Source: https://www.patentdocs.org/articles_cases_obviousness/
Timestamp: 2019-04-18 10:48:57+00:00

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Earlier this month, the Federal Circuit affirmed a decision by the Patent Trial and Appeal Board (PTAB) that the claims of U.S. Reissue Patent No. RE38,551 challenged in inter partes review were not unpatentable for obviousness, in Mylan Pharmaceuticals Inc. v. Research Corporation Technologies, Inc.
derivatized by introduction of the X component, which is "a functionalized nitrogen, oxygen, or sulfur substituent." The Kohn reference disclosed that these compounds had an effectiveness for treating convulsions in mice. The reference taught that the most potent compound contained a functionalized oxygen atom two atoms removed from the alpha carbon (designated with an asterisk in the formula above). Petitioners relied upon Silverman for the motivation to modify this compound to produce lacosamide based on the drug development approach termed bioisosterism, purported in the reference to be useful for attenuating toxicity or modifying bioactivity. Here this drug development tool was purportedly relevant for groups having the same number of valence electrons but (perhaps) different atoms, such as -CH2-, -NH-, -O-, -S- and -Se-. The '729 patent, was directed to antiepileptyic compounds including racemic N-benzyl 2-acetamido-3-methoxypropionamide.
Despite being sufficiently persuaded to initiate an IPR on these grounds, the Board refused to provide a Final Written Decision that the claims were in fact unpatentable for obviousness. The Board was unpersuaded by the reasons asserted by Petitioner under Ground 1 for modifying the lead compound: "(1) that the methoxyamino moiety was not a common moiety in compounds that result in commercial pharmaceutical compounds and (2) that the methoxyamino moiety may present synthetic and stability problems." The skilled worker would have been motivated to substitute a -CH2- group for the -NH- group in the lead compound. Moreover, the Kohn reference had disclosed a 10-fold higher anticonvulsant activity when a compound having an -NH2 group was substituted with a compound having a -CH2OCH3 moiety. The Board disagreed, based on disclosure in the Kohn reference that "compounds  without a methoxyamino or nitrogen-containing moiety at the α-carbon had reduced activity." In addition, the Board accepted Patent Owner's evidence that "an ordinary artisan would have understood the methoxyamino moiety to confer significant activity to the compound and that substitution of nitrogen for carbon would have led to a significantly different conformation and biological activity." The bioisosterism teachings of Silverman did not cure these deficiencies, according to the Board, because the was "a lack of 'specific evidence suggesting an ordinary artisan would have understood that modifying the methoxyamino group of [the lead compound] would have reduced that compound's toxicity."
The Federal Circuit's affirmance was written by Judge Lourie joined by Judges Bryson and Wallach and first addressed the issue of standing, wherein all the appellants had joined the IPR more than one year after being sued by Patent Owner under 35 U.S.C. § 319. The panel held that the Board had exercised its discretion to permit joinder (permitted under 35 U.S.C. § 315(c)) and the absence of Petitioner Argentium (which would have lacked standing to bring this appeal for lack of Article III standing) vitiates the remaining Petitioners' capacity to pursue the appeal. (Interestingly, these parties apparently agreed that Argentium would not have had standing to appeal.) The Court agreed with the remaining Petitioners that, once joined under § 319, they that had "an express, statutory right to appeal." The Court made its determination under the "zone of interests" standard (which the Court assesses under "traditional principles of statutory interpretation, asking not 'whether in our judgment Congress should have authorized [the appeal], but whether Congress in fact did so,'" citing Lexmark Int'l, Inc. v. Static Control Components, Inc., 572 U.S. 118, 128 (2014). Using these rubrics, the Court found support in the plain language of § 315, which contemplates joining as a party "any person who properly files a petition under section 311" (emphasis in opinion). Combined with the provisions of § 319, granting parties the right to appeal, it was an easy exercise in statutory interpretation for the Court to find standing.
[W]as entitled to reject bioisosterism as a basis for a motivation to modify compound 3l. While Silverman does disclose that that bioisosterism may be useful to attenuate toxicity in a lead compound, the record does not indicate why bioisosterism would have been used to modify compound 3l in particular, which already had a high potency and low toxicity, and why methylene was a natural isostere of methoxyamino.
Finally, the opinion rejected Petitioners' contention, at oral argument (and rebuttal at that, timing that seemed to annoy the Court), that the Court should remand the case to the PTAB in view of the Supreme Court's intervening decision in SAS Institute, Inc. v. Iancu, 138 S. Ct. 1348 (2018), finding that issue to have been waived as in PGS Geophysical AS v. Iancu, 891 F.3d 1354, 1362–63 (Fed. Cir. 2018), due to untimeliness.
In addition to the SAS aspect, this case illustrates the capacity of the PTAB to enter a decision, after oral argument and Patent Owner's opportunity to present evidence, contrary to the decision to institute. This makes invalidation much less of a foregone conclusion in IPRs, which must be seen by Patent Owners as a welcome development.
Last week, in In re Ikeda Food Research Co., the Federal Circuit affirmed a decision by the U.S. Patent and Trademark Office Patent Trial and Appeal Board affirming the Examiner's rejection in an ex parte reexamination of claims 22 and 23 of U.S. Application No. 12/851,668 for obviousness. On appeal before the Board, the challenged claims were found obvious in view of three references: European Patent Application Publication No. 0 094 161 ("Senior") and U.S. Patent Nos. 6,656,702 ("Yugawa A") and 6,059,946 ("Yugawa B").
wherein the biosensor can quantify glucose concentrations ranging from 4.5 mM to 30 mM.
The '668 application purports to improve upon the prior art by claiming use of, inter alia, a specific enzyme: a "flavin"-dependent GDH ("FAD-GDH") designated as Enzyme Commission ("E.C.") 1.1.99.10, whose "relative reactivity" (or "substrate specificity"), was found to exhibit "high activity" on glucose, and "low activity" on the seventeen other substrates tested, including maltose.
The Board affirmed the Examiner's rejection, determining that even though Senior did not expressly disclose the low-maltose activity limitation of claim 22 of the '668 application, the enzyme preparation disclosed in Senior inherently contains the same enzymatic specificity for glucose relative to maltose as the challenged claims in the '668 application. More particularly, the Board concluded that it was reasonable to infer the FAD-GDH enzymes disclosed in Senior and the '668 application have the same low substrate specificity for glucose relative to maltose because both Senior and the '668 application classify the FAD-GDH enzymes in their enzyme preparations as E.C. 1.1.99.10.
The PTAB had a reasonable basis to conclude that because Senior discloses the use of the FAD-GDH enzyme described in the '668 application, classified under E.C. 1.1.99.10, the claimed low "5% or less" activity against maltose relative to glucose in the reaction layer is inherently disclosed in Senior's enzyme preparation.
The Federal Circuit also rejected the argument that the Board improperly shifted the evidentiary burden to Ikeda, citing In re Best, 562 F.2d 1252, 1255 (CCPA 1997), for the proposition that "the fairness of shifting the burden 'is evidenced by the [US]PTO's inability to manufacture products or to obtain and compare prior art products.'" The Court therefore concluded that "we see no reason to call into question the PTAB's finding 'that the 'possible presence of contaminants' in Senior's enzyme preparation [does not] render the claimed biosensor non-obvious.'"
Finally, with respect to Ikeda's argument that the Board discounted the objective indicia of nonobviousness, especially that of a long-felt need, the Federal Circuit disagreed that the Board erred by not crediting Ikeda's evidence of long-felt need for a GDH enzyme with no separate cofactor. The Court noted that because claim 22 employs the transitional phrase "comprising" in its preamble, the claim "does not exclude biosensors that employ a cofactor" (emphasis in opinion). Therefore, because claims 22 and 23 encompass biosensors that use cofactors, "it follows that they do not satisfy Ikeda's alleged need for dehydrogenase-based glucose sensors that do not rely on a cofactor." Rejecting all of Ikeda's arguments, the Federal Circuit therefore affirmed the decision of the Patent Trial and Appeal Board.
The Federal Circuit recently reviewed yet another decision by the Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office in Amerigen Pharmaceuticals Ltd. v. UCB Pharma GmbH, and once again reviewed whether a failed petitioner in an inter partes review (IPR) proceeding had standing to appeal an adverse judgment.
Fesoterodine, in contrast, differs from 5-HMT in having an isobutyryl ester in place of the hydroxyl group at the 2-position. This modification raised the core issue regarding patentability before the PTAB and the Federal Circuit: would it have been obvious to make this substitution to create an inactive prodrug requiring metabolic conversion to product the active 5-HMT in vivo?
The Petitioner asserted two grounds of obviousness: the first, over the combination of the Detrol® label; a scientific publication to Postlind et al. disclosing metabolism of tolterodine to 5-HMT; a treatise disclosing design of prodrugs (Bungaard); a PCT application naming Bungaard as an inventor (the '459 PCT): a separate scientific publication to Byrnne et al. further directed to metabolism of tolterodine to 5-HMT; and another scientific publication to Berge et al., disclosing preparation of pharmaceutical salts. The second asserted obviousness ground combined Byrnne, Bungaard, '459 PCT, and another PCT application to Johansson (the '337 PCT). The PTAB found that neither of these asserted combinations satisfied Petitioner's burden of showing the '650 patent claim were obvious, and Amerigen appealed.
The Federal Circuit affirmed, in an opinion by Judge Lourie joined by Judges Chen and Stoll. Before reaching the substantive patentability issues, the panel first addressed argument from UCB that Amerigen did not have standing to pursue the appeal. This argument was based on a decision in ANDA litigation that Amerigen failed to show the '650 patent was invalid and thus the FDA would not approve Amerigen's ANDA for a generic version of Tovoaz® until the '650 patent expired. As a consequence, according to UCB's argument, Amerigen could not be subject to infringement liability and thus could not suffer injury sufficient to support standing in the appeal. Amerigen countered by noting that invalidation of the '650 patent by the Federal Circuit reversing the PTAB would "advance the launch of its product" and that the continued viability of the '650 patent created a concrete injury sufficient to confer standing under Article III.
