# United States **Court of Appeals**  **for the Federal Circuit**

______________________ AMGEN INC., AMGEN MA NUFACTURING LIMITED, AMGEN USA, INC., Plaintiffs

- Appellees

v.

SANOFI, AVENTISUB LL C, 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 No s . 1:14

- cv

- 01317

- SLR, 1:14

- cv

01349 -SL R, 1:14

- cv

- 01393

- SLR, 1:14

- cv

- 01414

- SLR, Judge Sue L. Robinson.

______________________

Decided: October 5 , 2017

______________________

D ARYL J OSEFFER , King & Spalding LLP, Washington, DC, argued for plaintiffs

- appellees. Also represented by C HRISTOPHER R OBERT H EALY , J OSHUA N ATHANIEL M ITCHELL ; M ERRITT E LLEN M C A LISTER , Atlanta, GA; K

ATHERINE N ICOLE C LOUSE , S ARAH C HAPIN C OLUMBIA , McDermott, Will & Emery LLP, Boston, MA; W ILLIAM G. G AEDE , III , Menlo Park, CA; E RIC W. H AGEN , Los Angeles, CA; E MILY C URTIS J OHNSON , E RICA S. O LSON , D ENNIS J.AMGEN INC

. v. SANOFI 2

S MITH , S TEVEN D. T ANG , S TUART L. W ATT , W ENDY A. W HITEFORD , Amgen Inc., Thousand Oaks, CA; C HRISTOPHER M EAD , London & Mead, Washington, DC; M ELANIE K. S HARP , Young, Conaway, Stargatt & Taylor LLP, Wilmington, DE.

P AUL D. C LEMENT , Kirkland & Ellis LLP, Washington, DC, argued for defendants

- appellants. Also represented by G EORGE W. H ICKS , J R ., N ATHAN S. M AMMEN ; S IEW Y EN C HONG , V ISHAL C. G UPTA , J OHN J. M OLENDA , Steptoe & Johnson, LLP, New York, NY; R ICHARD P RASEUTH , Los Angeles, CA; K ILEY A NN W HITE , Washington, DC.

D UANE C HRISTOPHER M ARKS , Eli Lilly and Company, Indianapolis, IN, for amicus curiae Eli Lilly and Comp any. Also represented by G REGORY A LAN C OX , G ILBERT V OY , A LEXANDER W ILSON

.

B ARBARA A NNE J ONES , AAR P Foundation Litigation, Pasadena, CA, for amici curiae AARP and AARP Found ation.

D IMITRIOS T. D RIVAS , White & Case LLP, New York, NY, for amicus curiae Pfizer Inc. Also represented by E RIC M. M AJCHRZAK , A MIT T HAKORE ; J EFFREY N EIL M YERS , Pfizer Inc. , New York, NY.

D AVID A. K ELLY , Hunton & Williams LLP, Atlanta, GA , for amicus curiae Ipsen Pharma S.A.S.

M ELISSA A RBUS S HERRY , Latham & Watkins LLP, Washington, DC, for amicus curiae Abb V ie Inc. Also represented by M ICHAEL A. M ORIN , E MILY K. S AUTER

.

W ILLIAM M ARSILLO , 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., PaulAMGEN INC

. v. SANOFI 3

Thompson, M.D., Rosa DeBernardo, Alina Wilson. Also represented by M ICHAEL J AY , Santa Monica, CA.

______________________
Before P ROST , Chief Judge, T ARANTO and H UGHES , Circuit Judges.

P ROST , Chief Judge

. Appellants Sanofi, Aventisub LLC, Regeneron Pha rmaceuticals Inc., and Sanofi

- Aventis U.S., LLC ( collectiv ely, “ 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 in valid and grant ing a permanent injunction enjoining sales of Appe llants’ Praluent® alirocu mab (“Praluent”). 1 In particular, Appellants arg ue that the district court improperly e xcluded evidence regarding written description and en ablement, improperly instructed the jury on written description, improperly denied Ap pellants’ 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 Appe llants’ ev idence 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 d escription and no enablement. We affirm the district court’s grant of Appellees’ JMOL of non

- obviousness. Finally, w e vacate the district court’s permanent injun ction.

