United States Court of Appeals 

for the Federal Circuit ______________________

BIOGEN INTERNATIONAL GMBH, BIOGEN MA, 

INC.,

Plaintiffs-Appellants

v.

MYLAN PHARMACEUTICALS INC.,

Defendant-Appellee

______________________

2020-1933

______________________

Appeal from the United States District Court for the 

Northern District of West Virginia in No. 1:17-cv-00116-

IMK-JPM, Judge Irene M. Keeley.

______________________

Decided: November 30, 2021

______________________

WILLIAM F. LEE, Wilmer Cutler Pickering Hale and 

Dorr LLP, Boston, MA, argued for plaintiffs-appellants. 

Also represented by ANNALEIGH E. CURTIS, MADELEINE C.

LAUPHEIMER, LISA JON PIROZZOLO; SCOTT G. GREENE, New 

York, NY; THOMAS SAUNDERS, Washington, DC; PAUL 

WILLIAM BROWNING, J. MICHAEL JAKES, JAMES B. MONROE, 

JASON LEE ROMRELL, Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, Washington, DC.

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 DAVID LEE ANSTAETT, Perkins Coie, LLP, Madison, WI, 

argued for defendant-appellee. Also represented by 

ANDREW DUFRESNE, EMILY JANE GREB; DAN L. BAGATELL, 

Hanover, NH; SHANNON BLOODWORTH, NATHAN K. KELLEY,

BRANDON MICHAEL WHITE, Washington, DC; MATTHEW 

GREINERT, Mylan, Canonsburg, PA.

______________________

Before O’MALLEY, REYNA, and HUGHES, Circuit Judges.

Opinion for the court filed by Circuit Judge REYNA.

Dissenting opinion filed by Circuit Judge O’MALLEY.

REYNA, Circuit Judge.

This appeal from the United States District Court for 

the Northern District of West Virginia concerns a patentinfringement dispute between Biogen International 

GmbH, Biogen MA, Inc., and Mylan Pharmaceuticals, Inc. 

Biogen owns United States Patent 8,399,514 (the ’514 Patent), which claims a method of treating multiple sclerosis 

with a drug called dimethyl fumarate. In 2017, Biogen 

filed a lawsuit against Mylan alleging patent infringement. 

Mylan counterclaimed for declaratory judgment that the 

patent was invalid and not infringed. Following a bench 

trial, the district court determined that the asserted claims 

of the ’514 Patent were invalid for lack of written description. Biogen challenges the district court’s decision on appeal.

For the reasons set forth in this opinion, we hold that

the district court did not clearly err in determining that 

Mylan has established its burden of showing, by clear and 

convincing evidence, that the asserted ’514 Patent claims 

are invalid for lack of written description under 35 U.S.C. 

§ 112. Accordingly, we affirm the judgment of the district 

court.

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I. BACKGROUND

Under the Drug Price Competition and Patent Term 

Restoration Act of 1984 (the Hatch-Waxman Act), a manufacturer of a new generic drug that is bioequivalent1 to a 

previously approved drug may seek approval from the US 

Food and Drug Administration (FDA) to market the generic product by filing an Abbreviated New Drug Application (ANDA). See Pub. L. No. 98-417, § 101, 98 Stat. 1585, 

1585–86 (1984) (codified as amended at 21 U.S.C.

§ 355(j)(2)(A)). The statute requires the generic-drug manufacturer to submit a certification regarding the status of 

1 For purposes of Hatch-Waxman litigation, a generic drug is considered bioequivalent to a brand-name 

drug if:

(i) the rate and extent of absorption of the [generic] 

drug do not show a significant difference from the 

rate and extent of absorption of the listed [brandname] drug when administered at the same molar 

dose of the therapeutic ingredient under similar experimental conditions in either a single dose or 

multiple doses; or

(ii) the extent of absorption of the [generic] drug 

does not show a significant difference from the extent of absorption of the listed [brand-name] drug 

when administered at the same molar dose of the 

therapeutic ingredient under similar experimental 

conditions in either a single dose or multiple doses 

and the difference from the listed drug in the rate 

of absorption of the drug is intentional, is reflected 

in its proposed labeling, is not essential to the attainment of effective body drug concentrations on 

chronic use, and is considered medically insignificant for the drug.

21 U.S.C. § 355(j)(8)(B)(i)–(ii).

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any patent that purportedly protects the brand-name drug, 

including information as to whether no such patent exists

or the patent already expired, and if the patent has not expired the manufacturer must indicate the date on which 

the patent will expire. 21 U.S.C. § 355(j)(2)(A)(vii)(I)–(III).

If a patent that covers the brand-name drug has not 

expired, the generic-drug manufacturer may file what is 

known as a paragraph IV certification, attesting that the 

“patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug for which the application 

is submitted.” Id. § 355(j)(2)(A)(vii)(IV). The manufacturer

filing the ANDA and paragraph IV certification must 

promptly notify the owner of any patent subject to the certification. Id. § 355(j)(2)(B)(iii). And the FDA must approve the ANDA, unless the patent owner objects by filing 

an action for patent infringement against the generic-drug 

manufacturer within forty-five days of receiving notice of 

the paragraph IV certification. Id. § 355(j)(5)(B)(iii). If the 

patent owner brings the infringement suit under the 

Hatch-Waxman Act within the statutory period, the law 

triggers an automatic, thirty-month stay in the FDAapproval process of the generic drug, pending the outcome 

of the litigation. See id. § 355(j)(5)(B)(iii).

Mylan Pharmaceuticals, Inc. (Mylan) filed an ANDA 

seeking to manufacture, use, and market a generic dimethyl fumarate (DMF) product for the treatment of multiple 

sclerosis (MS) before the expiration date of the ’514 Patent. 

J.A. 6001–02. On June 30, 2017, Biogen International 

GmbH and Biogen MA, Inc. (collectively Biogen) sued 

Mylan for patent infringement in the Northern District of 

West Virginia pursuant to the Hatch-Waxman Act. Id. In 

its original complaint, Biogen asserted six patents2

2 In addition to the ’514 Patent, Biogen asserted US 

Patents 6,509,376; 7,320,999; 7,619,001; 7,803,840; and 

8,759,393. J.A. 6002.

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purportedly covering Tecfidera®, Biogen’s trademarked

DMF-capsule formulation for the treatment of patients suffering from relapsing-remitting forms of MS. Id. Only the 

’514 Patent is at issue in this appeal. See J.A. 2–3.

A. The ’514 Patent

The ’514 Patent claims priority to United States Provisional Application 60/888,921 (the ’921 Application), which 

Biogen filed on February 8, 2007. U.S. Patent No. 

8,399,514, at [60] (filed Feb. 13, 2012) (issued Mar. 19, 

2013). As issued, the patent is entitled “Treatment for 

Multiple Sclerosis.” ’514 Patent, at [54].