The opinion recites the canonical requirements for standing (an appellant must have "(1) suffered an injury in fact, (2) that is fairly traceable to the challenged conduct of the defendant, and (3) that is likely to be redressed by a favorable judicial decision," citing Spokeo, Inc. v. Robins, 136 S. Ct. 1540, 1547 (2016)) and held that Amerigen satisfied these requirements. It was not disputed that launch of Amerigen's generic product was blocked by the continued vitality of the '650 patent and that a decision invalidating the patent (by the PTAB or the Court) would "advance [the] drug's launch." The opinion explains that the '650 patent is listed in the FDA's "Orange Book" and that UCB would have the obligation of delisting this patent if the Court reversed the Board's decision in the IPR. In that case, the predicate basis for Amerigen's Paragraph III certification would be lifted and Amerigen would be able to begin marketing its drug upon expiration of UCB's other listed patents; this will occur about three years before the expiration date of the '650 patent. This constitutes a "concrete, economic interest" in Amerigen selling its tentatively approved drug (wherein all approval requirements except UCB's patent have been satisfied) according to the opinion. The panel cited Apotex, Inc. v. Daiichi Sankyo, Inc., 781 F.3d 1356, 1359–61 (Fed. Cir. 2015), in support of its decision here, where the Court had held that listing of a patent in the Orange Book could create a controversy "of sufficient immediacy and reality" to satisfy Article III standing requirements. The opinion did not credit UCB's argument that the issue was controlled by the Federal Circuit's decision in Janssen Pharmaceutica, N.V. v. Apotex, Inc., 540 F.3d 1353 (Fed. Cir. 2008), noting that the Janssen decision involved considerations relating to the Hatch-Waxman Act that were not shared by the IPR provisions of the America Invents Act (which provided much more broadly for parties to challenge granted U.S. patents).
then a compound can be expected to have a "bioavailability problem." 5-HMT did not evince expected reduced bioavailability using the Rule of 5, and thus the PTAB credited UCB's expert's testimony on this issue (which Amerigen's expert did not rebut).
Having made this determination, the Board held that a skilled person would not have esterified the 2-position of 5-HMT to solve a bioavailability problem that she would not recognize existed in the prior art. In addition, Petitioner had not produced evidence that 5-HMT esterified at the 2-position would be inactive (i.e., actually be a prodrug). The Board also found that even if a skilled worker would have been motivated to modify 5-HMT, expert testimony supported a conclusion that producing such a prodrug would not have been "a matter of routine optimization," at least in part due to the "many possible molecular modifications of 5-HMT consistent with a prodrug design." While there were a number of possible embodiments of esterified 5-HMT (including esterifying the hydroxyl group at the 5-position), even if the universe of esters were limited to alkyl esters of six carbons or fewer at the 2-position there would be 86 possible compounds and testing each one would not have been routine.
In affirming the PTAB's decision the Federal Circuit noted its limited basis for review regarding the Board's factual determinations under In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000). Almost the entirety of the panel's decision focused on the substantial evidence relied upon by the Board in making its nonobviousness determination, culminating in the statement that "[i]t was Amerigen's burden to show that the 'prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention,'" citing Takeda Chem. Indus., Ltd. v. Alapharm Pty., Ltd., 492 F.3d 1350, 1356 (Fed. Cir. 2007) (emphasis added) (quoting In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995)). Under the facts before the Court, there was no basis for reversing the PTAB's decision and the panel declined to do so.
On January 3, 2019, the U.S. Patent and Trademark Office Patent Trial and Appeal Board (PTAB) issued a Final Written Decision in Insys Development Co., Inc. v. GW Pharma Ltd. (IPR2017-00503), a landmark inter partes review (IPR) decision involving a cannabis patent. Although the PTAB found claims 1 and 2 to be unpatentable as obvious, the remaining 11 claims that were challenged survived and remain valid (and potentially enforceable).
At issue in this IPR was U.S. Patent No. 9,066,920 ("the '920 Patent," entitled "Use of one or a combination of phyto-cannabinoids in the treatment of epilepsy"), which was originally assigned to GW Pharma Ltd. and Otsuka Pharmaceuticals Co., Ltd.
GW Pharma owns an extensive patent portfolio with many patents directed to treating diseases using cannabis-based formulations. Notably, GW Pharma, along with its U.S. subsidiary, Greenwich Biosciences, made history in the cannabis industry by becoming the first entity to receive FDA approval of a drug (Epidiolex) that contains an active ingredient (cannabidiol or CBD) derived from a cannabis plant. CBD is a non-psychoactive cannabinoid that can be naturally produced and derived from portions of cannabis plants, typically hemp.
Insys Development Company, Inc., a pharmaceutical company that focuses on cannabinoids and drug delivery systems, petitioned to cancel all thirteen claims of the '920 Patent as obvious based on three different combinations of references that included scientific articles as well as one of GW Pharma's own published PCT applications.
1. A method of treating partial seizure comprising administering cannabidiol (CBD), to a patient wherein the CBD is present in an amount which provides a daily dose of at least 400 mg.
2. The method of claim 1, wherein CBD is present in an amount which provides a daily dose of from 400 to 800 mg.
Before conducting the obviousness analysis, the PTAB considered whether the term "partial seizure" in claim 1 needed to be construed. Insys argued that "partial seizures" meant seizures that can include secondary generalized seizures. However, GW Pharma argued that the term did not need to be construed because, even under Insys's construction, Insys had failed to show that a person of ordinary skill in the art (POSA) would have been motivated to increase the dosage of CBD described by one of the primary references and would have had a reasonable expectation of success that the higher dosage could treat partial seizures. Ultimately, because GW Pharma did not dispute that the asserted references applied to the treatment of partial seizures, the PTAB did not find it necessary to construe the term in order to determine the patentability of the challenged claims.
Regarding the obviousness challenge, Insys argued that all claims of the '920 Patent were obvious because the primary reference taught treatment of epilepsy with CBD, and a POSA "would have concluded that the claimed daily dosage of at least 400 mg of CBD is predictable, safe, and expected" in view of the combination of asserted references. GW Pharma countered that, at the time of invention, CBD was "at best, a promising candidate for further study" and that a POSA would have "no reasonable expectation that CBD would treat partial seizures at all, let alone at doses of 400 mg or higher," as claimed by the patent.
The PTAB found that Insys demonstrated by a preponderance of the evidence that claim 1 (the broadest claim of the patent) and dependent claim 2 were obvious over two of the three asserted combinations of references. Both combinations relied on the same primary reference, which described clinical studies involving administering CBD to epileptic patients. Although the primary reference described a daily dose of CBD that was less than 400 mg, the PTAB found that the combination of asserted references, when read together, would have led a POSA to reasonably believe that the amount of CBD could be safely increased to the claimed dosage of at least 400 mg/day because, as of the time of invention, "CBD had been shown to be well tolerated in humans without any serious side effects or toxicities at doses up to 600 mg."
Regarding claims 3-13, Insys argued that those claims were obvious over the asserted combinations of references for the same reasons that claims 1 and 2 were obvious. GW Pharma argued that Insys failed to identify where most of the limitations of claims 3-13 were disclosed in the prior art, and also did not present expert testimony as to why those dependent claims would be obvious. The PTAB agreed with GW Pharma on this point, and found that Insys failed to meet its burden to show that claims 3-13 were obvious over any of the asserted combinations of references.
Although claims 1 and 2 were deemed unpatentable, the '920 Patent remains largely intact following the PTAB's decision with claims that are still fairly broad relative to claim 1. In particular, dependent claims 6 and 9 only further require that "the CBD is present as a plant extract" and "the CBD is present as a pure or isolated cannabinoid," respectively.
Whether Insys or GW Pharma will appeal the Final Written Decision remains to be seen. If they do, there are essentially two routes: (1) panel rehearing, then potentially the Federal Circuit (and maybe even the Supreme Court); or (2) straight to the Federal Circuit. Either way, the industry will be watching closely over the next two months to see where the parties go next before the deadline to challenge this opinion passes.
And, as we have previously noted, this IPR raises some important implications for challenging and enforcing patents in the cannabis space. One key takeaway from this decision is that the PTAB seemed to treat this cannabis patent just like any other patent subject to an IPR challenge (the fact that cannabis remains a Schedule I drug was not an issue). Therefore, this decision may provide some clarity (or at least hope) to canna-patent owners and third-party challengers that IPR proceedings (and likely other USPTO post-grant proceedings) are at least one option for challenging cannabis patents.
Additionally, as canna-patents continue to make their way through the federal courts (including, e.g., one of the first cannabis patent infringement lawsuit underway in the U.S. District Court for the District of Colorado—United Cannabis Corp. v. Pure Hemp Collective Inc. (1:18-cv-01922)), the industry may expect to see even more IPR challenges of cannabis patents, as well as more frequent patent application filings, following the legitimization of canna-patent infringement cases in district courts.
At bottom, in light of these decisions and others, the message to canna-patent owners and applicants seeking to protect their innovations is what it has always been—obtaining canna-patents is highly valuable for companies in this industry, as these canna-patents will serve as irreplaceable stakeholders as the market continues to normalize and expand. And the stakes will continue to increase as courts and federal agencies take note.
 Final Written Decision, p. 15.
 Final Written Decision, p. 27.
A certain amount of comment has recently been evinced from the patent bar by the voicing from several members of the Federal Circuit, including the Chief Judge, of their dismay over the number of patent cases coming to the Court. In particular, this increase in the patent case census in Court is due in not some small degree to the number of cases arising from decisions by the Patent Trial and Appeal Board (PTAB) that the Court is tasked with reviewing regarding the validity vel non of patents from the various post-grant review proceedings (the largest number of which arise from inter partes reviews, IPRs). Perhaps in reaction to its dismay, the Court in several cases has remanded PTAB decisions based on failure of the Board to properly support their decisions to be amenable to appellate review; see, for example, Securus Tech v. Global Tel*Link (Fed. Cir. 2017) (IPR2014-01278) (Pat. No. 7,860,222); Ultratec v. CaptionCall and Matal (Fed. Cir. 2017). This basis for eschewing review has been much more rare in district court appeals but arose last week in the Court's decision in Tris Pharma Inc. v. Actavis Laboratories FL, Inc.
The case arose in ANDA litigation regarding Quillivant XR®, an extended release methylphenidate (MPH) formulation for the treatment of Attention Deficit Hyperactive Disorder (ADHD). The District Court found the asserted claims of U.S. Patent Nos. 8,465,765 ('765 patent), 8,563,033 ('033 patent), 8,778,390 ('390 patent), 8,956,649 ('649 patent), and 9,040,083 ('083 patent) were invalid as being obvious under 35 U.S.C. § 103. As explained in the opinion, MPH is a widely used psychostimulant that has been used for treating ADHD since the 1950's. Both immediate-release (IR) and extended-release (ER) formulations of the drug were also known in the art, and sustained-release (SR) formulations were developed more recently to overcome drawbacks of both IR and ER formulations. Unfortunately, prior art SR formulations were disadvantageous for having slow onset action properties. The claimed invention was a combination formulation comprising an IR component and an SR component that showed "a 45-minute therapeutic onset and 12 hours of therapeutic effect."
