United States Court of Appeals
`for the Federal Circuit
`______________________
`
`AMGEN INC., AMGEN MANUFACTURING
`LIMITED, AMGEN USA, INC.,
`Plaintiffs-Appellees
`
`v.
`
`SANOFI, AVENTISUB LLC, REGENERON
`PHARMACEUTICALS INC., SANOFI-AVENTIS U.S.,
`LLC,
`Defendants-Appellants
`______________________
`
`2017-1480
`______________________
`
`Appeal from the United States District Court for the
`District of Delaware in Nos. 1:14-cv-01317-SLR, 1:14-cv-
`01349-SLR,
`1:14-cv-01393-SLR,
`1:14-cv-01414-SLR,
`Judge Sue L. Robinson.
`______________________
`
`Decided: October 5, 2017
`______________________
`
` DARYL JOSEFFER, King & Spalding LLP, Washington,
`DC, argued for plaintiffs-appellees. Also represented by
`CHRISTOPHER ROBERT HEALY, JOSHUA NATHANIEL
`MITCHELL; MERRITT ELLEN MCALISTER, Atlanta, GA;
`KATHERINE NICOLE CLOUSE, SARAH CHAPIN COLUMBIA,
`McDermott, Will & Emery LLP, Boston, MA; WILLIAM G.
`GAEDE, III, Menlo Park, CA; ERIC W. HAGEN, Los Angeles,
`CA; EMILY CURTIS JOHNSON, ERICA S. OLSON, DENNIS J.
`
`

`

`2
`
`
`
` AMGEN INC. v. SANOFI
`
`SMITH, STEVEN D. TANG, STUART L. WATT, WENDY A.
`WHITEFORD, Amgen
`Inc., Thousand Oaks, CA;
`CHRISTOPHER MEAD, London & Mead, Washington, DC;
`MELANIE K. SHARP, Young, Conaway, Stargatt & Taylor
`LLP, Wilmington, DE.
`
`PAUL D. CLEMENT, Kirkland & Ellis LLP, Washington,
`
`DC, argued for defendants-appellants. Also represented
`by GEORGE W. HICKS, JR., NATHAN S. MAMMEN; SIEW YEN
`CHONG, VISHAL C. GUPTA, JOHN J. MOLENDA, Steptoe &
`Johnson, LLP, New York, NY; RICHARD PRASEUTH, Los
`Angeles, CA; KILEY ANN WHITE, Washington, DC.
`
` DUANE CHRISTOPHER MARKS, Eli Lilly and Company,
`Indianapolis, IN, for amicus curiae Eli Lilly and Compa-
`ny. Also represented by GREGORY ALAN COX, GILBERT
`VOY, ALEXANDER WILSON.
`
`BARBARA ANNE JONES, AARP Foundation Litigation,
`
`Pasadena, CA, for amici curiae AARP and AARP Founda-
`tion.
`
` DIMITRIOS T. DRIVAS, White & Case LLP, New York,
`NY, for amicus curiae Pfizer Inc. Also represented by ERIC
`M. MAJCHRZAK, AMIT THAKORE; JEFFREY NEIL MYERS,
`Pfizer Inc., New York, NY.
`
` DAVID A. KELLY, Hunton & Williams LLP, Atlanta,
`GA, for amicus curiae Ipsen Pharma S.A.S.
`
` MELISSA ARBUS SHERRY, Latham & Watkins LLP,
`Washington, DC, for amicus curiae AbbVie Inc. Also
`represented by MICHAEL A. MORIN, EMILY K. SAUTER.
`
` WILLIAM MARSILLO, Boies, Schiller & Flexner, LLP,
`Armonk, NY, for amici curiae Luis Aparicio, M.D., W.
`Ross Davis, M.D., Avichai Eres, M.D., Norman Lepor,
`M.D., Mary McGowan, M.D., Narendra Singh, M.D., Paul
`
`

