Biogen Ma Inc. v. Emd Serono, Inc.

976 F.3d 1326

• Court: Court of Appeals for the Federal Circuit
• Decided: September 28, 2020
• Docket: 19-1133
• Status: Published

Opinion

Case: 19-1133 Document: 90 Page: 1 Filed: 09/28/2020

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 plain- tiff-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, Chat- ham, NJ. Case: 19-1133 Document: 90 Page: 2 Filed: 09/28/2020

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, Wash- ington, DC, for amicus curiae Bayer Healthcare Pharma- ceuticals 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. (col- lectively “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 Inter- feron, 19(2) Gut 91 (1978) (“Kingham”) and Sundmacher et

1 Biogen also asserted infringement claims against Bayer Healthcare Pharmaceuticals Inc. (“Bayer”) and No- vartis 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: 3 Filed: 09/28/2020

BIOGEN MA INC. v. EMD SERONO, INC. 3

al., Human Leukocyte and Fibroblast Interferon in a Com- bination Therapy of Dendritic Keratitis, 208(4) Albrecht von Graefes Archiv für Klinische & Experimentelle Opthal- mologie 229 (1978) (“Sundmacher”). The jury also held the asserted claims not invalid for lack of enablement or writ- ten description, or for obviousness. Finally, the jury held that patients and prescribers directly infringed the as- serted 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 anticipa- tion. 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 invalid- ity based on written description or enablement; overturn- ing 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 infringe- ment, 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 anticipa- tion 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 ad- ministration 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: 4 Filed: 09/28/2020

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 tu- mors comprising the step of administering to a patient in need of such treatment a therapeuti- cally effective amount of a composition compris- ing: a recombinant polypeptide produced by a non-human host transformed by a recombi- nant DNA molecule comprising a DNA se- quence selected from the group consisting of: (a) DNA sequences which are capa- ble 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 G- pBR322(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 de- generate 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: 5 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 se- lection 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 polypep- tide by reference to the DNA sequence inserted into the host during the recombinant manufacture of the polypep- tide. Claim 3, dependent from claim 1, limits the polypep- tide to a particular linear polypeptide sequence. Because the claimed IFN-β DNA and polypeptide sequences are de- rived from human IFN-β, it is indisputable that native hu- man IFN-β is capable of hybridizing with the DNA sequences in claim 1, is produced by one of the DNA se- quences 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 recombi- nant 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 capa- ble of hybridizing to one or more of the DNA inserts be- cause 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 limita- tions. 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-by- process claim,” and that it was “aware of no binding Case: 19-1133 Document: 90 Page: 6 Filed: 09/28/2020

precedent requiring method of treatment claims to be treated as product-by-process claims in the claim construc- tion context.” Id. at 14. The district court did not construe “polypeptide,” “therapeutically effective amount,” or “anti- viral activity,” and neither party asked the court to con- sider whether the claims covered the linear sequence of amino acids or the three-dimensional structure of the pro- tein. 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 effec- tive 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 se- quence 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, obvious- ness, enablement, written description, and contributory and induced infringement to the jury. In its charge on an- ticipation, the district court told the jury that “[t]he term ‘polypeptide’ means ‘a linear array of amino acids con- nected one to the other by peptide bonds between the α- amino 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: 7 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 pa- tent were invalid as anticipated by native IFN-β; not inva- lid for obviousness, lack of enablement or lack of written description; and that Serono was liable for contributory in- fringement but not induced infringement. Jury Verdict Form at 1–6, Feb. 23, 2018, ECF No. 977. Both parties renewed their JMOL motions. As rele- vant 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 Ser- ono’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 dis- closed “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 treat- ment in the prior art entailed administration of native IFN-β, which was undisputedly not recombinantly pro- duced, 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 recombi- nant erythropoietin (“EPO”) by prior art urinary (i.e. natu- ral) 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-by- process claims—to enable an inventor to claim an Case: 19-1133 Document: 90 Page: 8 Filed: 09/28/2020

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 rea- sonable 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 admin- istration of a “therapeutically effective amount” of a recom- binant 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 Opin- ion at 28, Jan. 9, 2018, ECF No. 892). The district court held that the jury lacked substantial evidence that the na- tive 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 at- tached carbohydrate groups in recombinant IFN-β were not glycosolated, and that this change affected the three-di- mensional 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 cre- ated by InterPharm Laboratories Ltd. entitled “Compara- tive 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 antic- ipation. Id. at 710–11 (relying primarily on this court’s de- cision in Amgen, 580 F.3d at 1367–69, in which we affirmed a holding of no anticipation based on structural differ- ences). Finally, the district court discounted the conclusion in the InterPharm study that recombinant IFN-β and Case: 19-1133 Document: 90 Page: 9 Filed: 09/28/2020

