No. _____
`
`
`IN THE
`Supreme Court of the United States
`————
`BIOGEN MA INC.,
`Petitioner,
`
`v.
`
`
`
`
`
`EMD SERONO, INC., PFIZER INC.,
`
`
`
`Respondents.
`————
`On Petition for a Writ of Certiorari
` to the United States Court of Appeals
`for the Federal Circuit
`————
`
`PETITION FOR A WRIT OF CERTIORARI
`
`————
`NICHOLAS GROOMBRIDGE
`JEFFREY A. LAMKEN
`Counsel of Record
`ERIC ALAN STONE
`PETER SANDEL
`MOLOLAMKEN LLP
`JENNY C. WU
`The Watergate, Suite 500
`JOSEPHINE YOUNG
`600 New Hampshire Ave., N.W.
`PAUL, WEISS, RIFKIND
`Washington, D.C. 20037
` WHARTON & GARRISON
`(202) 556-2000
` LLP
`jlamken@mololamken.com
`1285 Ave. of the Americas
`New York, NY 10019
`(212) 373-3000
`
`
`
`Counsel for Petitioner
`
`
`
`
`IN THE
`Supreme Court of the United States
`————
`BIOGEN MA INC.,
`Petitioner,
`
`v.
`
`
`
`
`
`EMD SERONO, INC., PFIZER INC.,
`
`
`
`Respondents.
`————
`On Petition for a Writ of Certiorari
` to the United States Court of Appeals
`for the Federal Circuit
`————
`
`PETITION FOR A WRIT OF CERTIORARI
`
`————
`NICHOLAS GROOMBRIDGE
`JEFFREY A. LAMKEN
`Counsel of Record
`ERIC ALAN STONE
`PETER SANDEL
`MOLOLAMKEN LLP
`JENNY C. WU
`The Watergate, Suite 500
`JOSEPHINE YOUNG
`600 New Hampshire Ave., N.W.
`PAUL, WEISS, RIFKIND
`Washington, D.C. 20037
` WHARTON & GARRISON
`(202) 556-2000
` LLP
`jlamken@mololamken.com
`1285 Ave. of the Americas
`New York, NY 10019
`(212) 373-3000
`
`
`
`Counsel for Petitioner
`
`
`
`
`QUESTION PRESENTED
`The patent in this case claims a method of medical
`treatment that requires use of a “recombinant,” or syn-
`thetic version, of a human protein. That synthetic, re-
`combinant version does not exist in nature. The Federal
`Circuit held, in violation of this Court’s longstanding
`precedent, that the claim term “recombinant” must be
`ignored in assessing whether the method of treatment is
`novel. The question presented is:
`Whether courts may disregard the express claim term
`“recombinant” so as to render a method-of-treatment
`patent anticipated—and thus invalid—in light of prior-art
`treatments that used the naturally occurring human
`protein, where it is undisputed that the recombinant
`protein was not used in the prior art?
`
`(i)
`
`
`
`ii
`PARTIES TO THE PROCEEDINGS
`Petitioner is Biogen MA Inc. (“Biogen”). Respondents
`are EMD Serono Inc. and Pfizer Inc. (together except
`where noted, “Serono”).
`Bayer Healthcare Pharmaceuticals, Inc. and Novartis
`Pharmaceuticals Corp. (together except where noted,
`“Bayer”) were defendants in a parallel district court
`proceeding, previously consolidated with this case but
`later severed, at Bayer’s request.
`
`
`
`
`
`iii
`CORPORATE DISCLOSURE STATEMENT
`Pursuant to Rule 29.6 of the Rules of this Court,
`Petitioner Biogen MA Inc. states that it is a wholly
`owned subsidiary of Biogen Inc., which is a publicly held
`corporation traded on the Nasdaq Stock Market under
`the symbol BIIB. No other publicly held corporation
`owns 10% or more of the stock in Biogen MA Inc.
`
`
`
`
`
`
`
`TABLE OF CONTENTS
`
`Question Presented .....................................................
`Parties to the Proceedings .........................................
`Corporate Disclosure Statement ...............................
`Opinions Below .............................................................
`Statement of Jurisdiction ...........................................
`Statutory Provisions Involved ...................................
`Preliminary Statement ...............................................