MS is a disabling autoimmune disease that affects the 

central nervous system (CNS) and involves an abnormal 

inflammatory response, which leads to damage and the 

eventual destruction of the myelin sheath that surrounds 

neuronal axons—the nerve fibers that transmit electrical 

signals across CNS nerve cells. See ’514 Patent col. 1 

ll. 15–20. The myelin sheath, which comprises a mixture 

of proteins and lipids, is a substance that acts as a protective covering to insulate nerve fibers—much like the insulation material that surrounds and protects an electrical 

wire—and permits nerve cells to adequately conduct the 

electrical signals. See John S. O’Brien, Stability of the Myelin Membrane, 147 SCIENCE 1099, 1099 (1965); J.A. 4–5. 

MS-induced deterioration of the myelin sheath interferes 

with the proper transmission of such electrical signals 

across nerve cells and eventually contributes to neurodegeneration, death of neurons, and progressive neurological dysfunction in individuals suffering from the disease. 

See ’514 Patent col. 1 ll. 17–20, 29–30; J.A. 4–5.

In its action alleging patent infringement against 

Mylan, Biogen asserted claims 1–4, 6, 8–13, 15, and 16 of 

the ‘514 Patent. J.A. 15–17. Claim 1 is representative and 

recites:

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A method of treating a subject in need of treatment 

for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical 

composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, 

monomethyl fumarate, or a combination thereof, 

and (b) one or more pharmaceutically acceptable 

excipients, wherein the therapeutically effective 

amount of dimethyl fumarate, monomethyl 

fumarate, or a combination thereof is about 

480 [milligrams] per day [(mg/day)].

Id. col. 27 ll. 59–67. Relevant to this appeal is Biogen’s use 

of DMF, a fumaric-acid ester compound, at a specific dose 

of 480 mg/day (DMF480) under the brand name Tecfidera®

for the treatment of MS.

The ’514 Patent specification largely tracks that of the 

original ’921 Application, which Biogen entitled “Nrf2 

Screening Assays and Related Methods and Compositions.”3 J.A. 3289–92. The specification casts a wide net 

for a myriad of neurological disorders, including neurodegenerative diseases such as amyotrophic lateral sclerosis 

(ALS), Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease; demyelinating neurological diseases, 

such as various forms of MS and at least twenty-eight other 

disorders related to demyelination; polyneuritis; and mitochondrial disorders with demyelination. See ’514 Patent 

col. 16 ll. 18–63. Although the specification does not focus 

exclusively on MS, it discusses MS-related background 

3 On February 7, 2008, Biogen filed International 

Patent Application PCT/US2008/0016902 (the ’902 Application), which maintained the same title, claims, and inventor as the ’921 Application but added to its specification. 

J.A. 10. On August 7, 2009, the international ’902 Application entered the national phase and became US Patent 

Application 12/526,296 (the ’296 Application). Id.

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information in two paragraphs that appear in the first column. See id. col. 1 ll. 15–52.

The specification further describes five methods to explore a potential protective role for the activation of the 

Nrf2 pathway in neurodegenerative and neuroinflammatory diseases. J.A. 66–67. Methods 1–3 relate to screening,

evaluating, and comparing the bioequivalence of compounds for their use against neurological diseases. 

J.A. 68–69. Methods 4 and 5 relate to the treatment of such

neurological diseases. J.A. 69. Consistent with the disclosure’s original title concerning Nrf2 screening, the totality 

of the specification focuses primarily on drug discovery. Indeed, the invention’s title was only amended to “Treatment 

for Multiple Sclerosis” in 2011 after Biogen acquired Phase 

III clinical data for the use of DMF480 in treating MS. See

J.A. 12–13; J.A. 3490–91.

Because the claims at issue concern methods to treat 

MS, we must look to methods 4 and 5 as disclosed in the 

specification. Method 5 is largely irrelevant for our purposes because it relates to combination therapy comprising 

the administration of a compound that upregulates the 

Nrf2 pathway with at least one other compound that cannot upregulate the pathway. ’514 Patent col. 8 ll. 54–63. 

But method 4 is instructive, as it discloses “methods of 

treating a neurological disease by administering to the subject in need thereof at least one compound that is at least 

partially structurally similar to DMF and/or [monomethyl 

fumarate (MMF)],” as well as “a method of treating a mammal who has or is at risk for a neurological disease . . . [by] 

administering to the mammal a therapeutically effective 

amount of at least one neuroprotective compound” such as 

DMF or MMF, and “a method of slowing or preventing neurodegeneration” induced by demyelination or the death or 

neurons. Id. col. 8 ll. 35–53.

Save for one paragraph in the specification, the disclosure does not teach potential dosage levels for DMF 

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monotherapy. The sole DMF-dosage paragraph is not 

linked to treatment of any specific disease but recites:

Effective doses will also vary, as recognized by 

those skilled in the art, dependent on route of administration, excipient usage, and the possibility of 

co-usage with other therapeutic treatments including use of other therapeutic agents. For example, 

an effective dose of DMF or MM[F] to be administered to a subject orally can be from about 0.1 g to 

1 g per pay, 200 mg to about 800 mg per day (e.g., 

from about 240 mg to about 720 mg per day; or 

from about 480 mg to about 720 mg per day; or 

about 720 mg per day). For example, the 720 mg 

per day may be administered in separate administrations of 2, 3, 4, or 6 equal doses.

Id. col. 18 ll. 54–64 (emphasis added). As shown above, the 

specification explicitly mentions “effective doses” at various concentration ranges within an overall DMF dosage 

range of 100–1,000 mg/day.

Importantly for this appeal, the specification reveals 

two crucial aspects of the invention. First, the above paragraph features the one and only reference to DMF480 in 

the entire specification, which puts the DMF480 dose that 

the ’514 Patent claims at the bottom end of the spectrum of

a DMF 480–720 mg/day range. Second, the specification 

defines the term “effective” within a therapeutic, rather 

than drug-discovery, context. Thus, according to the specification, the terms “‘therapeutically effective dose’ and 

‘therapeutically effective amount’ refer to that amount of a 

compound which results in at least one of prevention or delay of onset or amelioration of symptoms of a neurological 

disorder in a subject or an attainment of a desired biological outcome, such as reduced neurodegeneration (e.g., demyelination, axonal loss, and neuronal death) or reduced 

inflammation of the cells of the CNS.” Id. col. 5 ll. 52–59 

(emphases added).

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B. Clinical Development and Procedural History

Between 2004 and 2006, Biogen conducted a Phase II,

clinical, dose-ranging study to test the efficacy of DMF at 

120, 360, and 720 mg/day concentrations (DMF120, 

DMF360, and DMF720, respectively) for the treatment of 

MS. J.A. 2184–91. The May 2006 results of this study 

showed that DMF720 was efficacious in treating MS, but 

DMF120 and DMF360 were not. J.A. 7. In August 2006, 

the FDA recommended that Biogen add a DMF480 dosing 

regimen in the Phase III study because the lower dose 

“might improve patient compliance and/or minimize dropouts from adverse effects during the study.” J.A. 1724–25. 

According to Biogen, the Phase II lead scientist, Dr. 