`

`AMGEN INC. v. SANOFI
`
`3
`
`Thompson, M.D., Rosa DeBernardo, Alina Wilson. Also
`represented by MICHAEL JAY, Santa Monica, CA.
`______________________
`
`
`
`Before PROST, Chief Judge, TARANTO and HUGHES,
`Circuit Judges.
`
`PROST, Chief Judge.
`
`Appellants Sanofi, Aventisub LLC, Regeneron Phar-
`maceuticals Inc., and Sanofi-Aventis U.S., LLC (collective-
`ly, “Appellants”) appeal from a final judgment of the
`district court holding U.S. Patent Nos. 8,829,165 (“’165
`patent”) and 8,859,741 (“’741 patent”) not invalid and
`granting a permanent injunction enjoining sales of Appel-
`lants’ Praluent® alirocumab (“Praluent”).1 In particular,
`Appellants argue that the district court improperly ex-
`cluded evidence regarding written description and ena-
`blement, improperly instructed the jury on written
`description, improperly denied Appellants’ motion seeking
`JMOL of no written description and no enablement,
`improperly granted Appellees’ motion seeking JMOL of
`non-obviousness, and improperly issued the permanent
`injunction. Appellants’ Br. 1. Because we conclude that
`the district court (i) erred by excluding Appellants’ evi-
`dence regarding written description and enablement, and
`(ii) improperly instructed the jury on written description,
`we reverse-in-part and remand for a new trial on written
`description and enablement. We also conclude that
`Appellants are not entitled to JMOL of no written de-
`scription and no enablement. We affirm the district
`court’s grant of Appellees’ JMOL of non-obviousness.
`Finally, we vacate the district court’s permanent injunc-
`tion.
`
`
`1 Appellants stipulated to infringement of the ’165
`and ’741 patents. Appellants’ Br. 11.
`
`

`

`4
`
`
`
` AMGEN INC. v. SANOFI
`
`I
`A
`The patents at issue generally relate to antibodies
`
`that help reduce low-density lipoprotein cholesterol (LDL-
`C), or “bad cholesterol.” High levels of LDL-C in the
`bloodstream can cause heart attacks, strokes, and cardio-
`vascular disease. Typically, high LDL-C is treated using
`small molecules called statins. In some cases, however,
`statins have adverse side effects or cannot reduce a pa-
`tient’s LDL-C to a healthy level, requiring alternative
`treatment. One such alternative treatment is a PCSK9
`inhibitor—the medicine claimed by the patents at issue.
`PCSK9 is a naturally occurring protein that binds to and
`causes the destruction of liver cell receptors (LDL recep-
`tors, or LDL-Rs) that are responsible for extracting LDL-
`C from the bloodstream.
`Appellees Amgen Inc., Amgen Manufacturing, Ltd.,
`and Amgen USA, Inc. (collectively, “Appellees”) first
`began studying PCSK9 in early 2005. This research
`resulted in the development of Appellees’ drug Repatha™
`which uses the active ingredient “evolocumab.” Evo-
`locumab is a monoclonal antibody that targets PCSK9 to
`prevent it from destroying LDL-R proteins. Appellees
`filed for FDA approval on August 27, 2014. The FDA
`approved Repatha in August 2015.
`The two patents at issue, both of which share the
`same specification, are entitled “Antigen binding proteins
`to proprotein convertase subtilisin kexin
`type 9
`(PCSK9).”2 The ’165 patent issued on September 9, 2014,
`and the ’741 patent issued on October 14, 2014. The
`patents have an undisputed priority date of January 9,
`2008. Appellants’ Br. 12. The relevant claims cover the
`
`2 All references are to the ’165 patent unless other-
`wise indicated.
`
`