1. A methylphenidate aqueous extended release oral suspension comprising (1) an immediate release methylphenidate component, (2) a sustained release methylphenidate component comprising a water-insoluble, water-permeable, pH-independent, barrier coated methylphenidate-ion exchange resin complex, and (3) water, wherein said suspension has a pH of about 3.5 to about 5 and said suspension provides a single mean average plasma concentration peak for methylphenidate and a therapeutically effective plasma profile for methylphenidate for about 12 hours.
6. The suspension according to claim 1, wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for d-methylphenidate has an area under the curve (AUC)0-∞ of about 114 ng-hr/mL to about 180 ng-hr/mL, Cmax of about 11 ng/mL to about 17 ng/mL, Tmax of about 4 hours to about 5.25 hours and T1/2 of about 5 hours to about 7 hours following a single oral administration of an aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults.
The prior art considered by the District Court included several commercially available, extended-release MPH formulations (Concerta®, Daytrana®, Focalin XR®, Metadate CD®, and Ritalin LA®), U.S. Patent Application Publication No. 2010/0260844, and certain scientific publications. The commercial products all exhibited various pharmacokinetic and pharmacodynamics properties regarding a single or multiple PK peak profile, initial onset time and total duration. The '844 patent publication disclosed "a formulation of MPH that provides a rapid onset of action within 1 to 1.5 hours, a single Tmax of 5.5 to 7.5 hours, and a therapeutic duration of about 12 to 14 hours." Actavis relied on the '844 application in combination with Concerta®, Daytrana®, and Metadate CD® as teaching "a single mean peak PK profile, exhibiting an early onset of action, and exhibiting an extended duration of effect" that would have suggested to the skilled worker the early onset and extended duration formulation in the asserted claims. Tris Pharma argued to the contrary that the prior at taught combinations of IR and ER MPH formulations that resulted in a bimodal PK profile. This feature of combined IR and ER MPH formulations was designed to "mimic the peaks and valleys of multiple immediate release dosing regimens" which was not a feature of the claimed invention. In addition, the commercially available formulations showed a later Tmax that was important to achieve the longer duration.
The District Court disagreed (too cryptically, according to the Court's opinion) stating that "'[w]hile [it] believe[d] Tris'[s] evidence regarding the second generation products [wa]s persuasive, it [wa]s not dispositive on the obviousness inquiry.'" The District Court also found that the '844 application taught "an oral form of MPH with a long duration of action, rapid onset, and a single mean peak PK profile" and thus the skilled worker would have been motivated to produce the claimed formulations despite these formulations in the application had not in fact been made. The opinion also notes that the District Court relied on Actavis's expert's testimony regarding how a skilled worker would have interpreted the cited art and the meaning of specific terms and relationships between the features recited in the claims. Finally, the District Court rejected Tris Pharma's assertion of unexpected results, long-felt need, commercial success, and copying. The Court's opinion did not find that Tris Pharma had performed the requisite comparison experiments to show the results were unexpected, and that the existence of some of the commercially available formulations (specifically, Concerta®, Metadate CD®, and Ritalin LA®) rebutted long-felt need based on Tris Pharma's own expert testimony. The District Court also found only modest commercial success and that evidence of copying was "not compelling." This appeal followed.
[T]he district court failed to make the necessary factual findings and provide sufficient analysis of the parties' arguments to permit effective appellate review. Specifically, the district court's opinion merely recites the parties' arguments but fails to explain or identify which arguments it credits or rejects. We thus cannot reach the merits of whether the Quillivant XR® formulation would have been obvious over the prior art. Rather, we identify gaps in the district court's opinion and remand for the district court to conduct further fact-findings and detailed analysis consistent with this opinion.
For example, regarding the obviousness of producing an MPH formulation having the characteristics of a single mean peak profile, 45-minute onset, and 12-hour duration, the Federal Circuit found that the District Court's opinion was devoid of adequate fact finding to support the conclusion that formulations having these properties would have been obvious. For example, although the District Court found that the prior art would provide the skilled worker with an expectation that "a single mean peak PK profile could provide for rapid onset of action and extended duration of effect" it "never articulated which prior art references do so and how." Even when asserting the factual bases for its opinion, the panel stated that "it is unclear if these statements amount to actual fact-findings as opposed to a mere recounting of Actavis's arguments." The panel also found "holes" in the District Court's opinion, for example, "the district court never made explicit findings that Daytrana®, Concerta®, Metadate CD®, and/or the '844 application] also teach a 45-minute onset of action or 12-hour duration of effect." The panel opinion also characterized certain portions of the District Court's opinion as being "vague" and "imprecise" regarding "central, disputes issues on appeal."
Without the requisite factual findings and adequate explanation for such findings, we cannot affirm the district court's conclusion that a formulation with (1) a single mean peak PK profile, (2) 45-minute onset of action, and (3) 12-hour duration of effect would have been obvious over the prior art. We thus vacate those portions of the district court's opinion and remand those issues to the district court for specific factual findings [citations omitted].
The Federal Circuit found similar deficiencies in the District Court's opinion regarding issues related to the relationship between "early Tmax and [the] 12-hour duration of effect." The District Court's opinion on these elements was "very cursory," according to the Federal Circuit, and "[t]he entirety of the district court's discussion of Tmax appears amounts to a mere recitation of Actavis's experts' testimony regarding how (1) Tmax does not control the onset or duration of effect and (2) Tmax ranges in the prior art formulations overlap with the claimed Tmax range of 3.6 to 5.78 hours (factoring in the district court's construction of "about")."
Turning to the District Court's treatment of the objective indicia of non-obviousness, the Federal Circuit agreed with Tris Pharma that the District Court did not compare the properties of Tris Pharma's claimed invention with the prior art with regard to whether the invention showed unexpected results. Regarding long-felt but unmet need the Federal Circuit criticized the District Court for finding prior art products each having properties of "(1) a liquid MPH product that does not require swallowing a tablet; (2) a 45-minute onset of action; and (3) 12-hour duration of effect" but did not find a product having all three of these properties.
Based on all these deficiencies the Federal Circuit remanded to the District Court for "further fact-finding." Whether an increased frequency of these types of decisions based on Rule 52(a) in appeals from District Court opinions by a beleaguered Federal Circuit remains to be seen.
The Federal Circuit reversed a finding of non-obviousness in a Patent Trial and Appeal Board decision in an inter partes review, in an opinion handed down Monday in E. I. du Pont de Nemours & Co. v. Synvina C.V.
The patent was directed to methods for oxidizing 5-hydroxymethylfurfural or derivatives thereof under reaction conditions specified by the claims ("temperature, pressure, catalyst, and solvent"), to form 2,5-furan dicarboxylic acid ("FDCA"). FDCA can be produced from sugars and thus is considered by the Department of Energy to be a "green" or environmentally beneficial precursor to other materials.
1. A method for the preparation of 2,5-furan di-carboxylic acid comprising the step of contacting a feed comprising a compound selected from the group consisting of 5-hydroxymethylfurfural ("HMF"), an ester of 5-hydroxymethylfurfural, 5-methylfurfural, 5-(chloromethyl)furfural, 5-methylfuroic acid, 5-(chloromethyl)furoic acid, 2,5-dimethylfuran and a mixture of two or more of these compounds with an oxygen-containing gas, in the presence of an oxidation catalyst comprising both Co and Mn, and further a source of bromine, at a temperature between 140° C. and 200° C. at an oxygen partial pressure of 1 to 10 bar, wherein a solvent or solvent mixture comprising acetic acid or acetic acid and water mixtures is present.
(4) a catalyst comprising cobalt ("Co"), manganese ("Mn"), and bromine ("Br") ("based on both cobalt and manganese and suitably containing a source of bromine"; "The catalyst may also contain 'one or more additional metals, in particular [zirconium] and/or [cerium].'").
The opinion also consulted the specification to further explicate the meaning of these terms, as shown in the parenthetical annotations above. According to the opinion, "the specification states that the inventors 'surprisingly' achieved high yields of FDCA," which were asserted during the IPR proceedings to constitute one of the "secondary considerations" (aka objective indicia) of non-obviousness.
All of the cited references disclosed methods for producing oxidized HMF or a derivative under differing conditions, which overlapped the claimed conditions of temperature, pressure, solvent and catalyst. Depending on the reference, yields varied from 14% to 58.8%. Paradoxically, the prior art reference having the best yield (98%) specified water as solvent and using a platinum catalyst. The opinion set forth a table comparing the various reaction conditions.
"The two additional references, Lewkowski and Oae, are relevant to the FDCA esterification claims 7–9. Consistent with the '921 patent's acknowledgment that esterification of FDCA was known at the time of the invention, '921 patent col. 5 l. 42, Lewkowski and Oae both disclosed esterifying FDCA."
At final hearing, DuPont argued that "a burden-shifting framework" applied to the question of obviousness. The Board rejected this contention under In re Magnum Oil Tools International, Ltd., 829 F.3d 1364, 1375 (Fed. Cir. 2016), and Dynamic Drinkware, LLC v. National Graphics, Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015), which the PTAB held foreclosed this burden shift in an IPR. This was the error that caused the Federal Circuit to reverse the Board's judgment. The Board based its non-obviousness decision on its recognition that while the prior art disclosed performing the claimed reaction (oxidizing HMF or derivatives to FDCA), "none of the references relied upon by Petitioners expressly taught a process in which HMF or its derivatives were oxidized to FDCA using a Co/Mn/Br catalyst at a reaction temperature of between 140°C and 200°C while also maintaining the [PO2] between 1 and 10 bar," nor that adjusting the temperature and pressure variables to be within the claimed range would be a matter of mere routine experimentation.
The Board also considered the objective indicia of non-obviousness is arriving at its conclusion, but found that evidence to be "less probative in supporting a conclusion of non-obviousness" particularly with regard to unexpectedly high yields.
(1) DuPont has built a demonstration plant to produce FDCA and an FDCA ester ("FDME"), and the plant is capable of operating under conditions within the claimed ranges of the '921 patent; (2) Synvina is a competitor that alleged before the Board that Archer-Daniels-Midland Company's ("ADM") processes for producing FDCA were "embraced by the claims in the '921 patent," and (3) Synvina rejected DuPont's request for a covenant not to sue.
Turning to the merits, the opinion states it is applying the "old" legal principle that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," citing In re Aller, 220 F.2d 454, 456 (CCPA 1955); In re Geisler, 116 F.3d 1465, 1469–70 (Fed. Cir. 1997); and In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990). Said another way, "[a] prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art," citing In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003), and "such overlap creates a presumption of obviousness," citing Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731, 737–38 (Fed. Cir. 2013); Ormco Corp. v. Align Technology, Inc., 463 F.3d 1299, 1311 (Fed. Cir. 2006); and Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004). The presumption can be rebutted, according to the opinion, in the usual manner: by establishing one of the secondary considerations (aka objective indicia) of non-obviousness (unexpected results, typically by identifying a "critical" range of one of the recited parameters; or teaching away). Alternatively, "a change to a parameter may be patentable if the parameter was not recognized as 'result-effective,'" citing In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012), relying on In re Antonie, 559 F.2d 618, 620 (CCPA 1977)). Finally, prior art that recites very broad ranges of variables "may not invite routine optimization."
