# 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

___ ___________________

W ILLIAM F. L EE , Wilmer Cutler Pickering Hale and Dorr LLP, Boston, MA, argued for plaintiffs

- appellants. Also represented by A NNALEIGH E. C URTIS , M ADELEINE C. L AUPHEIMER , L ISA J ON P IROZZOLO ; S COTT G. G REENE , New York, NY; T HOMAS S AUNDERS , Washington, DC; P AUL W ILLIAM B ROWNING , J. M ICHAEL J AKES , J AMES B. M ONROE , J ASON L EE R OMRELL , Finnegan, Henderson, Farabow, Garrett & Dunner, LLP , Washington, DC. Case: 20-1933 Document: 65 Page: 1 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 2

D AVID L EE A NSTAETT , Perkins Coie, LLP, Madison, WI

, argued for defendant

- appellee. Also represented by A NDREW D UFRESNE , E MILY J ANE G REB ; D AN L. B AGATELL , Hanover, NH ; S HANNON B LOODWORTH , N ATHAN K. K ELLEY , B RANDON M ICHAEL W HITE , Washington, DC ; M ATTHEW G REINERT , Mylan, Canonsburg, PA

.

__________________ ____
Before O’M ALLEY , R EYNA , and H UGHES , Circuit Judges

. Opinion for the court filed by Circuit Judge R EYNA

. Dissenting o pinion filed by Circuit Judge O’M ALLEY

.
R EYNA , Circuit Judge

. This appeal from the U nited States District Court for the Northern District of West Virginia concerns a patent

infringement dispute between Biogen International GmbH

, Biogen MA

, Inc

. , and Mylan Pharmaceuticals, Inc

. Biogen owns United States Patent 8,399,514 (the ’ 514 P atent), which claim s a method of treating multiple sclerosis with a drug called dimethyl fumarate

. In 2017, Biogen filed a lawsuit a gainst Mylan alleging patent infringemen t

. Mylan counterclaimed f or declaratory judgment that the patent was invalid and not infringed. Foll owing a bench trial, the district court determined that the asserted claims of the ’514 P atent were invalid for lack of written description. Biogen challenges the district court’s decision on appeal.

For the reasons set forth in t his 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 P atent claims are invalid for lack of written description under 35 U.S.C. § 112 . Accordingly, we affirm the judgment of the district
court

. Case: 20-1933 Document: 65 Page: 2 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 3

I. B ACKGROUND 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 bioequivalent 1 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 a mended at 21 U.S.C. § 355 (j)(2)(A) ). The statute requires the generic

- drug m anufacturer 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 [brand

name] drug when administered at the same molardose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses; or
(ii) th e extent of absorption of the [generic] drugdoes 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 i n 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 reflectedin its proposed labeling, is not essential to the attainment of effective body drug concentrations on chroni c use, and is considered medically insignificant for the drug.

21 U.S.C. § 355(j)(8)(B)(i)

– (ii). Case: 20-1933 Document: 65 Page: 3 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 4

any patent that purportedly protect s the brand

- name drug, including information as to whether no such paten t exist s

o r the patent already expired , and if the patent has not expired the manufacturer must indicate t he date on which the patent will expire. 21 U.S.C. § 355(j)(2)(A)( vi i) (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 m anufacturer 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 t he FDA must approve the ANDA

, unless the patent owner obje cts by filing an action for patent infringement against the generic

- drug manufacturer within forty

- five days of receiving notic e 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 FDA

approval process of the generic drug, pending the outcome of the litigation

. See id. § 355(j)(5)(B)(iii)

. Mylan Pharmaceuticals, Inc. (Mylan) filed an ANDAseeking 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 P atent. J.A. 600 1

– 0 2. On June 30, 2017, Biogen International GmbH and Biogen MA

, In c . (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 patents 2

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. Case: 20-1933 Document: 65 Page: 4 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 5

purportedly covering Tecfidera®

, Biogen’s trademark ed DMF

- capsule formulation for the treatment of patients suffering from relapsing

- remitting forms of MS

. Id. Only the ’514 P atent is at issue in this appeal. See J.A. 2

– 3.

