United States Court of Appeals 

for the Federal Circuit ______________________

BIOGEN MA INC.,

Plaintiff -Appellee

v.

EMD SERONO, INC., PFIZER INC.,

Defendants-Appellants

BAYER HEALTHCARE PHARMACEUTICALS INC., 

NOVARTIS PHARMACEUTICALS CORPORATION,

Defendants

______________________

2019-1133

______________________

Appeal from the United States District Court for the 

District of New Jersey in No. 2:10-cv-02734-CCC-MF, 

United States District Judge Claire C. Cecchi.

______________________

Decided: September 28, 2020

______________________

NICHOLAS P. GROOMBRIDGE, Paul, Weiss, Rifkind, 

Wharton & Garrison LLP, New York, NY, argued for plaintiff-appellee. Also represented by PETER SANDEL, ERIC 

ALAN STONE, JENNY CHIA CHENG WU, JOSEPHINE YOUNG; 

DAVID J. BALL, JR., Washington, DC; JOHN D. TORTORELLA, 

KEVIN H. MARINO, Marino Tortorella & Boyle, PC, Chatham, NJ.

Case: 19-1133 Document: 90 Page: 1 Filed: 09/28/2020
2 BIOGEN MA INC. v. EMD SERONO, INC.

 MARK ANDREW PERRY, Gibson, Dunn & Crutcher LLP, 

Washington, DC, argued for defendants-appellants. Also 

represented by CHRISTINE RANNEY, Denver, CO; WAYNE M.

BARSKY, TIMOTHY P. BEST, Los Angeles, CA; JAYSEN 

CHUNG, San Francisco, CA. 

 BRUCE GENDERSON, Williams & Connolly LLP, Washington, DC, for amicus curiae Bayer Healthcare Pharmaceuticals Inc. Also represented by DAVID I. BERL, SETH 

BOWERS, DAVID M. KRINSKY. 

 ______________________

Before NEWMAN, LINN, and HUGHES, Circuit Judges.

LINN, Circuit Judge.

This appeal arises from a suit filed by Biogen MA, Inc. 

(“Biogen”) against EMD Serono, Inc. and Pfizer, Inc. (collectively “Serono”) in the District of New Jersey.1 The suit 

alleged contributory and induced infringement of Biogen’s 

U.S. Patent Number 7,588,755 (“’755 patent”) by the sale 

and marketing in the United States of Rebif, a recombinant 

interferon-β (“IFN-β”) product used for the treatment of 

Multiple Sclerosis (“MS”). After a five-week trial, a jury 

found that the ’755 patent claims were anticipated by two 

references teaching the use of native IFN-β to treat viral 

diseases: Kingham et al., Treatment of HBsAg-positive 

Chronic Active Hepatitis with Human Fibroblast Interferon, 19(2) Gut 91 (1978) (“Kingham”) and Sundmacher et 

1 Biogen also asserted infringement claims against 

Bayer Healthcare Pharmaceuticals Inc. (“Bayer”) and Novartis Pharmaceuticals Corp. (“Novartis”). The actions 

against Bayer and Novartis were severed from those giving 

rise to this appeal. Order Granting Bayer’s Motion to 

Sever, Oct. 27, 2017, ECF No. 743. Bayer filed an amicus 

brief here.

Case: 19-1133 Document: 90 Page: 2 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 3

al., Human Leukocyte and Fibroblast Interferon in a Combination Therapy of Dendritic Keratitis, 208(4) Albrecht 

von Graefes Archiv für Klinische & Experimentelle Opthalmologie 229 (1978) (“Sundmacher”). The jury also held the 

asserted claims not invalid for lack of enablement or written description, or for obviousness. Finally, the jury held 

that patients and prescribers directly infringed the asserted claims and that Serono contributorily infringed the 

claims but did not induce infringement thereof.

On cross-motions, the district court granted judgment 

as a matter of law (“JMOL”) of no anticipation in favor of 

Biogen and conditionally granted a new trial on anticipation. In re Biogen ’755 Patent Litig., 335 F. Supp. 3d 688 

(D.N.J. 2018) (“Biogen I”). The district court also ruled in 

favor of Biogen: sustaining the jury’s verdict of no invalidity based on written description or enablement; overturning the verdict of no induced infringement; sustaining the 

verdict of contributory infringement; and holding that the

’755 patent claims were not patent ineligible. Id. Serono

appeals the district court’s JMOL rulings on anticipation, 

written description, enablement, contributory infringement, induced infringement and patent eligibility. We 

have jurisdiction under 28 U.S.C. § 1295(a).