These cases applied this evidentiary standard in the context of district court litigation. The Federal Circuit held that there was no basis for the same standard not to be applied in IPR proceedings, and held the Board had erred in not considering this case law and instead relying on recent cases (In re Magnum Oil Tools International, Ltd., 829 F.3d 1364 (Fed. Cir. 2016), and Dynamic Drinkware, LLC v. National Graphics, Inc., 800 F.3d 1375 (Fed. Cir. 2015)) that were inapposite to the question (albeit involving IPRs). The panel cautioned that broad statements in their case law "must be interpreted in context" and that in overlapping range cases, "a patent challenger would have every incentive to point out the existence of an overlapping range, and virtually none to differentiate the claimed range from what was disclosed in the prior art." That latter task is left to Patent Owner, and general principles of burden shifting must accommodate this reality.
Further, the panel agreed with Petitioner that the Board erred in holding that the PO2 and temperature variables were not "result-effective variables." The opinion found error in the Board not applying the proper legal standard ("[a]lthough the Board correctly articulated the basic standard for result-effective variables , it did not follow it"): "a person of ordinary skill would not always be motivated to optimize a parameter "if there is no evidence in the record that the prior art recognized that [that] particular parameter affected the result," citing In re Antonie. In that case, the changes an inventor made in such a parameter could result in a non-obvious advance in the art, and provide an exception to the rule that "the discovery of an optimum value of a variable in a known process is normally obvious," citing In re Aller. Here, according to the opinion, the Board imposed the improper burden on Petitioner "to prove that the disclosures in the prior art 'necessarily required' the variable to be within the claimed range, or that the variables 'predictably affected FDCA yields.'" All that DuPont was required to show to support its obviousness contention was that the prior art recognized, either expressly or impliedly, that what was claimed (a method of oxidizing HMF and related molecules) was affected by the reaction temperature and PO2. The references supported DuPont's argument that the art recognized the dependence of the oxidation reaction on these parameters and thus these were "results-effective variables." Accordingly, mere optimization of them rendered the claimed methods prima facie obvious. Applying this proper legal standard to each of the challenged claims, the panel arrived at the conclusion that each claim was obvious. Importantly, the panel further refined its understanding of the Board's error insofar as "the Board did not consider the 'normal desire of scientists or artisans to improve upon what is already generally known,' which 'provides the motivation to determine where in a disclosed set of . . . ranges is the optimum combination,'" citing In re Peterson.
Finally, the Federal Circuit held that the Board's refusal to credit the Patent Owner's evidence of secondary considerations was supported by substantial evidence and thus not subject to being second guessed by the Court. With regard to long-felt need, the panel cited in support disclosure in the '921 of laboratory-scale, rather than industrial-scale, improvement in yields. Should this become the standard, of course, it is unlikely that long-felt need would ever be sufficient as a persuasive objective index of non-obviousness.
At bottom, this case involves a strong case of obviousness based on very close prior art and weak evidence of nonobviousness. We conclude that the Board therefore erred in not concluding that claims 1–5 would have been obvious at the time of the claimed invention.
The Court invalidated claims 7-9 using the same legal standard as applied to the art cited against claims 1-5 and the additional Lewkowski and Oae references, and that Synvina did not argue that claims 7-9 were separately patentable from claims 1-5.
This decision illustrates an application (in the chemical arts) of the principle regarding claims encompassing an incremental change to a known process that this Court (and undoubtedly, the Supreme Court; see KSR Int’l. v. Teleflex) considers undeserving of patent protection, because it falls within the art's ordinary skill to optimize a known process by varying parameters known to be important to how the process achieves a desired goal. As such there is nothing particularly remarkable about this case, except (as with all cases) to test whether the consequence of the application of this principle arrives at an outcome consistent with the purposes of patent law and thus affirm the correctness of the principle. The extent to which this depends on the "eye of the beholder" is apparent and perhaps unavoidable. But it is a proper exercise of the Federal Circuit's mandate, both to establish clear and (to the extent possible) consistent standards for patent law and provide a judicial check on the USPTO. In the IPR era, this latter function is more important than ever, nicely illustrated by the decision in this case.
Even with billions of dollars of funding and the cumulative knowledge and experience of over a hundred years of experimental pharmacology, de novo discovery of effective and safe therapeutics remains a costly and risky endeavor. The number of unsuccessful attempts to obtain Food and Drug Administration (FDA) approval of drugs for specific indications is far greater than the number of successes. As a result, there is an extensive and ever growing list of "failed" drugs, most of which are ultimately abandoned by pharmaceutical companies.
More recently, failed drugs previously considered to be lost causes are being reconsidered as possible therapies for different indications than those for which they had originally been considered. Such drug "repurposing" provides researchers and clinicians with a cost-effective way to identify potential new therapies without needing to start from scratch. Many failed drugs have already established their relative safety in Phase I clinical trials, which can simplify and reduce the cost of obtaining FDA approval should a new indication be found. Drug repurposing is not limited to failed drugs but is also being considered for currently marketed drugs as well as "off patent" generic compounds to expand and extend their usefulness.
But because drug repurposing primarily concerns previously-known drugs, obtaining patent protection can be challenging. In some cases, a drug to be repurposed is still protected by a patent that can be acquired and/or in-licensed, but often the drug itself is not protected by patent. Without patent protection, commercialization of a repurposed drug (i.e., maximizing the potential beneficial impact of the drug) is not realistic. This article discusses certain issues to be considered when trying to obtain new patent protection for repurposed drugs. It should be expected that each attempt to patent a repurposed drug will have its own factspecific challenges. Accordingly, the concepts discussed here are generalized and nonexhaustive.
The foundational inquiry for determining whether a repurposed drug can be patented in the United States is to consider whether, under 35 U.S.C. § 101, the drug constitutes patentable subject matter. Section 101, in relevant part, provides: "[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor . . . ." Repurposed drugs are often non-nature-based compositions of matter (i.e., synthetic compounds that are not naturally occurring) that can be used in useful processes (e.g., methods of treating a disease by administering to a patient in need thereof a therapeutically effective dose of a drug). Therefore, claims directed to repurposed drugs and methods of their use should not typically run afoul of § 101. Even repurposed drugs that are nature-based compositions of matter may still be patentable, for example, if recited in a method of treatment claim. Indeed, method of treatment claims reciting nature-based compositions of matter seem to be on more secure footing under § 101 in light of the recent decision in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, at least because the United States Patent and Trademark Office has issued a recent memorandum to the Patent Examining Corps advising that the Patent Office intends to follow the legal reasoning in this case. Nevertheless, care must be taken when drafting claims to avoid § 101 issues.
Another significant hurdle to overcome with respect to patenting repurposed drugs is 35 U.S.C. § 102. Section 102, as applied to a repurposed drug, requires that it was not previously patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before a patent application is filed to cover the repurposed drug. In other words, a claim to the repurposed drug itself must be novel, in that it must recite something not previously publicly known. Practically speaking, most composition of matter claims reciting only the repurposed drug will be excluded from patentability under § 102, because (almost by definition for a "repurposed" drug) the drug was previously known and thus its earlier public disclosure would be prior art to any subsequent patent filing. Accordingly, composition claims directed to the repurposed drug itself will likely be anticipated because they are not reciting anything new. Yet there are ways to overcome § 102 to obtain composition claims on repurposed drugs.
One useful approach for overcoming a § 102 rejection is to incorporate the repurposed drug into a composition that includes one or more other compounds to form a novel combination not previously known. Importantly, the claimed combination can be any practical combination that is novel for purposes of overcoming § 102. However, as discussed below, claims to pharmaceutical compositions that recite combinations with more than one key constituent (e.g., a therapeutically effective amount of a repurposed drug and a therapeutically effective amount of a second drug) are more likely to be patentable. Additional details regarding specific amounts of drugs included in combinations or ratios between the drugs in the combination can add further grounds for finding such claims patentable over what was previously known in the prior art.
A further approach to obtaining claims directed to previously known drugs that are patentable in a § 102 context is to draft claims to novel pharmaceutical dosage forms. Pharmaceutical dosage forms can be, for example, solids, liquids, delayed or extended release forms, and/or for a specific type of administration (e.g., oral, parenteral, intramuscular, etc.). Many types of variations are possible with pharmaceutical dosage forms, which lend themselves to drafting novel claims. For example, desired release characteristics and/or routes of administration may differ for the new use of the repurposed drug compared to its previous use, which would provide the basis of a novel claim.
As a final and particularly important example, a method claim reciting a repurposed drug may more easily overcome § 102 rejections. Repurposing a drug for a new indication is typically a novel use of the drug. Therefore, a method-of-use claim that recites a repurposed drug for treating a subject with the new indication should also be novel. Such method claims are particularly useful because they are difficult for competitors to design around, and they are also available in many foreign jurisdictions (though with potentially different formats).
A patent for a claimed invention may not be obtained . . . , if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Here, the basic calculus is that if a skilled artisan (e.g., a clinician or researcher in the same field of practice or study as the person seeking to repurpose a drug and with the average skill level of such clinicians or researchers) who understands the prior art would have reasonably expected the drug to be useful for the new indication, then a claim to a repurposed drug for the new indication may be obvious. Obviousness rejections of claims to repurposed drugs can be very complex and can be based on a combination of several prior art references, each teaching one or more aspects of the rejected claims.
Unfortunately, the relatively straightforward strategies for overcoming a § 102 rejection are mostly ineffective for overcoming obviousness rejections. Simple chemical combinations of repurposed drugs with other drugs that may make a novel composition are arguably obvious if they are nothing more than a routine exercise for a skilled pharmacologist. Fortunately, there are ways to overcome obviousness rejections, but they can require planning well before filing a patent application, and indeed, experiments to investigate the usefulness of a repurposed drug should be designed with obviousness rejections in mind. This is because one of the most powerful arguments against an obviousness rejection of claims directed to a repurposed drug is a showing of unexpected results. In this context, a showing of unexpected results can be a presentation of scientific data (often in the patent application, but data can also be presented after filing) that, for example, show a surprising effect of a drug that would not have been expected based on what was known at the time. Examples of unexpected results can include that a drug surprisingly works as intended for a new indication, or that a drug works at the dose used (e.g., a surprisingly low dose), or that a combination of drugs demonstrates synergy when used together (their combined effect being greater than each drug acting alone), among others. Another powerful example of unexpected results is the discovery that the drug acts via a different target or has a different mechanism of action for the new use than for its previous use. Such examples of unexpected results can overcome obviousness rejections for claims directed to method of use, or pharmaceutical dosage forms, or pharmaceutical compositions comprising a combination of drugs, respectively. Therefore, care should be given to experimental design and the types of data that are collected in support of such evidence of non-obviousness.