O’Neill, had conceived the idea of using DMF480 as early 

as 2003 and advocated testing the DMF480 dose as part of

the trial in February 2004. J.A. 7. At the time, Biogen had 

decided not to include the DMF480 dose in the study for 

commercial reasons. See J.A. 1364. Although Biogen told 

the FDA that DMF720 was the best option, it eventually 

included DMF480 in the Phase III clinical testing. See

J.A. 1726. The Phase III results showed efficacy for the 

DMF480 and DMF720 doses. J.A. 2060.

Based on the 2006 Phase II results—and before starting the Phase III trial to test the DMF480 dose—Biogen 

filed the provisional ’921 Application on February 8, 2007. 

The original application listed Dr. Lukashev, a Biogen scientist who, at the time, focused on research related to the 

Nrf2 pathway, as the sole inventor. J.A. 8–10. O’Neill was 

not listed as a co-inventor on the ’921 Application; his name 

was added in 2011 as part of an amendment refocusing the 

invention on methods of treatment for MS, which Biogen 

filed after gathering the Phase III results that demonstrated therapeutic efficacy of DMF480.4 J.A. 3437–39; 

4 Biogen amended the ’296 Application—the national-phase application filed in 2009, see supra note 3—

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J.A. 3481–86. O’Neill, however, had not been involved 

with any of the Nrf2 research that led to the ’514 Patent. 

When asked during trial, Lukashev testified that he did not 

know why O’Neill was added as an inventor. J.A. 1318. 

Lukashev also corroborated the original application’s emphasis on drug discovery by noting that his work had encompassed “a more exploratory nature. It[ was] to explore 

potential for follow-on compound discovery . . . .” J.A. 9 (alteration in original). And, more importantly, he “denied 

that his research could be extrapolated to a clinical dose of 

DMF; it ‘was never the focus of [his] work to inform the 

clinical dosing of [DMF].’” Id. (alterations in original). Besides the amendments related to inventorship and the invention’s title, Biogen did not make any other changes to 

the specification. This enabled Biogen to claim a priority 

date of February 8, 2007, despite filing wholly new claims 

alongside the amendments. J.A. 13.

In 2017, Biogen filed its patent infringement suit 

against Mylan in the Northern District of West Virginia. 

J.A. 6001. Biogen sued after Mylan sought ANDA approval to market a generic DMF product for treating MS. 

Mylan counterclaimed for declaratory judgment that the 

’514 Patent was invalid and not infringed. J.A. 6136–44. 

after acquiring its Phase III clinical-data results in April 

2011. J.A. 10. Biogen left the specification of the ’296 Application unchanged, but it amended the invention’s title 

and claims on June 20, 2011. J.A. 47. On October 28, 2011, 

Biogen subsequently amended the ’296 Application again 

to add O’Neill as an inventor. Id. Biogen then abandoned 

the ’296 Application in favor of US Patent Application 

13/326,426 (the ’426 Application), a continuing application 

filed on February 13, 2012. J.A. 11. The ’426 Application 

eventually led to issuance of the ’514 Patent on March 19, 

2013. Id. Biogen claims a February 8, 2007 priority date 

for the ’514 Patent based on the ’921 Application. Id.

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The district court held a four-day bench trial starting on 

February 4, 2020. J.A. 1001. On February 5, 2020, the Patent Trademark and Appeal Board (Board) issued a final 

written decision in a related inter partes review (IPR) proceeding, which Mylan initiated on July 13, 2018 and is the 

subject of a companion case to this appeal. See Mylan 

Pharms. Inc. v. Biogen MA Inc. ̧ No. IPR2018-01403, 

2020 WL 582736 (P.T.A.B. Feb. 5, 2020). In the IPR case, 

the Board rejected an obviousness challenge to the asserted

’514 Patent claims, which estopped Mylan from litigating 

obviousness issues in the trial court. See J.A. 3 n.2.

During trial, the parties agreed that, for purposes of 

this case, a person of ordinary skill in the art (POSA) is 

someone with “at least a medical degree, at least three 

years of training in neurology, and at least three years of 

clinical experience treating multiple sclerosis patients.”

J.A. 20. The parties presented expert testimony from two 

neurologists who treat patients with MS—Dr. Greenberg 

for Mylan and Dr. Wynn for Biogen. J.A. 20. At the conclusion of the trial, the district court found that the specification did not reasonably convey to a POSA that the ’514 

Patent inventors had “actually invented” a method of treating MS with a therapeutically effective dose of DMF480 as 

of February 8, 2007. J.A. 45. The court also found that 

Biogen’s arguments and Wynn’s testimony that a POSA 

would be drawn to the DMF480 dose upon reading the patent specification were “neither credible nor persuasive,” 

J.A. 30–31, and noted that Wynn conceded during cross examination that the sole DMF-dosage paragraph in the 

specification did not teach a POSA that DMF480 would be 

therapeutically effective for treating MS, J.A. 31.

The district court opined that Biogen’s attempt to 

“combin[e] a few selectively[ ]plucked disclosures from the 

specification . . . has been squarely rejected by the Federal 

Circuit.” J.A. 45. Based on the testimony offered at trial, 

the context of the ’514 Patent prosecution history, and “significant omissions from the specification,” the district court

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ultimately concluded that Mylan had satisfied its burden 

of showing by clear and convincing evidence that the asserted ’514 Patent claims were invalid for lack of written 

description under 35 U.S.C. § 112. Id. Biogen now appeals 

the district court’s decision.

II. STANDARD OF REVIEW

Whether a claim meets the written-description requirement is a question of fact, which this court reviews for clear 

error on appeal from a bench trial. Nuvo Pharm. (Ireland) 

Designated Activity Co. v. Dr. Reddy’s Laboratories Inc., 

923 F.3d 1368, 1376 (Fed. Cir. 2019), cert. denied, 

140 S. Ct. 902 (2020). The clear-error standard requires 

courts to exercise deference when reviewing findings of 

fact, unless there is a “definite and firm conviction that a 

mistake has been made.” Scanner Techs. Corp. v. ICOS 

Vision Sys. Corp. N.V., 528 F.3d 1365, 1374 (Fed. 

Cir. 2008) (internal quotation marks and citation omitted). 

Patent invalidity under the written-description doctrine 

must be established by clear and convincing evidence. 

Hynix Semiconductor Inc. v. Rambus Inc., 645 F.3d 1336, 

1351 (Fed. Cir. 2011). Courts of appeals cannot reweigh a 

district court’s assessment of witness credibility, Advanced 

Magnetic Closures, Inc. v. Rome Fastener Corp., 607 F.3d 

817, 832 (Fed. Cir. 2010), and must take into account the 

“unchallenged superiority” of a district court’s ability to 

make witness-credibility determinations and findings of 

fact, see Salve Regina Coll. v. Russell, 499 U.S. 225, 233 

(1991).