1 Appellants stipulated to infringement of the ’165 and ’741 patents. Appellants’ Br. 11.AMGEN INC

. v. SANOFI 4

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 cardi ovascular disease. Typically, high LDL

- C is treated using small molecules called statins. I n some cases, however, statins have adverse side effects or cannot reduce a p atient’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 rece ptors, 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 RepathaTM which uses the active ingr edient “evolocumab.” Ev olocumab 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 whi ch 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 un dispute d priority date of January 9, 2008. Appellants’ Br. 12. T he relevant claims cover the

2 All references are to the ’165 patent unless othe rwise indicated.AMGEN INC

. v. SANOFI 5

entire genus of antibodies that bind to specific amino acid

res id ue s 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 p atent col. 427 ll. 47

– 53.
The patents disclose the trial

- and

- error process Appe llees 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 bin ding to wild

- type PCSK9 to confirm stab [ility] ,” id. at col. 78 ll. 4

– 6, which were eventually narrowed to “ 85 antibo dies that blocked interaction between the PCSK9

. . . and the LDLR [at] greater than 90 %, ” i d. at col. 8 0 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 f ig. 3E

, f ig. 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 153 rd pos ition of PCSK9’s seq uence.AMGEN INC

. v. SANOFI 6

compete with these antibodies for binding to PCSK9. Id.
at f igs. 2A

– 2D, f igs. 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 a nd 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 obviou sness grounds

. Over the course of litigation, t he district court made several rulings and decisions that are challenged here on appeal . First, the district court excluded all of Appellants’ post -p riority

- date evidence proffered to show that the patents in suit did not provide adequate written descri ption. Second

, the district court instructed the jury, over Appellants’ objection, that written description can be satisfied “by the disclosure of a ne wly

- 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 ant igen was conventional or routine.” J.A. 15 80. Third , the district c ourt denied Appellants’ post

- trial motions see king 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 ofAMGEN INC

. v. SANOFI 7

non

- obviousness. And fifth, the district court issued a permanent injunction removing Appellants’ Praluent from the market.

This c ourt stayed the injunction pending appeal.

II

A

We first review whether the district court impro p erly 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 ther e is sufficient disclo sure 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 e xcluded.”). Because the district court’s decision was based on a misappl ication of the law, we reverse.

Section 112 states that “[t] he specification shall co ntain 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 . . . .” Th is requirement ensure s “that the inve ntor actually invented the invention claimed.” Ariad Pharm., Inc . v. Eli Lilly & Co. , 598 F.3d 1336, 135 1 (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 “requir es a precise definition” of the invention. Id. To provide this “precise definition” for a claim to a genus, a patentee must disclose “a repr e-AMGEN INC

. v. SANOFI 8

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 di scloses “a representative number of species.” Id. Appe llants 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 stat e 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 illumina ting 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 co mmon to the members of the genus so that one of skill in the art can ‘visualize or recognize’ t he members of the
genus .” Id. at 1351

. E vidence showing that a claimed genus does not disclose a representative number of sp ecies may include evidence of species that fall within theAMGEN 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 . I f 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 sho w that the patent purportedly did not disclose a repr esentative number of species. Appellants’ Br. 12

. As a logical matter, such evidence is relevant to the represen tativeness question. Simply, post

- priority

- date evidence of

a particular species can reasonably bear on whether a patent “fails to disclose a representative number of sp ecies 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 recogniz e’ 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 descriptio n. 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 th e unrepresen t ativeness argument, introducing evidence that it s antibody “differ[ed] considerably from the

. . . antibodies described in [the asserted] pa tents ,” id. at 1300. T he 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 unse t-AMGEN INC