[A] written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same.
Section 112 also requires an application to have one or more claims "particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention." Basically, § 112 requires that, at the time of filing, the written description must enable a skilled artisan to replicate the invention (much like a scientific paper should enable a researcher to replicate the experiments and data presented in the paper) and that the claims must be fully supported by the written description.
Careful patent application planning and drafting can avoid or overcome § 112 rejections. At a minimum, literal support for each claim should be provided, examples of various embodiments of the invention described (e.g., the repurposed drugs and indication, possible drug substitutions and/or derivatives, dosing amounts, dosage forms, excipients, dosing regimens, methods of treatment, etc.), and experimental data establishing drug effectiveness included. The written description should also be drafted with sufficient detail and distinct variations of the invention to permit claim amendments that can dispose of a prior art rejection (under either § 102 or 103). Indeed, all important details and variations of the invention envisioned must be included before filing because § 112 prohibits addition of "new matter" after filing.
In conclusion, patent protection is possible for previously known drugs being repurposed for new indications. The best chances for patenting repurposed drugs occur when care is given to initial experimentation to establish the usefulness of the drugs and for identifying any unexpected properties of the drugs. By combining robust invention disclosures with thoughtful and detailed application preparation, patent applications directed to repurposed drugs will be better prepared to successfully navigate the rigors of the Patent Office.
 887 F.3d 1117 (Fed. Cir. 2018).
 See Memorandum from Robert W. Bahr, Deputy Comm'r for Patent Examination Policy, to Patent Examining Corps (Jun. 7, 2018), available at https://www.uspto.gov/sites/default/files /documents/memo-vanda-20180607.PDF.
 Other important objective evidence of non-obviousness, also known as "secondary considerations," includes evidence of commercial success, long-felt but unsolved needs, and failure of others. See Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17 (1966).
 See Manual of Patent Examining Procedure §§ 716.02, 2145.
The varying appellate fortunes of patentees regarding the question of obviousness is illustrated nicely in the Federal Circuit decision in Orexo AB v. Actavis Elizabeth LLC handed down earlier this month. The statute, 35 U.S.C. § 103, was intended to tether the question of obviousness to the prior art (and untether it from judicial whim regarding "inventiveness" or "invention" as found in several Supreme Court decisions stating with Hotchkiss, and, to patent law's detriment, resurrected under § 101 by Justice Breyer and in other recent decisions from the Court). Nevertheless, there cannot help to be a subjective aspect to the issue of obviousness, which is illustrated by this decision when placed in contrast, for example, with other recent obviousness determinations by the Federal Circuit (see, for example, "Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc.").
and a disintegrant selected from the group consisting of croscarmellose sodium, sodium starch glycolate, crosslinked polyvinylpyrrolidone and mixtures thereof.
6. The composition as claimed in claim 1, wherein the particles of citric acid are presented and act as carrier particles.
(wherein the italicized terms are relevant to the Court's determination).
The District Court found the asserted claims of the '330 patent to be obvious, based on prior art disclosure of sublingual formulations of buprenorphine and naloxone in 4:1 concentration ratios known to be effective for treating opioid dependence. Formulations according to the '330 patent provided smaller doses of buprenorphine that were effective and were less subject to abuse (which in the prior art comprised dissolving the formulation and injecting it directly into the bloodstream). There was no dispute between the parties regarding the improved effectiveness of the '330 patent formulations. The opinion states that the evidence presented at trial showed a 66% increase in bioavailability for buprenorphine for tablets containing 29% less of this drug. The District Court's obviousness determination rested on the components recited in the claims being known in the art, and that "although the specific formulation was not shown or suggested in any reference" the claims to the specific formulation were obvious. The District Court also held that evidence provided by Orexo regarding the objective indicia (aka secondary considerations) did not rebut its obviousness determination.
[T]he mere presence of citric acid in the sublingual tablets formulated according to the prior art (e.g. Cairns) is insufficient to achieve the superior pharmacokinetic profile exhibited by the instant invention. Applicant has persuasively demonstrated that the instant tablet exhibits unexpectedly superior sublingual buprenorphine bioavailability due to the ingredients as well as the structural characteristics recited in the instant claims [emphasis in opinion].
Also in the prior art were Suboxone® provided as "orally dissolvable films," which have the disadvantage (according to the opinion) that they cannot be easily removed once applied and limit the dosages that can be achieved (because no more than two films can be applied at one time). In addition to buprenorphine and naloxone in a 4:1 ratio, the films contain citric acid to reduce the pH to 3.0-3.5 in order to provide optimum bioavailability. This form of the drug dosage does not have the improved bioavailability or reduced amount of buprenorphine as provided in the '330 patent formulations.
The District Court also relied on an earlier Orexo published application (which did not mention citric acid as a component) and a European patent, EP 0 324 725, which listed a "large number of water-soluble carrier particles." Neither citric acid carrier particles, sublingual tablets, nor application of these formulations to opioids were mentioned in this reference.
The Federal Circuit opinion characterizes the District Court's error(s) as relying on the prior art for not excluding Orexo's formulation, for example with regard to including citric acid in the formulation (and, sub silentio appearing to consider inherent the bioavailability-improving properties of using citric acid as carrier particles for the buprenorphine microparticles specified in the '330 patent claims). The District Court also discounted Orexo's argument that lowering the pH using citric acid would change the effective concentrations of buprenorphine and naloxone, thus disrupting the 4:1 ratio known to be effective, saying that the ratio itself was an "unclaimed feature" and that this went to whether there would have been a reasonable expectation of success rather than any motivation to combine the prior art. The District Court was persuaded by Actavis's expert's testimony that citric acid "fits the definition of a carrier particle" and would act as one, although the panel notes the cited art did not disclose using citric acid as a carrier.
Regarding the objective indicia, although the District Court acknowledged that "the unexpected result of increased bioavailability provides some support for nonobviousness," the improved bioavailability was "a difference in degree,' not a difference in 'kind.'" The District Court also was unpersuaded by Orexo's evidence regarding teaching away, long-felt need, and copying.
The panel opinion rejected the District Court's analysis as being infected by hindsight and using the '330 patent disclosure as a template for finding the disclosed aspects of the claimed invention in the prior art. The prior art disclosure of using citric acid to lower the pH of buprenorphine/naloxone formulations either disrupted the 4:1 drug ratio or did not increase buprenorphine bioavailability and thus did not support Actavis's argument nor the District Court's persuasion by it. The Federal Circuit also did not find assertion of Orexo's earlier published application to support non-obviousness, insofar as this reference made no mention of including citric acid in any opioid formulation. And the cited EP'725 patent merely recited a "general description of interactive mixtures as pharmaceutical formulations" and did not recite any specific disclosure relating to sublingual tablets, opioid formulations, citric acid as a carrier particle (despite reciting an "extensive list of carrier particles") or anything else relevant to the question of obviousness of the '330 patent claims.
Actavis Counsel: Your Honor, I will confirm what counsel said before and what we've said in our briefs. There is no piece of prior art that was presented that says citric acid is a carrier particle or should be used as a carrier particle.
Court: If both of those things are really well known, then one would think that if citric acid were routinely or it was obvious to use it as a carrier particle, you could have found some reference that used it. . . . Your expert didn't even testify that he was familiar with this industry and that citric acid was routinely used as a carrier particle in interactive mixtures. He just said it was the right size and it could be used.
Actavis Counsel: Well. You're right Your Honor in terms of your characterization of the record. There was not citric acid used as a carrier particle that was in the record.
The opinion illustrates the District Court's error in accepting as evidence supporting obviousness testimony that, if selected, citric acid as a carrier particle would have been expected to work, citing In re Gordon, 733 F.2d 900, 902 (Fed. Cir. 1984) ("The mere fact that the prior art could be so modified would not have made the modification obvious unless the prior art suggested the desirability of the modification."). A similar error arose concerning the District Court's dismissal of Orexo's argument regarding preserving the 4:1 ratio of buprenorphine to naloxone, the panel stating the error to be the District Court's finding that "there is nothing in the prior art which would have discouraged a person of ordinary skill from following the path set out in the various references" instead of recognizing that "no reference or combination of references proposes the path of the '330 Patent." Put more succinctly the opinion states "[t]he question is not whether the various references separately taught components of the '330 Patent formulation, but whether the prior art suggested the selection and combination achieved by the '330 inventors."
Finally, the opinion turns to the objective indicia, which "guide the analysis of obviousness," citing Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346, 1357–58 (Fed. Cir. 2013). Without expressly stating it, the Court here finds clear error in the District Court's discounting these factors, for example, stating that a 66% increase in buprenorphine bioavailability was "more than a trivial 'degree.'"
Determining obviousness is always a reconstruction, imperfectly done, of a past that never was. The prior art is consulted and the question asked, would the worker of ordinary skill in the art have been able to achieve the claimed invention with a reasonable expectation of success? Of course, this question is posed against a backdrop of the ordinarily skilled worker not having achieved the invention; that accomplishment was attained by the named inventor. Nevertheless, the Supreme Court since Hotchkiss and the Patent Act since 1952 has recognized that sometimes the answer to the question must be no, if only to ensure that the constitutional mandate that Congress only grant patents that will "promote the progress of . . . the useful arts" be satisfied.
In patent litigation, defendants have the motivation to cast the imperfect past in light most favorable to the claimed invention being obvious, and to balance the rhetorical scales they also bear the burden of establishing obviousness (as in all invalidity pleadings) by clear and convincing evidence. But what is clear and convincing to some is not to others, and the Federal Circuit's split decision affirming the District Court's obviousness determination in Acorda Therapeutics, Inc. v. Roxane Labs., Inc. illustrates the point -- and at the same time shows that even the "objective" indicia of non-obviousness identified by the Supreme Court in Graham v. John Deere do not always provide a reliable, fact-and historically based shield to a finding of non-obviousness.
The lawsuit arose when Roxane and co-Defendants Mylan Pharmaceuticals, Inc., and Teva Pharmaceuticals USA, Inc. each filed an Abbreviated New Drug Application (ANDA) for Acorda's multiple sclerosis drug (Ampyra®) and sent Paragraph IV letters to Acorda (and co-Plaintiff Alkermes Pharma Ireland Ltd.) asserting that four Orange Book-listed patents (U.S. Patent Nos. 8,007,826; 8,663,685; 8,354,437; and 8,440,703) were invalid. As the Federal Circuit panel stated, there was one additional patent, U.S. Patent No. 5,540,938, owned by Elan Corp. plc and exclusively licensed to Acorda. That patent broadly claimed therapeutic formulations of 4-aminopyridine (4-AP); Acorda's patents were for more narrow formulations having specific characteristics and properties that distinguished (undisputedly, for novelty purposes) these claims from the claims of the '938 patent.
whereby an in vivo CmaxSS:CminSS ratio of 1.0 to 3.5 and a CavSS of 15 ng/ml to 35 ng/ml are maintained in the human.