`

`AMGEN INC. v. SANOFI
`
`5
`
`entire genus of antibodies that bind to specific amino acid
`residues on PCSK9 and block PCSK9 from binding to
`LDL-Rs.3 The patents do not specifically claim Repatha,
`or any other antibody, by amino acid sequence. Claim 1 of
`the ’165 patent is representative. It recites:
`An isolated monoclonal antibody, wherein, when
`bound to PCSK9, the monoclonal antibody binds
`to at least one of the following residues: S153,
`I154, P155, R194, D238, A239, I369, S372, D374,
`C375, T377, C378, F379, V380, or S381 of SEQ ID
`NO:3, and wherein the monoclonal antibody
`blocks binding of PCSK9 to LDL[-]R.
`’165 patent col. 427 ll. 47–53.
`The patents disclose the trial-and-error process Appel-
`lees used to generate and screen antibodies that bind to
`PCSK9 and block PCSK9 from binding to LDL-Rs. Id. at
`col. 73 l. 29–col. 124 l. 31. In particular, the specification
`explains that to discover the claimed antibodies, 3,000
`human monoclonal antibodies were “rescreened for bind-
`ing to wild-type PCSK9 to confirm stab[ility],” id. at col.
`78 ll. 4–6, which were eventually narrowed to “85 antibod-
`ies that blocked interaction between the PCSK9 . . . and
`the LDLR [at] greater than 90%,” id. at col. 80 ll. 35–37.
`The specification also discloses the three-dimensional
`structures, obtained via x-ray crystallography, of two
`antibodies known to bind to residues recited in the
`claims—21B12 (Repatha) and 31H4. Id. at fig. 3E, fig.
`3JJ, col. 99 l. 29–col. 103 l. 60. Finally, the specification
`discloses the amino acid sequences of twenty-two other
`antibodies that “bin” with Repatha or 31H4, meaning they
`
`
`3 A “residue” is a particular amino acid along
`
`PCSK9’s amino acid sequence. Thus, the residue “S153”
`refers to the amino acid serine, located at the 153rd posi-
`tion of PCSK9’s sequence.
`
`

`

`6
`
`
`
` AMGEN INC. v. SANOFI
`
`compete with these antibodies for binding to PCSK9. Id.
`at figs. 2A–2D, figs. 3A–3JJ, col. 88 l. 30–col. 89 l. 37.
`In September 2007, Appellants also started exploring
`antibodies targeting PCSK9. This research resulted in
`development of Praluent. The active ingredient in
`Praluent is a monoclonal antibody that targets PCSK9 to
`prevent it from binding to and destroying LDL-R proteins.
`The LDL-R proteins then extract LDL-C thereby lowering
`overall LDL-C levels in the bloodstream. In November
`2011, the PTO issued Appellants a patent that claimed
`Praluent by its amino acid sequence. Appellants filed for
`FDA approval of Praluent in November 2014. The FDA
`approved Praluent in July 2015.
`B
`In October 2014, Appellees sued Appellants, claiming
`that Praluent infringed the patents in suit. Appellants
`stipulated to infringement but challenged the patents’
`validity on written description, enablement, and obvious-
`ness grounds.
`Over the course of litigation, the district court made
`several rulings and decisions that are challenged here on
`appeal. First, the district court excluded all of Appellants’
`post-priority-date evidence proffered to show that the
`patents in suit did not provide adequate written descrip-
`tion. Second, the district court instructed the jury, over
`Appellants’ objection, that written description can be
`satisfied “by the disclosure of a newly-characterized
`antigen . . . if you find that the level of skill and
`knowledge in the art of antibodies at the time of filing was
`such that production of antibodies against such an anti-
`gen was conventional or routine.” J.A. 1580. Third, the
`district court denied Appellants’ post-trial motions seek-
`ing JMOL on written description and enablement.
`Fourth, the district court excluded two purported prior art
`references, Novartis and Schering, for being improper
`prior art and granted Appellees’ motion seeking JMOL of
`
`