III. DISCUSSION

A. The Written-Description Requirement

To secure a patent for an invention under the laws of 

the United States, an inventor must comply with the written-description requirement outlined in 35 U.S.C. § 112, 

which prescribes:

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The [patent] specification shall contain 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, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying 

out the invention.5

35 U.S.C. § 112 (emphasis added). The statutory mandate 

for a written description as a prerequisite for patenting an 

invention has been a fixture of our laws for more than two 

centuries. The Supreme Court recognized, as far back as 

1822, that the purpose of requiring a written description 

under the Patent Act of 1793 was to “put the public in possession of what the party claims as his own invention, so 

as to ascertain if he claim[s] anything that is in common 

use, or is already known . . . .” Evans v. Eaton, 20 U.S. 356, 

434 (1822). “[P]ossession as shown in the disclosure,” 

therefore, represents the hallmark of written description. 

Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 

(Fed. Cir. 2010) (en banc). The written-description statutory language has undergone little change despite the enactment and revisions of numerous patent statutes since

the Founding era. See Univ. of Rochester v. G.D. Searle & 

Co., 358 F.3d 916, 925 (Fed. Cir. 2004).

5 Following the enactment of the Leahy–Smith 

America Invents Act (AIA), Pub. L. No. 112-29, 125 Stat 

284 (2011), the first paragraph of § 112 was redesignated 

as § 122(a). The AIA amendments, which took effect on 

September 16, 2012, replaced the words “of carrying out his 

invention” in the pre-AIA § 112 with “or joint inventor of 

carrying out the invention” in the current § 112(a). 

125 Stat. at 296–97. The amendments bear no significance 

for purposes of our written-description analysis.

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This court’s precedents dictate that the § 112 writtendescription “requirement is satisfied only if the inventor 

‘convey[s] with reasonable clarity to those skilled in the art 

that, as of the filing date sought, he or she was in possession of the invention,’ and demonstrate[s] that by disclosure in the specification of the patent.” Nuvo, 923 F.3d at

1376–77 (quoting Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1348 (Fed. Cir. 2011)). A precise 

definition of the invention is pivotal to establishing possession. Amgen Inc. v. Sanofi, 872 F.3d 1367, 1373 (Fed. Cir. 

2017). An applicant may show possession of the claimed 

invention by describing it with all of its limitations using 

“such descriptive means as words, structures, figures, diagrams, formulas, etc.” Lockwood v. Am. Airlines, Inc., 

107 F.3d 1565, 1572 (Fed. Cir. 1997). The term “possession” in the context of written-description jurisprudence 

entails an “objective inquiry into the four corners of the 

specification from the perspective of a [skilled artisan].” 

Ariad, 598 F.3d at 1351.

Whether a claimed invention satisfies the written-description requirement of § 112 will depend on the nature of 

the invention. Enzo Biochem, Inc. v. Gen-Probe Inc., 

323 F.3d 956, 963 (Fed. Cir. 2002) (citations omitted). 

Thus, the written-description analysis is highly dependent 

on the facts of each case. Nuvo, 923 F.3d at 1383 (citations 

omitted). In general, “written description is judged based 

on the state of the art as of the priority date. . . . [E]vidence

illuminating the state of the art subsequent to the priority 

date is not relevant to written description.” Amgen, F.3d 

at 1373–74 (internal citation omitted).

B. Possession of the Claimed Invention

The core issue in this appeal is whether the specification Biogen filed on February 8, 2007 supports the 2011 

claims that issued in the ’514 Patent. Even more precisely, 

the narrow ground on which this question turns is whether 

the original specification describes “possession” of the

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claimed therapeutically effective DMF480-dose limitation

to treat MS.

The district court began by properly noting that “it is 

the specification itself that must demonstrate possession.”

J.A. 23 (quoting Ariad, 598 F.3d at 1352). The specification covers a broad array of nearly three dozen neurological 

disorders, and MS may arguably constitute an important 

element of the disclosure from the start. See ’514 Patent

col. 1 ll. 12–52 (explaining that the overall purpose of the 

invention is to treat “demyelinating neurological diseases,”

such as MS). Next, DMF appears more than two-dozen 

times throughout the specification, including in the three 

examples listed in the disclosure. The prior art demonstrates the existence of a link between DMF-mediated activation of the Nrf2 pathway and the neuroprotective and 

therapeutic effects of said activation, which could be exploited for the treatment of certain neurological disorders

such as MS. See id. col. 5 ll. 20–24. Thus, assuming that 

a skilled artisan would understand the disclosure to be unambiguously focused on MS despite its inclusion among approximately three-dozen neurological disorders—a 

determination we need not reach in this case—the specification may arguably provide adequate information to convey to a skilled artisan that the invention supports methodof-treatment claims directed to MS and, perhaps, that the 

use of DMF may be therapeutically linked to MS treatment.6

6 We note, however, that method 4, which is the only 

relevant method to this appeal, is devoid of any specific reference to MS. See ’514 Patent col. 8 ll. 35–53; J.A. 27 (noting that MS is merely listed as one of a slew of neurological 

diseases). The district court further found that Mylan’s expert “credibly testified” that nothing in the specification 

“ties an effective dose of DMF specifically to the treatment 

of MS.” J.A. 29.

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The skilled artisan would then look in the specification 

for guidance vis-à-vis a suitable therapeutic-DMF dosage. 

This is where the district court noted the lack of written 

description, upon which it primarily based its finding of invalidity. The DMF480 dose is listed only once in the entire 

specification. See ’514 Patent col. 18 l. 62. The specification’s sole reference to DMF480 constitutes a significant 

fact that cuts against Biogen’s case, particularly because it 

appears at the end of one range among a series of ranges, 

including DMF concentrations of 100–1,000, 200–800, 

240–720, and 480–720 mg/day. That is in stark contrast to 

DMF720, which is referenced independently as one dose 

and was known to be effective as of the February 2007 priority date. The ’514 Patent, as issued, features multiple 

claims that are drawn exclusively to the specific DMF480 

dose, but the specification’s focus on basic research and 

broad DMF-dosage ranges show that the inventors did not 

possess a therapeutically effective DMF480 dose at the 

time of filing in 2007. On this point, Lukashev, the original 

inventor listed in the ’921 Application, offered testimony in 

which he “denied that his research could be extrapolated to 

a clinical dose of DMF; it ‘was never the focus of [his] work 

to inform the clinical dosing of [DMF].’” J.A. 9 (alterations 

in original); see also J.A. 34 (noting that the district court 

found Lukashev’s testimony credible as to the fact that all 

the examples listed in the specification were part of his research and would not have been “helpful in identifying a 

therapeutically effective” DMF dose). Likewise, the district court credited Mylan’s expert testimony at trial that 

the paragraph containing the sole DMF480 reference fails 

to specifically link an effective dose of DMF to the treatment of MS. J.A. 29.

This court has previously held that “[s]atisfaction of 

the description requirement [e]nsures that . . . a claim subsequent to the filing date of the application was sufficiently 

disclosed at the time of filing so that the prima facie date 

of invention can fairly be held to be the filing date of the 

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application.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 

1562 (Fed. Cir. 1991) (quoting In re Smith & Hubin, 

481 F.2d 910, 914 (CCPA 1973)). An inventor need not 

“prove that a claimed pharmaceutical compound actually 

achieves a certain result. But when the inventor expressly 

claims that result, our case law provides that [such] result 

must be supported by adequate disclosure in the specification.” Nuvo, 923 F.3d at 1384. Based on the evidence in 

the record, the district court did not clearly err in determining that Mylan established its burden of showing, by 

clear and convincing evidence, that the specification does 

not adequately support the asserted claims of the ’514 Patent. More specifically, the district court did not clearly err 

in finding that a skilled artisan would not have recognized, 

based on the single passing reference to a DMF480 dose in 

the disclosure, that DMF480 would have been efficacious 

in the treatment of MS, particularly because the specification’s only reference to DMF480 was part of a wide DMFdosage range and not listed as an independent therapeutically efficacious dose.