`Statement of the Case .................................................
`I.(cid:3) Technological Background of the
`Invention and the Resulting Patent .............
`A.(cid:3) The Unfulfilled Promise of
`
`Interferon-(cid:574), and Dr. Fiers’s
`
`Solution ......................................................
`B.(cid:3) The ’755 Patent .........................................
`I.(cid:3) Procceedings Below ........................................
`A.(cid:3) Proceedings Before the Trial Court ......
`B.(cid:3) The Federal Circuit’s Decision ..............
`Reasons for Granting the Petition ............................
`I.(cid:3) The Federal Circuit’s Decision
`Contravenes This Court’s Settled
`Precedents ........................................................
`A.(cid:3) The Federal Circuit’s Decision
`Conflicts With the Patent Act and
`This Court’s Precedents ..........................
`
`(iv)
`
`Page
`i(cid:3)
`ii(cid:3)
`iii(cid:3)
`1(cid:3)
`1(cid:3)
`2(cid:3)
`2(cid:3)
`7(cid:3)
`
`8(cid:3)
`
`8(cid:3)
`10(cid:3)
`12(cid:3)
`12(cid:3)
`15(cid:3)
`17(cid:3)
`
`17(cid:3)
`
`18(cid:3)
`
`
`
`v
`TABLE OF CONTENTS—Continued
`
`Page
`
`24(cid:3)
`
`29(cid:3)
`29
`
`B.(cid:3) The Federal Circuit’s Decision Will
`Undermine Longstanding
`Incentives and Discourage
`Investment Essential To
`Developing New Therapeutic
`Treatments ................................................
`C.(cid:3) This Is an Appropriate Vehicle To
`Address These Important Issues ..........
`Conclusion .....................................................................
`Appendix A – Amended Court of Appeals
`Opinion (Sept. 28, 2020) ..............................................
`Appendix B – Errata for the Court of Appeals
`Opinion (Nov. 20, 2020) ............................................... 22a
`Appendix C – Errata for the Court of Appeals
`Opinion (Oct. 9, 2020) .................................................. 24a
`Appendix D – Original Court of Appeals Opinion
`(Sept. 28, 2020) ............................................................. 25a
`Appendix E – District Court Opinion
`(Sept. 7, 2018) ............................................................... 46a
`Appendix F – Order of the Court of Appeals
`Denying Rehearing and Rehearing En Banc
`(Mar. 23, 2020) .............................................................. 155a
`Appendix G – Relevant Statutory Provision ............ 157a
`
`
`1a
`
`
`
`
`
`vi
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`
`Amgen Inc. v. Hoffman-La Roche Ltd.,
`580 F.3d 1340 (Fed. Cir. 2009) ............... 16, 19, 20
`Ass’n for Molecular Pathology v. Myriad
`Genetics, Inc.,
`569 U.S. 576 (2013) ..................................... 6, 21, 23
`Cochrane v. Badische Anilin & Soda Fabrik,
`111 U.S. 293 (1884) .............................................
`Dewey & Almy Chem. Co. v. Mimex Co.,
`124 F.2d 986 (2d Cir. 1942) ...............................
`Gen. Elec. Co. v. Wabash Appliance Corp.,
`304 U.S. 364 (1938) .......................................... 19, 22
`Graham v. John Deere Co. of Kansas City,
`383 U.S. 1 (1966) .................................................
`Le Roy v. Tatham,
`63 U.S. 132 (1860) ...............................................
`Lind v. Schenley Indus., Inc.,
`278 F.2d 79 (3d Cir. 1960) .................................
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) .........................
`Planing-Mach. Co. v. Keith,
`101 U.S. 479 (1880) .............................................
`Summit 6, LLC v. Samsung Elecs. Co.,
`802 F.3d 1283 (Fed. Cir. 2015) .........................
`STATUTES AND RULES
`28 U.S.C. § 1254(1) ..................................................
`
`
`18
`
`15
`
`1
`
`19
`
`19
`
`18
`
`18
`
`15
`
`21
`
`
`
`vii
`TABLE OF AUTHORITIES—Continued
`Page(s)
`28 U.S.C. § 1292(c)(2) ..............................................
`15
`35 U.S.C. § 101 ........................................................
`21
`35 U.S.C. § 102(a)-(b) (2006) ..................................