Because a reasonable jury could find the claims of the 

’755 patent anticipated on the record presented in this 

case, we reverse the district court’s JMOL of no anticipation and its conditional grant of new trial on that ground. 

We remand with instructions to reinstate the jury verdict 

of anticipation. We need not and do not address the other 

grounds asserted on appeal.

I

The ’755 patent is directed to a method of treating a 

viral condition, a viral disease, cancers or tumors, by administration of a pharmaceutically effective amount of a 

recombinant polypeptide related to human interferon-β 

(“IFN-β”). The human immune system naturally produces 

Case: 19-1133 Document: 90 Page: 3 Filed: 09/28/2020
4 BIOGEN MA INC. v. EMD SERONO, INC.

IFN-β in small amounts, and it is undisputed that IFN-β 

harvested from human cells (“native IFN-β”) was used in 

the prior art to treat viral conditions. See ’755 patent, col. 

2, l. 53–col. 4, l. 22.

Representative claim 1 of the ’755 patent reads:

1. A method for immunomodulation or treating a 

viral condition[ ], a viral disease, cancers or tumors comprising the step of administering to a 

patient in need of such treatment a therapeutically effective amount of a composition comprising:

a recombinant polypeptide produced by a 

non-human host transformed by a recombinant DNA molecule comprising a DNA sequence selected from the group consisting 

of:

(a) DNA sequences which are capable of hybridizing to any of the DNA 

inserts of G-pBR322(Pst)/HFIF1, 

G-pBR322(Pst)/HFIF3 (DSM 

1791), G-pBR322(Pst)/HFIF6 

(DSM 1792), and GpBR322(Pst)/HFIF7 (DSM 1793) 

under hybridizing conditions of 

0.75 M NaCl at 68° C. and washing 

conditions of 0.3 M NaCl at 68° C., 

and which code for a polypeptide 

displaying antiviral activity, and

(b) DNA sequences which are degenerate as a result of the genetic 

code to the DNA sequences defined 

in (a);

said DNA sequence being operatively 

linked to an expression control sequence in 

the recombinant DNA molecule.

Case: 19-1133 Document: 90 Page: 4 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 5

’755 patent, col. 49, l. 59–col. 50, l. 12. Dependent claim 2 

replaces the “capable of hybridizing” limitation with a selection from two particular DNA sequences, one of which is 

the DNA sequence of human interferon-beta. Id. at col. 50, 

ll. 13–52. Claims 1 and 2 thus define the claimed polypeptide by reference to the DNA sequence inserted into the 

host during the recombinant manufacture of the polypeptide. Claim 3, dependent from claim 1, limits the polypeptide to a particular linear polypeptide sequence. Because 

the claimed IFN-β DNA and polypeptide sequences are derived from human IFN-β, it is indisputable that native human IFN-β is capable of hybridizing with the DNA 

sequences in claim 1, is produced by one of the DNA sequences laid out in claim 2, and comprises the amino acid 

sequence set out in claim 3. See J.A. 47784 (Fiers Aff. to 

the Canadian Patent Office, indicating that the recombinant IFN-β was derived from human IFN-β cDNA); 

J.A. 77897 (Dr. Green Test., testifying that the sequences

claimed in claim 1 are “DNA that will hybridize to one of 

the four human beta interferon clones”); J.A. 77904 (Dr. 

Green Test., testifying that accused-product Rebif is capable of hybridizing to one or more of the DNA inserts because the DNA sequence it used is identical to the 

published sequence of human IFN-β). For purposes of this 

opinion, we refer to “recombinant IFN-β” as shorthand for 

the recombinant protein that meets these claim limitations. 

During Markman, the district court held that claim 1 

covers a “one-step method of ‘administering’ to a patient in 

need the specified recombinant HuIFN-β.” Markman 

Opinion at 17, Mar. 28, 2016, ECF No. 403. The district 

court considered the claimed “produced” and “transformed” 

steps “merely descriptive of the recombinant polypeptide to 

be administered,” i.e. merely source limitations. Id. at 15. 

