By Kevin E. Noonan —

The Federal Circuit recently granted a panel rehearing and vacated a panel decision between these parties decided earlier this year (see Novartis Pharmaceuticals Corp. v. Accord Healthcare), and rendered a decision that reversed the District Court finding in that earlier opinion.

To recap, the case arose in ANDA litigation over U.S. Patent No. 9,187,405, which recites methods for treating recurring remitting multiple sclerosis (RRMS), a degenerative disorder of the myelin surrounding nervous tissue, with fingolimod (2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol) sold by Novartis under the brand name Gilenya®.  Claim 1 was included in the opinion as representative:

A method for reducing or preventing or alleviating relapses in Relapsing-Remitting multiple sclerosis in a subject in need thereof, comprising orally administering to said subject 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, in free form or in a pharmaceutically acceptable salt form, at a daily dosage of 0.5 mg, absent an immediately preceding loading dose regimen.

The italicized limitation in this claim was the focus of that appeal, the Court's opinion, and Chief Judge Moore's dissent.  As set forth therein, the practice in the prior art had been (for drugs having a necessary therapeutic threshold) to administer a "loading dose," defined as "a higher-than-therapeutic level dose, usually given . . . as the first dose in order to get therapeutic levels up quickly" by undisputed expert testimony.  Similarly undisputed was that loading dose regimens had been used in the prior art for treating multiple sclerosis (MS).  Defendant HEC Pharm Co. Ltd. (the only remaining defendant at trial from more than two dozen generic drug makers and ANDA filers sued by Novartis under 35 U.S.C. § 271(e)(2)) maintained that the '405 patent was invalid because its specification and its priority British patent application (filed eight years before) did not provide an adequate written description of an invention comprising the "absent an immediately preceding loading dose regimen" limitation under 35 U.S.C. § 112(a).  As the Federal Circuit's earlier opinion set out, these applications both disclosed results of an animal model of MS by treatment by oral administration of a hydrochloride salt of fingolimod at 0.3 mg/kg/week dosages.  Both also recited a prophetic example of a human clinical trial using "preferred daily dosage range [of] about from 0.1 to 100 mg" and "a dose of 0.5 to 30 mg [of fingolimod hydrochloride] every other day or once a week" and specifically "0.5, 1.25, or 2.5mg[/day]."  Nowhere in either specification was there express disclosure that a loading dose was to be avoided (but similarly nowhere in either specification was administration of a loading dose expressly taught).

The District Court found that HEC's ANDA product would infringe the '405 patent and that HEC had not shown by clear and convincing evidence that the '405 patent failed to satisfy the written description provisions of § 112(a).  The Court found that the skilled worker would "make the leap" of increasing the dose from 0.3 mg in a rat to 0.5 mg in a human based on expert testimony, and that this specific dosage was found in the recited range of "from 0.1 to 100 mg."  Regarding the absence of a loading dose in the claimed regimen, the District Court found persuasive expert testimony that "'[i]f a loading dose were directed, the Patent would say that a loading dose should be administered 'initially.'"  This was enough for the District Court to find that the specification provided an adequate written description of this negative limitation.

The Federal Circuit affirmed in the earlier appeal, with the majority holding that the District Court's decision regarding the adequacy of the '405 patent specification's disclosure of this limitation was supported by substantial evidence including expert testimony.  With regard to that expert testimony (and its consistency with the disclosure in the '405 specification), the Court noted that "[a] 'disclosure need not recite the claimed invention in haec verba,'" citing Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010), and held that "[t]o accept HEC's argument would require us to ignore the perspective of the person of ordinary skill in the art and require literal description of every limitation, in violation of our precedent."  Furthermore, the majority rejected HEC's assertion that the '405 specification contained insufficient "blazemarks" regarding the 0.5 mg/day dose because the blazemarks considerations are only relevant "where the specification describes a broad genus and the claims are directed to a single species or a narrow subgenus"; in such cases "'blazemarks' . . . would lead an ordinarily skilled investigator toward such a species among a slew of competing possibilities," citing Novozymes v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1349 (Fed. Cir. 2013).  But the need for blazemarks does not arise "where the claimed species is expressly described in the specification, as the 0.5 mg daily dosage is here" according to the majority, citing Snitzer v. Etzel, 465 F.2d 899, 902 (C.C.P.A. 1972).  The absence of "laundry-list-type disclosure" (which Judge O'Malley discussed in her dissent in Biogen Int'l GmbH v. Mylan Pharmaceuticals Inc.) made a difference in this regard, further used by the majority in supporting its decision.  Finally, the majority opinion noted that the specification had literal description support for the 0.5 mg/day dose.  Accordingly, the majority held that the District Court's determination that HEC failed to show inadequate written description on these grounds was supported by both the specification and "ample expert testimony" and thus affirmed.