. v. SANOFI 10

tled: the PTO, in an interference, had found that Cent ocor’s antibody postdate d AbbVie’s invention, as AbbVie argued, and the subsequent litigation of the question under 35 U.S.C. § 146 was unresolved. S ee Abbott , 870 F. Supp. 2d at 246

. The Centocor antibody, in short, was a basis for the unrepr esentativeness 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 pate nt 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 gi ving 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 t he district court and Appellees misread In re Hogan by conflat ing 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 t he 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 applicat ion 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 se cond, “a morphous 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 appl icant 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 stim ulate invention, and particularly to encourage its early disclosure. ” Id.
Here, unlike in In re Hogan , Appellants were not o ffering 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 disc lose a representative number of species. As explained above, the use of post

- priority

- date evidence to show that a patent does not disclose a repr esentative number of species of a claimed genus is proper

. It was thus legal error for the district court to categorica lly preclude all of Appellants’ post

- priority

- date evidence o f 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 i mproper 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 in vention without undue experimentation.” Genentech, Inc. v. Novo Nordisk A/S , 108 F.3d 1361, 1365 (Fed. Cir. 1997). Appellants purportedly sought to intr oduce post

- priority

- date evidence showing that Appellees engaged in lengthy and potentially undue expe riment ation to enable the full scope of the claims. Such evidenceAMGEN INC

. v. SANOFI 12

c ould 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 “11⁄2 to 2 man years of effort” would be n eeded to practice an invention, that patent claims were not en abled)

. 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 im properly 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 fe atures 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 :
I n the case of a claim to antibodies, the correlation between structure and function may also be sati sfied by the disclosure of a newly characterized a ntigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowled ge in the art of antibodies at the time of filing was such that production of antibo dies 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 inAMGEN 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 i s not legally sound and is not based on any binding precedent. Accordingly, we co nclude th at 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 sele ctively hybridizing to the genetic material of certain bact eria

. Enzo Biochem , 323 F.3d at 960. W e noted in that

case that not “all functional descriptions of genetic mat erial fail to meet the written description requir e ment.” Id. at 964. Instead, we c ited the PTO’s Guidelines on written description for the proposition that “functional characteristics when coupled with a known or disclosed correlation between function and structure ” may satisfy the written description requirement. Id. (citing Guid e line s for Exa mination of Patent Applications Under the 35 U.S.C. 112, ¶ 1, “Written Description” Requirement 66 F ed. Reg. 1099

– 01, 1106 (“Guidelines”) ). 4 We further noted , in dicta, that

4 The Guidelines were f irst published on Feb. 28, 2000 as the Revised Interim Written Description Guid elines Training Material s. I n March 2008, the training materials were revised and republished as Written D escription Training Materials, Revision 1, available at https://www.uspto.gov/sites/default/files/web/menu/ written.pdf. The PTO now notes that the Training Mat erials 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 Gui dance and Training Materials, United States Patent andAMGEN INC

. v. SANOFI 14

“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 ant ibody, in light of the well

- defined structural characteristics for the five classes of antibody, the functional characteri stics 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
, available at https://web.archive.org/ web/20041101121800/ http: / /www

. uspto.gov/web/menu/wri tten.pdf ).

I n Noelle

, the patent owner claimed an antibody and sought to claim priority to an earlier filed patent. 355 F.3d at 1349. Noelle argued th at “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 di sclose the structural elements of [the] antibody or antigen in his earlier . . . application.” Id. In reaching this co nclusion, we acknowledged that according to Enzo

, “a s long as an applicant has disclosed a ‘ fully characterized ant igen,’ either by its structure, formula, chemical n ame, or physical properties, or by depositing the protein in a public depository, the applicant can then claim an ant ibody by its binding affinity to that described antigen.” Id

. But because Noelle did not disclose structure for the antibody or the antig en, 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/examinationpolicy/examinati on- guidance

- and

- training

- materials

.AMGEN INC

. v. SANOFI 15

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 descri ption. 636 F.3d at 135 1– 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 cla imed 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 vari able region that have particularly desirable therapeu tic 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

p atentee 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 claim s were still invalid. Id. at 1352

– 53. We

ques tioned 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 135 2.