Wherein asserted dependent claim 7 includes the limitation "whereby an increase in walking speed is obtained in said human."
1. A method of increasing walking speed in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein said 10 milligrams of 4-aminopyridine twice daily are the only doses of 4- aminopyridine administered to said patient during said time period.
Wherein claim 18 recites that the dosage form is a tablet, and claim 22 recites that the tableted formulation of 4-aminopydirine "exhibit[s] a release profile to obtain a release profile of about CavSS of 15 ng/ml to 35 ng/ml."
In the ensuing ANDA litigation the Defendants stipulated to infringement but recited as counterclaims that all claims at issue were invalid for obviousness. The District Court found the '826, '685, '437, and '703 (but not the '938 patent) obvious, and entered final judgment and an injunction that precluded final approval by the FDA of Defendants' ANDAs until July 20, 2018 (the expiration date of the '938 patent). This appeal ensued.
The Federal Circuit affirmed, in an opinion by Judge Taranto joined by Judge Dyk; Judge Newman dissented (vigorously). The opinion set forth the extensive prior art asserted against Acorda's claims, as well as evidence that Elan had tried (and failed) to produce a suitable 4-AP formulation, and that Sanofi had also attempted making such a formulation without success. Distinctions with the prior art included the need to titrate the dose of 4-AP, which (as the opinion concedes) had a "narrow toxic-to-therapeutic range"; also noted in the opinion was the variable reports of efficacy and frequent reports of serious side effects (including seizures) and that Acorda's methods, administration regimens, and sustained-release formulations were the only ones the FDA approved to improve walking speed in MS patients.
Nevertheless, the majority affirmed based on finding the salient limitations (set forth above numbered 1-4) recited in the prior art, and that the skilled worker would have had a reasonable expectation of success in achieving the claimed invention in view of this extensive prior art. The majority rejected Acorda's three contentions: "that the district court erred in finding that a person of skill would have had a motivation to combine the prior art to arrive at the Acorda invention and a reasonable expectation of success in doing so"; "that the claim limitations relating to pharmacokinetics—i.e., achieving 4-AP serum levels of 15–35 ng/ml— are inherent in the claimed invention and therefore obvious"; and "that the court improperly applied a categorical rule that a blocking patent (the Elan patent) negates any findings in favor of Acorda on the objective indicia of commercial success, failure of others, and long felt but unmet need." While the majority appears to have cherry-picked the prior art and reconstructed the invention using the claims as a roadmap (illustrating why the Supreme Court might have underestimated the pernicious effects of hindsight in obviousness determinations in KSR Int'l. Co. v. Teleflex. Inc.), it is the majority's rejection of Acorda's third argument that makes this decision noteworthy.
Merck II's reasoning reflects a common-sense recognition that, as a theoretical matter, a blocking patent may or may not deter innovation in the blocked space by commercially motivated potential innovators other than the owners or licensees of the blocking patent. Where the owner of the blocking patent or exclusive licensee is different from the owner of the patent in suit, the granting of a license may be a realistic possibility. Even where, as here, the owner of the patent in suit and the exclusive licensee of the blocking patent are the same, such a potential innovator might or might not think it could successfully challenge the blocking patent. And such a potential innovator might or might not be willing to research in the blocked space without a license to a blocking patent—even if the research itself is within the safe harbor provided by 35 U.S.C. § 271(e)(1)—and wait until it has already developed and patented its aimed-at improvement to negotiate for a cross-license with the blocking patent's owner to share the profits from the improvement. Besides the assessment of whether the blocking patent can be successfully challenged, a number of variables appear generally relevant to the calculus, including: the costliness of the project; the risk of research failure; the nature of improvements that might arise from the project, and whether such improvements will be entirely covered by the blocking patent; the size of the market opportunities anticipated for such improvements; the costs of arriving at the improvements and getting them to market; the risk of losing the invention race to a blocking-patent owner or licensee; the risk that the blocking-patent owner (making its own economic calculations, perhaps in light of its own other products or research activities) will altogether refuse to grant a license to the improvement or will demand so large a share of profits that the whole project is not worthwhile for the potential innovator—all evaluated in light of other investment opportunities.
Taking these factors and the prior art into consideration (including the fact that Acorda been given an exclusive license to Elan's patent), the majority held that the District Court had not erred in its analysis, a conclusion supported by the deference due the District Court on the factual question of commercial success. The same blocking effect was also fatal (to the panel majority) to the assertion of "long-felt need" and "failure of others" as objective indicia of non-obviousness.
The record shows that many scientists in many institutions studied and eventually abandoned 4-AP as a treatment prospect for multiple sclerosis. These abandoned studies constitute the prior art on which the district court and my colleagues rely for obviousness of the Acorda Patents. However, the experimentation with 4-AP shows just the opposite – it shows that work with 4-AP was abandoned due to the inability to balance the compound's potential effectiveness with its toxicity.
Over and over, through her litany of the prior art, she shows that the majority used prior art to support obviousness that revealed failure to achieve the therapeutic goals without risking (and incurring) serious side effects. Judge Newman sets forth instances where the majority apparently ignored or downplayed evidence that prior art upon which their decision relied reported abandonment of research and development efforts on 4-AP due to "toxicity and seizures," encephalopathy, and hepatitis, or "dizziness, hypotension, or nausea" that accompanied the drug's use. The record shows that even Acorda, like all the other researchers, initially failed to develop a sustained release formulation and administration regimen effective in improving walking speed in MS patients, and that it was only when Acorda achieved an "analytical breakthrough" (i.e., a reevaluation of the clinical data) that its Ampyra® product was successfully developed.
Acorda is correct that there was no suggestion in the prior art that the claimed combination should be tried, and there is no hint of a reasonable expectation of success. Acorda points to the decades of failure of others to develop a safe and effective treatment for multiple sclerosis using 4-AP, despite its known toxicity. The district court's selection of separate limitations from separate sources, and retrospectively fitting them into the Acorda template, is achieved only with the hindsight knowledge of Acorda's eventual success. See Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1086 (Fed. Cir. 2008) ("The determination of obviousness is made with respect to the subject matter as a whole, not separate pieces of the claim."). Here, only the Acorda Patents teach the combination that successfully treats this multiple sclerosis impairment while avoiding toxicity and seizures.
Commercial success is measured against the products available for the same purpose, not against infringing copies of the patented product. Defendants do not contend that they are precluded from providing or developing other treatments for multiple sclerosis. The Acorda product met a long-felt need, for which the failure of others, despite decades of experimenting with the neurological properties of 4-AP, is evidence of the unobviousness of the Acorda achievement. Such evidence is an important aid to a court that is attempting to divine whether the patentee's discovery was obvious in accordance with law [emphasis added].
For good measure, Judge Newman ends her dissent by noting that "[t]he district court was advised that the Patent Trial and Appeal Board sustained the validity of the Acorda Patents in inter partes review, at Coalition for Affordable Drugs (ADROCA), LLC v. Acorda Therapeutics, Inc., 2017 WL 950736 (P.T.A.B. Mar. 9, 2017). Although the majority reports this event, as did the district court, its consequences are not explored, including issues of privity, estoppel, and finality."
Luminara Worldwide, LLC appealed from three inter partes review (IPR) decisions, in which the Patent Trial and Appeal Board held unpatentable a total of 31 claims across Luminara's three patents. On appeal, Luminara challenged the Board's decisions as to one claim from each patent and asserted that the Board's application of the 35 U.S.C. § 315(b) time-bar was improper as to the '319 patent. The Federal Circuit dismissed the IPR with respect to the '319 patent, holding that the § 315(b) time-bar applied, and affirmed the other two IPR decisions.
In instituting review of the '319 patent, the Board first addressed whether the IPR was time barred under 35 U.S.C. § 315(b), since the petition was filed more than a year after Liown was served with a complaint alleging infringement.
35 U.S.C. § 315(b) provides that inter partes review may not be instituted if the petition requesting the proceeding is filed more than 1 year after the date on which the petitioner is served with a complaint alleging infringement of the patent.
Specifically, on November 2, 2012, Candella, LLC, a predecessor in interest of Luminara, filed a complaint in the District of Minnesota against Liown for infringement of the '319 patent. Service of the complaint was acknowledged on December 3, 2012. On December 16, 2013, the parties having agreed to a dismissal, the District Court entered a voluntary dismissal without prejudice.
On August 5, 2014, Luminara commenced another lawsuit against Liown, again alleging infringement of the '319 patent as to the same products involved in the earlier case. On July 31, 2015, within one year of service of the second action, Liown filed for an IPR of the '319 patent.
Luminara argued that Liown was time-barred as to the '319 patent under 35 U.S.C. § 315(b) because the petition was filed more than one year after service of the first action. In instituting the IPR, the Board rejected the timeliness argument because the first action had been voluntarily dismissed without prejudice.
However, now, in Click-To-Call Technologies, LP, v. Ingenio, Inc, No. 15-1242 (Fed. Cir. Aug. 16, 2018), the en banc court held that § 315(b)'s time-bar applies in such a scenario present here. Thus, because the § 315(b) time-bar applies when the underlying complaint alleging infringement has been voluntarily dismissed without prejudice, the Board erred in instituting the IPR challenging the '319 patent. Thus, the Board's final written decision as to the '319 IPR was vacated, and remanded for dismissal of that IPR.
On the merits, the Board issued final written decisions determining that the claims were either anticipated or would have been obvious over the prior art.
Specifically, the Board determined that claim 14 of the '166 patent would have been obvious over the prior art. Claim 14 reads: "[t]he apparatus of claim 13, wherein the pivot hole is larger in diameter than an exterior dimension of the support element, whereby the flame body swings or pivots freely about the support element."
The ability to rotate "about" or "around" a supporting rod means that there is relative motion between the two parts. The Expert explained that such relative motion necessarily implies that the hole is bigger than the rod, and that parts of the prior art drawings indeed show a hole bigger than the rod.
While Luminara argued that the claim limitation necessitates movement in additional directions, the claim only requires the ability to "swing or pivot," not necessarily movement in other directions.
Thus, the Federal Circuit found that the conventional usage of rotation about a structure suggests movement relative to the structure, and if relative movement is possible, a person of ordinary skill would know that the pivot hole is larger in diameter than the rod.
wherein the pendulum support member is coupled to the housing to remain stationary during pivotal movement of the pendulum member by the drive mechanism.