`

`AMGEN INC. v. SANOFI
`
`7
`
`non-obviousness. And fifth, the district court issued a
`permanent injunction removing Appellants’ Praluent from
`the market.
`This court stayed the injunction pending appeal.
`II
`A
`We first review whether the district court improperly
`excluded Appellants’ evidence about antibodies, including
`Appellants’ infringing Praluent, developed after the
`patents’ priority date of January 9, 2008. Appellants
`proffered this evidence to show that the patents lack 35
`U.S.C. § 112 written description support. The district
`court excluded this evidence, concluding that because the
`evidence did not “illuminate[] the state of the art at the
`time of filing,” it was not relevant “to determine whether
`there is sufficient disclosure of the claimed invention.”
`Amgen Inc. v. Sanofi, No. 14-1317, 2016 WL 675576, at *2
`(D. Del. Feb. 18, 2016); see also J.A. 1030 (“I concluded
`that, because the written description requirement is
`tested as of the filing date, such evidence should be ex-
`cluded.”). Because the district court’s decision was based
`on a misapplication of the law, we reverse.
`Section 112 states that “[t]he specification shall con-
`tain a written description of the invention . . . in such full,
`clear, concise, and exact terms as to enable any person
`skilled in the art to which it pertains . . . to make and use
`the same . . . .” This requirement ensures “that the inven-
`tor actually invented the invention claimed.” Ariad
`Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
`Cir. 2010) (en banc). To show invention, a patentee must
`convey in its disclosure that it “had possession of the
`claimed subject matter as of the filing date.” Id. at 1350.
`Demonstrating possession “requires a precise definition”
`of the invention. Id. To provide this “precise definition”
`for a claim to a genus, a patentee must disclose “a repre-
`
`

`

`8
`
`
`
` AMGEN INC. v. SANOFI
`
`sentative number of species falling within the scope of the
`genus or structural features common to the members of
`the genus so that one of skill in the art can ‘visualize or
`recognize’ the members of the genus.” Id.
`Here, the parties dispute whether a court may rely on
`post-priority-date evidence to determine if a patent dis-
`closes “a representative number of species.” Id. Appel-
`lants argue that because the “written description
`requirement protects against ‘attempts to preempt the
`future before it has arrived,’” Appellants’ Br. 28 (quoting
`Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)), it
`“would make [no] sense if future innovators were barred
`from introducing evidence of their own innovations in
`written description challenges,” id. Appellees counter
`that because “[w]ritten description and enablement are
`judged at the time of filing,” Appellees’ Br. 34 (citing
`Ariad, 598 F.3d at 1355), “post-priority-date evidence may
`be relevant only if it illuminates the state of the art at the
`filing date,” id. (first citing In re Koller, 613 F.2d 819, 825
`(CCPA 1980); then citing In re Hogan, 559 F.2d 595, 605
`(CCPA 1977)). And because Praluent and the other
`antibodies Appellants proffered did not exist until after
`the priority date, “they [were] not part of the state of the
`art . . . and therefore cannot ‘illuminate’ it.” Id.
`Appellees are correct that written description is
`judged based on the state of the art as of the priority date.
`Ariad, 598 F.3d at 1355. Accordingly, evidence illuminat-
`ing the state of the art subsequent to the priority date is
`not relevant to written description. Id. Appellants,
`however, are also correct that a patent claiming a genus
`must disclose “a representative number of species falling
`within the scope of the genus or structural features com-
`mon to the members of the genus so that one of skill in
`the art can ‘visualize or recognize’ the members of the
`genus.” Id. at 1351. Evidence showing that a claimed
`genus does not disclose a representative number of spe-
`cies may include evidence of species that fall within the
`
`

`

`AMGEN INC. v. SANOFI
`
`9
`
`claimed genus but are not disclosed by the patent, and
`evidence of such species is likely to postdate the priority
`date. If such evidence predated the priority date, it might
`well anticipate the claimed genus.
`Here, Appellants sought to introduce evidence not to
`illuminate the state of the art on the priority date but to
`show that the patent purportedly did not disclose a repre-
`sentative number of species. Appellants’ Br. 12. As a
`logical matter, such evidence is relevant to the represent-
`ativeness question. Simply, post-priority-date evidence of
`a particular species can reasonably bear on whether a
`patent “fails to disclose a representative number of spe-
`cies falling within the scope of the genus or structural
`features common to the members of the genus so that one
`of skill in the art can ‘visualize or recognize’ the members
`of the genus.” Ariad, 598 F.3d at 1350.
`We have not ruled on that question to date, but the
`common-sense logic of admissibility finds support in
`AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc.,
`759 F.3d 1285 (Fed. Cir. 2014). There, Centocor, the
`accused infringer of AbbVie’s functional claim to a genus
`of antibodies, stipulated to infringement and challenged
`validity based on written description. Centocor argued
`that the antibodies disclosed in AbbVie’s patents were
`“not representative of the entire genus,” id. at 1298, and it
`relied heavily on its own accused antibody to support the
`unrepresentativeness argument,
`introducing evidence
`that
`its
`antibody
`“differ[ed]
`considerably
`from
`the . . . antibodies described in [the asserted] patents,” id.
`at 1300. The jury found that the patents lacked adequate
`written description, and both the district court and this
`court relied heavily on that evidence in upholding the
`invalidity verdict. See AbbVie, 759 F.3d at 1301; Abbott
`GmBH & Co., KG v. Centocor Ortho Biotech, Inc., 971
`F.3d 171, 176–80 (D. Mass. 2013). That is significant
`because, at the time of trial, the timing of Centocor’s
`antibody in relation to AbbVie’s priority date was unset-
`
`