`2
`35 U.S.C. § 103 .........................................................
`18
`35 U.S.C. § 271(b) ....................................................
`13
`35 U.S.C. § 271(c) ....................................................
`13
`Fed. R. Civ. P. 50(c) ................................................
`14
`OTHER AUTHORITIES
`Arthritis by the Numbers, Arthritis
`Foundation (2019), https://www.arthritis.
`org/getmedia/e1256607-fa87-4593-aa8a-
`8db 4f291072a/2019-abtn-final-march-
`2019.pdf ...............................................................
`Biotechnology Innovation Organization,
`Clinical Development Success Rates 2006-
`2015 (2016) ......................................................... 4, 28
`Derek Burkhard, et al., The Top 10 Best-
`Selling Drugs of 2020, Scrip (Apr. 23,
`2021), https://scrip.pharmaintelligence.
`informa.com/SC 144160/The-Top-10-Best-
`Selling-Drugs-Of-2020 .......................................
`J. Cody, et al., Recombinant human
`erythropoietin for chronic renal failure
`anaemia in pre-dialysis patients,
`Cochrane Database Syst. Rev. (2005) .............
`
`26
`
`27
`
`25
`
`
`
`
`
`viii
`TABLE OF AUTHORITIES—Continued
`Page(s)
`
`Coronavirus (COVID-19) Update: FDA
`Authorizes Monoclonal Antibodies for
`Treatment of COVID-19, U.S. Food &
`Drug Administration (Feb. 9, 2021),
`https://www.fda.gov/ news-events/press-
`announcements/coronavirus-covid-
`19update -fda-authorizes-monoclonal-
`antibodies-treatment-covid-19-0 .....................
`Joseph A. DiMasi, et al., Innovation in the
`pharmaceutical industry: New estimates
`of R&D costs, 47 J. of Health Econ. 20
`(2016) ....................................................................
`Fast Facts Data and Statistics About
`Diabetes, American Diabetes Association
`(Dec. 2015), https://professional.diabetes.
`org/sites/professional.diabetes.org/files/me
`dia/fast_ ...............................................................
`Michael L. Ganz, et al., The Economic and
`Health-related Impact of Crohn’s Disease
`in the United States: Evidence from a
`Nationally Representative Survey, 22(5)
`Inflamm. Bowel Dis. 1032 (2016) .....................
`
`27
`
`28
`
`26
`
`27
`
`
`
`
`
`ix
`TABLE OF AUTHORITIES—Continued
`Page(s)
`
`Global Therapeutic Proteins Market Report
`2020: Market was Valued at $93.14 Billion
`in 2018 and is Expected to Grow to $172.87
`Billion through 2022, Business Wire (Dec.
`21, 2019), https://www.businesswire.com/
`news/home/2019122 3005228/en/Global-
`Therapeutic-Proteins-Market-Report-
`2020-Market-was-Valued-at-93.14-Billion-
`in-2018-and-is-Expected-to-Grow-to-
`172.87-Billion-through-2022---
`ResearchAndMarkets.com ...............................
`Bruce Goldman, Stanford scientists link
`ulcerative colitis to missing gut microbes,
`Stanford Medicine (Feb. 25, 2020),
`https://med.stanford.edu/ news/all-
`news/2020/02/stanford-scientists-link-
`ulcerative-colitis-to-missing-gut-
`micro.html#:~:text=About%201%
`20million%20people%20in,condition%20to
`%20a%20missing%20microbe ..........................
`Humira, https://www.humira.com/ ......................
`Kidney Disease Statistics for the United
`States, National Institute of Health (2015),
`https://www.niddk.nih.gov/health-
`information/health-statistics/kidney-
`disease#:~:text=More%20than%20661%2
`C000%20Americans%20have,with%20a%2
`0functioning%20kidney%20transplant ...........
`Wolfgang Landgraf & Juergen Sandow,
`Recombinant Human Insulins—Clinical
`Efficacy and Safety in Diabetes Therapy,
`12(1) Eur. Endocinology 12 (2016) ..................
`
`24
`
`27
`27
`
`26
`
`25
`
`
`
`
`
`x
`TABLE OF AUTHORITIES—Continued
`Page(s)
`
`Preventing Infections in Cancer Patients,
`Centers for Disease Control and
`Prevention (Nov. 10, 2020), https://www.