Turning to the negative limitation regarding the absence of a loading dose, the majority opinion began by noting that, under Inphi Corp. v. Netlist, Inc., 805 F.3d 1350, 1356 (Fed. Cir. 2015), there is no "new and heightened standard for negative claim limitations" and supported the continued vitality of this principle by citation to several Federal Circuit opinions, including Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1344, 1350–51 (Fed. Cir. 2012); In re Bimeda Research. & Development Ltd., 724 F.3d 1320, 1324 (Fed. Cir. 2013); and Nike, Inc. v. Adidas AG, 812 F.3d 1326, 1348 (Fed. Cir. 2016).  The majority perceived HEC's argument as "attempt[ing] to create a new heightened written description standard for negative limitations" contrary to the "central tenet of [the Court's] written description jurisprudence—that the disclosure must be read from the perspective of a person of skill in the art" as well as specific precedent such as All Dental Prodx, LLC v. Advantage Dental Prod., Inc., 309 F.3d 774, 779 (Fed. Cir. 2002).  The majority opinion distinguished HEC's argument (and Chief Judge Moore's dissent, vide infra) that "[t]he mere absence of a positive recitation is not a basis for an exclusion" (M.P.E.P. § 2173.05(i)), and "silence alone is insufficient" (citing the dissent) with the concept of context, specifically "how a skilled artisan reads a disclosure" which is what "matters" to the majority.  For Judges O'Malley and Linn, both HEC and the Chief Judge "urge us to elevate form over substance by creating a new rule that a limitation which is not expressly recited in the disclosure is never adequately described, regardless of how a skilled artisan would read that disclosure."  The adequacy of the '405 specification's written description regarding the negative loading dose limitation was supported, according to the majority, by the District Court who "correctly, and quite carefully, conducted 'an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art'" (which the opinion then summarized and quoted).  Based on this analysis, the majority stated that they could find no clear error and thus affirmed.

In the earlier appeal, Chief Judge Moore's dissent focused on the adequacy vel non of the written description of the negative limitation regarding the absence of a loading dose of fingolimod hydrochloride.  The Chief Judge asserted that "[t]he majority dramatically expands a patentee's ability to add, years after filing a patent application, negative claim limitations that have zero support in the written description" (emphasis added), summarizing her position as "[s]ilence is not disclosure."  The dissent illustrated how readily answers to questions like the one before the Court can be completely divergent depending on which "policy lever" (as legal academics might call them) are considered most relevant.  The Chief focused on disclosure, which carries with it a requirement for affirmative statements and definitions that without question are not found in the '405 specification.  The dissent noted that the limitation was added in response to an obviousness rejection asserted against claims in a co-pending priority application to the '405 patent.  According to the dissent "the district court (and now the majority) [engaged in] rewriting the specification with expert testimony" to arrive at their conclusion regarding such adequacy.  The Chief concluded her dissent by stating:

The inventors do not get to claim as their invention something they did not disclose in the patent.  There are no fact findings here to defer to—the patent is silent as to loading doses.  The district court relied upon that silence: "The absence of an immediately preceding loading dose from the specification, and from the Prophetic Trial, would tell a person of skill that loading doses are excluded from the invention."  . . .  This is not a finding of fact; it is a misunderstanding of the law.  An inventor cannot satisfy the written description requirement through silence.  And when the majority concludes otherwise, it creates a conflict with our long-standing, uniformly-applied precedent . . . .  While the negative limitation need not be recited in the specification in haec verba, there must be something in the specification that conveys to a skilled artisan that the inventor intended the exclusion:  disadvantages, alternatives, inconsistencies, just something.  This specification is entirely silent and ambivalent about loading doses.  These inventors did not disclose treatment that must exclude a loading dose, and the district court's finding to the contrary is clearly erroneous.  After this case, negative limitations are supported by a specification that simply never mentions them [citations to the record and precedent omitted].

In the current decision, by Chief Judge Moore joined by Judge Hughes (Judge O'Malley having left the Court in May), and with a dissent by Judge Linn, the Chief's understanding and opinion on the issues before the Court prevailed ("the district court clearly erred in finding that the negative claim limitation 'absent an immediately preceding loading dose' added during prosecution to overcome prior art satisfies the written description requirement of 35 U.S.C. § 112(a)").  The panel majority opinion tracks the Chief Judge's dissent in the Court's earlier decision, that negative limitations do bear a burden of disclosure different from affirmative ones.  As set forth in the opinion, this burden can be satisfied for example by including "a reason to exclude the relevant [element]," citing inter alia Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1351 (Fed. Cir. 2012); and Inphi Corp. v. Netlist, Inc., 805 F.3d 1350, 1355 (Fed. Cir. 2015), or by including "'statements in the specification expressly listing the disadvantages of using' that element," or by distinguishing among the excluded element and advantageous alternatives.  The opinion calls "the common denominator" of all these rubrics disclosure of the element to be excluded, repeating the Chief's aphorism from her earlier dissent that "silence is not disclosure."  While not disputing the principle that "a negative limitation need not be recited in the specification in haec verba," the majority opinion asserts the need for "something" to be disclosed in the specification "that conveys to a skilled artisan that the inventor intended the exclusion, such as a discussion of disadvantages or alternatives."  The opinion concedes under some circumstances in some particular fields where "the absence of mention of a limitation necessarily excluded that limitation, [then] written description could be satisfied despite the specification's silence," citing Tronzo v. Biomet, Inc., 156 F.3d 1154, 1159 (Fed. Cir. 1998) (constituting a kind of inherent disclosure of the excluded element, an argument Novartis expressly did not make at trial or on appeal).  And expert testimony does not suffice, according to the panel majority, because if it could "such testimony could effectively eliminate the written description requirement."  In coming to its conclusion, the panel majority revisits and reinterprets the evidence adduced at trial in finding the District Court's consideration thereof to be clearly erroneous.