The district court also held that it was “unclear that [the] 

method of treatment claim can be treated as a product-byprocess claim,” and that it was “aware of no binding 

Case: 19-1133 Document: 90 Page: 5 Filed: 09/28/2020
6 BIOGEN MA INC. v. EMD SERONO, INC.

precedent requiring method of treatment claims to be 

treated as product-by-process claims in the claim construction context.” Id. at 14. The district court did not construe 

“polypeptide,” “therapeutically effective amount,” or “antiviral activity,” and neither party asked the court to consider whether the claims covered the linear sequence of 

amino acids or the three-dimensional structure of the protein.

Biogen, Serono, and Bayer all moved for summary 

judgment. Before Bayer was severed, Bayer argued that it 

was entitled to summary judgment of anticipation because 

the claimed recombinant IFN-β and the prior art native 

IFN-β shared the same linear amino acid sequence. The 

district court denied Bayer’s motion, holding, inter alia, 

that the claims require the polypeptide to have “antiviral 

activity” and be administered in a “therapeutically effective amount.” Summary Judgment Opinion at 28, Jan. 9, 

2018, ECF No. 892. The district court concluded that those 

requirements necessitate that the polypeptide “be folded 

into its appropriate three-dimensional structure,” and that 

Bayer was therefore not entitled to summary judgment of 

anticipation by merely showing that the amino acid sequence of recombinant IFN-β and the amino acid sequence 

of native IFN-β were identical. Id.

After a five-week trial, Biogen and Serono both moved 

for JMOL under Federal Rule of Civil Procedure 50(a). The 

district court deferred ruling until the jury verdict. Among 

other issues, the court submitted anticipation, obviousness, enablement, written description, and contributory 

and induced infringement to the jury. In its charge on anticipation, the district court told the jury that “[t]he term 

‘polypeptide’ means ‘a linear array of amino acids connected one to the other by peptide bonds between the αamino and carboxy groups of adjacent amino acids,’” and 

that the jury “must accept my definition of these words in 

the claims as correct.” Final Jury Instructions at 17, Feb. 

21, 2018, ECF No. 968. Biogen did not object to these 

Case: 19-1133 Document: 90 Page: 6 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 7

instructions and did not request any instruction defining 

the polypeptide in terms of its three-dimensional structure 

or requiring identity of the three-dimensional structures of 

native IFN-β and recombinant IFN-β proteins to establish 

anticipation.

The jury held, inter alia, that all claims in the ’755 patent were invalid as anticipated by native IFN-β; not invalid for obviousness, lack of enablement or lack of written 

description; and that Serono was liable for contributory infringement but not induced infringement. Jury Verdict 

Form at 1–6, Feb. 23, 2018, ECF No. 977.

Both parties renewed their JMOL motions. As relevant here, the district court granted Biogen’s motion of no 

anticipation as a matter of law. Biogen I, 335 F. Supp. 3d 

at 713. In a comprehensive opinion, the district court held 

that no reasonable jury could find anticipation under Serono’s reading of the claims. First, applying a structural 

reading of the recombinant limitations, the district court 

held that Serono had not identified any prior art that disclosed “treatment with a ‘therapeutically effective amount’ 

of a composition comprising a ‘recombinant’ interferon-β 

polypeptide produced in a ‘non-human host’ that had been 

‘transformed by a recombinant DNA molecule.’” Id. at 704. 

[JA21]. The district court reasoned that because treatment in the prior art entailed administration of native 

IFN-β, which was undisputedly not recombinantly produced, no reasonable jury could find anticipation. Id. at 

705. The district court cited but did not distinguish Amgen 

Inc. v. Hoffman-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 

2009), which analyzed anticipation of a claimed recombinant erythropoietin (“EPO”) by prior art urinary (i.e. natural) EPO. Biogen I, 335 F. Supp. 3d at 1367. The district 

court declined to apply a product-by-process analysis to a 

product-by-process limitation contained within a method of 

treatment claim, concluding that no precedent required 

such an analysis and that the policy informing product-byprocess claims—to enable an inventor to claim an 

Case: 19-1133 Document: 90 Page: 7 Filed: 09/28/2020
8 BIOGEN MA INC. v. EMD SERONO, INC.

otherwise difficult-to-define product—was inapplicable to 

the instant method of treatment claims. Id. at 712–13.