`

`10
`
`
`
` AMGEN INC. v. SANOFI
`
`tled: the PTO, in an interference, had found that Cento-
`cor’s antibody postdated AbbVie’s invention, as AbbVie
`argued, and the subsequent litigation of the question
`under 35 U.S.C. § 146 was unresolved. See Abbott, 870 F.
`Supp. 2d at 246. The Centocor antibody, in short, was a
`basis for the unrepresentativeness ruling without regard
`to whether it postdated the patent’s priority date.
`Appellees argue, and the district court held, that our
`predecessor court’s decision in In re Hogan prohibits the
`use of post-priority-date evidence to show that a patent
`fails to disclose a representative number of species. See
`Appellees’ Br. 34 (“[P]ost-priority-date evidence may be
`relevant only if it illuminates the state of the art at the
`filing date.”); J.A. 1032 (“By giving its imprimatur to the
`jury’s verdict [in AbbVie], the Federal Circuit arguably
`departed from its own precedent, established in In re
`Hogan, 559 F.2d 595 (CCPA 1977), that later-developed or
`later-discovered products should not be used to test
`compliance with 35 U.S.C. § 112[, ¶] 1.”). But the district
`court and Appellees misread In re Hogan by conflating the
`difference between post-priority-date evidence proffered to
`illuminate the post-priority-date state of the art, which is
`improper, with post-priority-date evidence proffered to
`show that a patent fails to disclose a representative
`number of species. In re Hogan prohibits the former but
`is silent with respect to the latter.
`In In re Hogan, the U.S. Patent and Trademark Office
`(“PTO”) rejected an application directed to “Solid Polymer
`of Olefins” for failing to enable the claimed invention. 559
`F.3d at 597. The relevant claim at issue recited, in its
`entirety, “[a] normally solid homopolymer of 4-methyl-1-
`pentene.” Id. The application disclosed “a method of
`making the crystalline form” of the claimed homopolymer
`which was “the only then existing way to make such a
`polymer.” Id. at 606. The PTO rejected the application,
`however, because the application did not disclose a sec-
`ond, “amorphous form” of making the polymer “which . . .
`
`

`

`AMGEN INC. v. SANOFI
`
`11
`
`did not exist” as of the priority date. Id. Our predecessor
`court reversed the PTO, holding that “[t]o now say that
`appellants should have disclosed in 1953 the amorphous
`form which on this record did not exist until 1962, would
`be to impose an impossible burden on inventors and thus
`on the patent system.” Id. Further, because the appli-
`cant had claimed the homopolymer and not a particular
`method of making the polymer, the court further held that
`“[t]o restrict appellants to the crystalline form disclosed,
`under such circumstances, would be a poor way to stimu-
`late invention, and particularly to encourage its early
`disclosure.” Id.
`Here, unlike in In re Hogan, Appellants were not of-
`fering post-priority-date evidence to show that Appellees’
`claimed genus is not enabled because of a change in the
`state of the art. Instead, Appellants offered Praluent and
`other post-priority-date antibodies to argue that the
`claimed genus fails to disclose a representative number of
`species. As explained above, the use of post-priority-date
`evidence to show that a patent does not disclose a repre-
`sentative number of species of a claimed genus is proper.
`It was thus legal error for the district court to categorical-
`ly preclude all of Appellants’ post-priority-date evidence of
`Praluent and other antibodies. Accordingly, we reverse
`the district court’s decision and remand for a new trial on
`written description.
`For many of the same reasons, the district court’s im-
`proper exclusion of post-priority-date evidence requires a
`new trial on enablement as well. Under the enablement
`requirement, “the specification of a patent must teach
`those skilled in the art how to make and use the full scope
`of the claimed invention without undue experimentation.”
`Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1365
`(Fed. Cir. 1997). Appellants purportedly sought to intro-
`duce post-priority-date evidence showing that Appellees
`engaged in lengthy and potentially undue experimenta-
`tion to enable the full scope of the claims. Such evidence
`
`

