When does the absence of evidence turn into evidence of absence, and when does such absence amount to an adequate written description of the absence of a step of a method claim?  This is a question that comes readily to mind when reading the Federal Circuit's opinion (and Chief Judge Moore's dissent) in Novartis Pharmaceuticals Corp. v. Accord Healthcare, Inc. (Fed. Cir. 2022).

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 the 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 opinion sets 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.  This appeal followed.

The Federal Circuit affirmed, in an opinion by Judge O'Malley joined by Judge Linn; Chief Judge Moore dissented.  The majority made short work of HEC's argument regarding the purported inadequacy of the written description of the 0.5 mg/day fingolimod hydrochloride dose, finding 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 supporting the majority's decision against HEC's argument.  Finally, the majority opinion noted that the specification has 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.

Chief Judge Moore's dissent, as foreshadowed in the majority opinion, focused on the adequacy vel non of the written description of the negative limitation regarding the absence of a loading dose of fingolimod hydrochloride.  Perhaps sensitized to the issue by the Court's recent Biogen decision, 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 with appropriate pith as "[s]ilence is not disclosure."  The dissent illustrates 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 (although it can be appreciated that there must be a limit to the requirement for affirmatively disclosing what an invention does not comprise, lest a specification become overburdened with unnecessary verbiage directed to irrelevancies).  The dissent provided a basis for the Chief's apprehension that in this case the question of whether the absence of an initial loading dose was not so straightforward when it 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.  The Chief Judge found support for her position in many of the same cases cited by the majority or distinguished them, to the point that these cases require that a patent specification must "describe[] a reason to exclude the relevant limitation," citing Sartorius (emphasis in dissent).  And the Chief parsed the specification and the testimony to support her conclusion that the District Court's interpretation of the adequacy of the written description regarding the negative limitation concerning a loading dose, and the majority's affirmance thereof, was error.  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].

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