In the alternative, the district court held that no reasonable jury could have found anticipation even applying a 

product-by-process analysis. Id. at 705–11. The district 

court explained that because the claims required administration of a “therapeutically effective amount” of a recombinant polypeptide that “displays antiviral activity,” the 

product resulting from the claimed recombinant process is 

defined by the folded three-dimensional structure of the 

protein. Id. at 705 (discussing Summary Judgment Opinion at 28, Jan. 9, 2018, ECF No. 892). The district court 

held that the jury lacked substantial evidence that the native IFN-β protein as disclosed in Kingham and 

Sundmacher was structurally or functionally identical to 

the claimed three-dimensional recombinant IFN-β protein. 

Id.

With respect to structural identity, the district court 

emphasized that whereas the attached carbohydrate 

groups in native IFN-β protein were glycosolated, the attached carbohydrate groups in recombinant IFN-β were not

glycosolated, and that this change affected the three-dimensional structure of the protein. Id. The district court—

relying on expert testimony by Serono’s expert, Dr. Lodish, 

and statements found in a post-priority date reference created by InterPharm Laboratories Ltd. entitled “Comparative Biochemical Analysis of Native Human Fibroblast 

lnterferon and Recombinant Beta Interferon Expressed by 

Chinese Hamster Ovary Cells” (“InterPharm”)—concluded 

that native and recombinant IFN-β were not identical but 

merely very similar. Id. at 706–07. The district court 

opined that the structural differences alone preclude anticipation. Id. at 710–11 (relying primarily on this court’s decision in Amgen, 580 F.3d at 1367–69, in which we affirmed 

a holding of no anticipation based on structural differences). Finally, the district court discounted the conclusion 

in the InterPharm study that recombinant IFN-β and 

Case: 19-1133 Document: 90 Page: 8 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 9

native IFN-β were identical. It held that there was no substantial evidence that the generic “native IFN-β” analyzed 

in the InterPharm study and found to be identical to recombinant IFN-β was the same native IFN-β taught in the 

prior art. Id. at 708.

As for functional identity, the district court held that 

the relative ease of manufacture of recombinant IFN-β in 

large quantities functionally distinguished it from native 

IFN-β. Id. at 709–10.

For these reasons, the district court granted JMOL of 

no anticipation. Id. at 713. The district court also conditionally granted Biogen’s motion for a new trial on anticipation “[f]or the same reasons the Court grants Biogen’s 

JMOL motion.” Id. The district court added that the trial 

was complex and was “noticeably focused on issues other 

than anticipation,” such that that the jury verdict deserved 

close scrutiny. Id.

Serono appeals. We have jurisdiction under 28 U.S.C. 

§ 1295.

II

We review the grant of JMOL and the grant of new trial 

under the law of the regional circuit. Uniloc USA, Inc. v. 

Microsoft Corp., 632 F.3d 1292, 1301, 1309 (Fed. Cir. 2011).

The Third Circuit reviews the grant of JMOL for a fact 

question de novo, affirming “only if, viewing the evidence 

in the light most favorable to the nonmovant and giving it 

the advantage of every fair and reasonable inference, there 

is insufficient evidence from which a jury reasonably could 

find liability.” Lightning Lube, Inc. v. Witco Corp., 4 F.3d 

1153, 1166–67 (3d Cir. 1993); Garzier ex rel. White v. City 

of Phila., 328 F.3d 120, 123 (3d Cir. 2003) (“A district court 

should grant such a motion only if, viewing all the evidence 

in favor of the nonmoving party, no reasonable jury could 

find liability on a particular point.”). The Third Circuit reviews the conditional grant of a new trial against the 

Case: 19-1133 Document: 90 Page: 9 Filed: 09/28/2020
10 BIOGEN MA INC. v. EMD SERONO, INC.

weight of the evidence for an abuse of discretion, “unless 

the court’s denial is based on the application of a legal precept, in which case the standard of review is plenary.” 

Lightning Lube, 4 F.3d at 1167.

III

A claim is anticipated only if “each and every [limitation] is found within a single prior art reference.” Summit 

6, LLC v. Samsung Elecs. Co., 802 F.3d 1283, 1294 (Fed. 

Cir. 2015). Anticipation is a factual question and thus 

within the ordinary provenance of the jury. Lighting Ballast Control LLC v. Phillips Elecs. N. Am. Corp., 790 F.3d 

1329, 1340 (Fed. Cir. 2015).

In evaluating the evidentiary record presented to the 

jury on the question of anticipation, the district court: 

(1) declined to apply a product-by-process analysis to the 

claimed recombinant IFN-β source limitation; and (2) in its 

alternative ground analysis, required identity of three-dimensional structures not specifically recited in the claims 

rather than the claimed and lexicographically defined “polypeptide.” Both of these determinations led to an erroneous conclusion on anticipation.