The Board explained that a gimbal mechanism in one piece of prior art could be replaced by a wire of another prior art reference to render the invention obvious and that there was motivation to combine the prior art references. On appeal, Luminara argued that it was not afforded proper notice, because while Liown's petition specified the replacement of a rod in the prior art, it did not specify that the gimbal mechanism would be replaced and that this represents a change in the obviousness theory.
The Federal Circuit disagreed, and concluded that the Board did not change the obviousness argument midstream. Liown's petition explained that the proposed combination of art would remove the entire gimbal structure. The petition specifically pointed out that the support wire, with its both ends connected to the housing, would provide a support. The Federal Circuit found that these descriptions made it clear from the outset that the modification involved eliminating the entire gimbal. Further, in its preliminary response, Luminara responded to the argument that the entire gimbal would be replaced. Liown's reply further explained that the entire gimbal would be replaced. Thus, the obviousness theory did not change, and the Federal Circuit affirmed the Board's decision.
Looking at the specific rejection, however, it's hard to understand the theory of motivation, or how the first reference, when modified by the second reference, could be seen to arrive at the claimed invention. Figure 6 of the primary reference is shown below, which includes the gimbaled mechanism allegedly modified by the secondary reference in which Figure 1 is reproduced showing the "wire" mechanism.
Finally, below is Figure 1 of the '869 patent. It would seem that many arguments could have been made to address the substantive obviousness rejection, however, such arguments were left on the table.
Last month, in Endo Pharmaceuticals Solutions, Inc. v. Custopharm Inc., the Federal Circuit affirmed a decision by the U.S. District Court for the District of Delaware finding that Defendant-Appellant Custopharm Inc. had not proven that claim 2 of U.S. Patent No. 7,718,640 or claim 18 of U.S. Patent No. 8,338,395 were invalid as obvious under 35 U.S.C. § 103. The '640 and '395 patents are owned by Plaintiffs-Appellees Bayer Intellectual Property GmbH and Bayer Pharma AG.
Seeking approval to market a generic version of Aveed®, a long-acting injectable testosterone replacement therapy for men suffering from physiologically low levels of testosterone, for which Plaintiff-Appellee Endo Pharmaceuticals Solutions, Inc. holds the approved New Drug Application, Paddock Laboratories, LLC (Custopharm's predecessor-in-interest) filed an Abbreviated New Drug Application (ANDA) with the FDA. In response to that filing, Endo and Bayer brought an action for infringement of the '640 and '395 patents. During the proceedings, Custopharm stipulated to infringement, and Endo and Bayer limited their asserted claims to claim 2 of the '640 patent and claim 18 of the '395 patent.
A composition formulated for intramuscular injection in a form for single injection which contains 250 mg/ml testosterone undecanoate in a vehicle containing a mixture of castor oil and benzyl benzoate wherein the vehicle contains castor oil in a concentration of 40 to 42 vol %.
A composition formulated for intramuscular injection in a form for single injection according to claim 1, which contains 750 mg testosterone undecanoate.
(ii) a maintenance phase comprising subsequent intramuscular injections of a dose of TU at an interval of 10 weeks between injections, each dose including 500 mg to 1000 mg of TU.
The method of claim 14, in which each dose contains 750 mg of TU.
The key elements of both claims in dispute are: (1) 750 mg TU, (2) vehicle consisting of castor oil and a co-solvent (benzylbenzoate in the '640 patent) where the castor oil is 42% or less by volume, and (3) an injection schedule comprising two initial injections at an interval of four weeks followed by injections at ten week intervals ('395 patent only).
At trial, Custopharm argued that the claims-at-issue were obvious in view of three primary references: Behre et al., 140 Eur. J. Endocrinol. 414 (1999); Nieschlag et al., 51 Clin. Endocrinol. 757 (1999); and von Eckardstein et al., 23(3) J. Androl. 419 (2002). These references describe clinical studies using 1000 mg TU injections, wherein the administered composition comprises 250 mg/mL TU in castor oil. The parties agreed that these references do not describe the use of a co-solvent. Custopharm also relied on two additional references: Pushpalatha et al., 90 Naturwissenschaften 40 (2003); and Riffkin et al., 53(8) J. Pharm. Sci. 891 (1964). Pushpalatha describes the effects of an injectable composition of hydroxyprogesterone in a mixture of 40% castor oil and 60% benzyl benzoate (Proluton Depot), which is administered once a week to pregnant women to prevent miscarriage. Riffkin describes the use of castor oil for the parenteral administration of steroids.
The District Court determined that Custopharm had not met its burden of proving that the claims-at-issue were obvious. In particular, the District Court found that (a) the prior art did not disclose the 750 mg TU injection dosage, (b) Custopharm failed to show by clear and convincing evidence that a skilled artisan would have been motivated to lower the dosage of TU from 1000 mg to 750 mg due to concerns that patients were being overdosed, (c) the cited references do not inherently disclose benzyl benzoate as a co-solvent or the particular ratio of solvent to co-solvent recited in the claims-at-issue, and (d) the prior art did not disclose the specific injection schedule claimed in the '395 patent, and this specific schedule would not have been obvious to a skilled artisan.
The '640 and '395 patents disclose three primary elements in the composition and administration of Aveed®: (1) 750 mg TU in (2) a 40% castor oil and 60% benzyl benzoate vehicle (the benzyl benzoate element only applies to the '640 patent; the '395 patent only requires a cosolvent) (3) administered at an initial interval of two injections four weeks apart and maintenance injections at ten week intervals thereafter (’395 patent only).
Custopharm argued that a skilled artisan would have recognized that patients were being overdosed with 1000 mg TU injections at a concentration of 250 mg/ml, and therefore that it would have been obvious to a skilled artisan to reduce the amount of injected fluid to 3 ml while maintaining the same TU concentration for a total of 750 mg TU per injection. Custopharm also argued that the cited references inherently describe the vehicle formulation (40% castor oil and 60% benzyl benzoate). Cusotpharm further argued that such a dose adjustment would have made it obvious to adjust the injection interval to use a two-phase dosing regimen. The Federal Circuit, however, disagreed with each of Custopharm's arguments, finding no clear error in the District Court's underlying factual findings.
With respect to Custopharm's argument that the District Court clearly erred in finding no motivation to lower the dose of TU from 1000 mg to 750 mg in view of the American Association of Clinical Endocrinologists (AACE) Guidelines (which Cusotpharm contended showed that patients were being overdosed in prior art clinical studies), the Federal Circuit noted that "Custopharm's overdose argument is predicated on the assumption that a skilled artisan would have applied the AACE Guidelines to the exclusion of other guidelines that existed at the time, including the FDA Guidelines." The opinion also notes that the most prevalently applied guidelines in clinical practice and the guidelines cited in the patents-at-issue were, in fact, the FDA guidelines, which differed from the AACE guidelines. The Federal Circuit therefore concluded that "the district court reasonably rejected Custopharm's argument that a skilled artisan would consider 1000 mg of TU to be an overdose and would have been motivated to lower the dosage to the patented 750 mg."
[W]ere about inherently present properties or characteristics for a "known" prior art product. But here, the TU injection composition recounted in the Articles cannot be said to be "known" in the same way; the Articles failed to disclose that the composition's vehicle formulation included another, key ingredient, benzyl benzoate, let alone the ratio of benzyl benzoate to castor oil. And there was no evidence in the record that a skilled artisan could determine the non-disclosed vehicle formulation based on the reported pharmacokinetic performance profile, or that the non-disclosed vehicle formulation was necessarily a feature of the TU injection studied in the Articles. Under the circumstances of this case, the incomplete description of the TU injection composition elements denied skilled artisans from having access to that composition, thereby precluding use of the inherency doctrine to fill in disclosure about the product missing from the Articles.
Thus, the Court concluded that "the district court did not err in finding that Custopharm did not present clear and convincing evidence showing the 40% castor oil to 60% benzyl benzoate as claimed was necessarily present in the Articles."
As for Custopharm's argument that a skilled artisan would have been motivated to combine the vehicle formulation of Proluton with the lowered dose and modified injection schedule, the Federal Circuit again disagreed. In particular, the Court noted that neither Pushpalatha nor Riffkin suggest the use of benzyl benzoate as a co-solvent, adding that Proluton is not a testosterone product for men, but rather is administered to pregnant women to prevent miscarriage, and further, that it is not an injectable steroid with prolonged activity. The Federal Circuit therefore concluded that "the district court did not err in rejecting Custopharm's argument that the patented formulation for Aveed® was obvious over Proluton in view of the prior art."
The opinion turned next to Custopharm's final argument on appeal, that once a skilled artisan recognized that patients injected with 1000 mg TU were being overdosed, the specific injection schedule claimed in claim 18 of the '395 patent would be the result of routine treatment of individual patients and thus obvious. The Federal Circuit, however, dismissed this argument as well, explaining that "this argument is predicated on Custopharm's overdose theory, which we have already rejected supra." The Court also noted that the cited references do not explicitly teach the use of loading doses, and could be interpreted as reasonably teaching a skilled artisan to increase the intervals between doses, not to initially shorten them to four weeks and then to lengthen them to ten weeks. The Federal Circuit therefore concluded that "the district court properly found that Custopharm failed to meet its burden of showing that a skilled artisan would combine the lowered dose with the injection schedule in the manner claimed."
Concluding that the District Court did not commit reversible error in finding that claim 2 of the '640 patent and claim 18 of the '395 patent were not proven to be obvious over the prior art, the Federal Circuit affirmed the District Court's decision that neither claim 2 of the '640 patent nor claim 18 of the '395 patent were invalid as obvious under 35 U.S.C. § 103.
In a nonprecedential decision, the Federal Circuit found all challenged claims directed to a graphical user interface of a U.S. Patent obvious over a combination of prior art. Valmont Industries, Inc. appealed from the final decision of the Patent Trial and Appeal Board in an inter partes review, finding claims 1–10, 12–15, 17, and 18 of U.S. Patent No. 7,003,357 unpatentable as obvious. Lindsay Corp. also cross-appealed the Board's determination that claim 11 was not obvious. Reviewing all prior art, the Federal Circuit found that all of these claims were, in fact, obvious.
The '357 patent is directed to remotely monitoring and controlling irrigation equipment using handheld devices. A remote user interface displays icons, referred to in this patent as graphical user interfaces ("GUIs"), which show the status of irrigation equipment and allow its control. Prior art systems monitored and controlled irrigation equipment through personal computers. Because personal computers are typically located at a base station, these systems required users to return to the base station to control the irrigation equipment. The '357 patent is directed to the use of handheld devices to allow a user to view the status of and control irrigation equipment from any location using wireless telemetry technology, as shown below in Figure 1 of the patent.
