`
`
`
`APPENDICES
`APPENDICES
`
`
`
`1a
`
`APPENDIX A
`
`UNITED STATES COURT OF APPEALS
`FOR THE FEDERAL CIRCUIT
`
`No. 2020-1933
`
`
`BIOGEN INTERNATIONAL GMBH,
`BIOGEN MA, INC.,
`Plaintiffs-Appellants,
`
`v.
`
`MYLAN PHARMACEUTICALS INC.,
`Defendant-Appellee.
`
`
`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
`
`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
`
`
`
`
`
`2a
`
`patent-infringement dispute between Biogen Interna-
`tional GmbH, Biogen MA, Inc., and Mylan Pharmaceu-
`ticals, 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 declar-
`atory judgment that the patent was invalid and not in-
`fringed. Following a bench trial, the district court de-
`termined 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.
`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 bio-
`equivalent1 to a previously approved drug may seek
`
`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 ex-
`tent of absorption of the listed [brandname] drug when
`administered at the same molar dose of the therapeutic
`ingredient under similar experimental conditions in ei-
`ther 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 ab-
`
`
`
`
`
`3a
`
`approval from the US Food and Drug Administration
`(FDA) to market the generic product by filing an Ab-
`breviated 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 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 ex-
`pired 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, attest-
`ing 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 pa-
`tent subject to the certification. Id. § 355(j)(2)(B)(iii).
`And the FDA must approve the ANDA, unless the pa-
`tent owner objects by filing an action for patent in-
`fringement against the generic-drug manufacturer
`
`
`
`sorption of the listed [brand-name] drug when adminis-
`tered at the same molar dose of the therapeutic ingredi-
`ent under similar experimental conditions in either a sin-
`gle dose or multiple doses and the difference from the
`listed drug in the rate of absorption of the drug is inten-
`tional, is reflected in its proposed labeling, is not essen-
`tial to the attainment of effective body drug concentra-
`tions on chronic use, and is considered medically insignif-
`icant for the drug.
`
`21 U.S.C. § 355(j)(8)(B)(i)–(ii).
`
`
`
`
`
`4a
`
`within forty-five days of receiving notice of the para-
`graph IV certification. Id. § 355(j)(5)(B)(iii). If the pa-
`tent 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 AN-
`DA 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, Bio-
`gen asserted six patents1 purportedly covering Tecfid-
`era®, 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 Applica-
`tion), which Biogen filed on February 8, 2007. U.S. Pa-
`tent 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 ab-
`normal inflammatory response, which leads to damage
`
`1 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.
`
`
`
`
`
`5a
`
`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 sub-
`stance 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 neurodegen-
`eration, 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:
`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 consist-
`ing 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/day)].
`
`
`
`
`
`6a
`
`Id. col. 27 ll. 59–67. Relevant to this appeal is Biogen’s
`use of DMF, a fumaric-acid ester compound, at a specif-
`ic 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.”1 J.A. 3289–92. The specification casts a
`wide net for a myriad of neurological disorders, includ-
`ing neurodegenerative diseases such as amyotrophic
`lateral sclerosis (ALS), Parkinson’s disease, Alz-
`heimer’s disease, and Huntington’s disease; demyelinat-
`ing neurological diseases, such as various forms of MS
`and at least twenty-eight other disorders related to
`demyelination; polyneuritis; and mitochondrial disor-
`ders with demyelination. See ’514 Patent col. 16 ll. 18–
`63. Although the specification does not focus exclusive-
`ly on MS, it discusses MS-related background infor-
`mation in two paragraphs that appear in the first col-
`umn. 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 neuroin-
`flammatory diseases. J.A. 66–67. Methods 1–3 relate to
`screening, evaluating, and comparing the bioequiva-
`lence 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. Con-
`sistent with the disclosure’s original title concerning
`
`1 On February 7, 2008, Biogen filed International Patent Ap-
`plication PCT/US2008/0016902 (the ’902 Application), which main-
`tained the same title, claims, and inventor as the ’921 Application
`but added to its specification. J.A. 10. On August 7, 2009, the in-
`ternational ’902 Application entered the national phase and be-
`came US Patent Application 12/526,296 (the ’296 Application). Id.
`
`
`
`
`
`7a
`
`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 clini-
`cal 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 up-
`regulates 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 neuro-
`degeneration” induced by demyelination or the death or
`neurons. Id. col. 8 ll. 35–53.
`Save for one paragraph in the specification, the dis-
`closure does not teach potential dosage levels for DMF
`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 possi-
`bility of co-usage with other therapeutic treat-
`ments
`including use of other therapeutic
`
`
`
`
`
`8a
`
`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 administra-
`tions 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 re-
`veals 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, con-
`text. 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 bio-
`logical 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).
`B. Clinical Development and Procedural History
`Between 2004 and 2006, Biogen conducted a Phase
`II, clinical, dose-ranging study to test the efficacy of
`
`
`
`
`
`9a
`
`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 compli-
`ance 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 advocat-
`ed testing the DMF480 dose as part of the trial in Feb-
`ruary 2004. J.A. 7. At the time, Biogen had decided not
`to include the DMF480 dose in the study for commer-
`cial 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 Febru-
`ary 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 in-
`ventor. 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 af-
`ter gathering the Phase III results that demonstrated
`therapeutic efficacy of DMF480.1 J.A. 3437–39; J.A.