A. The Recombinant Source of the Polypeptide

The district court, focusing on the process of making 

recombinant IFN-β, concluded that it need not analyze 

whether native IFN-β and recombinantly produced IFN-β 

were identical because neither Kingham nor Sundmacher 

prior art reference taught a method of treatment using recombinant IFN-β. Biogen I, 335 F. Supp. 3d at 704. It categorized the “produced” and “transformed” limitations as 

meaningful “source limitations.” Id. at 711–12. The district court was convinced that because the recombinant 

source limitations here overcame the shortcoming of the 

prior art—namely, the unavailability of native IFN-β in 

sufficient quantity to facilitate practical treatment—the 

recombinant nature of the claimed IFN-β “lies at the heart 

Case: 19-1133 Document: 90 Page: 10 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 11

of the benefit of this invention” [and] should be given “force 

and effect in the anticipation analysis.’” Id. (quoting Biogen’s statements at JMOL hearing, Trial Tr. 6/6/18 at 12:7–

10). The district court reasoned that no binding precedent 

required it to apply a product-by-process analysis to a limitation contained in a method of treatment claim, and held 

that the rationale underlying the use of product-by-process 

claims—to allow claiming of an otherwise difficult-to-define invention, see SmithKline, 439 F.3d at 1315—did not 

apply to the claims here because the “product” itself was 

sufficiently described. Biogen I, 335 F. Supp. 3d. at 713. 

The district court thus concluded there could be no anticipation, regardless of whether Serono had shown the identity of native IFN-β and recombinant INF-β.

Serono contends that Biogen has waived any argument 

that the recombinant source of the IFN-β can alone confer 

novelty because Biogen’s pre-verdict JMOL motion only argued that native IFN-β and recombinant IFN-β were not 

identical. We find no waiver. The source limitation was 

one of the bases for Biogen’s argument of non-identity and 

was considered by the district court at Summary Judgment 

and in its opinion on JMOL.

On the merits, Serono asserts that a source limitation 

alone cannot confer novelty unless the product itself is 

novel. Serono argues that the district court erred by holding that the lack of a recombinantly produced IFN-β product in the prior art compelled a finding of no anticipation. 

Biogen argues that the source of the IFN-β matters is an 

independent limitation.

We agree with Serono. The district court’s refusal to 

consider the identity of recombinant and native IFN-β runs 

afoul of the longstanding rule that “an old product is not 

patentable even if it is made by a new process.” Amgen,

580 F.3d at 1366. See also Gen. Elec. Co. v. Wabash Appliance Corp., 304 U.S. 364, 373 (1938) (“[A] patentee who 

does not distinguish his product from what is old except by 

Case: 19-1133 Document: 90 Page: 11 Filed: 09/28/2020
12 BIOGEN MA INC. v. EMD SERONO, INC.

reference, express or constructive, to the process by which 

he produced it, cannot secure a monopoly on the product by 

whatever means produced.”); Cochrane v. Badische Anilin 

& Soda Fabrik, 111 U.S. 293, 311 (1884) (“While a new process for producing [an old product] was patentable, the 

product itself could not be patented, even though it was a 

product made artificially for the first time.”); SmithKline

Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1317 (Fed. 

Cir. 2006) (“It has long been established that one cannot 

avoid anticipation by an earlier product disclosure by 

claiming the same product . . . as produced by a particular 

process.”).

In Amgen, we explained that a claim to a recombinant 

EPO composition must be analyzed for novelty by comparing the recombinant EPO to the prior art urinary EPO. We 

further explained that simply because prior art urinary 

EPO was not made recombinantly was not enough to avoid 

anticipation as a matter of law.2 580 F.3d at 1370 (“To 

prove invalidity, Roche had to show that recombinant EPO 

was the same as urinary EPO, even though urinary EPO 

was not made recombinantly.”) (emphasis added). The key 

2 The key claim in Amgen read: “A pharmaceutical 

composition comprising a therapeutically effective amount 

of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant or carrier, wherein said erythropoietin is purified from mammalian cells grown in culture.” 

580 F.3d at 1364. An additional independent claim in a 

related patent read: “A non-naturally occurring glycoprotein product of the expression in a mammalian host cell of 

an exogenous DNA sequence comprising a DNA sequence 

encoding human erythropoietin said product possessing 

the in vivo biological property of causing bone marrow cells 

to increase production of reticulocytes and red blood cells.” 