That Biogen later established the therapeutic efficacy 

of DMF480 is of no import to the written-description analysis. What matters for purposes of the inquiry in this case 

is whether, at the time of filing the disclosure—well before 

the Phase III study even commenced—a skilled artisan

could deduce simply from reading the specification that 

DMF480 would be a therapeutically effective treatment for 

MS. As to this point, the specification’s focus on drug discovery and basic research further buttresses the district 

court’s conclusion that the specification lacks an adequate 

written description to support the DMF480 claims. At the 

time of filing the original disclosure in 2007, the Nrf2 insights that proved critical in the Phase III study had not 

yet been translated to clinical use. See J.A. 35 (finding 

that, based on the evidence presented at trial, Lukashev’s 

research related to Nrf2 activation and small-molecule 

screening “had nothing to do with the clinical development 

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of Tecfidera®”). Regardless of whether O’Neill had in fact 

hypothesized or even conceived the idea of treating MS 

with a DMF480 dose as early as 2003, see J.A. 1586–87, the 

law is clear that a patent cannot be awarded for mere theoretical research without more, see Ariad, 598 F.3d 

at 1353. The written-description requirement limits patent protection only to individuals who perform the difficult 

work of producing a complete and final invention featuring 

all its claimed limitations and publicly disclose the fruits of 

that effort. Id. We therefore determine that, based on the 

evidence in the record, the district did not clearly err in 

finding that Biogen did not possess an invention directed 

to the specific use of a therapeutically effective DMF480 

dose for the treatment of MS as of 2007.

Confronted with the lack of a specific reference to 

DMF480, Biogen and its expert argued that a skilled artisan would be drawn to the DMF480 dose because it was 

“anchored” to the effective DMF720 dose. J.A. 1548–49. 

But the very same sentence in the specification that discloses the DMF 480–720 mg/day range also “anchors” 

DMF240 (a known ineffective dose) to DMF720 (according 

to the DMF 240–720 mg/day range). See ’514 Patent col.

18 ll. 54–64. Not only does the specification anchor an ineffective dose, it also expands the purported range of therapeutic efficacy from DMF100 and DMF200 (doses that a 

skilled artisan would expect to be ineffective) to DMF1,000 

(a dose well above the therapeutically effective DMF720 

mg/day dose). See id. col. 18 ll. 54–64; Appellee’s Br. 26. 

That column 18 of the ’514 Patent specification recites several DMF doses in the 100–1,000 mg/day range as “effective” without even identifying a target disease is further

indicative that the inventors were not in possession of a 

complete and final invention as of February 2007.

Lastly, the court noted that Mylan had impeached 

Wynn’s credibility by pointing out his inconsistent statements and evasiveness when asked, during the district 

court proceedings, why a skilled artisan would be drawn to 

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the purported DMF480 efficacy upon reading the patent 

specification—all while consistently maintaining that a 

skilled artisan would not have reasonably expected 

DMF480 to provide the therapeutic efficacy claimed in the 

patent during the IPR proceeding. J.A. 31–33. After hearing live testimony from the parties’ experts at trial, the district court found that the Biogen expert’s opinion that a 

skilled artisan would be drawn to a DMF480 dose was “neither credible nor persuasive.” JA 30–31. We discern no 

principled reason to disturb the district court’s assessment 

as to the credibility of Biogen’s expert testimony. See Salve 

Regina Coll. v. Russell, 499 U.S. 225, 233 (1991) (describing the “unchallenged superiority” of a district court as to 

the assessment of witness credibility and making findings 

of fact); Highmark, Inc. v. Allcare Health Mgmt. Sys., Inc., 

701 F.3d 1351, 1366 (Fed. Cir. 2012) (Reyna, J., dissenting

from the denial of the petition for rehearing en banc) (noting that intervention as to issues of fact finding should be 

limited to instances of clear error, especially given that “an 

appellate court cannot adequately, if at all, assess credibility of [expert] testimony because the witness is not before 

[the appellate panel] in person.”).

Viewing the record before us in its totality, we discern 

no clear error in the district court’s judgment that Mylan 

established its burden of showing, by clear and convincing 

evidence, that the asserted ’514 Patent claims are invalid 

for lack of written description under 35 U.S.C. § 112.

* * *

Biogen raises several ancillary issues in an effort to reverse the district court decision. For example, Biogen 

claims that the district court “misinterpret[ed] this 

[c]ourt’s ‘blaze[-]marks’ jurisprudence; fail[ed] to consider 

the specification as a whole; erroneously appl[ied] judicial 

estoppel; disregard[ed] the specification’s express disclosure of the claimed dose because it was not described as the 

most preferred; and confus[ed] the written-description 

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requirement with principles of obviousness and unexpected 

results.” Appellant’s Br. 2. But our conclusion that the

district court did not clearly err in finding the ’514 Patent 

invalid for lack of written description under § 112 renders 

all these arguments superfluous.

Notably, the Dissent claims that the district court legally erred by conflating therapeutic and clinical efficacy.

See Dissent Op. at 6, 8. However, when viewed through 

the lens of the ’514 Patent, this is not a legal issue, but a 

factual one. The district court, as the finder of fact, did not 

find it necessary or appropriate to distinguish between

therapeutic effects and clinical efficacy based on the specification’s definition of “therapeutically effective dose” and 

the record before it, and such a determination was not

clearly erroneous.

Most notably, the specification’s definition of “therapeutically effective dose” indisputably features both clinical and therapeutic insignia. For example, the 

specification defines a “therapeutically effective dose” as 

an “amount of a compound” that results in the “prevention 

or delay of onset or amelioration of symptoms of a neurological disorder in a subject,” namely, clinical insignia, “or 

an attainment of a desired biological outcome, such as reduced neurodegeneration (e.g., demyelination, axonal loss, 

and neuronal death) or reduced inflammation of the cells 

of the CNS,” which constitute therapeutic insignia. 

’514 Patent col. 5 ll. 52–59 (emphases added).

On redirect examination, Biogen’s expert attempted to 

characterize the specification’s definition as solely describing therapeutic effects—“demyelination, axonal loss, and 

neuronal death” as well as “fewer [brain] scars”—that once 

could “see on [an] MRI scan, for example.” J.A. 1553–54. 

He distinguished these from clinical endpoints, such as “a 

person hav[ing] less episodes” or “no[ ] progression” of 

symptoms, including “weakness, numbness, loss of bladder 

or bowel control, [sight deterioration], [and] less relapses.” 