`

`12
`
`
`
` AMGEN INC. v. SANOFI
`
`could have been relevant to determining if the claims
`were enabled as of the priority date and should not have
`been excluded simply because it post-dated the claims’
`priority date. See, e.g., White Consol. Indus., Inc. v. Vega
`Servo-Control, Inc., 713 F.2d 788, 791 (Fed. Cir. 1983)
`(determining, based on post-priority-date expert evidence
`that “1½ to 2 man years of effort” would be needed to
`practice an invention, that patent claims were not ena-
`bled). Accordingly, we reverse the district court’s decision
`excluding Appellants’ post-priority-date evidence of
`enablement and remand for a new trial on enablement.
`B
`We next consider whether the trial court improperly
`instructed the jury on written description. The district
`court correctly instructed the jury that in order to satisfy
`the written description requirement, a patentee may
`disclose either a representative number of species falling
`within the scope of the genus or disclose structural fea-
`tures common to the members of the genus so that one of
`skill in the art can visualize or recognize the members of
`the genus. Additionally, however, the district court
`further instructed the jury that:
`In the case of a claim to antibodies, the correlation
`between structure and function may also be satis-
`fied by the disclosure of a newly characterized an-
`tigen by its structure, formula, chemical name, or
`physical properties if you find that the level of
`skill and knowledge in the art of antibodies at the
`time of filing was such that production of antibod-
`ies against such an antigen was conventional or
`routine.
`J.A. 1580. Appellants argue that this instruction is
`erroneous because disclosing an antigen does not satisfy
`the written description requirement for a claim to an
`antibody. Appellees respond that the instruction was
`proper because it merely restates the law as set forth in
`
`

`

`AMGEN INC. v. SANOFI
`
`13
`
`Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed.
`Cir. 2002), Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir.
`2004), and Centocor Ortho Biotech, Inc. v. Abbott Labs.,
`636 F.3d 1341 (Fed. Cir. 2011). As discussed below, the
`district court’s instruction is not legally sound and is not
`based on any binding precedent. Accordingly, we con-
`clude that the instruction was improper.
`The district court’s instruction traces its roots back to
`PTO guidelines first discussed by this court in Enzo
`Biochem. That case involved claims directed to nucleic
`acid probes that were defined by their function of selec-
`tively hybridizing to the genetic material of certain bacte-
`ria. Enzo Biochem, 323 F.3d at 960. We noted in that
`case that not “all functional descriptions of genetic mate-
`rial fail to meet the written description requirement.” Id.
`at 964. Instead, we cited the PTO’s Guidelines on written
`description for the proposition that “functional character-
`istics when coupled with a known or disclosed correlation
`between function and structure” may satisfy the written
`description requirement. Id. (citing Guidelines for Exam-
`ination of Patent Applications Under the 35 U.S.C. 112, ¶
`1, “Written Description” Requirement 66 Fed. Reg. 1099–
`01, 1106 (“Guidelines”)).4 We further noted, in dicta, that
`
`
`4 The Guidelines were first published on Feb. 28,
`2000 as the Revised Interim Written Description Guide-
`lines Training Materials. In March 2008, the training
`materials were revised and republished as Written De-
`scription Training Materials, Revision 1, available at
`https://www.uspto.gov/sites/default/files/web/menu/
`written.pdf. The PTO now notes that the Training Mate-
`rials have been “archived” and that “[a] new version will
`be prepared to reflect changes in the law since 2008,
`including any required clarifications due to developments
`in the law relating to 35 U.S.C. 112.” Examination Guid-
`ance and Training Materials, United States Patent and
`
`