Id. In relevant part, we applied the same analysis to both 

claims.

Case: 19-1133 Document: 90 Page: 12 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 13

question was “whether the production of EPO by recombinant technology resulted in a new product,” id. at 1367, or, 

“[i]n other words, does the source limitation ‘purified from 

mammalian cells grown in culture’ distinguish recombinant EPO from [prior art] urinary EPO?” Id.

The nature of the origin or source of the composition 

recited in the claims at issue in this case is, in all relevant 

respects, identical to that considered in Amgen. As in 

Amgen, the recombinant origin of the recited composition 

cannot alone confer novelty on that composition if the product itself is identical to the prior art non-recombinant product. The requirements that the claimed polypeptide is 

“recombinant” and “produced by a non-human host transformed by a recombinant DNA molecule” (in the case of 

Claim 1 of the ’755 patent) describe the process by which 

the product, i.e. the “polypeptide,” is formed. These are not 

additional structural limitations. See Purdue Pharma L.P. 

v. Epic Pharma, LLC, 811 F.3d 1345, 1353 (Fed. Cir. 2016) 

(holding that because a source limitation of a composition 

“has no effect on its structure . . . [that] limitation . . . cannot be a structural limitation”). The key question for anticipation here, as in Amgen, is thus whether the 

recombinant product is identical to the prior art product—

not whether the prior art product was made recombinantly.

Biogen argues that Amgen is limited to composition 

claims and is not applicable to the method of treatment 

claims at issue here. To support this proposition, Biogen 

relies on general statements in product-by-process cases 

such as In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985) 

(applying product-by-process analysis for “an otherwise patentable product”) (emphasis added), and the well-recognized distinction patent law draws between the scope of 

composition and method of treatment claims. See, e.g.,

Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 

U.S. 576, 595 (2013) (recognizing the distinct scope for composition and method of treatment claims in the context of 

35 U.S.C. § 101).

Case: 19-1133 Document: 90 Page: 13 Filed: 09/28/2020
14 BIOGEN MA INC. v. EMD SERONO, INC.

Biogen’s only basis for novelty of the method of treatment claims at issue here is the novelty of the recombinant 

IFN-β composition that is administered. That composition 

is claimed in terms of the process by which it is manufactured. If the novelty of the recombinant IFN-β composition

requires comparing its structure to the structure of native 

IFN-β, as Amgen requires, it would defy all reason to excuse that analysis for a method of administration claim using that composition. Such a rule could have the absurd 

result that a recombinant composition could be non-novel, 

the method of administration could be non-novel, but the 

method of administration of the composition defined by the 

process of its manufacture would be novel as a matter of 

law. 

There is no logical reason why the nesting of a productby-process limitation within a method of treatment claim 

should change how novelty of that limitation is evaluated. 

Indeed, we have previously applied product-by-process 

analysis to a nested limitation. In Purdue Pharma, we interpreted a claim to “an oral dosage form comprising . . . oxycodone hydrochloride active pharmaceutical 

ingredient having less than 25 ppm 14-hydroxy[ ], wherein 

at least a portion of the 14-hydroxy [ ] is derived from 8α[ ] 

during conversion of oxycodone free base to oxycodone hydrochloride” as including a product-by-process limitation; 

namely, the 14-hydroxy as derived. Purdue Pharma, 811 

F.3d at 1353 (emphasis omitted). Similar to our analysis 

here, the court in Purdue Pharma held that it was appropriate to focus on the identity of the products of the claimed 

and prior art processes, and not on the source limitation, in 

analyzing obviousness. See id. at 1353–54. The nesting of 

the product-by-process limitation within a method of treatment claim does not change the proper construction of the 

product-by-process limitation itself.

We are also unpersuaded by the district court’s and Biogen’s reasoning that a product-by-process-type analysis is 

inappropriate here because the composition was otherwise 

Case: 19-1133 Document: 90 Page: 14 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 15

capable of definition other than by the process. That argument is precluded by Amgen, where the product was also 

well-defined in the claims: “human erythropoietin . . . wherein said erythropoietin is purified from mammalian cells grown in culture.” 580 F.3d at 1364. 

