Is Silence Disclosure? The Federal Circuit Clarifies its Position on Negative Claim Limitations

In Novartis Pharms. Corp. v. Accord Healthcare, Inc., No. 21-1070, slip op. at 7 (Fed. Cir. Jan. 3, 2022), the defendant posed two distinct written-description challenges to Novartis’s patent claims, regarding (1) a daily dosage of 0.5 mg and (2) “absent an immediately preceding loading dose.” The Federal Circuit again “resisted imposition of heightened written description standards for negative limitations” and relied primarily on expert testimony to uphold the district court’s finding that the written description in Novartis’s patent was sufficient.¹ The Federal Circuit’s decision was 2-1, with Judge O’Malley authoring the opinion. Judge Linn joined the majority opinion, and Chief Judge Moore wrote a dissenting opinion.

Gilenya® is Novartis’s branded 0.5 mg daily dose of fingolimod hydrochloride used to treat a form of multiple sclerosis (“MS”) called relapsing remitting multiple sclerosis (“RRMS”).² This case began when HEC filed an ANDA seeking approval to market a generic version of Gilenya®, and Novartis sued, alleging infringement of its 9,187,405 patent (“the ’405 patent”).³ Claim 1 of the ’405 patent reads:

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.⁴

The specification of the ’405 patent⁵ describes the results of an Experimental Autoimmune Encephalomyelitis (“EAE”) experiment, in which a disease mimicking RRMS was induced in laboratory rats.⁶ Administration of fingolimod hydrochloride (Compound A) was reported to “significantly block[] disease-associated neo-angiogenesis when administered to the animals at a dose of from 0.1 to 20 mg/kg p.o.”⁷ Furthermore, “disease relapse was completely inhibited in rats to which Compound A was administered daily at a dose of 0.3 mg/kg or administered p.o. at 0.3 mg/kg every 2nd or 3rd day or once a week.”⁸ The EAE model does not recite a loading dose.⁹ Both parties’ experts agreed that a loading dose is a higher than daily dose, usually given as the first dose.¹⁰

The specification also describes a prophetic human clinical trial, which is a trial described on paper but not performed, “in which RRMS patients would receive 0.5, 1.25, or 2.5 mg of an S1P receptor modulator, e.g., Compound A (fingolimod hydrochloride), per day for two to six months.”¹¹ There is no loading dose mentioned in the prophetic trial.¹² The specification also describes a wide range of potential dosages including a “preferred daily dosage range [of] about 0.1 to 100 mg” and “a dose of 0.5 to 30 mg [of Compound A] every other day or once a week.”¹³ The district court found that HEC’s ANDA product would infringe certain claims of the ’405 patent, and that HEC had not shown that those claims are invalid for insufficient written description.¹⁴ HEC appealed.¹⁵

First, for the claimed 0.5 mg daily dose, the district court credited expert testimony to arrive at the claimed 0.5 mg/day human dosage from the EAE experiment’s 0.3 mg/kg per week rat dosage.¹⁶ The expert testimony was that a skilled artisan would immediately recognize that the weekly rat dosage is approximately 60% lower than the lowest known effective dose in the prior art, and “would understand that the EAE results in the ’405 Patent therefore demonstrate that a proportionally lower dose (again, roughly 60% lower) could be effective in humans.”¹⁷ The Federal Circuit found no clear error in the district court’s conclusion, and emphasized that a disclosure does not need to recite the claimed limitation in haec verba.¹⁸ Rather, the disclosure only needs to “clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed.”¹⁹

Moreover, the Federal Circuit pointed out that “blaze marks are not necessary where the claimed species is expressly described in the specification, as the 0.5 mg daily dosage is here.”²⁰ Rather, “[b]laze marks directing an investigator of ordinary skill in the art to the claimed species from among a forest of disclosed options” must be present “where the specification describes a broad genus and the claims are directed to a single species or a narrow subgenus.”²¹ Any requirement for blaze marks in the ’405 patent would nonetheless be satisfied by the prophetic trial and the 0.5 to 30 mg/day dosage range.²²

As for the negative limitation, the Federal Circuit has repeatedly “resisted imposition of heightened written description standards for negative limitations, such as that urged by HEC.”²³ In Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1344, 1350-51 (Fed. Cir. 2012), the Federal Circuit stated that negative claim limitations are adequately supported when the specification describes a reason to exclude the relevant limitation, but did not hold that a specification must describe a reason to exclude a negative limitation.²⁴ In contrast, in In re Bimeda Research. & Development Ltd., 724 F.3d 1320, 1324 (Fed. Cir. 2013), the Federal Circuit found that a written description describing a non-antibiotic approach to preventing mastitis did not adequately describe a claim that excluded acriflavine but not other anti-infectives or antibiotics.²⁵ Essentially, “a negative limitation which is inconsistent with the disclosure is not adequately described.”²⁶

