichia kluyveri are pectinolytic. According to the Examiner, a skilled artisan would have had a reason to select Pichia kluyveri from the secondary reference for use as the pectinolytic yeast in the primary reference.

The Appellant disagreed because the secondary reference “focused on examination of pectinolytic activity on a coffee substrate, not cocoa” and there was no evidence the Pichia kluyveri would have exhibited similar activity on all pectin-containing substrates, or would otherwise have been useful for cocoa bean fermentation. In response, the Examiner argued that “pectinolytic activity is universal,” and predictably stated that “Appellants are reminded that only a ‘reasonable expectation of success’, not an ‘absolute success’ would have been required in an obviousness rejection.” Examiner’s Answer at 15.

Reversing the Examiner’s rejection, the Board held that “the prior art must give some indication of which parameters were critical or which of many possible choices is likely to be successful.” Here, however, the secondary reference relied on by the Examiner showed significantly different Pichia kluyveri activity when cultured on yeast polygalacturonic acid medium vs. coffee broth. Consequently, the evidence of record showed that Pichia kluyveri activity would have been considered substrate-specific in complete contradiction to the Examiner’s unsubstantiated finding that “pectinolytic activity is universal,” irrespective of whether the substrate is coffee or cocoa.

Accordingly, the Board found that a skilled artisan would not have been guided by the secondary reference to substitute Pichia kluyveri for any of the yeasts in the primary reference, and reversed the Examiner’s rejection.

Takeaway: It can be difficult to persuade an Examiner who has already concluded there would have been a reasonable expectation of success even when the subject matter claimed is unpredictable, as with the chemical and biological arts. This is illustrated in Saerens, where the Examiner maintained the obviousness rejection despite the experimental data in the secondary reference itself contradicting his conclusion of “universal activity.” Nevertheless, it is important to present any experimental data, technical publications, and/or expert testimony that shows unpredictability as these will be more persuasive than mere attorney argument. In the event that an Examiner is not persuaded by such evidence, the evidence can serve as a basis for reversal in a formal appeal.

Judges: C. Timm, G. Best, J. Snay


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January 13, 2021by Yanhong Hu

Obviousness requires both a reason to modify or combine prior art to achieve a claimed invention and a reasonable expectation of success.  Evidence showing there was no reasonable expectation of success would support a conclusion of nonobviousness.  In Ex parte Hewes (Appeal 2019-006474), the Patent Trial and Appeal Board (“Board”) reversed the Examiner’s obviousness rejection because the Board found Appellant’s evidence showing no reasonable expectation of success was persuasive.

The claimed invention in Hewes, as recited in the illustrative claim 17, was directed to “a method for treating a BcrAbl positive leukemia in a subject that is resistant to imatinib.”  Imatinib is a drug typically used to treat patients with chronic myelogenous leukemia (CML) because it blocks an abnormal protein called “the tyrosine kinase protein ‘BcrAbl’” that drives overproduction of abnormal white blood cells characteristic of leukemia.  Some patients, however, develop resistance to imatinib “due to point mutations in the bcr/abl gene.”  F317L is such a mutation.  The claimed method at issue comprises “administering to the subject a therapeutically effective amount of [bosutinib], wherein the subject has a mutation in BcrAbl protein selected from F317L.”

The Examiner rejected claim 17 as obvious over Manley and over Boschelli ‘780 in view of Shah.

In the obviousness rejection over Manley, the Examiner admitted Manley did not disclose a single embodiment regarding administration of bosutinib to a patient suffering from imatinib resistant BcrAbl positive leukemia.  However, the Examiner asserted a skilled artisan would have been motivated to practice the claimed method with reasonable expectation of success based on Manley’s teaching that bosutinib was one of a class of promising new inhibitor compounds for treating imatinib-resistant CML, that imatinib resistance was due to emergence of clones expressing mutant proteins, and that F317L was alleged to be among the “most frequently occurring mutants.”

Appellant contended that Manley did not suggest any promising new CML drug, including bosutinib, could treat imatinib-resistant CML associated with F317L and that F317L was actually a rare mutation.  More importantly, Appellant argued for unpredictability in treatment of imatinib-resistant leukemia in patients with the F317L mutation, citing, in particular, the affidavit by Dr. Murray.  The Murray affidavit testified that the F317L mutant was especially resistant to treatment even with second generation drugs like dasatinib and nilotinib, citing several references.  The Murray affidavit explained that different patients, even with the same mutation, were known to display different clinical response upon treatment.  Therefore, along with other documentary references, the Murray affidavit proved that imatinib resistance arising from mutations of the Bcr-Abl gene was poorly understood at the time of the invention.  The Murray affidavit also testified that “clinical findings show F317L to be a[n] imatinib/dasatinib-resistant mutation” although preclinical models might have predicted drug potency against F317L mutants; and thus proved the preclinical models in this area were poor predictors of clinical efficacy and success.

Although the Board agreed with many of the Examiner’s readings of Manley, the Board agreed with Appellant that none of the second-generation drugs in Manley were disclosed as effectively treating imatinib-resistant CML associated with the F317L mutation.  The Board found Appellant’s argument and supporting evidence that showed a lack of predictability in treating imatinib-resistant patients particularly with the F317L mutation were convincing.  The Board noted that Appellant’s evidence, especially Dr. Murray’s testimony, “calls into significant doubt whether the ordinarily skilled person would have reasonably expected success with bosutinib when other second-generation, Bcr-Abl/Src inhibitors were known and shown to be ineffective in treating subjects with the F317L mutation.”  The Board found that the Examiner provided no persuasive rebuttal in the face of Appellant’s argument and evidence.

In addressing the Examiner’s characterization of the Murray affidavit as “merely opinions” on the state of the art, the Board noted that the affidavit could not be summarily swept aside in this way because “Dr. Murray cites repeatedly to the scientific literature[, including Manley and Shah, which are the references asserted by the Examiner,] in support of his opinions, grounding those opinions in an adequate factual basis.”  The Board found it was the Examiner who failed to “grapple persuasively with Dr. Murray’s opinions or the facts on which they are based.”

The Board thus concluded that even if the Examiner’s reasoning provided some motivation to treat patients with the F317L mutation with bosutinib, considering the totality of the evidence, the Examiner’s rejection failed “on the issue of reasonable expectation of success.”  Accordingly, the Board reversed the Examiner’s obviousness rejection over Manley.

Regarding the obviousness rejection over Boschelli ‘780 in view of Shah, the Board found it was unsustainable for substantially the same reason.

Takeaway:   As noted by the Board in Hewes, there are two different inquiries in an obviousness rejection – the motivation and the reasonable expectation, with the latter referring to the likelihood of success in modifying prior art to reach a claimed invention.  A determination of obviousness is not proper if, upon consideration of all the evidence, the outcome would not have been reasonably predictable and there would not have been a reasonable expectation of success at the time of the invention.  As illustrated by Hewes, such evidence could be in the form of an expert’s affidavit.  To provide a probative expert’s affidavit, the expert should set up facts suggesting the unpredictability and corroborate her opinions with scientific literature preferably authored by other people skilled in the field.

Judges:  D. E. Adams, E. B. Grimes, and T. G. Majors