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 , w e 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 e xtremely 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 toAMGEN INC

. v. SANOFI 16

dispense with the required finding of a “written descri ption of the invention.” 35 U.S.C. § 112. Our en banc decision in Ariad , reflecting ear lier 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 unde rstand the instruction to permit it to deem any antibod y within the claim adequately described merely because the antibody could easily be “produc[e d]” ( and , implicitly, used a s an antibody). J.A. 1580 (requirement “may

. . . be satisfied” if antigen is newly characterized and “produ ction of antibodies against such an antigen was conve ntional or routine”). Indeed, the instruction does not even requi re any particular antibody to be easily made; all it requires is that “production of antibodies ”— some, not all —“ against [a newly characterized] antigen ” be conve ntional or routine. By permitting a finding of adequate written description merely from a find ing of ability to make and use, the challenged sentence of the jury instruction 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. Fo r 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.AMGEN INC

. v. SANOFI 17

An adequate written desc ription 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 disting uish 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 b oth 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 info rmation 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 a ll about the structure of the an tibody” ); J.A. 1314 (836:9

– 11) (Appellees’ expert Dr. Petsko being informe d of Dr. Eck’s testimony and responding that “[m]y opinion is that [he’s] right”); Centocor , 636 F.3d at 1352 ( analogizing the ant ibody

- antigen re lationship as searching for a key “ on a ring with a million keys on it ” ) (internal citations and quotation mar ks 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 reaso nably 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 (18 75) )) . Because the scien tific premise behind the “newly characterized ant igen” test stated in the instruction in this case was neither “generally known” nor “accurately and readily” ascertai nable, we cannot take judicial notice of the premise and displace the required fact finding with what amounts to aAMGEN INC

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rule of law. We are not required to conclude otherwise

, and depart from the plain restriction on judicial notice, by the statement in Enzo , which was unnecessary to its holding, about what PTO Guidelines i ndicated the PTO would find.
Further, the “newly characterized antigen” test flouts basic legal principles of the written description requir ement

. Section 112 requires a “written description of the invention

. ” But this test allows patentees to claim ant ibodies by describing something that is not the invention, i.e., the antigen . The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law’s other requirements are met, one obtains a patent. ” Ariad , 598 F.3d at 1345. Indeed , w e have generally eschewed judicial exceptions to the written description requirement based on the subject matter of the claims. See Univ. of Rochester v. G.D. Searle & Co. , 358 F.3d 916, 925 (Fed. Cir. 2004) (noting t hat “the
statute applies to all types of inventions”). And Congress has not created a special written description requirement for antibodies as it has, for example, for plant patents. See

, e.g. , 35 U.S.C. § 162 (exempting plant patents from § 112 “if the description is as complete as is reasonably possible”).
For those reasons, i t was improper for the district court to instruct the jury as it did in the sentence at issue here. On remand, the district court should amend its jury instructions accordingly

. C
Next, we consider whether the district court impro perly denied Appellants’ post

- trial motion seeking JMOL o f

no written description and no enablement. Appellants argue that the asserted patents fail to provide written description support because they merely teach “where an antibody binds to an antigen” which “tells one nothing about the structure of any other antibody.” Appellants’AMGEN INC

. v. SANOFI 19

Br. 53. Appellants also argue that the patents are not enabling because one must engage in several steps inclu ding a trial

- and

- error process of generating and screening antibodies, performing x

- ray crystallography, and still potentially failing to “get a sufficient number of antibo dies that enable the full scope of the claims.” Id

. JMOL is proper when “a reasonable jury would not have a legally sufficient evidentiary basis to find for the party.” Fed. R. Civ. P. 50(a)(1). “A determination that a patent is invalid for failure to meet the written descri ption requirement of 35 U.S.C. § 112, ¶ 1 is a question of fact, an d we review a jury’ s determinations of facts rela ting to compliance with the written description requir ement for substantial evidence.” Ariad , 598 F.3d at 1355 (citing PIN/NIP, Inc. v. Platte Chem. Co., 304 F.3d, 1235, 1243 (Fed. Cir. 2002) ). And “ [t] o b e enabling, 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 experimen tation.” Genentech