In addition, in Erfindergemeinschaft Uropep GBR v. Eli Lilly & Co., 276 F. Supp. 3d 629, 657-58 (E.D. Tex. 2017), aff’d, 739 F. App’x 643 (Fed. Cir. 2018), Judge Bryson, sitting by designation in the Eastern District of Texas, explained that “a negative limitation that is contrary to the thrust of the invention” is prohibited; otherwise, “a patentee can choose to claim any particular embodiments identified in the specification and exclude others, without explanation, as long as the claim does not indicate to persons of skill that it covers embodiments inconsistent with, and therefore unsupported by, the disclosure.”²⁷

Here, “context and the knowledge of those skilled in the art matter.”²⁸ “The disclosure must be read from the perspective of a person of skill in the art,” which is consistent with the Federal Circuit’s approach here of crediting expert testimony.²⁹ In other words, “[w]ritten description may take any form, so long as a skilled artisan would read the disclosure as describing the claimed invention.”³⁰ While § 2173.05(i) of the Manual of Patent Examining Procedure (“MPEP”) states that “the mere absence of a positive recitation is not a basis for an exclusion[,]” one must take into account how the skilled artisan would read a disclosure.³¹ The MPEP also states that written description can be implicit: “[N]ewly added claims or claim limitations must be supported in the specification through express, implicit, or inherent disclosure.”³²

The Federal Circuit concluded that the district court did not clearly err in finding that there was no clear and convincing evidence that the claims lacked adequate written-description support.³³ For instance, the Federal Circuit noted that the prophetic trial describes administration “at a daily dosage of 0.5, 1.25 or 2.5 mg p.o.” and states that “[i]nitially patients receive treatment for 2 to 6 months.”³⁴ One of Novartis’s expert witnesses testified as a skilled artisan that the patent would explicitly state that there were a loading dose, if this were the case:

So the first place one might explicitly say there was—there was a preceding loading dose is when you describe the daily dosage, the reason being a loading dose would occur before the first daily dose. The second place is even more dramatic, because they say, ‘Initially patients received treatment for 2 to 6 months.’ So now they’re really zooming in on Day 1, what is that treatment, it’s a daily dose of 0.5.³⁵

Another of Novartis’s expert witnesses testified that a person of skill in the art “would have viewed the patent as a document, as a complete document, that should give you all the information you need to carry out the claims, and that information of having a loading dose is not there, and what’s instead there is examples of daily dose, daily dose, daily dose.”³⁶ Moreover, HEC’s expert agreed that “a loading dose is a higher-than-therapeutic level dose, usually given . . . as the first dose.”³⁷ The district court also “credited the testimony of multiple expert witnesses who testified that the EAE model did not include a loading dose.”³⁸

Chief Judge Moore wrote a dissenting opinion. The dissent found that the ’405 patent did not contain adequate written description support for the “absent an immediately preceding loading dose regimen” limitation.³⁹ Loading doses are not discussed in any capacity—nowhere does the patent say loading doses should not be administered, or provide any reason to exclude them.⁴⁰ Santarus, Inc. supports the proposition that “[n]egative claim limitations are adequately supported when the specification describes a reason to exclude the relevant limitation,” such as by listing the disadvantages of some embodiment.⁴¹ Moreover, “all the experts agreed that loading doses are sometimes given to MS patients,” making them a known possibility.⁴² The patent’s silence lacks any discussion showing “that the inventors in fact invented this treatment method that is not just ambivalent to, but expressly excludes, a loading dose.”⁴³

The dissent noted the MPEP guidance that “[t]he mere absence of a positive recitation is not a basis for an exclusion” remains true despite how a skilled artisan would read a disclosure.⁴⁴ The Federal Circuit previously held in Rivera v. Int’l Trade Comm’n, 857 F.3d 1315, 1322 (Fed. Cir. 2017) that “[t]he knowledge of ordinary artisans may be used to inform what is actually in the specification, but not to teach limitations that are not in the specification, even if those limitations would be rendered obvious by the disclosure.”⁴⁵

Thus, what the majority sees as upholding its precedent that there is no “new and heightened standard for negative claim limitations,”⁴⁶ Chief Judge Moore characterizes as “relegating the legal determination of a term’s meaning to the backseat of an expert’s post-hoc rationalization.”⁴⁷ As a consequence, according to the dissent, “negative limitations are [now] supported by a specification that simply never mentions them.”⁴⁸