BIOGEN MA INC. v. EMD SERONO, INC. 9

native IFN-β were identical. It held that there was no sub- stantial evidence that the generic “native IFN-β” analyzed in the InterPharm study and found to be identical to re- combinant 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 condi- tionally granted Biogen’s motion for a new trial on antici- pation “[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 re- views the conditional grant of a new trial against the Case: 19-1133 Document: 90 Page: 10 Filed: 09/28/2020

weight of the evidence for an abuse of discretion, “unless the court’s denial is based on the application of a legal pre- cept, 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 [limita- tion] 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 Bal- last 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-di- mensional structures not specifically recited in the claims rather than the claimed and lexicographically defined “pol- ypeptide.” Both of these determinations led to an errone- ous 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 re- combinant IFN-β. Biogen I, 335 F. Supp. 3d at 704. It cat- egorized the “produced” and “transformed” limitations as meaningful “source limitations.” Id. at 711–12. The dis- trict 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: 11 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 Bio- gen’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 lim- itation 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-de- fine 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 antici- pation, regardless of whether Serono had shown the iden- tity 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 ar- gued 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 hold- ing that the lack of a recombinantly produced IFN-β prod- uct 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 Appli- ance 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: 12 Filed: 09/28/2020

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 pro- cess 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 compar- ing 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 accepta- ble diluent, adjuvant or carrier, wherein said erythropoi- etin 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 glycopro- tein 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: 13 Filed: 09/28/2020

BIOGEN MA INC. v. EMD SERONO, INC. 13

question was “whether the production of EPO by recombi- nant 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 recombi- nant 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 prod- uct itself is identical to the prior art non-recombinant prod- uct. The requirements that the claimed polypeptide is “recombinant” and “produced by a non-human host trans- formed 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 . . . can- not be a structural limitation”). The key question for an- ticipation 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 pa- tentable product”) (emphasis added), and the well-recog- nized 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 com- position and method of treatment claims in the context of 35 U.S.C. § 101). Case: 19-1133 Document: 90 Page: 14 Filed: 09/28/2020

Biogen’s only basis for novelty of the method of treat- ment 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 manufac- tured. 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 ex- cuse that analysis for a method of administration claim us- ing 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 product- by-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 in- terpreted a claim to “an oral dosage form compris- ing . . . 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 hy- drochloride” 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 appro- priate 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 treat- ment claim does not change the proper construction of the product-by-process limitation itself. We are also unpersuaded by the district court’s and Bi- ogen’s reasoning that a product-by-process-type analysis is inappropriate here because the composition was otherwise Case: 19-1133 Document: 90 Page: 15 Filed: 09/28/2020

BIOGEN MA INC. v. EMD SERONO, INC. 15

capable of definition other than by the process. That argu- ment is precluded by Amgen, where the product was also well-defined in the claims: “human erythropoi- etin . . . wherein said erythropoietin is purified from mam- malian cells grown in culture.” 580 F.3d at 1364. Furthermore, as noted supra, the rule in Amgen is a neces- sary 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 pre- sent case; an old method of administration of an old prod- uct 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 dis- tinctly 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 ad- vantages of the recombinant process—the new capability of manufacturing sufficient quantities of IFN-β through re- combinant technology—as a reason not to apply a product- by-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, re- gardless of its novelty, does not make an old product cre- ated 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 pol- ypeptide but on a comparison of the claimed recombinant polypeptide and the prior art native polypeptide, the Case: 19-1133 Document: 90 Page: 16 Filed: 09/28/2020

district court erred in concluding that the mere absence of recombinantly produced IFN-β in the prior art was suffi- cient to grant JMOL of no anticipation. B. The Three-Dimensional Structure of the Polypeptide The district court also held that even applying a prod- uct-by-process type analysis, no reasonable jury could have found anticipation because the jury lacked sufficient evi- dence of identity between the claimed recombinant “poly- peptide” 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 dis- trict court took the position that native polypeptide antici- pates 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 pro- tein, 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 compris- ing: a recombinant polypeptide produced by a non-human host . . . .”). As noted supra, the key question for anticipa- tion is whether the native “polypeptide” is identical to the “polypeptide” “produced by” the recited recombinant pro- cess. Biogen explicitly defined “polypeptide” in the ’755 pa- tent: Polypeptide—A linear array of amino acids con- nected one to the other by peptide bonds between Case: 19-1133 Document: 90 Page: 17 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 re- gard 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. Bio- gen did not object to this charge and did not ask the court for a jury instruction requiring identity of the folded pro- tein 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 se- quential 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 poly- peptide and the claimed recombinant IFN-β polypeptide are identical for purposes of the instant claim. Biogen argues that the district court was correct in re- quiring identity not just of the polypeptide, but also of the folded proteins, because the claims require the administra- tion 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 therapeuti- cally 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 se- quence. 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: 18 Filed: 09/28/2020

patentee acted as his own lexicographer and clearly set forth a definition of the disputed claim term in . . . the spec- ification’” (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 spec- ification. 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 three- dimensional 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 ac- tivity can arise from the administration of any three-di- mensional 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 objec- tion, 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-Pack- ard 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 admin- istration of native IFN-β that has a linear amino acid Case: 19-1133 Document: 90 Page: 19 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 activ- ity. See ’755 patent, col. 3, ll. 4–14. The jury thus had suf- ficient evidence to find that native IFN-β polypeptide is identical to recombinant IFN-β polypeptide, was adminis- tered in therapeutically effective amounts, and showed an- tiviral 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 inde- pendently 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 anticipa- tion and the conditional grant of a new trial on anticipa- tion. 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 Inter- Pharm study or the evidence or lack thereof of structural identity. Case: 19-1133 Document: 90 Page: 20 Filed: 09/28/2020

REVERSED AND REMANDED