(c) transmitting signals to the irrigation equipment to control the irrigation equipment in accordance with said user's commands.
11. The remote user interface of claim 10 wherein said software is further operative on said processor to change the shape of said plurality of GUIs change [sic] in response to a change in the status of the irrigation equipment.
The Board found that all of the challenged claims, except claim 11, would have been obvious to a person of ordinary skill in the art, but that claim 11 would not have been obvious.
In particular, the Board found that claims 1–3, 6–10, 12–14, 17, and 18 would have been obvious in view of two prior art references including a primary reference that described remotely monitoring and controlling an irrigation system using a computer to display GUIs, and a secondary reference brought in for describing remotely monitoring and controlling various types of field devices for industrial processes using a handheld device displaying GUIs.
On appeal, Valmont argued that there was insufficient evidence of a motivation to combine the references because the handheld devices in the secondary reference lacked sufficient display capabilities and computing capacity to operate the system described in the primary reference. The '357 patent has a 2001 priority date, and expert testimony was provided to demonstrate that at the time of the invention, a person of ordinary skill would be able to employ the system of the primary reference on a mobile device disclosed in the secondary reference. In particular, mobile phones at the time, could display GUIs and receive user commands through manipulation of GUIs.
The Federal Circuit agreed and found that substantial evidence supported the Board's determination that a person of ordinary skill would have had a reasonable expectation of success in combining the references and would have been motivated to make the combination.
Addressing dependent claim 11, which requires that the software be operative "to change the shape of said plurality of GUIs change [sic] in response to a change in the status of the irrigation equipment," a third reference was cited for teaching a display of circle-shaped or square-shaped GUIs in which status information as to irrigation patterns is indicated in various ways, including by shading.
The question to consider was whether a change in shading constituted a change in "shape." Applying the broadest reasonable construction, the Board concluded that "shading within the original GUI does not change the shape of the GUI." But the Federal Circuit disagreed and found that a change in shape occurs when there is a change in pattern, such as through shading.
The Federal Circuit first turned to a dictionary definition of "shape" as "the visible makeup characteristic of a particular item or kind of item," and found that a change in shading falls within this definition as it is a change in the visible makeup characteristics of the circle.
Most importantly, however, the specification discusses shading and discloses that shading constitutes a change in shape as well. For example, the specification describes a GUI to represent a pivot irrigation system that could be partitioned into wedges to depict different settings along the pivot path. It then states, "[d]ifferent colors or patterns can be used to shade each wedge to depict the particular spray pattern chosen for each wedge," and further describes how "cross-hatching" may represent one setting and a "speckled pattern" may represent another. Thus, changes in shading of the GUI reflect a change in status of irrigation patterns. The Federal Circuit thus found that this suggests that a change in shading is a change in shape within the scope of claim 11.
One thing to keep in mind is that when it says the shape or the status information in the GUI, shape doesn't necessarily have to be just that it's a circle or just that it's a triangle. It could potentially be that it's a circle that's got lines through it or a triangle that has a checkerboard pattern across it. So there's different kinds of shapes that it could be that would allow it to show all of these different products.
Thus, under Valmont's own definition or under the broadest reasonable construction standard, a change in shading would constitute a change in shape of the GUI. As a result, since the third reference describes a change in shading to reflect a change in irrigation pattern, the resulting combination of references encompassed the limitations of claim 11. Thus, the Federal Circuit also found claim 11 obvious as well.
Last week, the Federal Circuit found all patent claims invalid for obviousness in an inter partes review, in Praxair Distribution, Inc. v. Mallinckrodt Hospital Products IP Ltd. But the Court did not render its decision without engendering a judicial disagreement between the majority and Judge Newman on the proper role of the printed matter doctrine in obviousness determinations.
in accordance with the recommendation of [claim 7], discontinuing the treatment with inhaled nitric oxide due to the neonatal patient's pulmonary edema.
The Board found claims 1-8, 10, and 11 to be obvious over a combination of four prior art references, but found claim 9 not to be obvious, its analysis for this claim resting on its construction of the phrase "in accordance with" (as discussed below).
The PTAB gave the limitations set forth in italics above to implicate the printed matter doctrine, insofar as they recited information transmitted to a doctor or other medical practitioner. These encompassed mental steps, according to the Board, and on these grounds were given no patentable weight in the Board's obviousness assessment. So construed, the Board found claims 1-8, 10, and 11 to be obvious because the skilled worker would have been motivated to combine the prior art, which disclosed the provisions of claim 1 having patentable weight (i.e., not disclosing the information regarding neonatal risk to nitric oxide (NO) administration). On the contrary the Board found claim 9 not obvious because the prior art did not teach excluding from NO treatment neonates identified using the method recited in the claim.
The Federal Circuit affirmed the Board's obviousness determination for claims 1-8, 10, and 11 and reversed the Board's finding that claim 9 was nonobvious, in a decision by Judge Lourie, joined by Chief Judge Prost and Judge Newman; Judge Newman filed a concurring opinion. As discussed in the opinion, Mallinckrodt argued that the Board's application of the printed matter doctrine for claim construction was improper and should be limited to determining whether the claims were invalid after the claims were construed. The Federal Circuit disagreed, holding that it was proper not to give printed matter patentable weight under these circumstances, and that the printed matter doctrine (and exclusion of these limitations) was proper when what the limitation recites is the content of the information provided according to the claims as recited here.
The Board and the panel majority did not apply the printed matter doctrine on grounds that the claims did not recite patent eligible subject matter under Section 101, but limited its consideration to obviousness, citing AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1064 (Fed. Cir. 2010), to the effect that merely adding an instruction sheet or other informational content to a drug product, even if required by the FDA for approval, is not sufficient to create a functional relationship that could form a basis for distinguishing the prior art.
[T]he potential benefit of treating the [neonatal patient] with 20 ppm inhaled nitric oxide vs. the potential risk that inhaled nitric oxide could cause an increase in PCWP leading to pulmonary edema in patients who have pre-existing [LVD], in order to arrive at a decision of whether or not to treat the [neonatal patient] with inhaled nitric oxide.
And this, according to the opinion, is equivalent to a doctor thinking about the information provided. Relevant to Judge Newman's concurrence (albeit not expressly directed to it), the opinion states that "adding an ineligible mental process to ineligible information still leaves the claim limitation directed to printed matter."
The opinion also rejected Mallinckrodt's argument that the term "pharmaceutically acceptable" incorporates the information contained in what the Board considered the printed matter. Instead, the Federal Circuit held that the term is related to "the physical condition of the gas" rather than how or to whom the gas is administered, and that this phrase does not impart a functional relationship with the information recited in the limitation excluded under the printed matter doctrine.
With regard to Mallinckrodt's assertion that the Board erred with regard to the secondary considerations of non-obviousness it asserted before the Board, the panel agreed that secondary considerations must be taken into account. Here, these were not relevant because the evidence for secondary considerations was based on the information that the Board and Federal Circuit determined had no patentable weight ("No patentable weight means no patentable weight.").
Turning to the question of the obviousness of claim 9, the opinion recognized this question turned on construction of the phrase "in accordance with," and whether there was a functional relationship between the "recommending" step and the "discontinuing treatment" step. For the purpose of deciding this question, the panel assumed the Board's construction was proper, stating that the claim "requires a medical provider to take a specific action, discontinuing treatment, as a result of the recommendation limitation," a construction that suffices to create a functional relationship which neither party nor the panel disputed. This "interrelating" the information with the "concrete step" of discontinuing treatment meant to the panel that the Board had not erred in finding a functional relationship between the two limitations.
But that is not "the end of the inquiry," according to the opinion. The correct question was whether claim 9 as a whole would have been obvious, and the panel held that it is. The obviousness question regarding claim 9 was based on one reference, to Bernsasconi (A. Bernasconi & M. Beghetti, Inhaled Nitric Oxide Applications in Paediatric Practice, 4 Images in Paediatric Cardiology 4 (2002)), which disclosed that children with preexisting LDV were at risk when treated with nitric oxide and should be monitored to minimize severe adverse event occurrence. The Board found that the reference taught "that [nitric oxide] may be given to patients with LVD, as long as those patients are monitored carefully during treatment," which was contrary to the panel's interpretation of the claim language. The Federal Circuit held that this interpretation of the language of claim 9 was incorrect, and when properly understood the teachings of the Bernasconi reference were not contrary to what was claimed. The Board's error: "[t]he Board conflated excluding a patient with LVD from nitric oxide treatment and discontinuing nitric oxide treatment in a patient with LVD after that patient experiences a pulmonary edema," according to the opinion. The claim does not exclude patients from nitric oxide treatment, but provides that the treatment be discontinued if pulmonary edema ensues.
"[T]here is only one permissible factual finding," [citing] Corning v. Fast Felt Corp., 873 F.3d 896, 903 (Fed. Cir. 2017), that "careful observation and intensive monitoring" of patients with LVD treated with nitric oxide, motivated by the dangerous possibility of a pulmonary edema known to result from that treatment, includes or at least suggests to a person of ordinary skill discontinuing nitric oxide treatment after a patient with LVD administered nitric oxide suffers a pulmonary edema.
The panel also faulted the Board's reliance on secondary considerations, finding insufficient nexus to the claimed invention.
[T]he form of analysis whereby limitations are removed from the claim before the claim is analyzed for patentability, is contrary to the patent statute, which requires determination of patentability of the claimed subject matter as a whole. It is improper to pluck limitations out of the claims, as of "no patentable weight," and then to review patentability of the remainder. See In re Gulack, 703 F.2d 1381, 1385 (Fed. Cir. 1983) ("Under section 103, the board cannot dissect a claim, excise the printed matter from it, and declare the remaining portion of the mutilated claim to be unpatentable. The claim must be read as a whole."). The Board stated that it afforded no patentable weight to the "providing information" and "evaluating" limitations, but gave patentable weight to the "recommendation" limitation in claim 9. Such piece-meal analysis does not impart precision to patentability analysis.
As is frequently the case, Judge Newman makes the better argument. Perhaps due to Section 101 fatigue or because the Supreme Court's penchant for ignoring the statutory silos of eligibility, anticipation, and obviousness is contagious, the majority's decision imports the incoherence of eligibility law into the obviousness context (doing little to clarify the standards in either). And by extending the application of the printed matter doctrine to claims that don't recite printed matter, this precedential decision has the capacity to make mischief (having the Court's imprimatur) until such time that another panel can creatively avoid its application or in the unlikely event that the Federal Circuit considers the question en banc (an eventuality that seems likely only if the Court becomes enamored with this approach to invalidating claims on eligibility grounds under the auspices of an obviousness determination). Neither possibility can be particularly comforting to the patent community.

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