The opinion does contain a nod to Judge O'Malley's concerns in the original panel opinion, that the Court was being asked to create a "heightened standard for negative claim limitations," which the opinion says it is not (although it is clear from elsewhere in the opinion that requiring "something" imposes more than the original panel majority required).  The further concession that it is possible that under some circumstances "it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure," the opinion states clearly that "[t]his is not such a case."

Judge Linn (who with Judge O'Malley formed the majority in the earlier opinion) dissented, expressing his view that imposing a heightened standard for negative limitation disclosure in satisfying the written description requirement was exactly that the majority was doing.  Ultimately the question is the metes and bounds of what is required for a specification to "reasonably disclose" possession of the claimed invention, and Judge Linn cites some of the same cases (Inphi, for example) for the principle that "there is no 'new and heightened standard for negative claim limitations'" that the panel majority cited in support of the opposite conclusion.  And in Santarus, Judge Linn notes that while the Court "observed" that a specification could describe a reason to exclude a limitation or element, the decision did not require it to provide adequate written description support for a negative limitation.  While acknowledging that the panel majority cited principles regarding the adequacy of a written description with which he agreed, Judge Linn did not agree with the heightened standard of necessary exclusion enunciated in their opinion.  Citing In re Bimeda Research & Development Ltd., 724 F.3d 1320, 1324 (Fed. Cir. 2013), Judge Linn identified instances where a negative limitation was not adequately supported to include where "a negative limitation which is inconsistent with the disclosure is not adequately described."  And the dissent cites multiple examples of cases stating the lack of an in haec verba requirement (see All Dental Prods., LLC v. Advantage Dental Prod., Inc., 309 F.3d 774, 779 (Fed. Cir. 2002) (citing Eiselstein v. Frank, 52 F.3d 1035, 1039 (Fed. Cir. 1995)) and the lack of a heightened disclosure requirement for negative limitations, see Nike, Inc. v. Adidas AG, 812 F.3d 1326, 1348 (Fed. Cir. 2016), overruled on other grounds by Aqua Prods., Inc. v. Matal, 872 F.3d 1290 (Fed. Cir. 2017) (en banc).  Judge Linn even cites the M.P.E.P., explaining in a footnote "not because the court is bound by it but because I find its reasoning informative and persuasive."

In his own explication of the factual bases of the District Court's decision, Judge Linn finds that the District Court conducted "an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art" in arriving at its conclusion, supported by expert testimony to make "the unremarkable, and factually supported, determination that 'starting with a daily dose plainly implies that there is no loading dose.'"  With regard to the majority's reliance on its own interpretation of the word "initially," Judge Linn states the equally unremarkable rubric of appellate review that:

We are not free to substitute our own factual findings for those of the district court absent clear error because 'a district court judge who has presided over, and listened to, the entire proceeding has a comparatively greater opportunity to gain the necessary "familiarity with specific scientific problems and principles," . . . than an appeals court judge who must read a written transcript or perhaps just those portions referenced by the parties,'" citing Teva Pharms. USA, Inc. v. Sandoz, Inc., 574 U.S. 318, 319 (2015) (quoting Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 610 (1950)).

The majority decision, while well-reasoned, illustrates the flexibility of the deference reviewing courts are required under precedent to give district court decisions on questions of fact (written description being quintessentially a question of fact).  As set out in the opinion, a district court's factual determination is not to be overturned "in the absence of a definite and firm conviction that a mistake has been made," citing Scanner Techs. Corp. v. ICOS Vision Sys. Corp. N.V., 528 F.3d 1365, 1374 (Fed. Cir. 2008), and at trial HEC had the burden to show invalidity by clear and convincing evidence (under Hynix Semiconductor Inc. v. Rambus Inc., 645 F.3d 1336, 1351 (Fed. Cir. 2011), and ICU Med., Inc. v. Alaris Med. Sys., Inc., 558 F.3d 1368, 1376 (Fed. Cir. 2009), as cited in the opinion).  It is understandable that the majority thought rehearing and reversal was the proper outcome, but perhaps the issue might have been better reviewed en banc.

Novartis Pharmaceuticals Corp. v. Accord Healthcare, Inc. (Fed. Cir. 2022)
Panel: Chief Judge Moore and Circuit Judges Linn and Hughes
Opinion by Chief Judge Moore; dissenting opinion by Circuit Judge Linn