Furthermore, as noted supra, the rule in Amgen is a necessary outgrowth of the black-letter legal principle that an 

old product made by a new process is not novel and cannot 

be patented. Logic compels extending that rule to the present case; an old method of administration of an old product made by a new process is not novel and cannot be 

patented.

Biogen is certainly correct that the scope of composition 

and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty 

of the method of administration rests wholly on the novelty 

of the composition administered, which in turn rests on the 

novelty of the source limitation, the Amgen analysis will 

necessarily result in the same conclusion on anticipation 

for both forms of claims.

Finally, the district court erred in considering the advantages of the recombinant process—the new capability of 

manufacturing sufficient quantities of IFN-β through recombinant technology—as a reason not to apply a productby-process analysis. See Biogen I, 335 F. Supp. 3d at 713. 

That consideration may well be relevant in considering the 

novelty of the recombinant process, but, a new process, regardless of its novelty, does not make an old product created by that process novel. This does not fail to give “force 

and effect” to the heart of the claimed invention; it protects 

the public from attempts to excise old products from the 

public domain.

Because a proper anticipation analysis of the claims in 

the ’755 patent turns not on the source of the claimed polypeptide but on a comparison of the claimed recombinant

polypeptide and the prior art native polypeptide, the 

Case: 19-1133 Document: 90 Page: 15 Filed: 09/28/2020
16 BIOGEN MA INC. v. EMD SERONO, INC.

district court erred in concluding that the mere absence of 

recombinantly produced IFN-β in the prior art was sufficient to grant JMOL of no anticipation.

B. The Three-Dimensional Structure of the Polypeptide

The district court also held that even applying a product-by-process type analysis, no reasonable jury could have 

found anticipation because the jury lacked sufficient evidence of identity between the claimed recombinant “polypeptide” and the native IFN-β. In particular, the district 

court concluded that just because recombinant and native 

IFN-β “share the same linear amino acid sequence is not 

enough for purposes of anticipation.” Id. at 705. The district court took the position that native polypeptide anticipates the “recombinant polypeptide” only if their respective 

folded three-dimensional proteins share identical structure 

and function. Id. The district court reasoned that without 

a disclosure in the prior art of such three-dimensional protein, a showing of the native polypeptide alone would not 

necessarily produce “antiviral activity” when administered 

in a “therapeutically effective amount” as recited in the 

claims. Id. (citing Summary Judgment Opinion at 28, ECF 

No. 892). This was error.

The “product” administered in the claimed method is 

the “polypeptide.” See ’755 patent, col. 49, ll. 59–64 (“A 

method . . . comprising the step of administering . . . a 

therapeutically effective amount of a composition comprising: a recombinant polypeptide produced by a non-human 

host . . . .”). As noted supra, the key question for anticipation is whether the native “polypeptide” is identical to the 

“polypeptide” “produced by” the recited recombinant process.

Biogen explicitly defined “polypeptide” in the ’755 patent:

Polypeptide—A linear array of amino acids connected one to the other by peptide bonds between 

Case: 19-1133 Document: 90 Page: 16 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 17

the α-amino and carboxy groups of adjacent amino 

acids.

’755 patent, col. 8, ll. 62–64. The “polypeptide” structure is 

thus defined by reference to its “linear” array, without regard to its folded protein structure. The district court 

charged the jury with this definition, adding that the jury 

“must accept my definition of these words in the claims as 

correct.” Final Jury Instructions at 17, ECF No. 968. Biogen did not object to this charge and did not ask the court 

for a jury instruction requiring identity of the folded protein structures.

As the district court recognized on summary judgment, 

“Biogen does not dispute that ‘[t]he sequential order of the 

amino acid residues for native IFN-β is the same as the sequential order of the amino acid residues for recombinant 

IFN-β.’” Summary Judgment Opinion at 27, ECF No. 892. 

See also Biogen Brief at 19. Thus, the native IFN-β polypeptide and the claimed recombinant IFN-β polypeptide

are identical for purposes of the instant claim.

Biogen argues that the district court was correct in requiring identity not just of the polypeptide, but also of the 

folded proteins, because the claims require the administration of “a therapeutically effective amount of a composition” 

and that the DNA sequences in the claims must “code for a 

polypeptide displaying antiviral activity.” Biogen asserts 

that only three-dimensional proteins can be therapeutically effective and have antiviral activity, and therefore 

that the “product” to be analyzed for novelty is the folded 

three-dimensional protein, not just the amino acid sequence.