`cdc.gov/cancer/preventinfections/provider
`s.htm#:~:text=Each%20year%2C%20abo
`ut%20650%2C000%20cancer,clinic%20in%
`20the%20United%20States ..............................
`Psoriasis Statistics, National Psoriasis
`Foundation (Oct. 8, 2020), https://www.
`psoriasis.org/psoriasis-statistics/ .....................
`Recombinant Therapeutic Antibodies and
`Proteins Market, PharmiWeb (Dec. 17,
`2020), https://www.pharmiweb.com/
`press-release/2020-12-17/recombinant-
`therapeutic-antibodies-and-proteins-
`market-share-and-trend-analysis-by-top-
`leading-playe .......................................................
`Marzieh Rezaei & Sayyed H. Zarkesh-
`Esfahani, Optimization of production of
`recombinant human growth hormone in
`Escherichia coli, 17(7) J. Rsch. Med. Sci.
`681 (2012) .............................................................
`Treatment of Hemophilia, Centers for
`Disease Control and Prevention (July 17,
`2020), https://www.cdc.gov/ncbddd/
`hemophilia/treatment.html ..............................
`
`26
`
`27
`
`24
`
`25
`
`25
`
`
`
`
`
`
`IN THE
`Supreme Court of the United States
`————
`
`BIOGEN MA INC.,
`Petitioner,
`
`v.
`
`
`
`
`
`EMD SERONO, INC., PFIZER INC.,
`
`
`
`Respondents.
`
`————
`
`On Petition for a Writ of Certiorari
` to the United States Court of Appeals
`for the Federal Circuit
`
`————
`
`PETITION FOR A WRIT OF CERTIORARI
`
`————
`
`OPINIONS BELOW
`The opinion of the Federal Circuit is reported at 976
`F.3d 1326 and reproduced at App., infra, 1a-21a. The
`opinion of the district court is reported at 335 F. Supp. 3d
`688 and reproduced at App., infra, 46a-155a.
`STATEMENT OF JURISDICTION
`The Federal Circuit entered judgment on September
`28, 2020, App., infra, 1a, and denied rehearing and
`rehearing en banc on December 18, 2020, App., infra,
`157a. This petition is timely pursuant to this Court’s
`Rule 13 and this Court’s March 19, 2020 Order. The
`Court has jurisdiction under 28 U.S.C. § 1254(1).
`
`
`
`
`
`2
`STATUTORY PROVISIONS INVOLVED
`The relevant provision of Title 35 of the United States
`Code is reproduced at App., infra, 158a-159a. Section
`102 of Title 35, as applicable to pre-America Invents Act
`(“pre-AIA”) patents such as the patent here, states in
`relevant part:
`A person shall be entitled to a patent unless–
`(a) the invention was known or used by others
`in this country, or patented or described in
`a printed publication in this or a foreign
`country, before the invention thereof by the
`applicant for patent, or
`(b) the invention was patented or described in a
`printed publication in this or a foreign
`country or in public use or on sale in this
`country, more than one year prior to the
`date of the application for patent in the
`United States.
`35 U.S.C. § 102(a)-(b) (2006).
`PRELIMINARY STATEMENT
`The Federal Circuit’s decision in this case upends
`decades of settled jurisprudence that the invention of a
`new medical treatment is patentable. The decision holds
`that a novel, never-performed method of treating disease
`can be anticipated—i.e., deemed not new and thus un-
`patentable—even though the claimed method had never
`been disclosed or performed in the prior art.
`Here, the claimed method of treatment required the
`use of “recombinant” or genetically engineered biological
`material that was different from the naturally occurring
`human protein. The prior art did not disclose such treat-
`ment. The art did disclose treatment methods using the
`
`
`
`
`
`3
`analogue human protein, but such treatments were
`unworkable because the naturally occurring protein
`could not be harvested in sufficient quantities. Yet the
`Federal Circuit held the patent’s requirement of adminis-
`tering a structurally different “recombinant” protein
`could simply be ignored. As a result, it ruled that an old
`and unworkable treatment method using the natural
`protein could anticipate and invalidate the claim to a
`novel and new method that has transformed medicine.