`

`14
`
`
`
` AMGEN INC. v. SANOFI
`
`“the PTO would find compliance with 112, [¶] 1, for a
`claim to an isolated antibody capable of binding to antigen
`X, notwithstanding the functional definition of the anti-
`body, in light of the well-defined structural characteristics
`for the five classes of antibody, the functional characteris-
`tics of antibody binding, and the fact that the antibody
`technology is well developed and mature.” Id. (citing
`Synopsis of Application of Written Description Guidelines,
`at
`60,
`https://web.archive.org/
`available
`at
`web/20041101121800/http://www.uspto.gov/web/menu/wri
`tten.pdf).
`In Noelle, the patent owner claimed an antibody and
`sought to claim priority to an earlier filed patent. 355
`F.3d at 1349. Noelle argued that “because antibodies are
`defined by their binding affinity to their antigens, he
`sufficiently described [the claimed antibody] by stating
`that it binds to [a disclosed antigen].” Id. We rejected this
`argument and concluded that the claims were not entitled
`to the earlier priority date because “Noelle failed to dis-
`close the structural elements of [the] antibody or antigen
`in his earlier . . . application.” Id. In reaching this con-
`clusion, we acknowledged that according to Enzo, “as long
`as an applicant has disclosed a ‘fully characterized anti-
`gen,’ either by its structure, formula, chemical name, or
`physical properties, or by depositing the protein in a
`public depository, the applicant can then claim an anti-
`body by its binding affinity to that described antigen.” Id.
`But because Noelle did not disclose structure for the
`antibody or the antigen, we did not rely on Enzo to find
`that the patentee had satisfied the written description
`requirement.
`
`
`Trademark Office, available at https://www.uspto.
`gov/patent/laws-and-regulations/examination-
`policy/examination-guidance-and-training-materials.
`
`