Biogen is incorrect. First, Biogen’s argument fails to

give effect to Biogen’s explicit definition of “polypeptide” in 

the specification. We must respect this lexicographic 

choice. See Edward Lifesciences LLC v. Cook Inc., 582 F.3d 

1322, 1329 (Fed. Cir. 2009) (“[W]e will adopt a definition 

that is different from the ordinary meaning when ‘the 

Case: 19-1133 Document: 90 Page: 17 Filed: 09/28/2020
18 BIOGEN MA INC. v. EMD SERONO, INC.

patentee acted as his own lexicographer and clearly set 

forth a definition of the disputed claim term in . . . the specification’” (quoting CCS Fitness, Inc. v. Brunswick Corp., 

288 F.3d 1359, 1366–67 (Fed. Cir. 2002))). Biogen does not 

attempt to square its theory with the definition in the specification.

Second, Biogen draws the wrong conclusion from the 

claimed antiviral activity limitation. The claims, in calling 

for antiviral activity, do not recite any specific folded threedimensional structure that gives rise to that activity. 

While it is indisputable that an amino acid sequence alone 

cannot give rise to antiviral activity, it is also indisputable 

that every linear sequence of proteins will fold into some

three-dimensional configuration. The claimed antiviral activity can arise from the administration of any three-dimensional protein with a linear amino acid sequence 

identical to the claimed recombinant “polypeptide.”

Finally, and importantly, Biogen did not ask for a jury 

instruction on anticipation that required comparing the 

three-dimensional protein structures of prior art IFN-β and 

the claimed recombinant IFN-β. Neither Biogen nor the 

district court can reframe the anticipation inquiry on 

JMOL to focus on the unclaimed three-dimensional protein 

structure, where the jury was instructed, without objection, to decide anticipation based on the linear amino acid 

sequence. See Finjan, Inc. v. Blue Coat Sys., Inc., 879 F.3d 

1299, 1306 (Fed. Cir. 2018) (“[I]t is too late at the JMOL 

stage to . . . adopt a new and more detailed interpretation 

of the claim language and test the jury verdict by that new 

and more detailed interpretation.” (quoting Hewlett-Packard Co. v. Mustek Sys., Inc., 340 F.3d 1314, 1321 (Fed. Cir. 

2003))).

The jury was correctly instructed that “to be entitled to 

a patent, the invention must actually be ‘new.’” J.A. 81262. 

It is undisputed that the prior art here teaches the administration of native IFN-β that has a linear amino acid 

Case: 19-1133 Document: 90 Page: 18 Filed: 09/28/2020
BIOGEN MA INC. v. EMD SERONO, INC. 19

sequence identical to the linear amino acid sequence of the 

recited recombinant IFN-β and that shows antiviral activity. See ’755 patent, col. 3, ll. 4–14. The jury thus had sufficient evidence to find that native IFN-β polypeptide is 

identical to recombinant IFN-β polypeptide, was administered in therapeutically effective amounts, and showed antiviral activity in the prior art. The district court thus 

erred in granting JMOL of no anticipation.3

IV. Conditional Grant of New Trial

The district court also conditionally granted a new trial 

on anticipation. The district court’s grant of a new trial 

was based on the same legal errors supporting its grant of 

JMOL. Biogen I, 335 F. Supp. 3d at 713 (“For the same 

reasons the Court grants Biogen’s JMOL motion, the Court 

conditionally orders a new trial on anticipation.”). None of 

the additional considerations noted by the district court in 

support of its conditional grant of a new trial are independently sufficient to support its decision. We therefore

reverse the district court’s grant of a conditional new trial 

on anticipation.

CONCLUSION

For the reasons discussed above, we reverse the district 

court’s grant of judgment as a matter of law of no anticipation and the conditional grant of a new trial on anticipation. We remand with instructions to reinstate the jury 

verdict on anticipation. We need not and do not address 

the several other issues raised by the parties on appeal.

3 Because the proper construction of the claims does 

not require comparison of the three-dimensional structure 

of prior art native IFN-β and recombinant IFN-β, we need 

not consider the parties’ contested readings of the InterPharm study or the evidence or lack thereof of structural 

identity.

Case: 19-1133 Document: 90 Page: 19 Filed: 09/28/2020
20 BIOGEN MA INC. v. EMD SERONO, INC.

REVERSED AND REMANDED

Case: 19-1133 Document: 90 Page: 20 Filed: 09/28/2020