A. The ’514 Patent

The ’514 P atent claims priority to U nited States Provisional Application 60/888,921 (the ’921 Application) , which Biogen f iled 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

. ” ’51 4 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 t o 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 S CIENCE 1099, 1099 (1965); J.A. 4

– 5. MS

- induced deterioration of the myelin sheath interferes with the proper transmission of such electrical signals

a cross 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 i s representative and recites : Case: 20-1933 Document: 65 Page: 5 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 6

A method of treating a subject in need of treatment for multiple sclerosis comprising orally admini stering to the subject in need thereof a pharmaceuticalcomposition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and (b) one or more pharmaceutically acceptable excipi ents, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 [milligrams] per day [(mg/d ay )]

. Id. col. 27 ll. 59

– 67. Relevant to this appeal is Biogen’s use of DMF , a fumaric

- acid este r compound, at a specific dose of 480 mg/d ay (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 Meth ods 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. Al though the specification does not focus exclusively on MS , it discusses MS

- related background

3 On February 7, 2008, Bi ogen filed InternationalPatent 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 Applic ation entered the national phase and became US Patent Application 12/526,296 (the ’296 Application). Id. Case: 20-1933 Document: 65 Page: 6 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 7

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 theNrf2 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 focuse s primarily on drug discovery

. Indeed, the invention’s ti t le 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

. 349 0

– 9 1

. Because the claims at issue concern methods to t reat 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 therap y comprising the administration of a compound that upregulates the Nrf2 pathway with a t lea st one other compound that cannot upregulate the pathway. ’514 Patent col. 8 ll. 54

– 63. But method 4 is instructive

, as it discloses “ methods oftreating 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 n ot teach potential dosage levels for DMF Case: 20-1933 Document: 65 Page: 7 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 8

monotherapy

. The sole DMF

- dosage paragraph is not linked to treatment of a ny specific disease but re cites : Effective doses will also vary, as recognized bythose skilled in the art, dependent on route of administra tion, 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 pa y, 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 mgper day may be administered in separate administrations of 2, 3, 4, or 6 eq ual doses.

Id

. col. 18 ll. 54

– 64 (emphasis added)

. A s shown above , t he 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, t he 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 th e bottom end of the spectrum of

a DMF 480

– 720 mg/day range

. Second, t he specification defines the term “effective” within a therapeutic , rather than drug

- discovery, context

. Thus, a ccording 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 re duced neurodegeneration (e.g., demyelination, axonal loss, and neuronal death) or reduced inflammation of the cells of the CNS.” Id

. col. 5 ll. 52

– 59 (emphas e s added)

. Case: 20-1933 Document: 65 Page: 8 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 9

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 com pliance 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

. S ee J

. A

. 1726

. The Phase III results showed efficacy for the DMF480 and DMF720 doses

. J

. A

. 2060

. Based on the 2006 Phase II re sults

— 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 o n 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

— Case: 20-1933 Document: 65 Page: 9 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 10

J.A. 3481

– 86

. O’Neill, however, had not been involved with any of the Nrf2 research that led to the ’514 P atent

. 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 pot ential 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. (alteration s in original). B esides the amendments related to inventorship and the invention’s title, B iogen did not make any other changes to the specification. Th is enabled Biogen to claim a priority date of February 8, 2007 , despite filin g 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 P atent was invalid and not infringed

. J

. A

. 6136

– 44

.

after acquiring its Phase III clinical

- data resu lts 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. Case: 20-1933 Document: 65 Page: 10 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 11

The district court held a four

- day bench trial starting on February 4, 2020

. J.A. 1001. On February 5, 2020, the P atent T rademark and A ppeal B oard ( 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 th e IPR case, the Board rejected an obviousness challenge to the asserted ’514 P atent 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 c onclusion 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, 200 7

. J

. A

. 45

. The court also found that Biogen ’s arguments and Wynn’s testimony that a POSAwould be drawn to the DMF480 dose upon reading the patent specification w ere “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 B iogen ’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 Case: 20-1933 Document: 65 Page: 11 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 12

ultimately concluded that Mylan had satisfied its burden of showing by clear and convincing evidence that the asserted ’514 P atent claims were invalid for lack of written description under 35 U.S.C. § 112. Id

. Biogen now appeals the district court’s decision

. II. S TANDARD OF R EVIEW
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 Lab oratories 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 mi stake 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 con vincing 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 m ust take into account the “unchallenged superiority” of a district court ’s ability to make witness

- credibility determinations and findings of fact

, s ee Salve Regina Coll. v. Russell , 499 U.S. 225, 233 (1991).

III. D ISCUSSION
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: Case: 20-1933 Document: 65 Page: 12 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 13

The [patent] specificati on 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 co nnected, to make and use thesame, 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 pa tenting 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 wh at 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 (1 822)

. “[P]ossession as shown in the disclosure,” therefore, represents the hallmar k 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 revision s 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. Case: 20-1933 Document: 65 Page: 13 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 14

This court’s precedents dictate that t he § 112 written

description “requirement is satisfied only if the inventor ‘convey[s] with reasonable clarity to those skilled in the artthat, 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. Abbot t Lab oratorie s , 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

- descrip tion 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 depe nd on the nature of the invention. Enzo Biochem, Inc. v. Gen

- Probe Inc.