`If not corrected, the decision will have severe adverse
`consequences for biomedical research and development.
`Recombinant therapies have enormous medical signifi-
`cance. More than 140 recombinant proteins have been
`approved for therapeutic use by the Food and Drug Ad-
`ministration, and five of the top ten therapeutic products
`by sales value are recombinant proteins. Analysts esti-
`mate the annual global market for recombinant thera-
`peutics to be over $90 billion. Many diseases and condi-
`tions are caused by the human body failing to make, or
`failing to make enough of, a given human protein. Meth-
`ods of treatment using proteins made with recombinant
`techniques allow scientists and pharmaceutical inno-
`vators to replace or augment those human proteins with
`recombinant analogues. Across the medical landscape,
`from hemophilia to diabetes to cancer to multiple
`sclerosis, methods of treatment with recombinant pro-
`teins have revolutionized patient care for millions and
`millions of patients. For example, there are more than
`one million patients suffering from multiple sclerosis in
`
`this country; before recombinant interferon-(cid:574) there was
`
`no treatment available. Approximately six million Ameri-
`cans take recombinant insulin. Across the spectrum of
`diseases, millions of lives have been improved or saved
`with these therapies.
`
`
`
`
`
`4
`Those inventions, however, are highly expensive and
`risky. The most recent studies show that bringing a new
`biologic medicine (the category in which recombinant
`proteins fall) to market costs $2.6 billion on average. For
`every successful new treatment, there can be dozens of
`failures. See, e.g., Biotechnology Innovation Organiza-
`tion, Clinical Development Success Rates 2006-2015, at 3
`(2016).1 Robust patent protection allows the United
`States to maintain its position as the world’s leading bio-
`medical innovator. The Federal Circuit’s decision im-
`perils the scientific investments needed to develop these
`promising new therapies that may help millions of pa-
`tients. Personalized medicine is now moving to the fore
`and recombinant technology is becoming ever more im-
`portant. The timing of the Federal Circuit’s sea change
`could not be worse.
`This case concerns an invention that dates from the
`dawn of—and that helped prompt—the biotechnology
`revolution. In 1980, when today’s techniques for pro-
`ducing new biological products were mere hypotheses,
`scientist Walter Fiers did something unprecedented: He
`caused E. coli bacteria to produce an analogue to a pro-
`tein ordinarily generated by the human immune sys-
`
`tem—interferon-(cid:574). He determined, moreover, that the
`interferon-(cid:574) he was able to produce in bacteria matched
`Human interferon-(cid:574) was thought to be a treatment for all
`
`the biological activity of the native, human protein.
`Dr. Fiers thus solved a problem that had plagued
`science (and fascinated the popular press) for years.
`
`manner of viral conditions and diseases. It was, however,
`
`
`1 https://www.bio.org/sites/default/files/legacy/bioorg/docs/Clinical%2
`0Development%20Success%20Rates%202006-2015%20-%20BIO,%20
`Biomedtracker,%20Amplion%202016.pdf.
`
`
`
`
`
`5
`available in only infinitesimally small amounts, harvested
`with great difficulty from discarded human tissue. Dr.
`Fiers overcame this problem using “recombinant” DNA
`technology. That technology takes genetic material from
`different sources and joins them—or “recombines”
`them—before inserting them into a host cell. The host
`cell—in this case, a non-human host cell—in turn uses
`the DNA to produce a synthetic protein having similar
`properties but a different molecular structure from the
`
`human protein. By producing recombinant interferon-(cid:574)
`
`in a non-human cell, and proving that it had the same
`biological activity as the naturally occurring human ver-
`sion, Dr. Fiers overcame a barrier—scarcity—that had
`prevented that protein’s widespread medical use. Bio-
`gen, which underwrote Dr. Fiers’s research, made the
`financial investments needed to turn that discovery into
`Avonex®, a leading treatment for multiple sclerosis.
`Dr. Fiers’s patent application spent 29 years being
`thoroughly examined by the Patent Office.2 By the time
`the patent issued in 2009 as U.S. Patent No. 7,588,755
`(the “ ’755 Patent”), respondents EMD Serono, Inc. and
`
`Pfizer Inc. together sold their recombinant interferon-(cid:574)
`treatments using naturally occurring human interferon-(cid:574)
`anticipate treatments using recombinant interferon-(cid:574).