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J.A. 1553. But Biogen’s expert did not explain why these 

improved clinical outcomes would not qualify under the 

first half of the specification’s definition, which focuses on 

preventing, delaying the onset of, or ameliorating “symptoms of a neurological disorder” in patients. ’514 Patent 

col. 5 ll. 52–55 (emphasis added).

Based on the record, including at least the specification’s definition of a “therapeutically effective dose” and the 

witness and expert testimony, the district court did not find 

it necessary to distinguish between therapeutic effects and 

clinical efficacy with respect to its patentability determination, instead electing to consider both under the specification’s definition of “therapeutically effective dose.” We 

determine that such a finding was not clearly erroneous.

Accordingly, we conclude that the district court did not 

clearly err in determining that the original 2007 disclosure, 

which focused exclusively on screening compounds for activation of the Nrf2 biological pathway, did not disclose a 

method to administer a therapeutically effective dose of 

DMF480 for the treatment of MS. Nor did the district court 

clearly err in finding that “O’Neill’s hypothesis, that a 

[DMF480 dose] would be efficacious in treating MS, 

evolved from his review” of confidential information, which

a skilled artisan would not have been privy to in 2007 and 

was never included in the original disclosure. See J.A. 35, 

42, 1586–87.

Because we hold that the ’514 Patent is invalid under 

the written-description doctrine, we need not reach the 

merits of the parties’ arguments in the companion IPR 

case.

IV. CONCLUSION

For the reasons set forth in this opinion, we affirm the 

district court’s decision that Mylan satisfied its burden of 

showing, by clear and convincing evidence, that the asserted ’514 Patent claims are invalid for lack of written 

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description under 35 U.S.C. § 112. Viewed in its totality, 

the record shows that the inventors were not in possession 

of a method of administering a therapeutically effective 

dose of DMF480 to treat MS on or before the February 8, 

2007 priority date. We have considered the parties’ remaining arguments and find them unavailing or do not 

reach them.

AFFIRMED

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United States Court of Appeals 

for the Federal Circuit ______________________

BIOGEN INTERNATIONAL GMBH, BIOGEN MA, 

INC.,

Plaintiffs-Appellants

v.

MYLAN PHARMACEUTICALS INC.,

Defendant-Appellee

______________________

2020-1933

______________________

Appeal from the United States District Court for the 

Northern District of West Virginia in No. 1:17-cv-00116-

IMK-JPM, Judge Irene M. Keeley.

______________________

O’MALLEY, Circuit Judge, dissenting.

While I am loath to reverse district court determinations that rely heavily on credibility findings, I must respectfully dissent. There is no dispute over whether the 

district court erred in finding that Biogen was judicially estopped from drawing a distinction between clinical and 

therapeutic effects: it did. Mylan calls the error harmless 

and the majority finds it “ancillary” to its analysis. I, on 

the other hand, believe this threshold error impacted the 

district court’s entire written description analysis. I would 

therefore reverse and remand for reconsideration in light 

of a proper understanding of the distinction between the 

two effects and the written descriptions needed for each.

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I.

A. The district court erred in applying judicial estoppel

As it had tried to do throughout the trial, Biogen explained the distinction between clinical efficacy and therapeutic effects in its post-trial briefs before the district court. 

Clinical efficacy involves the type of scientific rigor associated with Phase III clinical trials: the investigative 

DMF480 dose must produce superior clinical endpoints to 

the standard of care for MS, Rebif®. See J.A. 8066. Therapeutic effects, by contrast, “do not require efficacy on clinical endpoints or superior efficacy to existing drugs.” Id.

It, instead, “refer[s] to the amount of [DMF480] which results in . . . prevention or delay of onset or amelioration of 

symptoms of a neurological disorder” like MS. ’514 patent, 

col. 5, ll. 52–55. 

Based on this distinction, Biogen took issue in its posttrial brief with Mylan’s contention that the ’514 patent 

lacked written description support because “a person of ordinary skill in the art would not have a reasonable expectation that the 480 mg/day [DMF] dose would provide

statistically significant and clinically meaningful effectiveness for treating MS.” J.A. 8064 (citing Mylan’s post-trial 

brief, which quoted Dr. Dawson’s testimony). Biogen

pointed out that, in addition to mixing up written description and obviousness inquiries (which I will discuss infra),

Mylan’s argument erroneously assumed that the claims required clinical efficacy when they only covered therapeutic 

effects. J.A. 8063–66. 

In a two-sentence footnote, the district court concluded 

that Biogen was judicially estopped from pointing out the 

distinction between clinical and therapeutic efficacy. Biogen Int’l GmbH v. Mylan Pharms. Inc., 2020 WL 3317105, 

at *8 n.15 (N.D.W. Va. June 18, 2020). Citing New Hampshire v. Maine, 532 U.S. 742 (2001), the district court reasoned that Biogen could not “deliberately chang[e] 

positions according to the exigencies of the moment.” Id. 

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I need not detail why the court’s footnote ruling on judicial estoppel constituted an abuse of discretion under 

Fourth Circuit law. See Martineau v. Wier, 934 F.3d 385, 

393 (4th Cir. 2019) (setting out a multi-factor test for the 

judicial estoppel inquiry, which the district court wholly 

failed to apply in this case). Biogen’s briefs explain this 

error in detail and neither Mylan nor the majority defends

the district court’s ruling under that governing law. 

I will, however, provide detail on how the erroneous judicial estoppel ruling led the district court to legally err in 

its interpretation of Federal Circuit written description 

precedent. In my view, the district court’s refusal to 

acknowledge the difference between therapeutic and clinical effects evinces a fundamental misunderstanding of 

what is claimed—and, thus, what requires written description support—in the ’514 patent. 

The ’514 patent explains that neurodegenerative disorders like MS are “characterized by inflammation in parts 

of the [central nervous system (CNS)], leading to the loss 

of the myelin sheathing around neuronal axons (demyelination), loss of axons, and the eventual death of neurons, 

oligodendrocytes and glial cells.” ’514 patent, col. 1, ll. 17–

20. The ’514 patent discusses the promise of treating MS 

using DMF, “a member of a large group of anti-oxidant molecules known for their cytoprotective and anti-inflammatory properties.” ’514 patent, col. 5, ll. 16–18. The ’514 

patent claims a “therapeutically effective amount” of 

DMF480, which the specification defines as

that amount of a compound which results in at 

least one of prevention or delay of onset or amelioration of symptoms of a neurological disorder in a 

subject or an attainment of a desired biological outcome, such as reduced neurodegeneration (e.g., demyelination, axonal loss, and neuronal death) or 

reduced inflammation of the cells of the CNS. 

’514 patent, col. 5, ll. 52–59. 

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Notably, the ’514 patent explains that the inventors 

measured DMF’s therapeutic efficacy in terms of its ability 

to enhance the expression levels of Nrf2—a transcription 

factor that activates the expression of genes responsible for 

protecting cells from the neurodegeneration commonly associated with MS. See ’514 patent, col. 5, ll. 16–24; see also 

’514 patent, col. 1, ll. 35–62. Figures 3 and 4 of the ’514 

patent provide in vivo data showing an increase in Nrf2 expression following DMF treatment. ’514 patent, Figures 3 

and 4; see also ’514 patent, col. 22, ll. 1–13. And, the ’514 

patent states: “the finding that DMF activates the Nrf2 

pathway . . . offers a rationale for identification of structurally and/or mechanistically related molecules that would be 

expected to be therapeutically effective for the treatment of 

neurological disorders, such as, e.g., MS.” ’514 patent, col. 