, 108 F.3d at 1365 (internal quotation marks omitted). But “[e] nablement is not precluded by the necessit y for some experimentation such as routine screening” of antibodies. In re Wands , 858 F.2d 731, 736

– 37 (Fed. Cir. 1988)

. Here, the jury did not hear relevant post

- priority

- date evidence regarding written description and enablement. This evidence may show, for example, that practicing the invention did not require undue experimentation or that the disclosed species are representative of the claimed genus. Because we are pre sented with an incomplete record on these issues, the court is unable to determine whether the jury would have a “ legally sufficient evide ntiary basis ” to determine if the patents provide sufficient written description or if the claims are enabled. Fed. R

. Civ. P. 50(a)(1). We therefore reject Appellants ’ arg ument s and conclude that Appellants are not entitled to J MOL of no written description and no enablement.AMGEN INC

. v. SANOFI 20

D
We next address whether the district court improperly granted Appellees’ JMOL of non -obvious ness. Because the district court correctly excluded Appellants’ proffered references as improper prior art , we conclude that the district court’s grant of Appellees’ motion seeking JMOL of non

- obviousness was proper.
During litigation, Appellants sought to invalidate the asserted patents by proffering two published PCT applic ations: Novartis (WO 2008/12563) and Schering (WO 2009/055783) . Neither refer ence pre dates the January 9, 2008 priority date of the asserted patents. But both appl ications claim priority to provisional applications that do predate the asserted patents ’ priority date

. 5 In the district court, Appellant s attempted to rely on the se PCT applications as pre

- AIA § 102(e)(1) art. 35 U.S.C. § 102(e)(1) ( providing “a n application for patent, pu blished un der section 122(b), by another filed in the United States before the invention by the applicant for patent”). Appellees argued, however, that the references were not proper prior art because Appellants had not shown that the provisional application s provided written description support for the claims of the PCT applications . The district court agreed, excluded the two references, and granted JMOL of non

- obviousness. Appellants argue that the district court erred by mi sapplying our decision in Dynamic Drinkware, LLC v. National Graphics, Inc.

, 800 F.3d 1375 (Fed. Cir. 2015)

. According to Appellants, that case only related to whether “a patent asserted as prior art und er § 102(e)(2) was prior art as of the filing date of a parent application” but does

5 It is undisputed that the provisional applications are not themselves prior art under § 102(e)(1) because they are not ap plications published under § 122(b).AMGEN INC

. v. SANOFI 21

not relate to whether “published patent applications asserted as prior art under § 102(e)(1)” were prior art as of the filing date of their provisional application s . Appe llants’ Br. 46. Appellants are incorrect.

In Dynamic Drinkware , we clearly explained that for

a non

- provisional application to claim priority to a prov isional application for prior art purposes, “the specification of the provisional [application] must c ontain a written description of the inven tion . . . in such full, clear, concise, and exact terms, to enable an ordinarily skilled artisan to practice the invention claimed in the non

- provisional application .” 800 F.3d at 1378 . Further, we have prev iously stated that “f or the non

- provisional utility applic ation to be afforded the priority date of the provi sional application,

. . . the written description of the provisional must adequately support the claims of the non

- provisional application .” New Railhead Mfg., L.L.C. v. Vermeer Mfg. Co.

, 298 F.3d 1290, 1294 (Fed. Cir. 2002)

. Here, Appellants challenge d the district court’s appl ication of Dynamic Drinkware , but did not proffer any evidence showing that the provisional applications co ntained representative species or common structural elements sufficient to satisfy the written description requirement for the monoclonal antibodies claimed in the PCT applications. Similarly, Appellants provided no evidence that the claims of the PCT appl ications were enabled by the provisional application. Because the district court properly excluded Novartis and Schering under Dynamic Drinkware , the court’s grant of JMOL of

non

- obviousness was proper.