`
`product Rebif® for use in a treatment that the jury found
`infringes Biogen’s patent. Following trial and verdict,
`the district court entered judgment for Biogen. It re-
`jected as a matter of law respondents’ argument that
`
`App., infra, 55a-81a. Under longstanding precedent,
`
`2 Much of that time was consumed by interference proceedings to
`determine who was the first inventor of the subject matter, as
`several applicants had filed for patents. Substantive review was
`suspended—in effect, stayed—for a lengthy period because of actual
`or potential interferences.
`
`
`
`
`
`6
`proof of anticipation requires the defendant to establish
`that each and every element of the patent claim was
`disclosed in a single prior art reference. “The evidence
`presented at trial,” the court explained, “demonstrates
`
`that native interferon-(cid:574) and recombinant interferon-(cid:574)
`prior art methods using native interferon-(cid:574) could not an-
`
`are not structurally identical,” App., infra, 65a, and thus
`
`ticipate Dr. Fiers’s patented method.
`The Federal Circuit’s decision reversing that judg-
`ment does violence to this Court’s precedents and
`threatens the viability of patent protection for—and thus
`the incentive to develop—treatments using recombinant
`technologies. It invoked “product-by-process law,” under
`which an old product does not become patentable merely
`because it is made by a new process. App., infra, 12a-
`17a. That law, it ruled, applies to and invalidates the ’755
`Patent’s method-of-treatment claims because the same
`
`treatment using natural (not recombinant) interferon-(cid:574)
`
`was previously known. App., infra, 17a-20a. That hold-
`ing runs headlong into this Court’s decision in Associ-
`ation for Molecular Pathology v. Myriad Genetics, Inc.,
`569 U.S. 576, 595 (2013), which recognizes that methods
`of treatment are patentably distinct from the products
`administered in those methods. In Myriad, this Court
`held that, although the DNA coding for a human protein
`could not be patented, methods of treatment based on
`that protein were analytically distinct: “It is important to
`note what is not implicated by this decision. First, there
`are no method claims before this Court. Had Myriad cre-
`ated an innovative method of manipulating genes while
`searching for the BRCA1 and BRCA2 genes, it could
`possibly have sought a method patent.” Id. at 595.
`Rejecting that very distinction here, the Federal
`Circuit held that the ’755 Patent’s method of treatment
`
`
`
`
`
`using recombinant interferon-(cid:574) was anticipated even
`ther ignored that recombinant interferon-(cid:574) made in a
`feron-(cid:574). That was error. And it rejected the district
`
`7
`
`though that method did not exist in the prior art. It fur-
`
`non-human cell is not identical to native, human inter-
`
`court’s exercise of its discretion to grant a new trial,
`holding such method-of-treatment claims invalid as a
`matter of law even though, all agree, the method had
`never before been practiced.
`The Federal Circuit’s ruling does not merely negate
`an unbroken line of cases stretching back to before the
`Patent Act. It threatens innovation where it is needed
`most: to cure diseases against which the body’s natural
`immune response is insufficiently robust. This Court
`should grant review, reverse the Federal Circuit, and
`either reinstate the district court’s judgment as a matter
`of law of no anticipation or reinstate its conditional grant
`of a new trial on that issue.
`STATEMENT OF THE CASE
`This case concerns the sort of breakthrough that the
`patent laws unquestionably should reward. The ’755
`Patent is directed to a treatment that was not previously
`possible—administering a new recombinant protein that
`has the biological activity of naturally occurring inter-
`
`feron-(cid:574). Recombinant interferon-(cid:574) was the first success-
`
`ful large-scale therapy for multiple sclerosis, a devas-
`tating disease in which the body’s own immune mecha-
`nism damages the material that insulates and protects
`the nerves.