5, ll. 19–24 (emphasis added). Taken together, it is clear 

on the face of the ’514 patent that the claimed “therapeutically effective amount” refers to DMF’s ability to mitigate 

MS symptoms vis-à-vis its modulation of Nrf2 expression; 

it has nothing to do with whether DMF480 outperforms the 

standard of care for MS (Rebif®) in a Phase III clinical trial 

setting. 

It is no wonder, then, why Biogen—in response to 

Mylan’s repeated contentions that the ’514 patent fails the 

written description requirement because it lacks Phase III 

clinical efficacy data—sought in its post-trial briefing to remind the district court that the written description inquiry 

should focus on therapeutic efficacy.1 Far from deliberately 

changing positions as the district court accused it of, Biogen was simply attempting to direct the district court’s attention to the claim language at issue. Judicially estopping 

Biogen from doing so was not just legally erroneous under 

1 To be sure, Mylan continues its erroneous conflation of therapeutic and clinical efficacy before our court. 

See, e.g., Appellee’s Resp. Br. at 48–49.

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Fourth Circuit law, it misapplied our written description 

precedents by ignoring the claims at a time when they 

should have been given primacy. Cf. Phillips v. AWH 

Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en banc) (“It is 

a bedrock principle of patent law that the claims of a patent 

define the invention to which the patentee is entitled the 

right to exclude.”) (citations omitted) (internal quotation 

marks omitted).2 

As discussed further below, the impact of the district 

court’s errant refusal to acknowledge the difference between therapeutic and clinical efficacy is evident throughout the rest of the opinion. 

2 The majority’s argument that there is no ascertainable difference between clinical and therapeutic efficacy is 

wrong for several reasons. See Maj. Op. at 20–21. As I 

have detailed above, the ’514 patent makes clear that “therapeutically effective amount” does not involve comparing 

the claimed DMF480 dosage to the standard of care for MS 

like a clinical trial would. And, neither party ever argued 

this—either to the district court or on appeal. Biogen, instead, advocated distinguishing the two while Mylan and 

the district court blithely proceeded as though there were 

no difference without ever providing any explanation. To 

make up for this deficiency in the trial record, the majority 

provides its own explanation: “clinical insignia” is somehow 

encompassed by the ’514 patent’s definition of “therapeutically effective dose.” Id. (citing ’514 patent, col. 5, ll. 52–

59). The majority appears to forget our role in this appeal: 

we are a court of review, not the primary factfinder. To the 

extent the majority fashions its own explanation of why 

therapeutic and clinical efficacy are one in the same, it 

crosses that line.

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B. The district court’s conflation of therapeutic and clinical efficacy caused it to erroneously require clinical data, 

rather than therapeutic effects

The district court’s failure to distinguish therapeutic 

effects and clinical efficacy also led it to conflate concepts 

of obviousness and written description. This conflation, in 

my view, caused the district court to erroneously require a 

showing of clinical data akin to what would be gathered in 

Phase III clinical trials in its written description analysis. 

Somewhat circularly, after acknowledging that clinical 

data demonstrating effectiveness is not required to satisfy 

written description, the district court went on to find that 

the ’514 patent does not demonstrate possession because it 

lacks clinical efficacy data. Biogen, 2020 WL 3317105, at

*15. To arrive at this conclusion, the district court relied 

on its interpretation of our precedent in Nuvo. According 

to the district court, the patentees in Nuvo could not establish possession because a POSA “would not have expected 

[the claimed drug] to be effective, and nothing in the specification would teach a [POSA] otherwise.” Id. (quoting 

Nuvo Pharms. (Ireland) Designated Activity Co. v. Dr. 

Reddy’s Lab’ys Inc., 923 F.3d 1368, 1377, 1381 (Fed. Cir. 

2019) (alteration in original). The district court reasoned 

that the same set of facts are at issue in this case: because 

Biogen had defended against Mylan’s obviousness challenges in this case and a related inter partes review proceeding by contending that a POSA would not have 

expected the DMF480 dose to clinically treat MS, the ’514 

patent’s failure to teach a POSA otherwise with clinical 

data dooms Biogen’s written description arguments. Id.

(citing Nuvo, 923 F.3d at 1381).

This cannot be right. Whether a claim satisfies the 

written description requirement of § 112 is a question of 

fact that we review for clear error. Ariad Pharms. v. Eli 

Lilly and Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). We 

provide de novo review, however, of a district court’s 

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interpretation of Federal Circuit precedent. Amgen Inc. v. 

Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1337 (Fed. 

Cir. 2003). Our court has long held that “the hallmark of 

written description is disclosure,” meaning that a patent 

must “reasonably convey[] to those skilled in the art that 

the inventor had possession of the claimed subject matter 

as of the filing date.” Ariad, 598 F.3d at 1351. 

Here, the district court’s reading of Nuvo does not accurately describe what we actually held in that case. The 

patent at issue in Nuvo claimed an acid inhibitor that was 

uncoated and effective at raising pH levels. Nuvo, 923 F.3d 

at 1373–1374, 1378. The patent specification in Nuvo, 

however, specifically discussed a known problem in the 

prior art involving uncoated acid inhibitors’ ineffectiveness

at raising pH levels. See id. at 1375 (reversing the district 

court for “not explain[ing] why the mere disclosure of [uncoated acid inhibitors], coupled with the known disadvantages of coated [acid inhibitors], is relevant to the 

therapeutic effectiveness of uncoated [acid inhibitors], 

which the patent recognized as problematic for efficacy due 

to its potential for destruction by stomach acid”) (emphasis 

added). Since the patentees in Nuvo did nothing to explain 

how the invention purported to overcome the commonly 

known problem with uncoated formulations that the patent 

specification explicitly discussed, our court invalidated the 

patent for lack of written description. Id. at 1381. Nowhere in Nuvo did we overlay a POSA’s reasonable expectation of success from the obviousness context onto the 

written description inquiry. To the extent Nuvo mentioned 

a POSA’s expectations, it cabined this discussion to what a 

POSA would have expected based on the explicit teachings 

of the patent specification—not of the prior art. See id. at 

1381 (“In light of the fact that the specification provides 

nothing more than the mere claim that uncoated [acid inhibitors] might work, even though persons of ordinary skill 

in the art would not have thought it would work, the specification is fatally flawed.”).

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The district court’s reliance on Nuvo to conclude that 

Mylan could use Biogen’s own obviousness defenses 

against it in the written description context is, therefore, 

legally erroneous. What a POSA would expect regarding 

clinical efficacy based on the prior art is a distinct question 

from whether a POSA would understand that the inventor 

possessed the claimed invention—i.e., a therapeutically effective dose—based on the patent’s written description. 