`
`
`1 Biogen amended the ’296 Application—the national-phase
`application filed in 2009, see supra note 3—after acquiring its
`
`
`
`
`
`10a
`
`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 applica-
`tion’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 dis-
`covery … .” J.A. 9 (alteration in original). And, more
`importantly, he “denied that his research could be ex-
`trapolated 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 inven-
`tion’s title, Biogen did not make any other changes to
`the specification. This enabled Biogen to claim a priori-
`ty 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 Virgin-
`ia. 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. The district court held a four-day bench trial
`
`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 Octo-
`ber 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 Febru-
`ary 8, 2007 priority date for the ’514 Patent based on the ’921 Ap-
`plication. Id.
`
`
`
`
`
`11a
`
`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 obvious-
`ness 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 testi-
`mony from two neurologists who treat patients with
`MS—Dr. Greenberg for Mylan and Dr. Wynn for Bio-
`gen. 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 Febru-
`ary 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
`
`
`
`
`
`12a
`
`the specification … has been squarely rejected by the
`Federal Circuit.” J.A. 45. Based on the testimony of-
`fered at trial, the context of the ’514 Patent prosecution
`history, and “significant omissions from the specifica-
`tion,” the district court 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 un-
`der 35 U.S.C. § 112. Id. Biogen now appeals the dis-
`trict court’s decision.
`II. STANDARD OF REVIEW
`Whether a claim meets the written-description re-
`quirement is a question of fact, which this court re-
`views for clear error on appeal from a bench trial. Nu-
`vo 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 “defi-
`nite 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 ac-
`count the “unchallenged superiority” of a district
`court’s ability to make witness-credibility determina-
`tions and findings of fact, see Salve Regina Coll. v.
`Russell, 499 U.S. 225, 233 (1991).
`
`
`
`
`
`13a
`
`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:
`The [patent] specification shall contain a writ-
`ten 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 con-
`nected, to make and use the same, and shall set
`forth the best mode contemplated by the inven-
`tor or joint inventor of carrying out the inven-
`tion.1
`35 U.S.C. § 112 (emphasis added). The statutory man-
`date 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 recog-
`nized, 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).
`
`1 Following the enactment of the Leahy–Smith America In-
`vents 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 cur-
`rent § 112(a). 125 Stat. at 296–97. The amendments bear no signif-
`icance for purposes of our written-description analysis.
`
`
`
`
`
`14a
`
`“[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 stat-
`utes since the Founding era. See Univ. of Rochester v.
`G.D. Searle & Co., 358 F.3d 916, 925 (Fed. Cir. 2004).
`This court’s precedents dictate that the § 112 writ-
`ten description “requirement is satisfied only if the in-
`ventor ‘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 demon-
`strate[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, dia-
`grams, formulas, etc.” Lockwood v. Am. Airlines, Inc.,
`107 F.3d 1565, 1572 (Fed. Cir. 1997). The term “posses-
`sion” in the context of written-description jurispru-
`dence 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 na-
`ture of the invention. Enzo Biochem, Inc. v. Gen-Probe
`Inc., 323 F.3d 956, 963 (Fed. Cir. 2002) (citations omit-
`ted). 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 descrip-
`
`
`
`
`
`15a
`
`tion is judged based on the state of the art as of the pri-
`ority 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 specifi-
`cation 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 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 posses-
`sion.” 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 “demyelinat-
`ing 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 exist-
`ence 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 disor-
`ders—a determination we need not reach in this case—
`
`
`
`
`
`16a
`
`the specification may arguably provide adequate infor-
`mation to convey to a skilled artisan that the invention
`supports method-of-treatment claims directed to MS
`and, perhaps, that the use of DMF may be therapeuti-
`cally linked to MS treatment.1
`The skilled artisan would then look in the specifica-
`tion 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 con-
`stitutes 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 concen-
`trations 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 orig-
`inal inventor listed in the ’921 Application, offered tes-
`timony in which he “denied that his research could be
`extrapolated to a clinical dose of DMF; it ‘was never the
`
`
`1 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.
`
`
`
`
`
`17a
`
`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 tes-
`timony 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 therapeu-
`tically 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 suf-
`ficiently 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 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 ade-
`quate disclosure in the specification.” Nuvo, 923 F.3d
`at 1384. Based on the evidence in the record, the dis-
`trict court did not clearly err in determining that Mylan
`established its burden of showing, by clear and convinc-
`ing 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 find-
`ing 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
`
`
`
`
`
`18a
`
`of a wide DMF-dosage range and not listed as an inde-
`pendent therapeutically efficacious dose.
`That Biogen later established the therapeutic effi-
`cacy 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 com-
`menced—a skilled artisan could deduce simply from
`reading the specification that DMF480 would be a ther-
`apeutically 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 writ-
`ten 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 (find-
`ing 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 of Tecfidera®”). Regardless of
`whether O’Neill had in fact hypothesized or even con-
`ceived 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 writ-
`ten-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.
`
`
`
`
`
`19a
`
`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.
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