, 323 F.3d 956, 963 (Fed. Cir. 2002) (citations omitted). Th us, th e written

- description analysis is highly dependent on the facts of each case. Nuvo , 923 F.3d at 1383 (citations omit ted). 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

. E ven more precisely, the narrow ground on which this question turns is whether the original specification describes “possession” of the Case: 20-1933 Document: 65 Page: 14 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 15

claimed therapeutically effec tive DMF480

- dose limitation to treat MS

. T he 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 135 2)

. T he 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 P atent 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, w hich could be exploited for the treatment of certain neurological dis orders 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 support s method

of

- treatment claims directed to MS and

, perhaps

, that theuse 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 appe al, 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 neurologicaldiseases). The district court further found that Mylan’s expert “credibly testified” that nothing i n the specification “ties an effective dose of DMF specifically to the treatment of MS.” J.A. 29. Case: 20-1933 Document: 65 Page: 15 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 16

The skilled artisan would then look in the specification for guidance vis

- à

- vis a suitable therapeutic

- DMF dosage. T his is where the district court noted the lack of written description

, upon which it primarily based its finding of invalidity

. The DMF 480 dos e 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 a t the end of one range among a series of ranges

, including DMF concentration s 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. T he ’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 therapeutical ly 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 t he 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 p art of his research and would not have been “helpful in identifying a therapeutically effective” DMF dose). Likewise, t he district court credited Mylan’s expert testimony at trial that the paragraph containing the sole DMF480 reference fails
to specifical ly 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 a t the time of filing so that the prima facie date of invention can fairly be held to be the filing date of the Case: 20-1933 Document: 65 Page: 16 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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) )

. A n 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] resultmust be supported by adequate disclosure in the specificatio n.” 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, t he 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 bee n efficacious in the treatment of MS

, particularly because the specification’s only reference to DMF480 w as part of a wide DMF

dosage range and not listed as a n 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 ev en 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, t he specification’s focus on drug discovery and basic research further buttress es the di strict court’s conclusion that the specification lacks an adequate written description to support the DMF480 claims . At thetime of filing the original disclosure in 2007, the Nrf2 insights that proved critical in the Phase III study had not yet been tran slated to clinical use. See J.A. 35 (finding that, based on the evidence presented at trial, Lukashev’s research related to Nrf 2 activation and small

- molecule screening “ had nothing to do with the clinical development Case: 20-1933 Document: 65 Page: 17 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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of Tecfidera® ”). Regardless of whet her 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, thelaw is clear that a patent cannot be awarded for mere theoretical research without more

, s ee 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 treatmen t 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

. 1 548

– 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 therapeutical ly 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 i ndicative that the inventors were not in possession of a complete and final invention as of February 2007.
Lastly, the court noted that Mylan had impeachedWynn’s credibility by pointing out his inconsistent statements and evasiveness when asked , during th e district court proceedings, why a skilled artisan would be drawn to Case: 20-1933 Document: 65 Page: 18 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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 the rapeutic efficacy claimed in the

p atent 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) ( desc ribing the “ unchallenged superiority ” of a district court as to the assess ment 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., dissent ing from the deni al 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 “ anappellate 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 P atent claims are invalid for lack of written description under 35 U.S.C. § 112

.

* * *
Biogen raises several ancillary issues in a n effort to revers e 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] judicialestoppel; disregard[ed] the specification’s express disclosure of the cl aimed dose because it was not described as the most preferred; and confus[ed] the written

- description Case: 20-1933 Document: 65 Page: 19 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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, t he Dissent claims that the district court legally erred by conflati ng 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. T he di stric t c our t
, a s th e fin de r of fa ct
, d id n ot fin d 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 no t clearly erroneous

. Most n otably, the specification ’s definition of “ therapeutically effective dose ” indisputably features both clinical and therapeutic insignia. For example, t he 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)

. O n redirect examination, Biogen’s expert attempted tocharacterize the specification’s definition as solely describing therapeutic e ffects

— “ 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 th ese 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.” Case: 20-1933 Document: 65 Page: 20 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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J.A. 1553. But Biogen’s expert did no t 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

– 5 5 (emphas i s added)

. Based on the record, including at least the specification’s definition of a “therapeutically effective dose” a nd 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 determin e that such a finding was not clear ly erroneo us

. 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 administ er 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 reac h the merits of the parties’ arguments in the companion IPR

case.
IV. C ONCLUSION 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 P atent claims are invalid for lack of written Case: 20-1933 Document: 65 Page: 21 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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 o n 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 Case: 20-1933 Document: 65 Page: 22 Filed: 11/30/2021

# 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’M ALLEY , 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 thedistrict court erred in finding that Biogen was judicially estopped from dra wing 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 t his 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. Case: 20-1933 Document: 65 Page: 23 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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I.