Since the district court never engaged in a proper written 

description inquiry, I would reverse and remand for further 

proceedings consistent with a proper written description 

analysis that minds the gaps between obviousness and 

written description, as well as therapeutic and clinical efficacy.3

C. The district court’s conflation of therapeutic and clinical efficacy caused it to erroneously apply our “blaze 

marks” precedent

The majority relieves me of the need to discuss the district court’s erroneous conclusion that the ’514 patent does 

not contain enough “blaze marks” to direct a POSA toward 

MS treatment. See Biogen, 2020 WL 3317105, at *10

(“Method 4 broadly describes treating neurological diseases with a therapeutically effective amount of DMF; MS 

is merely one such disease ‘among a slew of competing possibilities.’”) (citing Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1349 (Fed. Cir. 2013)). The 

majority opinion—appearing to recognize this obvious 

3 To the extent the majority accuses the dissent of 

reweighing the district court’s credibility determinations, I 

disagree. See Maj. Op. at 19–20. Because I believe the district court’s misguided interpretation of Nuvo led it to erroneously require clinical efficacy data for the written 

description inquiry, any expert witness testimony on which 

the district court relied to bolster that requirement is also 

legally unsound.

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error—says it operates under the assumption that the ’514 

patent satisfies written description in this regard. Maj. Op. 

at 15–16. Given the specification’s repeated references to 

MS, that is a wise decision on the majority’s part.

I do, however, need to discuss the district court’s finding (an erroneous one, in my view) that the ’514 patent does 

not contain enough “blaze marks” to “‘link’ a therapeutically effective amount of DMF to a dose of 480mg/day.” Biogen, 2020 WL 3317105, at *10. The district court cites our 

precedent in Ariad, as well as Dr. Greenberg’s trial testimony, to justify its application of our “blaze marks” precedent to this case. Id. I do not believe our case law required 

these patentees to include “blaze marks” in the ’514 patent,

however. And, the district court’s reliance on Dr. Greenberg’s testimony to conclude that the patentees should 

have included “blaze marks” only perpetuated its legally 

erroneous interpretation of our case law. See J.A. 1447–49.

It is axiomatic that, to satisfy the written description 

requirement, a patent specification must “clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.” Ariad, 598 F.3d at 1351 

(citations omitted) (alteration in original). This fundamental concept gets tested, however, whenever a patent’s specification discloses a broad genus and claims a particular 

species contained within that genus. In cases such as 

these, our court has crafted a subgenre within our written 

description jurisprudence that requires patents containing 

laundry list-type disclosures “to provide sufficient ‘blaze 

marks’ to guide a reader through the forest of disclosed possibilities toward the claimed compound.” Novozymes, 723 

F.3d at 1346; see also In re Ruschig, 379 F.2d 990, 994–995 

(C.C.P.A. 1967) (“It is an old custom in the woods to mark 

trails by making blaze marks on the trees. It is no help in 

finding a trail or in finding one’s way through the woods 

where the trails have disappeared . . . to be confronted 

simply by a large number of unmarked trees.”). Notably, 

our “blaze marks” jurisprudence does not apply in every

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case concerning written description; it, instead, provides a 

useful framework to analyze whether written description 

has been met in cases involving patents containing laundry 

list disclosures. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 

1559, 1571 (Fed. Cir. 1996) (“In the absence of such 

blazemarks, simply describing a large genus of compounds 

is not sufficient to satisfy the written description requirement as to particular species or sub-genuses.”). 

On my reading of the ’514 patent, the district court 

erred as a matter of law by requiring Column 18 to contain 

sufficient “blaze marks” regarding the claimed DMF480 

therapeutically effective dose. Method 4 of the ’514 patent 

provides a general discussion of treating neurological diseases, such as MS, with therapeutically effective amounts 

of DMF compounds. See ’514 patent, col. 8, ll. 35–53. Column 18 picks up where Method 4 left off by indicating 

which specific DMF doses the patentees considered therapeutically effective. See id., col. 18, ll. 52–64. Column 18 

does this by providing ranges of DMF doses—some large, 

see id. at col. 18, ll. 58–60 (“0.1 g to 1 g per [d]ay”), and some 

small, see id., col. 18, l. 61 (“240 mg to about 720 mg per 

day”). Notably, Column 18 contains an express disclosure 

of the claimed DMF480 dose4; this reference also comes in 

4 The majority’s decision affirming the district court 

partially rests on the fact that the ’514 patent only mentions the claimed DMF480 dose once. Maj. Op. at 16. But 

the majority cites no case law (and I know of none) for the 

proposition that the written description requirement demands that a patentee recite a claim element repeatedly to 

pass written description muster. The majority does not, 

and cannot, deny that the claimed DMF480 dose is expressly disclosed. To the extent the majority’s opinion may 

be read to establish a requirement that a claim element 

must be disclosed multiple times, I dissent from that holding as well.

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the form of a range. See id. at col. 18, l. 62 (“480 mg to 

about 720 mg per day.”). 

I do not believe our “blaze marks” precedent applies to 

the claimed DMF480 dose because Column 18 does not provide a laundry list disclosure of therapeutically effective 

doses. Despite providing a varying degree of ranges, Column 18 begins one such range with the exact DMF480 dose 

that is claimed. See id. Had the patentees instead listed 

this range as, e.g., “100 mg to about 720 mg per day” and 

expected a POSA to figure out that a 480 mg per day dose 

was therapeutically effective, I would agree that “blaze 

marks” would be necessary to “single out particular trees.” 

In re Ruschig, 379 F.2d at 995. But, because the range provided in Column 18 particularly points out the claimed 

DMF480 dose, I believe the claim satisfies Section 112 and 

our corresponding written description jurisprudence. The 

district court’s application of our “blaze marks” precedent 

and corresponding reliance on Dr. Greenberg’s testimony

thus are erroneous as a matter of law for two reasons. 

First, as discussed above, our “blaze marks” precedent is 

not applicable to this case because Column 18 lacks a laundry list disclosure. And, second, even if this precedent were 

to apply here, Column 18 provides a sufficient “blaze mark” 

by explicitly mentioning the claimed DMF480 dose. How 

much brighter need a disclosure blaze? 

The district court’s inability to “link” method 4 and Column 18, moreover, emanates from its original sin of judicially estopping Biogen from distinguishing between 

therapeutic and clinical effects. With a proper understanding of this distinction, the written description analysis in 

this case is straightforward: method 4 provides a general 

description of treating MS using a therapeutically effective 

DMF dose and column 18 demonstrates the patentees’ possession of the claimed DMF480 dose for that purpose. 

Case: 20-1933 Document: 65 Page: 33 Filed: 11/30/2021
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II.

Because I believe the entire course of the district 

court’s analysis might well change if the court were to adjust the lens through which it considers the evidence and 

testimony, I would remand for reconsideration of the record 

with the understanding that the patent is not about clinical 

efficacy—it is about therapeutic effect—and that the written description and obviousness inquiries are not the same.

Case: 20-1933 Document: 65 Page: 34 Filed: 11/30/2021