E

F inally , we address the district court’s permane nt i njunction removing Appellants’ Praluent from the ma r ket. As noted earlier, we stayed this injunction pending res olution of this appeal. B ecause we vacate the district court’s judgment as to written description and enabl e-AMGEN INC

. v. SANOFI 22

ment and remand for a new tria l, we also vacate the

perman ent injunction.

We write to note , however, that the district court’s permanent injunction analysis in this case was improper for two distinct reasons

. First, the district court misa pplied eBay, Inc. v. MercExchange, L.L.C.

, 54 7 U.S. 388 (2006) . In that case, the Supreme Court explained that : [A ] plaintiff seeking a permanent injunction must satisfy a four

- factor test before a court may grant such relief. A plaintiff must demonstrate : (1) that it has suffered an irreparable injury; (2) that re medies available at law, such as monetary damages, are inadequate to compensate for that injury; (3) that, considering the balance of hardships b etween the plaintiff and defendant, a remedy in equity is warranted; and (4) that the public inte rest would not be disserved by a permanent injun ction.

Id. at 391 (emphases added). Here, the district court concluded that issuing a permanent injunction would disserve the public interest. Despite that finding, the court issued a permanent injunct ion. J.A. 33

– 34. That was in clear violation of eBay . If a plaintiff fails to show “that the public interest would not be disserved by a permanent injunction,” then the district court may not issue an injunction. eBay , 547 U.S. at 391.
Second, the dis trict court also erred in its analysis of the “public interest” factor. In reaching its conclusion that the injunction would disserve the public , t he district court weighed “being a patent holder and a verdict wi nner” on the one hand and “taking an independently deve loped, helpful drug off the market” on the other. J.A. 33. It then “conclude[d] that the public interest of having a choice of drugs should prevail.” J.A. 33

– 34.AMGEN INC

. v. SANOFI 23

But eliminating a choice of drugs is not, by itself, su fficient to dis serve the public interest. Under s uch an

ap proach, courts could never enjoin a drug because doing

so would always reduce a choice of drugs. That, of course, is not the law. See 35 U.S.C. § 271(e)(4)(B) (“[I]njunctive relief may be granted against an inf ringer to prevent the commercial manufacture, use, offer to sell, or sale within the United States or importation into the United States of an approved drug, veterinary biological product, or biolo gical product.”) . We previously rejected such reasoning in WBIP, LLC v. Kohler Co. and explained that :
T he district court’ s decision is based on its reaso ning that having more manufacturers of a lifesa ving good in the market is better for the public interest. But this reasoning is true in nearly ev ery situation involving such goods, such that, if it alone is sufficient, it would create a categorical rule denying permanent injunctions for life

- saving goods, such as many patented pharmaceutical products. As the Supreme Court has warned, ca tegorical ru les regarding permanent injunctions are disfavored.
829 F.3d 1317, 1343 (Fed. Cir. 2016)

. Just as a patent

owner does not automatically receive an injunction merely by proving infringement, see eBay

, 547 U.S. at 394, an accused infringer cannot escape an injunction merely by producing infringing drugs. Accordingly, a reduction in choice of drugs cannot be the sole reason for a district court to deny an injunction

. III

For the for e going reasons, we conclude that the di strict court erred by (i) categorically excluding Appe l lants’ evidence of written description and enablement, and (ii) improperly instructing the jury on written d e scription. For these reasons we reverse the district court’s decision to exclude Appellants’ evidence of written d e scription andAMGEN INC

. v. SANOFI 2 4

enablement and remand for a new trial consistent with this opinion. We conclude that Appellants are not ent itled to JMOL of no written description and no enabl ement

. We also conclude that the district court properly granted Appell ee s’ JMOL of no n- obviousness. Finally, we vacate the permanent injunction and remand for further proceed ings consistent with this opinion.
REVERSED IN PART, AFFIRMED IN PART, VACATED IN PART, AND REMANDED