A. The district court erred in applying j udicial 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 ass ociated 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 eff ects , by contrast, “do not require efficacy on clinical endpoints or supe rior 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 i n its pos t

trial 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. Case: 20-1933 Document: 65 Page: 24 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 3

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

erro r in detail and neither Mylan nor the majority defend s th e 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 Fede ral 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 descripti on 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 lossof the myelin sheathing around neuronal axons (demyeli nation), 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 t heir 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 inflammat ion of the cells of the CNS.

’ 514 patent, col. 5, ll. 52

– 59. Case: 20-1933 Document: 65 Page: 25 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 4

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 forprotecting 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 st ructurally 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 th e 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 ( Reb if® ) 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 deliberatelychanging positions as the district court accused it of, Biogen was simply attempting to direct the district cour t’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. Case: 20-1933 Document: 65 Page: 26 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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 g iven 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 eff icacy 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 t rial 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 a ny explanation. To make up for this deficiency in the trial record, the majority provides its own explanation: “clinical insignia” is somehowencompassed by the ’514 patent’s definition of “therapeutically effective dose.” Id

. (citing ’514 p atent
, 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

cr osses that line

. Case: 20-1933 Document: 65 Page: 27 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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 eff ects The district court’s failure to distinguish th erapeutic effects and clinical eff icacy 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 Pha se 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 do es not demonstrate possession because it lacks clinical efficacy data. Biogen

, 2020 WL 3317105

, at *1 5 . To arrive at this conclusion, the district court relied on its interpretation of our precedent in Nuvo

. According to the district court, the patentee s 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 a re at issue in this case: becauseBiogen had defended against Mylan’s obviousness challenges in this case and a re lated 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

pro vide de novo review, however, of a district court’s Case: 20-1933 Document: 65 Page: 28 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

. 7

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 disclo sure,” 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 accura tely 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 disc ussed a known problem in the prior art involving uncoated acid inhibitors’ ineffectiveness
at rais ing pH levels. See i d. at 137 5 (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 d ue 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 explicit ly 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 skillin the art would not have thought it would work, the specification is fatally flawed.”). Case: 20-1933 Document: 65 Page: 29 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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 prio r 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 writte n 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 di sease ‘among a slew of competing possibilities.’”) (citing Novozymes A/S v. DuPont Nutrition Biosciences APS , 723 F.3d 1336, 1349 (Fed. Cir. 2013)). T he majority opinion

— appearing to recogniz e 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 erroneo usly 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. Case: 20-1933 Document: 65 Page: 30 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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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 erroneo us one, in my view) that the ’ 514 patent doesnot 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 th e ’ 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 axiom atic 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 writte n description jurisprudence that requires patents containing laundry list

- type disclosures “to provide sufficient ‘blazemarks’ 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 Case: 20-1933 Document: 65 Page: 31 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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case concerning written description ; i t, instead, provides a useful framework to analyze whether written description has been met in cases involving patents containing laundry lis t 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 compoundsis not sufficient to satisfy the written description requirement as to particular speci es 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 provi des 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 pat entees 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, Colum n 18 contains an express disclosure of the claimed DMF480 dose 4 ; 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 1 6 . But the majority cites no case law (and I know of none) for theproposition 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. Case: 20-1933 Document: 65 Page: 32 Filed: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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the form of a range

. S ee id. at col. 18, l. 62 (“480 mg to about 720 mg per day.”)

. I do not believe our “blaze marks” precedent applies tothe claimed DMF480 dose because Column 18 does not provide a laundry list disclosure of therapeutically effective doses. Despite providing a varying degree of ranges, C olumn 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., “ 1 00 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 “si ngle out particular trees.” In re Ruschig , 379 F.2d at 995. But

, because the range provided in C olumn 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 C olumn 18 lack s a laundry list disclosure. And, second, even if this precedent were to apply here, C olumn 18 provides a sufficient “blaze mark” by explicitly mentioning t he claimed DMF480 dose. How much brighter need a disclosure blaze?
The district court’s inability to “link” method 4 and C olumn 18, moreover, emanates from its original sin of judicially estopping Biogen from distinguishing between therapeutic and clinic al 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: 11/30/2021BIOGEN INTERNATIONAL GMBH v. MYLAN PHARMACEUTICALS INC

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II.

Because I believe the entire course of the districtcourt’s analysis might well change if the court were to adjust the lens through which it considers the evidence and testimony, I w ould 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