`
`
`
`
`
`8
`I. TECHNOLOGICAL BACKGROUND OF THE INVENTION
`AND THE RESULTING PATENT
`A. The Unfulfilled Promise of Interferon-(cid:574), and
`Dr. Fiers’s Solution
`The human immune system makes proteins called
`“interferons” to help fend off attacks by viruses. See,
`e.g., C.A. App. 7783 (24:30-18). Beginning in the 1950s,
`doctors sought to isolate human interferons and to use
`them to treat viral diseases, cancers, and other condi-
`tions. C.A. App. 118-119 (2:53-4:22); C.A. App. 7784
`(25:13-23). By the late 1970s, one form of human inter-
`
`feron, interferon-(cid:574), had shown great promise as a miracle
`drug. See C.A. App. 66140. But interferon-(cid:574) is found in
`(4:49-55). The most common source of interferon-(cid:574) was
`App. 119-120 (4:49-5:3). Harvesting interferon-(cid:574) from
`
`only infinitesimal amounts in human cells. C.A. App. 119
`
`fibroblast cells in discarded human foreskin. See C.A.
`
`those cells was inefficient and yielded impure composi-
`tions. Ibid. Thus, in 1979, Omni described interferons as
`the “miracle cure at $22 billion per pound.” C.A. App.
`66140. The next year, Time dubbed interferons “the IF
`drug,” playing on their name and their tantalizing unob-
`tainability. C.A. App. 66145-66146.
`1. As the ’755 Patent (with a priority date of June 6,
`1980) explained, human interferon “has potential appli-
`cation in antitumor and anticancer therapy,” but such
`
`“applications of IFN-(cid:574) have been severely hampered by
`lack of an adequate supply of purified IFN-(cid:574).” C.A. App.
`ducing interferon-(cid:574) with the “immunological or biological
`activity of ” human interferon-(cid:574). C.A. App. 120 (5:49-6:5).
`
`119 (3:57-4:13). Dr. Fiers noted that then-“recent ad-
`vances in molecular biology” created the possibility for
`recombinant expression of desired proteins in non-human
`cells. C.A. App. 120 (5:4-16). He achieved that goal, pro-
`
`
`
`
`
`9
`“By virtue of this invention,” he explained, “it is possible
`to obtain polypeptides displaying an immunological or
`
`biological activity of ” human interferon-(cid:574) “for use in anti-
`
`viral, antitumor or anticancer agents and methods. This
`invention allows the production of these polypeptides in
`amounts and by methods hitherto not available.” C.A.
`App. 120 (5:54-59).
`Dr. Fiers was not the only person working to achieve
`that goal. Several groups of the world’s leading scientists
`
`cell line and to determine whether the resulting, recombi-
`nant protein would have biological activity like that of
`
`to figure out how to achieve that goal. He was the first to
`
`demonstrate that, even though they are structurally dif-
`ferent from the human analogue, they have the biological
`
`Because recombinant proteins can be manufactured in
`large quantities, this meant they could be made in
`therapeutically effective amounts for treatment. See
`C.A. App. 136-140 (37:18-46:37). The United States
`Patent Office awarded Dr. Fiers the ’755 Patent, directed
`
`were attempting to express interferon-(cid:574) in a non-human
`native, human interferon-(cid:574). But Dr. Fiers was the first
`recombinantly express interferon-(cid:574)-like proteins and to
`and immunological activity of native, human interferon-(cid:574).
`to methods of treatment using recombinant interferon-(cid:574)
`2. While the recombinant interferon-(cid:574) mimics the ac-
`identical to naturally occurring human interferon-(cid:574). Like
`all proteins (or “polypeptides”), interferon-(cid:574) consists of
`Specifically, interferon-(cid:574) comprises 166 amino acids con-
`
`made in a non-human cell.
`
`tivity of native human interferon, it is not structurally
`
`amino-acid building blocks. C.A. App. 77878 (29:2-13).
`
`nected end-to-end. C.A. App. 77878 (29:19-22). Because
`of various molecular forces, that linear array of amino
`acids will conform or fold into a complex three-dimen-
`
`
`
`
`
`interferon-(cid:574) will be biologically active, C.A. App. 77880
`
`10
`sional shape. If the three-dimensional shape is correct,
`
`(31:8-14), modulating the immune system, reducing in-
`flammation, and increasing cells’ resistance to viruses.
`C.A. App. 77574 (62:2-9); C.A. App. 77872 (23:15-19); C.A.
`App. 47551 (47:14-15). In effect, the complex three-
`dimensional shape is like a key, fitting into a lock to set in
`motion subsequent biological processes.