`

`AMGEN INC. v. SANOFI
`
`15
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`Then, in Centocor, we examined Enzo and Noelle as
`well as the PTO Guidelines and held that the antibody
`claims at issue were invalid for lack of written descrip-
`tion. 636 F.3d at 1351–53. We noted that under the
`PTO’s Guidelines, “an applicant can claim an antibody to
`novel protein X without describing the antibody when
`(1) the applicant fully discloses the novel protein and
`(2) generating the claimed antibody is so routine that
`possessing the protein places the applicant in possession
`of an antibody.” Id. at 1351–52. The patentee there had
`claimed a “class of antibodies containing a human varia-
`ble region that have particularly desirable therapeutic
`properties: high affinity, neutralizing activity, and A2
`specificity.” Id. at 1352. The claimed antibodies could
`bind to “the human TNF-α protein.” Id. at 1351. The
`patentee there argued that under Noelle and the PTO
`Guidelines, “fully disclosing the human TNF-α protein
`provides adequate written description for any antibody
`that binds to human TNF-α.” Id. We held, however, that
`even though the patentee had disclosed the human TNF-α
`protein, the claims were still invalid. Id. at 1352–53. We
`questioned the propriety of the “newly characterized
`antigen” test and concluded that instead of “analogizing
`the antibody-antigen relationship to a ‘key in a lock,’” it
`was more apt to analogize it to a lock and “a ring with a
`million keys on it.” Id. at 1352.
`Centocor is the only case where we examined the
`“newly characterized antigen” test in some detail. The
`test was not central to the holding in either Enzo or Noelle
`and neither case explored it in much depth. And in
`Noelle, we cautioned that “each case involving the issue of
`written description[] ‘must be decided on its own facts.
`Thus, the precedential value of cases in this area is ex-
`tremely limited.’” Id. at 1349 (quoting Vas–Cath Inc. v.
`Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991)).
`The essential problem with the jury instruction given
`in this case is that it effectively permitted the jury to
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` AMGEN INC. v. SANOFI
`
`dispense with the required finding of a “written descrip-
`tion of the invention.” 35 U.S.C. § 112. Our en banc
`decision in Ariad, reflecting earlier decisions such as
`Schriber-Schroth Co. v. Cleveland Trust Co., 305 U.S. 47,
`56–57 (1938), and In re Ruschig, 379 F.2d 990, 991–95
`(CCPA 1967), made clear that, to satisfy the statutory
`requirement of a description of the invention, it is not
`enough for the specification to show how to make and use
`the invention, i.e., to enable it. Ariad, 598 F.3d at 1345–
`46, 1347–48. Yet the instruction in this case invites just
`that improper equation. A jury would naturally under-
`stand the instruction to permit it to deem any antibody
`within the claim adequately described merely because the
`antibody could easily be “produc[ed]” (and, implicitly,
`used as an antibody). J.A. 1580 (requirement “may . . . be
`satisfied” if antigen is newly characterized and “produc-
`tion of antibodies against such an antigen was conven-
`tional or routine”). Indeed, the instruction does not even
`require any particular antibody to be easily made; all it
`requires is that “production of antibodies”—some, not
`all—“against [a newly characterized] antigen” be conven-
`tional or routine. By permitting a finding of adequate
`written description merely from a finding of ability to
`make and use, the challenged sentence of the jury instruc-
`tion in this case ran afoul of what is perhaps the core
`ruling of Ariad.
`We cannot say that this particular context, involving
`a “newly characterized antigen” and a functional genus
`claim to corresponding antibodies, is one in which the
`underlying science establishes that a finding of “make and
`use” (routine or conventional production) actually does
`equate to the required description of the claimed products.
`For us to draw such a conclusion, and transform a factual
`issue into a legally required inference, we would have to
`declare a contested scientific proposition to be so settled
`as to be entitled to judicial notice. That we cannot do.
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`AMGEN INC. v. SANOFI
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`17
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`An adequate written description must contain enough
`information about the actual makeup of the claimed
`products—“a precise definition, such as by structure,
`formula, chemical name, physical properties, or other
`properties, of species falling within the genus sufficient to
`distinguish the genus from other materials,” which may
`be present in “functional” terminology “when the art has
`established a correlation between structure and function.”
`Ariad, 598 F.3d at 1350. But both in this case and in our
`previous cases, it has been, at the least, hotly disputed
`that knowledge of the chemical structure of an antigen
`gives the required kind of structure-identifying infor-
`mation about the corresponding antibodies. See, e.g., J.A.
`1241 (549:5–16) (Appellants’ expert Dr. Eck testifying
`that knowing “that an antibody binds to a particular
`amino acid on PCSK9 . . . does not tell you anything at all
`about the structure of the antibody”); J.A. 1314 (836:9–11)
`(Appellees’ expert Dr. Petsko being informed of Dr. Eck’s
`testimony and responding that “[m]y opinion is that [he’s]
`right”); Centocor, 636 F.3d at 1352 (analogizing the anti-
`body-antigen relationship as searching for a key “on a
`ring with a million keys on it”) (internal citations and
`quotation marks omitted).
`A court may take judicial notice of a fact only when it
`is either “generally known” or “accurately and readily
`[discernible] from sources whose accuracy cannot reason-
`ably be questioned.” Fed. R. Evid. 201(b); see B.V.D.
`Licensing Corp. v. Body Action Design, Inc., 846 F.2d 727,
`728 (Fed. Cir. 1988) (“Courts may take judicial notice of
`facts of universal notoriety, which need not be proved, and
`of whatever is generally known within their jurisdictions.”
`(citing Brown v. Piper, 91 U.S. 37 (1875))). Because the
`scientific premise behind the “newly characterized anti-
`gen” test stated in the instruction in this case was neither
`“generally known” nor “accurately and readily” ascertain-
`able, we cannot take judicial notice of the premise and
`displace the required fact finding with what amounts