`
`Native, human interferon-(cid:574) is a glycoprotein, which
`sugar branches can vary for individual interferon-(cid:574) pro-
`Thus, in any given sample of native interferon-(cid:574) taken
`from a human, each interferon-(cid:574) molecule can have one
`
`means it has sugars attached to one of its amino acids in a
`branched structure. C.A. App. 77882 (33:11-25). The
`
`teins, even when they are made within the same cell.
`
`of a variety of sugar branches attached to it. C.A. App.
`51646 (Kagawa); C.A. App. 80514-80515 (100:5-101:2).
`While similar proteins can be made by cells of dif-
`ferent species, the cells of different species make glycol-
`proteins with different sugar branches, or sometimes
`none at all, and are thus not identical. E. coli, for ex-
`ample, does not glycosylate proteins. C.A. App. 80514
`
`like proteins produced by E. coli thus lack the sugar
`
`a different molecular structure.
`B. The ’755 Patent
`The ’755 Patent discloses that therapeutic use of
`
`(100:5-20); C.A. App. 79094 (47:12-21). The interferon-(cid:574)-
`attachments of native, human interferon-(cid:574) and thus have
`native, human interferon-(cid:574) was known in the prior art,
`native, human interferon-(cid:574) had been prepared, C.A. App.
`
`C.A. App. 118-110 (2:53-4:22), and how compositions of
`
`119-120 (4:49-5:3). Its claims were limited to a method of
`treatment with “a therapeutically effective amount of a
`
`
`
`
`
`11
`composition,” said composition comprising a recombinant
`
`transformed by certain DNA sequences.
`During prosecution of a sister patent application,
`Biogen explained that the “non-human” host limitation
`was added for the purpose of distinguishing recombinant
`
`interferon-(cid:574)-like polypeptide made in a non-human host
`interferon-(cid:574) from native interferon-(cid:574):
`IFN-(cid:574) produced in human cells is glycosylated and
`
`As amended, the claims expressly recite production
`in non-human cells. * * * This is not semantics.
`
`has a particular type and content of sugar groups.
`The claimed polypeptides do not have the identical
`type or content of sugar groups. They cannot have.
`They are produced in non-human cells whose ability
`to post-translationally modify proteins is different
`from that of human cells.
`C.A. App. 24315.
`Claim 1 of the ’755 Patent thus recites:
`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 hybrid-
`izing 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 condi-
`
`
`
`
`
`12
`tions of 0.75 M NaCl at 68° C. and washing condi-
`tions 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 re-
`sult 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.
`App., infra, 4a-5a (emphasis added); see C.A. App. 142
`(49:59-50:12).
`II. PROCEEDINGS BELOW
`In 2010, Biogen sued respondents for infringement of
`claims 1 and 2 of the ’755 Patent.
`A. Proceedings Before the Trial Court
`1. During a nearly five-week trial, the jury heard
`about worldwide efforts in 1980 among leading scientists
`to do what had never been done: to use recombinant-
`DNA technology to engineer an analogue of a known
`
`human protein, interferon-(cid:574), that had biological activity
`that Dr. Fiers produced interferon-(cid:574)-like polypeptides in
`
`like the native, human protein and that thus could be
`used to treat disease. Pet’r C.A. Br. 2. The jury heard
`
`E. coli, rigorously tested and retested their biological
`activity to exclude false positives, and filed his patent
`application before anyone else. Ibid. The jury heard ex-
`tensive testimony about the patent’s 29-year history in
`the Patent Office (during much of which time prosecution
`was suspended due to multiple interference proceedings).
`And the jury heard respondents’ refrain, which the jury
`rejected, that all this was obvious. Id. at 3.
`
`
`
`
`
`13
`What the jury did not hear was any evidence that the
`’755 Patent was anticipated by the prior art. Pet’r C.A.
`Br. 15-16. No witness identified a prior-art reference in
`
`which recombinant interferon-(cid:574), made in a non-human
`ness testify that recombinant interferon-(cid:574) and native, hu-
`man interferon-(cid:574) are themselves identical. Id. at 23. In-
`
`host cell, was used to treat disease. Indeed, everyone
`agreed that had never happened. Ibid. Nor did any wit-
`
`deed, respondents’ expert conceded that they are not
`identical. Ibid. When it came time for summations, re-
`spondents did not even
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